Correspondence to Dr Ying Zhou; [email protected]
STRENGTHS AND LIMITATIONS OF THIS STUDY
Multicentre cross-sectional study exploring the current physical activity (PA) status in patients with inflammatory bowel disease in China.
Detailed survey on types and venues of PA, disease-related and non-disease-related barriers to PA.
Self-designed PA outcome expectation score with reliability tested.
Recruitment from biologics infusion centres and WeChat patient groups may cause selection bias.
Using the International Physical Activity Questionnaire short form may overestimate total PA.
Introduction
Inflammatory bowel disease (IBD), mainly comprised of ulcerative colitis (UC) and Crohn’s disease (CD), is lifelong chronic inflammation affecting the gastrointestinal tract, characterised by insidious early onset, relapsing and remission courses with no cure.1 In recent years, IBD has become a global disease with accelerating incidence in newly industrialised countries including China.2 The incidence in urban East China has reached as high as 21.77 (13.38 to 32.19) per 100 000 person-years in 2016.3 Physical activity (PA) and exercise are of potential health benefits for both the general population and patients with various chronic diseases.4 Until recently, growing evidence has noted the importance of PA for IBD patients, improving skeletomuscular strength, reducing stress and fatigue levels, as well as ameliorating anxiety and depression perception.5
In Western countries, increasing patients choose PA as a complementary therapy in addition to traditional pharmacological and surgical interventions.6 7 Several studies conducted in Europe and the USA have demonstrated considerably high PA levels despite disease activity, with a substantial proportion of patients engaging in regular leisure-time exercise.8–10 However, some literatures presented conflicting findings. A Canadian survey reported that adults with IBD tend to lead a less active lifestyle compared with non-IBD controls.11 Additionally, a recent Italian and several analogous cross-sectional studies conducted in Asia found notably low levels of PA among IBD patients, even under disease remission.12–14 This controversy necessitates a more in-depth investigation into PA levels, barriers and facilitators of PA engagement among IBD patients especially in newly industrialised countries with accelerating incidence.
Several studies on PA levels among IBD patients also examined the influencing factors of PA engagement. Disease-related symptoms, including abdominal pain, diarrhoea, arthralgia and fatigue, are important barriers to PA participation and are primarily associated with disease activity.8 15 Additionally, IBD patients frequently experience substantial mental health comorbidities, which may adversely affect self-management behaviours such as PA.16 17 However, findings from studies conducted in Asia have indicated low PA levels among patients in remission.13 14 Consequently, it is imperative to further investigate non-disease-related influencing factors, including demographic variables, outcome expectations of PA related to IBD control, and other modifiable lifestyle habits.
Despite the substantial rise in incidence and prevalence in China, there has been limited research on PA status in Chinese patients with IBD. The primary aim of our study was to investigate the current level, pattern, and influencing factors of PA engagement among IBD patients in East China. Our finding will help to identify limiting factors of PA participation and contribute to a better understanding of the determinants influencing PA among IBD patients in China.
Methods
Study design and participants
This is a cross-sectional study enrolling patients from IBD outpatient clinics, infusion centre for biologics, and WeChat patient groups of tertiary referral hospitals from six cities (Ningbo, Hangzhou, Wenzhou, Lishui, Taizhou and Quzhou) in East China between October and December 2023. Inclusion criteria were individuals aged between 18 and 65 who were diagnosed with either CD or UC for more than 3 months by an IBD specialist in a tertiary referral hospital. Pregnant or lactating IBD patients and those with severe chronic diseases or physical movement disorders that restrict PA engagement were excluded. Those who had difficulty reading or with no access to the internet were also excluded. A Chinese online questionnaire app was used to collect primary information for this study. Informed consent was acquired electronically online before respondents started to fill out the questionnaire. This study was approved by the Ethical Committee of Ningbo Medical Center Lihuili Hospital (KY2022SL225-01).
