Sedation is associated with higher polyp and adenoma detection rates during colonoscopy: a retrospective cohort study

Sedation is associated with higher polyp and adenoma detection rates during colonoscopy: a retrospective cohort study | 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 Sedation is associated with higher polyp and adenoma detection rates during colonoscopy: a retrospective cohort study Chenghu Xu, Dehua Tang, Ying Xie, Muhan Ni, Min Chen, Yonghua Shen, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1446898/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 Background and aims: Currently sedation is a common practice in colonoscopy to reduce pain of patients and improve the operator satisfaction, while its impact on examination quality, especially polyp detection rate (PDR) and adenoma detection rate (ADR) is still controversial. Thus, we aimed to investigate the association of sedation with PDR/ADR. Methods: Consecutive patients receiving colonoscopy between January 2017 to January 2020 at the Nanjing Drum Tower Hospital were collected. Univariate and multivariate logistic regression models were performed to investigate the association between sedation and PDR/ADR. Subgroup analysis and propensity score matching analysis (PSM), as sensitivity analysis, were performed to validate the independent effect. Results: The PDR and ADR were significantly higher in cases with sedation (PDR: 55.4% vs 46.6%, OR: 1.42, 95% CI: 1.32~1.53, P < 0.001; ADR: 37.3% vs 30.2%, OR: 1.37, 95% CI: 1.27~1.49, P < 0.001). Multivariate analysis showed that the sedation was an independent factor associated with PDR (OR: 1.54, 95% CI: 1.40~1.69, P < 0.001) and ADR (OR: 1.45, 95% CI: 1.32~1.60, P 0.05) and PSM analysis (PDR: 56.1% vs 46.4%, OR: 1.48, 95% CI: 1.35~1.62, P < 0.001; ADR: 37.4% vs 30.0%, OR: 1.40, 95% CI: 1.27~1.54, P < 0.001). Conclusion: Sedation was associated with a higher polyp and adenoma detection rates during colonoscopy, which can promote the quality of colonoscopy. Sedation Colonoscopy Polyp detection rate Adenoma detection rate Figures Figure 1 Figure 2 Figure 3 1. Introduction Colorectal cancer (CRC) is the third most common type of cancer and the second most common cause of cancer-associated mortality over the world 1, 2 . The prognosis of colorectal cancer remains poor in advanced-stage cancer, with the overall 5-year survival rate being less than 20%, while the early-stage cancer is approximately 90%. As the most effective measures to screening CRC, colonoscopy can detect high-risk lesions of colon cancer and significantly reduce the occurrence of CRC to improving the prognosis of colon cancer, and its inspection quality can be measured by some quality indicators 3 . The polyp detection rate (PDR) and adenoma detection rate (ADR) are established as quality indicators, and an increased ADR have been reported to be related to a reduced risk of interval CRC and mortality 4 . Sedation has become a common practice in endoscopic operation over the past decades 5–7 . Several previous studies have shown that sedation could reduce pain of patients and improve the operator satisfaction, thus shortened the time of colonoscopy. However controversy surrounding the effect of sedation on quality indicator of colonoscopy such as PDR and ADR had been reported in different country, yet little is known about the impact of sedation when controlling the other factors with a large-scale cohort. Although some previous studies have reported that sedation has little effect on the PDR and ADR of colonoscopy[ 5 , 8 , 17 , 18 ], some studies recently demonstrating the positive effects of sedation on colonoscopy[ 6 , 7 , 19 – 22 ]. Therefore, more studies are needed to evaluate whether the sedation is beneficial to ADR and PDR. The aim of this study was to investigate the impact of sedation on polyp and adenoma detection rates during colonoscopy. The logistic regression model, subgroup analyses and PSM were used to evaluate and validate the independent effect. 2. Methods Study design and patients This retrospective cohort study collected consecutive patients aged 45–85 years who underwent colonoscopy from January 2017 to January 2020 in Nanjing Drum Tower Hospital (Nanjing, China). Exclusion criteria were as follows : 1) history of colonic resection or CRC; 2) inflammatory bowel diseases and polyposis syndromes; 3) family history of CRC; 4) surveillance; urgent or intent therapeutic colonoscopy; 5) do not reach the cecum or terminal ileum; 6) invalid withdrawal time and bowel preparation quality. This study has been approved by the Ethics Committee of Nanjing Drum Tower Hospital (DTH-IRB- 2021-483-01). As a retrospective study, informed content is not required from participants. Variables and measures The primary outcome was the PDR and ADR for colonoscopies. PDR and ADR were defined as the proportion of colonoscopies in which at least one polyp and adenoma was detected, respectively 8 . Considering the situation that certain polyps need another procedure to remove it, biopsy was unnecessary. Among those colonoscopies without polyps’ specimens and marked by endoscopist need to another procedure and the lesions being confirmed as adenoma in 180 days, previous polyp would be treated as an adenoma. All the adenoma tissues were examined histopathologically, reviewed, and confirmed by the pathologists. Advanced adenoma were define as adenoma of at least 10 mm in size, with more than 25% villous features and/or with high-grade dysplasia 9 . The