Pediatric trauma: a retrospective analysis from 2018 to 2019

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1 LITHUANIAN UNIVERSITY OF HEALTH SCIENCES

MEDICAL ACADEMY

FACULTY OF MEDICINE

DEPARTMENT OF PEDIATRICS

Pediatric trauma: a retrospective analysis from

2018 to 2019

Master thesis

Student: Rugilė Benešiūnaitė Supervisor: Assoc. Prof. Lina Jankauskaitė MD, PhD

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SUMMARY

R. Benešiūnaitė. Pediatric trauma: a retrospective analysis from 2018 to 2019. The final thesis of Medicine programme, Lithuanian University of Health Sciences, Medical academy, Department of Pediatrics, Kaunas, 2021.

Background: Worldwide pediatric trauma is the main cause of concern regarding the frequency of admissions to the Pediatric Emergency Department (PED) and is the leading cause of death in this age group.

Aim: To investigate pediatric traumas that occurred between 2018 January 1st_{and 2019} December 31st_{in the PED of Lithuanian University of Health Sciences Hospital Kauno} Klinikos and compare the results to similar studies performed in other countries.

Objectives: 1. To analyze and compare the number of pediatric patients that visited PED in the years 2018 and 2019. 2. To analyze and compare patient demographics: age, gender. 3. To analyze and compare trauma types between different age groups. 4. To further analyze and compare fracture incidence, mechanism, and treatment options. 5. To present practical recommendations regarding pediatric trauma.

Methods: A retrospective analysis from the electronical record data system (LIS) was conducted of all trauma cases of children aged 0-18 years from 2018 1st_{of January to 2019} 31st_{of December referred to Lithuanian University of Health Sciences Hospital Kauno} Klinikos. The trauma categorization included all codes of S0-S99 from the ICD-10-AM classification. In total, we investigated 19923 pediatric trauma patient records. Additional analysis was conducted for 4058 patients with a fracture diagnosis.

Results: In 2018 there were 9698 and in 2019 – 10225 pediatric injury cases. Most patients were male (59.9%). The mean age of all patients was 8.7± 4.9 years. 1–14-year-olds comprised to a total of 81.8%. The most common injuries were as follows: <1 year old – superficial head injury, 1-5 years old – head and upper limb injury, 6-10 years old – lower limb injury, 11-18 years old – lower and upper limb injuries. Fractures made up to 20.4% of all pediatric injuries, most frequently sustained at home and after a fall. 25% patients were admitted, most often to the Orthopedics and traumatology department for surgical fracture reduction.

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4 Conclusions: The significant increase in pediatric trauma cases was observed (p<0.05). In both traumatic injury and fracture groups males made up the majority. The 6–10-year-old group had the highest incidence of sustained traumatic injuries (28.6%).

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SANTRAUKA

R. Benešiūnaitė. Vaikų traumos: retrospektyvinė 2018 ir 2019 metų analizė. Medicinos studijų programos baigiamasis mokslinis darbas, mokslinė vadovė doc. L. Jankauskaitė. Lietuvos sveikatos mokslų universitetas, Medicinos akademija, Vaikų ligų klinika, Kauans, 2021.

Temos aktualumas: Pasaulyje vaikų trauminiai sužalojimai yra aktuali visuomenės problema. Traumos yra pagrindinė apsilankymo vaikų skubiosios pagalbos skyriuje (VSPS) priežastis. Trauminiai sužalojimai užima pirmąją vietą tarp dažniausių mirties priežasčių šioje amžiaus grupėje.

Darbo tikslas: Ištirti vaikų traumas, įvykusias nuo 2018 m. sausio 1 d. iki 2019 m. gruodžio 31 d. Lietuvos sveikatos mokslų universiteto ligoninės Kauno klinikų PED, ir palyginti rezultatus su panašiais tyrimais, atliktais kitose šalyse.

Uždaviniai: 1. Išanalizuoti ir palyginti vaikų, apsilankiusių PED, skaičių 2018 ir 2019 metais. 2. Išanalizuoti ir palyginti pacientų demografinius rodiklius: amžių, lytį. 3. Išanalizuoti ir palyginti įvairių amžiaus grupių traumų tipus. 4. Išanalizuoti ir palyginti lūžių dažnį, mechanizmą ir gydymo galimybes. 5. Pateikti praktines rekomendacijas vaikų traumų mažinimui.

Tyrimo medžiaga ir metodai: Atlikta visų 0–18 metų vaikų traumų atvejų nuo 2018 m. sausio 1 d. iki 2019 m. gruodžio 31 d. atvykusių į Lietuvos sveikatos mokslų universiteto ligoninę Kauno klinikas retrospektyvinė analizė iš elektroninių įrašų duomenų sistemos (LIS). Traumų kategorija apėmė visus TLK-10-AM klasifikacijos S0-S99 kodus. Iš viso ištyrėme 19923 vaikų traumų pacientų įrašus. Papildoma analizė buvo atlikta 4058 pacientams, kuriems diagnozuotas lūžis.

Rezultatai: 2018 m. buvo 9698, o 2019 m. - 10225 vaikų traumos atvejai. Dauguma pacientų buvo vyrai (59,9%). Vidutinis visų pacientų amžius buvo 8,7 ± 4,9 metai. 1–14 metų vaikai sudarė 81,8 proc. Dažniausios traumos buvo šios: <1 metų - paviršinė galvos trauma, 1-5 metų - galvos ir viršutinių galūnių trauma, 6-10 metų - apatinių galūnių trauma, 11-18 metų - apatinių ir viršutinių galūnių traumos. Lūžiai sudarė 20,4% visų vaikų traumų, dažniausiai patiriamų namuose ir po kritimo. Stacionarizuoti 25% pacientų, iš kurių dažniausiai į Ortopedijos ir traumatologijos skyrių dėl chirurginio lūžių gydymo.

Išvados: Pastebėtas reikšmingas vaikų traumos atvejų padaugėjimas (p <0,05). Tiek trauminių sužalojimų, tiek trauminių lūžių grupėse vyrai sudarė daugumą. Trauminius sužalojimus dažniausiai patyrė vaikai, priklausę 6–10 metų amžiaus grupei (28,6 proc.).

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ACKNOWLEDGEMENTS

I would like to express my gratitude to my supervisor, Lina Jankauskaitė MD, PhD.

CONFLICT OF INTEREST

The author reports no conflicts of interest.

