Daytime variation on clinical outcomes in elderly after total joint arthroplasty under general anaesthesia：a prospective study

Daytime variation on clinical outcomes in elderly after total joint arthroplasty under general anaesthesia：a prospective 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 Daytime variation on clinical outcomes in elderly after total joint arthroplasty under general anaesthesia：a prospective study Hao Guo, Heng-Li Li, Fei Xiao, Hao Wang, Bo-Yu Xie This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6338495/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: The circadian rhythm influences various physiological processes, affecting health outcomes significantly. This study aims to explore the impact of daytime variation on outcomes following total joint arthroplasty, specifically focusing on the recovery of independent walking ability. Materials and Methods: Between May 2023 and May 2024, we prospectively evaluated 530 consecutive patients undergoing total joint arthroplasty. Daytime variation was categorized into morning (7:30 a.m. to 12:00 p.m.) and afternoon (12:00 p.m. to 6:00 p.m.) based on anesthesia records. Functional recovery, defined as the ability to independently walk across a room 30 days post-surgery, was assessed via telephone interviews. Multivariate logistic regression analyzed factors influencing functional recovery. Results: Of 362 patients, 177 (48.9%) underwent morning surgeries and 185 (51.1%) underwent afternoon surgeries. Before adjustment, a higher proportion of patients in the afternoon surgery group achieved functional recovery compared to the morning group (71.9% vs. 54.8%). After adjusting for potential confounders, patients undergoing morning surgeries were less likely to regain independent walking ability compared to those undergoing afternoon surgeries (adjusted odds ratio [aOR], 1.94; 95% CI, 1.18 to 3.20; P=0.009). Incidences of postoperative delirium (aOR, 0.50; 95% CI, 0.29 to 0.88; P=0.015) and postoperative sleep disturbances (aOR, 0.49; 95% CI, 0.32 to 0.77; P=0.002) within the first 7 days were lower in the afternoon surgery group. Multivariable regression analysis, afternoon surgery was found to be statistically associated with increased odds of functional recovery (aOR: 1.75; 95% CI, 1.03 to 2.97; P=0.039). No significant differences were observed in other clinical outcomes. Conclusion: Daytime variation appears to significantly influence outcomes following total joint arthroplasty, particularly in achieving independent walking ability at 30 days postoperatively. Clinical trial number: not applicable. Daytime variation circadian rhythm total joint arthroplasty general anesthesia Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Circadian rhythms, internal timing mechanisms aligned with the environment, influence various physiological functions, including cardiovascular health and brain activity [ 1 – 3 ]. Animal studies show that the circadian clock in cardiomyocytes affects tolerance to ischemia/reperfusion throughout the day [ 4 ]. Clinical investigations have further demonstrated that circadian rhythms significantly affect human health outcomes. For instance, studies have revealed lower incidences of adverse cardiovascular events in patients undergoing afternoon surgeries compared to morning surgeries [ 5 ]. Moreover, disruptions in circadian rhythms have been associated with increased risks of metabolic and cardiovascular diseases [ 6 , 7 ]. Time-of-day variations impact outcomes across specialties, including general surgery, cardiac surgery, and neurosurgery [ 8 – 11 ], underscoring its critical relevance in clinical practice. Older adults, who experience changes in circadian rhythm influencing sleep quality and cognitive function [ 12 ], represent a population of particular interest regarding the impact of timing on surgical outcomes such as total joint arthroplasty (TJA). TJA stands as a cornerstone treatment for alleviating joint pain and disability associated with hip and knee degenerative conditions, offering substantial improvements in overall health and quality of life [ 13 – 16 ]. The rising demand for TJA surgeries underscores its efficacy [ 17 – 19 ]. Despite its established benefits and increasing utilization, there is limited research on how surgical daytime variation impacts outcomes following TJA, particularly regarding the recovery of independent walking ability within a specific timeframe [ 20 ]. To address this gap, we conducted a prospective, single-center observational study to evaluate the effect of daytime variation on the recovery of walking ability after TJA under general anesthesia in older adults. We hypothesized that surgical outcomes, particularly the ability to walk independently at 30 days post-surgery, vary based on the time of day the surgery is performed, with better outcomes expected for afternoon surgeries compared to morning surgeries. Methods This was a prospective, single center, observation study conducted at a tertiary referral teaching hospital in China. The study findings adhere to the strengthening the reporting of cohort, cross-sectional, and case–control studies in surgery (STROCSS) reporting guidelines [21]. This study was registered with clinicaltrials.gov and all participants provided informed consent. Study Design and Patient Eligibility Criteria We enrolled 530 consecutive patients diagnosed with osteoarthritis or ischemic necrosis undergoing TJA (including total hip arthroplasty [THA] and total knee arthroplasty [TKA]) between May 2023 and May 2024. Eligible patients were aged 65 or older and classified as American Society of Anesthesiologists (ASA) physical health class II or III. Exclusion criteria included refusal to participate, language or cognitive barriers, bilateral or revision joint surgery needs, and severe systemic diseases such as liver, kidney, or cardiac failure. Patients who required TJA solely due to acute injuries, such as fractures, were also excluded due to their distinct pathophysiological characteristics. Additionally, patients transferred to the Intensive Care Unit (ICU) postoperatively were excluded to avoid potential disruptions to circadian rhythms caused by the ICU environment, including lighting and other factors. Exposure of Interest The exposure of interest was defined as afternoon surgery, identified from anesthesia records where anesthesia occurred between 12:00 p.m. and 18:00 p.m. Morning surgery was classified when anesthesia was administered between 7:30 a.m. and 12:00 p.m. Data collection Prior to scheduled surgical procedures, trained research assistants conducted a 60-minute baseline assessment in patient wards to gather demographic data. We examined perioperative parameters, distinguishing between "preoperative (pre-)" and "postoperative (post-)" assessments. These included demographics such as age, sex, body mass index (BMI), lifestyle factors (smoking, drinking, living arrangements), educational attainment, frailty status, sleep disturbance, cognitive function, pain intensity, depression, anxiety, and comorbidities such as hypertension, diabetes, coronary heart disease (CVD), cerebrovascular disease (CHD), ASA, presence of metabolic syndrome (Mets), and type of surgery (THA and TKA). Laboratory assessments before and after surgery utilized recent results for hemoglobin (Hb), hematocrit (HCT), glucose (Glu), serum electrolytes (sodium, potassium, calcium), C-reactive protein (CRP), albumin, fasting triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and lipoprotein(a). Inflammation-related variables such as platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and systemic immune-inflammation index (SII) were calculated from routine blood tests (SII = platelet × neutrophil / lymphocyte). Intraoperative data included surgery and anesthesia durations, estimated blood loss, fluid infusion volume, blood transfusions, dexmedetomidine use, hypotension episodes (defined as >20% reduction in mean arterial pressure or MAP <60 mmHg), analgesic consumption (converted to fentanyl equivalents), peripheral nerve block (PNB) use, and Patient-Controlled Analgesia (PCA). Anesthesia was standardized with sevoflurane inhalation and target-controlled infusion of intravenous agents (propofol or ciprofol with remifentanil), and consistent protocols for blood transfusions and multimodal pain management were employed. Outcomes The primary outcome assessed daytime variation (morning vs. afternoon) in functional recovery, defined as the ability to walk independently across a room 30 days post-surgery. Outcome data were collected via telephone interviews by trial staff, with caregiver input allowed for participants unable to complete the interview, and patients not reachable on three separate occasions were deemed lost to follow-up. Secondary outcomes encompassed clinical assessments within 7 weeks postoperatively, covering dizziness, postoperative nausea and vomiting (PONV), postoperative delirium (POD), postoperative sleep disturbances (PSD), postoperative anxiety and depression (PAD), postoperative pain, and scores related to postoperative recovery quality. Activity time is defined as the duration from the completion of surgery until the patient begins functional exercises using assistive devices to get out of bed. Additionally, 30-day postoperative outcomes included pain intensity, cognitive function, anxiety and depression scores, postoperative satisfaction, and sleep quality. Length of hospital stay (LOS) was defined as the interval between the end of surgery and hospital discharge. Postoperative hospitalization costs were also documented. Detailed definitions and justifications for each parameter are available in the supplementary materials. (Supplementary Materials and Methods) Statistical analysis Due to limited available data on the recovery of independent walking ability following TJA, we referenced the REGAIN study [22], which reported that approximately 81.5% of patients achieve independent walking by 60 days post THA. The sample size for this study was calculated based on the results of a pilot study. Our pilot study indicated that about 67.7% (8/12) of patients in the afternoon TJA group and 50% (4/8) in the morning group regained independent walking ability. Thus, our study aims to enroll 427 patients to achieve 90% statistical power in detecting significant differences in primary outcomes between the afternoon and morning groups. This calculation assumes a two-sided significance level of 0.05 and allows for a 20% follow-up loss. Continuous variables with normal distribution were presented as mean (standard deviation) and analyzed using Student's t-test. Non-normally distributed continuous variables were described as median and interquartile range (IQR), and compared using the Mann–Whitney test. Categorical variables were expressed as frequencies or percentages and compared using the χ2 test or Fisher's exact test. We assessed the impact of daytime variation on postoperative outcomes while adjusting for potential confounding factors identified through baseline and intraoperative characteristics. For categorical variables, we used logistic regression to adjust for potential confounders. For continuous variables, adjustments were made using least squares mean differences (LSMD). Statistical significance was set at the 0.05 level for two-tailed tests. Analysis was performed using R 4.0.1 (R Foundation for Statistical Computing, Vienna, Austria). To further investigate the effect of daytime variation on postoperative independent walking ability following TJA, we employed logistic regression to analyze factors influencing functional recovery after TJA. Variable selection for the multiple logistic regression was based on Boruta and Lasso methods, combined with relevant recommendations from the field. Ultimately, the variables included in the multiple logistic regression model were ASA, surgery site, M/A (morning/afternoon surgery), LOS, activity time, QoR-15, and PSD. Results Patients Of the 530 screened patients, 469 met the eligibility criteria and consented. Of these, 13 were excluded due to surgery cancellation, 2 died within the first postoperative days with no follow-up records, 36 were admitted to the ICU postoperatively, and an additional 56 were lost to follow-up by 30 days after surgery. Comprehensive outcome data were available for 177 patients in the morning group and 185 patients in the afternoon group (Figure 1). The cohort included 362 participants with a median age of 70 years (interquartile range [IQR] 67-75), 240 females (66.3%) and 122 males (33.7%). Among them, 155 (42.8%) had received only primary school education, while 27 (7.5%) had completed college education. Regarding surgical specifics, 130 patients (35.9%) underwent THA, with 74 in the morning group (89.2%) and 56 in the afternoon group. Additionally, 119 participants (32.9%) reported sleep disturbances, and 292 (80.7%) were categorized as prefrail or frail at enrolment. Patients undergoing afternoon surgeries were noted to be younger, had a higher prevalence of hypertension, and included a greater proportion of ASA class II patients compared to those undergoing morning surgeries (Table 1). Intraoperative characteristics Intraoperatively, patients in the afternoon surgery group experienced significantly longer surgical and anesthesia durations compared to those in the morning group. However, patients in the afternoon group had fewer incidences of intraoperative hypotension events (90.4% vs. 75.7%). There were no significant differences between the two groups in estimated blood loss, blood