AMINO IMSTC 2020: Scientific Paper by AMSA-Indonesia

AMINO | IMSTC 2020

FOREWORD

Christina Wunardi Secretary of Academic AMSA-Indonesia 2019/2020

AMSA National Competition Archive, or AMINO, is an archive of all academic works submitted to AMSA-Indonesia’s competitions, consisting of Pre-Conference Competition East Asian Medical Students’ Conference (PCC EAMSC), Indonesian Medical Students’ Training and Competition (IMSTC), and Pre-Conference Competition Asian Medical Students’ Conference (PCC AMSC). AMINO aims to provide thorough overview of AMSA-Indonesia’s national competitions to all members of AMSA-Indonesia. On the second volume, all the qualified works that was submitted to the IMSTC 2020 committee have been compiled and are expected to draw forth inspiration and motivation in creating academic works in the field of Scientific Paper, Scientific Poster, Public Poster, Photography, and Videography. I would like to thank and express my sincere appreciation to all the participants of IMSTC 2020, the Academic Team, Executive Boards of AMSA-Indonesia 2019/2020, and other parties that have contributed to the creation of this AMINO. I would also like to give my utmost gratitude to AMSA-Universitas Brawijaya for organizing this very successful event. Hopefully, the release of AMINO for IMSTC 2020 can enhance and intensify the academic enthusiasm and interest of all members of AMSA-Indonesia. “Enhancing Collaboration, Influencing Community” Viva AMSA!

AMINO | IMSTC 2020

TESTIMONY

AMINO | IMSTC 2020

Dennis Ievan Hakim AMSA-Universitas Brawijaya 1st Winner of Scientific Paper Category

I participated in IMSTC because as I heard before that IMSTC is one of the incredible events held by AMSA which could improve your skill in academic and non-academic aspects. And also you can get novel information about current issues that are happening on a health basis. Moreover, I got trained in some specified skills such as making posters or videos which I was having no idea how to make them. Even more, we can meet all medical students from different places and sharing our thoughts and ideas thus increasing friendship and knowledge together. Not only limited to these, but we also could contribute to improving the health status of society by joining IMSTC activities. I do guarantee it is very worth it for you to join IMSTC. I already participate in IMSTC twice, 2019 and 2020. I was following all activities before in IMSTC 2019 but only half in 2020 due to other duties in another place. IMSTC is a very “worth to join” because you will get many benefits “in a package” that reflects the AMSA Vision namely “Knowledge, Action, Friendship”. And also, besides that the accommodation also well thus you have to join this event next year! For Scientific Paper, Discipline and motivation are number one. Having many ideas but with zero motivation and will to do the duty is vain. After you have to build the motivation, then everything will be as easy as riding on the highway, of course by the guidance of seniors and teachers that are good on Scientific Paper. Don’t forget to do the teamwork because you can not do everything as a single man-army in constructing scientific papers, especially if you have limited time added with very hectic campus activities

AMINO | IMSTC 2020

David Nugraha AMSA-Universitas Airlangga 1st Winner of Scientific Poster Category

IMSTC is a national event that has always been awaited by AMSA members, including me. This national event has made an extraordinary and unforgettable experiences. Beside of being able to met with other AMSA members, here I also got a lot of training related to scientific world which is certainly very useful for the future. Moreover, this year IMSTC was held in Malang, so it’s very near to my hometown. Honestly, IMSTC this year’s preparation is arguably very short because from the beginning until the final process was very very close to the submission deadline. At first I felt that it would not be possible to submit my team’s work because it was only five days remaining and we hadn’t had finish it yet. But, from this I learned that if everything is done with full intention and determination also supported with high curiosity, then nothing is impossible to do. For those who are still hesitant to join, don’t be afraid to try because if you don’t try then you will never know. Take every opportunity because it doesn’t come twice. Viva AMSA!

AMINO | IMSTC 2020

Bagas Danadipa AMSA-Universitas Muhammadiyah Malang 1st Winner of Public Poster Category

I joined IMSTC because I wanted to learn and find experience to take part in the competitions at AMSA. I registered in the public poster contest because it is simple and not complicated, and I also like making posters. I am grateful that good luck came to my team and we qualified for the finals for the presentation. I was a little lacking in confidence because the other participants averaged 17 and 18, while I was a freshman. But I instilled in me the principle of “Nothing To Lose”. Nothing is impossible once again luck approached me and managed to become a champion one. The point is when we want to do something, don’t let us stress out about it. Try to always be happy and happy to do it.

AMINO | IMSTC 2020

Nitya Fithra Salsabila AMSA-Universitas Pembangunan Nasional “Veteran” Jakarta 1st Winner of Photography Category

IMSTC was my first national event. From the very first time joining amsa, I know I really wanted try one of the competitions held by AMSA. And finally, I got the chance to participate in IMSTC. When I saw my name on the mailing list, I was full of hesitation and doubts. But I realized that, at some point, I had to try and just do it! Despite feeling tense and nervous during half of the events, I had a really good time in IMSTC. Not only did I have fun, but I also got so much to learn from the trainings provided. It was one of the best experiences for me! For tips and trick, just go for it! Give the best you can do. Brainstorming is essential to explore ideas and let you think outside the box. Find something unique, authenticity should be your number one weapon. Also, being nervous is totally normal! but try your best to have it under control. I know that being outside of your comfort zone is scary, but it’s totally worth it! Also, they weren’t kidding when they say that hardwork never betrays the result.

AMINO | IMSTC 2020

Aldy Bachtiar Hidayat AMSA-Universitas Jember 1st Winner of Videography Category

IMSTC is my first national event in AMSA-Indonesia, which gives an experience and a good impression for me and other AMSA JEMBER delegations, the event that was presented was very interesting and fun from the event I was able to get acquainted with friends from another AMSA University, and this is the first time I took part in academic delegates as a videography participant, and I was very grateful and proud that our team managed to become the first champion in this competition.

AMINO | IMSTC 2020

TABLE OF CONTENTS Scientific Paper 1st Winner Comprehensive Assessment of Full-face Helmet Utilization in Preventing 3 Head and Neck Injury in Motorcycle Accidents: A Systematic Review 2nd Winner Effectiveness of Novel Trauma Scoring Systems in Predicting Survival 14 of Patients with Traumatic Brain Injury: A Systematic Review 3rd Winner Review of Readable Driverâ&#x20AC;&#x2122;s License as Traffic Accident and Trauma 25 Prevention Technology Combination of Mesenchymal Stem Cells and Vitamin B12 for Spinal Cord Injury Treatment The Prognostic Value of S100B Level as A Biomarker of Early Prognosis in Patients with Traumatic Brain Injury: A Systematic Review of Cohort Studies First Aid Knowledge, Attitude, Practice, and Factors Related to The First Line Treatment of Traumatic Injury: A Systematic Review The Efficacy of Blood Transfusion in Damage Control Resuscitation (DCR) as A Non Invasive Life Saving Procedure for Severely Hemorrhagic Patients Group Counselling as Rehabilitation Care for Individual with Childhood Trauma Related to Neuroendocrine Response: A Literature Review Systematic Review of Effect of Extracorporeal Shock Wave Therapy for Burn Patients Systematic Review of The Effectiveness of Pharmacological Treatment for Post Traumatic Stress Disorder Diagnosed Patients Compared to Placebo Assessment of Factors Associated with Unfavourable Prognosis of Traumatic Brain Injury Patients in Asian Countries as a Comprehensive Consideration for Trauma Care after Road Traffic Injury: A Systematic Review of Cohort Studies Handling Trauma in Elderly Patient Protective Effect of Erythropoietin in Traumatic Brain Injury Systematic Review of the Effect of Post-traumatic Stress Disorder Symptoms on Executive Function in Children The Effectiveness of Phytochemical Constituents in Moringa Leaves (Moringa Oleifera Lam) on The Wound Healing Process Efficacy of Chitosan Wound Healing Potential as a Wound Dressing on Treating Acute Wound: A Systematic Review of Case Control Studies The Effectiveness of Glial Fibrillary Acidic Protein (GFAP) and Ubiquitin C-Terminal Hydrolase-L1 (UCTH-L1) as Traumatic Brain Injury (TBI) Biomarker in Patients with CT Negative Proved by MRI Positive The Use of Telemedicine to Ensure a Successful Traumatology Treatment Extract of Onion (Alium cepa L.) as Antimicrobial and Antioxidant Agent: The Alternative Solution for Contact Lens-related Corneal Ulcer Combination of Nanozyme-based Bandage with Pt/CeO2 Atom Catalysis and Electrospinning Nanofibers N-Type Voltage-gated Calcium Channel Blocker (SNX-185): A Potential Novel Way to Reduce Secondary Injury of

34 44 61 72 83 97 110 120 150 161 174 184 195 207 217 228 239

AMINO | IMSTC 2020 Traumatic Barin Injury Stem Cell for Spinal Cord Injury: A Comparison Between Human Embryonic, 253 Induced Pluripotent, and Ependymal Stem Cell Treatments of Blunt Cardiac Injury and How Mortality Rates Could be Reduced 264 Treatment of Spinal Cord Injury and Complication Prevention Using Stem Cell Methods 278 Scientific Poster 1st Winner Glial Fibrillary Acidic Protein (GFAP) as A Promising Serum Biomarker in 291 detecting Mild Traumatic Brain Injury (mTBI) in Emergency Settings: A Systematic Review 2nd Winner Performance of Glial Fibrillary Acidic Protein as A Biomarker for Mild Traumatic Brain 293 Injury Among Children: A Systematic Review and Meta-Analysis of Cohort Studies 3rd Winner Biodegradable Magnesium Screw as An Alternative Implant for Traumatic-Related 295 Fractures Comparing the Curative Efficacy of Different Skin Grafting Methods for Third-Degree 298 Burn Wounds Effectivity of Airway Management in OHCA Subjects Using Laryngeal Mask Airway 300 Performed by Non-Physician Systematic Review of Effect of Extracorporeal Shock Wave Therapy for Burn Patients 303 Hyaluronic Acid Potency as Antibiotic-loaded Biomaterials for Staphylococcus aureus 305 Strain on Surgical Site Infection Handling Trauma in Elderly Patient 307 Systematic Review of the Effectiveness of Pharmacological Treatment for Post 309 Traumatic Stress Disorder Diagnosed Patients Compared to Placebo Can We Really Become the Iron Man Doctors? Virtual Reality Application for Traumatic 311 Surgery Training Comparison of Serum and CSF Levels of S100B Protein as Biomarkers in Detection and 314 Outcome Prediction of Traumatic Brain Injury: A Systematic Review Unfavourable Prognosis Predictors of Traumatic Brain Injury Patients in Asian: A 316 Systematic Review The Application of Carboxymethyl Cellulose for Corneal Epithelial Wound Healing: A 318 Systematic Review Tilapia Skin as a Xenograft for Skin Burn 321 The Efficacy of Blood Transfusion in Damage Control Resuscitation (DCR) As a Non 324 Invasive Life Saving Procedure for Severely Hemorrhagic Patients Effectiveness of Damage Control Resuscitation in Trauma Management 326 The Future Prospect of Combination between Dynamic Intraligamentary Stabilization 329 (DIS) and Bio-Enhancement Technique for Treatment of Anterior Ligament Injury The New Trauma Score (NTS): A Modification of The Revised Trauma Score for 333 Better Trauma Mortality Prediction Outcome of Cervical Spinal Cord Injrury Treatment in Developed and Developing 336 Countries: A Systematic Review Effectiveness of Novel Trauma Scoring Systems in Predicting Survival of Patients with 339 Traumatic Injury: A Systematic Review

AMINO | IMSTC 2020 The Role of Tranexamic Acid (TXA) in Minimizing Mortality of Traumatic Brain Injury Combining Protein as Biomarker for Detecting Brain Lesion in Mild Traumatic Brain Injury: Foundation of Point-Of-Care Testing (POCT) Tool Platelet-Rich as a Booster in Anterior Cruciate Ligament Injury Recovery Bone Marrow Stromal Cells Therapy for Traumatic Brain Injury (TBI): A Systematic Review of Preclinical Studies Comprehensive Evaluation of Optimal Burn Wounds Dressing Materials to Accelerate Wound Healing and Alleviate Pain: A Systematic Review of Clinical Trials Public Poster 1st Winner PREVENT HYPOTHERMIA WITH “JAKET” 2nd Winner SPRAIN VS STRAIN: remember THE RECIPE! 3rd Winner Treat Early Recover Quickly Treatment of burns with tilapia skin Treat Your Wound with Bubble Bush TREAT YOUR WOUND RIGHT! CRUCIAL PHENOMENON RELIEVE BEAT THE HEAT WITH THIS WAY!! Save Someone’s Life with OMGS The Proper Ways to Remove Helmet from Casualty HELP: Break the Barrier of Ignorance, Helping More People AMBULANSA: Get Your Ambulance with AMSA Spinal Cord Injury: Don’t Let Others Die, Help with ABCD Be A Hero, Save A Life! Your Body is Your Biggest Treasure Herbiotic Exemplum, an Alternative to Antivenom Reactions MARCHing Towards Brain Injury MATTERS: No More Elderly Falls Don’t do it like a MASTER Post-Traumatic Stress Disorder IT HAPPENS WITHIN US TREAT FRACTURES LIKE SIA! MANAGE BURN WOUND WITH ABCD: Don’t Wait! Get Care! Stop the Burns with RECIPE VIVA: An App to Save Your Life, His and Hers ORTHOKUN BITCOIN: Burn Trauma Comprehension and Interception TRAFFIC ACCIDENT-CAUSING TRAUMA ON THE DRIVER WITHOUT A LICENSE MORE REST, More Life to be Saved 112: One Call Away ONE SECOND ONE LIFE ACOUSTIC TRAUMA REACT: Responsive, Encourage, Active, Clear Treat

