{"paper_id":"000af2c4-c541-4553-ad1e-1dd29b21ffb3","body_text":"Predictors for Effectiveness of Naldemedine in Patients with Cancer Pain: A Retrospective, Single-Institution Analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Predictors for Effectiveness of Naldemedine in Patients with Cancer Pain: A Retrospective, Single-Institution Analysis YUKO KANBAYASHI, Mayumi Shimizu, Yuichi Ishizuka, Shohei Sawa, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1192993/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose To identify predictors for the effectiveness of naldemedine. Methods Participants comprised 106 advanced cancer patients receiving pain treatment with opioids who were prescribed naldemedine for OIC at Seirei Hamamatsu General Hospital in Japan between November 2016 and June 2021.For the regression analysis of factors associated with OIC, variables were extracted manually from medical charts. The effectiveness of naldemedine was evaluated 3 days after administration, based on whether patients showed OIC. Presence of OIC was defined based on Rome IV diagnostic criteria. Multivariate logistic regression analysis was performed to identify predictors for naldemedine effectiveness. Values of P < 0.05 (two-tailed) were considered significant. Results Significant factors identified included chemotherapy with taxanes within 1 month of evaluation of naldemedine effectiveness (odds ratio [OR] = 0.063, 95% confidence interval [CI] = 0.007–0.568; P = 0.014), and addition of or switching to naldemedine due to insufficient prior laxatives (OR = 0.352, 95%CI = 0.129–0.966; P = 0.043). Conclusion No chemotherapy that included taxanes within 1 month of evaluation of naldemedine effectiveness and no addition of or switching to naldemedine due to insufficient prior laxatives were identified as predictors for effectiveness of naldemedine in patients with cancer pain. opioid constipation taxane naldemedine cancer pain Introduction Opioid-induced constipation (OIC) is one of the most common adverse events of opioid therapy and can severely reduce quality of life (QOL) [ 1 – 3 ]. OIC is common among patients with advanced cancers, with a prevalence of approximately 51–87% among patients receiving opioids for pain management [ 1 – 5 ]. Naldemedine is the newest orally available, peripheral-acting µ-opioid receptor antagonist (PAMORA). Naldemedine improves OIC by binding to opioid receptors in the gastrointestinal tract and antagonizing opioid analgesics. The analgesic effects of many opioid analgesics are expressed mainly via the central µ-opioid receptors. Naldemedine is a PAMORA designed so as not to inhibit the action of opioid analgesics in the central nervous system [ 6 , 7 ]. Naldemedine has also been shown to improve patient-rated constipation-related symptoms and QOL [ 6 – 10 ]. Previous studies have suggested that no baseline variables affect the efficacy or safety of once-daily oral naldemedine 0.2 mg in patients with OIC [ 11 , 12 ]. On the other hand, in daily clinical practice, some advanced cancer patients have shown insufficient OIC control even while receiving naldemedine [ 3 , 12 ]. This retrospective study was thus undertaken to identify predictors for the effectiveness of naldemedine, to help guide future strategies toward improving QOL in advanced cancer patients receiving pain treatment with opioids. Patients And Methods Study Period and Participants This study retrospectively analysed 139 patients with cancer pain prescribed naldemedine for OIC at Seirei Hamamatsu General Hospital in Japan between November 2016 and June 2021. All study protocols were approved by the Medical Ethics Review Committee at Seirei Hamamatsu General Hospital (approval no. 3310) and the Faculty of Pharmacy at Osaka Medical Pharmaceutical University (approval no. 0088). Extraction of Variables Variables associated with the effectiveness of naldemedine were extracted from clinical records and used for regression analysis. Variables extracted were factors potentially affecting the effectiveness of naldemedine: demographic data (age, height, weight, body surface area, body mass index [BMI]), Eastern Cooperative Oncology Group performance status, daily dosage of opioid in milligrams of morphine-equivalents, types of concomitant laxatives, types of opioids, stage of cancer, anti-cancer drugs administered within 1 month of the evaluation of naldemedine effectiveness, timing of naldemedine administration, and cancer type. The effectiveness of naldemedine was evaluated 3 days after administration, based on whether the patient had OIC. The presence of OIC was defined based on Rome IV diagnostic criteria [ 3 ]. Details of the Rome IV diagnostic criteria for the diagnosis of OIC used in this study have been published previously [ 13 – 15 ]. Statistical Analysis The analytical procedure employed was logistic regression, with the response = Y being a binary categorical variable (naldemedine effective or naldemedine not effective) and evaluated simultaneously with multiple predictors of effectiveness of naldemedine = X . To improve accuracy, predictors that were not essential to explain the response = Y were excluded. Independent variables were analysed for multicollinearity (correlation coefficient |r| ≥ 0.7), since correlations among variables can lead to unreliable and unstable results of regression analyses. Independent variables were extracted based on the strength of the correlation with effectiveness of naldemedine or clinical significance. First, univariate logistic regression analyses between outcomes and each potential independent variable were performed. Subsequently, a multivariate logistic regression model was constructed by employing the forward-backward stepwise selection procedure with the resulting candidate variables. For all statistical analyses, values of P < 0.05 (two-tailed) were considered significant. All analyses were conducted using JMP version 14.3.0 (SAS Institute, Cary, NC). Results All 139 patients were newly prescribed naldemedine, but 33 patients were excluded from this study due to insufficient data. Table 1 presents the clinical characteristics of the remaining 106 enrolled patients, potential variables related to OIC, and the results of univariate analyses. The forward-backward stepwise selection procedure identified the following candidate variables: BMI, chemotherapy with taxane within 1 month of evaluation of naldemedine effectiveness, daily dosage of opioid, use of naldemedine prescription within 2 days of opioid initiation, and addition of or switching to naldemedine due to insufficient prior laxatives. Table 1 Patient characteristics, extracted variables, and results of univariate analyses (n = 106) Laxative not effective (n = 42) Laxative effective (n = 64) P value Odds ratio (95%CI) Demographic data Sex, male, n (%) 30 (71.4) 39 (60.9) 0.269 0.62 (0.27–1.44) Age (y), median (range) 42–88 (69) 42–89 (70) 0.777 1.01 (0.97–1.04) Height (cm), median (range) 145–176 (163) 143–180 (160) 0.585 0.99 (0.94–1.04) Weight (kg), median (range) 32.5–73.7 (54) 35–84 (51.1) 0.363 0.98 (0.94–1.02) Body mass index (kg/m 2 ), median (range) 13.0–28.9 (19.7) 14.2–28.8 (19.6) 0.434 0.95 (0.84–1.08) Body surface area (m 2 ), median (range) 1.22–1.84 (1.58) 1.24–2.04 (1.55) 0.365 0.30 (0.02–4.06) Eastern Cooperative Oncology Group performance status (0/1/2/3/4) 0/4/21/15/2 0/8/25/24/7 0.483 1.19 (0.73–1.94) Stage of cancer (1/2/3/4) 0/3/0/39 0/2/5/57 0.062 1.01 (0.37–3.33) Chemotherapy given within 1 month of evaluation of naldemedine