transfusion requirements, amount of analgesic medication used, or the proportion of patients using PNB or PCA for pain management (Table 2). Primary outcome Over the 30 days following surgery, 230 out of 362 participants (63.5%) achieved functional recovery. Specifically, 94 out of 177 patients (53.1%) were in the morning surgery group, while 136 out of 185 patients (73.5%) were in the afternoon surgery group (Figure 2 and Supplementary Table 1). After adjusting for age, osteoarthritis, ASA, surgery site, hypertension, and intraoperative hypotension, patients undergoing morning surgeries were less likely to regain independent walking ability across a room compared to those undergoing afternoon surgeries (adjusted odds ratio [aOR], 1.94; 95% confidence interval [CI], 1.18 to 3.20; P = 0.009) (Table 3). Secondary outcomes When evaluating secondary outcomes during the first 7 days postoperatively, significant differences were noted in the lower incidence of POD (aOR, 0.50; 95% CI, 0.29 to 0.88; P = 0.015) and PSD (aOR, 0.49; 95% CI, 0.32 to 0.77; P = 0.002) in the afternoon surgery group (Table 3). Patients who underwent afternoon surgeries reported higher pain VAS scores during movement on the third postoperative day (LSMD, -0.23; 95% CI, -0.4 to -0.05; P = 0.010) (Table 3). Additionally, laboratory analyses indicated lower levels of CRP (LSMD, -14.27; 95% CI, -20.77 to -7.78; P < 0.001) but higher NLR (LSMD, 5.33; 95% CI, 3.99 to 6.66; P < 0.001), PLR (LSMD, 112.7; 95% CI, 85.29 to 140.12; P < 0.001), and SII (LSMD, 1335.67; 95% CI, 959.63 to 1711.72; P < 0.001) on the first postoperative day among patients in the afternoon surgery group (Supplementary Table 1). None of the other secondary outcomes over the following 7 days showed significant differences, including LOS, activity time, postoperative recovery quality assessed by QoR-15, and incidences of dizziness, PONV, and PAD (Table 3). Analysis of postoperative pain VAS scores at different time points revealed differences only in VAS scores during movement on the third postoperative day (LSMD, -0.23; 95% CI, -0.4 to -0.25; P=0.01) (Figure 3 and Supplementary Table 2). Assessment of secondary outcomes at 30 days postoperatively revealed no significant differences in any measures, whether before or after adjustment. This includes VAS scores for pain at rest or during movement, cognitive function as assessed by TICS-m, depression and anxiety as measured by PHQ-9 and GAD-7, patient satisfaction, and sleep quality evaluated using the RCSQ (Table 3). Please refer to Supplementary Table 2 for detailed information regarding all secondary outcomes related to the morning surgery group and afternoon surgery group. The potential confounding factors include age, osteoarthritis, ASA, surgery site, hypertension, and intraoperative hypotension, were adjusted for all of secondary outcomes. Univariable and multivariable logistic regression To further investigate the impact of daytime variation on functional recovery following TJA, we utilized both univariable and multivariable logistic regression analyses. Initially, univariable logistic regression included all baseline variables listed in Supplementary Table 3. Variables selected through Boruta and Lasso methods were subsequently included in the multivariable regression model (Supplementary Figures 1-3). In the multivariable regression analysis, afternoon surgery was found to be statistically associated with increased odds of functional recovery (aOR: 1.75; 95% CI, 1.03 to 2.97; P=0.039). Additionally, variables such as ASA classification, surgery site, active time, and PSD were also identified as significant factors associated with functional recovery at 30 days post-surgery (Figure 4). Discussion In our prospective cohort study of patients undergoing TJA, we found a significant association between the daytime variation and post-operative outcomes under general anesthesia, particularly in terms of functional recovery. After adjusting for potential confounders, patients undergoing surgery in the afternoon were more likely to regain independent walking ability within 30 days post-operatively compared to those undergoing morning surgery. Additionally, the incidence of POD and PSD was lower in the afternoon surgery group. Both univariable and multivariable logistic regression analyses corroborated these findings. Furthermore, our comparison of postoperative laboratory results revealed that patients undergoing afternoon surgery had lower levels of CRP but higher levels of hemoglobin and several immune inflammation indices (NLR, PLR, and SII) compared to those undergoing morning surgery. Extensive basic and clinical research has firmly established the influence of circadian rhythms on various biological processes. Previous studies integrating clinical trials and animal experiments consistently demonstrate a correlation between the timing of procedures and perioperative myocardial injury, which is regulated by the circadian clock [ 5 ]. These findings suggest that afternoon surgeries may provide protective benefits for perioperative myocardial health and overall patient outcomes, aligns with our results. However, conflicting results exist in major studies. A large propensity-matched cohort study involving 7,148 patients undergoing aortic valve replacement found no notable time-of-day-dependent effects on perioperative myocardial injuries [ 23 ]. Similarly, a retrospective study of 2,720 patients also indicated no statistically significant differences in risk-adjusted morbidity and mortality between morning and afternoon surgeries [ 24 ]. Studies on daytime variation primarily focus on cardiac-related surgeries, contributing to varying conclusions [ 24 – 30 ]. These divergent findings underscore the intricate nature of circadian influences across diverse surgical contexts and patient populations. Indeed, in the realm of TJA, studies exploring the impact of daytime variation on postoperative recovery have yielded inconsistent results. Li et al. investigated the impact of surgical sequence on TJA-related complications and noted an increasing trend in joint-related complications as surgeries progressed, although overall complications did not differ significantly [ 31 ]. While this contrasts with our findings, considering our older patient cohort and the unclear relationship between sequence and actual surgery start times studied by Li et al., our results remain credible. Conversely, Young et al. reported that patients undergoing THA in the afternoon showed quicker recovery of cortisol to baseline levels and lower inflammatory marker levels (IL-6 and IL-8), consistent with our observations where afternoon surgery correlated with reduced postoperative CRP levels [ 32 ]. Given the close link between circadian rhythms and physiological functions, we advocate for heightened scrutiny of daytime variation in various surgical procedures, particularly in elderly patients who may be more susceptible to environmental and physiological changes. Our study focused on evaluating the recovery of independent walking ability as the primary outcome in patients undergoing TJA, drawing parallels with the approach taken in the REGAIN study [ 22 ]. Unlike REGAIN, we specifically included patients with arthritis or ischemic necrosis lesions, conditions that significantly limit mobility preoperatively for many TJA patients. Notably, a substantial majority of our patients (80.7%) were categorized as pre-frail or frail before surgery, primarily due to compromised walking ability, which markedly impacts their quality of life and often drives them to seek surgical intervention. Within 30 days following surgery, approximately 63.5% of patients (230 out of 362) achieved independent walking ability. Our study focused exclusively on assessing the relationship between morning and afternoon surgery timing and functional recovery, without delving into potential impacts of poor postoperative functional recovery on other patient outcomes. It remains unclear whether inadequate recovery, particularly in terms of independent walking ability, could contribute to emotional changes such as anxiety or depression, diminished quality of life, or potentially affect joint function and overall surgical outcomes due to delayed mobility recovery. These aspects warrant further investigation. In conclusion, restoring independent walking ability post-TJA should be regarded as a critical component of patient-reported outcomes, necessitating heightened attention and proactive exploration of perioperative strategies aimed at enhancing recovery. These strategies might encompass optimizing surgical techniques, refining anesthesia protocols, enhancing postoperative care and patient education, and implementing comprehensive rehabilitation efforts involving patients and their families. Our findings regarding the impact of daytime variation on functional recovery suggest a promising avenue for future research in this field. While our study indicates potential benefits of afternoon surgery for TJA patients in terms of postoperative recovery, it's important to acknowledge that scheduling surgery timing remains a complex variable to manage. Identifying specific patient groups who might benefit most from afternoon surgeries and developing effective implementation strategies will require further investigation. Our study has unveiled significant associations between daytime variation and several key postoperative clinical outcomes, including reduced incidences of POD and PSD, along with modest improvements in postoperative pain, particularly notable on the third day following surgery. Researches indicates that disturbances in circadian rhythms are linked to increased risks of delirium and dementia [ 33 – 35 ], consistent with findings from present studies. Moreover, Yang et al. reported that elderly patients undergoing THA experienced decreased postoperative sleep quality, but those undergoing surgery in the afternoon demonstrated better sleep quality compared to those in the morning group, possibly due to transient changes in melatonin secretion post-surgery [ 36 ]. Even after adjusting for potential confounding factors, our study found a significantly lower risk of PSD among patients undergoing afternoon surgery compared to morning surgery (aOR, 0.49). However, there was no discernible difference in sleep quality at 30 days postoperatively, suggesting that any impact of anesthesia on patient sleep quality may be transient. Nevertheless, given the close association between PSD and early postoperative recovery [ 37 – 40 ], it is crucial to maintain heightened vigilance and consider early intervention for patients reporting early postoperative sleep disturbances to enhance overall sleep quality and potentially improve recovery outcomes. While the precise mechanisms through which time variation or circadian rhythms influence postoperative outcomes remain unclear, our study integrates findings from postoperative laboratory results to speculate on potential underlying mechanisms contributing to better recovery observed in the afternoon surgery group. Specifically, we observed that patients undergoing afternoon surgery exhibited significantly lower levels of CRP postoperatively, alongside higher levels of immune-inflammation markers such as NLR, PLR, and SII. Elevated NLR, PLR, and SII have been associated with adverse outcomes in prior research [ 41 – 43 ], highlighting the complex role of the immune system under different physiological conditions. In the context of surgical anesthesia, the body's response to surgical stimuli resembles its response to injury, necessitating an amplified immune response. The heightened levels of NLR, PLR, and SII observed in patients undergoing afternoon surgery may reflect an increased immune response during this time, potentially contributing to the observed reductions in incidences of POD and PSD. Additionally, insights from studies on circadian rhythms indicate that circadian regulatory mechanisms play critical roles in both humoral and innate immune responses to surgery-induced inflammation [ 5 , 44 – 47 ]. The present study contributes to the expanding understanding of how circadian rhythms impact health outcomes, particularly regarding the interplay between inflammation, immune response dynamics, and circadian rhythms. These insights underscore the potential for future research to explore optimized perioperative care strategies tailored to individual circadian rhythms, potentially enhancing surgical outcomes and promoting patient recovery. Our study possesses several inherent limitations that necessitate careful consideration. Firstly, unlike many previous studies that analyze the impact of timing variation on surgical outcomes [ 48 – 51 ], we did not account for factors such as surgeon fatigue or exhaustion. We acknowledge that these factors could potentially influence postoperative outcomes. However, similar to the findings of Anand et al., who noted no significant differences in postoperative outcomes when surgeries were performed by surgeons the day after night shifts [ 52 ], our study involved elderly patients undergoing TJA under the oversight of a collaborative effort between senior and attending surgeons at our institution. This collaborative approach may mitigate the influence of surgeon fatigue or exhaustion on our study outcomes. Additionally, while our single-center study design allowed us to control for many confounding factors arising from heterogeneous perioperative patient management (e.g., variations in anesthetic drugs), our findings would benefit from validation