The Characteristics of Post-Intensive Care Syndrome to Inform Occupational Therapy Practice During the Post-Intensive Care Period: A Systematic Scoping Review.

Background: As the demand for intensive care treatment increases, so too does the number of people surviving critical illness. Since 2010, the term “post-intensive care syndrome” has been used to describe the constellation of new or worsening physical, cognitive, and psychological impairments that persist after intensive care discharge. This review aimed determine the characteristics of PICS present during the rst year following discharge from the ICU to inform occupational therapists working with this population during the post-intensive care period. Methods: A systematic scoping review has been conducted according to the PRISMA-ScR Checklist. Seven key databases were searched from inception to 2020. A single reviewer screened available literature against eligibility criteria then cross-checked by a second reviewer. Data were abstracted from relevant publications and results were narratively synthesised through application of a biopsychosocial model. Results: Twenty-ve studies were identied for inclusion. Characteristics were categorised as biological, psychological, or social and contextual. Overarching outcomes were also considered. Results demonstrated that characteristics were complex and interwoven between domains. Results were grouped into four key themes: 1) An increased worldwide demand for intensive care, 2) ADL performance, 3) HRQOL, and 4) Consideration of social and contextual characteristics. No studies were found to detail the role of occupational therapists working with post-intensive care survivors. Conclusions: The complex and interwoven of care syndrome highlights the need to consider a holistic rehabilitation approach. Considering the COVID-19 pandemic, occupational therapists have the potential to play an increased role during the post-intensive care period to reduce the global healthcare burden and improve patient outcomes. Future research is needed to determine the best model of care to support occupational therapists working with survivors of critical illness.

for ICU treatment and mechanical ventilation has exceeded the current capacity [6,7]. As reported by the Critical Care Resources registry, the total annual operational cost for ICU care in Australia was $2119 million prior to the COVID-19 pandemic [8]. While the focus has been on patients admitted to the ICU, there is growing interest in the increase in patients surviving critical illness.
In Australia, the ICU mortality rate of COVID-19 patients is 22.2% [9]. The remaining 78% represents a large number of patients who are surviving critical illness. While survival rates are improving, recovery does not end upon discharge from the ICU [10]. Studies have shown that many patients experience persisting functional impairments secondary to their original condition [11,12,13]. During the 2002 Brussels Roundtable, "Surviving Intensive Care", participants described the recovery trajectory of critical illness. They emphasised that critical illness is not limited to the period an individual spends within the ICU but also extends before and well after discharge from hospital [14].
A framework to describe the multidimensional recovery following discharge from the ICU was developed at the 2010 Society of Critical Care Medicine Conference [15]. Collectively referred to as 'post-intensive care syndrome' (PICS), many ICU survivors nd themselves facing a constellation of new or worsening physical, cognitive, and psychological impairments that persist well after discharge [16]. As such, the use of the term 'PICS' subsequently emerges in the literature after 2010.
Since its inception, PICS has been described in terms of physical, cognitive, and psychological factors [10,12]. The most reported characteristic is f physical deconditioning, documented in approximately 70% of patients discharged from the ICU [17]. Prolonged bed rest, coupled with ICU treatments such as mechanical ventilation, can result in a globalised reduction in muscle strength and physical functioning [18]. This is referred to in the literature as ICU-acquired weakness (ICU-aw) [19].
Often more easily overlooked are the changes patients experience to their cognitive or psychological state. While in the ICU, critically ill patients face high levels of physical and psychological stress [12].
Following discharge, new or worsening cognitive impairments can include impairments in memory, executive function, language, attention, and visual-spatial abilities [17,20]. Additionally, depression, anxiety, and post-traumatic stress disorder (PTSD) are common during admission and following discharge from the ICU [21,22]. This constellation of symptoms can signi cantly impact quality of life and an individual's ability to reintegrate back into society [10].
Rehabilitation following critical illness has been acknowledged as an area of increasing importance. However, there is limited evidence to underpin practice during the post-acute recovery phase [23]. Schandl et al. [24] identi ed that multidisciplinary follow-up within 6-months of discharge from the ICU could be of value in identifying untreated physical and psychological problems. However, there remains no consensus on the best model of intervention to use among survivors of critical illness [10].
Physical therapy during ICU admission and following discharge is prominent in the literature [11,16]. However, the occupational therapy role in working with ICU survivors remains somewhat unexplored.
Occupational therapy is concerned with promoting health and well-being through "doing" [25].
Occupational therapists support individuals in performing activities or "occupations" that are needed, wanted, or individually meaningful [26]. Occupational therapy is a holistic profession committed to supporting individuals through addressing a constellation of contextual, environmental, physical, psychological, and social factors that support engagement in desired occupations [27].
The biopsychosocial model aligns with the philosophy of occupational therapy and has been recognised in facilitating a shift towards a more integrated approach to care [28]. Under this model, consideration is given to physical dysfunction, psychological and social factors [29]. A study conducted by Kobylanska et al. [30] considered the e cacy of post-stroke rehabilitation in the context of the biopsychosocial approach. They concluded that external factors play a pivotal role in the rehabilitation journey. The study highlighted the importance of considering biopsychosocial factors, such as acceptance of illness and a sense of self-e cacy, for optimising the recovery trajectory.
Ohtake et al. [16] conducted the most recent systematic review of PICS. They considered only the scope and magnitude of physical characteristics and classi ed these according to the World Health Organization's International Classi cation of Functioning, Disability, and Health (ICF) framework. Limited research considering the holistic management of PICS and increased demand for ICU care highlights an opportunity for occupational therapists to reduce the growing healthcare burden. Therefore, this systematic scoping review aims to determine the characteristics of PICS present during the rst year following discharge from the ICU to inform occupational therapists working with this population during the post-intensive care period.