CLEARANCE ISSUED BY THE ETHICS COMMITTEE

Permission to conduct this study was issued by Kaunas Regional Biomedical Research Ethics Committee (Protocol No.: BEC-MF-89).

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ABBREVIATIONS

CBC – Complete blood count CCF – Craniofacial fracture CRP – C-reactive protein

ESR – Erythrocyte sedimentation rate F – Female

GCS – Glasgow Coma Scale h – Hour

ICD – International Classification of Disease IQR - Interquartile range

ISS – Injury Severity Score kg – Kilogram

LIS – Licencijų informacinė sistema LLF – Lower limb fracture

LSMUL KK – Lithuanian University of Health Sciences Hospital Kauno Klinikos m – Meter

mmHg – Millimeter of mercury M – Male

MVC – Motor vehicle collision n – Number

OT – Orthopedics and Traumatology PED – Pediatric Emergency Department PTS – Pediatric Trauma Score

RR – Respiratory rate

RTS – Revised Trauma Score SBP – Systolic blood pressure SD – Standard deviation TBI – Traumatic brain injury

TNAS IS – Traumų ir nelaimingų atsitikimų stebėsenos sistema ULF – Upper limb fracture

US – Ultrasound y – year

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INTRODUCTION

Background: Pediatric trauma is a serious health issue that is being addressed through prevention, however, it remains a global public health problem. Worldwide it is the most common reason for showing up to the Pediatric Emergency Department (PED) and leads to the most deaths in the children population [1]. Injury risk is highly affected by age, gender, cognitive functions, and environment. All male children despite their age group have higher injury and mortality rates, perhaps in part because of their more aggressive behavior and higher exposure to contact sports. In the infant and toddler age groups, falls are the most common cause of severe injury, whereas bicycle-related accidents, with or without the interaction of motor vehicles, are the main culprits for injury of older children and adolescents. The home environment is the next most common scene of pediatric injury. Approximately a third of significant traumatic injuries occur as the result of accidents in the very environment that should be the most sheltering and nurturing to children.

Practical use: In Lithuania prior 2015 there have been no studies dedicated to the epidemiology of pediatric trauma in local hospitals. However, after the launch of the Injury and Accident Monitoring Information System (Traumų ir nelaimingų atsitikimų stebėsenos

informacinė sistema (TNAS IS)) the first report of pediatric trauma causes, and incidence

summarized 83113 PED visits in 2015 [2]. In this study, we aim to analyze newer epidemiological data of pediatric trauma in Lithuanian University of Health Sciences Hospital Kauno Klinikos (LSMUL KK) and compare our data to previous local and international studies. The findings can be used to issue curated practical recommendations in preventing injuries for the pediatric population in Lithuania.

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AIMS AND OBJECTIVES

Aim: To investigate pediatric traumas that occurred between 2018 January 1st_{and 2019} December 31st_{in the Pediatric Emergency Department of Lithuanian University of Health} Sciences Hospital Kauno Klinikos and compare the results to similar studies performed in other countries.

Objectives:

1. To analyze and compare the number of pediatric trauma patients that visited PED in the years 2018 and 2019.

2. To analyze and compare trauma patient demographics, such as age, gender; to analyze period of arrival.

3. To analyze and compare trauma types between different age groups.

4. To analyze and compare fracture incidence, type of referral, trauma circumstances (such as environment, etc.), mechanism, and treatment options.

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1. LITERATURE REVIEW

1.1 Significance of pediatric trauma

Pediatric injury is a major public health problem and is one of the leading causes of children‘s death globally [3]. Pediatric trauma makes up to over 20% of all complaints when referring to the pediatric emergency department (PED) [4,5]. Annually countries spend about 87 billion dollars on healthcare to pediatric patients reporting for trauma [6].

1.2 Childhood injury classification

Childhood injuries can be classified by intent, trauma severity, and mechanism. Classification by intent has two categories following unintentional and intentional injuries. Injuries sustained during a traffic accident, sports, after a fall or collision with an object are classified under the unintentional injury category. In the United States, unintentional injury is the most common cause of childhood death, representing 40% of all deaths in children 1-18 years of age annually [7]. The second category is intentional injuries, which include violent acts, self-harm, or suicide [3].

While analyzing trauma severity there are a few scoring systems used by different hospitals such as Injury Severity Score (ISS) (Table 1), Pediatric Trauma Score (PTS) (Table 2), or Revised Trauma Score (RTS) (Table 3) – these systems mainly reflect the results of trauma and not the mechanism. ISS mainly focuses on an anatomical injury site for patients that sustained polytrauma. PTS helps triage patients in a limited resource environment predicting injury with a high mortality rate. RTS measures the functional consequences of an injury using the Glasgow Coma Scale (GKS), systolic blood pressure (SBP), and respiratory rate (RR).

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11 Table 1. Injury severity score (ISS)

Adapted from: Khak et al. Damage Control Orthopedics in Multitrauma Patients: A Pediatric Case Presentation and Literature Review, 2016 [8]

Table 2. Pediatric Trauma Score (RTS)

Adapted from: Loy, M. Jocelyn. Pediatric Trauma and Anesthesia, 2015 [9] kg – kilograms; mmHg – millimeter of mercury

Table 3. Revised Trauma Score (RTS)

Adapted from: Ringdal et al. The Utstein template for uniform reporting of data following major trauma: a joint revision by SCANTEM, TARN, DGU-TR and RITG, 2008 [10]

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12 To better understand the traumatic event, a physician needs to know if the injury was caused by low or by high energy force. Low energy traumas are described as falling from a standing height or a low height and collisions with slowly moving objects. On the other hand, high-energy traumas are caused by a force (traffic injuries, crush injuries, falling from heights), affecting the body surface, and transferring high amounts of kinetic energy, which results in great damage to the tissue [11]. However, in clinical practice, it is easier to define two main groups: minor and major trauma. Examples of minor trauma are shallow cuts or abrasions, sprains or muscle strains, dislocations, bruises, skin lesions, and minor low-degree burns. The main mechanisms for sustaining minor traumas include low falls – from a child‘s height for a younger child and below 2 meters for an adolescent [12], accidental contact with an inanimate object, and sports [13-15]. These types of minor traumas do not usually require admission to the hospital and are managed in a few hours. On the contrary, major trauma can potentially lead to prolonged or permanent loss of function and even death. These are considered high energy [17] and include polytrauma, fractures, any type of head injury, deep lacerations, and severe burns. In the PED, major traumas are often more common than minor (49.6 – 66% vs. 34 – 50.4% respectively) [13-15,17]. The management of major pediatric traumas is more difficult and must be approached with a systematic plan of action [18]. Most common childhood traumas according to Sweden’s 10-year study were contusions (24.1%), followed by open wounds/abrasions (20.6%), fractures (19.2%), and sprains (17%) [13]. Iran’s study confirmed, that in pediatric patients, fractures make up to one-fifth of all injuries (21%) [17].

