Background Understanding patient experiences is crucial to evaluating care quality in EDs. However, while previous reviews describe the determinants of ED patient experiences (ie, factors that influence patient experiences), few have described actual patient experiences. The aim of this systematic mixed studies review was to describe patient experiences in the ED from the patient’s perspective.
Methods Embase, Medline, ProQuest Nursing and Allied Health, the Cumulative Index to Nursing and Allied Health Literature and the Cochrane Library electronic databases were searched, with publication dates limited between 1 January 2001 and 16 September 2019. Studies describing adult patient experiences in the ED were included. Studies describing patient satisfaction, proxy-reported experiences or child/adolescent experiences were excluded. The quality of included studies was appraised using the Mixed Methods Appraisal Tool (2018 version). An inductive, convergent qualitative synthesis of the extracted data was undertaken following Thomas and Harden’s (2008) methods.
Results Fifty-four studies were included and of those, only five (9%) studies included a standardised definition of patient experience. Two inter-related themes emerged: Relationships between ED patients and care providers; and Spending time in the ED environment. The first theme included four subthemes regarding respect, communication, caring behaviours and optimising patient confidence. A key finding related to the potential for power imbalances between patients and their care providers. The second theme included two subthemes regarding physical aspects of the ED environment and patients’ waiting experience. Patients attributed more importance to the waiting experience itself rather than the duration they had to wait.
Conclusions Patients in the ED have unique and complex experiences. Greater research is needed to understand the relational and environmental factors that contribute to power imbalances between patients and care providers, how to support more positive waiting experiences, and developing a standardised definition of patient experience in the ED.
PROSPERO registration number CRD42020150154.
- emergency department
Data availability statement
There are no data in this work.
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What is already known on this subject
Optimising patient experiences is associated with improved patient safety and clinical outcomes, reduced health service utilisation, and is recognised as a critical measure of healthcare quality.
Patient experiences in the ED are gaining interest as EDs often serve as the front door to other hospital services and are universally recognised for having a high workload.
Patient experiences in the ED are poorly understood, impacting our ability to conceptualise and measure them.
What this study adds
Patient experiences in the ED are complex and best conceptualised by interplay among patients, care providers and the ED environment.
Our findings reveal that power imbalances underscore some ED patient–care provider relationships, which may be exacerbated by the inherent complexities and fast-paced care delivered in ED environments.
The psychological experience of waiting in the ED appears to be more important to patients than the duration of the wait itself.
Patient experience in the ED is one area of patient-centred care provision that continues to garner attention. EDs are often the first point of contact for unwell patients entering hospital, and present unique challenges to providing optimal care experiences. This may be due to ED patients’ heightened sense of fear and distress1; the anxiety associated with not knowing the type of treatment they may receive2; crowded and often chaotic environments3 4; or a combination of these factors. ED staff also experience challenges associated with ambulance ramping (the inability of paramedics to transfer patients’ clinical care to the ED),5–7 delays in accessing inpatient beds,8 ED overcrowding,9 10 and patient violence directed towards staff11; all of which can directly and indirectly impact on patient experiences. Given the unique complexities associated with providing and receiving ED care, measuring and optimising patient experiences is a priority for many health service managers and organisational leaders globally.12–14
A primary challenge associated with measuring patient experiences in the ED is that we currently do not have a robust understanding of the core themes of ED patient experiences. Poor conceptualisation has limited robust measurement of patient experience in the ED. Recent reviews have reported the common determinants of ED patient experiences,12 15 such as how wait time affects experiences of care. Yet, while existing reviews enable us to understand the factors that control or influence patient experiences in the ED, they do not describe actual experiences in the ED. This is a crucial and necessary step towards operationalising (measuring) a concept.16
There is also ongoing confusion related to the interchangeable use of ‘patient experience’ and ‘patient satisfaction’ in the literature.13 15 17 18 There is agreement that the ‘patient experience’ encompasses what happened during a care encounter and how it happened from the patient’s perspective.19–25 Alternatively, ‘patient satisfaction’ can be defined as whether the care a patient received did or did not meet their expectations.26 27 These two concepts are also operationalised differently. Unlike satisfaction measures, patient experiences provide actionable feedback to health services about what can improve care experiences, thereby optimising the opportunity to provide patient-centred care.