in a randomized multicenter study to enhance generalizability across different practice settings. Moreover, another limitation of our research is the single-time-point follow-up (30 days post-surgery), which precludes the use of more intuitive visualizations of recovery over time, such as Kaplan-Meier curves. This limitation affects our ability to provide a detailed interpretation of the recovery trajectory across different time points. Lastly, we did not employ specific assessment tools or scoring criteria, such as the Timed Up and Go (TUG) test, for evaluating the primary outcomes. Additionally, our study lacked long-term follow-up on postoperative outcomes, particularly in terms of assessing joint function through imaging and specialized orthopedic evaluations. Future research collaborations with orthopedic surgeons could offer a more comprehensive and standardized assessment of how timing variation affects patients' long-term postoperative recovery, especially regarding joint function. Addressing these limitations could yield deeper insights into the influence of daytime variation on postoperative recovery, facilitating the development of tailored perioperative strategies aimed at optimizing patient outcomes. Conclusion In summary, our study provides an essential piece of evidence suggesting that the time-of-day variation influences recovery from surgery. Among patients undergoing TJA, daytime variation appears to impact several outcomes, particularly the independent walk ability at 30 days postoperatively. These findings suggest that the timing of TJA may play a role in enhancing postoperative recovery after general anesthesia, with afternoon surgery potentially offering a protective effect. Declarations Ethics approval and consent to participate This study was approved by the Ethics Committee of the First Affiliated Hospital of Guangxi Medical University, and all patients signed written informed consent. Consent for publication Not applicable. Availability of data and materials The datasets used during the present study are available from the corresponding author upon reasonable request. Competing interests The authors declare no competing interests. Funding This study was supported by a Guangxi Key Research and Development Program (No. AB24010066); Guangxi Clinical Research Centre for Anaesthesiology (No. GK AD22035214); Special Fund of Neurotoxicity of General Anaesthetics and Its Prevention and Treatment Innovation Team of the First Affiliated Hospital of Guangxi Medical University (No. YYZS2022001). Authors' contributions All authors have made substantial contributions to conception and design of the study, or acquisition of data, or analysis and interpretation of data, drafting the article or revising it. All contributors who do not meet the criteria for authorship were listed in the acknowledgements section. Hao Guo: Conceptualization, Methodology, Data curation, Formal Analysis, Investigation, Visualization, Writing – Original Draft. Heng-Li Li: Conceptualization, Methodology, Formal Analysis, Investigation, Visualization, Writing – Original Draft. Fei Xiao: Methodology, Formal Analysis, Investigation, Visualization, Data curation, Writing – Review & Editing. Hao Wang: Methodology, Investigation, Writing – Review & Editing. Bo Yu Xie: Conceptualization, Methodology, Validation, Writing – Review & Editing, Supervision. Acknowledgements None. References Yamanaka Y: Basic concepts and unique features of human circadian rhythms: implications for human health . Nutrition Reviews 2020, 78 (Supplement_3):91-96. Scheer FAJL, Hu K, Evoniuk H, Kelly EE, Malhotra A, Hilton MF, Shea SA: Impact of the human circadian system, exercise, and their interaction on cardiovascular function . Proceedings of the National Academy of Sciences 2010, 107 (47):20541-20546. 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Tables Table 1 Patient demographics and baseline characteristics Characteristic M/A P-value Overall, N = 362 a Morning, N = 177 a Afternoon, N = 185 a Age (years) 70.0 (67.0, 75.0) 71.0 (68.0, 76.0) 70.0 (67.0, 73.0) <0.001 b Gender 0.713 c male 122 (33.7%) 58 (32.8%) 64 (34.6%) female 240 (66.3%) 119 (67.2%) 121 (65.4%) BMI ( kg·m 2 ) 24.7 (22.5, 27.1) 24.8 (22.8, 27.3) 24.6 (22.3, 26.9) 0.557 b Living condition 0.817 c With family 351 (97.0%) 172 (97.2%) 179 (96.8%) Alone 11 (3.0%) 5 (2.8%) 6 (3.2%) Education level (years) 0.562 c ≤6 155 (42.8%) 71 (40.1%) 84 (45.4%) 6～12 180 (49.7%) 93 (52.5%) 87 (47.0%) ＞12 27 (7.5%) 13 (7.3%) 14 (7.6%) Smoking (yes) 40 (11.0%) 20 (11.3%) 20 (10.8%) 0.882 c Drinking (yes) 45 (12.4%) 24 (13.6%) 21 (11.4%) 0.524 c Hypertension (yes) 174 (48.1%) 101 (57.1%) 73 (39.5%) <0.001 c Diabetes (yes) 50 (13.8%) 27 (15.3%) 23 (12.4%) 0.437 c CHD (yes) 27 (7.5%) 17 (9.6%) 10 (5.4%) 0.128 c CVD (yes) 32 (8.8%) 20 (11.3%) 12 (6.5%) 0.107 c Mets (yes) 129 (35.6%) 72 (40.7%) 57 (30.8%) 0.050 c Frailty 0.548 c Non-frail 70 (19.3%) 35 (19.8%) 35 (18.9%) Prefrail 194 (53.6%) 90 (50.8%) 104 (56.2%) Frailty 98 (27.1%) 52 (29.4%) 46 (24.9%) MIC (yes) 74 (20.4%) 39 (22.0%) 35 (18.9%) 0.463 c pre-SD (yes) 119 (32.9%) 65 (36.7%) 54 (29.2%) 0.127 c Anxiety/Depression (yes) 55 (15.2%) 27 (15.3%) 28 (15.1%) 0.975 c Osteoarthritis (yes) 252 (69.6%) 115 (65.0%) 137 (74.1%) 0.060 c pre-Hb (g/L) 128 (116, 137) 128 (118, 137) 128 (115, 137) 0.983 b pre-HCT (%) 0.39 (0.36, 0.41) 0.39 (0.36, 0.42) 0.39 (0.36, 0.41) 0.788 b Na + (mmol/L) 139.9 (138.0, 141.3) 139.7 (137.6, 141.4) 140.0 (138.0, 141.2) 0.209 b K + (mmol/L) 4.00 (3.75, 4.24) 4.00 (3.74, 4.26) 3.99 (3.76, 4.20) 0.545 b Ca 2+ (mmol/L) 2.30 (2.23, 2.37) 2.29 (2.24, 2.37) 2.30 (2.23, 2.36) 0.644 b Glu (mmol/L) 6.00 (5.18, 7.11) 6.10 (5.31, 7.15) 5.92 (5.02, 7.07) 0.259 b ALB (g/L) 40.6 (38.2, 42.4) 40.7 (38.1, 42.4) 40.5 (38.3, 42.4) 0.668 b pre-CRP (mg /L) 3 (1, 7) 3 (1, 7) 3 (1, 7) 0.353 b TG ( mmol/L ) 1.83 (1.30, 2.89) 1.84 (1.21, 2.85) 1.82 (1.30, 2.89) 0.956 b HDL-C ( mmol/L ) 1.30 (1.07, 1.54) 1.28 (1.05, 1.53) 1.31 (1.11, 1.55) 0.424 b High Lpa (yes) 101 (27.9%) 46 (26.0%) 55 (29.7%) 0.428 c pre-NLR 2.35 (1.77, 3.21) 2.31 (1.87, 3.17) 2.38 (1.65, 3.25) 0.682 b pre-PLR 150 (114, 187) 150 (110, 188) 150 (117, 186) 0.538 b pre-SII 623 (432, 863) 614 (430, 817) 634 (441, 911) 0.521 b pre-VAS 2.00 (2.00, 3.00) 2.00 (2.00, 3.00) 2.00 (2.00, 3.00) 0.367 b ASA 0.005 c Ⅱ 227 (62.7%) 98 (55.4%) 129 (69.7%) Ⅲ 135 (37.3%) 79 (44.6%) 56 (30.3%) Surgery site 0.022 b THA 130 (35.9%) 74 (41.8%) 56 (30.3%) TKA 232 (64.1%) 103 (58.2%) 129 (69.7%) Note: a Median (IQR); n (%), b Wilcoxon rank sum test, c Pearson's Chi-squared test. Frailty was defined as the FRAIL Scores (0 was Non-frail, 1~2 was prefrail, ＞2 was frailty); MIC was defined as the Mini-Cog Score＜2; Mets was defined as ≥3 of 5 criteria[53]: (1) obesity, (2) elevated fasting triglyceride, (3) reduced HDL-C, (4) elevated blood pressure, and (5) elevated glucose; Hypotension was defined as a reduction in mean arterial pressure [MAP] exceeding 20% from baseline or a MAP <60 mmHg); SD (sleep disturbance) was defined as the sleep-NRS ≥6 or RCSQ≤50. Abbreviations: Abbreviations: BMI, Body Mass Index; CHD, Coronary Heart Disease; CVD, Cerebrovascular Disease; Mets, Metabolic syndrome; MIC, Mild Cognitive Impairment; pre-SD, preoperative Sleep Disturbance; Hb, hemoglobin; HCT, hematocrit; Glu, Blood glucose; ALB, albumin; CRP, C-reactive protein; TG, Triglyceride; HDL-C, high-density lipoprotein cholesterol; Lp(a), lipoprotein(a); NLR, Neutrophil-to-Lymphocyte Ratio; PLR, Platelet-to-Lymphocyte Ratio; SII, Systemic-immune-inflammation index; VAS, Visual Analog Scale; ASA, American Society of Anesthesiology; THA, total hip arthroplasty; TKA, total knee arthroplasty. Table 2 Intraoperative variables of patients accepting morning or afternoon surgery Characteristic M/A P-value Morning, N = 177 a Afternoon, N = 185 a Propofol (yes) 116 (65.5%) 124 (67.0%) 0.764 b Ciprofol (yes) 61 (34.5%) 61 (33.0%) 0.764 b Remazolam (yes) 63 (35.6%) 60 (32.4%) 0.526 b Dexmedetomidine (yes) 86 (48.6%) 92 (49.7%) 0.828 b Remifentanil consumption 0.60 (0.49, 0.77) 0.62 (0.50, 0.84) 0.205 c Analgesic consumption 0.15 (0.10, 0.20) 0.10 (0.10, 0.20) 0.341 c Infusion volume 1,310 (1,080, 1,630) 1,265 (1,020, 1,620) 0.540 c Estimate bleed 100 (50, 200) 50 (50, 200) 0.352 c Duration of Anesthesia 136 (117, 157) 149 (126, 170) 0.007 c Duration of surgery 95 (81, 113) 105 (85, 130) 0.007 c Intraoperative Hypotension (yes) 160 (90.4%) 140 (75.7%) <0.001 b Blood transfusion (yes) 71 (40.1%) 63 (34.1%) 0.233 b PNB (yes) 149 (84.2%) 160 (86.5%) 0.535 b PCA (yes) 130 (73.4%) 136 (73.5%) 0.988 b Note: a Median (IQR); n (%), b Wilcoxon rank sum test, c Pearson's Chi-squared test. Abbreviations: PNB, Peripheral Nerve Block; PCA, Patient Controlled Analgesia. Table 3 Primary Outcome and Prespecified Secondary Outcomes on daytime variation (afternoon vs. morning) Various Unadjusted Adjusted OR (95%CI) Mean Difference (95% CI) P OR (95%CI) LS Mean Difference (95% CI) P Primary outcome Functional recovery a 2.45 (1.58, 3.81) <0.001 1.94 (1.18,3.20) 0.009 Secondary outcomes (7-days) POD a 0.43 (0.25, 0.73) 0.002 0.50 (0.29, 0.88) 0.015 PSD a 0.49 (0.32, 0.74) <0.001 0.49 (0.32, 0.77) 0.002 PAD a 0.72 (0.48, 1.10) 0.13 0.67 (0.43, 1.05) 0.078 Dizzy a 0.89 (0.58, 1.35) 0.57 0.87 (0.56, 1.36) 0.540 PONV a 0.75 (0.49, 1.15) 0.19 0.76 (0.48, 1.19) 0.230 LOS -0.48 (-1.6, 0.65) 0.409 -0.24 (-1.42, 0.94) 0.693 Active day -0.16 (-0.38, 0.05) 0.043 0.05 (-0.15, 0.25) 0.622 Cost -637.7 (-4016.7, 2741.4) 0.712 91.1 (-3417.4, 3599.6) 0.959 Qor-15 0.35 (-0.85, 1.55) 0.565 -0.16 (-1.40, 1.08) 0.796 Secondary outcomes (30-days) TICS-m b 0.53 (-0.9, 1.16) 0.097 0.04 (-0.57, 0.64) 0.906 Satisfaction b 0.16 (-0.01, 0.32) 0.066 0.06 (-0.11, 0.23) 0.475 RCSQ b 0.08 (-0.03, 0.18) 0.171 0.03 (-0.09, 0.14) 0.656 GAD-7 b -0.14 (-0.33,0.05) 0.157 -0.08 (-0.29, 0.12) 0.428 PHQ-9 b -0.09 (-0.28, 0.09) 0.303 -0.03 (-0.22, 0.16) 0.760 VAS-rest b -0.05 (-0.18, 0.07) 0.402 -0.08 (-0.21, 0.05) 0.219 VAS-move b -0.11 (-0.28, 0.05) 0.177 -0.11 (-0.28, 0.06) 0.221 Note: a Number (%), b Mean (Standard Deviation), Analysis were adjusted for age, ASA, Osteoarthritis, Surgery site, Hypertension, Intraoperative hypotension. Functional recovery defined as ability to walk without human assistance at 30 days. Abbreviations: POD, postoperative delirium; PSD, postoperative sleep disturbances; PAD, postoperative anxiety and depression; PONV, postoperative nausea and vomiting; LOS, length of hospital stay; Qor-15, quality of recovery; TICS-m, Telephone Interview for Cognitive Status-modified; RCSQ, Richards–Campbell Sleep Questionnaire; GAD-7, Generalized Anxiety Disorder-7; PHQ-9, Patient Health Questionnaire-9; VAS, Visual Analog Scale. Additional Declarations No competing interests reported. Supplementary Files Additionalfile.docx 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. 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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-6338495","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":451827875,"identity":"e5964919-3332-43c4-9c27-364dd89560b7","order_by":0,"name":"Hao Guo","email":"","orcid":"","institution":"The First Affiliated Hospital of Guangxi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Hao","middleName":"","lastName":"Guo","suffix":""},{"id":451827876,"identity":"87fa5639-e459-46ba-99b0-f1c8c003e7ac","order_by":1,"name":"Heng-Li Li","email":"","orcid":"","institution":"The First Affiliated Hospital of Guangxi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Heng-Li","middleName":"","lastName":"Li","suffix":""},{"id":451827877,"identity":"88455819-7f39-4bce-8350-9ec9303cb574","order_by":2,"name":"Fei Xiao","email":"","orcid":"","institution":"Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Fei","middleName":"","lastName":"Xiao","suffix":""},{"id":451827878,"identity":"f4058b3c-163d-47a2-ad98-fc8b28895975","order_by":3,"name":"Hao Wang","email":"","orcid":"","institution":"The First Affiliated Hospital of Guangxi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Hao","middleName":"","lastName":"Wang","suffix":""},{"id":451827879,"identity":"57716496-2d00-4c60-9af7-0072e73f1e93","order_by":4,"name":"Bo-Yu Xie","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAt0lEQVRIiWNgGAWjYFACHgYJMM3e2PjwAwlaDID04WZjCdK0SKS3CfAQo8HgRu7BGx9q/siZz3zYBtRsJ6fbQECL5Iy8ZMsZxwyMZW4ntj0oYEg2NjtAQAu/RI6ZNG+DQeIM6cR2AwmGA4nbCGlhg2uRPNgmwUOMFoQtEoxEapHseQfyi7GxBE8iMJANiPCLwXFwiMnJSbAff/jwQ4WdHEEtDAIJKCYQUg4C/AQNHQWjYBSMghEPAPK8PRtJ7wY2AAAAAElFTkSuQmCC","orcid":"","institution":"The First Affiliated Hospital of Guangxi Medical University","correspondingAuthor":true,"prefix":"","firstName":"Bo-Yu","middleName":"","lastName":"Xie","suffix":""}],"badges":[],"createdAt":"2025-03-30 12:53:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6338495/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6338495/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":82311378,"identity":"264c2db8-e343-4f90-a44f-3428ea194395","added_by":"auto","created_at":"2025-05-09 01:54:55","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":102346,"visible":true,"origin":"","legend":"\u003cp\u003eDiagram of Study Participant Flow\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6338495/v1/0b7e2b3c6bd7d85b8d125108.png"},{"id":82311876,"identity":"ca2bc057-b04c-49d3-aaa5-c40efca3ecf2","added_by":"auto","created_at":"2025-05-09 02:02:55","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":51003,"visible":true,"origin":"","legend":"\u003cp\u003eFunctional recovery of patients among morning surgery and afternoon surgery.