|
ORIGINAL ARTICLE |
https://doi.org/10.5005/jp-journals-10071-24432
|
“Nurse—The Archer” Fighting Against the Hidden Enemy
1,3,4Department of Nursing, Apollo Hospitals, Chennai, Tamil Nadu, India
2,5,7Department of Infectious Disease, Apollo Hospitals, Chennai, Tamil Nadu, India
6Department of Critical Care Medicine, Apollo Hospitals, Chennai, Tamil Nadu, India
Corresponding Author: Samundeeswari Premkumar, Department of Nursing, Apollo Hospitals, Chennai, Tamil Nadu, India, Phone: +91 9500019148, e-mail: sam.varnith@gmail.com
How to cite this article: Premkumar S, Ramanathan Y, Varghese JJ, Morris B, Nambi PS, Ramakrishnan N, et al. “Nurse—The Archer” Fighting Against the Hidden Enemy. Indian J Crit Care Med 2023;27(4):246–253.
Source of support: Nil
Conflict of interest: None
Received on: 23 November 2022; Accepted on: 10 March 2023; Published on: 31 March 2023
ABSTRACT
Background and aim: The coronavirus disease-2019 (COVID-19) pandemic is a global threat spreading like a wildfire and taking the world by its storm. It has challenged the healthcare delivery systems and disrupted them in a way no one ever imagined before. We at Apollo Hospitals, Chennai, Tamil Nadu, India received many patients in the COVID critical care unit (CCU) and found a gradual lack of bundle care compliance resulting in an upsurge of central line-associated bloodstream infection (CLABSI) amid the patients.
Materials and methods: A qualitative research approach and quasi-experimental research design were selected to assess the knowledge of the 150 frontline COVID CCU nurses regarding the CLABSI bundle and its prevention strategies.
Results: This study revealed that 57% [mean (M) = 12.6; standard deviation (SD) = 2.37] of nurses had inadequate knowledge of the CLABSI bundle and its prevention strategies, in the pretest and scored 80% (M = 6.7; SD = 2.28) in the post-test, with “t” = 22.06 at p < 0.00001 after the hands-on training. The percentage of compliance to CLABSI bundle care increased to 83% and thereafter in an increasing trend. This was clearly evident through the reduction in the preventable CLABSI rate among critically ill COVID-19 patients.
Conclusion: Nurses are on the frontline in preventing and controlling healthcare-associated infections (HAIs). Fighting with all the visible and invisible challenges, our research focused on hands-on training for frontline warriors to adhere to the CLABSI bundle care which drove us to the reduction in preventable CLABSI rate in our hospital through improved CLABSI bundle compliance.
Keywords: Bundle compliance, Central line-associated bloodstream infections, Coronavirus disease-2019, Critical care unit, Infection control, Staff nurses.
HIGHLIGHTS
We expound the nurses as the archers to fight against the battle, targeting hands-on training. This study was commenced to evaluate the knowledge and monitor the CLABSIs bundle care compliance of the COVID CCU nurse, focused on hands-on training about bundle care components and thereby reduce the preventable CLABSI.
INTRODUCTION
The COVID-19 Pandemic: A Global Threat Which Turned Critical Care Units into the Battlefield
The COVID-19 pandemic is a global threat spreading like a wildfire and has taken the world by storm. The pandemic has challenged the healthcare delivery systems and disrupted them in a way no one imagined before. The pandemic led to a dramatic loss of human life worldwide and presents an unprecedented challenge in innumerable ways.1 Hospitalized COVID patients admitted during the pandemic were more in need of critical care support and for a prolong period. Furthermore, most of the COVID-19 patients were Category C, requiring keen monitoring and tertiary levels of care, including ventilatory and critical care support.2 Central lines were used in 30–40% of the patients admitted to CCU, with an average time period of 7 days, which put COVID-19 patients at a higher risk of CLABSI.3
Criticality of patients, usage of steroids, need for a central line, difficult access to a central line in patients in prone positions, and attrition of nursing manpower during the COVID-19 crisis were the major factors contributing to the increase in CLABSI rate among COVID-19 patients.4 The effects of the pandemic were catastrophic, exposing vulnerable patients to more risk of acquiring nosocomial infections. Among HAIs, CLABSI, has an arduous impact on the health of the patients, increasing their mortality and morbidity, and adding to their financial burden, resulting in dire, consequences affecting the final clinical outcome of the patient and impacting patient safety.5 Recent studies have reported enormous rise in CLABSI events among COVID-19 patients.3
The COVID-19 pandemic had a disruptive effect on our healthcare system, resulting in an abrupt drop in admissions for most usual conditions and leading to a selective increase in the severity of illness among COVID-19 hospitalized patients.6 A precipitous drop in elective surgical cases and an avoidance of patients being admitted for other medical conditions, which were cataclysmic, led to the redeployment of non-CCU nurses to COVID-19 CCU. Staffing challenges and attrition of manpower played a major role while caring for COVID-19 patients, which put tremendous pressure on healthcare workers.4 In the course of second wave of COVID-19, the ratio of nurses with less than 6 months of CCU experience (novice nurses) to trained nurses was 3:1 in our hospital. The pandemic itself made the situation more intense, adding to it, the non-CCU nurse’s knowledge of the care of the patients in CCU was inadequate.