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355 357 359 365 367 369 371 374 376 379 381 383 385 387 390 392 394 396 398 400 402 405 408 410 412 414 416 418 420 423 426 429 431

AMINO | IMSTC 2020 The Effect of Saltwater on Wound Healing Motor Vehicle Accident is More than Just Being a Mere Disaster How to Deal with Ankle Sprain Using “RIPE” How to Not Break a Neck! Blowing Your Eye is a Myth Traumatic Brain Injury Care with THANOS TELE-ME SOMETHING GOOD: TELETRAUMA IS A NEW WAY! Treat A Burn with HONEY Is It Epidural Hematoma? Spot the AGENTS! One Click for Save One Life First Aid Care for Fracture with LIMBS A STARTER Pack for Safer Sports: Remember Do CARE and Do Not HARM LET’S BEAT ALZHEIMER WITH REMEMBER TREAT ACID WITH A.C.I.D. Do “The Conch is Aware of Crabs” to Saves Lives Don’t be Freaked and Tricked by a Venomous Snake Antibiotics in open fracture 3C: An Extraordinary Way to Settle Tension Pneumothorax Your Appearance Saves Your Feet DROMEDS: Assistance Is a Drone Away Pass De Crab and Splint Treat Burns Better SMART Farmer Every Drop is Worth ELECTRICITY: CONTROL ITS SAFETY, BE A HERO! SAFE: (S)mart (A)ctions to decrease (F)atality Rate in Traffic (E)xperience Child Abuse Issues that Affect Growth in Traumatology “How to Handle the Initial Accident Trauma Victims” “Whiplash: Not Just A Pain in the Neck” DO 3C & DON’T HARM FOR BURN INJURY

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Photography 1st Winner Time is Life 505 2nd Winner Be careful, Madam! 507 3rd Winner MIRACLE SPICE TURMERIC: THE NEXT GENERATION OF HOME REMEDIES 509 Revamping the Layperson 511 Prevention id The Best Solution 513 A Butterfly-Like Wound 515 Boys don’t get hurt 517 Heist of an Existence 519 Low Back Pain: Be Aware because It is Right Behind You 521 Effective Model for First Aid Training 523 “Break the Barrier of Ignorance, Helping More People” 525 I’ll Stay Stronger 527 Preventing Infection Following Trauma or Surgery 529

AMINO | IMSTC 2020 WHO LIVES SEES, WHO SAVE SEES MORE First Aid Treatment Simulation for Agricultural Workers: Health Promotion to Reduce Mortality and Morbidity due to Agricultural Accidents in Community Virtual Reality for PTSD Treatment and Trauma Prevention We’ll Do It Together The Usage of Knee Pads for Knee Bursitis Prevention for Badminton Athlete Your Concern, It’s Powerful New Modified Portable X-Ray for Immediate Emergency Action [Untitled] Not Only Helping but also Saving Them Dear, Stay Alive Videography 1st Winner Against the Myth 2nd Winner How to survive from Venomous Snake Bites 3rd Winner Deal the Burn with Rice Wrap SILENCE Before It Happens Break the Stigma Let’s be a helper, everyone can be a helper The Unsettling Truth of Bone Setting Trauma: It Matters Facial Trauma: Dare to Face It? The Change Is in Our Hand A Guide to First Aid of Trauma Care First Aid for Fractured Bone In A Traffic Accident

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AMINO | IMSTC 2020

Comprehensive Assessment of Full-face Helmet Utilization in Preventing Head and Neck Injury in Motorcycle Accidents : A Systematic Review 1

Dennis Ievan Hakim, 1John Thomas Rayhan Huwae, 1Emanuel Hananto 1

Asian Medical Student Association, Batch 2017 ABSTRACT

Introduction: Despite increasing effort and attention to reduce the burden of road traffic accidents, morbidity and mortality due to motorcycle accidents are still becoming the major problem that cannot be solved. From 1990 the most common cause of deaths due to motorcycle road accidents is not changed, namely due to head-facial and neck injuries. One of the simple ways to overcome this problem are using a helmet, but the types of helmet that confer best protection is not specified by many nation s policy. This review aimed to evaluate the best type of helmet in reducing the mortality and morbidity rate due to head-facial and cervical trauma. Material and Methods: A Systematic review evaluating the most prominent helm in conferring protection was carried out using PRISMA statement guidelines. Studies search were conducted using search engine ScienceDirect, ProQuest, and PUBMED database with criterion papers published in English between 2009 to 2019 and comparing full face, partial face, and open face helmet effectivity in confer protection. Appraisal tools of selected studies using Centre for Evidence-Based Medicine (CEBM) appraisal tools. Result and Discussion : From the search, 1477 studies were identified and finally obtained 8 studies that fulfill the criterion of this systematic review. The studies are organized according to the comparison of full-face helmet with partial face helmet and full-face helmet with partial face helmet. Studies show that full-face helmet gives significant protection against head-facial and cervical injury. However, because many of the studies criteria are not uniformed, the need for further study with better quality is a must. Conclusion : Full-face helmet reduces head-facial and neck injuries better than other helmets in motorcycle accidents thus reducing the morbidity and mortality rate. Policy makers may need to specify the full-face helmet as the recommended helmet especially in low-middle income countries.

Comprehensive Assessment of Full-face Helmet Utilization in Preventing Head and Neck Injury in Motorcycle Accidents : A Systematic Review Participate in IMSTC 2020 by AMSA-Indonesia

Arranged by: Dennis Ievan Hakim

175070107111010

John Thomas Rayhan H

175070100111053

Emanuel Hananto

175070100111045

FACULTY OF MEDICINE 2019

INTRODUCTION World Health Organization stated that every minute, three people are death worldwide due to road traffic accidents1. A Road traffic accident has still become unsolved problems and it is predicated as the most common cause of death in children and young productive adults (age 5-29 years) on a trauma basis thus causing a high burden in many aspects, especially in economic basis[1]. Moreover, the rate of events, and also the morbidity and mortality rates, keep increasing every year and it was known that it is three times higher in low-middle income countries than in high-income countries, especially in Thailand, Malaysia, and Indonesia[1,2]. In Indonesia, the mortality rate due to road traffic accidents from 2010 until 2014 are increasing with motorcycles are the most commonly used vehicle on the accidents (627.116 units or 70% from all of the vehicles used)[2]. These data are supported by empirical facts that motorcycles are the most commonly used vhicle in many low-middle income countries. From 1990 until 2018, the most common cause of deaths due to motorcycle road accidents is not changed[3]. Head and neck injuries were cause of death of more than 53% motorcycle accidents in the world and recent reports from Cochrane review also stating that craniocerebral, facial, and neck injuries were common too[3,4]. In Indonesia, Indonesian Health Department (DepKes) stated that head-cervical traumas related to motorcycle accidents were the most common cause of death (74%) followed by hip and lower limb traumas (10%)[2]. Based on these problems, factors which caused the high rate, morbidity, and mortality rate due to road traffic accidents, especially motorcycle-related, must be evaluated. Referring to the epidemiological triangle which is modified from Haddon s matrix, there are three main factors that are related to each other in determining the incidence of road accidents, namely agent (the human), host (vehicle factor), and environment (the road)[5]. In low-middle income countries, and also supported by data on Indonesia, undisciplined behavior is the leading cause of the incidence, morbidity, and mortality rate increase in road accidents and the commonest undisciplined behavior that still being neglected in Indonesia is the usage of helmet[2,5]. One of the effective preventive strategies of motorcycle accident severity is to use a helmet while riding motorcycle due to its protective effect on death and head injuries based on Cochrane review with OR 0.58 and 0.31, respectively[4]. There are three common types of the helmet that are currently approved by SNI (Standart Nasional Indonesia), namely full-face, open face, and partial face helmet. But the law in many countries, including Indonesia, is not specifying the types of helmet[6]. Whereas a 1 5

case-control based review conducted by Lam, et al in Taiwan shows that the types of helmet that are used by the motorcyclist does influence the outcome of the motorcycle accidents patients including the rate of head-facial fracture and cervical spine injury compared to nonhelmet user (OR = 0.19, 95% CI and OR = 0.35%, 95% CI respectively) [7]. Based on these problems, we have an initiation to find which helmet is the best to overcome the high morbidity and mortality rate due to motorcycle accidents with an idea stated on a systematic review. This study aimed to review what is the best helmet type to prevent head and cervical injuries in motorcycle accidents thus could support and determine the best helmet type that may be documented and implemented in the helmet law, especially in low middle-income countries such as Indonesia. MATERIAL AND METHODS A systematic review of large observational studies comparing the protective effect of full-face, open face, and partial face helmet against head-facial and cervical traumas in motorcycle road accidents was carried out using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement rules. We searched works of literature published in Pubmed, ScienceDirect, and ProQuest databases with keyword motorcycle accident (s), helmet, head injury (s), cervical injury (s) and only papers published in English from 2009 until 2019 which are included. The eligible studies were 1) those which are comparing the full-face helmet with other types of the helmet (open face, and partial face) on motorcyclists who had traffic accidents 2) the outcomes of studies involved head-facial and cervical injuries (including spinal cord injuries). We appraised eight Selected studies by using the Centre for Evidence-Based Medicine (CEBM) appraisal tools. The literature selections were summarized in Figure 1.

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Figure 1. Diagram flow of study search and selection criteria.

RESULT From 1477 published papers from Pubmed, ScienceDirect, and ProQuest databases, we include 1154 studies because the other studies are not published in English and published below 2009. Of those, we finally include eight eligible and valid studies because of the other studies discussing other topics besides the comparison of full-face, open face, and partial face helmet in preventing head-facial and cervical injuries, unsuitable study design, studies not found, and study duplication. The final eligible and valid studies (n=8) then were reviewed here and the results were summarized in Table 1. Table 1. Summary of Studies Comparing Between Full-face Helmet, Partial Face, and Open Helmet on Head-facial and Cervical Outcomes in Motorcyclists Who Had Road Accidents. 3 7

Lam et al7 Taiwan 2015 Observational Case-control study Patients intracranial hemorrhage, skull-face fracture, and brain concussion Motorcycle crash Over 17 years of age Datas from 2000 until 2009 in taiwan Head injury registry

Ramli et al Malaysia 2014 Observational Case-control

Cini et al9 Brazil 2014 Observational Case-control

All motorcyclists (Pillion or single rider) All age groups (<16 25) All types and severity of injuries Were involved in a motorcycle crash within the catchment Datas from 2010 until 2011 in South Klang Malaysia

Patients injured in the face in a motorcycle accident

Those with injuries to any other part of the body or whose injuries resulted in death

Not wearing any helmet at the time of crash Unidentified types of helm

5,225 participants

Motorcyclists who did not sustain any injury, or discharged themselves from hospital care without a definitive diagnosis, Involved in a road crash outside South Klang Valley, Malaysia 755 participants

1,628 participants

151

Cervical spine injuries

Facial injuries

Full-face helmet with head injury, n Full-face helmet without head injury, n Partial helmet with head injury, n Partial helmet without head injury, n Open Helmet with head or cervical injury, n Open Helmet without head or cervical injury, n

28 (2.1%)

2 (14%)

12 (16%)

Skull-facial fractures, traumatic brain injury, cervical spine fractures 16 (19%)

1,259 (97.9%)

12 (86%)

63 (84%)

68 (81%)

104 (3%)

304 (51%)

3,385 (97%)

293 (49%)

9 (26%)

49 (73%)

25 (74%)

18 (27%)

Study Country Year Study Design

Erhardt et al11 United States 2015 Observational Cohort Retrospective Riders who is using either full-face, half, and openface helmet Aged > 15 years old

Albuquerque et al12 Brazil 2014 Observational Retrospective cohort Motorcycle accident victims had to be referred to the outpatient clinic at the hospital

Yu et al13 Taiwan 2011 Observational Matched casecontrol Age â&#x2030;Ľ 15y

Sung et al14 Korea 2016 Observational Cohort Retrospecitve study All drivers and passengers over 15 years old who were riding motorcycle Wearing helmet with known types

Study Country Year Study Design Inclusion

Exclusion

Number Participants Primary Outcome

Inclusion

Any cases with missing data on helmet use, types of helmet used, or cervical spine injury of

Lived in Taichung Visited the emergency room at China Medical University

4 8

Brewer et al10 United States 2013 Observational Cohort Retrospecitve study All helmeted adults patients older than 18 years old Crashes on all terrain vehicle

Any tipe of collision except that is located on opendesert Unhelmeted Riders Riders who fall on opendesert environtment

Exclusion

Number Participants Primary Outcome

Hospital due to motorcycle injuries Incomplete hospital records or refusion to participate

Riders who were not operating a motorcycle i.e. those who were riding a minibike, a bicycle or a tricycle or wore a safety helmet for construction or were involved in a crash outside the city of Taichung 45 participants

Incomplete Record

6460

253

509

Neck and head injury

Head Injury

542 (12,7%)

Facial Injury Severity Scale, traumatic brain injury, facial fractures 24 (52%)

50 (40%)

52 (20%)

3698 (87.3%)

22 (48%)

73 (60%)

209 (80%)

256 (24.7%)

274 (57%)

44 (40%)

780 (75.3%)

208 (43%)

66 (60%)

125 (21%)

39 (76%)

63 (45%)

468 (89%)

12 (34%)

72 (55%)

Full-face Helmet Versus Partial Face Helmet This systematic review comparing the effectivity of the full-face helmet and many types of helmet, one of them is a partial type helmet[7,8,11,13]. There were four studies from Malaysia, Taiwan, United States comparing the full-face helmet against partial type helmet. The output evaluated were head and neck injuries (Table 1). Overall, using full-face helmet compared to a partial helmet could reduce the incidences of cervical and head injuries by 17% compared to four prior studies that evaluated here (95% CI p-value <0.001). And also, all of the participants that are included were aged more than 17 years old and only include the rider of the motorcycle, which has a high risk to cause face and cervical injuries[1]. A study from Lam, et al stated that using a full-face helmet could reduce the chance of having intracranial hemorrhage and brain concussion. The study from Ramly evaluated the significant factors related to crash injuries on faces which will be discussed later. The disadvantages of the data collected were lacking