Survey and definitions
The questionnaire was designed by IBD physicians (YZ and HL) and revised by senior gastroenterologists (XZ and FX). A preliminary survey and interview were carried out among 30 IBD patients to improve the feasibility and validity of the questionnaire before the final version was adopted. A translated English version of the questionnaire can be found in the online supplemental file 1. The questionnaire consisted of three sections. (1) Patient demographic and clinical information. Patient-reported outcomes 2 (PRO-2) was used to assess the clinical disease activity. Clinical remission was defined as an abdominal pain score ≤1 and ≤3 bowel movements for CD; partial Mayo score <3 and no single score >1 for UC, according to an update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE-II) guideline.18 If these criteria were not met, the disease was considered active. (2) Physical activity level and sedentary behaviour assessment: the Chinese version of the International Physical Activity Questionnaire (IPAQ-C) short form was used to assess the PA level covering the past week.19–21 Since IPAQ-C short form does not include sitting questions, the time spent in a sitting state was recorded using the two questions on sedentary behaviour in the IPAQ-C long form.22 The questionnaire also investigated changes in PA after IBD diagnosis, the most frequently practised types of PA, and the most visited exercise venues. (3) Influencing factors of PA: a five-question outcome expectation score of PA was designed on a Likert scale (online supplemental table 1), two of which were reverse-scored. A total score of five questions is calculated to determine the final score. This five-question outcome expectation score was designed based on the purpose of our survey with reference to the validated Exercise Benefits and Barriers Scale and Multidimensional Outcome Expectations for Exercise Scale.23 24 Three of the questions pertained to patients’ outcome expectation of PA on IBD control or flare-up. The remaining two questions focused on PA outcome expectation of well-documented improvement in skeletomuscular health and mental-emotional well-being. Disease-related and non-disease-related factors limiting PA engagement were also questioned.
Scoring protocol of PA levels
Calculating total PA and categorising PA levels was performed according to the guidelines for Data Processing and Analysis provided by the IPAQ website (www.ipaq.ki.se). A total PA score is the sum of walking, moderate and vigorous metabolic equivalent of task (MET)-min/week. PA levels are classified into high, moderate and low. The category high is defined as vigorous-intensity activity on at least 3 days achieving a minimum total PA of at least 1500 MET-min/week, or 7 days of any combination of walking, moderate-intensity or vigorous-intensity activities achieving a minimum total PA of at least 3000 MET-min/week. The category moderate requires three or more days of vigorous-intensity activity of at least 20 min/day, or five or more days of moderate-intensity activity and/or walking of at least 30 min/day or five or more days of any combination of walking, moderate-intensity or vigorous-intensity activities achieving a minimum total PA of at least 600 MET-min/week. If the above high or moderate criteria are not met, the category low was used. Sedentary time was calculated by summing the minutes spent in a sitting state on weekdays and weekends, expressed in min/week.
Patient and public involvement
Patients or the public were not involved in the design, conduct, reporting or dissemination plans of our research.
Statistical analysis
The sample size was calculated by multiplying the number of questionnaire variables by 20, resulting in a total of 380 cases. As none of the continuous variables in this study conformed to the normal distribution, they were all expressed as median (IQR). Missing values were filled in by the median. The Mann-Whitney U test was used to compare CD and UC groups. Categorical variables were expressed as cases (%), and comparisons between two groups were performed using theχ2 test. Missing values were filled in by the mode.
A two-stage strategy was used to identify significant influencing factors of PA levels. First, univariate analysis was conducted using the Kruskal-Wallis H test. Second, variables with p<0.1 in univariate analysis were further analysed by multivariate logistic regression. To evaluate the reliability of the five-question PA outcome expectation score, we analysed Cronbach’s alpha coefficient, resulting in a value of 0.71. Differences were considered statistically significant at p<0.05. Statistical analyses were conducted using SPSS® 26.0 software (IBM®) and graphs with GraphPad PRISM® 9.
Results
Participant characteristics
Among the initial 405 questionnaires collected, 14 cases were excluded, of which five respondents were younger than 18 or older than 65 years old, two were pregnant or lactating, four had other concomitant PA-limiting diseases and three were diagnosed for <3 months. Overall, there were 391 eligible respondents, of which 237 (60.6%) were male and 271 (69.3%) had CD. The median age was 35 (28, 43) years old, median disease duration was 48 (20, 100) months, 326 (83.4%) were in remission, 336 (85.9%) were on biologics and 137 (35.0%) had a history of IBD-related surgery (table 1).