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6338495/v1/bc1d86f918e828f76446d46e.png"},{"id":82311380,"identity":"47d9f472-2330-46e9-b768-267475c38c55","added_by":"auto","created_at":"2025-05-09 01:54:55","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":108141,"visible":true,"origin":"","legend":"\u003cp\u003ePostoperative pain at rest (A) and move (B) during the study follow-up among morning surgery and afternoon surgery. *:P＜0.05.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-6338495/v1/117a0d78858618a125c0ac31.png"},{"id":82312384,"identity":"049d4393-5140-4596-b254-4c31cf72f50f","added_by":"auto","created_at":"2025-05-09 02:10:56","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":87307,"visible":true,"origin":"","legend":"\u003cp\u003eMultivariable logistic regression to examine the factors correlated with functional recovery. ASA: American Society of Anesthesiologists; THA: total hip arthroplasty; TKA: total knee arthroplasty; LOS: length of hospital stays; PSD: postoperative sleep disturbance.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-6338495/v1/a45d5dd115c9e4bca2714c33.png"},{"id":107211466,"identity":"05a90f97-c4fe-41df-9868-d188b2c3f081","added_by":"auto","created_at":"2026-04-18 08:54:36","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2844353,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6338495/v1/4a476d58-f6dc-4149-acb4-32188207f773.pdf"},{"id":82311382,"identity":"8b2ec043-6ed5-4837-bbc0-21ed8f0bfd24","added_by":"auto","created_at":"2025-05-09 01:54:55","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":296430,"visible":true,"origin":"","legend":"","description":"","filename":"Additionalfile.docx","url":"https://assets-eu.researchsquare.com/files/rs-6338495/v1/57b834d09c2a06837a34f8b7.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Daytime variation on clinical outcomes in elderly after total joint arthroplasty under general anaesthesia：a prospective study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCircadian rhythms, internal timing mechanisms aligned with the environment, influence various physiological functions, including cardiovascular health and brain activity [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Animal studies show that the circadian clock in cardiomyocytes affects tolerance to ischemia/reperfusion throughout the day [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Clinical investigations have further demonstrated that circadian rhythms significantly affect human health outcomes. For instance, studies have revealed lower incidences of adverse cardiovascular events in patients undergoing afternoon surgeries compared to morning surgeries [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Moreover, disruptions in circadian rhythms have been associated with increased risks of metabolic and cardiovascular diseases [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Time-of-day variations impact outcomes across specialties, including general surgery, cardiac surgery, and neurosurgery [\u003cspan additionalcitationids=\"CR9 CR10\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], underscoring its critical relevance in clinical practice.\u003c/p\u003e \u003cp\u003eOlder adults, who experience changes in circadian rhythm influencing sleep quality and cognitive function [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], represent a population of particular interest regarding the impact of timing on surgical outcomes such as total joint arthroplasty (TJA). TJA stands as a cornerstone treatment for alleviating joint pain and disability associated with hip and knee degenerative conditions, offering substantial improvements in overall health and quality of life [\u003cspan additionalcitationids=\"CR14 CR15\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The rising demand for TJA surgeries underscores its efficacy [\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Despite its established benefits and increasing utilization, there is limited research on how surgical daytime variation impacts outcomes following TJA, particularly regarding the recovery of independent walking ability within a specific timeframe [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTo address this gap, we conducted a prospective, single-center observational study to evaluate the effect of daytime variation on the recovery of walking ability after TJA under general anesthesia in older adults. We hypothesized that surgical outcomes, particularly the ability to walk independently at 30 days post-surgery, vary based on the time of day the surgery is performed, with better outcomes expected for afternoon surgeries compared to morning surgeries.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis was a prospective, single center, observation study conducted at a tertiary referral teaching hospital in China. The study findings adhere to the strengthening the reporting of cohort, cross-sectional, and case\u0026ndash;control studies in surgery (STROCSS) reporting guidelines [21]. This study was registered with clinicaltrials.gov and all participants provided informed consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy Design and Patient Eligibility Criteria\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe enrolled 530 consecutive patients diagnosed with osteoarthritis or ischemic necrosis undergoing TJA (including total hip arthroplasty [THA] and total knee arthroplasty [TKA]) between May 2023 and May 2024. Eligible patients were aged 65 or older and classified as American Society of Anesthesiologists (ASA) physical health class II or III. Exclusion criteria included refusal to participate, language or cognitive barriers, bilateral or revision joint surgery needs, and severe systemic diseases such as liver, kidney, or cardiac failure. Patients who required TJA solely due to acute injuries, such as fractures, were also excluded due to their distinct pathophysiological characteristics. Additionally, patients transferred to the Intensive Care Unit (ICU) postoperatively were excluded to avoid potential disruptions to circadian rhythms caused by the ICU environment, including lighting and other factors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eExposure of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe exposure of interest was defined as afternoon surgery, identified from anesthesia records where anesthesia occurred between 12:00 p.m. and 18:00 p.m. Morning surgery was classified when anesthesia was administered between 7:30 a.m. and 12:00 p.m.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData collection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePrior to scheduled surgical procedures, trained research assistants conducted a 60-minute baseline assessment in patient wards to gather demographic data. We examined perioperative parameters, distinguishing between \u0026quot;preoperative (pre-)\u0026quot; and \u0026quot;postoperative (post-)\u0026quot; assessments. These included demographics such as age, sex, body mass index (BMI), lifestyle factors (smoking, drinking, living arrangements), educational attainment, frailty status, sleep disturbance, cognitive function, pain intensity, depression, anxiety, and comorbidities such as hypertension, diabetes, coronary heart disease (CVD), cerebrovascular disease (CHD), ASA, presence of metabolic syndrome (Mets), and type of surgery (THA and TKA).\u003c/p\u003e\n\u003cp\u003eLaboratory assessments before and after surgery utilized recent results for hemoglobin (Hb), hematocrit (HCT), glucose (Glu), serum electrolytes (sodium, potassium, calcium), C-reactive protein (CRP), albumin, fasting triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and lipoprotein(a). Inflammation-related variables such as platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and systemic immune-inflammation index (SII) were calculated from routine blood tests (SII = platelet \u0026times; neutrophil / lymphocyte).\u003c/p\u003e\n\u003cp\u003eIntraoperative data included surgery and anesthesia durations, estimated blood loss, fluid infusion volume, blood transfusions, dexmedetomidine use, hypotension episodes (defined as \u0026gt;20% reduction in mean arterial pressure or MAP \u0026lt;60 mmHg), analgesic consumption (converted to fentanyl equivalents), peripheral nerve block (PNB) use, and Patient-Controlled Analgesia (PCA). Anesthesia was standardized with sevoflurane inhalation and target-controlled infusion of intravenous agents (propofol or ciprofol with remifentanil), and consistent protocols for blood transfusions and multimodal pain management were employed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOutcomes\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe primary outcome assessed daytime variation (morning vs. afternoon) in functional recovery, defined as the ability to walk independently across a room 30 days post-surgery. Outcome data were collected via telephone interviews by trial staff, with caregiver input allowed for participants unable to complete the interview, and patients not reachable on three separate occasions were deemed lost to follow-up.\u003c/p\u003e\n\u003cp\u003eSecondary outcomes encompassed clinical assessments within 7 weeks postoperatively, covering dizziness, postoperative nausea and vomiting (PONV), postoperative delirium (POD), postoperative sleep disturbances (PSD), postoperative anxiety and depression (PAD), postoperative pain, and scores related to postoperative recovery quality. Activity time is defined as the duration from the completion of surgery until the patient begins functional exercises using assistive devices to get out of bed. Additionally, 30-day postoperative outcomes included pain intensity, cognitive function, anxiety and depression scores, postoperative satisfaction, and sleep quality.\u003c/p\u003e\n\u003cp\u003eLength of hospital stay (LOS) was defined as the interval between the end of surgery and hospital discharge. Postoperative hospitalization costs were also documented. Detailed definitions and justifications for each parameter are available in the supplementary materials. (Supplementary Materials and Methods)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDue to limited available data on the recovery of independent walking ability following TJA, we referenced the REGAIN study [22], which reported that approximately 81.5% of patients achieve independent walking by 60 days post THA. The sample size for this study was calculated based on the results of a pilot study. Our pilot study indicated that about 67.7% (8/12) of patients in the afternoon TJA group and 50% (4/8) in the morning group regained independent walking ability. Thus, our study aims to enroll 427 patients to achieve 90% statistical power in detecting significant differences in primary outcomes between the afternoon and morning groups. This calculation assumes a two-sided significance level of 0.05 and allows for a 20% follow-up loss.\u003c/p\u003e\n\u003cp\u003eContinuous variables with normal distribution were presented as mean (standard deviation) and analyzed using Student\u0026apos;s t-test. Non-normally distributed continuous variables were described as median and interquartile range (IQR), and compared using the Mann\u0026ndash;Whitney test. Categorical variables were expressed as frequencies or percentages and compared using the \u0026chi;2 test or Fisher\u0026apos;s exact test. We assessed the impact of daytime variation on postoperative outcomes while adjusting for potential confounding factors identified through baseline and intraoperative characteristics. For categorical variables, we used logistic regression to adjust for potential confounders. For continuous variables, adjustments were made using least squares mean differences (LSMD). Statistical significance was set at the 0.05 level for two-tailed tests. Analysis was performed using R 4.0.1 (R Foundation for Statistical Computing, Vienna, Austria).\u003c/p\u003e\n\u003cp\u003eTo further investigate the effect of daytime variation on postoperative independent walking ability following TJA, we employed logistic regression to analyze factors influencing functional recovery after TJA. Variable selection for the multiple logistic regression was based on Boruta and Lasso methods, combined with relevant recommendations from the field. Ultimately, the variables included in the multiple logistic regression model were ASA, surgery site, M/A (morning/afternoon surgery), LOS, activity time, QoR-15, and PSD.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003ePatients\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOf the 530 screened patients, 469 met the eligibility criteria and consented. Of these, 13 were excluded due to surgery cancellation, 2 died within the first postoperative days with no follow-up records, 36 were admitted to the ICU postoperatively, and an additional 56 were lost to follow-up by 30 days after surgery. Comprehensive outcome data were available for 177 patients in the morning group and 185 patients in the afternoon group (Figure 1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe cohort included 362 participants with a median age of 70 years (interquartile range [IQR] 67-75), 240 females (66.3%) and 122 males (33.7%). Among them, 155 (42.8%) had received only primary school education, while 27 (7.5%) had completed college education. Regarding surgical specifics, 130 patients (35.9%) underwent THA, with 74 in the morning group (89.2%) and 56 in the afternoon group. Additionally, 119 participants (32.9%) reported sleep disturbances, and 292 (80.7%) were categorized as prefrail or frail at enrolment. Patients undergoing afternoon surgeries were noted to be younger, had a higher prevalence of hypertension, and included a greater proportion of ASA class II patients compared to those undergoing morning surgeries (Table 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIntraoperative characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIntraoperatively, patients in the afternoon surgery group experienced significantly longer surgical and anesthesia durations compared to those in the morning group. However, patients in the afternoon group had fewer incidences of intraoperative hypotension events (90.4% vs. 75.7%). There were no significant differences between the two groups in estimated blood loss, blood transfusion requirements, amount of analgesic medication used, or the proportion of patients using PNB or PCA for pain management (Table 2).