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Medical

participants and the majority of studies are case-control which has a high chance of participants bias[7,8,11,13]. The summary can be evaluated in Table 2 (on attatchment). Full-face Helmet Versus Open Face Helmet On the comparison between a full-face helmet with open face helmet, this paper reviewed five observational publications with study settings conducted in Brazil, United States, and Korea[9,10,11,12,14]. The outcome that was evaluated from these studies including head-facial injuries, cervical injuries, and traumatic brain injuries. From this review, it is stated that using a full-face helmet could reduce the incidences of head-facial and neck trauma 24.26% better than using an open face helmet (95% CI p-value <0.005). The prominent of studies included were all of the studies taken is a cohort-based studies with the five latest year publication that were included[9,10,11,12,14]. The setting of the studies also variates from countries with many setting of the event thus the validity of helm use in preventing motorcycle accidents has better external validity. The weakness of the studies was conducted with few subjects and some studies that included in the cohort are only patients who have been admitted to the hospital that cooperate with the researcher. The summary can be evaluated in Table 3 (on attatchment). DISCUSSION Road traffic accidents until now still become unsolved problems, and most of the incidences are caused by motorcycle accidents, especially in low-middle income countries worldwide[1,2]. Many actions can be done to overcome the burden of these problems and based on the current review, using a helmet is one of the best ways to reduce the morbidity and mortality rate of motorcycle accidents[4]. Here, we reviewed the best helm that can be used to reduce the burden of motorcycle accidents. This review of large observational studies found that the overall full-face helmet is the most prominent to prevent head and cervical injuries in motorcycle accidents[7-14]. The Fullface helmet could ameliorate the outcomes of the victim compared to other helmet types of helmet either in preventing fracture or brain-spinal cord injuries. But, it does not mean that the full-face helmet did not have disadvantages. Lam, et al stated that a full-face helmet is heavier thus cause discomfort[7]. The Full-face helmet also reduces the eye view of the rider compared to the other helmet. The main finding of this systematic review is that a full-face helmet was better than either partial or open face helmet in preventing head-facial and cervical injuries of motorcycle riders on accident. The risks of head-facial and cervical injuries (including

6 10

neurological deficit) were lower by 17% when compared with partial helmet and 24.26% when compared with open face helmet[7-14]. The reason why a full-face helmet could confer better protection, especially in head injuries, is that three causative factors determining the prognosis of motorcycle-related accidents are helmet wearing, helmet fixation status and visor damage[8]. It is highlighted that helmet fixation is a stronger predictor in determining the head injury than helmet types. Usage of the full-face helmet could prevent dislodgement due to its effect in fixating the head of the user. The problems arising from these cases are the removal of the full-face helmet may be harder and causes discomfort due to more heat and moisture in tropical countries, such as Indonesia[8]. Moreover, it needs support from the government in promoting and cutting the cost of the full-face helmet, especially in low-middle income countries to prevent more burden caused by disability or death due to motorcycle accidents. There were some limitations to this review. First, the outcome criterion was not uniformed in the comparison between all helmet due to different specific types of head-facial and neck injuries. Second, the eligible participants vary among studies based on inclusion and exclusion criteria and there was still no study conducted in Indonesia, which is one of the main aims in this review implementations. Our findings are in agreement and consistent with previous literature comparing the protective effect between full-face, partial, and open face helmet conducted by Liu, et al on 2008 published on Cochrane review[4]. This systematic review suggests that using a full-face helmet offer the best solutions to overcome high morbidity and mortality rate due to head-facial and cervical trauma due to its protective advantages[4]. By implementing the law of using fullface helmet, namely in Indonesia, we are one step closer to achieve sustainable development goals for road safety (SDGs), namely good health and well-being by halving the number of global deaths and injuries from road traffic crashes and sustainable cities and communities by providing access to safe, affordable, accessible, and sustainable and safe transport system for all[1]. CONCLUSION In General, this review conclude that full-face helmet reduce head-facial and neck injuries better than other helmets in motorcycle accidents thus reducing the morbidity and mortality rate. Policy markers may need to specify the full-face helmet as the recommended helmet especially in low-middle income countries. 7 11

REFERENCES 1. World Health Organization. Global action plan on physical activity 2018-2030: more active people for a healthier world. World Health Organization; 2019 Jan 21. 2. Djaja S, Widyastuti R, Tobing K, Lasut D, Irianto J. Situasi Kecelakaan Lalu Lintas Di Indonesia, Tahun 2010-2014. Jurnal Ekologi Kesehatan. 2016 Jul 6;15(1):30-42. 3. Faduyile F, Emiogun F, Soyemi S, Oyewole O, Okeke U, Williams O. Pattern of injuries in fatal motorcycle accidents seen in Lagos State University teaching hospital: an autopsy-based study. Open access Macedonian journal of medical sciences. 2017 Apr 15;5(2):112. 4. Liu BC, Ivers R, Norton R, Boufous S, Blows S, Lo SK. Helmets for preventing injury in motorcycle riders. Cochrane database of systematic reviews. 2008(1). 5. Goniewicz K, Goniewicz M, Paw owski W, Fiedor P. Road accident rates: strategies and programmes for improving road traffic safety. European journal of trauma and emergency surgery. 2016 Aug 1;42(4):433-8. 6. Indonesia. Undang-undang RI No. 14 Tahun 1992 Tentang Lalu-lintas dan Angkutan Jalan. VisiMedia; 2009. 7. Lam C, Lin MR, Chu SF, Tsai SH, Bai CH, Chiu WT. The effect of various types of motorcycle helmets on cervical spine injury in head injury patients: a multicenter study in Taiwan. BioMed research international. 2015;2015. 8. Ramli R, Oxley J, Hillard P, Sadullah AF, McClure R. The effect of motorcycle helmet type, components and fixation status on facial injury in Klang Valley, Malaysia: a case control study. BMC emergency medicine. 2014 Dec;14(1):17. 9. Cini MA, Prado BG, de Fragas Hinnig P, Fukushima WY, Adami F. Influence of type of helmet on facial trauma in motorcycle accidents. British journal of oral and maxillofacial surgery. 2014 Nov 1;52(9):789-92. 10. Brewer BL, Diehl III AH, Johnson LS, Salomone JP, Wilson KL, Atallah HY, Feliciano DV, Rozycki GS. Choice of motorcycle helmet makes a difference: a prospective observational study. Journal of trauma and acute care surgery. 2013 Jul 1;75(1):88-91. 11. Erhardt T, Rice T, Troszak L, Zhu M. Motorcycle helmet type and the risk of head injury and neck injury during motorcycle collisions in California. Accident Analysis & Prevention. 2016 Jan 1;86:23-8.

8 12

12. Albuquerque CE, Arcanjo FP, Cristino-Filho G, Lopes-Filho AM, de Almeida PC, Prado R, Pereira-Stabile CL. How safe is your motorcycle helmet?. Journal of Oral and Maxillofacial Surgery. 2014 Mar 1;72(3):542-9. 13. Yu WY, Chen CY, Chiu WT, Lin MR. Effectiveness of different types of motorcycle helmets and effects of their improper use on head injuries. International journal of epidemiology. 2011 Mar 9;40(3):794-803. 14. Sung KM, Noble J, Kim SC, Jeon HJ, Kim JY, Do HH, Park SO, Lee KR, Baek KJ. The preventive effect of head injury by helmet type in motorcycle crashes: a rural Korean single-center observational study. BioMed research international. 2016;2016.

ATTACHMENT Table 2. Summary of comparison of Full-face Helmet Versus Partial Face Helmet on Headfacial and Cervical Trauma on Motorcyclist Who Had Accidents based on This Review. Outcomes Yes

Total

626

5042

5668

Partial helmet

938

4666

5,604

Total

1564

9708

5,996

Full-face helmet

Table 3. Summary of comparison of Full-face Helmet Versus Open Face Helmet on Headfacial and Cervical Trauma on Motorcyclist Who Had Accidents based on This Review. Outcomes

Full-face

Yes

Total

759

4060

4819

285

595

880

1044

4655

5,996

helmet Open face helmet Total

9 13

Effectiveness of Novel Trauma Scoring Systems in Predicting Survival of Patients with Traumatic Injury: A Systematic Review Azyumar Luthfi Muhammad Alfariz, Wahyuda Nuzul Fahmi, Rivo Junieta Alicia

Introduction: Trauma still becomes the main concern in the medical field to reduce its number and increase patients survival. To objectify this goal, trauma scoring systems were invented. One of them is the Revised Trauma Score (RTS). In the last decade, a better scoring, MGAP (Mechanism, Glasgow Coma Scale, Age, and Arterial Blood Pressure) and GAP (Glasgow Coma Scale, Age, and Arterial Blood Pressure), start to replace RTS in use. This systematic review aims to compare the effectivity of novel trauma scoring system, MGAP or GAP, with RTS or TRTS to predict the survival of patients with a traumatic injury. Materials and Methods: This systematic review is organized according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement 2009 Checklist and applied Population, Intervention, Comparison, and Outcome (PICO) approach. The databases used are Scopus, PubMed, ScienceDirect, ClinicalKey, EBSCOhost, and PMC by using specific keywords. The risk of bias was assessed using the JBI Systematic Reviews Checklist for Case Series and Cohort Studies. Oxford Centre for Evidence-Based Medicine Level of Evidence was used to determine the level of evidence of the studies. Results and Discussion: Searches yielded 41 studies, 8 studies met the inclusion criteria. There were 3 prospective studies and 5 retrospective studies. The studies evaluated in correlation with in-hospital and prehospital mortality, mortality and severity prediction accuracy, and discrimination ability. 6 studies showed MGAP had the highest AUC compare to GAP, RTS, and T-RTS. MGAP and GAP showed no significant differences in performance. Conclusion: MGAP and GAP have better performance than RTS statistically in prehospital and in-hospital mortality and severity. This score potentially provides a more feasible mean of estimating injury severity in low-middle income countries, further validation required to applicate the score.

EFFECTIVENESS OF NOVEL TRAUMA SCORING SYSTEMS IN PREDICTING SURVIVAL OF PATIENTS WITH TRAUMATIC INJURY: A SYSTEMATIC REVIEW

Authors: Azyumar Luthfi Muhammad Alfariz Wahyuda Nuzul Fahmi Rivo Junieta Alicia

2019

A. INTRODUCTION Trauma is one of the leading causes of death in adolescents and adults worldwide. It still becomes the main concern in the medical field to reduce its number and increasing patient's survival. According to Jassy (2016), "In Indonesia, trauma placed 4th as a cause of death overall, while at age group 15-25 years old trauma placed first." 1 Nur Yuniarti2 reported in her publication that the death rate caused by trauma projected to increase from 5.1 million to 8.4 million and estimated to place 3rd in Disability Adjusted Life Years (DALYs) in 2020 worldwide. To improve the survival of all patients with traumatic injuries, a scoring system to grade the severity of the injury introduced since 1969. The first one is known as the Abbreviated Injury Score (AIS) and acts as the basis of the new Injury Severity Score (ISS) later on. Up until now, three groups of Trauma Scoring System has identified. Those are anatomic scores which include AIS and ISS, physiologic scores such as RTS and T-RTS, and combined scores such as TRISS.3 One of the most popular trauma scoring systems that often used in assessing patients pre-hospital and in-hospital is the Revised Trauma Score (RTS). The assessment components of the RTS are the Glasgow Coma Scale, Systolic blood pressure, and respiratory rate. The triage version of RTS, T-RTS, adds coded value for each assessment component.4 However, Kondo et al.5 reported that the calculation of RTS is too complicated for easy use in ED and not reliable enough when used by paramedics. Moreover, the assessment of respiratory rate is less reliable than other factors because it is influenced by the patient s age, mechanism of injur , and mechanical ventilation. The problem also goes when T-RTS used although it offers easier use.5 In the last decade, two new trauma scoring systems introduced to replace the RTS and T-RTS. Those two new scores are MGAP (Mechanism, Glasgow Coma Scale, Age, and Arterial Blood Pressure) developed by Sartorius et al6 and GAP (Glasgow Coma Scale, Age, and Arterial Blood Pressure) developed by Kondo et al5. As the name stands, both MGAP and GAP assess the awareness of the patients through GCS, age, and also the arterial/systolic blood pressure. In MGAP, it adds the mechanism of trauma to the assessment. Because of its novelty, both scoring systems still rarely used to assess the severity of the injury caused by trauma. Several systematic reviews had conducted in the past regarding trauma scoring systems. There is one systematic review that correlates well with this systematic

review. That systematic review offers an evaluation summarize of physiologic score measures that can be used in emergency situation.7 Although has a close correlation, this review has a different aim with the previous one. This systematic review aims to compare the effectivity of novel trauma scoring system, MGAP or GAP, with RTS or T-RTS to predict the survival of patients with traumatic injury. B. MATERIALS AND METHODS Protocol and Registration This review is organized according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement 2009 Checklist.8 The checklist will be shown in appendix I. Eligibility Criteria and Outcomes The most following intervention study types included are retrospective and prospective studies. This systematic review applied Population, Intervention, Comparison, and Outcome (PICO) approach.9 The population included were patients with traumatic injuries in all ages. This intervention used the MGAP or GAP scoring system as an intervention to assess patients with trauma. GAP is the modification of the MGAP scoring system. The comparison used the RTS or T-RTS. MGAP or GAP and RTS or T-RTS were chosen because they are at the same cluster that is a physiological scoring system for predicting the outcomes for trauma patients, not anatomical. The outcomes included in this review were mortality rate, death, and survival or prognosis prediction. Information Sources This systematic review performed extensive literature searching in the following databases: Scopus, PubMed, ScienceDirect, ClinicalKey, EBSCOhost, and PMC using keywords protocol: ("Traffic Accident" or "Road Injury" or "Trauma") AND ("MGAP Score" or "GAP Score" or "Glasgow Coma Scale, Age, Arterial Blood Pressure") AND ("RTS" or "Revised Trauma Score") AND ("Mortality" or "Mortality Rate" or "Prognosis") in advanced search fields at several databases except for ScienceDirect and Clinical Key. The keywords used for the latter are ("MGAP score" OR "GAP score") AND "Revised Trauma Score AND "Trauma". Inclusion and Exclusion Criteria

