Correspondence to Dr Huang Xiaojie; [email protected] ; Shaoyong Xu; [email protected]
Strengths and limitations of this study
This randomised controlled non-inferiority trial is bolstered by a pragmatic design, meticulous recruitment processes, allocation concealment and a comprehensive follow-up programme.
The incorporation of the secondary analyses enhances the potential for a more nuanced interpretation of the findings and permits the detection of intervention effect heterogeneity across various covariates.
The generalisability of the findings is constrained by the single-centre design.
The intervention’s nature of unblinding could have influenced the outcome assessors.
Patient self-reporting for the time to first flatus and certain secondary outcomes raises the possibility of recall or reporting bias.
Introduction
Gynaecological oncology surgery, an abdominal procedure with significant surgical invasiveness, often leads to postoperative complications, including ileus, which occurs in 10.6%‒50.0% of patients undergoing pelvic and para-aortic lymph node dissection for gynaecological malignancies.1 2 Postoperative ileus is linked to extended hospital stays,3 delayed recovery and increased healthcare costs.4 5 Thus, minimising complications and fostering early recovery in gynaecological oncology surgery patients is a critical clinical focus.
The Enhanced Recovery After Surgery (ERAS) protocol, an evidence-based, multidisciplinary approach, has been established to facilitate early postoperative recovery.6 It encompasses preoperative bowel preparation, intraoperative pain management4 and enteral nutrition postoperatively.7–9 The ERAS programme aims to diminish complication rates, expedite bowel function recovery and shorten hospital stay by integrating a suite of interventions across the perioperative period.10 11 Early postoperative ambulation is a vital component of recovery for surgical patients, significantly mitigating risks of pulmonary complications (eg, atelectasis and pneumonia), ileus, metabolic imbalances, venous thromboembolic and cardiovascular events.12–15 Accordingly, the 2016 and 2019 ERAS guidelines for gynaecologic oncology advocate for early ambulation within 24 hours postoperatively.16 17
However, early ambulation is significantly impacted by preoperative and postoperative pain management,18 postoperative fatigue and upright intolerance.19 20 To date, a standard definition of early postoperative ambulation is lacking, and the ERAS guidelines fall short in providing clear guidance and assessment for patient ambulation.6 Prior studies have assessed early ambulation strategies in thoracoscopic lobectomy,21 22 bowel resection,23 hepatectomy24 and prostate cancer surgery,25 utilising fixed daily ambulation distances or activity frequencies. These strategies fail to account for individual patient health status, disease severity, comorbidities and specifically, patient fatigue and acceptability.
We propose an early postoperative ambulation intervention strategy utilising a self-assessed fatigue intervention to address these shortcomings. Our hypothesis is that this self-assessed fatigue intervention-based strategy for guiding early postoperative ambulation is easy, individualised and safe compared with fixed-activity distance or frequency-based interventions. While both strategies may yield comparable early recovery outcomes, the self-assessed fatigue intervention approach may boast superior compliance. However, no relevant studies have substantiated this evidence. The randomised controlled trial aims to evaluate the effectiveness and safety of a self-assessed fatigue intervention strategy for guiding early postoperative ambulation in patients undergoing gynaecological oncology surgery.
Methods
Study design
This prospective, open-label, randomised clinical trial was conducted in Xiangyang, China, from June 2021 to October 2022. The study comprised a screening phase of 2–3 days, an intervention phase of 1–7 days and a follow-up phase lasting several days. In accordance with the Declaration of Helsinki, the trial was approved by the Ethics Committee of Xiangyang Central Hospital (approval number: 2021C12) and registered with the China Clinical Trials Registry (registered on 30 May 2021). The study protocol has been published previously.26 All participants provided written informed consent before the study commenced. This report adheres to the Consolidated Standards for Reporting Trials (CONSORT) 2010 guidelines.
Patients
Between June 2021 and October 2022, 552 patients underwent gynaecological oncology surgery at Xiangyang Central Hospital and were invited to participate in this study if they met the following inclusion criteria: females aged≥18 years, with no cognitive impairment, a Body Mass Index (BMI) of 18.5–24.9 kg/m2, undergoing elective gynaecological oncological surgery (open or laparoscopic), with normal preoperative limb movement, stable surgical conditions, ability to ambulate independently, an American Society of Anesthesiologists (ASA) Physical Status Classification I–III and who provided written informed consent. Exclusion criteria included postoperative delirium, cardiac function grade 3 or higher according to the New York Heart Association classification,25 confirmed lower extremity venous thrombosis, reoperation within 1 month prior to the study, pregnancy or breastfeeding, or persistent fever≥38.5°C postoperatively. Basic demographic data were collected preoperatively from initially eligible patients. Postoperatively, Patients were screened for vital signs and fall risk. Eligible patients were randomly assigned to different interventions.