effectiveness , n (%) 19 (45.2) 23 (35.9) 0.339 0.68 (0.31–1.50) Anti-cancer drug administered within 1 month of evaluation of naldemedine effectiveness Taxanes, n (%) 7 (16.7) 2 (3.1) 0.028 0.16 (0.03–0.82) Fluorouracil, n (%) 5 (11.9) 10 (15.6) 0.592 1.37 (0.43–4.34) Platinum, n (%) 9 (21.4) 15 (23.4) 0.809 1.12 (0.44–2.86) Types of opioids Morphine, n (%) 4 (9.5) 11 (17.2) 0.606 1.00 (1.00–1.01) Fentanyl, n (%) 2 (4.8) 3 (4.7) 0.986 0.98 (0.16–6.15) Oxycodone, n (%) 31 (73.8) 42 (65.6) 0.375 0.68 (0.29–1.60) Daily dose, morphine-equivalents (mg), median (range) 10–144 15–576 0.606 1.00 (1.00–1.01) Concomitant laxative Magnesium oxide, n (%) 5 (11.9) 13 (20.3) 0.265 1.89 (0.61–5.75) Sennoside, n (%) 2 (4.8) 6 (9.4) 0.388 2.07 (0.39–10.8) Lubiprostone, n (%) 1 (2.4) 2 (3.1) 0.822 1.32 (0.12–15.1) Naldemedine prescription within 2 days of opioid initiation, n (%) 4 (9.5) 6 (9.4) 0.980 0.98 (0.26–3.71) Addition of or switching to naldemedine due to insufficient prior laxative, n (%) 29 (69.0) 34 (53.1) 0.105 0.51 (0.22–1.15) Cancer type Colon, n (%) 3 (7.1) 7 (10.9) 0.516 1.60 (0.39–6.56) Gastric, n (%) 1 (2.4) 4 (6.3) 0.376 2.73 (0.29–25.3) Pancreatic, n (%) 13 (31.0) 15 (23.4) 0.392 0.68 (0.29–1.64) Esophageal, n (%) 3 (7.1) 4 (6.3) 0.856 0.86 (0.18–4.08) Lung, n (%) 6 (14.3) 10 (15.6) 0.851 1.11 (0.37–3.33) Breast, n (%) 0 3 (4.7) - - Head and neck, n (%) 9 10 (15.6) 0.47 0.69 (0.25–1.88) Urologic, n (%) 4 (9.5) 4 (6.3) 0.54 0.63 (0.15–2.68) CI, confidence interval *P<0.05 Multivariate logistic regression analysis was performed using these variables. Significant factors identified included chemotherapy with taxanes within 1 month of evaluation of naldemedine effectiveness (odds ratio [OR] = 0.063, 95% confidence interval [CI] = 0.007–0.568; P = 0.014), and addition of or switching to naldemedine due to insufficient prior laxatives (OR = 0.352, 95% CI = 0.129–0.966; P = 0.043) (Table 2 ). Table 2 Results of multivariate ordered logistic regression analysis for variables extracted by forward-backward stepwise selection procedure (n = 106) Variable P value Odds ratio 95% confidence interval Lower endpoint Upper endpoint Body mass index 0.098 0.890 0.776 1.022 Taxanes 0.014* 0.063 0.007 0.568 Daily dosage in morphine-equivalents (mg) 0.585 1.002 0.995 1.009 Naldemedine prescription within 2 days of opioid initiation 0.268 0.411 0.085 1.981 Addition of or switching to naldemedine due to insufficient prior laxative 0.043* 0.352 0.129 0.966 * P <0.05 Discussion The multivariate logistic regression analysis performed in this study showed that predictors for naldemedine effectiveness included chemotherapy with taxanes within 1 month of evaluation of naldemedine effectiveness and addition of or switching to naldemedine due to insufficient prior laxatives. The results of this study showed that OIC was poorly controlled when chemotherapy with taxane was given within 1 month of evaluation of naldemedine effectiveness. Taxanes are anticancer drugs that have a side effect of constipation due to neuropathy [ 16 ]. Taxane-induced neuropathy persists for a long period in clinical practice. If taxanes was administered within 1 month of evaluation of naldemedine effectiveness, side effects may persist. OIC control may thus be difficult. On the other hand, naldemedine is primarily metabolized by cytochrome P450 3A4 (CYP3A4) to form nor-naldemedine [ 17 ]. In this study, some patients were receiving chemotherapy with taxanes at the time of evaluation of naldemedine effectiveness. Molecular species such as CYP3A4 are involved in metabolism of taxanes such as paclitaxel and docetaxel [ 18 , 19 ]. Although there are no reports of drug-drug interactions between naldemedine and taxanes, it is necessary to consider the possibility to reduce naldemedine effectiveness due to drug-drug interactions, especially in patients undergoing chemotherapy with taxanes. This point needs further verification in daily clinical practice. In recent years, new opioid prescriptions are often made by oncologists during chemotherapy, rather than by palliative care physicians. Oncologists who prescribe opioids need to consider OIC control during chemotherapy, particularly in patients receiving taxane-based chemotherapy. Addition of or switching due to insufficient prior laxatives was also extracted as a risk factor for OIC. Naldemedine is a PAMORA, and the mechanism of action clearly suggests that the shorter the period of exposure to opioids, the more likely the effects of naldemedine are to manifest. On the other hand, in the present study, the factor “naldemedine prescription within 2 days of opioid initiation” was not extracted as a significant factor. Some of the patients were undergoing chemotherapy at the time of evaluation of naldemedine effectiveness. In other words, the serotonin receptor antagonist may have also acted on serotonin receptors in the intestine and decreased intestinal motility [ 20 ]. The guidelines for OIC also suggest that classic laxatives should be used first, with the use of novel constipation treatments or PAMORA recommended only if the effects prove insufficient [ 21 – 23 ]. The appropriate timing of naldemedine administration needs to be verified in the future. Several limitations to the current study need to be considered. First, the retrospective nature of the study may have decreased the validity of the data obtained. Second, since this study was performed at a single institute, prospective studies involving multiple centres are needed to confirm the results. In conclusion, no administration of a chemotherapeutic regimen that included taxanes within one month before the evaluation of naldemedine effectiveness and no addition of or switching to naldemedine due to insufficient prior laxatives were identified as predictors of effectiveness of naldemedine in advanced cancer patients with cancer pain. However, our findings need to be confirmed in further studies. Nevertheless, these results may assist to improve QOL among advanced cancer patients with cancer pain. Declarations Acknowledgements We wish to thank all the patients and medical staff at Seirei Hamamatsu General Hospital who were involved in this study. Author contributions YK: concept and design, data analysis, data interpretation, manuscript writing; MS, YI, SS & KY: concept and design, data acquisition, data interpretation; MU: concept and design, data interpretation, supervision of the manuscript. All authors read and approved the final manuscript. Funding No funding was received for conducting this study. Data availability Data not available due to ethical restrictions. Code availability Not applicable Ethical approval The Medical Ethics Review Committee of Seirei Hamamatsu General Hospital approval no.3310 and Faculty of Pharmacy, Osaka Medical Pharmaceutical University approved this study, approval no.0088. All procedures were performed in accordance with the ethical standards of the Seirei Hamamatsu General Hospital and Osaka Medical Pharmaceutical University of Medicine Institutional Medical Ethics Review Committee and the 1964 Declaration of Helsinki and its later amendments. No prospective studies with human participants or animals were performed by any of the authors for this article. This study retrospectively analysed 139 patients with cancer pain prescribed naldemedine for OIC at Seirei Hamamatsu General Hospital in Japan between November 2016 and June 2021. All study protocols were approved by the Medical Ethics Review Committee at Seirei Hamamatsu General Hospital (approval no. 3310) and the Faculty of Pharmacy at Osaka Medical Pharmaceutical University (approval no. 0088). Consent to participate Given the retrospective nature of this work, the need to obtain informed consent was waived for the individual participants included in the study, in accordance with the standards of the Seirei Hamamatsu General Hospital and Osaka Medical Pharmaceutical University of Medicine Institutional Medical Ethics Review Committee. Consent for publication All authors give their consent for this manuscript to be published in Supportive Care in Cancer. