Breaking down barriers: Overcoming bottlenecks in the health- care system for newborns with hypoxic ischemic encephalopathy

doi:10.21203/rs.3.rs-2824100/v1

Purpose: To evaluate the practices of neonatologists and pediatricians for neonates with hypoxic-ischemic encephalopathy (HIE) in Jordan to identify gaps in diagnosis, management, and follow-up of HIE, including the availability of long-term follow-up services. This is an important clinical issue to address as HIE is the fourth leading cause of infant mortality in Jordan.

Methods: This was a cross-sectional study including 15 neonatologists and 42 pediatricians treating neonates with HIE in Jordan. Data were collected using a custom-designed, self-report questionnaire, consisting of 35 items across four dimensions: participant demographics; indicators used for HIE diagnosis; criteria used to determine HIE severity and HIE management strategy, including therapeutic hypothermia practice; and availability of long-term services for HIE follow-up. Items were answered on a 5-point Likert scale, with anchors measuring the extent to which practices were used: 1, never; 2, seldom; 3, sometimes; 4, frequent; and 5, always.

Results: The Apgar score was used by 70% of participants to evaluate neonates’ status at birth and the SARNAT staging score to determine the severity of HIE. Management strategy included the transfer of neonates to intensive care (30%), initiation of therapeutic hypothermia within 6 h post-natal (70%), and continuation of hypothermia for the full recommended 72 h (63.2%). Timely access to brain imaging was not available to all participants. Technology to assess brain activity was insufficient.

Conclusion: The development of a bundle for HIE practices would be recommended in Jordan to improve the quality of care for neonates with HIE.

Newborn

hypoxic-ischemic encephalopathy

therapeutic hypothermia

middle-income country

Intrapartum or late antepartum asphyxia is the primary cause of hypoxic-ischemic encephalopathy (HIE) [1]. HIE is a serious birth complication of full-term infants, leading to abnormal neurologic behavior in the neonatal period [1, 2]. Hypoxemia is defined by a low blood oxygen level, reducing oxygen to tissues including the brain, with ischemia defined as a reduction in tissue blood flow, with each component exacerbating the other. Asphyxia causes impairment in gas exchange, leading to anoxia and extreme hypercarbia [3]. Perinatal asphyxia leading to HIE accounts for 23% of neonatal deaths worldwide [4]. In addition, neonatal HIE causes injury to neurons and white matter tracts and, thus, is a major cause of long-term neurological disorders, including epilepsy and cerebral palsy [5]. Worldwide, the incidence of HIE is estimated at 1.5 per 1000 birth lives in developed countries, with the incidence varying between 2.3 and 26.5 per 1000 live births in developing countries [6].

Therapeutic hypothermia (TH), lowering the rectal temperature to between 33°C and 34°C, aims to reduce neurologic damage associated with moderate to severe HIE by lowering the energy demand of tissues [7]. Early initiation of TH, at 6–24 h post-natal, has been shown to significantly decrease the risk of mortality and neurologic disorder in neonates with HIE [3]. Based on this evidence, TH is considered the standard care for neonatal HIE in high-income countries [8]. However, this standard has not been established in other countries. As an example, in Jordan, a Middle East country, national guidelines for the identification and management of newborns with perinatal asphyxia were developed in 2017 by neonatology consultants to standardize care, based on evidence. However, the status of care and management of patients with HIE in Jordan has not been evaluated.

The safety and efficacy of cooling therapy established in high-income countries cannot be readily extrapolated to low- and middle-income countries (LMICs) [9, 10] and low-resources settings [8] due to various challenges that can include inadequate neonatal critical care (such as sedation, ventilatory support, and excessive oxygen use) and availability of suboptimal cooling systems (such as water-circulating cooling caps, frozen gel packs, ice, water bottles, and phase-changing material). In this regard, we do note a recent systemic analysis that indicated that TH, regardless of income and country level, significantly reduces the risk of mortality in neonates with moderate-to-severe HIE [3]. Therefore, to improve the quality of care provided within Jordan, it is necessary to first understand the problem and the issues that healthcare providers face.

Aim of the study

Our aim in this study was to evaluate the clinical practices used for HIE diagnosis, management, and follow-up among healthcare practitioners involved with the birth and follow-up of neonates with HIE.