The design of the inclusion criteria aimed to select a representative group of patients who could potentially benefit from the intervention. We targeted female patients aged≥18 because they typically possess better physiological recovery capabilities and are capable of understanding and adhering to the study requirements. Additionally, we set the BMI range from 18.5 to 24.9 kg/m2, as patients within this range are generally considered to have lower surgical risks and better postoperative recovery potential. We also required patients to have normal preoperative limb movement capabilities and stable surgical conditions, which helps ensure their ability to engage in early postoperative activities. Finally, we selected patients classified as ASA Physical Status Classification I–III because their physical conditions allow them to participate in such research and provide valid data. The exclusion criteria were designed to exclude patients who might affect the study results or who could not benefit from the intervention. For instance, patients who experienced postoperative delirium were excluded as they might not accurately assess fatigue levels. Patients with cardiac function classified as grade 3 or higher were also excluded due to the increased postoperative risks they might face. Additionally, patients diagnosed with lower extremity deep vein thrombosis during or after surgery were excluded because they require specialised treatment and care, which could affect their early ambulation. We also excluded patients who had undergone reoperation within the past month prior to the study to avoid interference from surgery-related complications affecting the study results. Pregnant or breastfeeding women were excluded because their physiological status and medication use might impact the study results. Finally, patients with persistent fever of 38.5°C or higher during or after surgery were excluded, as fever could be a sign of infection or other complications, potentially affecting the patients’ mobility and the accuracy of the study results.
Patient and public involvement
Patients and the public were not involved in the study’s design, implementation or outcome measurement, and no effort was undertaken to evaluate the intervention’s burden on the patients.
Randomisation, allocation and blinding
Prior to the intervention, a sufficient number of randomised sequences were generated using a block randomisation method with a block size of 4, ensuring a 1:1 allocation ratio for participants to either the self-assessed fatigue intervention group or fixed-activity distance group. A researcher uninvolved in recruitment, registration or intervention delivery utilised the statistical software SAS V.9.4 PROC PLAN generate the randomisation sequences. Allocation concealment was maintained through the use of sequentially numbered, opaque, sealed envelopes, which were distributed by the Centre for Clinical Evidence and Translational Medicine. Due to the nature of the trial design, it was not feasible to blind patients and therapists to group allocation. However, assessors and data analysts were blinded to the group assignments to minimise bias.
Intervention
The control group was assigned a standard fixed-activity distance intervention strategy. Although a routine strategy for early postoperative ambulation has not been published, previous research has explored optimal activity levels for early ambulation,27 28 particularly in gynaecological surgery. Studies have suggested that 500 m of ambulation before discharge may not be ineffective.28 Consequently, informed by the existing literature and pilot experiments, we adjusted the activity distance for control group to enhance efficacy. Patients were instructed to walk 1000–1200 m for 1–2 hours within the first 24 hours postsurgery. Subsequently, the daily activity distance was incremented by 500 m every 24 hours for the same duration until the primary outcome achieved. An electronic bracelet (Huawei Honour 5i, HUAWEI TECHNOLOGIES, Shenzhen, China) was utilised to monitor the postoperative activity distance in metres.
In the intervention group, patients self-assessed their fatigue levels using a modified Borg Rating of Perceived Experience (RPE) scale ranging from 0 to 10.29 They initiated ambulation at a fatigue level of 5–6 (indicating severe discomfort, fatigue and mild difficulty in continuing to walk), as determined by a pretest. Interventions and assessments were conducted every 24 hours until the primary outcome occurred. Comprehensive details on the interventions components for both groups are presented in online supplemental table S1. Therapists guided all interventions, and patients from both groups were encouraged to ambulate within 24 hours postsurgery to mitigate the risk of adverse events.
Assessments and outcomes
Baseline data were collected by the principal investigator through the administration of custom-designed questionnaires and a review of electronic medical records, encompassing demographics details, disease-specific information, surgical approaches and types of anaesthesia utilised. Postoperative assessments were conducted at 24-hour intervals for all patients, continuing until hospital discharge.
Primary outcome
The primary outcome measure was the patient-reported time to first flatus, rounded to two decimal points for precision. The parameters is crucial for gauging the recovery of gastrointestinal function and directly influences a patient’s ability to resume dietary intake. The time to first flatus was delineated as the interval, measured in hours, from the conclusion of surgery to the patient’s initial reported of flatulence.
Secondary outcomes
Secondary outcomes encompassed several metrics: (1) the time to first defecation in hours, (2) incidence of moderate-to-severe abdominal distention, (3) occurrence of ileus, (4) frequency of postambulation adverse events such as nausea, vomiting and dizziness, (5) patient satisfaction with early ambulation instructions, (6) adherence to early ambulation protocols and (7) average hospital costs and length of stay for each patient group. Abdominal distention was categorised into four levels—none, mild, moderate and severe—based on clinical assessment. Postoperative nausea and vomiting were quantified using a 10-point scale,30 with 0 representing no symptoms and 10 indicating severe symptoms. Patient compliance with early ambulation was determined by adherence to intervention objectives during the initial three 24-hour postoperative periods, which are pivotal for recovery. Hospital costs are presented in Chinese Yuan (CNY), with an average exchange rate of 0.1372 for the period 2021‒2022, used to convert CNY to USD.