use of sedation and endoscopic manifestation were recorded as binary variables (yes/no). The withdrawal time as the time from the cecum identification to the time across the anus 10 , was calculated by the program which can recognize the picture of cecum using the machine learning and the last captured picture and acquire the time from the documents. The Boston bowel preparation scale (BBPS) was used to assess the quality of bowel preparation and quantified by endoscopists during operation 11 . Endoscopist annual volume was determined from the number of colonoscopies performed by endoscopists annually in recent 3 years. Endoscopist experience was defined as years since completing colonoscopy independently. The complaint and diagnosis were collected from medical history. In subgroups and interactions analyses, age categorized as 45–49, 50–59, 60–69, 70–79, 80–95 years, annual volume of colonoscopy categorized as 700 per year and endoscopist experience categorized as 7 years. Statistical Analysis Continuous variables with normal distribution were expressed as the mean ± standard deviation (SD). Categorized variables were summarized as counts and proportions. Continuous variables were compared between groups using the Student’s t-test (normal distribution). Continuous data with non-normal distribution presented as medians and interquartile ranges and compared with. Other categorical variables were compared between groups using the chi-squared test. The univariate logistic regression model was used to investigate the effect size of factors for ADR and PDR and the results were presented by odds ratio (OR) and 95% confidence interval (CI). Multivariate logistic regression was further performed to evaluate the association between sedation and ADR and PDR in two models adjusting for selected confounding variables. Confounders adjusted in the model I was selected based on their associations with the outcomes of a change in effect estimate of more than 10%. Model II adjusted all potential confounders. Subgroup and interaction analysis were performed to ensure the stability of the result for sensitivity analysis. Propensity score matching (PSM) analysis was performed as sensitivity analysis in a 1:1 ratio to balance the baseline between groups using a greedy nearest neighbor-matching technique. A caliper width of 0.05 of the SD for the logit of the PSM was used for the developed PSM. On matching, 7 of baseline covariates that could possibly influence the detection rate were used, age, sex, year of colonoscopies, reason for colonoscopy, endoscopist volume, endoscopist experience and endoscopist sex. These covariates were acknowledged risk factors of colorectal cancers according to previous studies or influencing factors of quality of colonoscopy. All reported P values were two-tailed, and a confidence interval (CI) of 95% was used throughout. A P value < 0.05 was considered statistically significant. All the analyses were using the statistical software SPSS version 22.0 (IBM Corporation, Somers, NY). 3. Results 3.1 Baseline Characteristics Overall, we identified 20319 ambulatory patients who underwent colonoscopy between January 1, 2017, and January 31, 2020. 6840 cases were excluded according to exclusion criterion. A total of 13479 patients were finally included for final analysis in our study, of which 9682 (71.8%) patients received sedation (Fig. 1) . Table 1 showed the characteristics of the 2 groups of patients and the comparison results. The mean age (SD) of patients in the no-sedation group was 60.2 (9.8) years, older than the sedation group which was 58.7 (8.7) years ( P < 0.001). There was a higher proportion of male in the no-sedation group than sedation group (55.1% vs 50.0%, P < 0.001). 98.8% no-sedation colonoscopies were manipulated in the afternoon. The average withdrawal time was shorter in sedation group ( P < 0.001). The reasons for colonoscopy, 77.6% were diagnosis, 19.5% was followed by screening in no-sedation group, and compared with sedation group, 67.2% and 9.6% respectively. The group of sedation colonoscopy have a greater rate of treatment towards polyp. 3.2 Outcomes Both PDR and ADR were higher in group with sedation (PDR: 55.4% vs 46.6%, P < 0.001; ADR: 37.3% vs 30.2%, P < 0.001). (Table 2) 3.3 The Effect of Sedation and Interaction Effects between Sedation and Other Factors To explore the effect of the factors on the PDR and ADR of the colonoscopy, univariate and multivariate logistic regression analysis were performed. In univariate logistic regression analysis, for patient-level factor, we found that the female patients(OR = 0.48, 95% CI: 0.45–0.52) were negatively associated, whereas age (OR = 1.03, 95% CI: 1.03–1.04), Sedation(OR = 1.42, 95% CI: 1.32–1.53), Withdrawal time (OR = 1.18, 95% CI: 1.16–1.19) were positively associated with PDR. Similarly, the female patients(OR = 0.54, 95% CI: 0.51–0.58) were negatively associated, whereas age (OR = 1.03, 95% CI: 1.03–1.04), sedation(OR = 1.37, 95% CI: 1.27–1.49), withdrawal time (OR = 1.14, 95% CI: 1.13–1.15) were positively associated with ADR. (Tables 3,5) . Furthermore, for multivariate analyses, we had constructed regression analysis models including crude, Model I included the factors were statistically significant and Mode II included all factors we collected. After adjusting for sex, age, time of colonoscopy, withdrawal time and experience of endoscopist in Model I and all potential confounders in Model II, the association between sedation and ADR and PDR were still stable in both models[Model I: PDR (OR: 1.57, 95% CI: 1.44 ~ 1.72, P < 0.001) and ADR (OR: 1.48, 95% CI: 1.35 ~ 1.64, P < 0.001) ;Model II: PDR (OR: 1.54, 95% CI: 1.40 ~ 1.69, P < 0.001) and ADR (OR: 1.45, 95% CI: 1.32 ~ 1.60, P < 0.001)] (Tables 4, 6) . 