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePrimary outcome\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOver the 30 days following surgery, 230 out of 362 participants (63.5%) achieved functional recovery. Specifically, 94 out of 177 patients (53.1%) were in the morning surgery group, while 136 out of 185 patients (73.5%) were in the afternoon surgery group (Figure 2 and Supplementary Table 1). After adjusting for age, osteoarthritis, ASA, surgery site, hypertension, and intraoperative hypotension, patients undergoing morning surgeries were less likely to regain independent walking ability across a room compared to those undergoing afternoon surgeries (adjusted odds ratio [aOR], 1.94; 95% confidence interval [CI], 1.18 to 3.20; P = 0.009) (Table 3).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSecondary outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWhen evaluating secondary outcomes during the first 7 days postoperatively, significant differences were noted in the lower incidence of POD (aOR, 0.50; 95% CI, 0.29 to 0.88; P = 0.015) and PSD (aOR, 0.49; 95% CI, 0.32 to 0.77; P = 0.002) in the afternoon surgery group (Table 3). Patients who underwent afternoon surgeries reported higher pain VAS scores during movement on the third postoperative day (LSMD, -0.23; 95% CI, -0.4 to -0.05; P = 0.010) (Table 3). Additionally, laboratory analyses indicated lower levels of CRP (LSMD, -14.27; 95% CI, -20.77 to -7.78; P \u0026lt; 0.001) but higher NLR (LSMD, 5.33; 95% CI, 3.99 to 6.66; P \u0026lt; 0.001), PLR (LSMD, 112.7; 95% CI, 85.29 to 140.12; P \u0026lt; 0.001), and SII (LSMD, 1335.67; 95% CI, 959.63 to 1711.72; P \u0026lt; 0.001) on the first postoperative day among patients in the afternoon surgery group (Supplementary Table 1). None of the other secondary outcomes over the following 7 days showed significant differences, including LOS, activity time, postoperative recovery quality assessed by QoR-15, and incidences of dizziness, PONV, and PAD (Table 3). Analysis of postoperative pain VAS scores at different time points revealed differences only in VAS scores during movement on the third postoperative day (LSMD, -0.23; 95% CI, -0.4 to -0.25; P=0.01) (Figure 3 and Supplementary Table 2).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAssessment of secondary outcomes at 30 days postoperatively revealed no significant differences in any measures, whether before or after adjustment. This includes VAS scores for pain at rest or during movement, cognitive function as assessed by TICS-m, depression and anxiety as measured by PHQ-9 and GAD-7, patient satisfaction, and sleep quality evaluated using the RCSQ (Table 3). Please refer to Supplementary Table 2 for detailed information regarding all secondary outcomes related to the morning surgery group and afternoon surgery group. The potential confounding factors include age, osteoarthritis, ASA, surgery site, hypertension, and intraoperative hypotension, were adjusted for all of secondary outcomes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eUnivariable and multivariable logistic regression\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo further investigate the impact of daytime variation on functional recovery following TJA, we utilized both univariable and multivariable logistic regression analyses. Initially, univariable logistic regression included all baseline variables listed in Supplementary Table 3. Variables selected through Boruta and Lasso methods were subsequently included in the multivariable regression model (Supplementary Figures 1-3). In the multivariable regression analysis, afternoon surgery was found to be statistically associated with increased odds of functional recovery (aOR: 1.75; 95% CI, 1.03 to 2.97; P=0.039). Additionally, variables such as ASA classification, surgery site, active time, and PSD were also identified as significant factors associated with functional recovery at 30 days post-surgery (Figure 4).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn our prospective cohort study of patients undergoing TJA, we found a significant association between the daytime variation and post-operative outcomes under general anesthesia, particularly in terms of functional recovery. After adjusting for potential confounders, patients undergoing surgery in the afternoon were more likely to regain independent walking ability within 30 days post-operatively compared to those undergoing morning surgery. Additionally, the incidence of POD and PSD was lower in the afternoon surgery group. Both univariable and multivariable logistic regression analyses corroborated these findings. Furthermore, our comparison of postoperative laboratory results revealed that patients undergoing afternoon surgery had lower levels of CRP but higher levels of hemoglobin and several immune inflammation indices (NLR, PLR, and SII) compared to those undergoing morning surgery.\u003c/p\u003e \u003cp\u003eExtensive basic and clinical research has firmly established the influence of circadian rhythms on various biological processes. Previous studies integrating clinical trials and animal experiments consistently demonstrate a correlation between the timing of procedures and perioperative myocardial injury, which is regulated by the circadian clock [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. These findings suggest that afternoon surgeries may provide protective benefits for perioperative myocardial health and overall patient outcomes, aligns with our results. However, conflicting results exist in major studies. A large propensity-matched cohort study involving 7,148 patients undergoing aortic valve replacement found no notable time-of-day-dependent effects on perioperative myocardial injuries [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Similarly, a retrospective study of 2,720 patients also indicated no statistically significant differences in risk-adjusted morbidity and mortality between morning and afternoon surgeries [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Studies on daytime variation primarily focus on cardiac-related surgeries, contributing to varying conclusions [\u003cspan additionalcitationids=\"CR25 CR26 CR27 CR28 CR29\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. These divergent findings underscore the intricate nature of circadian influences across diverse surgical contexts and patient populations.\u003c/p\u003e \u003cp\u003eIndeed, in the realm of TJA, studies exploring the impact of daytime variation on postoperative recovery have yielded inconsistent results. Li et al. investigated the impact of surgical sequence on TJA-related complications and noted an increasing trend in joint-related complications as surgeries progressed, although overall complications did not differ significantly [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. While this contrasts with our findings, considering our older patient cohort and the unclear relationship between sequence and actual surgery start times studied by Li et al., our results remain credible. Conversely, Young et al. reported that patients undergoing THA in the afternoon showed quicker recovery of cortisol to baseline levels and lower inflammatory marker levels (IL-6 and IL-8), consistent with our observations where afternoon surgery correlated with reduced postoperative CRP levels [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Given the close link between circadian rhythms and physiological functions, we advocate for heightened scrutiny of daytime variation in various surgical procedures, particularly in elderly patients who may be more susceptible to environmental and physiological changes.\u003c/p\u003e \u003cp\u003eOur study focused on evaluating the recovery of independent walking ability as the primary outcome in patients undergoing TJA, drawing parallels with the approach taken in the REGAIN study [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Unlike REGAIN, we specifically included patients with arthritis or ischemic necrosis lesions, conditions that significantly limit mobility preoperatively for many TJA patients. Notably, a substantial majority of our patients (80.7%) were categorized as pre-frail or frail before surgery, primarily due to compromised walking ability, which markedly impacts their quality of life and often drives them to seek surgical intervention. Within 30 days following surgery, approximately 63.5% of patients (230 out of 362) achieved independent walking ability. Our study focused exclusively on assessing the relationship between morning and afternoon surgery timing and functional recovery, without delving into potential impacts of poor postoperative functional recovery on other patient outcomes. It remains unclear whether inadequate recovery, particularly in terms of independent walking ability, could contribute to emotional changes such as anxiety or depression, diminished quality of life, or potentially affect joint function and overall surgical outcomes due to delayed mobility recovery. These aspects warrant further investigation. In conclusion, restoring independent walking ability post-TJA should be regarded as a critical component of patient-reported outcomes, necessitating heightened attention and proactive exploration of perioperative strategies aimed at enhancing recovery. These strategies might encompass optimizing surgical techniques, refining anesthesia protocols, enhancing postoperative care and patient education, and implementing comprehensive rehabilitation efforts involving patients and their families. Our findings regarding the impact of daytime variation on functional recovery suggest a promising avenue for future research in this field. While our study indicates potential benefits of afternoon surgery for TJA patients in terms of postoperative recovery, it's important to acknowledge that scheduling surgery timing remains a complex variable to manage. Identifying specific patient groups who might benefit most from afternoon surgeries and developing effective implementation strategies will require further investigation.\u003c/p\u003e \u003cp\u003eOur study has unveiled significant associations between daytime variation and several key postoperative clinical outcomes, including reduced incidences of POD and PSD, along with modest improvements in postoperative pain, particularly notable on the third day following surgery. Researches indicates that disturbances in circadian rhythms are linked to increased risks of delirium and dementia [\u003cspan additionalcitationids=\"CR34\" citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e], consistent with findings from present studies. Moreover, Yang et al. reported that elderly patients undergoing THA experienced decreased postoperative sleep quality, but those undergoing surgery in the afternoon demonstrated better sleep quality compared to those in the morning group, possibly due to transient changes in melatonin secretion post-surgery [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Even after adjusting for potential confounding factors, our study found a significantly lower risk of PSD among patients undergoing afternoon surgery compared to morning surgery (aOR, 0.49). However, there was no discernible difference in sleep quality at 30 days postoperatively, suggesting that any impact of anesthesia on patient sleep quality may be transient. Nevertheless, given the close association between PSD and early postoperative recovery [\u003cspan additionalcitationids=\"CR38 CR39\" citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e], it is crucial to maintain heightened vigilance and consider early intervention for patients reporting early postoperative sleep disturbances to enhance overall sleep quality and potentially improve recovery outcomes.