Statistical analysis
The sample size for this non-inferiority study was informed by prior research and a pretrial, encompassing 552 participants.31 32 The statistical rationale for the sample size was grounded in the primary outcome hypothesis: non-inferiority of the self-assessed fatigue intervention group compared with the fixed-activity distance assessment group in terms of the time to first postoperative flatus. Drawing from a literature review and pretrial data, the assumed SD for the change in the postoperative time to first flatus was 8 hours, with a non-inferiority margin of 2 hours. Accounting for a two-sided alpha level of 0.05 and an anticipated 20% dropout rate, the calculated sample of 276 patients per group ensured at least 85% power to detect a minimum 2 hour difference in the change in the time to first postoperative flatus.
The primary analysis adhered to the full analysis set (FAS), following the intention-to-treat principle.33 The FAS included all randomised patients who engaged in at least one instance of early postoperative ambulation. Missing data were imputed using multiple imputation techniques. Continuous variables were presented as means±SD or medians (IQR), while categorical variables were expressed as counts (percentages). A non-inferiority t-test was conducted to assess the difference in the time to first flatus (transformed into a normal distribution by log) between the two groups.34 For the comparison of skewed or non-normally distributed continuous variables, we used non-parametric Mann‒Whitney U test; for categorical variables, χ2 test was applied to compare the groups.
To further elucidate the intervention’s impact and variability in effects across different patient populations,35 a post hoc analysis was conducted assuming 75% compliance in each group. Additionally, an exploratory subgroup analysis was undertaken to evaluate the influence of specific covariates, such as opioids treatment and type of surgery (open/laparoscopic), on all outcomes. All statistical analyses were conducted using SAS V.9.4 (SAS Institute, Cary, NC, USA), with a significance threshold set at p<0.05.
Results
Characteristics of patients
From the 1014 patients initially screened, 462 were deemed ineligible, leaving 552 to undergo randomisation. Of these, 276 were assigned to the self-assessed fatigue intervention group, and 276 to the fixed-activity distance assessment group (figure 1). Postrandomisation exclusions totaled 60 patients: 33 from the fixed-activity distance assessment group due to experiencing the first flatus prior to intervention, and 27 from the self-assessed fatigue intervention group for the same reason. Protocol violations occurred in eight patients: five in the fixed-activity distance assessment group (two with venous thromboembolism, three transferred to other hospitals) and three in the self-assessed fatigue intervention group (one with venous thromboembolism, two transferred to other hospitals). Baseline characteristics between the two groups were comparable, with mean (SD) ages of 50.13 (12.12) years and 50.17 (11.37) years, respectively, and hypertension prevalence at 15.77% and 15.66%. No significant differences were observed in BMI (23.40 (3.22) vs 23.80 (3.17) kg/m2), educational attainment, ASA status (78.75% class 2 in the fixed-activity group vs 82.26% in the self-assessed fatigue group), surgical method (74.49% open surgery in the fixed-activity group vs 74.19% in the self-assessed fatigue group), opioid usage (56.67% in the fixed-activity group vs 54.03% in the self-assessed fatigue group) or surgery duration (medians (IQR) of 2.40 (1.65‒3.50) hours vs 2.30 (1.50‒3.40) hours). Detailed baseline demographic and clinical characteristics of the 493 participants are presented in table 1.
Enlarge this image.Figure 1. CONSORT flowchart of the study participants. CONSORT, Consolidated Standards for Reporting Trials.