Study design and study sample selection

This was a cross-sectional study with data collected over 2 months, from October to November 2021. Eligible were all neonatologists and pediatricians who provide care to neonates with HIE in neonatal intensive care units (NICUs) across Jordan. Participants were identified and recruited through the Jordan Medical Council-Jordan's Pediatric and Neonatal Society. At the time of the study, 1184 certified general pediatricians and 34 neonatologists were registered; of these, we sent recruitment information to 72 (38 pediatricians and 34 neonatologists), with 57 providing consent (15 neonatologists and 42 general pediatricians). All healthcare centers providing treatment to neonates with HIE were included: Ministry of Health hospitals, university hospitals, private hospitals, and the hospitals of the Jordanian Royal Medical Services.

Ethics statement

The study methods were approved by the Ethics Review Board of the University of Jordan School of Medicine (IRB approval number 503/2021/76, 202127894). Informed consent was obtained from all participants before being provided with the questionnaire. Ethical principles in epidemiologic practice and research were met, including autonomy, confidentiality, privacy, freedom from harm and exploitation, and the risk/benefit ratio. All data were anonymized, using coded identifiers, to ensure confidentiality.

Custom-designed, self-report questionnaire

Information on practice for HIE was collected using a structured, self-report questionnaire. The questionnaire was distributed electronically to participants (by phone text, email, or social media, such as WhatsApp, LinkedIn, and Facebook Messenger). The questionnaire was provided in the English language and was adapted from two previous publications [11, 12]. The questionnaire (Supplementary Material) consists of 41 items, distributed across the following four dimensions: participant demographics, clinical workplace description, and guideline awareness (15 items); criteria used for HIE diagnosis, newborn care, and parent’s support and care (8 items); criteria used to determine HIE severity and management strategy, including TH practice (14 items); and availability of long-term services for HIE follow-up (4 items). All items are answered on a 5-point Likert scale, with anchors measuring the extent to which practices are used, as follows: 1, never; 2, seldom; 3, sometimes; 4, frequent; and 5, always (Supplementary Material). The frequency of practices used was classified by the Likert score, as follows: low, 1.00-2.33; medium, 2.34–3.67; and high, 3.68-5.00. The questionnaire was piloted on 10% of the sample size, including senior pediatric residents, to evaluate its validity and reliability before use in this study; the pilot data was not included in the study analysis. The face validity of the questionnaire was confirmed by three academic reviewers. With regards to reliability, Cronbach’s Alpha values were 0.793 for the dimension of diagnosis, 0.786 for management, and 0.715 for follow-up.

Level of neonatal care

The level of neonatal care was defined as previously described [13]. Level II care is provided to infants born at ≥ 32 weeks gestation and weighing ≥ 1500 g. Admitted neonates require recovery after NICU discharge and care provided can include the provision of mechanical ventilation, continuous positive airway pressure, or both, for a brief duration (< 24 h). Level II care can also be used to stabilize infants born before 32 weeks of gestation and weighing < 1500 g awaiting transfer to a NICU facility. Level III neonatal care provides comprehensive management for infants born at < 32 weeks of gestation and weighing < 1500 g, as well as all other critical neonates. Level III care facilities provide access to a full range of pediatric medical subspecialists and respiratory support methods, as well as advanced imaging.

Statistical analysis

Descriptive statistics were used to summarize information across the four domains of the questionnaire, including mean (standard deviation) or frequency (percentage) as appropriate for the data type and distribution. Descriptive statistics were calculated using IBM SPSS Statistics (version 24).

Demographics of the study sample

The questionnaire was completed by 57 participants, 15 neonatologists, and 42 general pediatricians. Relevant characteristics of the study sample are reported in Table 1, with key characteristics as follows: 28% of participants had >10 years of clinical experience, 84% worked in a tertiary care center, and 74% and 72%, respectively, were aware of HIE and TH guidelines in Jordan.

