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      Naldemedine is associated with earlier defecation in critically ill patients with opioid-induced constipation: A retrospective, single-center cohort study

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          Abstract

          Introduction

          There are few reports describing the association of naldemedine with defecation in critically ill patients with opioid-induced constipation. The purpose of this study was to determine whether naldemedine is associated with earlier defecation in critically ill patients with opioid-induced constipation.

          Methods

          In this retrospective cohort study, patients admitted to the Intensive Care Unit (ICU) without defecation for 48 hours while receiving opioids were eligible for enrollment. The primary endpoint was the time of the first defecation within 96 hours after inclusion. Secondary endpoints included presence of diarrhea, duration of mechanical ventilation, ICU length of stay, ICU mortality, and in-hospital mortality. The Cox proportional hazard regression analysis with time-dependent covariates was used to evaluate the association naldemedine with earlier defecation.

          Results

          A total of 875 patients were enrolled and were divided into 63 patients treated with naldemedine and 812 patients not treated. Defecation was observed in 58.7% of the naldemedine group and 48.8% of the no-naldemedine group during the study (p = 0.150). The naldemedine group had statistically significantly prolonged duration of mechanical ventilation (8.7 days vs 5.5 days, p < 0.001) and ICU length of stay (11.8 days vs 9.2 days, p = 0.001) compared to the no-naldemedine group. However, the administration of naldemedine was significantly associated with earlier defecation [hazard ratio:2.53; 95% confidence interval: 1.71–3.75, p < 0.001].

          Conclusion

          The present study shows that naldemedine is associated with earlier defecation in critically ill patients with opioid-induced constipation.

          Related collections

          Most cited references30

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          Investigation of the freely available easy-to-use software ‘EZR' for medical statistics

          Y Kanda (2012)
          Although there are many commercially available statistical software packages, only a few implement a competing risk analysis or a proportional hazards regression model with time-dependent covariates, which are necessary in studies on hematopoietic SCT. In addition, most packages are not clinician friendly, as they require that commands be written based on statistical languages. This report describes the statistical software ‘EZR' (Easy R), which is based on R and R commander. EZR enables the application of statistical functions that are frequently used in clinical studies, such as survival analyses, including competing risk analyses and the use of time-dependent covariates, receiver operating characteristics analyses, meta-analyses, sample size calculation and so on, by point-and-click access. EZR is freely available on our website (http://www.jichi.ac.jp/saitama-sct/SaitamaHP.files/statmed.html) and runs on both Windows (Microsoft Corporation, USA) and Mac OS X (Apple, USA). This report provides instructions for the installation and operation of EZR.
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            A simulation study of the number of events per variable in logistic regression analysis.

            We performed a Monte Carlo study to evaluate the effect of the number of events per variable (EPV) analyzed in logistic regression analysis. The simulations were based on data from a cardiac trial of 673 patients in which 252 deaths occurred and seven variables were cogent predictors of mortality; the number of events per predictive variable was (252/7 =) 36 for the full sample. For the simulations, at values of EPV = 2, 5, 10, 15, 20, and 25, we randomly generated 500 samples of the 673 patients, chosen with replacement, according to a logistic model derived from the full sample. Simulation results for the regression coefficients for each variable in each group of 500 samples were compared for bias, precision, and significance testing against the results of the model fitted to the original sample. For EPV values of 10 or greater, no major problems occurred. For EPV values less than 10, however, the regression coefficients were biased in both positive and negative directions; the large sample variance estimates from the logistic model both overestimated and underestimated the sample variance of the regression coefficients; the 90% confidence limits about the estimated values did not have proper coverage; the Wald statistic was conservative under the null hypothesis; and paradoxical associations (significance in the wrong direction) were increased. Although other factors (such as the total number of events, or sample size) may influence the validity of the logistic model, our findings indicate that low EPV can lead to major problems.
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              Emerging treatments in neurogastroenterology: a multidisciplinary working group consensus statement on opioid-induced constipation.

              Opioids are effective for acute and chronic pain conditions, but their use is associated with often difficult-to-manage constipation and other gastrointestinal (GI) effects due to effects on peripheral μ-opioid receptors in the gut. The mechanism of opioid-induced constipation (OIC) differs from that of functional constipation (FC), and OIC may not respond as well to most first-line treatments for FC. The impact of OIC on quality of life (QoL) induces some patients to decrease or stop their opioid therapy to relieve or avoid constipation.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: MethodologyRole: Writing – review & editing
                Role: Formal analysisRole: MethodologyRole: Writing – review & editing
                Role: MethodologyRole: Writing – review & editing
                Role: MethodologyRole: Writing – review & editing
                Role: MethodologyRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLOS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                3 January 2024
                2024
                : 19
                : 1
                : e0295952
                Affiliations
                [1 ] Department of Anesthesiology and Critical Care Medicine, Jichi Medical University, Saitama Medical Center, Omiya, Saitama, Japan
                [2 ] Data Science Center, Jichi Medical University, Shimotsuke, Tochigi, Japan
                [3 ] Department of Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan
                Sao Paulo State University (UNESP), Botucatu Medical School, BRAZIL
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                ‡ TM, AKL and MS also contributed equally to this work.

                Author information
                https://orcid.org/0000-0003-2148-5556
                https://orcid.org/0000-0001-6673-5630
                https://orcid.org/0000-0002-0184-0381
                Article
                PONE-D-23-14424
                10.1371/journal.pone.0295952
                10763934
                4f4ef76f-6c20-43be-9dde-a9447751522c
                © 2024 Nishiyama et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 27 May 2023
                : 28 November 2023
                Page count
                Figures: 2, Tables: 3, Pages: 12
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                Biology and Life Sciences
                Physiology
                Physiological Processes
                Defecation
                Medicine and Health Sciences
                Health Care
                Health Care Facilities
                Hospitals
                Intensive Care Units
                Medicine and Health Sciences
                Pharmacology
                Drugs
                Analgesics
                Opioids
                Medicine and Health Sciences
                Pain Management
                Analgesics
                Opioids
                Medicine and Health Sciences
                Pharmacology
                Drugs
                Opioids
                Medicine and Health Sciences
                Gastroenterology and Hepatology
                Constipation
                Medicine and Health Sciences
                Clinical Medicine
                Signs and Symptoms
                Constipation
                Medicine and Health Sciences
                Gastroenterology and Hepatology
                Diarrhea
                Medicine and Health Sciences
                Clinical Medicine
                Signs and Symptoms
                Diarrhea
                Medicine and Health Sciences
                Pharmacology
                Drugs
                Sedatives
                Biology and Life Sciences
                Nutrition
                Medicine and Health Sciences
                Nutrition
                Biology and Life Sciences
                Psychology
                Relaxation (Psychology)
                Social Sciences
                Psychology
                Relaxation (Psychology)
                Custom metadata
                All relevant data are within the manuscript and its Supporting Information files.

                Uncategorized
                Uncategorized

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