Baseline demographics and clinical characteristics of the study population*
| Patient characteristics | Full analysis set population (n=492) | ||
| Fixed-activity distance assessment group (n=243) | Self-assessed fatigue intervention group (n=249) | P value | |
| Age (years), mean (SD) | 50.13±12.12 | 50.17±11.37 | 0.783 |
| BMI (kg/m2), mean (SD) | 23.90±3.22 | 23.80±3.17 | 0.489 |
| Systolic BP (mm Hg) | 123.29±14.75 | 123.86±14.30 | 0.673 |
| Diastolic BP (mm Hg) | 77.71±8.68 | 78.23±9.13 | 0.442 |
| Educational level, n (%) | 0.098 | ||
| Primary school or below | 58 (24.07) | 51 (20.48) | |
| Junior high school | 93 (38.59) | 120 (48.19) | |
| Senior high school or above | 90 (37.34) | 78 (31.33) | |
| Co-morbidities, n (%) | |||
| Hypertension, n (%) | 38 (15.77) | 39 (15.66) | 0.974 |
| Diabetes, n (%) | 14 (5.81) | 13 (5.22) | 0.775 |
| Cardiovascular disease, n (%) | 11 (4.56) | 6 (2.41) | 0.223 |
| Method of surgery, n (%) | 0.911 | ||
| Laparoscopic | 62 (25.51) | 64 (25.81) | |
| Open | 181 (74.49) | 184 (74.19) | |
| Time (hours), median (IQR) | |||
| Anaesthesia | 3.20 (2.40–4.45) | 3.10 (2.40–4.40) | 0.721 |
| Surgical | 2.40 (1.65–3.50) | 2.30 (1.50–3.40) | 0.541 |
| Nature of tumours | 0.739 | ||
| Benign tumours | 186 (77.18) | 189 (75.90) | |
| Malignant tumours | 55 (22.82) | 60 (24.10) | |
| Stage of malignant tumours | 0.948 | ||
| I | 36 (66.67) | 39 (66.10) | |
| II | 7 (12.96) | 7 (11.86) | |
| III | 11 (20.37) | 13 (22.03) | |
| ASA classification, n (%) | 0.628 | ||
| 1 | 4 (1.67) | 2 (1.09) | |
| 2 | 189 (78.75) | 204 (82.26) | |
| 3 | 47 (19.58) | 42 (16.94) | |
| Treatment with opioids, n (%) | 0.558 | ||
| No | 104 (43.33) | 126 (45.97) | |
| Yes | 136 (56.67) | 150 (54.03) | |
*Descriptive analyses of continuous variables were analysed by means±SD or medians (IQR) and categorical variables were described by number (percentage). Two independent samples t test or Mann-Whitney U test was used for continuous variables, and χ2 test was used for categorical variables. Stage of malignant tumours is based on the FIGO.
ASA, American Society of Anesthesiologists; BMI, body mass index; BP, blood pressure; FIGO, International Federation of Gynaecology and Obstetrics.
Primary outcome
The self-assessed fatigue intervention group demonstrated a significantly non-inferior mean time to first flatus compared with the fixed-activity distance assessment group, as per patient self-reports (25.59±14.59 hours vs 26.10±14.19 hours, pnon-inferiority<0.001). Sensitivity analysis, which compared median times to first flatus, revealed no significant difference between the self-assessed fatigue intervention group (22.11 hours (IQR, 16.00‒34.16 hours)) and the fixed-activity distance assessment groups (21.83 hours (IQR, 14.67‒32.90 hours)), p=0.514. (table 2).
Table 2Treatment effects for primary and secondary outcomes within the full analysis set
| Outcomes | Fixed-activity distance assessment group (n=243) | Self-assessed fatigue intervention group (n=249) | T/Mann‒Whitney U/χ2 | P value |
| Primary outcome | ||||
| The time to first flatus (hours), mean (SD)* | 26.10±14.19 | 25.59±14.59 | 11.35 | <0.001¶ |
| The time to first flatus (hours), median (IQR)† | 21.83 (16.00–34.16) | 22.11 (14.67–32.90) | 0.652 | 0.514 |
| Secondary end points | ||||
| The time to to first defecation, hours† | 37.01 (25.33–47.58) | 33.58 (25.80–48.67) | 0.234 | 0.814 |
| Hospital cost, Chinese Yuan†§ | 17 405.93 (14 188.98–24 201.76) | 17 350.43 (14 249.70–23 912.21) | 0.033 | 0.973 |
| Length of stay, days† | 9.00 (6.00–12.00) | 9.00 (6.00–13.00) | 0.095 | 0.924 |
| Incidence of adverse reactions, n (%)‡ | 101 (41.56) | 100 (40.16) | 0.102 | 0.751 |
| Incidence of moderate-to-severe abdominal distention, n (%)‡ | 79 (33.33) | 99 (39.92) | 2.263 | 0.132 |
| Occurrence of ileus, n (%)‡ | 8 (3.38) | 13 (5.24) | 0.108 | 0.375 |
| Patient compliance, n (%)‡ | 85 (36.02) | 125 (50.40) | 10.189 | 0.001¶ |
| Patient satisfaction rate, n (%)‡ | 223 (94.49) | 239 (96.37) | 1.057 | 0.589 |
*The time to first flatus was transformed into a normal distribution by log and performed a non-inferiority t-test.
†The Mann‒Whitney U test.
‡Incidence of adverse reactions, incidence of moderate-to-severe abdominal distention, occurrence of ileus, patient compliance, patient satisfaction rate were analysed by χ2 value.
§Mean exchange rate for 2021–2022 (years of study period): 1 Chinese Yuan=0.1372 USD.
¶p<0.05.
