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. 2025 Jul 1;25:329. doi: 10.1186/s12871-025-03197-6

Comparison of the effects of remimazolam and propofol on postoperative delirium in elderly surgical patients: a meta-analysis

Jiayu Huang 1, Zhenke Xiao 1, Junming Lao 1, Lingli Pan 1, Zhou Chen 1, Zehua Lin 1,✉
PMCID: PMC12220280  PMID: 40597650

Abstract

Objective

This meta-analysis evaluated the effectiveness of remimazolam compared to propofol in preventing postoperative delirium among elderly surgical patients.

Methods

We systematically searched PubMed, CNKI, Cochrane Library, Web of Science, Embase, Wangfang, and VIP for randomized controlled trials (RCTs) comparing remimazolam and propofol for postoperative delirium prevention in elderly surgical patients (last search: July 27, 2024). Data were analyzed using Stata 15.0.

Results

Eight randomized controlled trials (2,013 participants; remimazolam = 1,034, propofol = 979) found no significant differences in postoperative delirium incidence [RR = 0.67,95%CI(0.45–1.01)], severity [WMD=-0.28,95%CI(-0.61-0.04)], or duration [WMD=-0.06,95%CI(-0.15-0.03)], nor in postoperative pain VAS scores [WMD=-0.08,95%CI(-0.18-0.02)]. remimazolam significantly reduced postoperative hypotension risk compared to propofol [RR = 0.48,95%CI(0.29–0.80)], demonstrating improved safety.

Conclusion

This meta-analysis demonstrates comparable efficacy between remimazolam and propofol in preventing postoperative delirium, with remimazolam demonstrating superior safety through significantly lower postoperative hypotension rates.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12871-025-03197-6.

Keywords: Remimazolam, Propofol, Postoperative delirium, Elderly, Anesthesia, Meta-analysis

Introduction

Delirium is an acute disorder of brain function characterized by sudden changes in consciousness, attention, and cognition. Postoperative delirium (POD) is prevalent among older adults, with incidence rates ranging from 11–51% [1]. Symptoms of POD include impaired consciousness, hallucinations, poor concentration, and insomnia.

Postoperative delirium can significantly impact surgical outcomes. In cardiac valve replacement surgeries with cardiopulmonary bypass, POD incidence can reach 25%. Similarly, reported rates among elderly colorectal cancer surgery patients range from 13.8–30% [1]. Postoperative delirium not only disrupts the recovery process but also contributes to increased postoperative complications and mortality rates, ultimately leading to higher healthcare costs [2, 3]. Furthermore, it prolongs hospital stays, exacerbates morbidity, and adversely affects long-term cognitive function [4].

The mechanisms of postoperative delirium are complex and not fully understood, but identified risk factors include advanced age, intraoperative opioid use, hypotension, benzodiazepine use, and postoperative pain [5–8]. Intraoperative anesthesia management significantly affects POD occurrence, with benzodiazepines and postoperative inflammatory responses being significant contributors. Studies suggest optimizing sedation and analgesia strategies can help mitigate these risk factors and improve patient outcomes [9]. Therefore, enhancing anesthesia management is crucial for reducing the risk associated with POD [10].

In summary, addressing the risk of postoperative delirium among older adults is of significant clinical importance [11]. Optimizing anesthesia protocols and enhancing postoperative care can reduce the incidence of POD, improve patient outcomes, and decrease healthcare costs. This comprehensive approach not only enhances the quality of life for older patients but also elevates the overall standards of medical services, thereby warranting serious attention and further research from anesthesiologists.

In contemporary surgical sedation and anesthesia, midazolam and propofol remain the primary hypnotics, frequently administered in conjunction with opioid analgesics such as fentanyl or sufentanil [12]. Propofol is notably recognized for its highly effective intravenous sedation properties, characterized by a rapid onset of 15 to 40 s, a brief half-life, and swift patient recovery. These attributes make propofol an optimal choice for both standalone applications and in combination with opioids [13, 14]. However, recent evidence suggests a potential correlation between propofol usage and the incidence of POD, which may be attributed to its interactions with muscarinic acetylcholine receptors [15].