Table 1Demographic and clinical characteristics
| CD (n=271) | UC (n=120) | IBD (n=391) | ||
| Gender n (%) | Male | 175 (64.6) | 62 (51.7) | 237 (60.6) |
| Female | 96 (35.4) | 58 (48.3) | 154 (39.4) | |
| Age, years | 32 (26, 39) | 42 (35, 48) | 35 (28, 43) | |
| Employment n (%) | Student | 40 (14.8) | 7 (5.8) | 47 (12.0) |
| Unemployed | 27 (10.0) | 11 (9.2) | 39 (9.7) | |
| Employed | 144 (53.1) | 53 (44.2) | 197 (50.4) | |
| Freelance | 60 (22.1) | 49 (40.8) | 109 (27.9) | |
| Education n (%) | Middle school and below | 47 (17.3) | 37 (30.8) | 84 (21.5) |
| High school | 49 (18.1) | 25 (20.8) | 74 (19.8) | |
| College and Bachelor | 170 (62.7) | 53 (44.2) | 223 (57.0) | |
| Postgraduate and above | 5 (1.8) | 5 (4.2) | 10 (2.6) | |
| BMI, kg/m2 | 20.99 (18.94, 23.19) | 22.46 (20.06, 25.59) | 21.30 (19.27, 23.78) | |
| Age at diagnosis, years | 27 (21, 34) | 34 (28, 41) | 29 (22, 36) | |
| Disease duration, months | 43 (18~84) | 53 (24.5~125) | 48 (20~100) | |
| Disease activity | Remission | 261 (96.3) | 65 (54.2) | 326 (83.4) |
| Active | 10 (3.7) | 55 (45.8) | 65 (16.6) | |
| Current medication | 5-aminosalicylates | 33 (12.2) | 70 (58.3) | 103 (26.3) |
| Corticosteroid | 11 (4.1) | 8 (6.7) | 19 (4.9) | |
| Immunomodulator | 39 (14.4) | 10 (8.3) | 49 (12.6) | |
| Biologics | 264 (97.4) | 72 (60.0) | 336 (85.9) | |
| Surgical history | 124 (45.8) | 13 (10.8) | 137 (35.0) | |
| Perianal surgery | 64 (23.6) | 0 | 64 (16.4) | |
| Small bowel surgery | 43 (15.9) | 0 | 43 (11.0) | |
| Ileocecal or right hemicolectomy | 11 (4.1) | 4 (3.3) | 15 (3.8) | |
| Proctocolectomy | 6 (2.2) | 2 (1.7) | 8 (2.0) | |
BMI, Body Mass Index; CD, Crohn's disease; IBD, inflammatory bowel disease; UC, ulcerative colitis.
Physical activity levels
The median total PA was 594 (0, 1695) MET-min/week, with 105 (26.9%) patients recording 0 MET-min/week because they had no PA duration longer than 10 min. Among the 391 respondents, 53 (13.6%) were of high level, 140 (35.8%) were moderate and 198 (50.6%) were low, with no significant difference between CD and UC (χ2=0.062, p>0.05). The median sedentary time was 2325 (1500, 3120) min/week, with CD patients exhibiting significantly more sedentary time than UC (Z=−3.950, p<0.01). In terms of PA change after IBD diagnosis, 180 (46.0%) patients reported a decrease, including 134 (49.4%) in CD and 46 (38.3%) in UC, which was significantly more in CD than in UC (χ2=4.135, p<0.05) (table 2).
Table 2PA levels and sedentary time
| IBD (n=391) | CD (n=271) | UC (n=120) | Z/χ2 | P value | ||
| Total PA MET-min/week | 594 (0, 1695) | 594 (66, 1695) | 545 (0, 1693) | −0.114 | 0.886 | |
| PA levels | High | 53 (13.6) | 36 (13.3) | 17 (14.2) | 0.062 | 0.970 |
| Moderate | 140 (35.8) | 97 (35.8) | 43 (35.8) | |||
| Low | 198 (50.6) | 138 (50.9) | 60 (50.0) | |||
| Sedentary time min/week | 2325 (1500, 3120) | 2460 (1680, 3360) | 2010 (1260, 2745) | −3.950 | <0.01* | |
| Change in PA after IBD diagnosis | Reduced | 180 (46.0) | 134 (49.4) | 46 (38.3) | 4.135 | <0.05* |
| Unchanged /increased | 211 (54.0) | 137 (50.6) | 74 (61.7) | |||
*Indicates a statistically significant difference between CD and UC groups.