3.4 Subgroup and sensitivity analysis In the subgroup analysis, there was no apparent interaction between any subgroup (Fig. 2 and Fig. 3). After PS matching, the baseline was well balanced between groups except for withdrawal time which was higher in the sedation group (8.83 vs 8.78 minutes, P = 0.042). The PDR and ADR were higher in the sedation group while withdrawal time was longer than in no-sedation group (PDR: 56.1% vs 46.4%, OR: 1.48, 95% CI: 1.35 ~ 1.62, P < 0.001; ADR: 37.4% vs 30.0%, OR: 1.40, 95% CI: 1.27 ~ 1.54, P < 0.001). Comparison between sedation and No-sedation groups after PSM showed that no significant difference was found on detection rate of advanced adenoma (8.2% vs 7.4%, P = 0.224). (Table 8) . 4. Discussion In this retrospective cohort study, we comprehensively analyzed the impact of sedation on PDR and ADR. Our results revealed that after adjusting potential confounding factors, the colonoscopy with sedation was significantly associated with higher PDR and ADR. After PSM, the results were still stable, which indicated that sedation was an independent factor associated with a higher PDR and ADR. To our knowledge, this is the largest study to date specifically evaluating the effects of sedation in PDR and ADR among outpatient colonoscopies. In previous studies, its’ reported that sedation can improve patient comfort and satisfaction 12–16 . However, the overall quality indicators, the findings are controversial, both in terms of demonstrating an increase and in terms of demonstrating similarity. Bannert 5 reported that ADR and PDR are unaffected by sedation, but without registered level of sedation and type of sedation remain in this study. Nakshabendi 17 et al. recognized a propofol sedation can lead to detection of more advanced polyps but did not find a difference in ADR in the use of sedation. Krigel 18 et al. found no association between Anesthesia assistance and ADR among trainees. Zhao 19 et al. found no help on ADR or PDR of sedation, but multivariate analysis for evaluating confounding factors were not performed. Huang and Zhang 7, 20 et al. found that sedation was a favorable factor to improve ADRs, but the history of colorectal disease didn’t been investigated. Khan 21 et al. also found that sedation as opposed to no sedation was significantly associated with a higher ADR, but only 179 of 24,795 patients underwent unsedated colonoscopies, which was too small to draw robust conclusion. Compared with previous studies, our study had a larger sample size with a screened population and considerable factors such as endoscopist gender and experience of endoscopist were considered as confounding factors to adjust the effect of sedation on PDR and ADR, which makes our outcome more reliable and convinced. However, the relationship between sedation and withdrawal time has rarely been studied. Previous studies have suggested that withdrawal time increases the detection of colonic lesions and thus improves PDR and ADR 4, 22–25 . Although with advances in computer and information technology and we can get the of cecal identification from machine learning, the time of biopsies and other operations are still not counted 26 . This makes it difficult to explore the relationship between withdrawal time and sedation, but for specific colonoscopies, such as screening-only colonoscopies it is comparable. we need to explore fully validate the relationship between withdrawal time and sedation in the future. Limitations: Firstly, this study has inherent limitations associated with retrospective data collection, and some potential confounders such as BMI, smoking status, alcohol intake and medication use may be neglected in the analysis. Thus, further prospective study was needed for qualified data collection and management. Secondly, biopsy time and polyp removal time were not precisely calculated and subtracted which leading a redundant withdrawal time. Although we performed subgroup analysis according to the operation in the examination, analysis of withdrawal time for PDR, ADR with subgroups of sedation remains to be confirmed by larger random controlled trials or more refined retrospective studies. Thirdly, limitation of our study is that our results are limited to a single institution. Therefore, a prospective multi-center study was essential to further validate our results. 5. Conclusion In conclusion, compared with colonoscopy without sedation, colonoscopy with sedation has a positive effect on PDR and ADR. When controlling for other confounding factors, Sedation was an independent predictor of higher PDR and ADR. From a quality improvement perspective, choosing the sedation procedures in colonoscopies is favorable. Declarations Funding This work is supported by the Natural Science Foundation of Jiangsu Province (SBK2019022491 & BK20180117), General Project of Nanjing Medical Science and Technology Development Project (YKK17077), Nanjing Science and Technology Development Plan Project (201715023), Nanjing Medical Science and Technology Development Key Project (ZKX18022), and Nanjing Science and Technology Project (201911038). Compliance with Ethical Standards Conflict of interest All authors declare that they have no conflicts of interest and nothing to declare. Ethics