Remimazolam besylate, a novel intravenous sedative, has been approved for anesthetic use in various clinical settings [16–18]. It offers several advantages, including rapid onset of action, swift metabolism, expedited patient recovery, minimal injection discomfort, independence from hepatic and renal metabolism, and negligible effects on respiratory and circulatory functions [19]. Despite its growing clinical use, evidence supporting its efficacy and safety remains limited [20]. Pharmacokinetic findings suggest that the context-sensitive decrement time (CSDT) of remimazolam is comparable to that of propofol, which may challenge its classification as an “ultra-short-acting” benzodiazepine [21, 22]. Recent studies indicate that remimazolam may improve hemodynamic stability during anesthesia induction, particularly in high-risk cardiac surgery patients [23, 24]. While these findings are promising, further investigation is required to define its clinical role better and optimize its application. Existing research exhibits certain methodological limitations, highlighting the need for larger, prospective trials to validate its safety and efficacy [25].

With its unique pharmacological profile, remimazolam could be a valuable alternative to propofol in selected clinical scenarios. While the safety and effectiveness of remimazolam and propofol in preventing POD are still subjects of ongoing debate, this study seeks to systematically evaluate and compare these two anesthetics through a meta-analysis [26]. By integrating available clinical data, we aim to provide a more evidence-based foundation for anesthetic decision-making and ultimately enhance postoperative patient care and outcomes.

Methods

The systematic review discussed in this paper was accepted by the online PROSPERO International Prospective Register of Systematic Reviews. The protocol has been registered with PROSPERO under the identifier CRD42024585998 (amended on May 15, 2025).

Inclusion and exclusion criteria

This study included elderly patients aged 60 years and above who underwent elective surgery. It conducted a comparative analysis between remimazolam and propofol for sedation or general anesthesia in these patients. The primary outcomes assessed included the incidence, duration, and severity of POD, while secondary outcomes encompassed Visual Analog Scale (VAS) scores and adverse events. Only randomized controlled trials (RCTs) were considered eligible for inclusion. Exclusion criteria comprised meta-analyses, systematic reviews, conference abstracts, animal studies, articles lacking complete text, case reports, and studies that did not measure the specified outcomes.

Literature retrieval

Randomized controlled trials comparing remimazolam and propofol regarding the impact of delirium were systematically searched in multiple databases, such as PubMed, CNKI, Cochrane Library, Embase, Web of Science, Wangfang, and VIP. The search was conducted with a cutoff date of July 27, 2024. We implemented a comprehensive strategy that utilized a mix of MeSH terms and free-text keywords, including “remimazolam,” “propofol,” and “delirium.” The detailed search strategies can be found in Table S1.

Data extract

According to established inclusion and exclusion criteria, a thorough review of the literature was conducted by two independent authors. In cases of difference of opinion, resolution was achieved via discussion or consulting a third party for an impartial opinion. The critical information extracted from the incorporated studies included the following details: author, country of study, year of publication, sample size (for both remimazolam and propofol groups), sex distribution, age range, type of surgery, specifics of the intervention, and reported outcomes.

Included studies’ risk of bias

The investigators conducted an independent evaluation of bias risk employing the Cochrane Collaboration’s tools, classifying the risk into three categories: low, unclear, or high. This evaluation included the following seven domains: completeness of outcome data (attrition bias), blinding of outcome assessors (detection bias), selective reporting of study results (reporting bias), allocation concealment (selection bias), blinding of participants and personnel (performance bias), generation of randomized sequences (selection bias), and other possible sources of bias. Each study that was included underwent an individual evaluation based on these criteria. Studies fulfilling all criteria were designated as having a “low risk” of bias, indicating high methodological quality with minimal overall risk for biases. Studies that partially fulfilled the requirements were categorized as presenting an “unclear risk,” signifying a moderate potential for biases. Conversely, studies failing to meet the criteria were classified as “high risk,” indicating substantial risks for biases and low methodological quality. The included studies were evaluated for bias risk utilizing Review Manager 5.4 software.

Data analysis

The data collected were analyzed using Stata 15.0 software. A random-effects model was employed to pool effect sizes, accounting for between-study heterogeneity (assessed via I² statistics). Given the variations in hospital settings, geographic regions, and interventions, the random-effects model ensured the generalizability of the results. Continuous outcomes were reported as weighted mean differences (WMD) and dichotomous outcomes as relative risks (RR), both with 95% confidence intervals (CIs). Sensitivity analyses and Egger’s test assessed result robustness and publication bias, respectively.