Secondary outcomes
Compliance with patient activity was significantly greater in the self-assessed fatigue intervention group than in the fixed-activity distance assessment group (125 patients (49.40%) vs 85 patients (36.02%) p<0.001), although it remained below 50% for both groups. No significant differences were observed between the two groups regarding the times to first defecation (median, 33.58 hours (IQR, 25.80‒48.67 hours) vs 37.01 hours (IQR, 25.33‒47.58 hours); p=0.814), length of hospital stay (median, 9.00 days (IQR, 6.00‒13.00 days) vs 9.00 days (IQR, 6.00‒12.00 days); p=0.973), incidence of moderate-to-severe abdominal distention (99 patients (39.92%) vs 79 patients (33.33%), occurrence of ileus (13 patients (5.24%) vs 8 patients (3.38%)), patient activity satisfaction rate (239 patients (96.37%) vs 223 patients (94.49%)) or hospital costs (median, CNY: ¥17405.93 (IQR, ¥14188.98‒¥24 201.76), USD equivalent: $2388.09 (IQR, $1946.72‒$3320.48)) vs CNY: ¥17350.43 (IQR, ¥14249.70‒¥23 912.21), USD equivalent: $2380.47 (IQR, $1955.06‒$3280.75)). Furthermore, the incidence of adverse reactions, including nausea, vomiting and dizziness, was similar between the self-assessed fatigue intervention group (100 patients (40.16%) and fixed-activity distance assessment group (101 patients (41.56%), as detailed in table 2).
Post hoc analysis of compliance
The FAS indicated varying levels of intervention compliance, with 36.02% in the fixed-activity distance assessment group and 49.40% in the self-assessed fatigue intervention group. Post hoc analysis, adjusting the intervention target to 75% compliance rate, revealed that patients in the fixed-activity distance group ambulated a minimum of 350 m within the first 24 postoperative hours, 840 m in the second 24-hour and 1330 m in the third 24-hour period. Similarly, patients in the self-assessed fatigue group were required to have fatigue scores of at least four during each of the first three 24-hour postoperative periods. After accounting for opioid treatment and surgical method, covariance analysis demonstrated no significant difference in the median time to first flatus between the two groups (22.44 hours (IQR, 15.33‒33.66 hours) for the self-assessed group vs 20.00 hours (IQR, 14.66‒30.66 hours) for the fixed-activity group; p=0.205). However, the self-assessed fatigue intervention group exhibited higher median hospital costs, length of stay and incidence of moderate-to-severe abdominal distension (refer to table 3).
Table 3Treatment effects for primary and secondary outcomes based on a 75% compliance threshold
| Outcomes | Fixed-activity distance assessment group (n=186) | Self-assessed fatigue intervention group (n=210) | T/Mann‒Whitney U/χ2 | P value |
| Primary outcome | ||||
| The time to first flatus (h), median (IQR)* | 20.00 (14.66–30.66) | 22.44 (15.33–33.66) | 10.35 | 0.205 |
| Secondary end points | ||||
| The time to first defecation, h* | 30.95 (24.50–46.95) | 36.50 (27.00–48.66) | 138.06 | 0.074 |
| Hospital cost, Chinese Yuan*‡ | 16 099.14 (13 421.07–20 291.16) | 17 561.06 (14 858.12–23 968.34) | 34.57 | 0.004§ |
| Length of stay, days* | 8.00 (6.00–11.00) | 9.00 (7.00–13.00) | 26.96 | 0.007§ |
| Incidence of adverse reactions, n (%)† | 59 (31.72) | 85 (40.48) | 3.26 | 0.07 |
| Incidence of moderate-to-severe abdominal distention, n (%)† | 54 (29.03) | 82 (39.05) | 4.38 | 0.03§ |
| Occurrence of ileus, n (%)† | 5 (2.69) | 9 (4.29) | 0.74 | 0.39 |
| Patient satisfaction rate, n (%)† | 178 (95.70) | 202 (96.19) | 1.13 | 0.565 |
*Analysed by the Mann‒Whitney U test.
†Incidence of adverse reactions, incidence of moderate-to-severe abdominal distention, occurrence of ileus, patient compliance, patient satisfaction rate were analysed by χ2.
‡Mean exchange rate for 2021–2022 (years of study period): 1 Chinese Yuan=0.1372 USD.
§p<0.05.
On further analysis, compliant patients in the fixed-activity distance assessment group experienced the shorter time to first flatus (median, 20.00 hours (IQR, 14.66‒30.66 hours) vs 28.33 hours (IQR, 22.16‒43.67 hours); p<0.001) and first defecation (median, 30.95 hours (IQR, 24.50‒46.95 hours) vs 41.67 hours (IQR, 32.33‒48.91 hours); p=0.01), lower median hospital costs (CNY: ¥16099.14 (IQR, ¥13421.07‒¥20 291.16), USD equivalent: $2208.80 (IQR, $1841.37‒$2783.94) vs CNY: ¥25210.56 (IQR, ¥18733.85‒¥28 903.79), USD equivalent: $3458.88 (IQR, $2570.28‒$3965.59); p<0.001) and shorter median length of stay (8.00 days (IQR, 6.00‒11.00 days) vs 13.00 days (IQR, 10.00‒15.00 days); p<0.001)), as well as lower incidence of adverse reactions (31.72% vs 73.68%; p<0.001) and moderate-to-severe abdominal distention (29.03% vs 49.02%; p=0.007). In contrast, the self -assessed fatigue intervention group displayed a reversed pattern, with non-compliant patients experiencing the shorter time to first flatus (median, 19.65 hours (IQR, 10.50‒30.00 hours) vs 22.44 hours (IQR, 15.33‒33.66 hours); p=0.049) and the time to first defecation (median, 25.62 hours (IQR, 19.75‒48.00 hours) vs 36.50 hours (IQR, 27.00‒48.66 hours); p=0.016) and lower median hospital costs (CNY: ¥15026.25 (IQR, ¥9856.85‒¥23 632.59), US dollar equivalent: $2016.60 (IQR, $1352.35‒$3242.39) vs CNY: ¥17561.06 (IQR, ¥14858.12‒¥23 968.34), US dollar equivalent: $2409.37 (IQR, $2038.53‒$3288.45)) (table 4 and online supplemental table S2).