Methods:
Search strategy: A systematic scoping review has been conducted in accordance with the PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation [31]. An unrestricted search of seven electronic databases was conducted (PubMed, Embase, CINAHL, Ovid (Medline), Cochrane Library, Web of Science) and overseen by the University librarian. Articles were included from inception to 20 October 2020.
The search strategy consisted of synonyms and subject headings derived from the following key terms: "post-intensive care syndrome", "intensive care", and "occupational therapy".

Eligibility criteria:
Studies were included if they referred to 'post-intensive care syndrome' or reported on one or more of the following outcomes: physical, cognitive, or psychological status following ICU discharge. For inclusion, studies reported on adults over 18-years who had spent at least 48-hours in an ICU. Data collection occurred between ICU discharge and within one year of discharge from the ICU. Studies were required to be published in English, with the full text available. Initially, only systematic reviews and randomised controlled trials were considered for inclusion. However, during the title and abstract screening, the challenges of randomising the included population became apparent. As such, cohort studies were also included. Qualitative studies, case studies, clinical trials (or pilot studies), protocols, opinion pieces, and conference proceedings were excluded as these constitute a lower level of evidence.
Studies were excluded if participants included individuals with diagnosed cancer, respiratory or neurological pathologies (e.g. stroke, traumatic brain injury, spinal cord injury, amyotrophic lateral sclerosis, or Guillian-barre syndrome). This was done to ensure outcomes were attributable to PICS and not a comorbidity that might also in uence recovery.
Study selection and data charting: Endnote was used to identify duplicate records prior to title and abstract screening. Titles and abstracts were screened by an individual (ZH) reviewer with two reviewers independently screening full-text articles (ZH) (SB). Reference lists of full-text articles were also screened to ensure all relevant papers were included. A non-standardised data extraction form was developed to summarise data from included articles (see Additional File 1.). Data were extracted by a single reviewer (ZH) and checked by another (SB). Individual methodological quality appraisal of included articles was not required as per the PRISMA-ScR guidelines however reviewers attempted to exclude poor quality of evidence by following the levels of evidence hierarchy [32].
Collating and summarising results: Authors deemed that the heterogenous nature of included articles was best to be described through thematic analysis to ensure a thorough and comprehensive review. Given the heterogeneous nature of outcome measures identi ed across the articles, only primary outcome measures were considered for our analysis. Characteristics were categorised using a biopsychosocial approach, with biological, psychological, and social/contextual characteristics considered [28]. Tables were developed to collate this information then converted into graphs as appropriate as part of the bibliometric analysis.

Results:
The search yielded 3054 articles. Duplicates were removed leaving 2210 articles. Due to the large number of remaining studies, both reviewers agreed to exclude articles published before 2010 (n=440). This decision was based on the knowledge that the term "post intensive care syndrome" was not common until after the 2010 [15]. Titles and abstracts of 1770 articles were screened by a single reviewer (ZH) with 55 full text articles identi ed for further screening. A quality audit was then conducted by a second reviewer (SB), with agreement to include twenty-ve articles in the nal analysis (see Figure 1.).