CD, Crohn's disease; IBD, inflammatory bowel disease; PA, physical activity; UC, ulcerative colitis.
Common patterns and limiting factors of physical activity
The most frequently engaged PA type among IBD patients was slow walking (90.0%). Other types such as brisk walking (27.4%), running (20.5%), cycling (22.8%) and ball games (13.0%) showed much lower frequencies (figure 1A). The common venues of PA were outdoors (73.7%), at home (49.9%) and ball field (10.2%) (figure 1B). Disease-related limiting factors for IBD patients to participate in PA included abdominal pain (55.2%), fatigue (47.8%), joint pain (29.9%), disease flare-up (28.6%), increased bowel frequency/urgency (25.3%) and fear of worsening symptoms (19.9%) (figure 1C). Non-disease-related limiting factors included lack of time for PA (50.1%), dislike of PA (32.0%), inaccessibility to venue/equipment (16.4%) and not being recommended to PA by a doctor (14.6%) (figure 1D).
Enlarge this image.Figure 1. Common patterns and limiting factors of PA. PA types (A) frequently participated in, and venues (B) frequently visited by IBD patients. Disease-related factors (C) and non-disease-related factors (D) limiting IBD patients engaging in PA. BF, bowel frequency; BU, bowel urgency; CD, Crohn’s disease; IBD, inflammatory bowel disease; PA, physical activity; UC, ulcerative colitis.
Influencing factors for physical activity levels
According to the PA levels in table 2, respondents were categorised into three groups: high, moderate and low. In univariate analysis (table 3), differences across the three groups were statistically significant for gender, education and PA outcome expectation score (all p<0.01) among total IBD patients. In the CD subgroup, univariate analyses showed that BMI, education and PA outcome expectation score were statistically different across three PA levels (all p<0.01). Gender (p=0.07) and PA reduction after diagnosis (p=0.088) were also included for multivariate analysis in the next step. In patients with UC, univariate analysis identified no variable with a significant difference.
Table 3Univariate analysis of PA levels
| Variable | IBD | CD | UC | |||
| Z value | P value | Z value | P value | Z value | P value | |
| Gender, male (vs female) | −2.722 | 0.006* | 5.318 | 0.07† | 2.500 | 0.286 |
| Age, years | 0.832 | 0.660 | 0.518 | 0.772 | 0.423 | 0.85 |
| BMI | 4.001 | 0.135 | 10.418 | 0.005* | 2.188 | 0.335 |
| Education | 13.752 | 0.003* | 13.101 | 0.001* | 1.303 | 0.521 |
| Employment | 3.044 | 0.385 | 3.330 | 0.189 | 1.073 | 0.585 |
| Diagnosis | −0.215 | 0.830 | – | – | ||
| Disease activity | 0.062 | 0.969 | 3.813 | 0.149 | 1.877 | 0.391 |
| Age at diagnosis | 1.882 | 0.390 | 2.472 | 0.291 | 0.045 | 0.978 |
| Disease duration | 2.085 | 0.353 | 3.209 | 0.201 | 0.169 | 0.919 |
| Surgical history | −0.64 | 0.522 | 0.811 | 0.667 | 0.498 | 0.779 |
| Current Biologics | −0.085 | 0.933 | 3.161 | 0.206 | 1.678 | 0.432 |
| Current steroid/immunomodulator | −1.145 | 0.252 | 1.075 | 0.584 | 3.962 | 0.138 |
| PA outcome expectation score | 20.158 | <0.001* | 22.615 | <0.001* | 2.332 | 0.312 |
| Sedentary time | 0.867 | 0.648 | 0.326 | 0.850 | 0.584 | 0.747 |
| PA reduction after IBD diagnosis | −0.874 | 0.382 | 4.856 | 0.088† | 3.592 | 0.166 |
| Electronic device use for PA recording | −0.942 | 0.346 | 2.530 | 0.282 | 5.352 | 0.069† |
*Indicates p<0.01
†Indicates 0.05 <p<0.1.
CD, Crohn's disease; IBD, inflammatory bowel disease; PA, physical activity; UC, ulcerative colitis.