Thus, given the limitations present in the ED patient experiences literature, the aim of this systematic mixed studies review (SMSR) was to describe patient experiences in the ED from the patient’s perspective.
This SMSR followed the 7-step approach proposed by Pluye and Hong.28 Reporting was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist,29 and registered with the international prospective register of systematic reviews (PROSPERO) (ID: CRD42020150154).30
Patient and public involvement
No patient/public involvement.
Step 1: Formulate a review question
This SMSR has three research questions: (1) how has ‘patient experience’ been defined in the ED literature; (2) how do patients describe their experiences in the ED; and (3) what is the quality of studies reporting on patient experiences in the ED. We define ‘patient experience’ as what happened during a care encounter and how it was perceived by the patient.19–25
Step 2: Define eligibility criteria
Table 1 outlines the eligibility criteria applied to studies identified through electronic database searching.
Step 3: Apply an extensive search strategy
The following electronic databases were systematically searched for studies published between 1 January 2001 and 16 September 2019: Embase (via Elsevier), Medline (via Ovid), ProQuest Nursing and Allied Health, CINAHL (via EBSCOhost) and the Cochrane Library. Searches used Medical Subject Headings where appropriate, Boolean operators (AND, OR), and proximity searching in accordance with the specifications of the databases. A university health librarian was consulted prior to undertaking the final database searches. Online supplemental file 1 contains the full search strategy for all electronic databases.
Steps 4 and 5: Identify and select potentially relevant studies
In September 2019, one author (CB) performed electronic database searching. Search results were imported into EndNote (V.X9.2, Clarivate Analytics) and duplicates removed. Using the inclusion and exclusion criteria (Table 1), two authors (CB, SL) undertook title and abstract screening independently. Articles that appeared to meet the eligibility criteria or were unable to be excluded based on title and abstract screening alone underwent independent full-text review (CB, SL). Discrepancies regarding the inclusion or exclusion of an article were discussed and adjudicated by a third author (BG), where necessary.
Step 6: Appraise the quality of included studies
The Mixed Methods Appraisal Tool (MMAT, 2018 version) was used to assess the methodological quality of the included studies.S32 The MMAT allows researchers to appraise five research designs (qualitative research, randomised controlled trials, non-randomised studies, quantitative descriptive studies, and mixed methods studies) based on whether design-specific criteria are met (‘Yes’, ‘No’ and ‘Can’t tell’).S32 Two authors (CB, SL) independently appraised the quality of included studies using the MMAT. Discrepancies between scores were first discussed between the appraising authors, and where necessary, adjudicated by a third author (BG). An inter-rater reliability (Kappa) score was calculated to ascertain the strength of agreement between the two authors’ ratings.S33
Step 7: Synthesise included studies
Verbatim data extraction of the included studies was undertaken by one author (CB) into a standardised extraction template, and cross-checked by another author (SL, BG, JC); ensuring data accuracy and enabling all authors the opportunity to develop a comprehensive understanding of the literature. An inductive, convergent qualitative synthesis approach was used to transform all data into qualitative findings.28 One author (CB) led the results synthesis using Thomas and Harden’s (2008) methods for thematic synthesisS34 by first undertaking line-by-line coding, organising codes into groups, and subsequently developing the initial descriptive subthemes and themes. Throughout this process, the lead author (CB) maintained detailed analytical audit trails and met frequently with the research team (SL, JC and BG) to discuss the analysis. During these meetings, authors discussed revisions to codes and their groupings, and collectively developed the final subthemes and themes. The development of the final subthemes and themes involved abstracting concepts of patient experiences in the ED based on the findings of the primary studies.S34
Summary of included studies
Fifty-four studies were included in this review (figure 1). Twenty-six (48%) were qualitative studies, 23 (43%) were quantitative studies and five (9%) were mixed-method studies (online supplemental file 2). Most studies were conducted in the USA (n=29; 35%) and half (50%) were published between January 2016 and September 2019. Patient populations varied substantially in age and reason for ED presentation. MMAT scores are presented separately in online supplemental file 3 demonstrating how the included studies scored against established criterion for the different study designs. Inter-rater reliability for MMAT scoring was 0.78 (substantial agreement).S33
Definitions of ‘patient experience’