1.3 Pediatric trauma causes

Most of the epidemiological studies report that falls are the number one source of injury in children [1,13,17,19-22]. Falling is a part of a child’s development and usually has no severe long-lasting effects. Falling can be categorized into two main groups, such as falls on the same level and falls from a certain height [23]. However, there has been no unified system that separates low from high falls [7,12, 24]. Risk factors for fall injury include age younger than six years, low socioeconomic status, and male sex [7].Although, low falls compile into a substantial part of about 75% of all fall cases, higher falls from planes onto different surfaces, more commonly result in a higher percentage of sustained traumatic

injuries, such as extremity fractures, contusions, and deep wounds [12,23]. A Canadian

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13 injuries and that falls were responsible for 90% of all head injuries seen in the PED. The most common mechanisms of falls in that study were from furniture, falls from car seats, falls downstairs with or without an infant walker, and those caused by being dropped by an older person [25]. However, though falling makes up the biggest part of pediatric trauma reasons there are other groups such as road traffic accidents or motor vehicle collisions (MVC), bicycle/scooter accidents, unintentional injuries due to inanimate objects, and

sports injuries caused by contact with a sports equipment (e.g., ball) or a teammate

[1,13,17,19-22]. Road traffic accidents with a child as a car occupant or a pedestrian predominantly causes head and neck injuries, followed by lower limb and thoracoabdominal injuries [26,27]. In the United States, MVC’s are a leading cause of death in children under 14 years of age [27]. Besides motor vehicles, bicycle-related injuries come in a second place, eliciting contusions/abrasions, lacerations, and fractures. Further analysis of bicycle-related injuries shows that falling from a bicycle or a collision with an object while riding, results in upper (36%) and lower (25%) extremity injuries, followed by face (15.4%) and head and neck injuries (14.9%) [28]. Sports-related injuries sustained during after-class activities are most frequently seen in the <12 age range group (~35%) and is one of the leading reasons for causing pediatric fractures. A retrospective Chinese study reported that the most common fracture sites were in the upper extremity – radius (24.9%), humerus (20.7%), and ulna (20.5%), followed by lower extremity – tibia (13.7%) and femur (9%) [29].

1.4 Trauma dependence on gender and age

Globally, studies report that males make up about two-thirds of all pediatric trauma patients (57.5 – 73.8%), which is likely to be a consequence of their higher risk-taking [1,13,17,19,20,30-33]. According to Australia’s results from a 10-year retrospective study, the most common age groups, that needed hospitalization after sustaining a traumatic injury, were as following - 11-16 years – 41%, 1-5 years – 30.9%, 6-10 years – 24.6% and <1 – 3.5% [1]. An international multicenter 1-month long study published slightly different results concluding following: 1-5 years – 39%, 6-10 years – 31%, 11-17 years – 28%, <1 year – 2% [14]. Iran, with data from one year, reported that 5-12 age group accounted for 33.2%,13-18 age group for 31%, 1-5 age group for 15% and <1 age group – 6% [17]. USA’s 9-year study of pediatric trauma tendencies showed that 1–4-year-olds made up to 24.2%, 10-15-year-olds – 17.8%, 5-9-year-olds – 15.9% and <1 – 9.6% of all pediatric trauma cases [34]. These numbers show that a specific age group does not imply a lower or higher risk for sustaining traumatic injuries. It is more important to know the trends in your own country than the international data because similar trauma tendencies usually indicate

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14 analogous socioeconomic, environmental, and cultural factors, that construct the foundation of the subject [23].

1.5 Pediatric peculiarities in traumatic injury patterns

Children are not just a smaller version of an adult as they have differences in their anatomy and physiology. Infants and small children have a proportionally bigger head and a different gravity center; thus, head injuries are more common than in older children and adults [35]. Anatomical structures of the cranium, such as sutures and fontanelles develop with time. As a result, infants (<1 year) tend to sustain more severe head injuries than toddlers (1-4 years) – 71% and 29% respectively. Skull fractures are more common in younger children due to a fall [36]. The musculoskeletal system in children is always growing and is stronger than in an adult’s body. The long bones of children are less dense and more porous than the long bones of the adults but have a significantly stronger periosteum. This quality allows to respond to mechanical stress by bowing and buckling rather than fracturing fully as in adults [37]. This means, that upon a traumatic event, a child’s ligaments and bones can tolerate a bigger mechanical force and can lead to injuries such as sprains, dislocations, and greenstick fractures more frequently than ligament ruptures and adult-like fractures (Figure 1). However, since bones are growing during the first two decades of a child’s life any fractures that damage the growth plates can cause function and mobility problems in the future [32]. This leads to the importance of appropriate surgical treatment when the fractures include physis – no directs screws and plates where the epiphyseal plate is, to prevent premature closure. In the pediatric population, the most typical location for fractures is in the upper limb (43-69%), usually of the humerus and forearm, followed by lower limb (24-42%) and craniofacial fractures (4-22%) [12,19,22,33,38]. Older children and adolescents tend to participate in various sports-related activities, thus leading to a higher percentage of traumas during collisions with other people or objects [38].

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15 Figure 1. Greenstick fracture in a pediatric patient’s fibula.

Red circle – fracture of the fibula. Adapted from: Muscat J (2014) Department of Paediatric X-ray and Ultrasound, Royal Alexandra Children's Hospital, BSUH NHS Trust, Brighton, UK DOI: 10.1594/ecr2014/C-2193

A child’s body is more compact in comparison to an adult’s, chest and abdominal cavities are in close proximity, hence, any high-energy trauma usually causes multisystemic injuries in the affected area [39]. For example, blunt thoracic trauma may not cause a rib fracture, bruising or laceration, but can result in lung contusion or heart commotion [40]. The child’s abdomen is relatively larger compared with the rest of the trunk, has underdeveloped musculature, and has relatively larger intra-abdominal organs, which predisposes to solid organ injuries in blunt abdominal trauma. Intraabdominal injury takes third place as a leading cause of pediatric trauma mortality with most injuries sustained by a blunt mechanism (85%), usually as a result of a motor vehicle accident [41].