Table 4Treatment outcomes for patients who underwent fixed-activity distance assessment and self-assessed fatigue intervention on a 75% compliance rate
| Outcomes | Fixed-activity distance assessment group (n=243) | Self-assessed fatigue intervention group (n=249) | ||||
| Non-compliance | Compliance | P value | Non-compliance | Compliance | P value | |
| Total patients, no. | 57 | 186 | NA | 39 | 210 | NA |
| Primary outcome | ||||||
| The time to first flatus (h), median (IQR)* | 28.33 (22.16–43.67) | 20.00 (14.66–30.66) | <0.001§ | 19.65 (10.50–30.00) | 22.44 (15.33–33.66) | 0.049§ |
| Secondary end points | YY | |||||
| The time to first defecation, h* | 41.67 (32.33–48.91) | 30.95 (24.50–46.95) | 0.01§ | 25.62 (19.75–48.00) | 36.50 (27.00–48.66) | 0.016§ |
| Hospital cost, Chinese Yuan*‡ | 25 210.56 (18 733.85–28 903.79) | 16 099.14 (13 421.07–20 291.16) | <0.001§ | 15 026.25 (9856.85–23 632.59) | 17 561.06 (14 858.12–23 968.34) | 0.009§ |
| Length of stay, days* | 13.00 (10.00–15.00) | 8.00 (6.00–11.00) | <0.001§ | 7.50 (4.00–15.00) | 9.00 (7.00–13.00) | 0.226 |
| Incidence of adverse reactions, n (%)† | 42 (73.68) | 59 (31.72) | <0.001§ | 15 (38.46) | 85 (40.48) | 0.813 |
| Incidence of moderate-to-severe abdominal distention, n (%)† | 25 (49.02) | 54 (29.03) | 0.007§ | 17 (44.74) | 82 (39.05) | 0.501 |
| Occurrence of ileus, n (%)† | 3 (5.88) | 5 (2.69) | 0.263 | 4 (10.53) | 9 (4.29) | 0.112 |
| Patient satisfaction rate, n (%)† | 45 (90.00) | 178 (95.70) | 0.085 | 37 (97.37) | 202 (96.19) | 0.621 |
*Analysis of covariance after adjusting treatment with opioids and method of surgery.
†Incidence of adverse reactions, incidence of moderate-to-severe abdominal distention, occurrence of ileus, patient compliance, patient satisfaction rate were analysed by χ2.
‡Mean exchange rate for 2021–2022 (years of study period): 1 Chinese Yuan=0.1372 USD.
§p<0.05.
Exploratory subgroup post hoc analysis
In the subgroup of patients receiving opioids, the self-assessed fatigue intervention group exhibited a notably higher incidence of moderate-to-severe abdominal distension compared with the fixed-activity distance assessment group (64 patients (47.76%) vs 46 patients (34.33%), p=0.025). Similarly, compliance was significantly greater in the self-assessed fatigue intervention group than in the fixed-activity distance assessment group (76 patients (56.72%) vs 35 patients (26.12%), p=0.001). However, no significant differences were observed between the groups concerning the time to first flatus, the time to first defecation, hospital cost, length of stay, incidence of adverse reactions, occurrence of ileus and patient satisfaction rate (all p-values>0.05). Among patients not treated with opioids, the self-assessed fatigue intervention group again demonstrated higher compliance (79 patients (69.29%) vs 50 patients (49.02%), p=0.001). Additional comparisons within the group yielded no significant intergroup differences (online supplemental table S3).
Among patients who underwent laparoscopic surgery, the fixed-activity distance assessment group reported a significantly higher incidence of moderate-to-severe abdominal distension compared with the fixed-activity distance assessment group (63 patients (34.24%) vs 46 patients (26.24%), p=0.046). Additionally, the self-assessed fatigue intervention group demonstrated a significantly greater level of patient compliance (108 patients (58.37%) vs 77 patients (44.00%), p=0.021). No significant intergroup differences were observed in the time to first flatus, the time to first defecation, hospital cost, length of stay, incidence of adverse reactions, occurrence of ileus or patient satisfaction rate (all p-values>0.05). In the cohort of patients who underwent open surgery, the self-assessed fatigue intervention group again showed a significantly higher rate of patient compliance (34 patients (53.13%) vs 8 patients (13.11%), p<0.001). Other comparative analyses revealed no significant differences between the groups (online supplemental table S4).