Researchers in 5 (9%) of the 54 studies provided a definition of patient experience (online supplemental file 4).S35-39 Three studies defined patient experience in relation to why it is a preferable measure for quality improvement as opposed to patient satisfaction.S35, 36, 39 These definitions stated that patient experiences "have shown to be more objective and to yield more detailed information for quality improvement" S35, 36 as they "provide information identifying where in the process problems may reside and what can be done to improve patient care".S39 In articulating the difference between patient experience and patient satisfaction, one study also stated that patient satisfaction is based on "expectations (or ‘needs’) and experiences" where "expectations are related to personal preferences, which make quality of care difficult to measure".S35
Another study proposed a patient experience definition based on the domains addressed by the patient experience survey they employed.S37 These domains included staff care, pain management, discharge communication, respect, medication communication, and wait time and crowding.S37 Another study defined the patient experience as a combination of “‘functional’ aspects of care (such as arranging the transfer of patients to other services, administering medication and helping patients to manage and control pain), ‘transactional’ aspects of care (in which the individual is cared ‘for’, for example, meeting the preferences of the patient as far as timings and locations of appointments are concerned) and ‘relational’ aspects of care (where the individual is cared ‘about’, for example, care is approached as part of an ongoing relationship with the patient)”.S38
Two overarching themes emerged: Relationships between ED patients and care providers, and Spending time in the ED environment (table 2). There is overlap between these themes due to the complex interplay among patients, care providers and the ED environment. The overlap contributes to a unified and holistic conceptualisation of patient experiences in the ED.
Theme 1: Relationships between ED patients and care providers
The theme Relationships between ED patients and care providers included four subthemes: Respecting patients; Communicating with patients to keep them informed; Caring for patients; and Building and maintaining patients’ confidence (table 2).
The overarching theme describes the unique relationship dynamics between ED patients and care providers, and the perceived distribution of power. ED patients acknowledged that relational power exists between themselves and their care providers, who possessed valuable medical knowledge and determined the type and timing of their treatment. Furthermore, the actions of some care providers significantly influenced how patients felt about themselves, causing some to question the validity of their ED presentation. These ED patients reported feeling like a "burden",S40 "dehumanised",S41-43 and "powerless",S41, 44 indicating that the relational power tipped in favour of care providers, and negatively impacted patient experiences. In turn, this influenced the behaviour patients exhibited towards their care providers with some becoming frustrated and angry. Other patients changed their behaviour so they could be viewed as the "best patient possible",S45 "compliant",S41 and avoid "adding to staff stress".S46 Further, some patients welcomed the "passive" S46 patient role because of their presenting condition (eg, trauma resuscitation). When an equal distribution of relational power existed between patients and care providers, the majority of patients felt included and treated like a "human being" instead of a "case" or "number".S41, 43, 47, 48 Care providers use of inclusive language made patients feel valued and involved in their care, contributing to positive patient experiences.S41, 49, 50
Respect was described by patients as the behaviours exhibited by care providers that considered their feelings, wishes and rights. The degree of respect patients received impacted on their sense of worth, power and vulnerability,S41, 42, 49 which influenced their care experience in the ED. Respect was demonstrated on a spectrum, ranging from a lack of respect to a high level of respect. Positive experiences were associated with being listened to carefully and attentively,S35–37, 40, 46, 47, 50-60 having the opportunity to talk uninterrupted,S47,50 being taken seriously,S36, 45, 49, 51, 61, 62 and feeling as though care providers had the time for them.S51, 53, 55, 59, 60, 63, 64 Similarly, care providers that were on the same level as patients (ie, down-to-earth)S41, 47, 65 and established rapport with patients and their familyS41, 47, 50, 66-70 also positively impacted patient experiences. However, when relational respect was minimal or absent, patients reported more negative experiences. This occurred when ED care providers talked in front of patients as if they were not there,S37, 58, 68, 70, 71 when patients felt they were not taken seriously,S45, 63, 65, 66, 72 were disregarded,S45, 73 treated with judgement or discrimination,S41, 42, 45, 68, 72, 74 or humiliated.S41, 45, 62, 74
Communicating with patients to keep them informed