approval This analysis was approved by the Ethics Committee of Nanjing Drum Tower Hospital (DTH-IRB- 2021-483-01) Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author or reasonable request. Authors contributions Study concept and design: Xiaoping Zou, Shu Zhang, Ying Lv ; acquisition of data: all authors; analysis and interpretation of data: Chenghu Xu, Dehua Tang, Ying Xie, Min Chen, Yonghua Shen, Xiaotan Dou, Lin Zhou, Guifang Xu; the manuscript: Chenghu Xu, Dehua Tang, Ying Xie; critical revision of the manuscript for important intellectual content: all authors; statistical analysis: Chenghu Xu, Dehua Tang, Muhan Ni. Consent for publication Not applicable Acknowledgement We acknowledge and appreciate our colleagues for their helpful comments on this paper. References Feng RM, Zong YN, Cao SM, et al. Current cancer situation in China: good or bad news from the 2018 Global Cancer Statistics? Cancer Commun (Lond) 2019; 39: 22. 2019/04/30 . DOI: 10.1186/s40880-019-0368-6. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68: 394–424. 2018/09/13. DOI: 10.3322/caac.21492. Kaminski MF, Regula J, Kraszewska E, et al. Quality indicators for colonoscopy and the risk of interval cancer. N Engl J Med 2010; 362: 1795–1803. 2010/05/14. DOI: 10.1056/NEJMoa0907667. Kaminski MF, Wieszczy P, Rupinski M, et al. Increased Rate of Adenoma Detection Associates With Reduced Risk of Colorectal Cancer and Death. Gastroenterology 2017; 153: 98–105. 2017/04/22. 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Supplementary Files Table1.jpg Table2.jpg Table3.jpg Table4.jpg Table5.jpg Table6.jpg Table7.jpg Table8.jpg Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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12:14:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1446898/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1446898/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":19291986,"identity":"165e67e3-be26-4935-9b29-421046fdc02e","added_by":"auto","created_at":"2022-03-16 15:26:18","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":520537,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-1446898/v1/5eda8e58416945d2488f1678.png"},{"id":19292448,"identity":"6584ed1c-9521-47de-b013-966ccd918600","added_by":"auto","created_at":"2022-03-16 15:29:18","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1083763,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-1446898/v1/7e2573923f0d8335fc6cd8e2.png"},{"id":19292450,"identity":"933ae23d-f75f-4513-ae16-e49c982c9668","added_by":"auto","created_at":"2022-03-16 15:29:18","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1074732,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-1446898/v1/769ed8c863028034729d7e57.png"},{"id":19319723,"identity":"f4c3f152-1b01-4650-b314-422f361fc8d1","added_by":"auto","created_at":"2022-03-17 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15:32:19","extension":"jpg","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":147945,"visible":true,"origin":"","legend":"","description":"","filename":"Table4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1446898/v1/bcb131202aa7ae22b205e0e4.jpg"},{"id":19292447,"identity":"3a77a4c9-fcc9-4723-a9ba-2206ac1dfa20","added_by":"auto","created_at":"2022-03-16 15:29:18","extension":"jpg","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":172669,"visible":true,"origin":"","legend":"","description":"","filename":"Table5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1446898/v1/d28dd0144c253033b5089e44.jpg"},{"id":19292452,"identity":"aa012e8b-3998-40c8-bd2f-4c67ee3990dd","added_by":"auto","created_at":"2022-03-16 15:29:19","extension":"jpg","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":147532,"visible":true,"origin":"","legend":"","description":"","filename":"Table6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1446898/v1/de140600cea914fcbbfd2d84.jpg"},{"id":19293009,"identity":"ae15a745-be05-4eab-a092-92ed64ae935e","added_by":"auto","created_at":"2022-03-16 15:32:18","extension":"jpg","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":296590,"visible":true,"origin":"","legend":"","description":"","filename":"Table7.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1446898/v1/fc02774e45f814d1db66f2cd.jpg"},{"id":19291993,"identity":"62aede39-ef66-4aaf-9e52-ff95a471212d","added_by":"auto","created_at":"2022-03-16 15:26:18","extension":"jpg","order_by":7,"title":"","display":"","copyAsset":false,"role":"supplement","size":139315,"visible":true,"origin":"","legend":"","description":"","filename":"Table8.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1446898/v1/b2a45605a7bf2da78dd22ab1.jpg"}],"financialInterests":"No competing interests reported.","formattedTitle":"Sedation is associated with higher polyp and adenoma detection rates during colonoscopy: a retrospective cohort study","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eColorectal cancer (CRC) is the third most common type of cancer and the second most common cause of cancer-associated mortality over the world\u003csup\u003e1, 2\u003c/sup\u003e. The prognosis of colorectal cancer remains poor in advanced-stage cancer, with the overall 5-year survival rate being less than 20%, while the early-stage cancer is approximately 90%. As the most effective measures to screening CRC, colonoscopy can detect high-risk lesions of colon cancer and significantly reduce the occurrence of CRC to improving the prognosis of colon cancer, and its inspection quality can be measured by some quality