The search results were downloaded and were selected based on the inclusion and exclusion criteria. The inclusion criteria used in our literature searching were retrospective or prospective study, the patients in the study were all trauma injury, the study compares MGAP or GAP to RTS or T-RTS. The exclusions criteria were: study that more than ten years, not correlated to the aim of this study and study that did not use the English. Data Collection and Assessment From all studies we obtained from literature searching, we excluded several studies that not relevant to the inclusion criteria but relevant to the exclusion area by reading the abstract and assessed them for relevance. The duplicated studies were excluded too. Studies identified as potentially relevant were retrieved and read the full text. The study that not correlated with the aim of our study excluded and the others were used in this review. The data that were explained in each study were extracted by PICO characteristics in this systematic review. Almost all of the studies that we reviewed to compare the quality and effectiveness between MGAP or GAP and RTS or T-RTS by using the data of sensitivity, specificity, AUROC (Area Under the Receiver Operating Characteristics Curve), and p-value. Literature Screening and Quality appraisal This review used the Oxford Centre for Evidence-Based Medicine (OCEBM) Level of Evidence to determine the level of evidence of the studies. According to Baldwin, et al.10, OCEBM provides a popular scale for stratifying evidence from strongest to weakest on the basis of susceptibility to bias and the quality of the study design. The risk of bias in individual studies was assessed using the JBI (Joanna Briggs Institute) Systematic Reviews Checklist for Case Series and Cohort Studies, the results of the assessment are shown in Appendix II. JBI approach was recommended to critical appraisal, study selection, data extraction, and data synthesis.11 Due to the different nature of these studies, no assessment of the risk of bias across studies was considered. No additional analyses were performed. RESULTS Study Selection

The electronic searching yielded 41 articles. Of these 41 articles, only 24 articles considered to fulfill the inclusion criteria. 11 duplicate studies were excluded next and 5 more studies also excluded the latter judged not having the same aim as our

systematic review. The complete process could be seen in figure 1. Full study characteristics reports are shown in table 1 below and assessment for bias for included reports is shown in appendix II.

Fig. 1: Literature searching flowchart

Table 1. Summary of Studies Characteristics

Study Characteristics

Interpretation: According to the table above, the study design from eight studies, four studies are case series, three studies are retrospective cohort, and one study is a prospective cohort. The pvalues <0,001 show that there is needed a significant difference between the MGAP or GAP score and the RTS or T-RTS score. According to the AUC, it was found that the MGAP or GAP score was better in scoring trauma injury compared to the RTS or T-RTS score. Based on its sensitivity shows that MGAP has the highest sensitivity level then followed by GAP, and RTS has the lowest sensitivity compared to MGAP and GAP. Based on the specificity, it was found that RTS or T-RTS was more specificity than MGAP and GAP. In the conclusion of this reviewed 8 articles above, it was found that MGAP and GAP were more effective in predicting patient survival in cases of trauma injury. DISCUSSION Summary of Evidence

Not all studies include GAP, MGAP, RTS, and T-RTS as the variable. Three of four studies that compare all these variables showed GAP and MGAP significantly better than RTS and T-RTS, while MGAP compares to GAP showed no significant result.12,16,19 Studies that compare one of these variables with other scoring systems showed either GAP or MGAP had better predicting ability in prehospital and inhospital mortality.13,14,15,18 GAP, MGAP, RTS, and T-RTS also showed good performance in predicting in-hospital mortality by assessed the physiology of the patient. The physiology components were easily assessed, but in particular condition, this could not be done. Missed data such as respiration rate, which was used in the calculation of RTS or T-RTS score, could affect the analysis. Some studies also showed incomplete data for some variables and analyze the subjects based on the data they have, but some studies also used imputation to robust their data despite the missed data.16,18 Further study to be required with complete data to analyze all variables to avoid sampling bias. Physiological scoring systems such as GAP, MGAP, RTS, and T-RTS potentially provide a more feasible mean of estimating injury severity in low-middle income countries using readily available clinics.17 Measurement of the component

such as vital signs still occurred at the time of hospital, not at that time after injury, so the validation and assessment of the physiological scoring systems first required to be done in low-middle income countries before being applied.18 In high-income countries, the limitation of RTS or T-RTS scoring system can occur due to intervention to the patient before scoring, such as sedation or intubation which affect the measurement of GCS. While GAP and MGAP approach their performance accurately in high-income countries.17 Limitation In this study review, there were two kinds of study, retrospective and prospective study. In the prospective study, patients data collected and measure at a particular time. In the retrospective study, some studies used a monocentric study, while others were multicentric study. Not all the studies compare GAP, MGAP, RTS, and T-RTS in one study, but just compare one of them with other severity scores. Some retrospective studies missed data for calculating severity score due to received data from the trauma center in this study could not obtain all variables needed for score calculation. Some studies imputed the data to keep the robustness of the statistical result, only one study did not impute the data which may result in sampling bias.17 Conclusion GAP, MGAP, RTS, and T-RTS all had good performance in severity or mortality prediction. But in comparison, GAP and MGAP had better performance than RTS or TRTS statistically. The application of GAP, MGAP, RTS, T-RTS must be first validated to the health system in Indonesia. GAP and MGAP most probably can be adapted in a traumatic management system in Indonesia. The studies we found still in low-level evidence for Indonesia. Further study needs to be conducted in Indonesia setting. FUNDING This systematic review is self-funded. REFERENCES Ranti J, Sapan H, Kalesaran L. Aplikasi revised trauma score, injury severity score, dan trauma and injury severity score dalam memrediksi mortalitas pada pasien multitrauma di IRDB BLU RSUP Prof. Dr. R. D. Kandou Manado. JURNAL BIOMEDIK (JBM). 2016;8(2): S31.

EPIDEMOLOGI TRAUMA SECARA GLOBAL [Internet]. PDF Download Gratis. [cited 2019Dec3].

Available

from:

https://docplayer.info/48453427-Epidemologi-trauma-

secara-global.html H Pohlman T, Bjerke H. Trauma Scoring Systems: Overview, Applications of Trauma Severity Scoring, Basic Statistical Concepts [Internet]. Emedicine.medscape.com.

2019 [cited 3 December 2019]. Available from: https://emedicine.medscape.com/article/434076-overview Champion H. Trauma Scoring. Scandinavian Journal of Surgery. 2002;91(1):15. Kondo Y, Abe T, Kohshi K, Tokuda Y, Cook E, Kukita I. Revised trauma scoring system to predict in-hospital mortality in the emergency department: Glasgow Coma Scale, Age, and Systolic Blood Pressure score. Critical Care. 2011;15(4):2. Sartorius D, Le Manach Y, David J, Rancurel E, Smail N, ThicoĂŻpĂŠ M et al. Mechanism, Glasgow Coma Scale, Age, and Arterial Pressure (MGAP): A new simple prehospital triage score to predict mortality in trauma patients*. Critical Care Medicine. 2010;38(3):832. Totten AM, Cheney TP, O Neil ME, et al. Ph siologic Predictors of Severe Injur : Systematic Review [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2018 Apr. (Comparative Effectiveness Review, No. 205.) Available from: https://www.ncbi.nlm.nih.gov/books/NBK537450/ Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. International Journal of Surgery. 2010;8(5):336 41. Methley AM, Campbell SM, Chew-Graham CM, Mcnally RM, Cheraghi-Sohi SM. PICO, PICOS and SPIDER: a comparison study of specificity and sensitivity in three search tools

for

qualitative

systematic

reviews.

BMC

Health

Services

Research.

2014Nov21;14(1):8. Rating Evidence in Medical Literature. AMA Journal of Ethics. 2011Jan;13(1):46. Baldwin S, Malone M, Sandall J, Bick D. Mental health and wellbeing during the transition to fatherhood. JBI Database of Systematic Reviews and Implementation Reports. 2018;16(11):2118. Ahun E, Koksal O, Sigirli D, Torun G, Donmez SS, Armagan E. Value of the Glasgow Coma Scale, Age, and Arterial Blood Pressure (GAP) Score for Predicting the Mortality of Major Trauma Patients Presenting to the Emergency Department. Turkish Journal of Trauma and Emergency Surgery. 2014Jul;20(4):241 7.

Bouzat P, Legrand R, Gillois P, Ageron F-X, Brun J, Savary D, et al. Prediction of intrahospital mortality after severe trauma: which pre-hospital score is the most accurate? Injury. 2016;47(1):14 8. Cassignol A, Markarian T, Cotte J, Marmin J, Nguyen C, Cardinale M, et al. Evaluation and Comparison of Different Prehospital Triage Scores of Trauma Patients on In-Hospital Mortality. Prehospital Emergency Care. 2018Nov20;23(4):543 50. Galvagno SM, Massey M, Bouzat P, Vesselinov R, Levy MJ, Millin MG, et al. Correlation Between the Revised Trauma Score and Injury Severity Score: Implications for Prehospital Trauma Triage. Prehospital Emergency Care. 2018Aug17;23(2):263 70. Hung YW, He H, Mehmood A, Botchey I, Saidi H, Hyder AA, et al. Exploring injury severity measures and in-hospital mortality: A multi-hospital study in Kenya. Injury. 2017;48(10):2112 8. Laytin AD, Kumar V, Juillard CJ, Sarang B, Lashoher A, Roy N, et al. Choice of injury scoring system in low- and middle-income countries: Lessons from Mumbai. Injury. 2015;46(12):2491 7. Laytin AD, Dicker RA, Gerdin M, Roy N, Sarang B, Kumar V, et al. Comparing traditional and novel injury scoring systems in a US level-I trauma center: an opportunity for improved injury surveillance in low- and middle-income countries. Journal of Surgical Research. 2017Apr3;215:60 6. Llompart-Pou JA, Chico-Fernรกndez M, Sรกnchez-Casado M, Salaberria-Udabe R, CarbayoGรณrriz C, Guerrero-Lรณpez F, et al. Scoring severity in trauma: comparison of prehospital scoring systems in trauma ICU patients. European Journal of Trauma and Emergency Surgery. 2016Apr18;43(3):351 7.

REVIEW OF READABLE DRIVER S LICENSE AS TRAFFIC ACCIDENT AND TRAUMA PREVENTION TECHNOLOGY Author : Kadek Egadia Calisto

(19/438962/KU/21268)

Ketut Shri Satya Wiwekananda

(19/438963/KU/21269)

Ketut Shri Satya Yogananda

(19/438964/KU/21270)

ABSTRACT Introduction In many low until middle-income countries, 30% until 86% trauma cases are caused by traffic accidents. Traffic accidents are the eighth largest cause of death in the world. According to the data from Headquarters of the Republic of Indonesia National police Traffic Corps (2013), 56% of traffic accidents involve driver without a license. It can be concluded that ownership of a driving license does affect driving safety and traffic accidents. Based on that problem, it is required to explore the possible use of readable driver’s license to prevent drivers without a license using the vehicle. Materials and Method The literature review was conducted using ProQuest, EBSCOhost, and Garba Rujukan Digital (Garuda) database to identify literatures that fit our topic. Key words that we use to search the literatures are: “readable” AND “driver’s license”; “driver’s license” AND “technology”; “traffic accident” AND “prevention” AND “technology”; “safety ride” AND “technology”; “Surat Izin Mengemudi”. Articles were included if they provide correlated and detailed information to this paper. Result and Discussion After searching for literatures, 12 journals that are relevant to the purpose of our study were obtained. Traffic accident prevention technology has been developed well. So far, there is no technology that can prevent driver without driver’s license to drive his vehicle. Readable driver’s license has been applied abroad with various technology applications. Readable driver license has also been applied in Indonesia to store driver’s data.

Conclusion There is no technology to prevent unlicensed driver from driving his vehicle, and readable driverâ&#x20AC;&#x2122;s license has not been applied as a traffic accident prevention technology. Readable driverâ&#x20AC;&#x2122;s license actually has a great potential as a traffic accident-causing trauma prevention technology. Readable driverâ&#x20AC;&#x2122;s license scanner can be connected to a vehicle engine, so the vehicle can only be activated if the driver has a license. .

REVIEW OF READABLE DRIVERâ&#x20AC;&#x2122;S LICENSE AS TRAFFIC ACCIDENTCAUSING TRAUMA PREVENTION TECHNOLOGY

Author : Kadek Egadia Calisto

(19/438962/KU/21268)

Ketut Shri Satya Wiwekananda

(19/438963/KU/21269)

Ketut Shri Satya Yogananda

(19/438964/KU/21270)

A ia Medical S de

cia i I d 2019

e ia (AMSA-Indonesia)

e l e he

ible

e f eadable d i e

lice e

e e di e

without a license using the vehicle. Materials and Method The literature review was conducted using ProQuest, EBSCOhost, and Garba Rujukan Digital (Garuda) database to identify literatures that fit our topic. Key words that we use to search the literatures are: echnology ; ech

eadable

AND

raffic accident AND

di e

lice e ;

evention AND

ech

di e l g ;

lice e

AND

afety ride AND

l g ; Surat Izin Mengemudiâ&#x20AC;?. Articles were included if they provide correlated and

detailed information to this paper. Result and Discussion After searching for literatures, 12 journals that are relevant to the purpose of our study were obtained. Traffic accident prevention technology has been developed well. So far, there i

ech

l g

ha ca

e e

di e

lice e

d i e hi

ehicle. Readable

driver license has been applied abroad with various technology applications. Readable driver lice e ha al

bee a

lied i I d

e ia

ed i e

da a.