Results

Study selection

Figure 1 presents the flowchart of our literature search process. Initially, 130 documents were retrieved. After removing 58 duplicates, we excluded 46 articles based on a review of their titles and abstracts. Furthermore, an additional 18 papers were excluded following full-text evaluation, including eight randomized controlled trials [11, 15, 20, 26–30] in the final analysis.

Fig. 1.

Fig. 1

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PRISMA flow diagram of the study process

Essential characteristics and risk of bias of the included studies

Figure 1 illustrates the process of our literature search. Initially, we identified 130 documents. After eliminating 58 duplicates, we excluded 46 articles according to their titles, and an additional 18 articles were excluded after a thorough review of the full text. As a result, eight RCT trials [11, 15, 20, 26–30] were included in the analysis. These studies collectively involved 2,013 participants: 1,034 individuals in the remimazolam group and 979 in the propofol group, all aged over 60 years. The dosages administered varied between 0.05 and 1.2 mg/kg for remimazolam and 0.3 to 10 mg/kg for propofol via intravenous administration. Table 1 illustrates the baseline features of these studies. All of them provided clear descriptions of their randomization methods. An assessment of bias risk is presented in Figs. 2 and 3, further substantiating the reliability of the incorporated studies.

Table 1.

Basic characteristics of the included studies

Study Year Country Sample size Gendr (M/F) Mean age(year) Type of surgery Intervention Outcome
R P R P R P
GC DUAN 2024 China 53 53 49/57 77.4 75.3 Orthopedic Surgery 0.05~0.3mg/kg 0.3~3mg/kg ①⑤
JP TIAN 2024 China 90 90 78/102 69.41 66.29 cardiac surgery 0.25~1mg/kg 1~4mg/kg ①②⑤
MY LI 2022 China 90 30 65/55 69.93 71.03 Orthopedic Surgery 0.25~0.35mg/kg 1.0mg/kg ①
JZ WANG 2024 China 80 80 76/84 72.5 71.6 Orthopedic Surgery 0.3~0.8mg/kg 2~4mg/kg ①④⑤
Q FAN 2024 China 160 159 137/182 71.31 70.92 cardiac surgery 0.5~1.0mg/kg 4~10mg/kg ①②③④⑤
TL LIU 2024 China 50 50 43/57 71.6 71.4 Colorectal Surgery 0.1~1.2mg/kg 1~10mg/kg ①④
PP FANG 2024 China 364 364 263/465 73.04 73.04 Orthopedic Surgery 0.2~0.25mg/kg 1.5~2.0mg/kg ①⑤
JJ YANG 2023 China 147 153 117/183 68 68 Orthopedic Surgery 0.2~0.35mg/kg 1.0~1.5mg/kg ①③⑤
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R Remimazolam, P Propofol, M/F Male/Female

①POD:postoperative delirium

②POD severity score

③Duration of POD

④VAS:visual analogue scale

⑤Hypotension

Fig. 2.

Fig. 2

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Risk of bias graph

Fig. 3.

Fig. 3

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Risk of bias summary

Result of meta-analysis

The incidence of POD

Eight studies [11, 15, 20, 26–30] report the incidence of postoperative delirium, which includes 163 cases in the remimazolam cohort and 196 cases in the propofol cohort. Significant heterogeneity is detected (I²=74%, P = 0.0003), requiring the application of a random-effects model; subgroup analyses are also conducted. The results, presented in Figs. 4 and 5, indicate no statistically significant difference in POD incidence between the remimazolam and propofol groups (RR 0.67; 95% CI: 0.45–1.01; P = 0.06; df = 7; I²=74%; Fig. 4). Given the high level of heterogeneity, sensitivity analyses and tests for publication bias—including funnel plots and Egger’s test—were performed. The supplementary figures (S1-S3) demonstrate low sensitivity and confirm the robustness of these findings.

Fig. 4.

Fig. 4

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Forest plot of the incidence of POD

Fig. 5.