Characteristics of included studies:
Of the 25 articles included for analysis, there were six systematic literature reviews, two randomised controlled trials, and seventeen cohort studies. At the time of this review, publications relating to PICS or ICU survivorship have been dominated by research from the UK (24%) and Germany (24%) (see Table 1.), with articles published across 11 countries. When looking at date of publication, an increasing number of publications is evident (see Figure 2.) Patient factors and characteristics of the patient's condition were commonly considered selection criteria of included studies (see Table 2.). Age (>18-years) and ICU discharge status remained consistent between studies. There was, however, considerable variability between studies regarding the patients' length of stay (LOS) in hospital and the ICU, and the duration of mechanical ventilation. Gender, the presence of comorbidities, education level, body mass index (BMI), and additional demographic factors were variables commonly considered. The impact of delirium and the acquisition of ICU-aw on recovery during the post-intensive care period were also considered [33]. Taking a biopsychosocial approach, the characteristics of PICS have been characterised into biological, psychological, and social/contextual characteristics. We identi ed that overarching the three categories, were ten key outcomes that have been used to describe the recovery trajectory of individuals (see Figure  3.).

Biological Characteristics
We de ned biological characteristics as those closely resembling the physical characteristics described in previous PICS models [12]. Eleven studies considered biological factors among ICU survivors. These factors were used to report on biopsychosocial outcomes, such as functional status, exercise capacity, physical functioning, participation, and HRQOL.
Muscle strength was commonly measured, either via the Medical Research Council (MRC) scale for muscle strength [34,35] or dynamometry [34,35,36]. Two studies used muscle strength as a determinant of functional status during the post-intensive care period, concluding that improved muscle strength positively correlates with functional status [34,35]. These two studies also highlighted the impact of ICUaw on the recovery trajectory, ascertaining that poorer functional outcomes are likely among patients diagnosed with ICU-aw.
Cardiopulmonary exercise testing (CPET) was used to measure peak oxygen consumption (VO2) and anaerobic threshold (AT) in two studies [37,38]. CPET is considered the gold standard for assessing an individual's exercise capacity [39]. McWilliams et al. [38] concluded that exercise capacity is likely to improve within 12-weeks following discharge from the ICU, regardless of whether rehabilitation is received following discharge from the hospital. However, for patients experiencing more severe illness or requiring mechanical ventilation for more than 14-days, the risk of persistent de cits in exercise capacity is heightened [37].
Considerable variation was evident between methods of data reporting among our included studies. Eggman et al. [40] considered patients' exercise capacity and functional status. However, data were reported via the 6-minute walk test (6MWT) and Functional Independence Measure (FIM). Despite a variation in reporting methodology compared to Benington et al. [37] and McWilliams et al. [38], results remain the same. Patients who experienced moderate-severe muscle weakness also experienced signi cantly poorer outcomes in the 6MWT (p=0.013), FIM (p=0.001), and hospital LOS (p=0.008). This emphasises the need to consider the characteristics of a patient's condition and social and contextual factors as risk factors for poorer outcomes during the post-intensive care period.
Pain and fatigue are considered primarily biological factors. However, their impact on psychosocial factors should be noted. One included study reported that around two-thirds of ICU survivors report "new" chronic pain during the rst 6-months following discharge from the ICU [40]. The interference of pain on everyday life signi cantly decreased (p=0.04) during the rst year following hospital discharge. However, pain remained the most common reason participants reported a reduced "enjoyment of life".
Similarly, fatigue is reported to impact nearly half of ICU survivors during the rst 6-months of their recovery [41]. Fatigue has been shown to signi cantly positively correlate with PTSD (p<0.001) and signi cantly negatively correlate with HRQOL (p<0.001). Additionally, patient factors, including comorbidities and gender (male), were associated with higher perceived fatigue. In contrast, a patient's level of social support provides a salutogenic factor.