Conclusion There is no technology to prevent unlicensed driver from driving his vehicle, and readable di e

lice e ha

di e

lice e ac all ha a g ea

ech

bee a lied a a affic accident prevention technology. Readable

l g . Readable d i e

e ial a a affic accide -causing trauma prevention

lice e ca e ca be c

vehicle can only be activated if the driver has a license.

ec ed

a ehicle e gi e,

Introduction A. Back Ground In many low until middle-income countries, between 30% until 86% trauma cases are caused by traffic accidents1. In United State, traffic accidents are the third leading cause of traumatic brain injury. From 2.8 million patients suffering traumatic brain injury, 383,293 patients were affected by brain trauma due to traffic accidents2. Traffic accidents are the eighth largest cause of death in the world3. Traffic accident number in Indonesia is raising significantly. In 2009 there were 62,960 cases of traffic accidents, in 2010 it increased to 109,319 and in 2011 there were 109,776 cases4. According to the data from Headquarters of the Republic of Indonesia National Police Traffic Corps (2013), 56% of traffic accidents involve drivers who do not have a drive

license5. It such a high number percentage and it's

very concerning because in Indonesia there is a regulation of driving license ownership before driving, namely Pasal 77 ayat (1) Undang-undang Nomor 22 Tahun 2009 concerned on Traffic and Road Transportation. Based on research, drivers who have a driving license also prioritize driving safety more than drivers who do not have a driving license6. It can be concluded that Ownership of a driving license does affect driving safety and traffic accidents. Based on that problem, it is required to explore the possible use of eadable d i e

lice e

e e

di e

a lice e

i g he ehicle.

So that we can prevent the incidence of traffic accidents-causing trauma by driver without a license. B. Objective With this study, it is expected to open up the possibility of making technology using readable d i e

lice e

prevent driver without a license

from driving their vehicles. Therefore, this study is aimed to review toward the development of existing traffic accident prevention technology, the application of readable driver lice e, a d he

ibili

as traffic accident prevention technology.

i g eadable d i e

lice e

II.

Materials and Methods The literature review was conducted using ProQuest, EBSCOhost, and Garba Rujukan Digital (Garuda) databases to identify literatures that fit our paper topic. Key words that are used to search the literatures are: readable AND d i e license ;

di e

lice e

prevention AND tech

AND

technology ;

l g ; safety ride AND

traffic accident ech

AND

l g ; Surat Izin

Mengemudiâ&#x20AC;?. Articles were entered if they meet this following criteria : The title is related to our study

Contain related information in abstract

Contain detailed information in result & discussion

Figure 1. The Inclusion Criteria III.

Results and Discussion After searching for literature, 12 articles that are relevant to the purpose of our study were obtained. From these 12 articles, we draw the core and combine the data to achieve the objectives of this literature review. It was seen that there was a very rapid development in the application of technology in motor vehicles to support the safety and prevention of traffic accidents. The following table shows the development of traffic accident prevention technology. Table 1. The Development of Safety Drive Technology Year

Technology

2004

there was an implementation of a data recorder in the form of a black box in vehicles to collect data and assist investigators in making a scene7

2008

CCTV-based vehicle surveillance technology was developed in the form of a Gatso camera that could take pictures of drivers and would match it with an existing driving license database8

2013

traffic accident prevention technology emerged using motor simulator technology which was used as training for prospective motorcyclists to prepare them before getting a driving license and jumping onto the highway9

2017

face recognition technology began to be implemented to improve the safety system in driving10

So far, there is no technology that can prevent driver without license from driving.

Readable d i e

lice es are widely used abroad. Real ID regulation in United

States recommend the use of readable technology for d i e

lice e reader11.

Department of Homeland Security (DHS) suggest the use of PDF417 barcode with 2005 AAMVA D i e

Lice e Ca d De ig Specifications12. PDF 417 barcode is

able to save 2000 alphanumeric or almost 3000 numeric characters, has a built-in error correction, easily printable, and flexibly readable13. The readable d i e license technology can also use an automatic identification and data capture system using magnetic stripe bars14. Enhanced Privacy ID (EPID) technology has also been developed f

eadable d i e

lice e. EPID technology can secure users privacy

data15. Radio Frequency Identification (RFID) technology was also developed for the readable d i e

lice e technology16. Automated Face Recognition

Technology (AFRT) can also be used to store data in a readable d i e technology17. Generally, readable d i e

lice e

lice e technology is considered more

practical to store data from users because it only needs to be scanned to show the user data. Di e

lice e i I d

e ia bec me a ma da

e i eme f

e e

to drive a vehicle in anticipation of a traffic accident. Readable d i e ech

l g

a de el

the validity f he d i e

ed b

i g a ba c de

lice e he

he d i e

lice e

di e lice e

de e mi e

lice c d c la e f ceme

road18. IV.

Conclusion So far, there is no technology to prevent driver without a license from driving his vehicle and readable d i e

lice e has not been applied as a traffic accident

prevention technology. Readable d i e

lice e actually has a great potential as a

traffic accident prevention technology. A readable d i e

lice e scanner can be

connected to a vehicle engine. Vehicles equipped with this technology will only turn on when the driver attaches his license

he d i e

lice e ca e ,

driver can only drive the car if the driver has a license. Implementation of this technology through further research project is hoped can reduce the number of traffic accidents-causing trauma because the driver does not have a d i e

license.

REFERENCES 1. World report on road traffic injury prevention. Geneva: World Health Organization; 2004.

2. Infographic: Leading Causes of Traumatic Brain Injury [Internet]. BrainLine. 2017 [cited

November

2019].

Available

from:

https://www.brainline.org

/slideshow/infographic-leading-causes-traumatic-brain-injury 3. World Healrh Organization. Global Status Report on Road Safety 2018. Geneva: World Health Organization; 2019. 4. Perhubungan Darat Dalam Angka (PDDA) [Internet]. Hubdat.dephub.go.id. 2012 [cited 7 November 2019]. Available from: http://hubdat.dephub.go.id/data-ainformasi/pdda 5. POLANTAS DALAM ANGKA. Jakarta: Headquarters of the Republic of Indonesia National Police Traffic Corps; 2013. 6. Asdar M, Rismayanti, Sidik D. Perilaku Safety Riding pada Siswa SMA di Kabupaten Pangkep

[Internet].2013

[cited

November

2019]

Available

from:

http://repository.unhas.ac.id/bitstream/handle/123456789/4246/MUHAMMAD%20ASDAR_ K11109367.pdf?sequence=1.

7. Accident Prevention Plus, Inc. Soon to Be Transportation Safety Technology, Inc.; National Highway Traffic Safety Administration Encourages the Use of Black Boxes. Business Wire 2004 Aug 11:1. 8. Corbett C. Techno-Surveillance of the Roads: High Impact and Low Interest. Crime Prevention and Community Safety 2008 02;10(1):1-18. 9. Balcius JA, Liang BA. Motorcycle Simulator Technology and Traffic-Related Injury Prevention: Global Health Potential: Research and Regulation. Journal of Commercial Biotechnology 2013 10;19(4) 10. Careem introduces 'facial recognition' technology to champion unprecedented passenger safety in ride-hailing. Al Bawaba 2017 Apr 11. 11. Marek AC. Will Real Id Cause Chaos at the DMV? US News & World Report [Internet]. 2006 December 18 [cited 2019 November 14];141(23):44. Available from: http://search.ebscohost.com/login.aspx?direct=true&db=a9h&AN=23397781&site=e host-live 12. Ha e J. A Re ie

f Eff

Sec e D i e

Lice e a d Ide ifica i

Ca d .

Vital Speeches of the Day [Internet]. 2007 May [cited 2019 Nov 14];73(5):208 12. Available

from:

http://search.ebscohost.com/login.aspx?direct=true&db=a9h&AN

=24855233&site=ehost-live 13. Marriott M. PDF417 portable data files a new dimension in barcodes. Sensor Review [Internet].

1995

[cited

2019

November

14];15(1):33-35.

Available

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https://search.proquest.com/docview/226847775/D2707D2E9D424897PQ/2?accounti d=13771 14. Da Costa B, Schulte J, Singer B. Surveillance Creep! New Manifestations of Data Surveillance at the Beginning of the Twenty-First Century. Radical History Review [Internet]. 2006 Spring [cited 2019 November 14];(95):70 88. Available from: http://search.ebscohost.com/login.aspx?direct=true&db=a9h&AN=20518467&site=e host-live 15. Brickell, E., & Li, J. Enhanced privacy ID: A direct anonymous attestation scheme with enhanced revocation capabilities. IEEE Transactions on Dependable and Secure Computing [Internet]. 2012 [cited 2019 november 14]; 9(3):345-360. Available from : http://dx.doi.org/10.1109/TDSC.2011.63 16. Smith K, McPhail B, Ferenbok J, Tichine A, Clement A. Playing with surveillance: The design of a mock RFID-based identification infrastructure for public engagement. Surveillance & Society [Internet]. 2011 [cited 8 November 2019];9(1):149-166. Available from: https://search.proquest.com/docview/1406196669/D2707D2E9D42 4897PQ/10?accountid=13771 17. MANN M, SMITH M. Automated Facial Recognition Technology: Recent Developments and Approaches to Oversight. University of New South Wales Law Journal [Internet]. 2017 January [cited 2019 November 14];40(1):121 45. Available from: http://search.ebscohost.com/login.aspx?direct=true&db=a9h&AN=122643180 &site=ehost-live 18. Suryani D, Yulianti A, Zulhelmi M. Aplikasi Legalitas Surat Izin Mengemudi (SIM) Berbasis Mobile (Studi Kasus : Polisi Resort Rengat). It Journal Research And Development [Internet]. 2018 [cited 14 November 2019];2(2):34 - 44. Available from: http://garuda.ristekdikti.go.id/documents/detail/726963 TABLE AND FIGURES

Figure 2. Design of The Future Project

Combination Therapy of Mesenchymal Stem Cells and Vitamin B12 for Spinal Cord

Injury Treatment Indonesian Medical Students T aining and Compe i ion 2019

Cici Yulian Anugraheni Rizqiko Pandai Hamukti Fandi Hendrawan Faculty of Medicine, Public Health, and Nursing Universitas Gadjah Mada Yogyakarta 2019

Combination Therapy of Mesenchymal Stem Cells and Vitamin B12 for Spinal Cord

Injury Treatment Cici Yulian Anugraheni*, Rizqiko Pandai Hamukti**, Fandi Hendrawan*** *ciciyuliananugraheni@gmail.com **kiko.hamukti@gmail.com ***hendrawanfandi4@gmail.com Introduction

disturbance the gastrointestinal system, urinary system and sexual function.[6]

Spinal cord injury (SCI) is one of the most common injury forms due to an accident

Nowadays, surgical treatment is the

like fall, road traffic accident (RTA), fall,

favorable treatment for the complete SCI

recreational or occupational accident.[1-3] In

treatment.

some countries, assault is also the main cause

developed such as double-door laminectomy,

of spinal cord injury.[1] From 4 forms of

corpectomy, open laminectomy, and etc.[7-9] In

Many

techniques

have

been

some countries, non-surgical treatments are

spinal cord injury; cervical, thoracal, lumbal,

developed.[7]

and sacral spinal cord injury, cervical spinal

also

cord injury is the most catastrophic event with

development of both therapies are already

the highest rates of morbidity and mortality.[4-

advanced,

doubt.[4][10]

Generally, SCI can be divided as complete

patient

SCI and incomplete SCI with worse prognosis

being

better

q ali

Since

Although

outcome the

of life i

the

still

improvement

he main arge of

complete SCI therapy, a better therapy is

in complete SCI. If the injury is induced by high-energy force, the complete spinal cord

needed in the case of complete SCI. Stem cell

injury will be likely happened. In the

transplantation

following year, complete SCI cases often

considerations in the way SCI is treated.

currently

one

the

Stem cell is an unspecialized cell

happens. It can impact on motor and sensory to

which has a potency to differentiate to be

complete SCI. Also, complete SCI cause

various types of cell.[11] There are 4 types of

disturbance of the cardiovascular system,

stem cells: totipotent stem cells, pluripotent

function,

especially

broncho-pulmonary

when

comes

system,

and

stem cells, multipotent stem cells, and

thermoregulation. Moreover, this injuries

unipotent stem cells. Recently, type of pluripotent stem cells become the most

favorable stem cells in medicine since it does

trial phase I to IV studies only. Literature

not contraindicated with bioethics.[11] Also,

searching process is shown in Figure 1.

MSCs can be cultured and induced in vitro. In nervous system, once the neuron is damaged, it can not be repaired.[12] The proliferation of neuron itself is limited, but mostly, it can not proliferate.