It was observed that there was a decrease in the CLABSI bundle compliance rate, whereby patients in the COVID-19 intensive care unit (ICU) developed CLABSI. An integral risk-reduction strategy for CLABSI is anchored in the optimal maintenance of the device which is played by the nursing population.5 There are strong shreds of evidence to prove that the CLABSI bundle care approach goes a long way in preventing HAI’s including CLABSI.7 The study was chosen to improve the level of knowledge and CLABSI bundle8 compliance among novice CCU nurses to improve the CLABSI bundle compliance thereby reducing the CLABSI rate among COVID-19 patients.9
OBJECTIVES
To assess the level of knowledge and practice on CLABSI prevention among COVID-19 CCU staff nurses.
To analyse the association between the level of knowledge and bundle care compliance on CLABSI prevention and years of experience among the CCU nurses.
To educate the nurses and demonstrate the CLABSI prevention strategies by hands-on training.
To determine the effectiveness of the hands-on training of the CCU nurses upon the trend in CLABSI rate.
To maintain CLABSI bundle compliance above 90% among COVID-19 patients with central line.
MATERIALS AND METHODS
Study Design
Quasi-experimental Single-group pretest–Posttest Design
The research design is represented diagrammatically as follows:
Study Location
This study was done in a 550-bedded quaternary care hospital in Chennai, Tamil Nadu, India.
Study Approach
The study was a qualitative study.
Study Duration
The study duration was between the period April 2021 and October 2021 (assessment phase, intervention phase, and analysis phase).
Sample Size
A total of 150 COVID CCU nurses who involved in direct patient care (frontline nurses).
Sampling Technique
In this study, purposive sampling technique was used.
Inclusion Criteria
The CCU staff nurses who were involved in direct patient care (frontline nurses) in the COVID-19 CCU during the study period were included in this study.
Procedure Methodology
Ethical clearance was procured from the institutional ethics committee of Apollo Hospitals Chennai, Tamil Nadu, India. Consent was obtained from the samples. The conceptualization framework (phases) was based on general system theory outlined by Ludwig von Bertalanffy (1968).
Assessment Phase: From April 2021 to May 2021
“Brainstorming meetings” were held with CCU consultants and with COVID-19 task force on CLABSI reduction strategies as listed in Appendix Table 1. Root cause analysis was done as explored in Appendix Fig. 1. This gave us the idea to generate a structured questionnaire to assess knowledge of the CLABSI prevention strategies and CLABSI bundle care practice among COVID CCU nurses. An assessment questionnaire was shared among staff included in the study through Google links. The research tool questionnaire comprised of 2 parts.
Part A: The questionnaire included demographic variables of the CCU nurses such as gender, educational status, area of work, CCU experience, and confidence in caring for central line patients.
Part B: The structured questionnaire to assess the knowledge and practice level of the CCU nurses related to CLABSI bundle care.
Along with Questionnaire-based Assessment
Direct observation and documentation method was exercised by the infection control nurse (ICN) to monitor and assess the CLABSI bundle care compliances according to strategies to prevent CLABSI in acute-care Hospitals – 2014 update among the COVID-19 CCU patients during daily surveillance monitoring.10
Follow-up on CLABSI rates.