1.6 Fracture treatment

Pediatric patients, that overall need admission for sustained traumatic injury, make up to 12 – 19% of all cases [14,17,31]. Those that require an operative fracture treatment compile to about 22 – 49% of all cases [12,20,33,42]. The most common indications for surgical treatment in pediatric patients are displaced physeal and intra-articular fractures (Salter-Harris classification, type III and IV, Figure 2), unstable or open fractures, multiple injuries, failure of a closed fracture reduction in adolescents.

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16 Figure 2. Salter-Harris classification

Adapted from: https://epomedicine.com/medical-students/salter-harris-classification-physeal-fracture-mnemonic/

The treatment aims to obtain anatomical alignment and relative stability [40]. The average time for staying in the hospital for a major traumatic injury (head trauma, chest or abdominal trauma, fractures) is reported to be 4-7 days [20,22,43]. However, it is important to comprehend the severity and type of injury – head and spine injuries require a longer monitoring time than extremity fracture postsurgical observation [22,43]. Minor injuries are generally treated in the PED and include pain relief, wound cleaning, and dressing, suturing if necessary, plaster casts for sprains/dislocations [44].

1.7 Differential diagnoses while treating an injured child

Children presenting to the PED with musculoskeletal symptoms is a common occurrence accounting for about a fifth of all cases [45]. However, although traumatic injury takes the first place in etiology, other musculoskeletal conditions should be considered if there was no known trauma, or the diagnosis is not clear after clinical examination and radiological tests (Table 4). All age groups are susceptible to septic arthritis after an injury that disrupts the skin barrier or reactive arthritis and transient synovitis after a viral infection. These patients can present with joint pain, redness, swelling, difficulty to freely use the joint, and fever. To confirm the diagnosis, complete blood count (CBC), C reactive protein (CRP), and an ultrasound (US) of the affected joint should be performed [46]. Another group of diseases that can lead to musculoskeletal symptoms is rheumatologic disorders, of which the most common is juvenile idiopathic arthritis, which affects all age groups and can present in different forms, from peripheral joint inflammation (pain, redness, swelling), rashes to uveitis and hepatosplenomegaly [45]. If a rheumatological disorder is suspected, CBC, CRP, ESR (erythrocyte sedimentation rate), and joint and the abdominal US should be performed with the referral to a further investigation by a pediatric

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17 rheumatologist. During adolescence children usually experience a few growth spurs, which can lead to developing a painful bump on the tibial tuberosity (Osgood-Schlatter disease) or a painful heel caused by the Achilles tendon pulling on the apophysis of the calcaneus [47]. Oncology is another field that should be considered in children with extremity pain. Most nonmalignant bone tumors are asymptomatic and are discovered incidentally during evaluation for trauma or another condition. However, when they are symptomatic, these tumors may present with localized pain, swelling, deformity, or pathologic fracture. In most cases, the differential diagnosis of these lesions can be narrowed based upon the age of the child, the involved bone, the location of the lesion within the bone, and other general radiographic characteristics [48]. Malignant bone tumors, such as osteosarcomas are the most common primary malignancy of bone in children and adolescents and the fifth most common malignancy among adolescents and young adults aged 15 to 19, thus, it should not be omitted while considering the causes of musculoskeletal pain in day-to-day clinical practice [49].

Table 4. Differential diagnoses for musculoskeletal pain in the pediatric population

Age <3 y 3-5 y 6-10 y 11-18 y Infections Septic arthritis + + + + Reactive arthritis + + + + Transient synovitis + + + Bacterial osteomyelitis + + + Rheumatology

Benign hypermobility syndrome + +

Juvenile idiopathic arthritis + + + +

Juvenile spondyloarthropathy + +

Oncology

Benign bone tumor + + + +

Solid tumor + +

Pediatric orthopedics

Osgood – Schlatter disease +

Severs disease + +

Legg – Calve – Perthes disease + +

Kohler’s disease + +

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2. RESEARCH METHODOLOGY

2.1 Patient data

The research was conducted in LSMU KK Pediatric emergency department (PED) with the permission from LSMU Bioethics committee.

This study included all children aged 0-18 years old, that sustained a traumatic injury from 1st_{of January 2018 to 31}st_{of December 2019.}

A retrospective analysis was conducted using electronical record data system (LIS). The trauma categorization included all codes of S0-S99 from the ICD-10-AM classification. The primary data selection included the patient’s gender, age, date of the accident, the type of traumatic injury. Additional data of type of arrival (ambulance or individual), location of the incident (home, kindergarten/school, sports training, road accident) mechanism of injury (accident, fall, violence), treatment in the PED (plaster/splint, suturing), and hospitalization (further examination, surgery, length of hospital stay) was collected manually of pediatric patients that sustained a bone fracture.

A total of 19923 records were analyzed for primary statistics. During additional data collection for patients that sustained a bone fracture, exclusion criteria included: absence of data and revisit. Out of 4958 fracture patients, 781 records lacked information, and 119 were revisits. After eliminating 900 patients, the final analysis of pediatric patients with fracture diagnosis was conducted for 4058 cases.

All children diagnosed with a traumatic injury were classified into 5 age groups: < 1-year-old, 1 – 5 years old, 6 – 10 years old, 11 – 14 years old, and 15 – 18 years old.

2.2 Statistical analysis

Primary statistical analysis was performed using Microsoft Excel 2019 and IBM SPSS Statistics version 26.0 software for Windows. Additional investigations were made by manually analyzing each patient’s records.

Descriptive statistics methods were used as following: average or median with standard deviation (SD) or interquartile range (IQR). The descriptive statistical methods were the T criterion for calculating pairs of samples and the Chi-square test. A p-value of <0.05 was selected to determine statistical significance.