Psychological Characteristics
Anxiety, depression, and PTSD are commonly considered psychological characteristics of PICS [12]. For this review, cognition is also considered a psychological factor due to the impact cognitive de cits can have on an individual's level of understanding and ability to participate in their recovery journey [28].
This review found the current literature inconclusive regarding the prevalence of impaired cognitive function following discharge from the ICU. Chung, Yoo, Park & Ryu [42] measured cognitive impairment using the Mini-Cog Test at ICU discharge, reporting that 43% of patients experienced cognitive de cits.
However, 12-months following discharge from the ICU, 88% of ICU survivors demonstrate cognitive functioning within a normal range [43].
As with biological factors, characteristics of the condition and patient factors can impact an individual's cognitive recovery trajectory. Sumida et al. [44] conducted an observational cohort study to evaluate cognitive function in patients following discharge from a cardiac intensive care unit. Multiple logistic regression analysis identi ed that older age (p=0.042), nutritional status (p=0.017), and physical function (p=0.012) are signi cant and independent factors associated with impaired cognition in ICU survivors [44]. Also emphasising the interwoven nature of characteristics, Thomas & Mehrholz [43] concluded that regaining walking function is the best predictor of normal cognitive function one year following hospital discharge.
Self-report questionnaires, including the EuroQol-5D (EQ-5D) and the Short Form 36 (SF-36) questionnaire, have been used to identify psychological characteristics such as anxiety, depression, and PTSD [43,45]. These are commonly re ected in an individual's perceived HRQOL. Research suggests that when symptoms of anxiety, depression, or PTSD are experienced, there is a marked reduction in HRQOL [46]. Chung et al. [42] found that 60% of patients exhibited depressive symptoms upon discharge from the ICU, with more than 75% recalling one or more stressful experience from their time within the ICU.
Patient characteristics also appear to contribute to the presence of psychological symptoms. Our review identi ed that at discharge from the ICU, female patients (88.9%) were signi cantly more likely to experience depressive symptoms than males (47.6%, p=0.03) [42]. Additionally, it is reported that fatigue is likely to be exacerbated by current or previous anxiety or depression, impacting not only HRQOL but also participation [41].
The recovery of psychological symptoms during the post-intensive care period has also been described by an improvement in HRQOL. However, support for rehabilitation services remains inconclusive. Taito et al. [47] found moderate-quality evidence suggesting that at 6-and 12-months post-ICU discharge, physical rehabilitation provided during the post-intensive care period did not signi cantly improve HRQOL

Social & Contextual Characteristics
Our strict inclusion criteria did not identify studies that described the characteristics of PICS as "social and contextual". We de ned social and contextual characteristics as the factors surrounding an individual externally -for example, the patient's social supports, life stressors, situational characteristics, and their rehabilitation or recovery environment. For occupational therapists, these characteristics align with the "environmental factors" depicted by the Person-Environment-Occupation (PEO) Model [48].
Our review found that contextual factors, such as the duration of mechanical ventilation and the patient's hospital or ICU LOS, were commonly considered. Frequently, these variables were considered in the study's selection criteria, although several studies report considerable impacts of these factors on patient outcomes. A cohort study conducted by Benington et al. [37] identi ed a positive correlation between more than 14-days on mechanical ventilation and a reduced exercise capacity [peak VO2: (p=0.022); AT: (p=0.009)]. Similarly, a longer duration on mechanical ventilation appears to negatively impact the recovery of sit-to-stand function [49].
The impact of contextual factors on post-intensive care recovery was also highlighted by Chao et al. [50]. Their cohort study considered long-term mortality rates (up to 10-years) and identi ed that patients at "high risk" of mortality had experienced more severe illness, required a longer stay in hospital or the ICU or had spent more time on mechanical ventilation. Their study identi ed that rehabilitation provided during the post-intensive care period is most bene cial for this "high risk" group. They recommend this group of patients should be routinely considered a target population for post-intensive care rehabilitation.
Being surrounded by social supports, such as rehabilitation providers, family, and friends, has been suggested to considerably improve outcome indicators [41]. Occupational therapists have the potential to provide such social support to facilitate holistic recovery during the post-intensive care period. The results of our review suggest that allied health input is currently being underutilised to support PICS recovery during the post-intensive care period. A cohort study conducted by Thomas & Mehrholz [43] reported that during the rst 12-months following discharge, 71% of patients received no follow-up from a physiotherapist, and 86% received no follow-up from an occupational therapist.
While the bene ts of allied health have been noted, no articles were identi ed that directly report on the role of occupational therapists working within the post-intensive care period. A single-centre cohort study reported that the time spent engaging in walking practice with a physiotherapist signi cantly increased the chance of regaining walking ability (p<0.0001) [51].

