Published online Jun 9, 2023. doi: 10.5492/wjccm.v12.i3.176
Peer-review started: April 14, 2023
First decision: May 9, 2023
Revised: May 15, 2023
Accepted: May 31, 2023
Article in press: May 31, 2023
Published online: June 9, 2023
Processing time: 54 Days and 17.6 Hours
The proficiency of nursing professionals in the infection prevention and control (IPC) practices is a core component of the strategy to mitigate the challenge of healthcare associated infections.
To test knowledge of nurses working in intensive care units (ICU) in South Asia and Middle East countries on IPC practices.
An online self-assessment questionnaire based on various aspects of IPC practices was conducted among nurses over three weeks.
A total of 1333 nurses from 13 countries completed the survey. The average score was 72.8% and 36% of nurses were proficient (mean score > 80%). 43% and 68.3% of respondents were from government and teaching hospitals, respectively. 79.2% of respondents worked in < 25 bedded ICUs and 46.5% in closed ICUs. Statistically, a significant association was found between the knowledge and expertise of nurses, the country’s per-capita income, type of hospitals, accreditation and teaching status of hospitals and type of ICUs. Working in high- and upper-middle-income countries (β = 4.89, 95%CI: 3.55 to 6.22) was positively associated, and the teaching status of the hospital (β = -4.58, 95%CI: -6.81 to -2.36) was negatively associated with the knowledge score among respondents.
There is considerable variation in knowledge among nurses working in ICU. Factors like income status of countries, public vs private and teaching status of hospitals and experience are independently associated with nurses’ knowledge of IPC practices.
Core Tip: The knowledge testing on infection prevention and control (IPC) practices among intensive care unit nurses in South Asia and the Middle East showed considerable variation. The higher economic status of the country and working experience were independently associated with better knowledge among respondents. Working in public or teaching hospital were inversely associated with knowledge of IPC practices. There is an urgent need for education and awareness among nurses regarding IPC practices, especially in lower-middle-income countries.
- Citation: Sodhi K, Chanchalani G, Arya M, Shrestha GS, Chandwani JN, Kumar M, Kansal MG, Ashrafuzzaman M, Mudalige AD, Al Tayar A, Mansour B, Saeed HM, Hashmi M, Das M, Al Shirawi NN, Mathias R, Ahmed WO, Sharma A, Agarwal D, Nasa P. Knowledge and awareness of infection control practices among nursing professionals: A cross-sectional survey from South Asia and the Middle East. World J Crit Care Med 2023; 12(3): 176-187
- URL: https://www.wjgnet.com/2220-3141/full/v12/i3/176.htm
- DOI: https://dx.doi.org/10.5492/wjccm.v12.i3.176
Healthcare-associated infections (HAI) pose a considerable threat to the patients who are admitted in hospitals, especially in intensive care units (ICU). According to the surveillance report published by the International Nosocomial Infection Control Consortium, despite appreciable efforts on prevention and control of HAI, the Device-Associated (DA)-HAI rates in the ICUs of developing countries are higher compared to the developed nations[1]. Though the device utilization rate is similar, the DA-HAI rates of the ICUs in the developing countries remain higher than the ones belonging to the Center for Disease Control and Prevention- National Healthcare and Safety Network[1,2]. Hence, a robust infection prevention and control (IPC) program involving multi-disciplinary stakeholders is essential to mitigate the threat of HAI[3]. However, the compliance with IPC practices has been a critical implication on the implementation of the IPC program. Nurses have frequent and direct contact with the patients due to which, their knowledge and awareness about the IPC practices are integral[4]. On the other hand, the nurses are also at-risk of self-infection when providing care to critically ill patients[5]. Several factors may affect the compliance with IPC practices, prominent of which are knowledge, education and training, and the experience of nurses[6]. The lack of knowledge among health care workers (HCWs) about the IPC practices or the occurrence of discrepancies when applying this knowledge in bedside has been linked to worsening healthcare delivery outcomes, especially in case of developing countries[6-8]. Recently, the global experts have recommended that the ICU nurses should be a part of the surveillance team that monitor adherence of IPC practices[9].
The countries in South Asia and the Middle East regions constitute one-third of the global population. In spite of such common neighborhoods and centuries of cultural and political exchange, these countries exhibit vast differences in terms of income, availability of the resources and healthcare dynamics[10].