Further multivariate logistic regression analysis revealed that gender (OR 1.704, 95% CI 1.132 to 2.565, p=0.011) and PA outcome expectation score (OR 1.176, 95% CI 1.090 to 1.270, p<0.01) were independent influences on PA levels in IBD patients, which were positively correlated (table 4). In patients with CD, multivariate logistic regression analyses revealed that only PA outcome expectation score (OR 1.247, 95% CI 1.126 to 1.383, p<0.01) was an independent influence on PA levels (online supplemental table 2).
Table 4Multivariate logistic regression of PA levels for IBD patients
| Variable | β | SE | Waldχ2 | OR (95% CI) | P value |
| PA outcome expectation score | 0.162 | 0.039 | 17.427 | 1.176 (1.090 to 1.270) | <0.01* |
| Gender, male/female | 0.533 | 0.209 | 6.532 | 1.704 (1.132 to 2.565) | 0.011* |
| Education middle school/high school | 0.209 | 0.684 | 0.094 | 1.232 (0.323 to 4.707) | 0.759 |
| High school/college and Bachelor | 0.488 | 0.684 | 0.508 | 1.629 (0.426 to 6.228) | 0.476 |
| College and Bachelor/Postgraduate | 0.952 | 0.654 | 2.118 | 2.591 (0.719 to 9.346) | 0.146 |
*Indicates statistical significance.
PA, physical activity.
Since PA outcome expectation score was the most significant modifiable influencing factor of PA level, we further analysed its differences by gender, disease type, disease activity and PA level categories. Only PA level showed a significant difference (figure 2). The low-level category had a significantly lower PA outcome expectation score than the moderate and high categories, with no significant difference between the latter two.
Enlarge this image.Figure 2. Differences of PA outcome expectation scores (median) by gender, (A) disease type, (B) disease activity (C) and PA level categories. ** indicates p<0.01. CD, Crohn’s disease; PA, physical activity; UC, ulcerative colitis; NS, no significance.
Discussion
In this study, a multicentre cross-sectional survey was conducted to understand the current PA pattern of patients with IBD in East China, including total PA, PA levels, sedentary time, PA type and venues. We also investigated the limiting factors that discourage IBD patients from exercising and their outcome expectations of PA on IBD. This is by far the largest size questionnaire survey in China on the topic of PA among IBD patients.
The results of this study showed that total PA and the proportion of moderate to high level were quite low among IBD patients in East China. Tew et al collected 859 IPAQ questionnaires among IBD patients in the UK. The percentages of CD and UC in active disease were 71.7% and 59.3%, respectively. The total PA was 1866 MET-min/week, with 17% at high, 49.6% at moderate and 33.3% at low PA level.8 Gravina et al.’s recent ‘BE-FIT-IBD’ study carried out in Italy assessed 219 non-severe IBD patients using PRO-2 and IPAQ methods, finding an average PA level of 834.5 MET-min/week, with 42.9% classified as physically inactive.12 25 Similar studies have been conducted in Asia. A Japanese study of 327 UC patients found 60.6% in clinical remission with an average of 165 min/week of PA.13 In a Korean study with 158 IBD patients, the total PA of CD patients was 398 MET-min/week with 80.6% in remission, and the total PA of UC patients was 469 MET-min/week with 94.5% in remission.14 Recently, Qiao R et al conducted a cross-sectional study on fatigue, PA and quality of life in 237 IBD patients at a single IBD centre in China, revealing a considerably low level of PA, with only 39.2% reaching moderate to high PA levels.26 The above data suggested that the PA level of Asian IBD patients, including those in China, may be much lower than IBD patients in Western countries, even when in remission. This West–East difference cannot be explained by disease activity. Thus, our study focused further on non-disease-related factors and outcome expectations of PA, particularly its effect on disease control or flare-ups.
Adult patients tended to reduce PA levels after the diagnosis of IBD. A cross-sectional study involving 158 adult IBD patients in remission revealed that about 1/3 of the patients decreased their PA after the diagnosis of IBD, with UC patients tending to reduce more than those with CD.27 In the present study, as much as 46.0% of patients with IBD had a decrease in PA after diagnosis, and the percentage of decrease in CD was significantly higher than in UC. The decline in PA levels observed in patients following an IBD diagnosis may be attributable to disease-related, comorbidity-related or even non-disease-related factors. Several studies have found that symptoms such as abdominal pain, diarrhoea, arthralgia and fatigue are important factors limiting PA participation in patients with IBD.8 15 It has also been shown that anxiety, depressive mood and patients’ negative perception of PA are significantly correlated with decreased PA level and increased sedentary time among IBD patients.16 Our study found that disease activity did not significantly affect PA levels, likely due to the high percentage of patients in remission, resulting in an insignificant difference. However, aside from fatigue, which was the second most reported barrier, disease-related factors limiting IBD patients’ participation were primarily related to disease activity, including abdominal pain, arthralgia, disease flare-up and increased bowel frequency or urgency. This suggests that disease activity remained critical for PA engagement.