Intervention Phase (June to July 2021)
Based on the findings of the assessment phase, the Intervention phase started focused on hands-on training for the COVID CCU nurses. Hands-on training for all the nurses included in the study was scheduled in a dedicated simulation room within COVID-19 unit. Hands-on training on CLABSI bundle care in accordance with CLABSI preventive strategies was enforced.9 Staff nurses were vigilantly supervised on the CLABSI bundle care practices. Knowledge and adherence to CLABSI bundle compliance were assessed for COVID CCU nurses, on CLABSI prevention strategies and bundle care by post-test. The effectiveness of the hands-on training of the CCU nurses and bundle care compliance was monitored during daily surveillance by ICN.
RESULTS
Statistical Analysis
The data were analyzed using descriptive statistics to find frequency and percentage distribution and inferential statistics (Chi-square test) was used to assess the association between the level of knowledge and bundle care compliance on CLABSI prevention, with experience among the CCU Nurses. The following were the findings based on the objectives to reduce the CLABSI among COVID-19 patients.
Table 1 reveals that 94% of nurses were females and 6% were males, 92.6% were bachelor in nursing science, 6% were general nursing and midwifery and 1.3% were master in nursing science. 72.6% were CCU nurses, while 27.3% were non-CCU nurses with 54.6% having less than 6 months of experience, 24.6% of nurses were experienced less than a year, and only 20.6% of nurses with more than a year of CCU experience. Only 28.6% of nurses had experience in handling central lines whereas 71.3% of them have not handled central lines.
| Demographic variables | Frequency | Percentage |
|---|---|---|
| Gender | ||
| Male | 9 | 6 |
| Female | 141 | 94 |
| Educational status | ||
| General nursing and midwifery | 9 | 6 |
| Bachelor in nursing science | 139 | 92.6 |
| Master in nursing science | 2 | 1.3 |
| Working unit | ||
| CCU | 109 | 72.6 |
| Non-CCU | 41 | 27.3 |
| Level of CCU experience | ||
| ><6 months | 82 | 54.6 |
| 6 months–1 year | 37 | 24.6 |
| >1 year | 31 | 20.6 |
| Experience in handling central line | ||
| Yes | 43 | 28.6 |
| No | 107 | 71.3 |
Figure 1 illustrates the knowledge level of the COVID CCU nurses on CLABSI prevention before and after the hands-on training. It clearly depicts that 57% of nurses had inadequate knowledge, 43% had moderately adequate knowledge, and 0.6% only had adequate knowledge in pretest, whereas 80% of nurses had adequate knowledge, 11% had moderately adequate knowledge and only 9% had inadequate knowledge in the post-test after the intervention.
Fig. 1: The knowledge level of the COVID CCU nurses on CLABSI prevention before and after the hands-on training
Table 2 shows that the calculated Chi-square test value is less than the table value which reveals that there was no significant association between the selected demographic variables such as gender and educational status of the nurses with their knowledge levels at p < 0.05 level of significance. At the same time, it also projects that there is a significant association between the selected demographic variables such as area of work, level of CCU experience, and their experience in handling central lines at p < 0.05 level of significance.
| Demographicvariables | Inadequate knowledge | Moderately adequate knowledge | Adequate knowledge | Chi-square | df | p-value (<0.05) | Remark |
|---|---|---|---|---|---|---|---|
| Gender | |||||||
| Male | 7 | 2 | 0 | ||||
| Female | 79 | 61 | 1 | 1.63 | 2 | 0.2 | Not-significant |
| Educational status | |||||||
| General nursing and midwifery (GNM) | 8 | 1 | 0 | ||||
| BSC – Nursing | 77 | 61 | 1 | ||||
| MSC – Nursing | 1 | 1 | 0 | 3.92 | 4 | 0.14 | Not-significant |
| Working unit | |||||||
| CCU | 53 | 55 | 1 | ||||
| Non-CCU | 33 | 8 | 0 | 12.36 | 2 | 0.000437 | Significant |
| Level of CCU experience | |||||||
| <6 months | 74 | 8 | 0 | ||||
| 6 months–1 year | 8 | 29 | 0 | ||||
| >1 year | 4 | 26 | 1 | 80.61 | 4 | <0.00001 | Significant |
| Experience in handling central line | |||||||
| Yes | 13 | 30 | 0 | ||||
| No | 94 | 12 | 1 | 49.79 | 2 | <0.00001 | Significant |
Figure 2 clearly projects the trends of CLABSI with the device utilization rate. There is a strong correlation between the device utilization and the CLABSI rate.