indicators\u003csup\u003e3\u003c/sup\u003e. The polyp detection rate (PDR) and adenoma detection rate (ADR) are established as quality indicators, and an increased ADR have been reported to be related to a reduced risk of interval CRC and mortality\u003csup\u003e4\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eSedation has become a common practice in endoscopic operation over the past decades\u003csup\u003e5\u0026ndash;7\u003c/sup\u003e. Several previous studies have shown that sedation could reduce pain of patients and improve the operator satisfaction, thus shortened the time of colonoscopy. However controversy surrounding the effect of sedation on quality indicator of colonoscopy such as PDR and ADR had been reported in different country, yet little is known about the impact of sedation when controlling the other factors with a large-scale cohort. Although some previous studies have reported that sedation has little effect on the PDR and ADR of colonoscopy[\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e], some studies recently demonstrating the positive effects of sedation on colonoscopy[\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e]. Therefore, more studies are needed to evaluate whether the sedation is beneficial to ADR and PDR.\u003c/p\u003e\n\u003cp\u003eThe aim of this study was to investigate the impact of sedation on polyp and adenoma detection rates during colonoscopy. The logistic regression model, subgroup analyses and PSM were used to evaluate and validate the independent effect.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy design and patients\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective cohort study collected consecutive patients aged 45\u0026ndash;85 years who underwent colonoscopy from January 2017 to January 2020 in Nanjing Drum Tower Hospital (Nanjing, China). \u003cstrong\u003eExclusion criteria were as follows\u003c/strong\u003e: 1) history of colonic resection or CRC; 2) inflammatory bowel diseases and polyposis syndromes; 3) family history of CRC; 4) surveillance; urgent or intent therapeutic colonoscopy; 5) do not reach the cecum or terminal ileum; 6) invalid withdrawal time and bowel preparation quality. This study has been approved by the Ethics Committee of Nanjing Drum Tower Hospital (DTH-IRB- 2021-483-01). As a retrospective study, informed content is not required from participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eVariables and measures\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe primary outcome was the PDR and ADR for colonoscopies. PDR and ADR were defined as the proportion of colonoscopies in which at least one polyp and adenoma was detected, respectively\u003csup\u003e8\u003c/sup\u003e. Considering the situation that certain polyps need another procedure to remove it, biopsy was unnecessary. Among those colonoscopies without polyps\u0026rsquo; specimens and marked by endoscopist need to another procedure and the lesions being confirmed as adenoma in 180 days, previous polyp would be treated as an adenoma. All the adenoma tissues were examined histopathologically, reviewed, and confirmed by the pathologists. Advanced adenoma were define as adenoma of at least 10 mm in size, with more than 25% villous features and/or with high-grade dysplasia\u003csup\u003e9\u003c/sup\u003e. The use of sedation and endoscopic manifestation were recorded as binary variables (yes/no). The withdrawal time as the time from the cecum identification to the time across the anus\u003csup\u003e10\u003c/sup\u003e, was calculated by the program which can recognize the picture of cecum using the machine learning and the last captured picture and acquire the time from the documents. The Boston bowel preparation scale (BBPS) was used to assess the quality of bowel preparation and quantified by endoscopists during operation \u003csup\u003e11\u003c/sup\u003e. Endoscopist annual volume was determined from the number of colonoscopies performed by endoscopists annually in recent 3 years. Endoscopist experience was defined as years since completing colonoscopy independently. The complaint and diagnosis were collected from medical history. In subgroups and interactions analyses, age categorized as 45\u0026ndash;49, 50\u0026ndash;59, 60\u0026ndash;69, 70\u0026ndash;79, 80\u0026ndash;95 years, annual volume of colonoscopy categorized as \u0026lt;\u0026thinsp;300, 300\u0026ndash;700, \u0026gt;\u0026thinsp;700 per year and endoscopist experience categorized as \u0026lt;\u0026thinsp;3, 3\u0026ndash;7, \u0026gt;\u0026thinsp;7 years.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eContinuous variables with normal distribution were expressed as the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD). Categorized variables were summarized as counts and proportions. Continuous variables were compared between groups using the Student\u0026rsquo;s t-test (normal distribution). Continuous data with non-normal distribution presented as medians and interquartile ranges and compared with. Other categorical variables were compared between groups using the chi-squared test. The univariate logistic regression model was used to investigate the effect size of factors for ADR and PDR and the results were presented by odds ratio (OR) and 95% confidence interval (CI). Multivariate logistic regression was further performed to evaluate the association between sedation and ADR and PDR in two models adjusting for selected confounding variables. Confounders adjusted in the model I was selected based on