Though studies have been conducted to evaluate the knowledge of the nurses from individual nations, the authors were unable to find any literature that compares the knowledge of the nurses across the South Asian and Middle Eastern nations[8,11,12]. So, the current study is aimed to analyse the knowledge of ICU nurses on various aspects of IPC practices across the countries in South Asia and the Middle East.
The study was conducted over three weeks, from April 20 to May 10, 2022. An online-based, cross-sectional survey was conducted using a multiple-choice questionnaire to evaluate the knowledge of nurses on various aspects of the IPC program. A 20-member steering committee comprising of critical care physicians, infection control professionals, microbiologist and the nursing administrator was involved in framing the questionnaire and its pilot run. The questionnaire was examined, revised and validated internally among the steering committee. Internal consistency among the questionnaire items using Cronbach's alpha (α) was found to be 0.90, which was considered within the acceptable range. The study was approved by the Ethics Committee (DHEC-2057/2022) of the institute, where the principal investigator (Kanwalpreet Sodhi) is affiliated and is exempted from other participating hospitals.
The final questionnaire has two portions in which the first portion covered the aspects like country name, profile of the hospital such as the type of setup, hospital accreditation and their teaching status, the type, size and the operating model of the ICU, and the nurses’ demographic data including their years of clinical experience. The operating model of the ICU had three options such as “Open ICU” in which the patients are admitted under the care of a non-intensivist physician, with the intensivists providing their expertise consultation when required, “Closed ICU” in which the patients are admitted under an intensivist-led team, and is held responsible for the primary care, and “Semi-closed ICU” in which the intensivist-led team provides direct patient care in collaboration with the non-intensivist physicians with shared decision making[13]. The second portion of the questionnaire consisted of 25 single best response types, i.e., multiple choice questions (MCQ) on different aspects of the IPC practices, categorized under five sections such as the general aspects of infection control, standard precautions, transmission-based precautions, care bundles, and severe acute respiratory syndrome coronavirus 2 transmission (Appendix). Each section had five MCQs, and respondents can score one mark for a correct response. The answers to the MCQs were decided a priori by the steering committee members (Kanwalpreet Sodhi, Muktanjali Arya Amandeep Sharma, Prashant Nasa). The knowledge level was categorized based on the mean overall score, secured by the participants, i.e., more than 81% score as proficient, 61%-80% as above average, 41%-60% as average and less than 40% as poor knowledge (Table 1).
Number of respondents (%) | Number of respondents (%) | ||
World Bank income classification | Working experience (yr) | ||
High-income countries | 608 (45.6) | < 2 yr | 232 (17.4) |
Upper middle-income countries | 69 (5.2) | 2-5 yr | 354 (26.6) |
Lower middle-income countries | 656 (49.2) | 5-10 yr | 351 (26.3) |
> 10 yr | 396 (29.7) | ||
Score attained by level of knowledge | |||
Proficient (81%-100%) | 480 (36) | Type of ICU | |
Above average (61%-80%) | 472 (35.4) | Medical and Surgical ICU | 607 (45.5) |
Average (41%-60%) | 296 (22.2) | Medical ICU | 408 (30.6) |
Below average (≤ 40%) | 85 (6.4) | Others | 318 (23.9) |
Type of hospital | Size of ICU (number of beds) | ||
Corporate/private | 524 (39) | < 25 bedded | 1056 (79.2) |
Medical college/university hospital | 239 (18) | 25-100 bedded | 251 (18.8) |
Public/government | 570 (43) | > 100 bedded | 26 (2.0) |
Hospital accreditation | Operating model of ICU | ||
International | 606 (45.5) | Closed ICU | 620 (46.5) |
National | 442 (33.2) | Open ICU | 355 (26.6) |
None | 285 (21.4) | Semi-closed ICU | 358 (26.9) |
Teaching status | |||
Non-teaching | 422 (31.7) | ||
Teaching | 911 (68.3) |
The survey was conducted using a web link circulated by the steering committee members of the respective participant countries. The study included around 4-5 tertiary care hospitals from each country. The questionnaire was distributed to the nurses who work full-time in ICUs, and they were asked to fill it anonymously and voluntarily. The nurse trainees were excluded from the study. The consent for participation in the study and the publication of the results was obtained from the respondents at the beginning of the online questionnaire. The STROBE checklist was used for reporting the results of this cross-sectional survey.