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-1192993\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":true,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":76822345,\"identity\":\"a043bbfc-c369-421e-a30e-740622d9f480\",\"order_by\":0,\"name\":\"YUKO KANBAYASHI\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABFklEQVRIiWNgGAWjYFACNiA+wMBgAGIzNkjIwSUYG4jUYkyyFoZEnAphwOBGWuIDhjN20ebsZww//txhkd4vdvaYBEONHQPzbOy6gVoOGzDcSM7d2ZNjLM17RiJ35uy8NAmGY8kMjHMO4NCS3ibB8IE5d8OBHANpxjaJ3A23c8wkGNgOMDDOSMCnpT53w/k3xj9/tkmkG4C1/MOnJQ3o8huHczfcAKrkbZNIAGthbMOtRfLMs2SDhDPHc3fOeFZmDdRiCPRLskViXzIPLr/wHU8zfPDhWHXudv7kzTd/ttXJ80vnHrzx4ZudnCGOEFMAmQRxAIcBVIwHLMJjOAOrDgZ5hEnsDxBawFIS2LWMglEwCkbBiAMA1/plR8qrtsEAAAAASUVORK5CYII=\",\"orcid\":\"https://orcid.org/0000-0002-0095-2293\",\"institution\":\"Osaka Ika Yakka Daigaku\",\"correspondingAuthor\":true,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"YUKO\",\"middleName\":\"\",\"lastName\":\"KANBAYASHI\",\"suffix\":\"\"},{\"id\":76822346,\"identity\":\"34bdd568-ea05-4811-a5e0-51d1eb0e4c50\",\"order_by\":1,\"name\":\"Mayumi Shimizu\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Seirei Hamamatsu Hospital: Seirei Hamamatsu Byoin\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Mayumi\",\"middleName\":\"\",\"lastName\":\"Shimizu\",\"suffix\":\"\"},{\"id\":76822347,\"identity\":\"ce51aa4b-e453-49be-a0f7-73a59e39505a\",\"order_by\":2,\"name\":\"Yuichi Ishizuka\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Seirei Hamamatsu Hospital: Seirei Hamamatsu Byoin\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Yuichi\",\"middleName\":\"\",\"lastName\":\"Ishizuka\",\"suffix\":\"\"},{\"id\":76822348,\"identity\":\"84c41f66-d48e-4d7a-86f9-61579c9ec1bd\",\"order_by\":3,\"name\":\"Shohei Sawa\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Seirei Hamamatsu Hospital: Seirei Hamamatsu Byoin\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Shohei\",\"middleName\":\"\",\"lastName\":\"Sawa\",\"suffix\":\"\"},{\"id\":76822349,\"identity\":\"2b88bb15-9ce8-4b82-bdff-dbecb3a53a07\",\"order_by\":4,\"name\":\"Katsushige Yabe\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Seirei Hamamatsu Hospital: Seirei Hamamatsu Byoin\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Katsushige\",\"middleName\":\"\",\"lastName\":\"Yabe\",\"suffix\":\"\"},{\"id\":76822350,\"identity\":\"b71d312b-a00b-4643-949f-2f145bb98653\",\"order_by\":5,\"name\":\"Mayako Uchida\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Doshisha Women's College of Liberal Arts: Doshisha Joshi Daigaku\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Mayako\",\"middleName\":\"\",\"lastName\":\"Uchida\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2021-12-21 16:19:06\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-1192993/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-1192993/v1\",\"draftVersion\":[],\"editorialEvents\":[],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":17609912,\"identity\":\"a71a9e4e-8a7e-4957-8920-b770dab1a003\",\"added_by\":\"auto\",\"created_at\":\"2022-01-24 21:19:08\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":326854,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-1192993/v1/6e1b3f2f-330b-433a-b763-ed41a1151823.pdf\"}],\"financialInterests\":\"\",\"formattedTitle\":\"\\u003cp\\u003ePredictors for Effectiveness of Naldemedine in Patients with Cancer Pain: A Retrospective, Single-Institution Analysis\\u003c/p\\u003e\",\"fulltext\":[{\"header\":\"Introduction\",\"content\":\"\\u003cp\\u003eOpioid-induced constipation (OIC) is one of the most common adverse events of opioid therapy and can severely reduce quality of life (QOL) [\\u003cspan additionalcitationids=\\\"CR2\\\" citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e]. OIC is common among patients with advanced cancers, with a prevalence of approximately 51\\u0026ndash;87% among patients receiving opioids for pain management [\\u003cspan additionalcitationids=\\\"CR2 CR3 CR4\\\" citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e]. Naldemedine is the newest orally available, peripheral-acting \\u0026micro;-opioid receptor antagonist (PAMORA). Naldemedine improves OIC by binding to opioid receptors in the gastrointestinal tract and antagonizing opioid analgesics. The analgesic effects of many opioid analgesics are expressed mainly via the central \\u0026micro;-opioid receptors. Naldemedine is a PAMORA designed so as not to inhibit the action of opioid analgesics in the central nervous system [\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e]. Naldemedine has also been shown to improve patient-rated constipation-related symptoms and QOL [\\u003cspan additionalcitationids=\\\"CR7 CR8 CR9\\\" citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e]. Previous studies have suggested that no baseline variables affect the efficacy or safety of once-daily oral naldemedine 0.2 mg in patients with OIC [\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e]. On the other hand, in daily clinical practice, some advanced cancer patients have shown insufficient OIC control even while receiving naldemedine [\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e]. This retrospective study was thus undertaken to identify predictors for the effectiveness of naldemedine, to help guide future strategies toward improving QOL in advanced cancer patients receiving pain treatment with opioids.\\u003c/p\\u003e\"},{\"header\":\"Patients And Methods\",\"content\":\"\\u003cdiv id=\\\"Sec3\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eStudy Period and Participants\\u003c/h2\\u003e \\u003cp\\u003eThis study retrospectively analysed 139 patients with cancer pain prescribed naldemedine for OIC at Seirei Hamamatsu General Hospital in Japan between November 2016 and June 2021. All study protocols were approved by the Medical Ethics Review Committee at Seirei Hamamatsu General Hospital (approval no. 3310) and the Faculty of Pharmacy at Osaka Medical Pharmaceutical University (approval no. 0088).\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec4\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eExtraction of Variables\\u003c/h2\\u003e \\u003cp\\u003eVariables associated with the effectiveness of naldemedine were extracted from clinical records and used for regression analysis. Variables extracted were factors potentially affecting the effectiveness of naldemedine: demographic data (age, height, weight, body surface area, body mass index [BMI]), Eastern Cooperative Oncology Group performance status, daily dosage of opioid in milligrams of morphine-equivalents, types of concomitant laxatives, types of opioids, stage of cancer, anti-cancer drugs administered within 1 month of the evaluation of naldemedine effectiveness, timing of naldemedine administration, and cancer type.