their associations with the outcomes of a change in effect estimate of more than 10%. Model II adjusted all potential confounders. Subgroup and interaction analysis were performed to ensure the stability of the result for sensitivity analysis. Propensity score matching (PSM) analysis was performed as sensitivity analysis in a 1:1 ratio to balance the baseline between groups using a greedy nearest neighbor-matching technique. A caliper width of 0.05 of the SD for the logit of the PSM was used for the developed PSM. On matching, 7 of baseline covariates that could possibly influence the detection rate were used, age, sex, year of colonoscopies, reason for colonoscopy, endoscopist volume, endoscopist experience and endoscopist sex. These covariates were acknowledged risk factors of colorectal cancers according to previous studies or influencing factors of quality of colonoscopy. All reported \u003cem\u003eP\u003c/em\u003e values were two-tailed, and a confidence interval (CI) of 95% was used throughout.\u003c/p\u003e\n\u003cp\u003eA \u003cem\u003eP\u003c/em\u003e value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. All the analyses were using the statistical software SPSS version 22.0 (IBM Corporation, Somers, NY).\u003c/p\u003e"},{"header":"3. Results","content":"\u003cp\u003e\u003cstrong\u003e3.1 Baseline Characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOverall, we identified 20319 ambulatory patients who underwent colonoscopy between January 1, 2017, and January 31, 2020. 6840 cases were excluded according to exclusion criterion. A total of 13479 patients were finally included for final analysis in our study, of which 9682 (71.8%) patients received sedation \u003cstrong\u003e(Fig. 1)\u003c/strong\u003e. \u003cstrong\u003eTable 1\u003c/strong\u003e showed the characteristics of the 2 groups of patients and the comparison results. The mean age (SD) of patients in the no-sedation group was 60.2 (9.8) years, older than the sedation group which was 58.7 (8.7) years (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). There was a higher proportion of male in the no-sedation group than sedation group (55.1% vs 50.0%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). 98.8% no-sedation colonoscopies were manipulated in the afternoon. The average withdrawal time was shorter in sedation group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The reasons for colonoscopy, 77.6% were diagnosis, 19.5% was followed by screening in no-sedation group, and compared with sedation group, 67.2% and 9.6% respectively. The group of sedation colonoscopy have a greater rate of treatment towards polyp.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.2 Outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBoth PDR and ADR were higher in group with sedation (PDR: 55.4% vs 46.6%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; ADR: 37.3% vs 30.2%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). \u003cstrong\u003e(Table 2)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.3 The Effect of Sedation and Interaction Effects between Sedation and Other Factors\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo explore the effect of the factors on the PDR and ADR of the colonoscopy, univariate and multivariate logistic regression analysis were performed. In univariate logistic regression analysis, for patient-level factor, we found that the female patients(OR\u0026thinsp;=\u0026thinsp;0.48, 95% CI: 0.45\u0026ndash;0.52) were negatively associated, whereas age (OR\u0026thinsp;=\u0026thinsp;1.03, 95% CI: 1.03\u0026ndash;1.04), Sedation(OR\u0026thinsp;=\u0026thinsp;1.42, 95% CI: 1.32\u0026ndash;1.53), Withdrawal time (OR\u0026thinsp;=\u0026thinsp;1.18, 95% CI: 1.16\u0026ndash;1.19) were positively associated with PDR. Similarly, the female patients(OR\u0026thinsp;=\u0026thinsp;0.54, 95% CI: 0.51\u0026ndash;0.58) were negatively associated, whereas age (OR\u0026thinsp;=\u0026thinsp;1.03, 95% CI: 1.03\u0026ndash;1.04), sedation(OR\u0026thinsp;=\u0026thinsp;1.37, 95% CI: 1.27\u0026ndash;1.49), withdrawal time (OR\u0026thinsp;=\u0026thinsp;1.14, 95% CI: 1.13\u0026ndash;1.15) were positively associated with ADR. \u003cstrong\u003e(Tables 3,5)\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003eFurthermore, for multivariate analyses, we had constructed regression analysis models including crude, Model I included the factors were statistically significant and Mode II included all factors we collected. After adjusting for sex, age, time of colonoscopy, withdrawal time and experience of endoscopist in Model I and all potential confounders in Model II, the association between sedation and ADR and PDR were still stable in both models[Model I: PDR (OR: 1.57, 95% CI: 1.44\u0026thinsp;~\u0026thinsp;1.72, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and ADR (OR: 1.48, 95% CI: 1.35\u0026thinsp;~\u0026thinsp;1.64, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) ;Model II: PDR (OR: 1.54, 95% CI: 1.40\u0026thinsp;~\u0026thinsp;1.69, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and ADR (OR: 1.45, 95% CI: 1.32\u0026thinsp;~\u0026thinsp;1.60, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001)]\u003cstrong\u003e(Tables 4, 6)\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.4 Subgroup and sensitivity analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn the subgroup analysis, there was no apparent interaction between any subgroup \u003cstrong\u003e(Fig. 2 and Fig. 3).