HIE diagnosis

The criteria used for HIE diagnosis are reported in Table 2. The Apgar score (1, 5, and 10 min) and general neurological assessment were most commonly used for HIE diagnosis, with only a medium-level use of electroencephalography (EEG). Nurses and year 3 and 4 pediatric residents were the medical staff more commonly responsible for complicated neonatal resuscitation in the delivery room, with neonatologists least present (Table 3). A general clinical assessment and the SARNAT Staging Score were used most frequently to determine the severity of HIE (Table 4). A medium-level use of cerebral activity monitoring was reported, with limited availability of EEG, aEEG, video EEG, and continuous cerebral function monitoring devices. Although trained radiologists provided interpretation of MR and ultrasound imaging, brain imaging had only a moderate level of availability, with a medium score for MR imaging performed within 1-2 weeks post-natal. Blood glucose within 6 h post-natal was performed by 73.7% of participants, and blood gases within the first post-natal hour were performed by 28.8% of participants.

HIE management

Information on the evaluation of HIE severity, management, and long-term follow-up services was provided by 38/57 (66.7%) of participants. Regarding TH, the Active Servo-Control System was generally used (Table 5). A medium-level use of TH was reported, initiated within 6 h post-natal by 71.1% of participants, and continued for the recommended 72 h by 36.3%. Treating physicians supported parents either ‘always’ (47.4%) or ‘frequently’ (39.5% ).

NICUs were located in level II or III critical care centers, with 15-30 beds (Figure 1). Of note, 89.5% of participants reported treating ≤5 cases of HIE per year. Pediatric Neurology and Neonatology departments were the most frequently involved in neurodevelopmental assessment (high-level response for both; Table 6). Long-term follow-up for neonates with HIE was available in 47.4% of centers in which participants worked. For follow-up, neurological examination was most frequently used (high-level response), with standardized screening tools, the Bayley Infant Neurodevelopmental Screen and ASQ, used at a medium level.

Goal 3.2 of the Sustainable Development Goals [14] calls for each country to reduce the neonatal mortality rate to < 12 per 1000 live births by 2030. In 2019, the neonatal mortality rate for Jordan was 14.1 per 1,000 live births, a rate which has remained constant over the last 15 years, with birth asphyxia being the fourth most common cause of neonatal death [15, 16]. This is why evaluating clinical practices for HIE in Jordan, an LMIC is important.

With regards to HIE diagnosis, we identified that nurses and year 3 or 4 pediatric residents are generally in charge of complicated births in Jordan. This is consistent with the recommendations of the Neonatal Resuscitation Program (NRP), at least one provider with NRP training should be present at every delivery [17]. Having birth attendants up-to-date with neonatal resuscitation skills increases their self-efficacy and lowers the risk of neonatal mortality due to asphyxia [18]. HIE risk is identified by a cluster of markers at birth, including a low Apgar score, the need for resuscitation, a low umbilical artery or first-hour pH < 7.1 (indicative of metabolic acidosis), and clinical findings, such as hypotonia, seizures, change in the level of consciousness, and a state of multiorgan dysfunction [19]. In this regard, the Apgar score at 1, 5, and 10 min post-natal is useful for identifying the need for neonatal resuscitation [20], consistent with our findings. Similarly, early neurological examination and the SARNAT Staging Score within the first 6 h post-natal were used to determine the severity of HIE in our study sample, as recommended to predict long-term outcomes of neonatal asphyxia [21]. Of note, however, EEG was not consistently used in Jordan to quantify HIE severity, as recommended. This could reflect the medium level of availability of EEG and aEEG devices in participating centers, as well as the low-level availability of video EEG and continuous cerebral function monitoring devices. We do note that despite reporting a high availability of radiologists trained in the interpretation of MR and ultrasound imaging, timely brain imaging (within week 1 post-natal), including diffusion-weighted MR imaging which is recommended, was not consistently performed, despite evidence of the importance of imaging for HIE diagnosis, differential diagnosis, and prognostic prediction [22]. As abnormal changes in blood glucose levels in the first 6 h post-natal have been linked to advanced HIE staging and abnormal neurodevelopmental outcomes, avoiding hypo- and hyper-glycemia early in HIE can have a neuroprotective effect [23]. However, 25% of our participants did not measure blood glucose levels within 6 h post-natal.

There is evidence that TH can lower the mortality rate of neonates with HIE [24], [25]. Our findings indicate that a lack of awareness of guidelines for TH may lead to variation in the early management of HIE, as previously reported [26]. Approximately one-third of the participants in our study were unaware of the national HIE guidelines and hypothermia protocol in Jordan. Moreover, most participants were exposed to fewer than 5 cases of neonatal HIE per year. This lack of awareness of national guidelines and experience with HIE could explain why only 71% of participants reported that they ‘always’ initiate TH within the recommended 6 h post-natal and that TH was not sustained for the recommended 72 h post-natal for all eligible neonates. We further note that one-third of participants transferred neonates in critical condition with HIE to other centers for care. This is an important finding as Jordan lacks a newborn transport system that employs active servo-controlled cooling during the transfer, compromising the safety and efficacy of TH.