Discussion:
In this systematic scoping review, we have appraised 25 articles, with the aim of answering our research question: what are the characteristics of PICS present within the rst year of discharge from the ICU, and how can these characteristics be used to inform occupational therapists working within the post-intensive care period? We applied an occupational therapy lens to our results, utilising the biopsychosocial model to organise PICS characteristics as biological, psychological, and social and contextual. Consideration has also been given to overarching biopsychosocial outcome indicators. Our results highlight the complex and interwoven nature of PICS characteristics during the post-intensive care period. We now turn our attention to the role of occupational therapists in providing a holistic rehabilitation approach to survivors of critical illness.

Theme 1: Worldwide demand for ICU care
Since 2012, the number of articles published relating to the PICS phenomena has steadily increased. This coincides with a gradual increase in demand for ICU treatment and a reduction in mortality as more and more individuals survive their stay in the ICU [52]. Up until the beginning of 2019, these trends have been gradual [52]. However, research is beginning to report on the signi cant spike in ICU patients seen as a result of the COVID-19 pandemic [53,54,55]. Recent Australian data suggests that the potential surge in patients requiring ICU treatment could reach 191% of the current capacity [55]. However, with reported mortality rates between 20-30%, the number of people surviving critical illness is also likely to increase dramatically [9].
While research is still emerging, it is reasonable to assume that the characteristics of PICS will be, to some extent, present in patients recovering from COVID-19. If so, the surge in demand for rehabilitation services following critical illness is inevitable. We suggest future research aims to determine the correlation between the recovery of PICS and COVID-19. This research should focus on supporting the role of allied health professionals, such as occupational therapists. Despite almost 20% of occupational therapists in Australia reporting rehabilitation as their primary scope of practice, we were unable to identify research supporting the role of occupational therapists during the post-acute phase of recovery from critical illness [56]. In the face of increased global demand, research is needed to provide patients access to occupational therapy services with the goal of improving performance in everyday activities and reducing the strain on healthcare systems globally.

Theme 2: ADL Performance
Occupational therapy is de ned by the World Federation of Occupational Therapy (WFOT) [57] as: "a client-centred health profession concerned with promoting health and well-being through occupation". WFOT [57] describes the primary goal of occupational therapy as "enabling people to participate in activities of daily living (ADLs)". ADLs include the fundamental tasks oriented toward taking care of one's own body and are considered essential to living in a social world [58].
Various biological characteristics, such as muscle strength and fatigue, are reported in the literature to directly correlate with ADL performance [59,60]. In our analysis however, the only paper to directly link PICS to ADL performance was a systematic review conducted by Ohtake et al. [16]. They found that at 3months following critical illness, 35% of patients had dependence in at least one ADL (including bathing, dressing, toileting, transferring, continence, or feeding) compared to 25% prior to their critical illness. Three additional systematic reviews reported limited or no research reporting on ADL performance in the context of PICS [47,61,62].
The impact of PICS on ADL performance has been identi ed as an area requiring future research. Based on our analysis, we predict that ADL performance is likely to be negatively impacted in patients with PICS during the post-intensive care period. Occupational therapists frequently use assessment tools speci cally designed to measure ADL performance -such as the Barthel Index and the Functional Independence Measure (FIM) [63]. We suggest that utilising such assessment tools will assist occupational therapists to lead the way in developing research to support the link between PICS and ADL performance. In doing so, an opportunity is created for occupational therapists to engage in postintensive care rehabilitation to facilitate positive patient outcomes.