Fig. 5

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Forest subgroup - The incidence of POD

POD severity score

Two studies [15, 20] assessed the severity of POD, comprising 250 cases in the remimazolam group and 249 cases in the propofol group. A test for heterogeneity revealed considerable variability (I²=77.9%, P = 0.033), necessitating a random-effects model. The results (Fig. 6) showed no statistically significant difference in POD severity between the remimazolam and propofol groups (WMD = −0.28; 95% CI: −0.61 to 0.04). Given the high level of heterogeneity, we performed a sensitivity analysis utilizing a one-by-one approach, which demonstrated low sensitivity and confirmed the robustness of this outcome (Supplementary Figure S4).

Fig. 6.

Fig. 6

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Forest plot of POD severity score

Duration of POD

The duration of POD was analyzed in two studies [20, 26], comprising 307 patients in the remimazolam group and 312 patients in the propofol group. Heterogeneity analysis revealed low variability among the included studies, with I² = 0% and P = 0.432. A random-effects model was applied to account for potential differences in hospital settings, geographic regions, and interventions. As illustrated in Fig. 7, no significant difference was observed in POD duration between the remimazolam and propofol groups [WMD = −0.06, 95% CI (−0.15, 0.03)].

Fig. 7.

Fig. 7

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Forest plot of Duration of POD

The VAS scores of postoperative pain

Postoperative pain, measured using visual analog scale (VAS) scores, was reported in three studies [11, 20, 29], including 290 patients in the remimazolam group and 289 in the propofol group. The analysis revealed minimal heterogeneity (I² = 0%, P = 0.773), indicating consistency across studies. A random-effects model was applied to address variability stemming from differences in clinical settings and interventions. As presented in Fig. 8, the pooled results showed no statistically significant difference in VAS scores between the remimazolam and propofol groups [WMD = −0.08, 95% CI (−0.18, 0.02)].

Fig. 8.

Fig. 8

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Forest plot of the VAS Scores of Postoperative Pain

The adverse events of hypotension

Six studies [15, 20, 26, 27, 29, 30] reported adverse events, encompassing 894 cases in the remimazolam group and 899 cases in the propofol group. Testing for heterogeneity indicated considerable variability (I² = 82.3%, P = 0.005), which required using a random-effects model for the analysis. The results (Fig. 9) suggested that remimazolam was linked to a significantly reduced incidence of postoperative hypotension compared to propofol [RR = 0.48; 95% CI: 0.29 to 0.80]. Given the high level of heterogeneity, a sensitivity analysis employing a one-by-one exclusion method was conducted. The findings (Supplementary Figure S5) demonstrated low sensitivity and stable outcomes regarding this effect.

Fig. 9.

Fig. 9

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Forest plot of Hypotension

Heterogeneity analysis

Significant heterogeneity was noted across most outcomes, with I² values exceeding 50%, suggesting moderate to high variability among included studies. Variations in hospital settings, geographic regions, and surgical interventions likely contributed to the observed heterogeneity. A random-effects model was consistently employed in the pooled analyses to account for these differences and improve the generalizability of results.

Published bias

Egger’s test assessed publication bias concerning the incidence of POD, postoperative VAS scores, and hypotension-related adverse events. The analysis indicated no evidence of publication bias regarding hypotension-related adverse events (P = 0.082; Supplementary Figure S6). Conversely, significant evidence of publication bias was found for the incidence of POD (P = 0.029; Supplementary Figure S3) and the postoperative VAS scores (P = 0.195; Supplementary Figure S7).

Discussion

This is the first meta-analysis comparing the effects of remimazolam and propofol on POD in elderly patients undergoing surgery. Our findings indicate no substantial difference between remimazolam and propofol regarding the incidence of POD, its severity score, or duration. Specifically, the results showed no significant differences between these agents concerning POD incidence (RR = 0.67, 95% CI: 0.45–1.01, P = 0.06), severity, or duration. However, remimazolam demonstrated a significantly lower risk of postoperative hypotension than propofol (RR = 0.48, 95% CI [0.29–0.80]). These results suggest that remimazolam is a safe and effective alternative to propofol for elderly patients, particularly those requiring hemodynamic stability during anesthesia. In addition to pharmacological approaches, non-pharmacological strategies, such as patient-clinician communication, can reduce anxiety and lower the risk of POD. Recent studies [31] emphasize that empathetic communication significantly alleviates preoperative anxiety, a key risk factor for POD. Incorporating these strategies into perioperative care may improve patient outcomes.