Non-disease-related factors influencing PA engagement, including outcome expectations of PA and cross-regional cultural or lifestyle differences, warrant further investigation. The ‘BE FIT IBD’ study revealed that a higher proportion of inactive patients, compared with their active counterparts, believed that PA could reactivate or exacerbate clinical activity.12 A posthoc analysis of this study highlighted the role of partner and social network status, suggesting that having a PA-supportive partner or social network may serve as an accelerator for PA engagement.25 Similarly, our study found that PA outcome expectation score was a significant modifiable influence of PA level. That is, the higher the outcome expectation score of PA, the higher the PA level. One novelty of our study is the investigation of non-disease-related factors limiting the participation of IBD patients in PA, of which ‘lack of time for PA’ and ‘dislike of PA’ are the two main factors. This may explain why total PA remained low even when in remission among Asian patients with IBD.
Given the current scarcity of relevant data in China, this study will serve as a foundation for future, larger observational studies and interventional clinical trials. However, this study had some limitations: (1) patients were recruited from IBD clinics, infusion centres and WeChat groups. This may have created selection bias resulting in a higher proportion of biologics users, higher clinical remission rates and better literacy levels. These factors could impact the study’s generalisability. (2) The study had an uneven proportion of patients with CD and UC due to various factors such as methods of enrolment, high incidence of CD in East China and WeChat patient groups with a high proportion of CD treated with biologics. As a result, significantly more CD patients responded to the questionnaire than UC patients, which may have led to statistically insignificant differences in all variables in the UC subgroup analysis due to the smaller sample number. (3) The IPAQ short form was used to measure PA level in our study. While IPAQ is a validated self-report PA questionnaire that is widely used, the IPAQ short form overestimated PA level by 36% to 173% in most published studies.28 Therefore, our results may be biased compared with more objective methods of PA recording, such as accelerometers. To generalise the findings to a broader population of IBD patients, future multicentre cross-sectional studies employing more representative sampling methods and encompassing a greater number of regions within China are warranted.
In summary, this is the largest questionnaire survey on the PA status of IBD patients in China. The results of this study suggested that IBD patients in East China had a considerably low level of PA engagement with both disease-related and non-disease-related limiting factors. CD patients had longer sedentary time and more PA reduction after IBD diagnosis than UC. Gender and PA outcome expectations are independent influences on PA levels. Therefore, improving the outcome expectations of PA among IBD patients, especially female and CD patients, may be an effective means to increase participation in PA. This is also one of the directions for future interventional studies.
We would like to thank Yan Chen of the Second Affiliated Hospital of Zhejiang University, Yi Jiang of the Second Affiliated Hospital of Wenzhou Medical University, Yabi Zhu of the Lishui People's Hospital, Qin Huang of the Taizhou Enze Hospital and Xiao Zhu of the Quzhou People's Hospital for their help in questionnaire forwarding and patient inclusion. We also acknowledge Danli Liu from Health Commission of Ningbo Jiangbei District for her support on the statistical design and analysis of this study.
Data availability statement
Data are available upon reasonable request.
Ethics statements
Patient consent for publication
Consent obtained directly from patient(s).
Ethics approval
This study involves human participants and was approved by the Ethical Committee of Ningbo Medical Center Lihuili Hospital (KY2022SL225-01). Participants gave informed consent to participate in the study before taking part.
Contributors YZ designed the study and drafted the manuscript. HL and LX did patient recruitment, questionnaire collection and data processing. XZ and FX revised the questionnaire and the manuscript. YZ is the guarantor.
Funding Qingfeng Scientific Research Fund of China Crohn’s & Colitis Foundation (CCCF-QF-2022C16-18).
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, conduct, 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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; Liu, Huiwei; Xu, Liyan; Xie, Zhang; Xu, Feng