\u003c/p\u003e \u003cp\u003eWhile the precise mechanisms through which time variation or circadian rhythms influence postoperative outcomes remain unclear, our study integrates findings from postoperative laboratory results to speculate on potential underlying mechanisms contributing to better recovery observed in the afternoon surgery group. Specifically, we observed that patients undergoing afternoon surgery exhibited significantly lower levels of CRP postoperatively, alongside higher levels of immune-inflammation markers such as NLR, PLR, and SII. Elevated NLR, PLR, and SII have been associated with adverse outcomes in prior research [\u003cspan additionalcitationids=\"CR42\" citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e], highlighting the complex role of the immune system under different physiological conditions. In the context of surgical anesthesia, the body's response to surgical stimuli resembles its response to injury, necessitating an amplified immune response. The heightened levels of NLR, PLR, and SII observed in patients undergoing afternoon surgery may reflect an increased immune response during this time, potentially contributing to the observed reductions in incidences of POD and PSD. Additionally, insights from studies on circadian rhythms indicate that circadian regulatory mechanisms play critical roles in both humoral and innate immune responses to surgery-induced inflammation [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan additionalcitationids=\"CR45 CR46\" citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]. The present study contributes to the expanding understanding of how circadian rhythms impact health outcomes, particularly regarding the interplay between inflammation, immune response dynamics, and circadian rhythms. These insights underscore the potential for future research to explore optimized perioperative care strategies tailored to individual circadian rhythms, potentially enhancing surgical outcomes and promoting patient recovery.\u003c/p\u003e \u003cp\u003eOur study possesses several inherent limitations that necessitate careful consideration. Firstly, unlike many previous studies that analyze the impact of timing variation on surgical outcomes [\u003cspan additionalcitationids=\"CR49 CR50\" citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e], we did not account for factors such as surgeon fatigue or exhaustion. We acknowledge that these factors could potentially influence postoperative outcomes. However, similar to the findings of Anand et al., who noted no significant differences in postoperative outcomes when surgeries were performed by surgeons the day after night shifts [\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e], our study involved elderly patients undergoing TJA under the oversight of a collaborative effort between senior and attending surgeons at our institution. This collaborative approach may mitigate the influence of surgeon fatigue or exhaustion on our study outcomes. Additionally, while our single-center study design allowed us to control for many confounding factors arising from heterogeneous perioperative patient management (e.g., variations in anesthetic drugs), our findings would benefit from validation in a randomized multicenter study to enhance generalizability across different practice settings. Moreover, another limitation of our research is the single-time-point follow-up (30 days post-surgery), which precludes the use of more intuitive visualizations of recovery over time, such as Kaplan-Meier curves. This limitation affects our ability to provide a detailed interpretation of the recovery trajectory across different time points. Lastly, we did not employ specific assessment tools or scoring criteria, such as the Timed Up and Go (TUG) test, for evaluating the primary outcomes. Additionally, our study lacked long-term follow-up on postoperative outcomes, particularly in terms of assessing joint function through imaging and specialized orthopedic evaluations. Future research collaborations with orthopedic surgeons could offer a more comprehensive and standardized assessment of how timing variation affects patients' long-term postoperative recovery, especially regarding joint function. Addressing these limitations could yield deeper insights into the influence of daytime variation on postoperative recovery, facilitating the development of tailored perioperative strategies aimed at optimizing patient outcomes.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn summary, our study provides an essential piece of evidence suggesting that the time-of-day variation influences recovery from surgery. Among patients undergoing TJA, daytime variation appears to impact several outcomes, particularly the independent walk ability at 30 days postoperatively. These findings suggest that the timing of TJA may play a role in enhancing postoperative recovery after general anesthesia, with afternoon surgery potentially offering a protective effect.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of the First Affiliated Hospital of Guangxi Medical University, and all patients signed written informed consent.\u0026nbsp;\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\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used during the present study are available from the corresponding author upon reasonable request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by a Guangxi Key Research and Development Program (No. AB24010066); Guangxi Clinical Research Centre for Anaesthesiology (No. GK AD22035214); Special Fund of Neurotoxicity of General Anaesthetics and Its Prevention and Treatment Innovation Team of the First Affiliated Hospital of Guangxi Medical University (No. YYZS2022001).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors have made substantial contributions to conception and design of the study, or acquisition of data, or analysis and interpretation of data, drafting the article or revising it. All contributors who do not meet the criteria for authorship were listed in the acknowledgements section.\u003c/p\u003e\n\u003cp\u003eHao Guo: Conceptualization, Methodology, Data curation, Formal Analysis, Investigation, Visualization, Writing \u0026ndash; Original Draft. Heng-Li Li: Conceptualization, Methodology, Formal Analysis, Investigation, Visualization, Writing \u0026ndash; Original Draft. Fei Xiao: Methodology, Formal Analysis, Investigation, Visualization, Data curation, Writing \u0026ndash; Review \u0026amp; Editing. Hao Wang: Methodology, Investigation, Writing \u0026ndash; Review \u0026amp; Editing. Bo Yu Xie: Conceptualization, Methodology, Validation, Writing \u0026ndash; Review \u0026amp; Editing, Supervision.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eYamanaka Y: \u003cstrong\u003eBasic concepts and unique features of human circadian rhythms: implications for human health\u003c/strong\u003e. \u003cem\u003eNutrition Reviews \u003c/em\u003e2020, \u003cstrong\u003e78\u003c/strong\u003e(Supplement_3):91-96.\u003c/li\u003e\n\u003cli\u003eScheer FAJL, Hu K, Evoniuk H, Kelly EE, Malhotra A, Hilton MF, Shea SA: \u003cstrong\u003eImpact of the human circadian system, exercise, and their interaction on cardiovascular function\u003c/strong\u003e. \u003cem\u003eProceedings of the National Academy of Sciences \u003c/em\u003e2010, \u003cstrong\u003e107\u003c/strong\u003e(47):20541-20546.\u003c/li\u003e\n\u003cli\u003eDurgan DJ, 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Cox B, Lee A, Barnajian M: \u003cstrong\u003eRobotic colorectal procedures: does operative start time impact short-term outcome?\u003c/strong\u003e \u003cem\u003eSurgical endoscopy \u003c/em\u003e2022, \u003cstrong\u003e36\u003c/strong\u003e(8):5669-5675.\u003c/li\u003e\n\u003cli\u003eLu Q, Shen Y, Zhang J, Ren YF, Dong J, Du ZQ, Liu XM, Wu Z, Lv Y, Zhang XF: \u003cstrong\u003eOperation Start Times and Postoperative Morbidity from Liver Resection: A Propensity Score Matching Analysis\u003c/strong\u003e. \u003cem\u003eWorld journal of surgery \u003c/em\u003e2017, \u003cstrong\u003e41\u003c/strong\u003e(4):1100-1109.\u003c/li\u003e\n\u003cli\u003eVinden C, Nash DM, Rangrej J, Shariff SZ, Dixon SN, Jain AK, Garg AX: \u003cstrong\u003eComplications of daytime elective laparoscopic cholecystectomies performed by surgeons who operated the night before\u003c/strong\u003e. \u003cem\u003eJama \u003c/em\u003e2013, \u003cstrong\u003e310\u003c/strong\u003e(17):1837-1841.\u003c/li\u003e\n\u003cli\u003eGovindarajan A, Urbach DR, Kumar M, Li Q, Murray BJ, Juurlink D, Kennedy E, Gagliardi A, Sutradhar R, Baxter NN: \u003cstrong\u003eOutcomes of Daytime Procedures Performed by Attending Surgeons after Night Work\u003c/strong\u003e. \u003cem\u003eThe New England journal of medicine \u003c/em\u003e2015, \u003cstrong\u003e373\u003c/strong\u003e(9):845-853.\u003c/li\u003e\n\u003cli\u003eFeinkohl I, Janke J, Hadzidiakos D, Slooter A, Winterer G, Spies C, Pischon T: \u003cstrong\u003eAssociations of the metabolic syndrome and its components with cognitive impairment in older adults\u003c/strong\u003e. \u003cem\u003eBMC geriatrics \u003c/em\u003e2019, \u003cstrong\u003e19\u003c/strong\u003e(1):77.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 Patient demographics and baseline characteristics\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"642\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristic\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 436px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eM/A\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 65px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 147px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOverall, N = 362\u003csup\u003ea\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMorning, N = 177\u003csup\u003ea\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 147px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAfternoon, N = 185\u003csup\u003ea\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge (years)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e70.0 (67.0, 75.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e71.0 (68.0, 76.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e70.0 (67.0, 73.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.713\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003emale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e122 (33.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e58 (32.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e64 (34.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003efemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e240 (66.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e119 (67.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e121 (65.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBMI\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e(\u003c/strong\u003e\u003cstrong\u003ekg\u0026middot;m\u003csup\u003e2\u003c/sup\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e24.7 (22.5, 27.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e24.8 (22.8, 27.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e24.6 (22.3, 26.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.557\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLiving condition\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.817\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eWith family\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e351 (97.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e172 (97.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e179 (96.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eAlone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e11 (3.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e5 (2.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e6 (3.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEducation level (years)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.562\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026le;6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e155 (42.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e71 (40.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e84 (45.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e6～12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e180 (49.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e93 (52.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e87 (47.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e＞12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e27 (7.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e13 (7.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e14 (7.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSmoking (yes)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e40 (11.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e20 (11.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e20 (10.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.882\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDrinking (yes)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e45 (12.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e24 (13.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e21 (11.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.524\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHypertension (yes)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e174 (48.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e101 (57.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e73 (39.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDiabetes (yes)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e50 (13.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e27 (15.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e23 (12.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.437\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCHD (yes)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e27 (7.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e17 (9.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e10 (5.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.128\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCVD (yes)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e32 (8.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e20 (11.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e12 (6.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.107\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMets (yes)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e129 (35.