Postoperative delirium is a common complication encountered in elderly individuals following surgical interventions. Postoperative delirium has complex triggers, including age, preoperative cognitive reserve, anesthesia drugs, depth of anesthesia, duration of surgery, intraoperative complications, and pain [32]. Although the intricate pathophysiological mechanisms underlying delirium remain inadequately understood, various biological factors interact, resulting in significant disruption of neural networks in the brain, leading to cognitive dysfunction and delirium [33]. However, intraoperative factors such as hypotension and disturbances within the internal environment may contribute to cerebral hypoxia, thereby increasing the risk of delirium [34].

Emerging evidence suggests that anesthetics, including propofol and benzodiazepines, may influence neural activity through epigenetic mechanisms, such as histone modification and DNA methylation, which alter gene expression and synaptic function. These processes are pivotal in neuronal health and may impact POD risk [35]. Understanding these mechanisms provides deeper insights into optimizing anesthetic strategies and reducing POD incidence. An in-depth comprehension of these complex, interrelated mechanisms is crucial for developing targeted interventions to reduce the incidence of POD among this vulnerable population undergoing surgery [15].

Remimazolam has demonstrated efficacy in decreasing the occurrence of postoperative delirium through the modulation of γ-aminobutyric acid (GABA) receptors. This mechanism enhances chloride ion channel activity, decreasing neuronal excitability [36]. Unlike traditional benzodiazepines, remimazolam is metabolized by non-specific esterases rather than hepatic or renal pathways, providing a significant advantage for elderly patients with liver or kidney impairment [37]. Patients with severe liver dysfunction exhibit reduced metabolism of remimazolam, necessitating careful dose adjustments or early discontinuation to ensure both safety and efficacy [26].

Emerging evidence robustly underscores the efficacy of remimazolam in mitigating postoperative delirium. Studies referenced in sources [38] and [39] indicate that remimazolam significantly reduces both the incidence and severity of delirium, likely attributable to its rapid metabolism and ability to stabilize cerebral oxygenation. This anesthetic demonstrates particular effectiveness in elderly patients when administered alongside alfentanil for painless gastrointestinal procedures. A retrospective analysis examined individuals receiving Transfemoral Transcatheter Aortic Valve Implantation (TF-TAVI) [40], revealing a substantially lower incidence of delirium among those treated with remimazolam compared to those treated with propofol. Furthermore, multivariate analysis confirmed that remimazolam was independently linked to a reduced chance of developing delirium.

This analysis reveals no notable difference between remimazolam and propofol concerning the incidence, duration, and severity of POD in geriatric patients. This finding confirms the noninferiority of remimazolam regarding these parameters. While the limited sample size may constrain the broader applicability of our findings, evidence suggests that remimazolam does not elevate the risk of POD compared to propofol. Consequently, in clinical settings where meticulous management of POD is essential, remimazolam emerges as a promising and effective alternative.

Maintaining hemodynamic stability during surgery is essential for minimizing the risk of postoperative delirium. Remimazolam proves particularly effective in sustaining stable blood pressure and heart rate, even in high-risk surgical contexts. Its relatively mild cardiovascular effects contribute to expedited patient recovery and a decreased likelihood of postoperative complications. These pharmacological characteristics position remimazolam as an optimal anesthetic choice, significantly lowering rates of postoperative delirium and enhancing surgical outcomes in geriatric patients.

A systematic review and meta-analysis [41] assessed the safety profiles of remimazolam in comparison to propofol during general anesthesia, revealing that remimazolam significantly reduces the incidence of hypotensive events. This analysis encompassed eight randomized controlled trials involving 998 participants, demonstrating a more stable mean arterial pressure (MAP) before and after intubation with remimazolam. Furthermore, another meta-analysis [42] corroborated these findings by indicating a significant reduction in hypotension associated with the administration of remimazolam compared to propofol in individuals undergoing general surgical procedures. The existing body of evidence strongly supports the endorsement of remimazolam as a safer anesthetic alternative, as it minimizes the risk of hypotension.