The findings of our study highlight the healthcare inequalities that exist in Jordan, both in terms of access and availability of resources. Specifically, only 60% of physicians treating neonates with HIE had access to active servo-controlled cooling systems. Passive cooling modalities were used by other physicians, including turning off post-natal warming systems, using cold-water mattresses, application of ice packs, and use of air conditioners. Overall, we note that whole-body cooling was used by 82% of participants and selective cooling by the other 18%. While there are no differences in neuroprotective effects between cooling methods [27], [28] with cooling methods available in Jordan, the target core temperature of 33–34 C⁰ for 72 h post-natal [29] was achieved by only 37% of treating physicians. This is an important finding considering that over the past two decades, Jordan has faced a high rate of newborn mortality of 14.1 per 1,000 live births [15].

Non-pharmacologic methods and, to a lesser extent, continuous sedative drug infusion can reduce stress in critical neonates [30]. In our study sample, 10% of participants reported ‘never’ using sedative drugs during TH. We further note that 81.6% of our participants adhered to an absolute fasting protocol, with only fluids provided during TH, despite some evidence that enteral feeding is both safe and beneficial during TK, with positive outcomes reported [31].

Long-term follow-up is recommended for neonates with HIE, with the duration and type of follow-up being helpful to diagnose cognitive impairment and learning deficits, sensory or motor impairment, and growth deficits [32]. Yet, only half of our participants reported the availability of long-term follow-up services for neonates with HIE in Jordan. Most frequently, a neurodevelopmental follow-up assessment was provided through pediatric neurology departments, with a detailed neurologic examination used to document potential developmental delay, as recommended [33–35]. However, we note the medium-level use of the Bayley Infant Neurodevelopmental Screen and ASQ as standardized neurodevelopmental assessments. Furthermore, we note that only 47.4% of participants reported ‘always’ providing support to parents, despite the recommendation for parent support [36]. Supporting families through communication, involving parents in their child's care, recognizing parents' mental health needs during their infant’s hospitalization, and connecting families with meaningful resources as they prepare to return home positively improves family outcomes.

The limitations of our study need to be acknowledged. Foremost is the small sample size, with only 15 of the 34 licensed registered neonatologists in Jordan responding to the survey, with general pediatricians involved in the care of neonates with HIE providing the remaining responses. Second, the majority of respondents were from the same hospital. As such, our findings might more accurately reflect differences in practice between physicians rather than between centers. Therefore, to prevent bias in establishing policies and guidelines for neonatal care in Jordan, recruitment from all centers and hospitals providing neonatal care will be needed.

In conclusion, our findings indicate the need to improve awareness and adoption of the national guidelines for the care of neonates with HIE among physicians in Jordan, through conferences, seminars, and lectures. Creating an HIE practice improvement bundle might be effective as a quality improvement strategy, including a focus on developing interdisciplinary teams for neonatal care to reduce variation in the diagnosis, management, and follow-up of neonates with HIE. Moreover, appropriate cooling devices should be provided to all NICU units in Jordan. As well, appropriate an appropriate neonatal transport system needs to be established to ensure the prompt and safe transfer of neonates with HIE to centers that can provide TH. Finally, given the potential long-term complications of HIE, establishing a comprehensive long-term follow-up protocol is needed in Jordan. Together, these measures could significantly improve neonatal HIE management in Jordan and reduce the associated morbidity and mortality rates.

Acknowledgments

We thank the physicians who participated in the survey and the specialists who reviewed our questionnaire for validity.

Statements and Declarations

Compliance with Ethical Standards

Funding

The authors declare they have no direct or indirect financial interests.

Disclosure of potential conflicts of interest

The authors have no conflicts of interest to declare relevant to this article's content.

Ethical approval and Informed consent

The study methods were approved by the Ethics Review Board of the University of Jordan School of Medicine (IRB approval number 503/2021/76, 202127894). Informed consent was obtained from all participants before being provided with the questionnaire.