\\u003c/p\\u003e \\u003cp\\u003eThe effectiveness of naldemedine was evaluated 3 days after administration, based on whether the patient had OIC. The presence of OIC was defined based on Rome IV diagnostic criteria [\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e]. Details of the Rome IV diagnostic criteria for the diagnosis of OIC used in this study have been published previously [\\u003cspan additionalcitationids=\\\"CR14\\\" citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e].\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec5\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eStatistical Analysis\\u003c/h2\\u003e \\u003cp\\u003eThe analytical procedure employed was logistic regression, with the response = \\u003cem\\u003eY\\u003c/em\\u003e being a binary categorical variable (naldemedine effective or naldemedine not effective) and evaluated simultaneously with multiple predictors of effectiveness of naldemedine = \\u003cem\\u003eX\\u003c/em\\u003e. To improve accuracy, predictors that were not essential to explain the response = \\u003cem\\u003eY\\u003c/em\\u003e were excluded.\\u003c/p\\u003e \\u003cp\\u003eIndependent variables were analysed for multicollinearity (correlation coefficient |r| \\u0026ge; 0.7), since correlations among variables can lead to unreliable and unstable results of regression analyses. Independent variables were extracted based on the strength of the correlation with effectiveness of naldemedine or clinical significance. First, univariate logistic regression analyses between outcomes and each potential independent variable were performed. Subsequently, a multivariate logistic regression model was constructed by employing the forward-backward stepwise selection procedure with the resulting candidate variables.\\u003c/p\\u003e \\u003cp\\u003eFor all statistical analyses, values of \\u003cem\\u003eP\\u003c/em\\u003e \\u0026lt; 0.05 (two-tailed) were considered significant. All analyses were conducted using JMP version 14.3.0 (SAS Institute, Cary, NC).\\u003c/p\\u003e \\u003c/div\\u003e\"},{\"header\":\"Results\",\"content\":\"\\u003cp\\u003eAll 139 patients were newly prescribed naldemedine, but 33 patients were excluded from this study due to insufficient data. Table \\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e presents the clinical characteristics of the remaining 106 enrolled patients, potential variables related to OIC, and the results of univariate analyses. The forward-backward stepwise selection procedure identified the following candidate variables: BMI, chemotherapy with taxane within 1 month of evaluation of naldemedine effectiveness, daily dosage of opioid, use of naldemedine prescription within 2 days of opioid initiation, and addition of or switching to naldemedine due to insufficient prior laxatives.\\u003c/p\\u003e \\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab1\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 1\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003ePatient characteristics, extracted variables, and results of univariate analyses (n = 106)\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"5\\\"\\u003e \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eLaxative not effective\\u003c/p\\u003e \\u003cp\\u003e(n = 42)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003eLaxative effective\\u003c/p\\u003e \\u003cp\\u003e(n = 64)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eP\\u003c/em\\u003e value\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003eOdds ratio\\u003c/p\\u003e \\u003cp\\u003e(95%CI)\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"5\\\" nameend=\\\"c5\\\" namest=\\\"c1\\\"\\u003e \\u003cp\\u003eDemographic data\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eSex, male, n (%)\\u003c/em\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e30\\u003c/p\\u003e \\u003cp\\u003e(71.4)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e39\\u003c/p\\u003e \\u003cp\\u003e(60.9)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.269\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.62\\u003c/p\\u003e \\u003cp\\u003e(0.27\\u0026ndash;1.44)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eAge (y), median (range)\\u003c/em\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e42\\u0026ndash;88\\u003c/p\\u003e \\u003cp\\u003e(69)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e42\\u0026ndash;89\\u003c/p\\u003e \\u003cp\\u003e(70)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.777\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e1.01\\u003c/p\\u003e \\u003cp\\u003e(0.97\\u0026ndash;1.04)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eHeight (cm), median (range)\\u003c/em\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e145\\u0026ndash;176\\u003c/p\\u003e \\u003cp\\u003e(163)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e143\\u0026ndash;180\\u003c/p\\u003e \\u003cp\\u003e(160)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.585\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.99\\u003c/p\\u003e \\u003cp\\u003e(0.94\\u0026ndash;1.04)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eWeight (kg), median (range)\\u003c/em\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e32.5\\u0026ndash;73.7\\u003c/p\\u003e \\u003cp\\u003e(54)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e35\\u0026ndash;84\\u003c/p\\u003e \\u003cp\\u003e(51.1)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.363\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.98\\u003c/p\\u003e \\u003cp\\u003e(0.94\\u0026ndash;1.02)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eBody mass index (kg/m\\u003c/em\\u003e\\u003csup\\u003e\\u003cem\\u003e2\\u003c/em\\u003e\\u003c/sup\\u003e\\u003cem\\u003e), median (range)\\u003c/em\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e13.0\\u0026ndash;28.9\\u003c/p\\u003e \\u003cp\\u003e(19.7)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e14.2\\u0026ndash;28.8\\u003c/p\\u003e \\u003cp\\u003e(19.6)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.434\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.95\\u003c/p\\u003e \\u003cp\\u003e(0.84\\u0026ndash;1.08)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eBody surface area (m\\u003c/em\\u003e\\u003csup\\u003e\\u003cem\\u003e2\\u003c/em\\u003e\\u003c/sup\\u003e\\u003cem\\u003e), median (range)\\u003c/em\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e1.22\\u0026ndash;1.84\\u003c/p\\u003e \\u003cp\\u003e(1.58)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e1.24\\u0026ndash;2.04\\u003c/p\\u003e \\u003cp\\u003e(1.55)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.365\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.30\\u003c/p\\u003e \\u003cp\\u003e(0.02\\u0026ndash;4.06)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eEastern Cooperative Oncology Group performance status (0/1/2/3/4)\\u003c/em\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0/4/21/15/2\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0/8/25/24/7\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.483\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e1.19\\u003c/p\\u003e \\u003cp\\u003e(0.73\\u0026ndash;1.94)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eStage of cancer (1/2/3/4)\\u003c/em\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0/3/0/39\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0/2/5/57\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.062\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e1.01\\u003c/p\\u003e \\u003cp\\u003e(0.37\\u0026ndash;3.33)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eChemotherapy given within 1 month of evaluation of naldemedine effectiveness\\u003c/p\\u003e \\u003cp\\u003e, n (%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e19\\u003c/p\\u003e \\u003cp\\u003e(45.2)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e23\\u003c/p\\u003e \\u003cp\\u003e(35.9)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.339\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.68\\u003c/p\\u003e \\u003cp\\u003e(0.31\\u0026ndash;1.50)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"5\\\" nameend=\\\"c5\\\" namest=\\\"c1\\\"\\u003e \\u003cp\\u003eAnti-cancer drug administered within 1 month of evaluation of naldemedine effectiveness\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eTaxanes, n (%)\\u003c/em\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e7\\u003c/p\\u003e \\u003cp\\u003e(16.7)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e2\\u003c/p\\u003e \\u003cp\\u003e(3.1)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.028\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.16\\u003c/p\\u003e \\u003cp\\u003e(0.03\\u0026ndash;0.82)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eFluorouracil, n (%)\\u003c/em\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e5\\u003c/p\\u003e \\u003cp\\u003e(11.9)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e10\\u003c/p\\u003e \\u003cp\\u003e(15.6)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.592\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e1.37\\u003c/p\\u003e \\u003cp\\u003e(0.43\\u0026ndash;4.34)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003ePlatinum, n (%)\\u003c/em\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e9\\u003c/p\\u003e \\u003cp\\u003e(21.4)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e15\\u003c/p\\u003e \\u003cp\\u003e(23.4)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.809\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e1.12\\u003c/p\\u003e \\u003cp\\u003e(0.44\\u0026ndash;2.86)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"5\\\" nameend=\\\"c5\\\" namest=\\\"c1\\\"\\u003e \\u003cp\\u003eTypes of opioids\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eMorphine, n (%)\\u003c/em\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e4\\u003c/p\\u003e \\u003cp\\u003e(9.5)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e11\\u003c/p\\u003e \\u003cp\\u003e(17.2)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.606\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e1.00\\u003c/p\\u003e \\u003cp\\u003e(1.00\\u0026ndash;1.01)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eFentanyl, n (%)\\u003c/em\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e2\\u003c/p\\u003e \\u003cp\\u003e(4.8)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e3\\u003c/p\\u003e \\u003cp\\u003e(4.7)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.986\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.98\\u003c/p\\u003e \\u003cp\\u003e(0.16\\u0026ndash;6.15)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eOxycodone, n (%)\\u003c/em\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e31\\u003c/p\\u003e \\u003cp\\u003e(73.8)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e42\\u003c/p\\u003e \\u003cp\\u003e(65.6)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.375\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.68\\u003c/p\\u003e \\u003cp\\u003e(0.29\\u0026ndash;1.60)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eDaily dose, morphine-equivalents (mg), median (range)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e10\\u0026ndash;144\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e15\\u0026ndash;576\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.606\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e1.00\\u003c/p\\u003e \\u003cp\\u003e(1.00\\u0026ndash;1.01)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"5\\\" nameend=\\\"c5\\\" namest=\\\"c1\\\"\\u003e \\u003cp\\u003eConcomitant laxative\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eMagnesium oxide, n (%)\\u003c/em\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e5\\u003c/p\\u003e \\u003cp\\u003e(11.9)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e13\\u003c/p\\u003e \\u003cp\\u003e(20.3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.265\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e1.89\\u003c/p\\u003e \\u003cp\\u003e(0.61\\u0026ndash;5.75)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eSennoside, n (%)\\u003c/em\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e2\\u003c/p\\u003e \\u003cp\\u003e(4.8)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e6\\u003c/p\\u003e \\u003cp\\u003e(9.4)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.388\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e2.07\\u003c/p\\u003e \\u003cp\\u003e(0.39\\u0026ndash;10.8)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eLubiprostone, n (%)\\u003c/em\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e1\\u003c/p\\u003e \\u003cp\\u003e(2.4)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e2\\u003c/p\\u003e \\u003cp\\u003e(3.1)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.822\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e1.32\\u003c/p\\u003e \\u003cp\\u003e(0.12\\u0026ndash;15.1)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eNaldemedine prescription within 2 days of opioid initiation, n (%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e4\\u003c/p\\u003e \\u003cp\\u003e(9.5)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e6\\u003c/p\\u003e \\u003cp\\u003e(9.4)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.980\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.98\\u003c/p\\u003e \\u003cp\\u003e(0.26\\u0026ndash;3.71)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eAddition of or switching to naldemedine due to insufficient prior laxative, n (%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e29\\u003c/p\\u003e \\u003cp\\u003e(69.0)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e34\\u003c/p\\u003e \\u003cp\\u003e(53.1)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.105\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.51\\u003c/p\\u003e \\u003cp\\u003e(0.22\\u0026ndash;1.15)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"5\\\" nameend=\\\"c5\\\" namest=\\\"c1\\\"\\u003e \\u003cp\\u003eCancer type\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eColon, n (%)\\u003c/em\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e3\\u003c/p\\u003e \\u003cp\\u003e(7.1)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e7\\u003c/p\\u003e \\u003cp\\u003e(10.9)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.516\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e1.60\\u003c/p\\u003e \\u003cp\\u003e(0.39\\u0026ndash;6.56)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eGastric, n (%)\\u003c/em\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e1\\u003c/p\\u003e \\u003cp\\u003e(2.4)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e4\\u003c/p\\u003e \\u003cp\\u003e(6.3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.376\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e2.73\\u003c/p\\u003e \\u003cp\\u003e(0.29\\u0026ndash;25.3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003ePancreatic, n (%)\\u003c/em\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e13\\u003c/p\\u003e \\u003cp\\u003e(31.0)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e15\\u003c/p\\u003e \\u003cp\\u003e(23.4)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.392\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.68\\u003c/p\\u003e \\u003cp\\u003e(0.29\\u0026ndash;1.64)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eEsophageal, n (%)\\u003c/em\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e3\\u003c/p\\u003e \\u003cp\\u003e(7.1)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e4\\u003c/p\\u003e \\u003cp\\u003e(6.3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.856\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.86\\u003c/p\\u003e \\u003cp\\u003e(0.18\\u0026ndash;4.08)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eLung, n (%)\\u003c/em\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e6\\u003c/p\\u003e \\u003cp\\u003e(14.3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e10\\u003c/p\\u003e \\u003cp\\u003e(15.6)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.851\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e1.11\\u003c/p\\u003e \\u003cp\\u003e(0.37\\u0026ndash;3.33)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eBreast, n (%)\\u003c/em\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e3\\u003c/p\\u003e \\u003cp\\u003e(4.7)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e-\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e-\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eHead and neck, n (%)\\u003c/em\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e9\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e10\\u003c/p\\u003e \\u003cp\\u003e(15.6)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.47\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.69\\u003c/p\\u003e \\u003cp\\u003e(0.25\\u0026ndash;1.88)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eUrologic, n (%)\\u003c/em\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e4\\u003c/p\\u003e \\u003cp\\u003e(9.5)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e4\\u003c/p\\u003e \\u003cp\\u003e(6.3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.54\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.63\\u003c/p\\u003e \\u003cp\\u003e(0.15\\u0026ndash;2.68)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003ctfoot\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"5\\\"\\u003eCI, confidence interval\\u003c/td\\u003e\\u003c/tr\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"5\\\"\\u003e*P\\u0026lt;0.05\\u003c/td\\u003e\\u003c/tr\\u003e \\u003c/tfoot\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003cp\\u003eMultivariate logistic regression analysis was performed using these variables. Significant factors identified included chemotherapy with taxanes within 1 month of evaluation of naldemedine effectiveness (odds ratio [OR] = 0.063, 95% confidence interval [CI] = 0.007\\u0026ndash;0.568; \\u003cem\\u003eP\\u003c/em\\u003e = 0.014), and addition of or switching to naldemedine due to insufficient prior laxatives (OR = 0.352, 95% CI = 0.129\\u0026ndash;0.966; \\u003cem\\u003eP\\u003c/em\\u003e = 0.043) (Table \\u003cspan refid=\\\"Tab2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e).\\u003c/p\\u003e \\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab2\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 2\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003eResults of multivariate ordered logistic regression analysis for variables extracted by forward-backward stepwise selection procedure (n = 106)\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"5\\\"\\u003e \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c1\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003eVariable\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c2\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eP\\u003c/em\\u003e value\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c3\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003eOdds ratio\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c5\\\" namest=\\\"c4\\\"\\u003e \\u003cp\\u003e95% confidence interval\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003eLower endpoint\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003eUpper endpoint\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eBody mass index\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.098\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0.890\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.776\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e1.022\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eTaxanes\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.014*\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0.063\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.007\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.568\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eDaily dosage in morphine-equivalents (mg)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.585\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e1.002\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.995\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e1.009\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eNaldemedine prescription within 2 days of opioid initiation\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.268\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0.411\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.085\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e1.981\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eAddition of or switching to naldemedine due to insufficient prior laxative\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.043*\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0.352\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.129\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.966\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003ctfoot\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"5\\\"\\u003e*\\u003cem\\u003eP\\u003c/em\\u003e\\u0026lt;0.05\\u003c/td\\u003e\\u003c/tr\\u003e \\u003c/tfoot\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e\"},{\"header\":\"Discussion\",\"content\":\"\\u003cp\\u003eThe multivariate logistic regression analysis performed in this study showed that predictors for naldemedine effectiveness included chemotherapy with taxanes within 1 month of evaluation of naldemedine effectiveness and addition of or switching to naldemedine due to insufficient prior laxatives.\\u003c/p\\u003e \\u003cp\\u003eThe results of this study showed that OIC was poorly controlled when chemotherapy with taxane was given within 1 month of evaluation of naldemedine effectiveness. Taxanes are anticancer drugs that have a side effect of constipation due to neuropathy [\\u003cspan citationid=\\\"CR16\\\" class=\\\"CitationRef\\\"\\u003e16\\u003c/span\\u003e]. Taxane-induced neuropathy persists for a long period in clinical practice. If taxanes was administered within 1 month of evaluation of naldemedine effectiveness, side effects may persist. OIC control may thus be difficult. On the other hand, naldemedine is primarily metabolized by cytochrome P450 3A4 (CYP3A4) to form nor-naldemedine [\\u003cspan citationid=\\\"CR17\\\" class=\\\"CitationRef\\\"\\u003e17\\u003c/span\\u003e]. In this study, some patients were receiving chemotherapy with taxanes at the time of evaluation of naldemedine effectiveness. Molecular species such as CYP3A4 are involved in metabolism of taxanes such as paclitaxel and docetaxel [\\u003cspan citationid=\\\"CR18\\\" class=\\\"CitationRef\\\"\\u003e18\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR19\\\" class=\\\"CitationRef\\\"\\u003e19\\u003c/span\\u003e]. Although there are no reports of drug-drug interactions between naldemedine and taxanes, it is necessary to consider the possibility to reduce naldemedine effectiveness due to drug-drug interactions, especially in patients undergoing chemotherapy with taxanes. This point needs further verification in daily clinical practice. In recent years, new opioid prescriptions are often made by oncologists during chemotherapy, rather than by palliative care physicians. Oncologists who prescribe opioids need to consider OIC control during chemotherapy, particularly in patients receiving taxane-based chemotherapy.