Fig. 2: The trends of CLABSI with the device utilization rate
Figure 3 projects, CLABSI rate decline during the intervention phase which clearly projects that the intervention phase reduces the CLABSI rate from 23.6 to 7.7 and the rate of reduction is sustained.
Fig. 3: The Trends of CLABSI rate
The findings from Table 3 show that the nurses scored significantly high after the hands-on training on CLABSI bundle care in the post-test (M = 12.6, SD = 2.37) compared to the pre-test (M = 6.7; SD = 2.28) at p < 0.00001. There was a significant improvement in the knowledge levels of the COVID CCU nurses with a mean difference of 5.97 at p < 0.00001. This clearly defines the effectiveness of the hands-on training on CLABSI bundle care.
| Knowledge component | Mean | SD | Mean difference | Paired t-value | p < 0.05 | Remarks |
|---|---|---|---|---|---|---|
| Pretest | 6.7 | 2.28 | ||||
| Posttest | 12.6 | 2.37 | 5.97 | 22.06 | <0.00001 | Significant |
Figure 4 depicts that 71% of the nurses were not confident in handling COVID-19 patients with central line before the training whereas, 100% of them were confident in it after the hands-on training.
Fig. 4: COVID CCU Nurses confidence level in handling the central lines
Figure 5 portrays the CLABSI bundle compliance during the pre-intervention, intervention, and post-intervention period which clearly shows the adherence rate sustenance in the analytic phase.
Fig. 5: The CLABSI bundle compliance during the pre-intervention, intervention, and post-intervention phases
DISCUSSION
One of the six building blocks of health systems strengthening (HSS) as defined by the World Health Organization (WHO) is the health workforce. A strong health system cannot be achieved without a well-performing health workforce, and the health of the population cannot be achieved without investing in the health workforce. As part of a changing health service system, health workers need to keep up with the evolving health needs, policies, technologies, and knowledge (Frenk et al.)11. Nosocomial infection is one of the quality indicators, and various measures are taken to ensure that the target of “0” is to be maintained in all CCU’s. Preventing such infections relies in part on adherence to the guidelines and protocols developed by national or international organizations which are supported by infection prevention and control personnel.
Our study revealed that 94% of nurses were female, 92.6% were bachelor in nursing science, 72.6% were CCU nurses with only 20.6% of nurses had more than a year of CCU experience. The findings of our study are consistent with the retrospective study conducted by Kathleen M. Mcmulleninin, from the United States in 2020, to assess the rate of CLABSIs and CAUTIs for 12 months before COVID-19 and 6 months during the COVID-19 pandemic and he concluded that CLABSI rates increased by 51.0% during the pandemic period. The highest impact on HAI from COVID-19 was CLABSI rates, and 2 of their facilities have seen rate increases.3 Fakih et al. conducted a retrospective study to evaluate the impact of COVID-19 pandemic on CLABSIs and catheter-associated urinary tract infections (CAUTIs) in the United States hospitals and interpreted that COVID-19 pandemic was correlated with substantial upsurge in CLABSIs but not CAUTIs.12
This stayed true in our hospital too, during the pandemic, where COVID-19 patients were at higher risk of CLABSI for many reasons as patients requiring hospitalization had increased acuity and had increased acuity and prolonged the stay. Complying with this study, we found that in our hospital also there was an upsurge in CLABSI rate to 23.3/1000 central line days among the COVID-19 patients during the second wave of COVID-19 pandemic.