Therefore,

neuron

needs

enhancer to induce the proliferate and repair the damage on itself.[12] Stem cells can stimulate and form myelin. So far BoneMarrow cell is the best option and the most polite way to used.[13] Although stem cells have many potentials to make a better outcome in complete SCI cases, adverse effects like inflammation, vomiting can be happened. Therefore, this article aims to evaluate the outcome stem cells therapy in Figure 1. Flow Diagram of Study Selection

complete SCI cases and prevents the future adverse effects.[14]

Result From this searching, with the first

Method Literature searching was conducted

group keywords, 8 articles were found. Two

using MEDLINE database with PubMed

journals were excluded due to irrelevant

search engine for articles published between

subject of the journals. For the second group,

2015 until 2019. Two groups of keywords are

22 journals were identified. Eleven journals

used in the search field: (1) complete spinal

were excluded since irrelevant subject. The

cord injury and mesenchymal stem cells and

rest of journals were assessed further by

bone

and

reading the abstract and 6 more journals were

neuroprotective. The article only includes

excluded due to the lack of data. In the end,

english articles. For complete spinal cord

11 journals are used in this literature.

marrow,

(2)

vitamin

B12

injury, study selection only includes clinical

Discussion

able to stand up with several support and 2016

sitting down without back support, 60% of the

showed using mesenchymal stem-cells (MSCs)

patients have improvement by their American

treatment in SCI patients can improve patient

Spinal Injury Association (ASIA) Impairment

quality of life. When induced-MSCs is injected

Scale

in spinal cord, it can secrete neurotrophic

improvement on feeling sensation (cold,

factors that can induce plasticity in the spinal

warm, touch). Motor scores on three patients

cord. The stem cells trials gives that the

have been better. MRI (Magnetic Resonance

progenitor and the stem can increase the

Imaging) illustrated that 4 patients showed

neuropathic factors and myelination. It also

improvement of structural neural feature that

can regenerative capacity of the nervous

correlated with recovery process. Moreover,

system.[6][15-16] The outcome of stem cells

MRI imaging for 12 months illustrated no

therapy depends on the dosage be injected.[17]

overgrowth of cells and no development of

The

research

conducted

Table

MSCs

patients

showing

imaging, the severity of injury can be

showed MSCs procedure in 10 patients with in

Six

posttraumatic syringomyelia. Based on MRI

A research conducted[6] in 2016 characteristic

(AIS).

classified with AIS system.[6] Furthermore,

were

MRI imaging can help to reduce the AIS

introduced to the patient via lumbar puncture injection. This procedure is repeated every 4

grade.[1] The outcome of patients is shown in

weeks 3 times. After 12 constructive weeks

Table 2.

with 12 months following up, 8 patients were

Table 1. Characteristic of spinal cord injury patients

[6]

Table 2. Patient outcome after mesenchymal stem cells injection

Although the MSCs treatment gives a

[6]

wrong use of antibiotics can lead to bacterial

promising outcome, there is no specific

resistance.

dosage to be injected.[17] The research

methylcobalamin can be used as anti-

reported every stem cell treatment give side

inflammation and prevention to develop

effect for the patients: 3 patients after injected

inflammation reaction.

complain

headache

after

months

Therefore,

vitamin

B12

Inflammation effect of bone marrow

procedure, 1 patient suffering from urinary

stem cell transplantation can be reduced by

tract infection after 6 months transplantations,

vitamin B12, or methylcobalamin, that can act

and 3 other patients complain vomiting and

nausea. Headache is mostly found in MSC

anti-inflammatory,

antibacterial,

and

antioxidant.[19] Inflammation is marked by

intrathectal injection. Also, inflammation reaction was reported in every patient. Since

increased level of homocysteine in blood or

the inflammation reaction can induce more

called with hyperhomocysteinemia. Vitamin

damage in spinal cord and cause spinal cord

B12 has a role to manage the level of homocysteine

syndrome, antibiotics and corticosteroids were

the

blood

the

inflammation effect can be alleviated.[20]

given.[17-18] Although the inflammation were

Recommended doses for healthy patients that

relieved, there was no evidence of bacterial

can be used is vary classified by age of

infection. Some antibiotics also can cause

patients. List of Recommended doses is

hypersensitivity in patients. Moreover,

presented in Table 3. The recommended

transplant patient is expected to give a positive effect to support the process of spinal

Table 3. Recommended Dietary Allowances (RDAs)

cord

for Vitamin B12 [21]

regeneration.

The

combination

vitamin B12 treatment and bone marrow stem Age

Male

0 6

Female

0.4 mcg

Pregnancy

Lactation

cell transplantation for spinal cord injury can enhance the effect of the treatment to help the

0.4 mcg

months*

patient with spinal cord injury.

7 12

0.5 mcg

Conclusion

months*

MSC is expected to be a salvage

1 3 years

0.9 mcg

therapy after the first treatment in the SCI. In

4 8 years

1.2 mcg

fact, neurons can not regenerate if the destruction

9 13 years

1.8 mcg

14+ years

2.4 mcg

can

not

avoidable.

overcome the emptiness due to the destruction 2.6 mcg

2.8 mcg

of any neuron, MSC can be used to replace

* Adequate Intake

the neuron and promote regeneration in the

source for vitamin B12 uptake is clams that

nervous system. Despite the side effects

contain a high level of vitamin B12. With

which can be happened after the injection of

adequate uptake for vitamin B12, it is

MSC, vitamin B12 can be used as an anti-

expected

inflammatory

alleviate

the

effect

agent

reduce

the

inflammation by bone marrow stem cell

inflammation reaction since the introduction

transplantation.

of MSC. Also, vitamin B12 can promote the synthesis of neurotrophic factor which leads

Besides the anti-inflammatory effect,

to promote the regeneration of myelin sheath

vitamin B12 also has another important role in

in injured neurons, especially in peripheral

promoting the synthesis of neurotrophic

nerves. The combination of vitamin B12

factors that support neuronal survival.[22] The

treatment

neurotrophic factors have a function to

and

bone

marrow

stem

cell

transplantation for spinal cord injury is

promote peripheral axon and regeneration of

expected to enhance the effect of the

myelin sheath that will lead to the acceleration

treatment to help the patient with spinal cord

of neuronal regeneration after nerve injury.[23]

injury.

Application of vitamin B12 uptake to the bone marrow stem cell

patients.

In the future, specific dosage of MSC

Therefore,

research

should

is needed to give a better outcome and reduce

conducted to determine vitamin B12 dose for

any side effects of MSC injection. Currently,

SCI patients.

vitamin B12 dose is only available for healthy

3. Lรถfvenmark I, Norrbrink C, Nilsson-

Acknowledgement

Wikmar L, Hultling C, Chakandinakira S,

We are grateful to dr. Prattama

Hasselberg M. Traumatic spinal cord injury

Santoso Utomo from department of medical

in Botswana: characteristics, aetiology and

education Universitas Gadjah Mada for the

mortality. Spinal Cord. 2015 Feb;53(2):150

support and constructive comments for this

study.

4. Furlan JC, Craven BC, Massicotte EM, Fehlings MG. Early Versus Delayed Surgical

Disclosure

Decompression

The article searching for this paper

Spinal

Cord

after

Traumatic Cervical Spinal Cord Injury: A

was supported by University of Gadjah Mada

Cost-Utility Analysis. World Neurosurgery.

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and clinical outcomes retrospectively. Global

May;24(5):975 84.

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2. Joseph C, Delcarme A, Vlok I, Wahman K,

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perioperative-outcomes-in-a-propensity-

SJ, Jeon SR. A Phase III Clinical Trial

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Showing Limited Efficacy of Autologous

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Scientific Paper Competition IMSTC 2020 THE PROGNOSTIC VALUE OF S100B LEVEL AS A BIOMARKER OF EARLY PROGNOSIS IN PATIENTS WITH TRAUMATIC BRAIN INJURY: A SYSTEMATIC REVIEW OF COHORT STUDIES

***

Ayers Gilberth Ivano Kalaij , Michael Sugiyanto , and Valencia Hadinata * Second Year Medical Student, AMSAUI (kalaijayers@gmail.com) ** Second Year Medical Student, AMSA-UI (Michael.sugiyanto@yahoo.co.id) *** Second Year Medical Student, AMSAUI (valenciahadinata@gmail.com)

Abstract Introduction: Traumatic brain injury is one of the most prevalent traumas and can cause mortality in 30% patients and mortality in 50% patients. In recent years, studies regarding the prognostic value of S100B in traumatic brain injuries has been conducted. Objective: this systematic review aims to evaluate the feasibility and prognostic value of S100B in patients with moderate or severe traumatic brain injury. Methods: This review selects studies found by database searching systematically using previously determined inclusion, such as cohort or RCT studies, moderate to severe traumatic brain injury patients, have outcome predictors, and have serum S100B data, and exclusion criteria, such as pediatric patients and studies published over 10 years. This review was arranged based on PRISMA guideline. Results: From the 5 studies reviewed that were done in 5 countries, S100B level is proven to be strongly correlated to the outcome of traumatic brain injury compared to CT scan as the gold standard in traumatic brain injury prognosis. Conclusion: This review has proven that S100B has a significant correlation with the outcome of traumatic brain injury patients, therefore S100B level can be considered as a promising prognostic value of traumatic brain injury outcome. Keywords: S100B, Traumatic Brain Injury, Prognosis

THE PROGNOSTIC VALUE OF S100B LEVEL AS A BIOMARKER OF EARLY PROGNOSIS IN PATIENTS WITH TRAUMATIC BRAIN INJURY: A SYSTEMATIC REVIEW OF COHORT STUDIES Scientific Paper

Ayers Gilberth Ivano Kalaij Michael Sugiyanto Valencia Hadinata 2019

Scientific Paper Competition IMSTC 2020 THE PROGNOSTIC VALUE OF S100B LEVEL AS A BIOMARKER OF EARLY PROGNOSIS IN PATIENTS WITH TRAUMATIC BRAIN INJURY: A SYSTEMATIC REVIEW OF COHORT STUDIES Ayers Gilberth Ivano Kalaij, Michael Sugiyanto, and Valencia Hadinata

Abstract Introduction: Traumatic brain injury is one of the most prevalent traumas and can cause mortality in 30% patients and mortality in 50% patients. In recent years, studies regarding the prognostic value S100B in traumatic brain injuries has been conducted. of Objective: this systematic review aims to evaluate the feasibility and prognostic value of S100B in patients with moderate or severe traumatic brain injury. Methods: This review selects studies found by database searching systematically using previously determined inclusion, such as cohort or RCT studies, moderate to severe traumatic brain injury patients, have outcome predictors, and have serum S100B data, and exclusion criteria, such as pediatric patients and studies published over 10 years. This review was arranged based on PRISMA guideline. Results: From the 5 studies reviewed that were done in 5 countries, S100B level is proven to be strongly correlated to the outcome of traumatic brain injury compared to CT scan as the gold standard in traumatic brain injury prognosis. Conclusion: This review has proven that S100B has a significant correlation with the outcome of traumatic brain injury patients, therefore S100B level can be considered as a promising prognostic value of traumatic brain injury outcome.

Keywords: S100B, Traumatic Brain Injury, Prognosis

Introduction

estimated to sustain a TBI every year.3 Injury

In recent years, traumatic brain injury (TBI)

grading is very various in range, from mild

is a major phenomenon confined to damage

with low mortality rate until severe with life-

injured

considered

threatening lesion. 4 About 30% of patients

heterogeneous pathological disease state

admitted after severe traumatic brain injury

by,

but

also

which can affect all ages.

1,2

Overall,

will die while 50% of them will be moderately disabled.5-6

according to recent study, sixty-nine million individuals across the world are

Despite recent improvement in management of TBI patients in intensive

care

and

standardise

care

guideline

evidence suggesting a potential clinical role

development, mortality and morbidity in

of S-100

these patients remains high. The treatment

association between S-100

for TBI objective is to reduce the extent of

short, mid, and long term outcome of

secondary brain-damage following the

prognosis is remains unclear in TBI

primary effect.4

patients.9,16

Lack

a b

a e, e

e a d

sufficient

Early prediction of prognosis in

discriminative capacity to inform clinical

TBI is currently based on demographic,

decision making also indicated that other

clinical and radiological features, including

type of prognostic indicators are needed.

age, initial Glasgow Coma Scale (GCS)

Measurements of using S-100

score, pupillary response, vital signs,

also not widely used in clinical practice and

significant

are not considered standard of care.10-11

non-cranial

injuries,

and

computed tomography (CT) indices7;

Therefore, evaluation of the prognostic

however,

outcome

value of this biomarker after moderate or

limitations

severe TBI could be a breakthrough in

these

predictions

clinical

have

several

because of lack of neurologic assessment

early prediction of prognosis.

based on use of many drugs compared to

Within the authors

initial

radiological

clinical

course,

7-8

information

especially

with

ed e,

there are no other study has evaluated

diffuse

specifically assess the feasibility and

Therefore, enormous diagnositic

prognostic value of this biomarker in

and prognostic opportunity promise in

moderate or severe traumatic brain injury

developing

assays

TBI-

patients. Thus, this systematic review aims

associated

biomarkers

and

to evaluate the feasibility and prognostic

injury.

measuring accurately

specifically has been studied recently.8

value of S100B in patients with moderate

Over the last 20 years, studies of

or severe traumatic brain injury are

biochemical markers of brain damage as a

desperately needed due to the emergence

potential tools for prognostic evaluation have

and its potential in early prediction of

been increasing.

9-13

100

e ,

Concentrations of Sb

prognosis. Through this endeavor, the results of this review is hoped to help to

f a ca c

binding protein present mainly in glial and

improve guidelines of advanced trauma

Schwann cells14, are being studied regarding

care systems considering this biomarker as

increase of this substance in human blood

an early prognostic biomarker, thereby

and cerebrospinal fluid which lead to brain

achieving the goals of reducing mortality

damage.15-16 Even though

and morbidity associated to TBI.