Consent for publication

Not applicable.

Authors' contributions

Eman F. Badran: conceptualization (lead); methodology (lead); writing of the original draft and final version submitted (lead); Ahmad Rawajbeh: conceptualization, critical review of manuscript and writing, and analysis (co-lead); Waseem Alhaj: conceptualization, critical review of manuscript and writing, analysis (co-lead); Abdallah Elqunj: conceptualization, critical review of manuscript and writing, analysis (co-lead); Mohammad Askar: a critical review of manuscript and analysis (lead); Maryam Al Jammal: conceptualization (co-lead), critical review and editing (equal); Ala’a AL-Qhaiwi: critical review and editing (equal); Rafeef Qawasmeh: critical review and editing (equal); and Majd AlHalaki: conceptualization (supporting role), critical review and writing (equal).

Data availability statement

Anonymized data is available from the corresponding author upon reasonable request.

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Table 1 Demographic characteristics of the participants (N=57)

	Frequency (n)	Percentage (%)
Sex
Male	23	40.4
Female	34	59.6
Age
<30 years	10	17.5
30-40 years	31	54.4
>40 years	16	28.1
Specialty
General pediatrician	42	63.2
Neonatologist	15	26.3
Years of clinical experience
<10 years	41	71.9
≥10 years	16	28.1
Type of hospital
Ministry of health hospital	14	24.6
Military hospital	10	17.5
Academic teaching hospital	14	24.6
Private hospital	19	33.3
Is your neonatal unit a tertiary center
Yes	48	84.2
No	9	15.8
Are you aware of the evidence-based HIE guidelines in Jordan?
Yes	42	73.7
No	15	26.3
Are you aware of the therapeutic hypothermia protocol used in Jordan?
Yes	41	71.9
No	16	28.1

Table 2 Likert scale scores for the criteria indicators used for diagnosing HIE (N=57)

Statements	Mean	Standard Deviation	Rank	Importance Level
Neurological manifestations	4.74	0.79	1	High
APGAR Score at one minute / 5 minute / 10 minutes	4.70	0.82	2	High
Blood tests	4.28	1.03	3	High
Brain MRI	3.91	1.20	4	High
Peripheral venous blood gas in first hour	3.89	1.03	5	High
Venous/artery cord gas in first hour	3.88	1.13	6	High
Head ultrasound	3.51	1.30	7	Medium
Umbilical artery blood gas in first hour	3.49	1.36	8	Medium
EEG	3.32	1.33	9	Medium
Brain CT	2.93	1.27	10	Medium
Total	3.86	0.62		High

MRI, magnetic resonance imaging; EEG, electroencephalogram; CT, computed tomography

Table 3 Medical staff responsible for neonate resuscitation in the delivery room for complicated deliveries performed by the participants (N=57)

Number	Statements	Mean	Standard Deviation	Rank	Importance Level
5	Delivery room staff nurse	4.44	1.05	1	High
2	Pediatric resident in year 3 or 4	4.18	1.27	2	High
7	Midwife	4.09	1.21	3	High
6	Nursery staff nurse	3.51	1.57	4	Medium
1	General pediatrician	3.42	1.35	5	Medium
8	Neonatal nurse	3.39	1.42	6	Medium
3	Pediatric resident in year 1 or 2	3.07	1.51	7	Medium
4	Neonatologist	2.74	1.06	8	Medium
Total		3.60	0.59		Medium

Table 4 Methods used to determine the severity of HIE and available resources for the management of neonates with HIE (N=38)