\u003c/strong\u003e After PS matching, the baseline was well balanced between groups except for withdrawal time which was higher in the sedation group (8.83 vs 8.78 minutes, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.042). The PDR and ADR were higher in the sedation group while withdrawal time was longer than in no-sedation group (PDR: 56.1% vs 46.4%, OR: 1.48, 95% CI: 1.35\u0026thinsp;~\u0026thinsp;1.62, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001; ADR: 37.4% vs 30.0%, OR: 1.40, 95% CI: 1.27\u0026thinsp;~\u0026thinsp;1.54, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Comparison between sedation and No-sedation groups after PSM showed that no significant difference was found on detection rate of advanced adenoma (8.2% vs 7.4%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.224). \u003cstrong\u003e(Table 8)\u003c/strong\u003e.\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eIn this retrospective cohort study, we comprehensively analyzed the impact of sedation on PDR and ADR. Our results revealed that after adjusting potential confounding factors, the colonoscopy with sedation was significantly associated with higher PDR and ADR. After PSM, the results were still stable, which indicated that sedation was an independent factor associated with a higher PDR and ADR.\u003c/p\u003e\n\u003cp\u003eTo our knowledge, this is the largest study to date specifically evaluating the effects of sedation in PDR and ADR among outpatient colonoscopies. In previous studies, its\u0026rsquo; reported that sedation can improve patient comfort and satisfaction\u003csup\u003e12\u0026ndash;16\u003c/sup\u003e. However, the overall quality indicators, the findings are controversial, both in terms of demonstrating an increase and in terms of demonstrating similarity. Bannert\u003csup\u003e5\u003c/sup\u003e reported that ADR and PDR are unaffected by sedation, but without registered level of sedation and type of sedation remain in this study. Nakshabendi\u003csup\u003e17\u003c/sup\u003e et al. recognized a propofol sedation can lead to detection of more advanced polyps but did not find a difference in ADR in the use of sedation. Krigel\u003csup\u003e18\u003c/sup\u003e et al. found no association between Anesthesia assistance and ADR among trainees. Zhao\u003csup\u003e19\u003c/sup\u003e et al. found no help on ADR or PDR of sedation, but multivariate analysis for evaluating confounding factors were not performed. Huang and Zhang\u003csup\u003e7, 20\u003c/sup\u003e et al. found that sedation was a favorable factor to improve ADRs, but the history of colorectal disease didn\u0026rsquo;t been investigated. Khan\u003csup\u003e21\u003c/sup\u003eet al. also found that sedation as opposed to no sedation was significantly associated with a higher ADR, but only 179 of 24,795 patients underwent unsedated colonoscopies, which was too small to draw robust conclusion. Compared with previous studies, our study had a larger sample size with a screened population and considerable factors such as endoscopist gender and experience of endoscopist were considered as confounding factors to adjust the effect of sedation on PDR and ADR, which makes our outcome more reliable and convinced.\u003c/p\u003e\n\u003cp\u003eHowever, the relationship between sedation and withdrawal time has rarely been studied. Previous studies have suggested that withdrawal time increases the detection of colonic lesions and thus improves PDR and ADR\u003csup\u003e4, 22\u0026ndash;25\u003c/sup\u003e. Although with advances in computer and information technology and we can get the of cecal identification from machine learning, the time of biopsies and other operations are still not counted\u003csup\u003e26\u003c/sup\u003e. This makes it difficult to explore the relationship between withdrawal time and sedation, but for specific colonoscopies, such as screening-only colonoscopies it is comparable. we need to explore fully validate the relationship between withdrawal time and sedation in the future.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eLimitations:\u003c/strong\u003e Firstly, this study has inherent limitations associated with retrospective data collection, and some potential confounders such as BMI, smoking status, alcohol intake and medication use may be neglected in the analysis. Thus, further prospective study was needed for qualified data collection and management. Secondly, biopsy time and polyp removal time were not precisely calculated and subtracted which leading a redundant withdrawal time. Although we performed subgroup analysis according to the operation in the examination, analysis of withdrawal time for PDR, ADR with subgroups of sedation remains to be confirmed by larger random controlled trials or more refined retrospective studies. Thirdly, limitation of our study is that our results are limited to a single institution. Therefore, a prospective multi-center study was essential to further validate our results.\u0026nbsp;\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eIn conclusion, compared with colonoscopy without sedation, colonoscopy with sedation has a positive effect on PDR and ADR. When controlling for other confounding factors, Sedation was an independent predictor of higher PDR and ADR. From a quality improvement perspective, choosing the sedation procedures in colonoscopies is favorable.