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3. RESULTS AND DISCUSSION

3.1 Demographics

A total of 19923 case records of pediatric patients referred to a PED between the year 2018 and 2019 due to a traumatic event were analyzed with 9698 and 10225 visits during 2018 and 2019 respectively. The difference in patient visits was statistically significant (p<0.05). The findings suggest that PED of our hospital serves a remarkably high number of pediatric patients during its 24-hour non-stop workdays. Also, since this department is one of the two trauma centers for children in Lithuania, it offers a multidisciplinary approach if the diagnosis is unclear. In our study, the mean age of all children was 8.7 ± 4.9 years. A Pan-African Pediatric Surgery Association’s study conducted in 2015 with 15 participating countries concluded it to be 7 years [14]. We found that in both time frames, most frequent trauma patients were aged from 1 to 14 years (81.8% from all cases) (p<0.05). The reason for this could be the growing everyday activity starting from learning to walk, learning to ride a bicycle, playing sports games, etc. Comparing 2018 and 2019, no statistical significance was observed in gender groups (p>0.05). 59.9% of all the patients were male (n=11941), which is similar with other authors’ reports [1,13,17,19,20,30-33]. The correlation between gender and age was significant (p<0.001). This trend is seen globally, meaning that in adolescence male patients tend to take more risks during sports activities and participate in dangerous ventures on daily basis. Male and female trauma patients’ distribution according to age is shown in Table 5.

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20 Table 5. Age distribution between female and male trauma patients in 2018 and 2019

Variable <1y 1-5y 6-10y 11-14y 15-18y Total

Male n (%) 2018 173 1503 1608 1593 928 5805 2019 170 1577 1755 1624 1010 6136 Total 343 (2.9) 3080 (25.8) 3363 (28.2) 3217 (26.9) 1938 (16.2) 11941 (100) Female n (%) 2018 158 1169 1134 907 525 3893 2019 154 1165 1210 1050 510 4089 Total 312 (3.9) 2334 (29.2) 2344 (29.4) 1957 (24.5) 1035 (13) 7982 (100) Total n (%) 2018 331 2672 2742 2500 1453 9698 2019 324 2742 2965 2674 1520 10225 Total 655 (3.3) 5414 (27.2) 5707 (28.6) 5174 (26) 2973 (14.9) 19923 (100)

n – number of patients; y – years

We analyzed the seasonal distribution and found that the biggest incidence of PED visits in both time frames was during spring (31% and 29.5% respectively), especially May (12.3% and 11.5% respectively). In comparison, summer seasons were 25% and 26%, autumn seasons were 25.7% and 25.4% followed by winter – 18.4% and 19% respectively (Figure 3). Rutkowska et al. made similar observations, which concluded that traumatic injuries sustained during spring and autumn seasons were the most common [50]. This is not surprising, as those are the best months for outdoor activities and sports. It is also the start of spring-summer holidays when children are not doing sedentary educational work, but spend more time playing inside and outside.

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21 Figure 3. Monthly distribution of PED patients with traumatic injury in 2018 and 2019

3.2 All trauma cases

3.2.1 Traumatic injury location

The most common injury locations during both periods were upper limb (28%) and lower limb (27.3%) injuries, such as bruising, skin laceration, sprain, and dislocation, followed by superficial head injuries (14%). Studies, performed in the USA, China, Sweden and Iran showed similar trends [12,19,22,33,38]. Having these results, we can presume, that children share comparable behavior and habits during daily activities across the world. The male and female populations distributed similarly with three leading injury localizations. For males it being a lower limb injury (27.3%), upper limb injury (26.2%), and superficial head injury (13.9%). Females had a slightly different, but not significant (p>0.05) dispersion of upper limb injury (30.8%), lower limb injury (27.3%), and superficial head injury (14%). The more thorough explanation of the possible trends will be made later on. The detailed analysis of pediatric trauma cases according to year and gender is shown in Table 6.

0 200 400 600 800 1000 1200 2018 2019 Co u n t Month 1 2 3 4 5 6 7 8 9 10 11 12

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22 Table 6. Traumatic injury localization according to year and gender

Injury location 2018 n (%) 2019 n (%) M n (%) F n (%) Total n (%)

Head injury (superficial) 1139 (14.9) 1041 (13) 1278 (13.9) 902 (14) 2180 (14) Head wound 560 (7.3) 634 (8) 814 (8.9) 380 (5.9) 1194 (7.6) Eye injury 453 (5.9) 453 (5.6) 581 (6.3) 325 (5) 906 (5.8)

Nose, ear injury 275 (3.6) 275 (3.5) 343 (3.7) 207 (3.2) 550 (3.5) Face injury 538 (7) 586 (7.4) 677 (7.4) 447 (6.9) 1124 (7.2) TBI* 110 (1.4) 100 (1.2) 123 (1.3) 87 (1.4) 210 (1.3)

Upper limb injury** 2193 (28.6) 2196 (27.6) 2406 (26.2) 1983 (30.9) 4389 (28.2)

Lower limb injury** 2015 (26.3) 2257 (28.4) 2511 (27.4) 1761 (27.3) 4272 (27.3)

Internal organ injury 16 (0.2) 12 (0.2) 20 (0.2) 8 (0.1) 28 (0.2)

Neck, chest, abdomen, back soft tissue injury

364 (4.8) 407 (5.1) 428 (4.7) 343 (5.3) 771 (4.9) Total 7663 7961 9181 6443 15624 n – number of patients; M – male; F – female ; * Traumatic brain injury; ** Fractures excluded

3.2.2 Traumatic fractures

During the analyzed time frame, there were a total of 4058 fractures diagnoses. In 2018 there were 1831 cases, which accounted for 18.9% of all traumatic injuries and 2227 cases in 2019, accounting for 21.8% respectively. This is a clear tendency of increasing fracture cases in children. Meanwhile, Chen et al. did a retrospective epidemiological study in 2015 of 512 187 patients with traumatic fractures and found that pediatric fractures compiled to a total of 15.8% [51]. The noted increase in our study could be due to different causes. First, LSMUL KK PED is the leading pediatric center for all trauma cases, thus the

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23 growing count of fractures and trauma cases in general could be due to increased referral from regional hospitals or ambulatory settings. However, a broader analysis for upcoming years (2020, 2021 etc.) could only lead to a better conclusion and picture of trauma situation of pediatric patients. Second, there is a tendency that parents come to PED faster, more X-rays are performed and some of the fractures are diagnosed in a child with minor symptoms. Thus, the partial increase could be due to parents’ fear and precaution to come early and physician’s precaution in performing more X-rays. Definitely, the third factor could be increased pediatric traumatism despite previously mentioned reasons. However, those growing numbers can only be explained as the result of multiple factors.