The data was described in terms of frequencies (number of cases) and relative frequencies (percentages) as appropriate. In order to compare the categorical data, the chi-square (χ2) test was used. Both univariate and multivariate linear regression analyses were conducted to compare the covariates. A probability value (P value) less than 0.05 was considered to be statistically significant. The outcome variable for the linear regression analysis was the total score secured from the questionnaire and no continuous data sets were present. Collinearity was checked for each predictor variable whereas non-linear regression underwent the same analysis and yielded the same conclusions. (Appendix) Those variables obtaining a P value < 0.05 in the univariate analysis, were included in the multivariate linear regression analyses. The beta coefficient and the confidence intervals were used to present of the multivariate linear regression analysis. All the statistical calculations were done using (Statistical Package for the Social Science) SPSS version 21 (SPSS Inc., Chicago, IL, United States) statistical program for Microsoft Windows.
The questionnaire was filled out by 1376 nurses across 13 countries. Out of the total responses, 43 were excluded from the final analysis (11 with negative consent for participation, and 32 had missing information). The data from 1333 respondents (nurses) was considered for the study (Figure 1).
The demographic profile of the respondents’ hospitals and the ICUs is provided in Table 2. For analysis, the countries of the respondents were divided according to the World Bank income classification criteria into high-income countries (HIC) (such as Bahrain, the United Arab Emirates, Oman, Qatar, Saudi Arabia, and Singapore); upper-middle-income countries (UMIC) (i.e., Lebanon); and lower-middle-income countries (LMIC) (such as Bangladesh, Bhutan, India, Sri Lanka, Nepal, and Pakistan). Most of the respondents belong to HIC (608, 45.6%) and LMIC (656, 49.2%). The respondents had varying level of experience, with 232 (17.4%) nurses having less than two years of experience and 396 (29.7%) nurses with more than ten years of experience. Among the responding nurses, 524 (39%) worked in corporate or private hospitals, whereas 570(43%) were in public hospitals. Most of the respondents worked in a hospital, accredited either by an international agency like Joint Commission International (606, 45.5%), or a national level agency (442, 33.2%). Further, majority of the respondents (1056, 79.2%) were working in less than 25-bedded ICUs and 607 (45%) were in mixed medical and surgical ICUs. In terms of the operational model of ICU, 620 (46.5%) respondents were working in closed ICUs and nearly equal proportion (27%) were in open and semi-closed ICUs. Further most of the respondents (911, 68.3%) worked in teaching hospitals.
Knowledge level categories | χ2 value | P value | ||||
Below average | Average | Above average | Proficient | |||
Working experience (yr) | ||||||
< 2 yr | 24 (28.2) | 69 (23.3%) | 86 (18.2%) | 53 (11%) | 57.09 | 0.001a |
2-5 yr | 29 (34.1%) | 84 (28.4%) | 109 (23.1%) | 132 (27.5%) | ||
5-10 yr | 15 (17.6%) | 48 (16.2%) | 125 (26.5%) | 163 (34.0%) | ||
> 10 yr | 17 (20%) | 95 (32.1%) | 152 (32.2%) | 132 (27.5%) | ||
World bank income classification | ||||||
High-income countries | 14 (2) | 119 (19.6) | 238 (39.1) | 237 (38.9) | 46.47 | 0.001a |
Lower-middle-income countries | 68 (10.4) | 164 (25) | 211 (32.2) | 213 (32.4) | ||
Upper-middle-income countries | 3 (4.3) | 13 (18.8) | 23 (33.3) | 30 (43.5) | ||
Type of hospital | ||||||
Corporate/private | 42 (8) | 98 (18.7) | 153 (29.2) | 231 (44.1) | 60.53 | 0.001a |
Medical college/university hospital | 26 (10.9) | 56 (23.4) | 72 (30.1) | 85 (35.6) | ||
Public/government | 17 (2.9) | 142 (24.9) | 247 (43.3) | 164 (28.8) | ||
Hospital accreditation | ||||||
International | 30 (4.9) | 120 (19.8) | 220 (36.3) | 236 (38.9) | 30.56 | 0.001a |
National | 42 (9.5) | 122 (27.6) | 153 (34.6) | 125 (28.3) | ||
None | 13 (4.6) | 54 (18.9) | 99 (34.7) | 119 (41.7) | ||
Teaching status | ||||||
Non-teaching | 18 (4.2) | 70 (16.6) | 149 (35.3) | 185 (43.8) | 23.61 | 0.001a |