This subtheme of patient experience involved the transfer or exchange of information between care providers and patients. Most communication was one way where care providers would provide instruction to patients. Yet, there was also some evidence of discussion, suggesting patient involvement and partnership in their ED care. Patient experiences were optimised when care providers delivered the right amount of information in an understandable way,S35-37, 47, 50-55, 57, 58, 60-62, 65, 67, 69, 70, 75-78 when they communicated with empathy and compassion,S47, 49, 56, 68, 69, 79 when patients were informed about care processes and treatment options,S46, 49, 52, 56, 62, 65, 68, 69, 72, 80 updated throughout their ED journey,S39, 66, 69 were able to discuss matters that were important to them,S35-37, 47, 52, 54, 67, 68 and were encouraged to talk and ask questions.S50, 65, 69 Generally, patients who felt informed by their care providers, reported better experiences characterised by feeling reassured, safe and confident.S46, 48, 49, 69, 72 Patients who felt uninformed however, reported poorer experiences characterised by anxiety, confusion and fear.S39, 40, 43, 63, 72 Patients described being uninformed as not being provided with sufficient verbal or written information about matters such as how long they might have to wait and what to do following discharge,S36, 39, 41, 46, 52, 56, 58, 60, 61, 63, 65, 72, 81-83 receiving information they could not understand,S46, 63, 68 when information was delivered abruptly,S68, 81, 82 when information from multiple care providers was inconsistent or contradictory,S36, 42, 58, 60, 78 and when they were asked to repeat themselves numerous times.S42, 45, 61, 66
Caring for patients
Being cared for encompassed both routine/ functional aspects of care (eg, tests, examinations and procedures; appropriate pain relief and management; and treatment or transfer),S35-42, 44-47, 49, 52, 54-56, 60, 63-65, 67, 68, 72, 74, 77, 80, 82, 84, 85 and emotional aspects of care. However, receiving either functional or emotional care in the absence of the other resulted in poorer patient experiences. Patients valued emotional aspects of care as it made them feel important and understood by their care providers,S40, 48, 49, 65, 81 such as when empathy and genuine concern was demonstrated.S38-40, 43, 45, 47, 49, 56, 60, 65, 81, 82, 86 This occurred when care providers used reassuring words, touch and body language,S40, 41, 47, 49, 68, 79 when they informed patients’ family or friends that they were in the ED,S48, 49, 61, 68, 75, 82 and by ensuring patients did not feel lonely.S37, 40, 48, 49, 64, 68, 80-82 Receiving an inadequate level of emotional supportS40, 43, 44, 49, 65, 72, 73 or follow-up support (eg, counselling, social work)S65, 67, 73, 82 had negative impacts on patient experiences.
Building and maintaining patients’ confidence
Patients described how their care providers instilled and preserved a sense of confidence in them and the care they provided. Patients who felt confident in their care providers reported feeling safer.S48, 68, 78 Confidence was instilled when care providers demonstrated competence, knowledge and skill,S36, 40, 41, 46, 47, 49, 52, 56, 60, 65, 68, 69, 78, 87 took responsibility for and control of patients’ care,S39, 41, 49, 61, 88 were efficient and responsive,S37, 40, 41, 45, 48, 49, 56, 66, 68, 69, 73, 84, 87 and when care providers operated as a team.S38, 41, 43, 46, 48, 49, 68 Yet, when patient confidence in their care providers was challenged, they reported poorer experiences because they felt they could no longer trust their care providers.S41, 64 Patients’ confidence diminished when care providers failed to demonstrate adequate competence, knowledge and skill,S42, 60, 65, 66, 68, 74 when care felt disjointed,S41, 46, 60, 61, 69 and when care providers failed to take responsibility for patients’ care.S41, 46, 61, 88
Theme 2: Spending time in the ED environment
The theme Spending time in the ED environment included two subthemes: Being aware of physical aspects of the ED environment; and Waiting in the ED environment (table 2).
The overarching theme describes patient experiences related to the physical attributes of the care environment (eg, comfort and privacy), and the psychological experience of waiting in the ED. Patients experiencing long waiting times were more aware of their physical environment "because [they] ha[d] nothing else to do".S80 Hence, characteristics such as equipment wear and tear,S80 cleanliness,S39, 48, 58, 80 noise,S48, 51, 65 and the health condition of other patientsS39, 87 were more noticeable. Patients who spent less time in the ED tended to report less about the physical aspects of the ED environment, instead focussing more on their relationships with care providers.S49, 68, 82 Some patients who experienced longer ED waiting times perceived that care providers had forgotten or abandoned them, especially if they received limited information regarding the reasons why they were waiting.S40, 43, 44, 46, 72 Thus, the ED environment influenced how patients perceived the humanistic characteristics of their care providers.