In our study males comprised 64.3% of all patients. We found that the most common fracture site that made up 2/3 of all fractures was in the upper limb in both males and females (Table 7), which matched the results of Naranje et al.’s epidemiological study [52]. As previously mentioned, males are more commonly involved in contact sports, outdoor activities or fights. During most of these activities, falling is the biggest factor in sustaining an upper limb injury and may correspond with the consequences of insufficient training on how to correctly land on the ground.

Table 7. Fracture location according to year and gender Fracture location 2018 n (%) M n (%) F n (%) 2019 n (%) M n (%) F n (%) Total n (%) Craniofacial 85 (4.6) 59 (5) 26 (4) 105 (4.7) 72 (5) 33 (4.1) 190 (4.7) Spinal 12 (0.7) 4 (0.3) 8 (1.2) 16 (0.7) 7 (0.5) 9 (1.1) 28 (0.7) Sternum, ribs 5 (0.3) 3 (0.3) 2 (0.3) 9 (0.4) 6 (0.5) 3 (0.4) 14 (0.3) Pelvis 6 (0.3) 4 (0.3) 2 (0.3) 8 (0.4) 7 (0.5) 1 (0.1) 14 (0.3) Upper limb 1309 (71.5) 849 (71.8) 460 (70.9) 1542 (69.2) 996 (69.8) 546 (68.3) 2851 (70.3) Lower limb 414 (22.6) 263 (22.3) 151 (23.3) 547 (24.6) 339 (23.8) 208 (26) 961 (23.7) Total 1831 1182 649 2227 1427 800 4058 n – number of patients; M – male, F – female

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24 3.2.3 Traumatic injuries according to age

To further understand the incidence of traumatic injury and its association with a specific age group, we systematized the data separately for 2018 and 2019. Both tables (Table 8 and 9) reveal that infants (n=655) had the highest prevalence of sustaining a superficial head injury (74%). Roda et al. reported that in infants 57.4% of sustained fractures were of the skull [53]. These results are not surprising, as infants have a proportionally bigger head, than toddlers or teenagers. Furthermore, their neurological system and motor skills are not yet fully developed, thus leading to frequent loss of balance and falls. However, the total number of cases is small, because children <1 years-old are constantly under parental supervision, which prevents most of the more serious injuries.

We found that for toddlers (n=5414) aged 1-5 years old most frequent injuries were of the head (30%), upper limb (17.8%), lower limb (11.8%), and face (11.4%). For this age group, radiologically confirmed fracture diagnoses consisted of 13.8%. The most common fractures were in the forearm (27.7%). Furthermore, Flavin et al. reported that the most common injury type in this age group was open wounds [15]. Toddlers in hindsight are extremely mobile and curious. For this reason, most injuries occur while playing, reaching for an object, climbing, or descending the stairs. During this period children also spend a lot of time playing in the parks and playgrounds, however these settings tend to have relatively dangerous structures, that are not adapted for small children, such as high monkey bars, rope swings and high slides [54].

Young children aged 6-10 years old (n=5707) had the highest incidence of sustained traumatic injuries (28.6%). The most commonly seen ones were lower limb injuries, followed by upper limb and superficial head injuries. This age group had 1395 (24.4%) radiologically confirmed fracture diagnoses, with the most common ones being of the forearm (37.8%) and hand (24.4%). Parket al. reported similar findings of most fractures being in the distal radius [55]. These results could suggest that children in this age group are sufficiently more independent, than previously discussed age groups, thus need less supervision from their parents. This behavior leads to children spending most of their free time after school playing with friends, participating in sports, riding bicycles and scooters in the park or near busy streets unsupervised. Children tend to overestimate their physical abilities during this period, so activities such as climbing trees or playing on high objects also increase the risk of falling. Thus, these dangerous pastimes could be leading to an increased number of traumatic injuries, seen in this age group particularly.

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25 11-14-year old group (n=5174) most frequently had lower (27.8%) and upper (27.2%) limb injuries. Fractures accounted for 25.6%, most commonly of the hand (38.3%). According to korean study, the highest incidence of fractures in this age group were of the distal radius [55]. During this period of their childhood children are starting their pubertal growth spurt, which in perspective puts a lot of new information on child’s body’s ability to process these new changes. An average of 10-15 cm growth spurt for a child is not a problem in daily life, however when participating in more strenuous activities, it can cause a few difficulties, such as more frequent falls and overuse injuries. As the limbs lengthen, the body needs time to adapt to the changed movements and coordination, which may lead to more frequent injuries not due to carelessness, but due to the longer processes of physiological adaptation [56].

Lastly, adolescents aged 15-18 years old made up 14.9% (n=2973). Recurrent injuries were of the lower (29.9%) and upper (28.2%) limbs, which correspond with the results of McAdams et al’s study [28]. Fractures were diagnosed for 18.8% of the patients, most frequently of the hand (41.3%). As the child comes closer to adulthood, generally we can see some behavioral changes, such as use of various substances, more frequent fights, and careless actions with the need to show off in front of others, which result in mostly extremity injuries.

Table 8. Injury localization according to children’s age in 2018

Injury localization <1 y n (%) 1-5 y n (%) 6-10 y n (%) 11-14 y n (%) 15-18 y n (%)

Soft tissue injury Head injury

(superficial)

249 (79.3) 458 (20) 226 (10.9) 118 (6.5) 88 (7.5)

Head wound 4 (1.3) 339 (14.8) 165 (7.9) 29 (1.6) 23 (2)

Eye injury 11 (3.5) 181 (7.9) 127 (6.2) 74 (4.1) 60 (5.1)

Nose, ear injury 5 (1.6) 116 (5.1) 65 (3.2) 44 (2.4) 45 (3.8)

Face injury 19 (6) 292 (12.7) 154 (7.5) 43 (2.4) 30 (2.6)

TBI* 3 (1) 30 (1.3) 26 (1.3) 29 (1.6) 22 (1.9)

Upper limb injury 15 (4.8) 486 (21.2) 553 (26.8) 690 (37.9) 449 (38.3)

Lower limb injury 6 (1.9) 320 (14) 622 (30.2) 695 (38.1) 372 (31.7)