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e72 (40.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e57 (30.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.050\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFrailty\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.548\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eNon-frail\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e70 (19.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e35 (19.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e35 (18.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003ePrefrail\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e194 (53.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e90 (50.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e104 (56.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eFrailty\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e98 (27.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e52 (29.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e46 (24.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMIC (yes)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e74 (20.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e39 (22.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e35 (18.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.463\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003epre-SD (yes)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e119 (32.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e65 (36.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e54 (29.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.127\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAnxiety/Depression (yes)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e55 (15.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e27 (15.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e28 (15.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.975\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOsteoarthritis (yes)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e252 (69.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e115 (65.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e137 (74.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.060\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003epre-Hb (g/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e128 (116, 137)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e128 (118, 137)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e128 (115, 137)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.983\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003epre-HCT (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e0.39 (0.36, 0.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e0.39 (0.36, 0.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e0.39 (0.36, 0.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.788\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNa\u003csup\u003e+\u0026nbsp;\u003c/sup\u003e(mmol/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e139.9 (138.0, 141.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e139.7 (137.6, 141.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e140.0 (138.0, 141.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.209\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eK\u003csup\u003e+\u0026nbsp;\u003c/sup\u003e(mmol/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e4.00 (3.75, 4.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e4.00 (3.74, 4.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e3.99 (3.76, 4.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.545\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCa\u003csup\u003e2+\u0026nbsp;\u003c/sup\u003e(mmol/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e2.30 (2.23, 2.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e2.29 (2.24, 2.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e2.30 (2.23, 2.36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.644\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGlu (mmol/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e6.00 (5.18, 7.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e6.10 (5.31, 7.15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e5.92 (5.02, 7.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.259\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eALB (g/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e40.6 (38.2, 42.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e40.7 (38.1, 42.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e40.5 (38.3, 42.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.668\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003epre-CRP (mg\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e3 (1, 7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e3 (1, 7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e3 (1, 7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.353\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTG (\u003c/strong\u003e\u003cstrong\u003emmol/L\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e1.83 (1.30, 2.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e1.84 (1.21, 2.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e1.82 (1.30, 2.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.956\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHDL-C (\u003c/strong\u003e\u003cstrong\u003emmol/L\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e1.30 (1.07, 1.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e1.28 (1.05, 1.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e1.31 (1.11, 1.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.424\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHigh Lpa (yes)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e101 (27.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e46 (26.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e55 (29.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.428\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003epre-NLR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e2.35 (1.77, 3.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e2.31 (1.87, 3.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e2.38 (1.65, 3.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.682\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003epre-PLR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e150 (114, 187)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e150 (110, 188)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e150 (117, 186)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.538\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003epre-SII\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e623 (432, 863)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e614 (430, 817)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e634 (441, 911)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.521\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003epre-VAS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e2.00 (2.00, 3.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e2.00 (2.00, 3.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e2.00 (2.00, 3.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.367\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eASA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.005\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eⅡ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e227 (62.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e98 (55.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e129 (69.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eⅢ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e135 (37.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e79 (44.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e56 (30.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurgery site\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.022\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eTHA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e130 (35.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e74 (41.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e56 (30.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eTKA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e232 (64.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e103 (58.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e129 (69.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eNote:\u003c/strong\u003e \u003csup\u003ea\u0026nbsp;\u003c/sup\u003eMedian (IQR); n (%), \u003csup\u003eb\u0026nbsp;\u003c/sup\u003eWilcoxon rank sum test, \u003csup\u003ec\u0026nbsp;\u003c/sup\u003ePearson\u0026apos;s Chi-squared test.\u003c/p\u003e\n\u003cp\u003eFrailty was defined as the FRAIL Scores (0 was Non-frail, 1~2 was prefrail, ＞2 was frailty); MIC was defined as the Mini-Cog Score＜2; Mets was defined as \u0026ge;3 of 5 criteria[53]: (1) obesity, (2) elevated fasting triglyceride, (3) reduced HDL-C, (4) elevated blood pressure, and (5) elevated glucose; Hypotension was defined as a reduction in mean arterial pressure [MAP] exceeding 20% from baseline or a MAP \u0026lt;60 mmHg); SD (sleep disturbance) was defined as the sleep-NRS \u0026ge;6 or RCSQ\u0026le;50.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e \u003cstrong\u003eAbbreviations:\u003c/strong\u003e BMI, Body Mass Index; CHD, Coronary Heart Disease; CVD, Cerebrovascular Disease; Mets, Metabolic syndrome; MIC, Mild Cognitive Impairment; pre-SD, preoperative Sleep Disturbance; Hb, hemoglobin; HCT, hematocrit; Glu, Blood glucose; ALB, albumin; CRP, C-reactive protein; TG, Triglyceride; HDL-C, high-density lipoprotein cholesterol; Lp(a), lipoprotein(a); NLR, Neutrophil-to-Lymphocyte Ratio; PLR, Platelet-to-Lymphocyte Ratio; SII, Systemic-immune-inflammation index; VAS, Visual Analog Scale; ASA, American Society of Anesthesiology; THA, total hip arthroplasty; TKA, total knee arthroplasty.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 2 Intraoperative variables of patients accepting morning or afternoon surgery\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristic\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 52px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eM/A\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMorning, N = 177\u003csup\u003ea\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAfternoon, N = 185\u003csup\u003ea\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePropofol (yes)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25px;\"\u003e\n \u003cp\u003e116 (65.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003e124 (67.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.764\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCiprofol (yes)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25px;\"\u003e\n \u003cp\u003e61 (34.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003e61 (33.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.764\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRemazolam (yes)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25px;\"\u003e\n \u003cp\u003e63 (35.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003e60 (32.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.526\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDexmedetomidine (yes)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25px;\"\u003e\n \u003cp\u003e86 (48.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003e92 (49.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.828\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRemifentanil consumption\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25px;\"\u003e\n \u003cp\u003e0.60 (0.49, 0.77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003e0.62 (0.50, 0.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.205\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAnalgesic consumption\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25px;\"\u003e\n \u003cp\u003e0.15 (0.10, 0.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003e0.10 (0.10, 0.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.341\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eInfusion volume\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25px;\"\u003e\n \u003cp\u003e1,310 (1,080, 1,630)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003e1,265 (1,020, 1,620)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.540\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEstimate bleed\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25px;\"\u003e\n \u003cp\u003e100 (50, 200)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003e50 (50, 200)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.352\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDuration of Anesthesia\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25px;\"\u003e\n \u003cp\u003e136 (117, 157)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003e149 (126, 170)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.007\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDuration of surgery\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25px;\"\u003e\n \u003cp\u003e95 (81, 113)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003e105 (85, 130)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.007\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIntraoperative Hypotension (yes)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25px;\"\u003e\n \u003cp\u003e160 (90.