Methods

and follow-up the association between

Study selection

S100

This systematic review of is conducted

outcome, which requires a period of time.

based on PRISMA statement. Cohort

Details of study search strategy are shown

studies that were published 10 years prior

in Figure 1.

c ce

a d

e c

to 3 December 2019 were reviewed to assess the Glasgow Outcome Scale (GOS) and mortality. There were two selection phases in finding eligible literature for this review. First, online databases such as PubMed, Scopus, and Cochrane Library were

searched

keywords

using terms:

the

following

((S100B)

AND

traumas) AND injury severity score). Studies was title screened based on relevance to the topic. Phase two involved studies screening according to the eligibility for inclusion as

Figure 1. Study search strategy

follows: (1) cohort and/or RCT studies, (2) studies included patients with moderate

Data extraction and risk of bias assessment

and

Subsequently, data were extracted from our

severe

traumatic

brain

injury

(GCS<13), (3) determined and report the

selected articles by two reviewers using

S-100

standardized forms. Then they were

concentrations in urine or

Cerebrospinal fluid (CSF) or blood, (4)

independently assured by the third

include outcome predictor (mortality or

reviewer. Duplicates were also removed in

glasgow outcome score (GOS) or brain

the prior process, therefore the identical

stem death), (5) at least one follow-up was

data will only be extracted once. Extraction

conducted. Exclusion criteria in this review

of study characteristics include author and

were:

year of publication, study design, sample

(1)

pediatric

patients,

(2)

inappropriate study types or design, and (3)

size, study location, inclusion and

published before 2009 to ensure the

exclusion criteria, follow-up, assay,

relevancy of the studies in today situation.

comparison group, and outcomes of study

Cohort studies were used for this review as

as expressed by GOS or mortality.

its outcome is more compatible to identify

Moreover, quality and bias assessment of the studies reviewed were assesed using 48

Newcastle-Ottawa Scale tools designed for

were cohort studies that were conducted in

cohort studies (NOS-Cohort). This scale

six different countries, including Serbia,

uses a

America, Netherlands, Sweden, and Spain.

c a

judged based on three broad perspective:

Outcomes were given in terms of GOS

study selection, comparability of the

and/or mortality after follow-up. Results of

groups, and the ascertainment of either the

quality assessment based on NOS-cohort

exposure of interest.17 Quality assessment

were given in the appendix part on the last

was

part of this paper.

done

collaboratively

three

reviewers until consensus were reached. Discussion Results

Summary of main results

Study selection

5 studies with total subject of 1.265 have been reviewed. Those studies was done in

Initially, searches from database searching using the keyword ((S100B)

Serbia18,

AND traumas) AND injury severity score)

Netherlands20, Sweden21, and Spain22.

yielded a total of 51 records. The process

Studies

of literature searching and selection is

excluded since traumas, whatever the

illustrated in Figure 1. After those records

causes is, is more prevalent in adults than

are identified, duplicates were removed,

titles and abstracts were screened, and full-

mechanisms in adults are different from

text articles were then assessed for

children, the prognostic value of S100B in

eligibility. In phase two of the selection

adults is thought to be more necessary to be

process,

further

assessed. To find a strong correlation

excluded due to irrelevant study types,

between the S100B level and the outcome

inappropriate study population, irrelevant

of traumatic brain injury, studies with

outcomes,

restrictions.

subject dominated by mild traumatic brain

Ultimately, this resulted in a final of 5

injury were excluded. Overall, S100B level

cohort studies to be included in qualitative

is proven as a good predictor in the

synthesis.

outcome of traumatic brain injury.

fifteen

and

studies

language

were

Study characteristics and outcomes

the

with

children.

United

pediatric

Since

States19,

subjects

the

were

physiological

Gold standard for prognosing traumatic

Study characteristics included in

brain injury

this review are shown in Table 1. Overall,

Clinicians all over the world, including in

this review included a total of 1295

Indonesia, use computed tomography (CT

samples of patients. All 5 included studies

scan) as a gold standard for prognosing

traumatic brain injury. CT scan uses

should not be included as a CT scan

computer-processed X-ray measurement

parameter and has led to confusion among

from various angles to produce many

clinicians. 23 Besides, many studies have

sectional images of a specific area in

proven

human

any

changes continuously occur up to the first

abnormality in head region, such as

48 hours after the trauma. A study by

infarctions, tumors, calcifications, and

Stenberg et al. demonstrated that severely

bone traumas, can be clearly visualized.

injured group scanned by CT increased by

Besides, with such a clear visualization, CT

50% from initial CT scan after trauma to

scan is relatively easy to perform. In daily

24 hours after trauma.24 It can be inferred

clinical

that the outcome of traumatic brain injury

traumatic brain injury patients is classified

cannot be predicted by performing CT scan

based on Marshall classification. Marshall

once or twice.

body.

Using

practice,

scan,

scan

result

that

pathological

intracranial

score serves as the gold standard in prognosing the outcome of traumatic brain

S100B protein assessment options

injury patients. Injury features that are

Several options of assay kits used in clinics

discriminated in Marshall classification are

and laboratories are available to measure

presence

intracranial

S100b concentrations in the human body,

abnormalities, presence or absence of mass

although ELISA has been named as the

lesions, shifting of basal cisterns, and

golden

absence

planned evacuation of mass lesions.

standard.

The

ELISA

kit

available from various manufacturers, such

Figure 2 shows the Marshall classification

as CanAG Diagnostics from Sweden, and

in tree structure.

Sangtec from Italy to name a few. However, ELISA assays generally take up

However, Marshall classification was not

to 4-6 hours long and may result in high

initially developed for prognostic purpose.

inter-assay and intra-assay coefficients of

First, Marshall classification does not

variation (CV) compared to other clinical

distinct the type of mass lesion. Many

assays.25

studies stated that patients with epidural hematoma have a better prognosis than

The two most frequently used assays in

subdural or intracranial hematoma. On the

clinical settings include the quantitative

contrary,

automated

Marshall

classification

luminometric

differentiates between evacuated and non-

LIAISON-mat

evacuated mass lesion. Many argued that it

electrochemiluminescence immunoassay or

S100

immunoassay

system

and

the

more commonly known as Elecsys S100B.

(OD) is measured at a wavelength of 450

The LIAISON system is designed to screen

S100B protein levels in cases of melanoma

concentration is proportional to the value

and other malignant tumors. It is not

of the OD.27

Âą

nm.

The

Human

S100B

designed for quick analysis, which makes it a less time-efficient assay. On the other

Advantages of S100B protein

hand, the Elecsys system is gradually

The

gaining

relatively

popularity

only

takes

S100b

protein

easily

can

and

also

handled

has

great

approximately 18 minutes to run a serum

reliability in analysis. This is because the

sample, which makes it very efficient for

S100b protein is a favorable and useful

TBI patients and suitable in NICU and

biomarker for clinical use which is very

emergency room (ER) use.25,26

stable and unaffected by storing, freezethaw cycles, and temperature changes.28

S100B protein ELISA kit

Another noticeable and key advantage of

The S100B ELISA kit uses the Sandwich-

the S100b protein is the resistance towards

ELISA principle. The kit includes a micro

hemolysis in the sample, making it a

ELISA plate which has been pre-coated with

competent biomarker in acute cases.29 The

Human S100B specific antibody. First,

cut-off value of S100B level is shown in

standards are combined with the specific

table 2 and 3.

antibody by mixing it to the micro ELISA plate wells. Next, a biotinylated detection

Limitations of the review

antibody specific for Human S100B and

This study is not without limitation due to

Avidin-Horseradish

(HRP)

the exclusion of inaccessible full-text

conjugate are added to each micro plate well

articles and studies with incompatible

and incubated. During this process, free

language. Moreover, the level of evidence

components are washed away and well are

regarding studies included due to specific

added with the substrate solution. Blue color

inclusion-exclusion criteria of may present

will only appear in wells that contain Human

limitations. Further review to find precise

S100B, biotinylated detection antibody and

methods to measure S100B could be done

Avidin-HRP conjugate. Lastly, the stop

as this review have not mentioned it.

Peroxidase

solution is added so that the enzymesubstrate reaction is terminated and the color

Implications for further research

turns yellow. Spectrophotometrically, the

Further researchs should try to standardize

optical density

testing methods and identifying optimal

threshold values and sampling time for the determination

prognosis

combining S-100

and

c ce

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Comparison of four different assays

simple,

Appendices Table 1. Characteristic of Studies Studi es

Study Design

Sample size

Stefa

Cohort

130

novic B et al. 2017

Prospe ctive

Polytrau matized patients with the associate d traumati c brain injuries

Goyal Cohort Serum et al. Prospe (n=80 subjects; 2013 ctive n=224 samples) and CSF (n=138 subjects; n=499 samples) samples

Study Locatio n

Inclusio n criteria

Exclusion criteria

Follo w-up

Assay

Compa rison Group

Main Outco me

Central Intensiv e Therapy Unit of the Clinic for Emerge ncy Surgery , Clinical Center of Serbia

Age 1865 years, polytrau matized patients with associate d TBI of varying severity

History of neurologi cal and psychiatri c diseases and disorders, and addicted to drugs, opioids and alcoholic beverages .

14 days after the brain injur y

Electrochemiluminesc ence immuno assay

Unfavo urable outcom e GOS 3 Favour able outcom e GOS 4-5

GOS at 14 da : 3 unfavou rable, 45 favoura ble

Level 1 trauma center, Univers ity of Pittsbur gh, Pittsbur gh, Pensylv ania

A e 16 years, GCS Sc e 8 indicatin g sTBI; at least two time points of CSF or serum sample collectio n during the first 6 days postinjur y

Have cardiac or respirator y arrest or document ed prolonged hypoxia or hypotensi on before admission ; evidence of brain death within the first 3 days after injury; an Abbreviat ed Injury Score (AIS) of 5 in any region other than the brain; or penetratin g TBI

6 mont hs postinjur y

NexusDx S100b enzyme-linked immunosorben t assay (ELISA)

GOS: 1, 2-3, 4-5

GOS at 6 months: 1= dead; 5 =good recover y

DRS: nonetopartial disabili ty (score, 0 3); modera te-tosevere disabili ty (score, 4 14), and extrem ely severe disabili ty to death (score, 15 30).

DRS at 6 months: 0= no disabilit y; 30dead

Vos et al. 2010

Cohort prospec tive

79 patients with TBI (Glasgo w Coma Scale score [GCS] 1 2), serum, taken at hospital admissio n

Theli

Cohort

417

n et al. 2016

Retrosp ective

patients with at least three measure ments of serum s100B and NSE (sampled twice daily)

Radbou d Univers ity Nijmeg en Medical Centre Emerge ncy Depart ment (RUNM CED), level I trauma center

Moderat e/ severe TBI admitted between October 2004 and March 2006

no blood sample taken, age <18 years, no informed consent, hospital admission more than 24 hours after the accident, alcohol or drug abuse or dementia, no possibility of followup, and inability to speak Dutch.

6 mont hs postinjur y

S100B STAT Assay

Unfavo urable outcom e GOSE 1-4 vs Favour able outcom e GOSE 5-8

GOSE at 6 months: 1-4 unfavou rable, 58 favoura ble

Neurointensiv e care unit at Karolin ska Univers ity Hospita l, Stockho lm, Sweden between 2005 and 2013

A e 18 years, at least three measure ments of S100B and NSE, where the first sample had to be obtained within 48 hours and three samples within 72 hours after trauma, the admissio n CT scan had to be available and the longterm function

Too few samples, early death, patients with short ICU stay and predomin antly higher GCS patients, GOS evaluation <3 months after trauma

3 mont hs after the trau ma

Quantitative automated immunoassay, then changed to an automated electrochemolu minescence assay throughout study

Unfavo urable outcom e GOS 1-3 vs Favour able outcom e GOS 4-5

GOS at dischar ge, after 3-6 months as the patient visits the operatin g physicia n in the clinic or at the rehabilit ation and after 12 months through a quality of life questio nnaire 1=dead, 2=veget ative state, 3=sever e,

Guerr ero et al. 2013

Cohort Prospe ctive

140 patients with severe TBI (Glasgo w Coma Scale score [GCS] 8)

Neurocr itical Care Unit at the Virgen de R c Â´o Univers ity Hospita l in Seville, Spain, from June 2008 through June 2011

depende

outcome had to be evaluate d 3 months after the trauma

nt state, 4=mode rately recover ed, indepen dent state and 5=good recover y.

Patients with severe TBI (GCS 8) , admitted to the Study Location Hospital, from June 2008 through 2011

Hospital admission > 6h posttrauma, pregnancy , being<15 years of age, alcohol or other drug abuse at the time of injury that would affect conscious ness level, diagnosis of mild or moderate TBI, acute or chronic renal failure, history of neoplastic processes such as melanoma , psychiatri c illness, neurodege nerative disease, or previous neurologi cal sequelae

24 hour post admi ssion

Electrochemilu minescence assay (ECLIA)

Brain Death or nonBrain Death

S100B concent rations for the BD group, higher than non-BD group through out the study period.

Figure 2. Marshall Classification in tree structure23

Table 2. Cut-off value of S100B protein in

Table 3. Cut-off value of S100B protein in

the diagnosis of unfavorable outcome after

the prediction of mortality after TBI30

TBI30

Sel Re coh Selection ecti pre ort of nonon sen interventi tati on cohort ven ess of the exp ose d

Stefanovic B et al.