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26 Neck, chest, abdomen, back 2 (0.6) 68 (2.9) 120 (5.8) 93 (5) 81 (6.9) Total 314 2293 2062 1822 1172 Fractures Craniofacial 9 (64.4) 19 (5.7) 18 (2.9) 14 (2.3) 25 (9.3) Spinal 0 0 3 (0.5) 5 (0.8) 4 (1.5) Sternum, ribs 0 0 2 (0.3) 3 (0.5) 0 Pelvis 0 0 2 (0.3) 2 (0.3) 2 (0.7) Clavicle, scapula 1 (7.1) 45 (13.5) 20 (3.3) 13 (2.2) 5 (1.9) Humerus 0 62 (18.6) 78 (12.8) 26 (4.3) 8 (3) Forearm 0 94 (28) 238 (39) 159 (26.3) 39 (14.6) Hand 0 44 (13.2) 144 (23.6) 223 (37) 111 (41.4) Femur, patella 1 (7.1) 12 (3.6) 7 (1.1) 14 (2.3) 8 (3) Tibia 2 (14.3) 25 (7.5) 11 (1.8) 32 (5.3) 19 (7.1) Fibula 0 8 (2.4) 27 (4.4) 18 (3) 23 (8.6) Foot 1 (7.1) 25 (7.5) 61 (10) 95 (15.7) 24 (8.9) Total 14 334 611 604 268 *Traumatic brain injury; y – years; n – number of patients

Table 9. Injury localization according to children’s age in 2019 Injury localization <1 y n (%) 1-5 y n (%) 6-10 y n (%) 11-14 y n (%) 15-18 y n (%)

Soft tissue injury

Head injury (superficial) 208 (68.6) 445 (19.3) 203 (9.4) 109 (5.6) 76 (6.2) Head wound 3 (1) 379 (16.4) 176 (8.1) 42 (2.2) 34 (2.8) Eye injury 13 (4.3) 180 (7.8) 142 (6.5) 66 (3.4) 52 (4.2)

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27

Face injury 26 (8.6) 325 (14) 141 (6.5) 58 (3) 36 (2.9)

TBI* 9 (3) 18 (0.8) 25 (1.2) 30 (1.5) 18 (1.5)

Upper limb injury 19 (6.2) 480 (20.8)

587 (27.1)

720 (37) 390 (31.6)

Lower limb injury 1 (0.3) 318 (13.7) 678 (31.2) 744 (38.3) 516 (41.9)

Internal organ injury 0 2 (0.1) 4 (0.1) 2 (0.1) 4 (0.3)

Neck, chest, abdomen, back 9 (3) 79 (3.4) 139 (6.4) 112 (5.8) 68 (5.5) Total 303 2312 2170 1944 1232 Fractures Craniofacial 6 (35.2) 25 (6.1) 21 (2.7) 28 (3.9) 25 (8.6) Spinal 0 0 4 (0.5) 2 (0.3) 8 (2.7) Sternum, ribs 0 1 (0.2) 1 (0.1) 4 (0.6) 3 (1) Pelvis 0 1 (0.2) 1 (0.1) 4 (0.6) 2 (0.8) Clavicle, scapula 2 (11.8) 49 (11.9) 30 (3.8) 21 (2.9) 10 (3.4) Humerus 2 (11.8) 74 (18) 86 (11) 26 (3.6) 7 (2.4) Forearm 3 (17.6) 112 (27.2) 290 (37) 169 (23.4) 41 (14) Hand 0 51 (12.4) 197 (25.2) 258 (35.7) 120 (41) Femur, patella 2 (11.8) 7 (1.7) 7 (0.9) 13 (1.8) 2 (0.8) Tibia 2 (11.8) 41 (9.9) 23 (2.9) 37 (5.1) 17 (5.8) Fibula 0 12 (2.9) 38 (4.8) 38 (5.2) 21 (7.2) Foot 0 39 (9.5) 86 (11) 122 (16.9) 36 (12.3) Total 17 412 784 722 292 *Traumatic brain injury; y – years; n – number of patients

3.3 Fractures

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28 During the study period, patients who experienced a fracture were more likely to enter the PED themselves (88%) than calling an ambulance (Table 10). The time between the initial trauma and the arrival to the PED was generally under 24 hours (81.4%). Korea’s study showed that parents tend to bring the child themselves, then call an ambulance (5.2%) [31]. This could be explained as most of the traumas do happen in home environment or the home outskirts where parents are present or not far away. Thus, it is faster for parents to bring the child to PED than to call an ambulance and wait for it to come. Most serious traumas (traffic accidents, trauma due to drowning etc.) if a child is unconscious or a profound bleeding is observed is always considered differently than minor injuries. However, more studies are necessary to clarify parents’ priority of transportation.

Table 10. Characteristics of arrival time and transport method of PED patients with fracture diagnosis Characteristics 2018 n (%) 2019 n (%) Total n (%) Way of arrival Ambulance 225 (12.3) 253 (11.4) 478 (11.8) Themselves 1606 (87.7) 1974 (88.6) 3580 (88.2)

Time after injury

<24 h 1493 (81.6) 1810 (81.3) 3303 (81.4)

24-48 h 209 (11.4) 265 (11.9) 474 (11.7)

48-72 h 52 (2.8) 79 (3.5) 131 (3.2)

>72 h 77 (4.2) 73 (3.3) 150 (3.7)

Total 1831 2227 4058 h – hour; n – number of patients

3.3.2 Fracture etiology

The most common places in which the patient experienced fracture were home environment (house, yard, playground, street) (69.2%), followed by sports (15.8%), and kindergarten/school (13.2%) (Table 11). Motor vehicle collision (MVC) and interpersonal violence related injuries accounted for 1.1% and 0.7% respectively. Akbaryan et al. reported

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29 similar results where 63.5% of traumatic injuries happened at home [17]. For patients that arrived with a fracture, the most common mechanism of injury was a fall (43.3%). More than a half of children fell from their own height (52.2%), others had a low fall (<1 m) between two different planes (36.3%). Hedstrom et al. found that 47% of fractures were a consequence of a fall, with 24% happening on the same plane and 23% between planes [13]. Rutkowska et al. reported that ground-level falls were responsible for 49% of sustained extremity injuries [50]. These results lead to the assumption, that children spend a big amount of time in the home environment, which may not always be the safest option. One of the biggest safety hazards is easily accessible stairs indoors and outside. That with the added carelessness and inadequate choice of speed often ends in sustaining a limb injury with a possibility of head trauma. In addition to our previous discussion, younger children tend to be more curious and active, thus injuries sustained from tripping, colliding with objects or playing amongst themselves are very common.