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work is supported by the Natural Science Foundation of Jiangsu Province (SBK2019022491 \u0026amp; BK20180117), General Project of Nanjing Medical Science and Technology Development Project (YKK17077), Nanjing Science and Technology Development Plan Project (201715023), Nanjing Medical Science and Technology Development Key Project (ZKX18022), and Nanjing Science and Technology Project (201911038). \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompliance with Ethical Standards\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e All authors declare that they have no conflicts of interest and nothing to declare. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e This analysis was approved by the Ethics Committee of Nanjing Drum Tower Hospital (DTH-IRB- 2021-483-01) \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author or reasonable request. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStudy concept and design: Xiaoping Zou, Shu Zhang, Ying Lv ; acquisition of data: all authors; analysis and interpretation of data: Chenghu Xu, Dehua Tang, Ying Xie, Min Chen, Yonghua Shen, Xiaotan Dou, Lin Zhou, Guifang Xu; the manuscript: Chenghu Xu, Dehua Tang, Ying Xie; critical revision of the manuscript for important intellectual content: all authors; statistical analysis: Chenghu Xu, Dehua Tang, Muhan Ni. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe acknowledge and appreciate our colleagues for their helpful comments on this paper.\u003cstrong\u003e \u003c/strong\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003e\u003cspan\u003eFeng RM, Zong YN, Cao SM, et al. 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Medicine (Baltimore) 2020; 99: e23685.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eAhmad A and Thomas-Gibson S. Optimum colonoscopy withdrawal: Is time everything? Gastrointest Endosc 2019; 89: 531\u0026ndash;532. DOI: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.gie.2018.10.045\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eSimmons DT, Harewood GC, Baron TH, et al. Impact of endoscopist withdrawal speed on polyp yield: implications for optimal colonoscopy withdrawal time. Aliment Pharmacol Ther 2006; 24: 965\u0026ndash;971. 2006/09/05. DOI: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/j.1365-2036.2006.03080.x\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eVavricka SR, Sulz MC, Degen L, et al. 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DOI: 10.1055/s-0035-1569674.\u003c/span\u003e\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 8 are available in the Supplemental Files section.\u003c/p\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":"[email protected]","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":"Sedation, Colonoscopy, Polyp detection rate, Adenoma detection rate","lastPublishedDoi":"10.21203/rs.3.rs-1446898/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1446898/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground and aims:\u003c/strong\u003e Currently sedation is a common practice in colonoscopy to reduce pain of patients and improve the operator satisfaction, while its impact on examination quality, especially polyp detection rate (PDR) and adenoma detection rate (ADR) is still controversial. Thus, we aimed to investigate the association of sedation with PDR/ADR. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eConsecutive patients receiving colonoscopy between January 2017 to January 2020 at the Nanjing Drum Tower Hospital were collected. Univariate and multivariate logistic regression models were performed to investigate the association between sedation and PDR/ADR. Subgroup analysis and propensity score matching analysis (PSM), as sensitivity analysis, were performed to validate the independent effect. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e The PDR and ADR were significantly higher in cases with sedation (PDR: 55.4% vs 46.6%, OR: 1.42, 95% CI: 1.32~1.53, \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001; ADR: 37.3% vs 30.2%, OR: 1.37, 95% CI: 1.27~1.49, \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001). Multivariate analysis showed that the sedation was an independent factor associated with PDR (OR: 1.54, 95% CI: 1.40~1.69, \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001) and ADR (OR: 1.45, 95% CI: 1.32~1.60, \u003cem\u003eP \u003c/em\u003e\u0026lt; 0.001). The effect was consistent in subgroup analyses(\u003cem\u003eP\u003c/em\u003e \u0026gt; 0.05) and PSM analysis (PDR: 56.1% vs 46.4%, OR: 1.48, 95% CI: 1.35~1.62, \u003cem\u003eP \u003c/em\u003e\u0026lt; 0.001; ADR: 37.4% vs 30.0%, OR: 1.40, 95% CI: 1.27~1.54, \u003cem\u003eP \u003c/em\u003e\u0026lt; 0.001). \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e Sedation was associated with a higher polyp and adenoma detection rates during colonoscopy, which can promote the quality of colonoscopy. \u003c/p\u003e","manuscriptTitle":"Sedation is associated with higher polyp and adenoma detection rates during colonoscopy: a retrospective cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-03-16 15:26:16","doi":"10.21203/rs.3.rs-1446898/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","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":"3a9d5d90-105b-4566-813d-f266ec69d26a","owner":[],"postedDate":"March 16th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-03-17T07:14:24+00:00","versionOfRecord":[],"versionCreatedAt":"2022-03-16 15:26:16","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1446898","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1446898","identity":"rs-1446898","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}