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003e140 (75.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBlood transfusion (yes)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25px;\"\u003e\n \u003cp\u003e71 (40.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003e63 (34.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.233\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePNB (yes)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25px;\"\u003e\n \u003cp\u003e149 (84.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003e160 (86.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.535\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePCA (yes)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25px;\"\u003e\n \u003cp\u003e130 (73.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003e136 (73.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.988\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eNote:\u003c/strong\u003e \u003csup\u003ea\u0026nbsp;\u003c/sup\u003eMedian (IQR); n (%), \u003csup\u003eb\u0026nbsp;\u003c/sup\u003eWilcoxon rank sum test, \u003csup\u003ec\u0026nbsp;\u003c/sup\u003ePearson\u0026apos;s Chi-squared test.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations:\u0026nbsp;\u003c/strong\u003ePNB, Peripheral Nerve Block; PCA, Patient Controlled Analgesia.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 3 Primary Outcome and Prespecified Secondary Outcomes on daytime variation (afternoon vs. morning)\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"746\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 117px;\"\u003e\n \u003cp\u003eVarious\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 314px;\"\u003e\n \u003cp\u003eUnadjusted\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 315px;\"\u003e\n \u003cp\u003eAdjusted\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 118px;\"\u003e\n \u003cp\u003eOR (95%CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003eMean Difference\u003c/p\u003e\n \u003cp\u003e(95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003eOR (95%CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003eLS Mean Difference\u003c/p\u003e\n \u003cp\u003e(95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"8\" style=\"width: 746px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrimary outcome\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 123px;\"\u003e\n \u003cp\u003eFunctional recovery \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 112px;\"\u003e\n \u003cp\u003e2.45 (1.58, 3.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e1.94 (1.18,3.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.009\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"8\" style=\"width: 746px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSecondary outcomes (7-days)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 123px;\"\u003e\n \u003cp\u003ePOD\u003csup\u003e\u0026nbsp;a\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 112px;\"\u003e\n \u003cp\u003e0.43 (0.25, 0.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e0.50 (0.29, 0.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.015\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 123px;\"\u003e\n \u003cp\u003ePSD\u003csup\u003e\u0026nbsp;a\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 112px;\"\u003e\n \u003cp\u003e0.49 (0.32, 0.74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e0.49 (0.32, 0.77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 123px;\"\u003e\n \u003cp\u003ePAD \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 112px;\"\u003e\n \u003cp\u003e0.72 (0.48, 1.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e0.67 (0.43, 1.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e0.078\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 123px;\"\u003e\n \u003cp\u003eDizzy\u003csup\u003e\u0026nbsp;a\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 112px;\"\u003e\n \u003cp\u003e0.89 (0.58, 1.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e0.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e0.87 (0.56, 1.36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e0.540\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 123px;\"\u003e\n \u003cp\u003ePONV\u003csup\u003e\u0026nbsp;a\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 112px;\"\u003e\n \u003cp\u003e0.75 (0.49, 1.15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e0.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e0.76 (0.48, 1.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e0.230\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 123px;\"\u003e\n \u003cp\u003eLOS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 112px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003e-0.48 (-1.6, 0.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e0.409\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e-0.24 (-1.42, 0.94)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e0.693\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 123px;\"\u003e\n \u003cp\u003eActive day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 112px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003e-0.16 (-0.38, 0.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e0.043\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e0.05 (-0.15, 0.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e0.622\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 123px;\"\u003e\n \u003cp\u003eCost\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 112px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003e-637.7\u003c/p\u003e\n \u003cp\u003e(-4016.7, 2741.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e0.712\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e91.1\u003c/p\u003e\n \u003cp\u003e(-3417.4, 3599.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e0.959\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 123px;\"\u003e\n \u003cp\u003eQor-15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 112px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003e0.35 (-0.85, 1.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e0.565\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e-0.16 (-1.40, 1.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e0.796\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"8\" style=\"width: 746px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSecondary outcomes (30-days)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 123px;\"\u003e\n \u003cp\u003eTICS-m \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 112px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003e0.53 (-0.9, 1.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e0.097\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e0.04 (-0.57, 0.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e0.906\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 123px;\"\u003e\n \u003cp\u003eSatisfaction\u003csup\u003e\u0026nbsp;b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 112px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003e0.16 (-0.01, 0.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e0.066\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e0.06 (-0.11, 0.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e0.475\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 123px;\"\u003e\n \u003cp\u003eRCSQ\u003csup\u003e\u0026nbsp;b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 112px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003e0.08 (-0.03, 0.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e0.171\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e0.03 (-0.09, 0.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e0.656\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 123px;\"\u003e\n \u003cp\u003eGAD-7\u003csup\u003e\u0026nbsp;b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 112px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003e-0.14 (-0.33,0.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e0.157\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e-0.08 (-0.29, 0.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e0.428\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 123px;\"\u003e\n \u003cp\u003ePHQ-9\u003csup\u003e\u0026nbsp;b\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 112px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003e-0.09 (-0.28, 0.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e0.303\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e-0.03 (-0.22, 0.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e0.760\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 123px;\"\u003e\n \u003cp\u003eVAS-rest\u003csup\u003e\u0026nbsp;b\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 112px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003e-0.05 (-0.18, 0.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e0.402\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e-0.08 (-0.21, 0.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e0.219\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 123px;\"\u003e\n \u003cp\u003eVAS-move\u003csup\u003e\u0026nbsp;b\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 112px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003e-0.11 (-0.28, 0.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e0.177\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e-0.11 (-0.28, 0.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e0.221\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eNote:\u003c/strong\u003e \u003csup\u003ea\u0026nbsp;\u003c/sup\u003eNumber (%), \u003csup\u003eb\u0026nbsp;\u003c/sup\u003eMean (Standard Deviation), Analysis were adjusted for age, ASA, Osteoarthritis, Surgery site, Hypertension, Intraoperative hypotension. Functional recovery defined as ability to walk without human assistance at 30 days.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e POD, postoperative delirium; PSD, postoperative sleep disturbances; PAD, postoperative anxiety and depression; PONV, postoperative nausea and vomiting; LOS, length of hospital stay; Qor-15, quality of recovery; TICS-m, Telephone Interview for Cognitive Status-modified; RCSQ, Richards\u0026ndash;Campbell Sleep Questionnaire; GAD-7, Generalized Anxiety Disorder-7; PHQ-9, Patient Health Questionnaire-9; VAS, Visual Analog Scale.\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":"Daytime variation, circadian rhythm, total joint arthroplasty, general anesthesia","lastPublishedDoi":"10.21203/rs.3.rs-6338495/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6338495/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eThe circadian rhythm influences various physiological processes, affecting health outcomes significantly. This study aims to explore the impact of daytime variation on outcomes following total joint arthroplasty, specifically focusing on the recovery of independent walking ability.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMaterials and Methods:\u003c/strong\u003e Between May 2023 and May 2024, we prospectively evaluated 530 consecutive patients undergoing total joint arthroplasty. Daytime variation was categorized into morning (7:30 a.m. to 12:00 p.m.) and afternoon (12:00 p.m. to 6:00 p.m.) based on anesthesia records. Functional recovery, defined as the ability to independently walk across a room 30 days post-surgery, was assessed via telephone interviews. Multivariate logistic regression analyzed factors influencing functional recovery.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Of 362 patients, 177 (48.9%) underwent morning surgeries and 185 (51.1%) underwent afternoon surgeries. Before adjustment, a higher proportion of patients in the afternoon surgery group achieved functional recovery compared to the morning group (71.9% vs. 54.8%). After adjusting for potential confounders, patients undergoing morning surgeries were less likely to regain independent walking ability compared to those undergoing afternoon surgeries (adjusted odds ratio [aOR], 1.94; 95% CI, 1.18 to 3.20; P=0.009). Incidences of postoperative delirium (aOR, 0.50; 95% CI, 0.29 to 0.88; P=0.015) and postoperative sleep disturbances (aOR, 0.49; 95% CI, 0.32 to 0.77; P=0.002) within the first 7 days were lower in the afternoon surgery group. Multivariable regression analysis, afternoon surgery was found to be statistically associated with increased odds of functional recovery (aOR: 1.75; 95% CI, 1.03 to 2.97; P=0.039). No significant differences were observed in other clinical outcomes.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e Daytime variation appears to significantly influence outcomes following total joint arthroplasty, particularly in achieving independent walking ability at 30 days postoperatively.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number: \u003c/strong\u003enot applicable.\u003c/p\u003e","manuscriptTitle":"Daytime variation on clinical outcomes in elderly after total joint arthroplasty under general anaesthesia：a prospective study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-09 01:54:51","doi":"10.21203/rs.3.rs-6338495/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":"6c94279a-fc83-4f7d-bc3f-b4d1869b62ff","owner":[],"postedDate":"May 9th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-04-18T08:53:19+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-09 01:54:51","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6338495","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6338495","identity":"rs-6338495","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}