Discussion
Early postoperative ambulation is recognised for its role in facilitating gastrointestinal recovery and prevent ileus. Nonetheless, determining the optimal level of ambulation for individual patients in clinical settings remains challenging, often resulting in either excessive or insufficient mobility. This study represents the first randomised controlled trial to evaluate the clinical effectiveness and safety of a self-assessed fatigue intervention strategy for early postoperative ambulation among patients undergoing gynaecological oncology surgery. The findings of our study can be summarised as follows: (1) The self-assessed fatigue intervention group exhibited non-inferior time to first flatus compared with the fixed-activity distance assessment group, with higher compliance rates, although less than 50% in both groups. (2) Post hoc analysis, considering a 75% compliance threshold, suggested that the fixed-activity distance assessment group outperformed the self-assessed fatigue intervention group. A recommended minimum fixed-activity distance of 350 m within the first 24 hours, 840 m in the second 24-hour period and 1330 m in the third 24-hours period postoperatively may be deemed appropriate. (3) An increased incidence of moderate-to-severe abdominal distension was observed in the self-assessed fatigue intervention group among patients treated with opioids and those who underwent laparoscopic surgery, indicating a need for cautious application of self-assessed fatigue intervention interventions strategies in these populations.
Previous research on early postoperative ambulation strategies has yielded valuable insights. For instance, Wiklund et al 27 randomly assigned 55 bariatric surgery patients into two groups, with the intervention group being tasked with achieving a daily fixed step count. This approach underscores the potential of daily ambulation goal to encourage patient activity and enhance postoperative mobility. The efficacy of a step-setting strategy in facilitating early ambulation received further validation in the work of Kim and Lee.36 Moreover, guidelines37 advocate for the establishment of a daily ambulation step count as a means to expedite gastrointestinal recovery and mitigate the risk of ileus. Several studies have employed electronic pedometers to track ambulation among patients undergoing abdominal and gynaecological surgeries,28 38 with findings indicating a significant increase in early patient mobility. In our investigation, the fixed-activity distance assessment group adhered to protocol informed by prior research27 28 and utilised electronic pedometers to monitor ambulation, thereby providing partial evidence of the intervention’s effectiveness. The results of this clinical trial align with our primary research hypothesis: the self-assessed fatigue intervention group demonstrated a non-inferior time to first flatus compared with time the fixed-activity distance assessment group. Consequently, our results suggest that a self-fatigue assessment-based approach to gauge the volume of early ambulation, targeting a 5‒6 level of self-fatigue, may be an effective strategy.
To date, no study has scrutinised the appropriateness of the daily ambulation target, a challenge arising from the targets’ intricate relationship with various diseases, surgical procedures and research centres. Furthermore, early postoperative ambulation is heavily influenced by a multitude of individual factors, including incisional pain,39 40 postoperative fatigue, upright intolerance,19 20 demographic characteristics41 and psychosocial elements, which collectively shape each patient’s tolerance for ambulation. Ideally, if daily ambulation objectives are tailored to account for patient’s age, comorbidities and postoperative fatigue levels, then self-assessed fatigue interventions should foster greater adherence to early ambulation protocols. However, our investigation revealed that the self-assessed fatigue intervention group exhibited disappointingly low activity compliance, potentially attributable to the demanding nature of the activity levels at a 5–6 fatigue rating, particularly among patients who underwent open surgeries and those receiving opioid treatment. Additionally, compliance might be influenced by cultural perceptions of Chinese patients, many of whom may not endorse early postoperative ambulation despite the guidance of caregivers. On readjusting the intervention targets for both groups to achieve a 75% compliance rate, the findings indicated that the fixed-activity distance assessment group experienced significantly reduced hospital costs, shorter length of stay and lower occurrences of moderate-to-severe abdominal distension. This outcome may stem from the fact that patients with fixed-activity distance assessment were required to meet specific ambulation targets, thereby minimising their subjective reliance. Moreover, the adjustment of the fatigue activity level from 5 to 6 may not have substantially benefited patients, although it did enhance activity compliance. Therefore, this study suggests that a prudently determined fixed-activity distance target—specifically, a minimum of 350 m within the first 24 postoperative hours, 840 m in the second 24-hour period and 1330 m in the third 24-hour period—could be a more effective strategy.