	Mean	Standard Deviation	Importance Level
Neurological staging scale used for HIE severity
SARNAT and SARNAT STAGING	4.19	1.04	High
General clinical assessment	4.19	1.27	High
THOMBSON Score	2.61	1.33	Medium
Total	3.67	0.80	Medium
Timing of first MRI
After post-natal month 1	3.40	1.28	Medium
Within post-natal week 1-2	3.32	1.24	Medium
Within post-natal week 1	3.21	1.50	Medium
Total	3.31	0.80	Medium
Availability of cerebral activity monitoring devices
Regular EEG	3.33	1.52	Medium
aEEG	2.37	1.41	Medium
Video EEG	2.33	1.41	Low
Continuous cerebral function monitor	2.16	1.40	Low
Total	2.55	1.04	Medium
Available professionals trained in brain neuroimaging interpretation
Radiologist trained in MRI interpretation	4.00	1.34	High
Radiologist trained in brain ultrasound interpretation	3.72	1.26	High
Neonatologist trained in brain ultrasound interpretation	3.30	1.57	Medium
Radiologist trained in Doppler ultrasound	3.25	1.54	Medium
Neonatologist trained in MRI interpretation	2.68	1.48	Medium
Neonatologist trained in Doppler ultrasound	2.26	1.38	Low
Total	3.20	1.01	Medium
How frequently do you measure blood glucose withen the first 6 hours after birth?	Frequency (N)	Percentage(%)	Mean (Standard Deviation)
Always	42	73.7	4.67 (0.69)
Frequently	13	22.8
Sometimes	1	1.8
Seldom	---	---
Never	1	1.8
Total	57	100.0	High

HIE, hypoxic-ischemic encephalopathy; EEG, electroencephalogram; aEEG, amplitude integrated electroMRI, magnetic resonance imaging

Table 5 Therapeutic hypothermia practice used (N=38)

Statements			Mean	Standard Deviation	Rank	Importance Level
Specialized active cooling system with servo-control			3.66	1.65	1	Medium
Turning off the heating			3.66	1.40	2	Medium
Hypothermia using ice packs			2.76	1.65	3	Medium
Cooled water mattress or bag			2.42	1.59	4	Medium
Turning on air conditioners			2.08	1.42	5	Low
Total			2.92	0.78		Medium
Type of cooling device
Whole-body cooling			4.29	1.29	1	High
Head cooling in combination with whole-body cooling			3.24	1.72	2	Medium
Selective head cooling			2.21	1.44	3	Low
Total			3.25	0.87		Medium
Method for temperature measurement
Rectal			4.48	1.00	1	High
Axillar			2.73	1.46	2	Medium
Total			3.61	0.78		Medium
Frequency of temperature measurement during hypothermia
Continuously	3.66			1.60	1	Medium
At 15-30 min intervals	2.92			1.36	2	Medium
At 30-60 min intervals	2.82			1.52	3	Medium
At 5-15 min intervals	2.76			1.17	4	Medium
At 60-120 min (1-2 hour) intervals	2.34			1.36	5	Medium
Total		2.90		0.78		Medium
How often is the therapeutic hypothermia initiated within 6 h post-natal		Frequency (N)			Percentage (%)
Never		---			---
Seldom		1			2.6
Sometimes		---			---
Frequently		10			26.3
Always		27			71.1
Total		38			100.0

Table 6 Availability of long-term follow-up services for the neonates with HIE (N=38)

Statement		Mean	Standard Deviation		Importance Level
Hospital department responsible for the neurodevelopmental assessment of neonates with HIE
Neurology	4.55			0.86		High
Neonatology	4.42			1.00		High
General child health care pediatric department	3.24			1.38		Medium
Child rehabilitation	3.21			1.32		Medium
Child development department	2.82			1.66		Medium
General child health care departments (primary health care)	2.55			1.37		Medium
Total	3.48			0.70		Medium

Statement		Frequency (N)		Percentage (%)
How often does your hospital provide long-term follow-up service for children with HIE?
Never		1		2.6
Seldom		4		10.5
Sometimes		6		15.8
Frequently		9		23.7
Always		18		47.4
Total		38		100.0
	Mean		Standard Deviation		Importance Level
Neurodevelopmental assessment used in the follow-up program
General neurological examination	4.82		0.51		High
Bayley Infant Neurodevelopmental Screen	3.21		1.30		Medium
Ages and Stages questionnaire (ASQ)	2.87		1.28		Medium
Total	3.66		0.80		Medium

HIE, hypoxic-ischemic encephalopathy

No competing interests reported.

supplementarymaterial.pdf

Breaking down barriers: Overcoming bottlenecks in the health- care system for newborns with hypoxic ischemic encephalopathy

Status:

Version 1

Abstract

Figures

Introduction

Aim of the study

Methods

Study design and study sample selection

Ethics statement

Custom-designed, self-report questionnaire

Level of neonatal care

Statistical analysis

Results

Demographics of the study sample

HIE diagnosis

HIE management

Discussion

Declarations

References

Tables

Additional Declarations

Supplementary Files

Status:

Version 1