Teaching | 67 (7.3) | 226 (24.8) | 323 (35.5) | 295 (32.4) | ||
Operating model of ICU | ||||||
Closed ICU | 46 (7.4) | 146 (23.5) | 215 (34.7) | 213 (34.4) | 5.74 | 0.45 |
Open ICU | 18 (5.1) | 81 (22.8) | 122 (34.4) | 134 (37.7) | ||
Semi-closed ICU | 21 (5.9) | 69 (19.3) | 135 (37.7) | 133 (37.1) | ||
Type of ICU | ||||||
Medical-surgical ICU | 30 (4.9) | 113 (18.6) | 221 (36.4) | 243 (40) | 19.39 | 0.004a |
Medical ICU | 30 (7.4) | 98 (24) | 134 (32.8) | 146 (35.8) | ||
Other | 25 (7.9) | 85 (26.7) | 117 (36.8) | 91 (28.3) | ||
Size of ICU (number of beds) | ||||||
< 25 | 61 (5.8) | 231 (21.9) | 390 (36.9) | 374 (35.4) | 17.27 | 0.008a |
25-100 | 18 (7.2) | 59 (23.5) | 77 (30.7) | 97 (38.6) | ||
> 100 | 6 (23.1) | 6 (23.1) | 5 (19.2) | 9 (34.6) |
The average score of the respondents was 72.8% (Figure 2). In terms of knowledge level categories, 480 (36%) respondents were categorized as proficient, and 472 (35.4%) had above-average knowledge. Only 11% of the respondents with less than two years of experience, were found to be proficient, compared to 34% respondents who had 5-10 years of experience. The knowledge of 32% of nurses with > 10 years of experience was above average, compared to 18% nurses with < 2 years of experience (Table 1). A statistically significant difference was found between the respondents on knowledge testing based on the working experience of the nurses (P = 0.001). Further, there was also statistically significant difference in the knowledge of the nurses based on World Bank income status (P = 0.001). The performance of the respondents working in HIC and UMIC was found to be better than the LMIC. Further, 237 (38.9%) and 30 (43.5%) respondents from the HIC and UMIC, respectively, were found to be proficient, compared to 213 (32.4%) respondents from LMIC.
The difference in the knowledge of the respondents, based on the type of hospital was found to be statistically significant (P = 0.001). A more significant proportion of the nurses, working in corporate/private hospitals (231, 44.1%) and medical college/university hospitals (85, 35.6%) was found to be proficient than those working in public hospitals (164, 28.8%). There was also a statistically significant difference found in the knowledge of the nurses based on the accreditation status and teaching status of the hospital (P = 0.001).
In terms of the ICU setup, a difference was found in the knowledge of responding nurses for the type (P = 0.004) and size (P = 0.007) of the ICU. However, no significant difference was found in the knowledge of the respondents based on the operating model of ICU (P = 0.453) (Table 2).
In terms of multivariate analysis, the income status of the country (P < 0.001), type of the hospital (P < 0.001), teaching status (P < 0.001) and the experience of the nurses (P = 0.001) showed an independent association with a difference in knowledge among the nurses. Working in HIC and UMIC was found to be strongly associated with the high knowledge score secured by respondents (β = 4.89, 95%CI: 3.55 to 6.22). The teaching status of the hospital was inversely associated with the knowledge score secured by the respondents (β = -4.58, 95%CI: -6.81 to -2.36) (Table 3).
Variables | Beta coefficient | P value | 95%CI | |
Lower bound | Upper bound | |||
Type of hospital | -3.76 | < 0.001a | -5.03 | -2.49 |
Hospital accreditation | 0.89 | 0.24 | -0.59 | 2.36 |
Teaching status | -4.58 | < 0.001a | -6.81 | -2.36 |
World bank income classification | 4.89 | < 0.001a | 3.55 | 6.22 |
Type of ICU | -1.04 | 0.13 | -2.40 | 0.32 |
Size of ICU | -2.01 | 0.07 | -4.21 | 0.19 |
Working experience | 1.71 | 0.001a | 0.70 | 2.71 |
The cross-sectional survey results, on knowledge testing of the nurses working in 13 countries of South Asia and the Middle East, showed a considerable variation. About 3/4th of the respondents secured above average or proficient scores. Some of the factors like the higher economic status of the country and working experience were found to be independently associated with better knowledge among the respondents. On the other hand, working in teaching or public hospitals was inversely associated with the knowledge level of IPC practices than the private and university hospitals.