\\u003c/p\\u003e \\u003cp\\u003eAddition of or switching due to insufficient prior laxatives was also extracted as a risk factor for OIC. Naldemedine is a PAMORA, and the mechanism of action clearly suggests that the shorter the period of exposure to opioids, the more likely the effects of naldemedine are to manifest. On the other hand, in the present study, the factor \\u0026ldquo;naldemedine prescription within 2 days of opioid initiation\\u0026rdquo; was not extracted as a significant factor. Some of the patients were undergoing chemotherapy at the time of evaluation of naldemedine effectiveness. In other words, the serotonin receptor antagonist may have also acted on serotonin receptors in the intestine and decreased intestinal motility [\\u003cspan citationid=\\\"CR20\\\" class=\\\"CitationRef\\\"\\u003e20\\u003c/span\\u003e]. The guidelines for OIC also suggest that classic laxatives should be used first, with the use of novel constipation treatments or PAMORA recommended only if the effects prove insufficient [\\u003cspan additionalcitationids=\\\"CR22\\\" citationid=\\\"CR21\\\" class=\\\"CitationRef\\\"\\u003e21\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR23\\\" class=\\\"CitationRef\\\"\\u003e23\\u003c/span\\u003e]. The appropriate timing of naldemedine administration needs to be verified in the future.\\u003c/p\\u003e \\u003cp\\u003eSeveral limitations to the current study need to be considered. First, the retrospective nature of the study may have decreased the validity of the data obtained. Second, since this study was performed at a single institute, prospective studies involving multiple centres are needed to confirm the results.\\u003c/p\\u003e \\u003cp\\u003eIn conclusion, no administration of a chemotherapeutic regimen that included taxanes within one month before the evaluation of naldemedine effectiveness and no addition of or switching to naldemedine due to insufficient prior laxatives were identified as predictors of effectiveness of naldemedine in advanced cancer patients with cancer pain. However, our findings need to be confirmed in further studies. Nevertheless, these results may assist to improve QOL among advanced cancer patients with cancer pain.\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eAcknowledgements\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eWe wish to thank all the patients and medical staff at Seirei Hamamatsu General Hospital who were involved in this study.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAuthor contributions\\u003c/strong\\u003e YK: concept and design, data analysis, data interpretation, manuscript writing; MS, YI, SS \\u0026amp; KY: concept and design, data acquisition, data interpretation; MU: concept and design, data interpretation, supervision of the manuscript. All authors read and approved the final manuscript.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eFunding\\u003c/strong\\u003e No funding was received for conducting this study.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eData availability\\u0026nbsp;\\u003c/strong\\u003eData not available due to ethical restrictions.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eCode availability\\u003c/strong\\u003e Not applicable\\u003cstrong\\u003e\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eEthical approval\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe Medical Ethics Review Committee of Seirei Hamamatsu General Hospital approval no.3310 and Faculty of Pharmacy, Osaka Medical Pharmaceutical University approved this study, approval no.0088. All procedures were performed in accordance with the ethical standards of the Seirei Hamamatsu General Hospital and Osaka Medical Pharmaceutical University of Medicine Institutional Medical Ethics Review Committee and the 1964 Declaration of Helsinki and its later amendments. No prospective studies with human participants or animals were performed by any of the authors for this article.\\u003c/p\\u003e\\n\\u003cp\\u003eThis study retrospectively analysed 139 patients with cancer pain prescribed naldemedine for OIC at Seirei Hamamatsu General Hospital in Japan between November 2016 and June 2021. All study protocols were approved by the Medical Ethics Review Committee at Seirei Hamamatsu General Hospital (approval no. 3310) and the Faculty of Pharmacy at Osaka Medical Pharmaceutical University (approval no. 0088).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConsent to participate\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eGiven the retrospective nature of this work, the need to obtain informed consent was waived for the individual participants included in the study, in accordance with the standards of the Seirei Hamamatsu General Hospital and Osaka Medical Pharmaceutical University of Medicine Institutional Medical Ethics Review Committee.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConsent for publication\\u003c/strong\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eAll authors give their consent for this manuscript to be published in \\u003cem\\u003eSupportive Care in Cancer.\\u003c/em\\u003e\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\u003cli\\u003e\\u003cspan\\u003eALMouaalamy N (2021) Opioid-Induced Constipation in Advanced Cancer Patients. Cureus 13:e14386\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eFarmer AD, Drewes AM, Chiarioni G, De Giorgio R, O'Brien T, Morlion B, Tack J (2019) Pathophysiology and management of opioid-induced constipation: European expert consensus statement. United European Gastroenterol J 7:7\\u0026ndash;20\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eWiffen PJ, Wee B, Derry S, Bell RF, Moore RA (2017) Opioids for cancer pain - an overview of Cochrane reviews. Cochrane Database Syst Rev 7:CD012592\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eKrashin D, Murinova N, Jumelle P, Ballantyne J (2015) Opioid risk assessment in palliative medicine. Expert Opin Drug Saf 14:1023\\u0026ndash;1033\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eMercadante S (2011) Emerging drugs for cancer-related pain. Support Care Cancer 19:1887\\u0026ndash;1893\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eKatakami N, Harada T, Murata T, Shinozaki K, Tsutsumi M, Yokota T, Arai M, Tada Y, Narabayashi M, Boku N (2017) Randomized Phase III and Extension Studies of Naldemedine in Patients With Opioid-Induced Constipation and Cancer. J Clin Oncol 35:3859\\u0026ndash;3866\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eWebster LR, Nalamachu S, Morlion B, Reddy J, Baba Y, Yamada T, Arjona Ferreira JC (2018) Long-term use of naldemedine in the treatment of opioid-induced constipation in patients with chronic noncancer pain: a randomized, double-blind, placebo-controlled phase 3 study. Pain 159:987\\u0026ndash;994\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eHale M, Wild J, Reddy J, Yamada T, Arjona Ferreira JC (2017) Naldemedine versus placebo for opioid-induced