Being aware of physical aspects of the ED environment
Patients described how the physical (structural, spatial, and material) characteristics of the ED environment impacted their experience. Patients reported better experiences when the ED was clean and hygienic,S35, 36, 39, 48, 51, 52, 54, 58, 67, 80, 88 when they were physically comfortable (eg, had comfortable seating, blankets),S37-39, 48, 68, 78, 80, 88 were able to access a range of amenities (eg, bathroom, food, drink, TVs, and magazines),S36, 39, 42, 63, 67-69, 78, 80, 88 and received an adequate level of privacy during physical examinations, procedures and discussions in the ED.S35, 42, 52, 58, 63, 71, 86, 87 However, the physical ED environment could also negatively impact patient experiences, such as when patients reported feeling uncomfortable in the ED unrelated to pain (eg, cold and draughty corridors, small beds),S80, 88 being surrounded by too many other peopleS37, 43, 49, 65, 68, 80, 83, 88 and a lot of noise,S48, 65, 88 not receiving an adequate level of privacy during physical examinations, procedures and discussions,S39, 42, 63-65, 73, 87 and being unable to access adequate amenities (eg, bathrooms, food, drink, and wheelchairs).S39-41, 69, 74, 80
Waiting in the ED environment
Patients acknowledged that waiting would be an important part of their ED experience. However, some patients felt mislead by the idea of a single "designated" waiting area,S56, 80 as waiting was not restricted to just the waiting room. They reported that having distractions (eg, TVs, magazines, company) during long waits,S64, 80 and being informed about why they were waiting or the order in which they would be seen relative to other patients,S36, 49, 58, 64, 76 positively impacted their experience. Receiving care quickly was also associated with better patient experiencesS40, 51, 56, 63, 66, 69; however, it was relatively uncommon for patients to report short wait times. When this did occur, it came as a pleasant and unexpected surprise to patients.S56, 69 Patients who perceived that their wait was too long,S39, 42, 44–46, 56, 60, 62, 64–66, 72, 73, 80, 83, 84, 88 waited in areas other than the actual waiting room,S39, 40, 56, 60, 73, 80, 88 and waited without knowing why they were waiting,S39, 40, 43, 44, 46, 56, 63, 72, 83 reported worse experiences as they became frustrated and felt abandoned by their ED care providers.S43, 44, 56, 88
The aim of this SMSR was to describe patient experiences in the ED from the patient’s perspective based on the current literature. Our findings suggest that ED patient experiences can be described in terms of two overarching and interrelated themes: Relationships between ED patients and care providers, and Spending time in the ED environment. The overlap between these themes represents the interaction among patients, care providers and the ED environment that is central to patient experiences in the ED.
A key finding of this review was that the concept of patient experience was rarely defined in the included studies. Most definitions articulated how patient experience differs to patient satisfaction. Yet, while this contributes to clearer conceptual boundaries between the two concepts, it fails to clarify exactly what the ED patient experience is. The lack of a standardised patient experience definition has significant implications including making it difficult to compare and contrast research findings. This limits the effective measurement of patient experiences and provides limited foundation on which to design future research and quality improvement activities that aim to optimise patient experiences. Previous research proposed that patient experiences (irrespective of the healthcare context) span across the continuum of care, go beyond survey results, align with patient-centred care principles and focus on individualised care.S89 However, while the authors suggested that patient experiences comprise "more than satisfaction",S89 they also recommended that a definition of patient experience should focus on expectations; an inherent determinant of patient satisfaction.S90 Consequently, more comprehensive investigations are required to generate a standardised conceptual definition of patient experience. It will also be important to understand whether differences between healthcare settings impact how we conceptualise the patient experience.