In general, the ICUs show the highest prevalence of HAIs in a hospital setting. This may adversely affect the patients' clinical outcomes like length of stay in the hospital and ICU, quality of life after discharge, and mortality[14,15]. Nurses are the first and the foremost formidable line of defense against the HAIs. Hence their training, and awareness levels, knowledge, and compliance for the IPC practices are crucial in preventing the HAIs. The regional studies conducted earlier found gaps in the knowledge of HCWs upon the IPC practices, whereas training was found to be independently associated with better knowledge[16,17]. The literature showed a positive correlation between knowledge and better compliance with IPC practices among the HCWs[18,19].
Among five sections, the performance of the respondents was found to be worst in the section in transmission-based precautions. This reflects the knowledge deficiency of the nurses in understanding the microbiology aspect of IPC among nurses, which can be a focal point for future training programs. A systematic review of 30 studies also identified few gaps in the knowledge of HCWs among different IPC areas, such as vaccinations for HCWs, modes of transmission of infectious diseases, and the risk of infection from needle-stick and sharps injuries[6].
A recent review found that the structure and the skills of the ICU nurses vary according to the patient population, and availability of the resources, and treatments[20]. The current study found a strong association between the economic status of the countries (either UMIC or HIC vs LMIC) and better knowledge among the nurses. This finding infers about the impact caused by better resources, training, and surveillance opportunities on IPC practices in HIC or UMIC compared to LMIC. However, this finding is worrisome since the burden of HAIs is considerably higher in LMICs[21]. A recent global survey conducted by the World Health Organization on core components of the IPC programme and its implementation in healthcare facilities also highlighted the existence of critical gaps in LMIC and low-income countries[22]. The core components involving the workload, staffing, bed occupancy, education and training were scored the lowest in the survey.
The respondents working in private hospitals had significantly better knowledge about the IPC compared to their counterparts working in public hospitals. Though no direct studies compare different hospital settings on IPC practices, a few single-center studies have shown sound knowledge of the nurses working in private hospitals[23]. This can be attributed to resource constraints in terms of equipment, medications and the availability of the trained HCWs in public hospitals compared to private hospitals[24]. The current study finding with regards to teaching status of the hospital being negatively associated with knowledge of the nurses, is surprising. However, this can be explained by the fact that most of the teaching hospitals are public hospitals in UMIC and LMIC countries. Few studies conducted with the small number of samples in these countries from the region also found a deficiency in the knowledge among nurses working in teaching hospitals[25-27]. This suggests that education and training on IPC should be incorporated into medical teaching.
In the current study, a statistically significant difference was found in the knowledge of respondents based on their hospital accreditation status. Patient safety remains the centerpiece of hospital quality accreditation programs. Periodic training of the HCWs on various hospital-based policies, including IPC, is a core component of patient safety. In the current study, it is surprising to find the deficiency in knowledge of among the respondents working in hospitals with a national-level accreditation compared to their counterparts in international accreditation. However, the accreditation status was found to be not independently associated with better knowledge. This may reflect a difference in the standards of accreditation among the participating hospitals.
The working experience of the nurses was another factor, independently associated with a better knowledge. Since experience is the best teacher, it is expected that the knowledge of the nurses gets enhanced with increasing number of years of practice along with periodic trainings. In our previous multi-center study conducted in India, the working experience had a significant association with better knowledge among nurses[28]. Another single-center study from Saudi Arabia also found that the age (> 34 years), training and experience (> 6 years) were a predictor of good knowledge[17].
The current study is a first-of-its-kind in this domain since the study conducted simultaneous knowledge testing of more than 1300 critical care nurses on IPC practices from 13 Asian countries. The survey intends to provide a snapshot of the knowledge of nursing professionals in terms of IPC practices, working in countries with a close cultural, social, and economic exchange. Besides testing the knowledge of the nurses on different aspects of IPC practices, the current study also tried to compare the knowledge based on a few factors such as the economic status of the country, working experience of the respondents; the type, accreditation, and the teaching status of the hospital, in which the respondents are working; and the type, size, and the operating model of ICUs by the respondents. The survey was participated by ICU nurses from large public and private hospitals with varying levels of accreditation and ICU setup.