Zingg and Pittet conducted a meta-analysis to assess the effectiveness of insertion and maintenance bundles to prevent CLABSI in critically ill patients and concluded that the incidence of infections decreased significantly after the implementation of bundles.13 Likewise multimodule approach14 was enhanced and we targeted our key implementation on hands-on training the nurses. Teaching via lecture method was not fruitful for the scenario, as the archer gains the skill through training and practice, we focussed our training on demonstration and return demonstration, which not only imparted sound knowledge but on the other hand tuned the nurses to refine their practical skills on bundle care approach which yielded a drastic increase in the CLABSI bundle compliance rate. Similar to their study, our results also showed that more than half of the nurses had inadequate knowledge during the pretest (57%), whereas after the implementation of the hands-on training program on CLABSI prevention strategies,9 the majority of the nurses gained adequate knowledge (80%). Our study clearly portrays that CLABSI bundle compliance improved significantly in the analytical phase to more than 90%. Our study also proved beyond doubt that post hands-on training increased their confidence level to 100% in handling central lines.
Wu Pin et al., in their prospective study, conducted in a CCU in Taiwan, analyzed that implementing multimodal interventions focusing on central line bundle improvement was effective in reducing the incidence rates of CLABSI and CRBSI in Taiwan’s adult CCUs.15 As these evidence-based studies emphasize that CLABSIs can be prevented through well-coordinated, multifaceted programs, we concentrated on the nursing population enhancing them as an archer, training them to fight against the hidden enemies to win the battle against CLABSI. However, the implementation of CLABSI prevention programs requires individualized strategies for different institutional situations, and the best strategy is to disseminate knowledge through evidence-based practice.16 Abiding with it, fighting with all the visible and invisible challenges, our research targeted on hands-on training for the direct patient care CCU nurses—the frontline warriors—to adhere to the CLABSI bundle care which drove us to the reduction in CLABSI in our Hospital.
Our study findings project that the improvement in knowledge and bundle care compliance has influenced the reduction in the preventable CLABSI rate among critically ill COVID patients as evident by the month-wise CLABSI reduction rate. The study results projected that the hands-on training was effective in improving the knowledge and bundle care compliance of the nurses irrespective of their selected demographic variables. A combination of questionnaires and training by a demonstration on CLABSI Prevention strategies to the nurses was used was found this program was beneficial to them in knowing the “scrub the hub” technique,17 sterile practices while handling central line, and daily assessment, concentrating on patient priority thereby reducing the preventable CLABSI rate among the critically ill COVID-19 patients.
Initially the team quite a few challenges in bundle care compliance adherence due to non-CCU nurses and new nurses but eventually, with the dedication of the whole team, desirable results were accomplished.
CONCLUSION
As this study is related to improving the current practices in Nursing, the feasibility of the project is across all the hospitals. It is easy to understand, implement and evaluate. Above all, it empowers the nurses to gain evidence-based scientific knowledge to improve patient care and reduce infections. To aid the success of the project, it should be endorsed by science, led by stakeholders, guided by measures, and supported by management. Bundle care maintenance is the key in having this excellent outcome in our study.
Thus, hands-on training improved 80% of the knowledge and compliance of the CCU nurses, and 100% of the nurses gained experience in handling the central line, which increased the bundle care compliance from 73% adherence to 97% bundle compliance adherence and reduction in CLABSI rate from 23.6 to 0. Beyond doubt, better practices and improvised knowledge and bundle care compliance reduces preventable CLABSI rates through hands-on training.
ORCID
Samundeeswari Premkumar https://orcid.org/0000-0002-4823-6632
Yamunadevi Ramanathan https://orcid.org/0000-0002-4403-6107
Juliet Joji Varghese https://orcid.org/0000-0003-0040-8682
Basemath Morris https://orcid.org/0000-0002-2447-0854
P Senthur Nambi https://orcid.org/0000-0003-0519-8768
Nagarajan Ramakrishnan https://orcid.org/0000-0001-5208-4013
Ramasubramanian Venkatasubramanian https://orcid.org/0000-0001-8566-2035
REFERENCES
1. Yehia BR, Winegar A, Fogel R, et al. Association of race with mortality among patients hospitalized with coronavirus disease 2019 (COVID-19) at 92 US Hospitals. JAMA Netw Open 2020;3(8):e2018039. DOI: 10.1001/jamanetworkopen.2020.18039.
2. Cummings MJ, Baldwin MR, Abrams D, et al. Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: A prospective cohort study. Lancet 2020; 395(10239):1763–1770.DOI: 10.1016/S0140-6736(20)31189-2.
3. McMullen KM, Smith BA, Rebmann T. Impact of SARS-CoV-2 on hospital acquired infection rates in the United States: Predictions and early results. Am J Infection Control 2020;48(11):1409–1411. DOI: 10.1016/j.ajic.2020.06.209.