The review findings also highlight the importance of patient-care provider relationships in the ED. This has been evidenced numerous times in the literature, particularly regarding the importance of effective communication.S91-94 However, our review revealed a novel insight into ED patient-care provider relationships—underlying many patient experiences in the ED are unequal distributions of power between patients and their care providers. Some patients felt they had to prove their worth and compete to gain ED care providers’ time by presenting themselves as the best possible patient, adopting passive and compliant behaviours, and not being burdensome by asking questions when the ED staff appeared busy. Relational power imbalances did not appear to be deliberate on the part of the care providers and arose due to the inherent complexities associated with EDs as healthcare services. Higher levels of patient anxiety,S95 more acute/urgent patient conditions,1 longer waiting times prior to receiving care,S96 and the escalating busyness of EDsS97 all contribute to patients having minimal control over their health and personal circumstances while in the ED. Moreover, many EDs are driven by organisational efficiency pressures (eg, discharging ED patients within an allocated period of time) and the need to prioritise life-saving medical care in emergency situations.S98-100 These factors may momentarily override the ability of ED care providers to optimise a more patient-centred approach to care for some patients, and suggests that EDs are not conducive to maintaining equal power distributions.
Patient involvement in shared decision-making regarding their care was minimally discussed in the included studies, further evidencing ED patient-care provider power imbalances. It has been asserted that patients are more susceptible to a ‘doctor knowns best’ mentality in the ED because it is a high stakes care environment where decisions may have significant impacts on the patient’s health and well-being.S101 This is despite mounting evidence that shared-decision making can positively impact patient experiences of care and their overall health outcomes.S102 While support for shared-decision making initiatives in the ED continues to grow,S103-112 the impact of shared-decision making on ED patient experiences is yet to be examined; warranting further research.
This review highlights that patients placed more importance on their psychological experience of waiting than the actual wait time. EDs globally are becoming increasingly busy. In Australia for example, the annual rate of ED presentations exceeds that of population growth (3.4% vs 1.4%, respectively).S113, 114 One explanation for this increase is that EDs in many countries serve as a safety net for low-income and socially disadvantaged citizens who are unable to afford or access community healthcare.S115 In turn, increased utilisation of ED services culminates in longer ED wait times. In our study, as in other studies, patients anticipated and accepted that an ED visit would involve a wait,15 but that being provided information during the wait was crucial to mitigating patients’ feelings of frustration, humiliation and powerlessness.S116, 117 Yet, much of the research about ED waiting relates to differences between perceived and actual wait times.S39, 118-121 The patient’s psychological experience of waiting has comparably received little attention, and warrants greater exploration. This finding also challenges the utility of capturing waiting times as part of patient experience evaluations.
Like all reviews, this review has limitations. First, despite systematic and rigorous searching, articles may have been missed. However, the assistance of a qualified health librarian during the development of our database search strategy was sought to minimise this risk. Second, grey sources of literature were not considered for inclusion due to their questionable quality (ie, not peer reviewed) and potential risk of bias. Third, there was a paucity of literature pertaining to the ED experiences of culturally and linguistically diverse patients, indigenous peoples, and patients with mental health problems. These gaps suggest that our conceptual understanding of ED patient experiences is not inclusive of all perspectives, and highlights areas of research that warrant greater attention. Finally, we excluded studies including proxy-reported experiences in the ED as this did not align with the review’s aim of describing patient experiences in the ED. However, proxy-reported experiences may be the only accounts available for patients with disability and cognitive impairment. As such, while this was not within the scope of the current review, this is an area that warrants greater research.
A standardised conceptual definition of patient experience is needed. This review identifies two inter-related themes regarding patient experience in the ED: Relationships between ED patients and care providers, and Spending time in the ED environment. Circumstances inherent in the ED visit can contribute to power imbalances between ED patients and their care providers, which can affect patient experiences and behaviours. The waiting experience, rather than the length of the wait, can also contribute to the patient experience, particularly whether they feel valued and cared for. Understanding these issues can help to improve the patient experience in the ED.
Data availability statement
There are no data in this work.
Handling editor Margaret Samuels-Kalow
Contributors All authors contributed to the conceptualisation of the research. The conduct of the research was primarily undertaken by CB and supported by SL, JC and BMG. The reporting of the research was primarily undertaken by CB and supported by SL, JC and BMG. All authors contributed to the development of the manuscript, have approved the final version of the manuscript and are responsible for its overall content.
Funding CB is supported by funding from an Australian Government Research Training Program (RTP) scholarship and a Griffith University Health Group top-up scholarship.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
Author note Supplementary file 5 contains additional references for this article.
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