The current study has a few limitations. Non-random convenience sampling method was followed for the study to obtain the data from only a set of selected hospitals from each participating nation. So, this data may not represent any individual country on the whole. We did make an effort to make the study population representative of nurses within respective countries with inclusion of public, corporate or university hospitals; teaching and non-teaching hospitals; and accredited as well as non-accredited hospitals, but still, this might not be an absolute representation. The number of entries received from each country varied from 57 to 228 which may have caused some statistical bias. The questionnaire did not include all the components of IPC as the intention was to evaluate only the knowledge of nurses working in the ICU. The questionnaire was made available to the study participants only in English and was not translated in their local language, due to concerns regarding accuracy and the misinterpretation of the questions. There is a potential for bias because of the gap in understanding the questions by the nurses due to language barrier. The knowledge testing of the IPC practices does not reflect the actual compliance with IPC practices and might not correlate with this self-answered knowledge evaluation. We did not capture the age, gender, qualification, and method of training rendered to the respondents, as these factors may have explained the variation in knowledge. Since the survey was an open-book and without any time restriction, the respondents might have answered the questions after taking external help, thus bringing a possible bias.
The current cross-sectional survey on testing the knowledge of nursing professionals on IPC practices from 13 Asian countries found a considerable variation. The higher economic status of the country and working experience were found to be independently associated with a better knowledge among the respondents. Working in public or teaching hospitals were found to be inversely associated with better knowledge about the IPC practices. There is an urgent need for periodic training and audits on the IPC practices of HCWs working in ICUs, especially in LMICs.
Healthcare-associated infections (HAI) pose a significant threat to patients in hospitals, particularly in intensive care units (ICU). Despite efforts to prevent and control HAI, rates of device-associated (DA)-HAI in ICUs of developing countries remain higher than those in developed nations. Compliance with infection prevention and control (IPC) practices is crucial, and nurses play a key role due to their frequent contact with patients.
The lack of knowledge and awareness among healthcare workers about IPC practices, as well as discrepancies in applying this knowledge, have been linked to poor healthcare outcomes, especially in developing countries. ICU nurses' knowledge and awareness are integral to an effective IPC program. However, there is a lack of literature comparing the knowledge of ICU nurses across South Asian and Middle Eastern countries.
The current study aims to analyse the knowledge of ICU nurses regarding various aspects of IPC practices across countries in South Asia and the Middle East.
The study conducted an online-based, cross-sectional survey using a multiple-choice questionnaire. The questionnaire was developed and validated by a 20-member steering committee comprising critical care physicians, infection control professionals, microbiologists, and nursing administrators. The survey was distributed to full-time ICU nurses in participating hospitals. The data were analysed using descriptive statistics, chi-square tests, and linear regression.
A total of 1333 nurses from 13 countries participated in the study. The average knowledge score was 72.8%, with 71.4% of respondents categorized as having above-average or proficient knowledge. Factors such as higher country income status, private hospital setting, and greater nursing experience were associated with better knowledge. Teaching hospitals and public hospitals showed lower knowledge levels.
The study revealed significant variation in knowledge levels among ICU nurses across South Asian and Middle Eastern countries. Factors such as country income status, hospital type, teaching status, and nursing experience were associated with knowledge differences. These findings highlight the need for targeted interventions and training programs to improve IPC knowledge and practices, particularly in public and teaching hospitals.
Future research should focus on developing comprehensive training programs and policies to enhance IPC knowledge and compliance among ICU nurses in South Asian and Middle Eastern countries. Comparative studies between different hospital settings and income groups can provide valuable insights into the factors influencing IPC practices and outcomes. Additionally, exploring the impact of improved IPC knowledge on healthcare delivery outcomes can further strengthen the evidence base for effective infection control strategies.
Provenance and peer review: Invited article; Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Critical care medicine
Country/Territory of origin: United Arab Emirates
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P-Reviewer: Bittner EA, United States; Marano L, Italy; Roilides E, Greece S-Editor: Ma YJ L-Editor: A P-Editor: Ma YJ
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