Table 11. The etiology characteristics of pediatric fractures

Variable 2018 n (%) 2019 n (%) Total n (%) Location characteristics Home 1253 (68.4) 1555 (69.9) 2808 (69.2) Kindergarten/school 254 (13.9) 282 (12.7) 536 (13.2) Sports 294 (16) 348 (15.6) 642 (15.8) MVC* 16 (0.9) 29 (1.3) 45 (1.1) Violence 14 (0.8) 13 (0.5) 27 (0.7) Total 1831 2227 4058 Fall characteristics same plane** between planes: 448 (54.5) 469 (50.2) 917 (52.2) <1 m 264 (32.1) 374 (40) 638 (36.3) 1-2 m 98 (11.9) 79 (8.5) 177 (10.1) 2-4 m 8 (1) 6 (0.6) 14 (0.8) >4 m 4 (0.5) 7 (0.7) 11 (0.6) Total 822 935 1757

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30 n – number of patients; m – meter; *MVC – motor vehicle collision; **Fell down, tripped, was pushed

3.3.3 Fracture treatment and admission

For patients that sustained a radiologically confirmed fracture, 68% of all visits resulted in putting on a cast/brace and the patient being discharged afterwards (Table 12). After being examined, less than 8% were sent home without any specific treatment, with a conclusion of a fracture that needed no additional treatment (nose, teeth, ribs). A quarter of all the visits resulted in the patient being admitted to a ward for monitoring or further surgical treatment. The most common department was Pediatric Orthopedics and traumatology (94.2%). Out of all admitted pediatric patients, 92.4% received surgical treatment of fracture reduction. Wang et al. reported that admission for traumatic fracture accounted for about 40% of all visits to the PED [33]. Although pediatric fracture nonunion is rare (<1%), the risk increases with the child getting closer to adulthood. The risk factors associated with fracture nonunion are increasing age, male gender, high body-mass index, severe fracture (e.g., open fracture, multiple fractures), and tobacco smoking (all, p< 0.0001). The bones that are more likely to go to nonunion in children are tibia/fibula, femoral neck, and scaphoid [57]. In our study less than 8% were monitored for additional symptoms, usually after having sustained a craniofacial fracture that did not need surgical treatment. The most frequent admission lengths calculated for patients with a fracture diagnosis were 1-day (35.2%) and 2-3 days (35.2%), while Oliver et al. in a retrospective 10-year study reported it to be 3.6 days [20]. The most likely explanation for the patient's stay being an average of up to 3 days is that the first day is usually used to prepare for the surgery and/or have it. The following 1-2 days are intended to ensure that there is no postoperative swelling, nerve or vascular damage and that the incisions show no sign of infection [40].

Table 12. Characteristics of treatment, admission length, and department of PED patients with fracture diagnosis

Variable 2018 n (%) 2019 n (%) Total n (%) Treatment in PED Cast/brace 1226 (67) 1541 (69.2) 2767 (68.2) No treatment 131 (7.2) 172 (7.7) 303 (7.5)

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31 Admission 474 (25.8) 514 (23.1) 988 (24.3) Admission length 1 d 161 (34) 187 (36.4) 348 (35.2) 2-3 d 176 (37) 172 (33.5) 348 (35.2) 4-7 d 88 (19) 120 (23.3) 208 (21.1) 8-10 d 22 (4.5) 10 (1.9) 32 (3.2) 11+ d 27 (5.5) 25 (4.9) 52 (5.3) Further treatment Surgery 441 (93) 472 (91.8) 913 (92.4) Monitoring 33 (7) 42 (8.2) 75 (7.6) Department OT* 443 (93.5) 488 (94.9) 931 (94.2)

Facial and maxillar surgery

10 (2.1) 2 (0.4) 12 (1.2)

Pediatric surgery 1 (0.2) 5 (1) 6 (0.6)

Pediatric neurosurgery 20 (4.2) 17 (3.3) 37 (3.8)

Intensive care unit 0 1 (0.2) 1 (0.1)

Neonatology 0 1 (0.2) 1 (0.1) n – number of patients; d – days; *OT – Orthopedics and traumatology

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32

4. CONCLUSIONS

1. In total there were 19923 pediatric patients that referred to the Pediatric Emergency Department in Lithuanian University of Health Sciences Hospital Kauno Klinikos during 2018 and 2019. In 2018 there were 9698 visits, while in 2019 – 10225 visits respectively, the statistical difference was significant (p<0.05).

2. Most patients were male (59.9%). The mean age of all patients was 8.7 ± 4.9 years. 1-14-year-olds comprised to a total of 81.8%.

3. The most common injury in infants was superficial head injury (74%). 1–5-year-olds most frequently sustained head (30%) and upper limb injuries (17.8%), while 6-10-year-olds – lower limb injuries (30.7%). 11-18-year-old group most frequently had lower and upper limb injuries.

4. Fractures made up 20.4% of all pediatric injuries, most frequently sustained at home and after a fall. 88% of patients arrived at the PED by themselves.

5. 68% of fractures were treated conservatively, with a same day discharge. 25% patients were admitted, most frequently to the Orthopedics and traumatology department, for surgical fracture reduction. Most common admission length for these patients were 1-3 days.

6. We recommend ensuring everyday safety for children in their closest environment, to create a permanent register for pediatric traumatic injuries and to educate primary care specialists on when to refer the patients to the PED.

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33

5. PRACTICAL RECOMMENDATIONS

1. Traumatic injury numbers in the pediatric population are still growing, thus it is necessary to ensure the everyday safety of the children – safe playgrounds, home care, kindergarten/school, etc.

2. To get a complete picture of yearly tendencies of traumatic injuries, permanent registers should be created, which would provide more information on the changes that occur overtime.

3. A better communication between the general public and health care providers should be developed to understand the importance of childhood injuries. It is crucial to educate all health care specialist (especially those working in the primary care institutions), when to provide the help to the child in outpatient clinic, and when to direct for more specific care in the PED.

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34

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Pediatric trauma: a retrospective analysis from 2018 to 2019

Pediatric trauma: a retrospective analysis from

2018 to 2019

Master thesis

TABLE OF CONTENTS

SUMMARY

SANTRAUKA

ACKNOWLEDGEMENTS

CONFLICT OF INTEREST

CLEARANCE ISSUED BY THE ETHICS COMMITTEE

ABBREVIATIONS

INTRODUCTION

AIMS AND OBJECTIVES

1. LITERATURE REVIEW

2. RESEARCH METHODOLOGY

3. RESULTS AND DISCUSSION

4. CONCLUSIONS

5. PRACTICAL RECOMMENDATIONS

REFERENCES