Subgroup analysis revealed no significant difference in the time to first flatus between the self-assessed fatigue intervention and fixed-activity distance assessment groups among patients undergoing both opioid treatment and open or laparoscopic surgery. However, the self-assessed fatigue intervention group exhibited a markedly higher incidence of moderate-to-severe abdominal distention in patients receiving opioids and undergoing laparoscopy. The postoperative recovery of gastrointestinal function is multifaceted, influenced by factors such as surgical trauma, activation of sympathetic inhibitory reflexes and the release of local and systemic inflammatory mediators.42 The negative impact of opioids on gastrointestinal motility is well documented, leading to an increased prevalence of abdominal distention in patients receiving opioid analgesia compared with those who do not.42 43 Reporting bias may also come into play, as self-assessed fatigue intervention are susceptible to subjective psychological influences, susceptible to the true activity levels of patients. This subjectivity may partially account for the higher incidence of moderate-to-severe abdominal distension observed in the self-assessed fatigue intervention group among opioid-treated patients. Moreover, despite laparoscopic surgery being associated reduced surgical trauma and inflammation compared with open surgery, the sympathetic and parasympathetic nervous system imbalance induced by surgical stress can elicit inhibitory bowel reflexes, resulting in abdominal distension and ileus.44 The fixed-activity distance assessment group’s mandatory target activity levels may effectively mitigate the incidence of moderate-to-severe abdominal distension by promoting a more controlled and gradual increase in postoperative activity.
Limitations
Due to the nature of study design, double blinding was not feasible. Data collection were conducted by a research assistant blinded to the random group allocation, although blinding participants to their assigned treatment group was not possible. Second, the stringent inclusion and exclusion criteria limit the generalisability of our findings to the broader population of women undergoing gynaecological oncology surgery. Additionally, only a quarter of the patients in our study underwent laparoscopic surgery, and less than a quarter had malignant tumours, which may limit the assessment of the self-assessed fatigue intervention’s efficacy in these specific patient groups. Consequently, further validation of our results in diverse clinical contexts is warranted. Third, while the time to first flatus and defecation are commonly used clinical indicators for bowel movement recovery, these measures rely on subjective patient reports and are susceptible to reporting bias. Fourth, self-assessed fatigue, also based on subjective patient reports, introduces a similar risk of reporting bias. Fifth, the secondary analyses were not rigorously preplanned, which may result in inadequate statistical power or interpretive biases, thus necessitating cautious interpretation of these results. Finally, the higher incidence of severe abdominal distension in the self-assessed fatigue intervention group suggests that the current 5‒6 fatigue level may not accurately represent the true ambulatory capacity of patients, the development of objective fatigue assessment tools is need to better understand the intervention’s effects at higher fatigue levels in the future. The strengths of our trial include its sample size, prospective design, rigorous recruitment processes, allocation concealment, and comprehensive follow-up protocols.
Conclusion
The findings from this randomised clinical trial indicate that although the use of a 5‒6 level of self-assessed fatigue scale may be an effective intervention strategy for early ambulation in patients following gynaecological oncology surgery, patient compliance with this approach is suboptimal. Consequently, self-assessed fatigue intervention should be applied with caution, particularly in patients receiving opioid treatment and those undergoing laparoscopic procedures. Moreover, an intervention strategy predicated on a fixed-activity distance, which is mandatory and reasonable, may currently represent the optimal treatment option (with a target of ≥350 m for the first 24 hours, ≥840 m for the second 24-hour period and ≥1330 m for the third 24-hour period postoperatively). Considering the benefits of easy implementation, personalisation and safety associated with fatigue assessment and the inherent limitations of self-assessment of fatigue, the development of more objective fatigue assessment tools is essential.
The authors affirm that the methods used in the data analyses are suitably applied to their data within their study design and context, and that the statistical findings have been implemented and interpreted correctly. The authors thank all the study participants for their time and feedback and all the staff who facilitated the recruitment and intervention delivery. We would also like to acknowledge Elsevier for language editing.
Data availability statement
Data are available upon reasonable request. The data that support the findings of this study are available from the corresponding author upon reasonable request.
Ethics statements
Patient consent for publication
Not applicable.
Ethics approval
This study involves human participants. The trial was approved by the Independent Ethics Committee of Xiangyang Central Hospital affiliated with Hubei University of Arts and Sciences, grant number: 2021-015-23. Participants gave informed consent to participate in the study before taking part.
QD, BC and XZ contributed equally.
Contributors QD: conceptualisation, methodology, validation, formal analysis, investigation, writing—original draft, writing—review and editing, supervision. BC: conceptualisation, software, validation, formal analysis, statistical analysis, investigation, writing—original draft, writing—review and editing, visualisation, supervision. XZ: conceptualisation, methodology, validation, formal analysis, investigation, writing—review and editing, supervision, project administration. HH: methodology, software, investigation, visualisation. XQ: methodology, project administration, investigation, supervision. LL and JD: data curation, investigation, supervision. XH: methodology, investigation, supervision. SX: project administration, data curation, supervision. XH: funding acquisition, project administration, data curation, supervision. The guarantor of manuscript: XH.
Funding This work was supported by the clinical trial centre of Xiangyang Central Hospital affiliated with Hubei University of Arts and Sciences, grant number 2021C12.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.
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Details
; Huang, Xiaojie 1
1 Department of Obstetrics and Gynecology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, China
2 Department of Endocrinology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, China; Evidence-Based Medicine Centre, Office of Academic Research, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, China
3 Department of Nursing, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, China