constipation (COMPOSE-1 and COMPOSE-2): two multicentre, phase 3, double-blind, randomised, parallel-group trials. Lancet Gastroenterol Hepatol 2:555\\u0026ndash;564\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eHanson B, Siddique SM, Scarlett Y, Sultan S, American Gastroenterological Association Institute Clinical Guidelines Committee (2019) American Gastroenterological Association Institute Technical Review on the Medical Management of Opioid-Induced Constipation. Gastroenterology 156:229\\u0026ndash;253\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eWebster LR, Yamada T, Arjona Ferreira JC (2017) A Phase 2b, Randomized, Double-Blind Placebo-Controlled Study to Evaluate the Efficacy and Safety of Naldemedine for the Treatment of Opioid-Induced Constipation in Patients with Chronic Noncancer Pain. Pain Med 18:2350\\u0026ndash;2360\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eKubota R, Fukumura K, Wajima T (2018) Population Pharmacokinetics and Exposure-Response Relationships of Naldemedine. Pharm Res 35:225\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eOsaka I, Ishiki H, Yokota T, Tada Y, Sato H, Okamoto M, Satomi E (2019) Safety and efficacy of naldemedine in cancer patients with opioid-induced constipation: a pooled, subgroup analysis of two randomised controlled studies. ESMO Open 4:e000527\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003ePalsson OS, Whitehead WE, van Tilburg MA, Chang L, Chey W, Crowell MD, Keefer L, Lembo AJ, Parkman HP, Rao SS, Sperber A, Spiegel B, Tack J, Vanner S, Walker LS, Whorwell P, Yang Y (2016) Rome IV Diagnostic Questionnaires and Tables for Investigators and Clinicians. Gastroenterology. S0016-5085(16)00180-3.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eSimren M, Palsson OS, Whitehead WE (2017) Update on Rome IV Criteria for Colorectal Disorders: Implications for Clinical Practice. Curr Gastroenterol Rep 19:15\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003ePalsson OS, Whitehead W, T\\u0026ouml;rnblom H, Sperber AD, Simren M (2020) Prevalence of Rome IV Functional Bowel Disorders Among Adults in the United States, Canada, and the United Kingdom. Gastroenterology 158:1262\\u0026ndash;1273e3\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eNyrop KA, Deal AM, Shachar SS, Basch E, Reeve BB, Choi SK, Lee JT, Wood WA, Anders CK, Carey LA, Dees EC, Jolly TA, Reeder-Hayes KE, Kimmick GG, Karuturi MS, Reinbolt RE, Speca JC, Muss HB (2019)Patient-Reported Toxicities During Chemotherapy Regimens in Current Clinical Practice for Early Breast Cancer.Oncologist.24:762\\u0026ndash;771\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eFukumura K, Kawaguchi N, Ishibashi T, Kubota R, Tada Y, Ogura E (2020) Clinical Drug-Drug Interaction Studies to Evaluate the Effects of a P-Glycoprotein Inhibitor, CYP3A Inhibitors, and a CYP3A Inducer on the Pharmacokinetics of Naldemedine in Healthy Subjects. Clin Drug Investig 40:529\\u0026ndash;540\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003evan Eijk M, Boosman RJ, Schinkel AH, Huitema ADR, Beijnen JH (2019) Cytochrome P450 3A4, 3A5, and 2C8 expression in breast, prostate, lung, endometrial, and ovarian tumors: relevance for resistance to taxanes. Cancer Chemother Pharmacol 84:487\\u0026ndash;499\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eJibodh RA, Lagas JS, Nuijen B, Beijnen JH, Schellens JH (2013) Taxanes: old drugs, new oral formulations. Eur J Pharmacol 717:40\\u0026ndash;46\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eKovac AL (2003) Benefits and risks of newer treatments for chemotherapy-induced and postoperative nausea and vomiting. Drug Saf 26:227\\u0026ndash;259\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eCrockett SD, Greer KB, Heidelbaugh JJ, Falck-Ytter Y, Hanson BJ, Sultan S, American Gastroenterological Association Institute Clinical Guidelines Committee (2019) American Gastroenterological Association Institute Guideline on the Medical Management of Opioid-Induced Constipation. Gastroenterology 156:218\\u0026ndash;226\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eGarcia JM, Shamliyan TA (2018) Management of Opioid-Induced Constipation in Patients with Malignancy. Am J Med 131:1041\\u0026ndash;1051e3\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eM\\u0026uuml;ller-Lissner S, Bassotti G, Coffin B, Drewes AM, Breivik H, Eisenberg E, Emmanuel A, Laroche F, Meissner W, Morlion B (2017) Opioid-Induced Constipation and Bowel Dysfunction: A Clinical Guideline. Pain Med 18:1837\\u0026ndash;1863\\u003c/span\\u003e\\u003c/li\\u003e\\u003c/ol\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":true,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":false,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true},\"keywords\":\"opioid, constipation, taxane, naldemedine, cancer pain\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-1192993/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-1192993/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003ch2\\u003ePurpose\\u003c/h2\\u003e \\u003cp\\u003eTo identify predictors for the effectiveness of naldemedine.\\u003c/p\\u003e\\u003ch2\\u003eMethods\\u003c/h2\\u003e \\u003cp\\u003e Participants comprised 106 advanced cancer patients receiving pain treatment with opioids who were prescribed naldemedine for OIC at Seirei Hamamatsu General Hospital in Japan between November 2016 and June 2021.For the regression analysis of factors associated with OIC, variables were extracted manually from medical charts. The effectiveness of naldemedine was evaluated 3 days after administration, based on whether patients showed OIC. Presence of OIC was defined based on Rome IV diagnostic criteria. Multivariate logistic regression analysis was performed to identify predictors for naldemedine effectiveness. Values of P \\u0026lt; 0.05 (two-tailed) were considered significant.\\u003c/p\\u003e\\u003ch2\\u003eResults\\u003c/h2\\u003e \\u003cp\\u003eSignificant factors identified included chemotherapy with taxanes within 1 month of evaluation of naldemedine effectiveness (odds ratio [OR] = 0.063, 95% confidence interval [CI] = 0.007\\u0026ndash;0.568; P = 0.014), and addition of or switching to naldemedine due to insufficient prior laxatives (OR = 0.352, 95%CI = 0.129\\u0026ndash;0.966; P = 0.043).\\u003c/p\\u003e\\u003ch2\\u003eConclusion\\u003c/h2\\u003e \\u003cp\\u003eNo chemotherapy that included taxanes within 1 month of evaluation of naldemedine effectiveness and no addition of or switching to naldemedine due to insufficient prior laxatives were identified as predictors for effectiveness of naldemedine in patients with cancer pain.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Predictors for Effectiveness of Naldemedine in Patients with Cancer Pain: A Retrospective, Single-Institution Analysis\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2022-01-18 18:08:26\",\"doi\":\"10.21203/rs.3.rs-1192993/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"2cf8baea-ad8d-4801-9beb-41066f006f84\",\"owner\":[],\"postedDate\":\"January 18th, 2022\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"posted\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2022-01-24T21:19:00+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2022-01-18 18:08:26\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-1192993\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-1192993\",\"identity\":\"rs-1192993\",\"version\":[\"v1\"]},\"buildId\":\"uwybb5PU2iWlRI8EIam5Y\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}