4. Centers for Disease Control and Prevention. Strategies to mitigate healthcare personnel staffing shortages. Available at: https://www.cdc.gov/coronavirus/2019-ncov/hcp/mitigating-staff-shortages.html. Accessed on: 22 December 2020.
5. Brunelli SM, Turenne W, Sibbel S, Hunt A, Pfaffle A. Clinical and economic burden of bloodstream infections in critical care patients with central venous catheters. J Crit Care 2016;35:69–74. DOI: 10.1016/j.jcrc.2016.04.035.
6. Birkmeyer JD, Barnato A, Birkmeyer N, Bessler R, Skinner J. The impact of the COVID-19 pandemic on hospital admissions in the United States. Health Aff (Millwood) 2020;39:2010–2017. DOI: 10.1377/hlthaff.2020.00980.
7. Gopal PB. The clasp of CLABSI. Indian J Crit Care Med 2020;24(1):3–5. DOI: 10.5005/jp-journals-10071-23335.
8. Khodare A, Kale P, Pindi G, Joy L, Khillon V. Incidence, microbiological profile, and impact of preventive measures on central line-associated bloodstream infection in liver care intensive care unit. Indian J Crit Care Med 2020;24(1):17–22. DOI: 10.5005/jp-journals-10071-23325.
9. Furuya EY, Dick AW, Herzig CT, Pogorzelska–Maziarz M, Larson EL, Stone PW. Central line-associated bloodstream infection reduction and bundle compliance in intensive care units: A national study. Infect Control Hosp Epidemiol 2016;37(7):805–810. DOI: 10.1017/ice.2016.67.
10. Marschall J, Mermel LA, Fakih M, Hadaway L, Kallen A, O’Grady NP, et al. Strategies to prevent central-line–associated bloodstream infections in acute-care hospitals: 2014 update. Infect Control Hosp Epidemiol 2014;35(7):753–771. DOI: 10.1086/676533.
11. Frenk J, Chen L, Bhutta ZA, et al, Health professionals for a new century: transforming education to strengthen health systems in an interdependent world. Rev Peru Med Exp Salud Publica. 2011 Jun; 28(2):337-41. Spanish. DOI: 10.1590/s1726-46342011000200023.
12. Fakih MG, Bufalino A, Sturm L, Huang RH, Ottenbacher A, Saake K, et al. Coronavirus disease 2019 (COVID-19) pandemic, central-line-associated bloodstream infection (CLABSI), and catheter-associated urinary tract infection (CAUTI): The urgent need to refocus on hardwiring prevention efforts. Infect Control Hosp Epidemiol 2022;43(1):26–31. DOI: 10.1017/ice.2021.70.
13. Zingg W, Pittet D. Central-line bundles need a multimodal implementation strategy. Lancet Infect Dis 2016;16:724–734. DOI: 10.1016/S1473-3099(15)00480-6.
14. Bell T, O’Grady NP. Prevention of central line-associated bloodstream infections. Infect Dis Clin 2017;31(3):551–559. DOI: 10.1016/j.idc.2017.05.007.
15. Lin WP, Chang Y-C, Wu U-I, Hung M-C, Chuang P-U, Wang J-T, et al. Multimodal interventions for bundle implementation to decrease central line associated blood stream infection in adult Intensive care units in a teaching hospitals, Taiwan 2009–2013. J Microbiol Immunol Infect 2018;51(5):644–651. DOI: 10.1016/j.jmii.2017.08.008.
16. Aloush SM, Alsaraireh FA. Nurses’ compliance with central line associated blood stream infection prevention guidelines. Saudi medical journal. 2018;39(3):273–279. DOI: 10.15537/smj.2018.3.21497.
17. Caspari L, Epstein E, Blackman A, Jin L, Kaufman DA. Human factors related to time-dependent infection control measures: “Scrub the hub” for venous catheters and feeding tubes. Am J Infect Control 2017;45:648–651. DOI: 10.1016/j.ajic.2017.01.004.
| Modifiable with nurses | Non-modifiable with nurses |
|---|---|
|
|
Appendix Fig. 1: Root cause analysis
________________________
© The Author(s). 2023 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and non-commercial reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.