Theme 3: HRQOL
The complex presentation of PICS characteristics highlights a prominent need for rehabilitation to occur across all domains of the biopsychosocial model. Our analysis suggests that HRQOL is undeniably linked to psychological characteristics. When symptoms of anxiety, depression, or PTSD are experienced, there is a marked reduction in HRQOL [46]. However, it is impossible to separate HRQOL from biological and social and contextual factors as well. Fatigue has been linked to a signi cant reduction in HRQOL, with fatigue also likely to exacerbate psychological symptoms such as PTSD [41]. Additionally, HRQOL is improved when patients feel supported by their social connections [41,46].
We identi ed that research to date has focused on physical rehabilitation and is not re ective of the potential bene ts of a holistic rehabilitation approach. The occupational therapy scope of practice encompasses more than just physical or biological rehabilitation [64]. Models, such as the PEO model, guide occupational therapists to consider the person and their ability to engage in meaningful occupations or life roles in the context of their broader environment [48]. Research suggests that when a person's abilities t well with the demands and opportunities in their environment, they experience improved quality of life and overall occupational performance [65]. Therefore, taking a holistic approach and utilising engagement in day-to-day tasks, occupational therapists working within the post-intensive care period have the potential to improve patient outcomes.

Theme 4: Social and contextual characteristics
As with HRQOL, the PEO model highlights the inability to separate a person's occupational performance from social and contextual in uences [48]. However, we found no direct reference made to the biopsychosocial model in facilitating recovery during the post-intensive care period. As such, the importance of considering social and contextual factors as unique characteristics was of high importance to our review.
The length of stay in the hospital or the ICU and the duration of mechanical ventilation can be considered uncontrollable contextual characteristics that can impact post-intensive care recovery [37,49,50].
Research regarding occupational therapy intervention within the ICU is emerging. A recent systematic review suggested that occupational therapists are well-equipped to facilitate environmental interventions within the ICU, such as physical setup, noise, and organisational structure [26]. These ndings support the opportunity for occupational therapists to transfer their skills in environmental modi cations into the ICU environment, potentially reducing the severity of PICS.
Our results indicate that allied health professionals remain underutilised within the post-intensive care period. Thomas and Mehrholz [43] reported that only 14% of patients received occupational therapy input following discharge from the ICU. Emerging research has predicted that social isolation and loneliness are likely to be signi cantly impacted by the COVID-19 pandemic [66]. From our analysis, we know that patient outcomes are favourable when patients feel they have access to a strong social support network [41]. Utilising digital platforms such as telehealth, occupational therapists can connect with patients and provide rehabilitation services despite growing social isolation.

Strengths and Limitations:
To our knowledge, this is the rst systematic scoping review explicitly focused on the role of occupational therapy in the management of PICS. We used a robust study design to determine the characteristics of PICS as they relate to occupational therapy practice and applied a biopsychosocial model to highlight how these characteristics are intertwined.
Scoping reviews have inherent limitations as they focus on breadth rather than depth [31]. Rapid growth in ICU demand and the COVID-19 pandemic means that new and emerging literature will likely have been published following our literature search. Additionally, we only considered data following discharge from the ICU, with there likely to be research available that considers rehabilitation interventions commencing within the ICU. Data were extracted and processed by a single reviewer only. A secondary reviewer then completed cross-referencing to reduce the risk of bias. Our robust study design meant our eligibility criteria could have excluded valuable data. For example, qualitative studies reporting on patients' or health professionals' perspectives could have supported the occupational therapy role in PICS management. This should be considered when conducting future research.
We acknowledge there are likely articles published since the completion of this review given the constantly changing COVID-19 situation globally. It is noted that these articles appear to focus on the impacts of COVID-19 whereas the current paper did not speci cally seek to identify articles relating to COVID-19.

Conclusion:
Our systematic scoping review found the characteristics of PICS to be complex and include biological, psychological, and social and contextual factors. We have highlighted the need to consider a holistic rehabilitation approach to facilitate the recovery trajectory during the post-intensive care period. We identi ed the characteristics of PICS amenable to occupational therapy intervention given their ability to provide a holistic approach to care, considering the person, their environment, and activities that provide them with meaning.
The COVID-19 pandemic increases the need for healthcare systems to utilise available resources to ensure optimal patient outcomes. Currently underutilised, occupational therapists have the potential to reduce the global healthcare burden and improve patient outcomes by providing client-centred care. Future research is needed to determine the best model of care to support occupational therapists in promoting recovery following critical illness. Availability of data and materials: Data sharing is not applicable to this article as no datasets were generated or analysed during the current study.
Competing interests: The authors declare that they have no competing interests.
Funding: Not applicable Authors' contributions: All those designated as authors have met all four ICMJE criteria for authorship: 1. Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; and 2. Drafting the work or revising it critically for important intellectual content; and 3. Final approval of the version to be published; and 4. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
All authors read and approved the nal manuscript.