In this systematic review and meta-analysis, we assessed the effects of remimazolam versus propofol on POD, pain levels measured by the VAS, and hypotension-related adverse events. The analysis included data on POD incidence, severity, duration, and VAS scores. The results indicated no notable differences between the two agents related to POD incidence (RR = 0.67, 95% CI: 0.45–1.01, P = 0.06), severity, duration, or VAS scores. However, remimazolam demonstrated a considerably lower risk of postoperative hypotension than propofol (RR = 0.48, 95% CI: 0.29–0.80). Despite some heterogeneity, sensitivity analyses and Egger’s test for publication bias confirmed these findings. Notably, publication bias was detected regarding POD incidence; however, there was no significant bias related to VAS scores or hypotension-related adverse events. These findings provide valuable insights for clinicians when selecting sedative agents in practice.

This analysis presents several limitations. Firstly, it encompasses only eight studies with a total of 2,013 participants. Secondly, some subgroup analyses still need to be completed as they did not fully incorporate all relevant studies. For instance, no substantial differences were identified in the duration and severity of delirium or postoperative VAS scores; these findings may be attributed to insufficient studies and small sample sizes, which could undermine the robustness of our conclusions. Additionally, this meta-analysis amalgamates data from the eight RCTs included in the analysis, which may increase heterogeneity and introduce biases, particularly selection bias. Variations in anesthesia duration due to differing types of surgery further complicate the standardization of induction and maintenance dosages. Consequently, inconsistent anesthetic drug dosages across studies represent another notable limitation of this investigation.

Conclusion

Our study demonstrates that remimazolam and propofol yield comparable outcomes concerning the incidence, duration, and severity of POD in geriatric patients. This finding supports the assertion of noninferiority for remimazolam. Hypotension occurred less frequently within the remimazolam cohort, suggesting a potential safety advantage. However, these results must be viewed with caution due to various limitations, such as small sample size, variability in study design, and short follow-up durations, which may impact the long-term assessment of postoperative delirium outcomes and should be considered when interpreting the results. Future studies should focus on conducting well-designed RCTs with larger sample sizes and longer follow-up durations to confirm these findings.

Supplementary Information

12871_2025_3197_MOESM1_ESM.docx (15.7MB, docx)

Supplementary Material 1: Table S1 Literature search strategy. Figure S1 sensitivity analyses-The Incidence of POD. Figure S2 funnel plots - The Incidence of POD. Figure S3 Eggers test - The Incidence of POD. Figure S4 sensitivity analyses - POD Severity Score. Figure S5 sensitivity analyses - The Adverse Events of Hypotension. Figure S6 Eggers test– Hypotension. Figure S7 Eggers test - The VAS Scores of Postoperative Pain.

Supplementary Material 2. (29.9KB, docx)

Acknowledgements

Not applicable.

Clinical trial number

Not applicable.

Conflict of interest

The authors declare that there are no conflicts of interest.

Authors’ contributions

All authors contributed to the study conception and design. Jiayu Huang: Conceptualization, Methodology, Software, Writing- Original draft, Data curation, Visualization were performed; Zhenke Xiao, Junming Lao, Lingli Pan and Zhou Chen: Investigation, Writing - Original Draft, Writing - Reviewing and Editing were performed; Zehua Lin: Conceptualization, Supervision, Project administration were performed. All authors read and approved the final manuscript.

Funding

1.Guangzhou Municipal Key Discipline in Medicine (2025–2027).

2.Project supported by the Natural Science Foundation of Guangdong Province, China (No.2023A1515011117).

3.Major clinical research project of Scientific research Capacity Improvement Program of Guangzhou Medical University (GMUCR2025-02030).

Data availability

The data used to support the findings of this study are included within the article.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Footnotes

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

12871_2025_3197_MOESM1_ESM.docx (15.7MB, docx)

Supplementary Material 1: Table S1 Literature search strategy. Figure S1 sensitivity analyses-The Incidence of POD. Figure S2 funnel plots - The Incidence of POD. Figure S3 Eggers test - The Incidence of POD. Figure S4 sensitivity analyses - POD Severity Score. Figure S5 sensitivity analyses - The Adverse Events of Hypotension. Figure S6 Eggers test– Hypotension. Figure S7 Eggers test - The VAS Scores of Postoperative Pain.

Supplementary Material 2. (29.9KB, docx)

Data Availability Statement

The data used to support the findings of this study are included within the article.

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