☆

Ascertain ment of interventi on

☆

D e m on str ati on of ou tc o m e int er es t w as

not prese nt at start of study

☆

C o m pa ri bi lit y

Age, Addition O sex, al factors ut and co marit m al e facto rs

Asses sment of outco me

Fo llo w up w as lo ng en ou gh fo r

outc ome s to occu r

Adequac y of follow up of cohorts

☆

2017 Goyal et al. 2013 al.

☆

Thelin et al. 2016

☆

Guerrero et al. 2013

☆

Vos et 2010

Table 4. NOS-Cohort of the included studies

☆

First Aid Knowledge, Attitude, Practice, and Factors Related to the First Line Treatment of Traumatic Injury A Systematic Review Chatrine Angelica D. C.1, Ardhito Rahadian2, Timothy V. P. Reba2 1

Second Year Medical Student, Universitas Kristen Indonesia

Third Year Medical Student, Universitas Kristen Indonesia

Introduction Traumatic injury is a health problem that is increasing significantly throughout the world. Around 5.8 million people die each year from injury and this accounts for 10% of world deaths where the mortality rate is 32% higher than the number of deaths from malaria, tuberculosis and HIV / AIDS. Globally, the three main causes of death from trauma injuries are traffic accidents, homicide, and suicide. In 2030, trauma due to accidents is expected to increase significantly which is the fifth leading cause of death in the world, suicide at 12th, and homicide on 16th. Accidents that cause trauma have life-threatening consequences, this can occur anywhere and at any time and there is a deliberate factor. This accident is an accident that requires immediate life-saving treatment to prevent disability. This first aid is an intervention that can be done by someone with or without medical equipment. Materials and Method We searched e-database (PubMed, Google Schoolar, and Research Gate) to conduct this literature and systematic review. While screening the title, abstract and full-text eligibility there are 5 journal that meet the full criteria. Results and Discussion In this study we can found there

l 40% e

had fi

aid k

ledge, 81%

had the appropriate attitude, and 40,8% respondent had practice and action related to traumatic injury. The results revealed that the status of first aid education and training was an important factor for first aid practice.

Conclusion The majority of respondents have the basic knowledge and attitude that first aid lives. However, based on systematic studies, it can be found that only a few respondents were trained in first aid. However, some respondents have given good results where several respondents have done first aid firsthand. Keywords: First-aid, first line treatment, traumatic injury.

First Aid Knowledge, Attitude, Practice, and Factors Related to the First Line Treatment of Traumatic Injury A Systematic Review

Authors: Chatrine Angelica Dwi Christy Arditho Rahadian Timothy Verellino Patrick Reba

Asian Medical Students A ocia ion-Indonesia (AMSA-Indonesia) 2019

Introduction Traumatic injury is a health problem that is increasing significantly throughout the world.(1) Around 5.8 million people die each year from injury and this accounts for 10% of world deaths where the mortality rate is 32% higher than the number of deaths from malaria, tuberculosis and HIV / AIDS. Not only mortality, there are several thousand people injured and many of them with permanent sequelae. Traumatic injuries greatly affect the socio-economic level which accounts for 16% of the global disease burden.(1)(2) Globally, the three main causes of death from trauma injuries are traffic accidents, homicide, and suicide. In 2030, trauma due to accidents is expected to increase significantly which is the fifth leading cause of death in the world, suicide at 12th, and homicide on 16th.(2)

Accidents that cause trauma have life-threatening consequences, this can occur anywhere and at any time and there is a deliberate factor. This accident is an accident that requires immediate life-saving treatment to prevent disability. This first aid is an intervention that can be done by someone with or without medical equipment. (3) If a person who is traumatized does not immediately receive first aid, his condition will worsen and will affect their future health, quality of life, or even lead to death. (4) Therefore, it is important to have basic knowledge about first aid.

Material and Methods Initial search result from PubMed, GoogleSchoolar, and Research gate (n=50) Irrelevant title excluded (n=25)

Title screening of authenticity and duplication (n=25)

Abstract screened (n=20)

Full-text assessed for eligibility (n=8) Full-text article excluded (n=3)

Full-text eligible cross-sectional articles included in review (n=5)

III. Results and Discussion Author (Year)

Ganfure

Study Design

Location Sample Size

Only 40% of the teachers were

A cross-

G., et al

sectional

(2018)

study

Results

Ethiopia 194

knowledgeable and 75% of them had a positive attitude for first aid to traumatic

injury. 80% of teachers encountered with children in need of first aid. A total of 42.8% of participants had a moderate level of first aid knowledge to traffic injury. However, 90.8% of Jamaludin A T., et al (2018)

quantitative

participants had a Malaysia

348

conscious attitude and

cross-

a positive attitude

sectional

towards first aid knowledge. 55.4% of study participants had not experienced taking first aid courses and they had little knowledge of this. The majority of participants were

Study Khatatbeh Population, M.

Cross-

Jordan

883

females (65.9%) with mean age (standard

Sectional

deviation) of 19.9

(2.6) years. Only 29.2% of students had previous first aid experience. When asked, only 11% of students knew the normal respiration rate of an adult in 1 min. 96.4% of the study participants were familiar with the term "first aid"; 92.1% were aware that first aid can save life, but only a negligible number of Awasthi

Cross-

S., et al

sectional

participants (1.2%) India

252

had received any formal training in first aid. 8.9% and 22.2% of the drivers prioritized breathing maintenance and chest compression, respectively. Only a sixth (16.3%) of

participants were aware of the signs of airway obstruction / problem; and only a third (31.7%) knew the correct recovery position for semiconscious or unconscious person. Only 57.9% of participants had the right knowledge on how to stop severe bleeding and about three-fourth of them (73.4%) knew that a splint was applied in bone fractures. About half (50.3%) of respondents had first Teshale A.

Crosssectional

aid knowledge more Ethiopia

785

than 80% had the appropriate attitude towards first aid, and only 44.3% assisted a

car accident victim in the past one year. First aid training: 26,8% Knowledge of first aid: 50,3% Discussion: This study found that there are still many people from every occupational circle such as students, drivers or teachers who are not trained in first aid, do not have a first aid kit, and have a low level of first aid knowledge, attitude, and practice regarding traumatic injuries. Less than half have helped victims of car accidents in the past year. In this study we can found there onl 40% e ponden had fi

aid

knowledge, 81% had the appropriate attitude, and 40,8% respondent had practice and action related to traumatic injury. The results revealed that the status of first aid education and training was an important factor for first aid practice. IV. Conclusion The majority of respondents have the basic knowledge and attitude that first aid lives. However, based on systematic studies, it can be found that only a few respondents were trained in first aid. However, some respondents have given good results where several respondents have done first aid firsthand.

References World Health Organization. Guidelines for essential trauma care. Geneva: World Health Organization. 2004. World Health Organization. Injuries and violence the facts. Geneva: World Health Organization. 2010. Ganfure G, Ameya G, Tamirat A, Lencha B, Bikila D. First aid knowledge, attitude, practice, and associated factors among kindergarten teachers of Lideta sub-city Addis Ababa, Ethiopia. Ethiopia: Plos One [Internet]. 2018 Mar 13 [cited 2019 Des 5]. Available from: https://journals.plos.org/plosone/article?id=10.1371/journal.pon e.0194263#sec005 Awasthi S, Pamei G, Solanki H, Kaur A, Bhatt M. Knowledge, attitude, and practice of first aid among the commercial drivers in the Kumaon region of India. India: J Family Med Prim Care [Internet]. 2019 Jun [cited 2019 Des 5]; 8 (6): 1994-1998. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6618230/#ref6

Jamaludin T, Zakaria M, Saidin S, Chan C. Knowledge, Awareness and Attitude of First Aid Among Health Sciences University Students. Malaysia: International Journal of Care Scholars[Internet]. 2018 Feb 2 [cited 2019 Dec 5]; 1 (1), 29-33. Available from:

https://journals.iium.edu.my/ijcs/index.php/ijcs/article/view/42/ 7

Khatatbeh M. First Aid Knowledge Among University Students in Jordan. Jordan: Int J Prev Med [Internet]. 2016 [cited 2019 Des 5]; 7: 24. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4755219/ Teshale A, Alemu Z. Knowledge, Attitude and Practice of first aid and factors associated with practice among taxi drivers in Addis Ababa, Ethiopia. Ethiopia: J. Health Dev. 2017 [cited 2019 Des 5}; 31 (3)

The Efficacy of Blood Transfusion in Damage Control Resuscitation (DCR) As a Non Invasive Life Saving Procedure for Severely Hemorrhagic Patients Anju Nadine Tiarma Putri Pardede, Bethaniel Roy Matthew

Abstract Injuries contribute to around 10% of total deaths and 15% of disability-adjusted life-years. Road traffic injuries (RTIs) place a huge burden on the health sector in terms of prehospital care, acute care, and rehabilitation. According to Indonesia Health Profile 2017 . Health crisis due to natural disasters was the most frequent incident in Indonesia in 2017 with a percentage of 72%. The remaining 27% were non-natural disasters, and only 1% of all disasters was included in social disasters. Most of the deaths occur due to poor decision and inappropriate interventions. Studies search were conducted by using search engine such as PubMed, Google Scholar, and NCBI massi e transfusion protocol

ith the criteria of studies which published 2005-2019 and related to this topic.

An estimated 10-20% of these deaths are potentially preventable with better control of bleeding .The mortality rate associated with Acute Trauma Coagulopathy (ATC) is increasing along with ISS (Injury Severity Score).Recent study that has been conducted by Holcomb JB et al found the evidence of the primary trial outcomes of mortality at 24 hours and 30 days were obtained on 100% and 99.4% of patients, respectively. No significant differences in mortality were detected at 24 hours. The pioneering data for a balanced ratio of PRBCs and FFPs came from military experience, where the survival of combat hospital patients receiving variable ratios of FFP:PRBC was studied. The survival of patients receiving FFPs in a 1:8 ratio compared to PRBCs was dramatically higher than those receiving FFPs in a 1:1.4 ratio (92.5% vs 37%, p < 0.001). DCR methods to resuscitate correcting coagulopathy and has shown to improve the chances of survival in the exsanguinating trauma patient by reversing the lethal trias of death by including permissive hypotension, body rewarming, minimization of fluid resuscitation, and early balanced administration of blood and blood products.

The Efficacy of Blood Transfusion in Damage Control Resuscitation (DCR) As a Non Invasive Life Saving Procedure for Severely Hemorrhagic Patients

Created by Anju Nadine Tiarma Putri Pardede Bethaniel Roy Matthew

Faculty of Medicine Universitas Kristen Indonesia 2019

The Efficacy of Blood Transfusion in Damage Control Resuscitation (DCR) As a Non Invasive Life Saving Procedure for Severely Hemorrhagic Patients

Introduction Injuries contribute to around 10% of total deaths and 15% of disability-adjusted lifeyears. Road traffic injuries (RTIs) place a huge burden on the health sector in terms of prehospital care, acute care, and rehabilitation. According to WHO, RTIs are the sixth leading cause of deaths in India with a greater share of hospitalizations, deaths, disabilities and socioeconomic losses in young and middle-age populations.1 According to Indonesia Health Profile 2017, during 2017 out of 2,263 monitored incidents, 198 were recorded as health crisis incidents due to disasters and potential disasters. Health crisis due to natural disasters was the most frequent incident in Indonesia in 2017 with a percentage of 72%. The remaining 27% were non-natural disasters, and only 1% of all disasters was included in social disasters.2 The concept of the distribution of mortality after injury along a chronological axis was initially characterized by Trunkey based on his experience and research in his seminal work describing the trimodal distribution of trauma death. This distribution of death after traumatic injury is classically described with death occurring during immediate, early, and late time frames after injury. Ea

occur within the first few hours after injury.

During this early interval, frequently injured patients have survived a period long enough to receive care from emergency medical services and hospitals. Most deaths in this time interval can be attributed to major CNS injuries or hemorrhage. As little can be done to ameliorate the effects of primary CNS injury, clinical efforts are directed toward optimization of brain perfusion and minimizing secondary brain injury.3 Assuming these tenets, the mortality of injured patients who succumb to CNS injury is largely not preventable. On the other hand, some of the deaths secondary to hemorrhage during this interval are potentially preventable and highlight opportunities to advance medical interventions and trauma systems. The interval between injury and definitive control of the focus of bleeding is most critical for this group of injured patients. The third

a a

injury, usually due to infection, multiple organ failure, or the latent effects of devastating brain injury. It is especially notable that death after trauma is largely an

50%

injury, another 25% to 30%

a 6

cc ,a

2 a

buted over the

subsequent days to weeks.4 Most of the deaths occur due to poor decision and inappropriate interventions. An estimated 10-20% of these deaths are potentially preventable with better control of bleeding. Early hemorrhage within 6 h after incurring an injury emerged as the biggest cause of preventable deaths. This has led trauma teams to investigate whether the change in practice could help reduce early mortality after severe trauma.4 Damage control resuscitation (DCR) is a systematic approach to the management of the trauma patient with severe injuries that starts in the emergency room and continues through the operating room and the intensive care unit (ICU). Damage control resuscitation (DCR) is a strategy for resuscitating patients from hemorrhagic shock to rapidly restore homeostasis. DCS is now incorporated as a component of DCR. DCR as a structured intervention begins immediately after rapid initial assessment in the emergency room and progresses through the operating theater into the ICU in combination with DCS.5 DCR strategies consists of 5 stages

: body rewarming, strictive fluid administration, permissive hypotension, balanced blood product administration, and the implementation of massive transfusion protocols.6 Efforts are focused on blood product transfusion with whole blood or component therapy closely approximating whole blood, limited use of crystalloid to avoid dilutional coagulopathy, hypotensive resuscitation until bleeding control is achieved, empiric use of tranexamic acid, prevention of acidosis and hypothermia, and rapid definitive surgical control of bleeding. In this study, we focus on the using of blood in resuscitation. According to recent studies, the plasma is beneficial in correcting coagulopathy.20 Therefore, this study aimed to explain why the use of plasma in DCR is beneficial on severe hemorrhage patients.

Material and Methods Studies search were conducted by using search engine such as PubMed, Google Scholar, and NCBI with keyword Da a resuscitation ,

Resuscitation , c

published 2005-2019 and related to this topic.

a c a

c , c

Result and Discussion The traditional view of resuscitation is focussed on fulfilling the loss of volume rather than the clotting process itself. The use of crystalloid or colloid fluid can b

replace

the loss of coagulation factors that has been reduced by the blood loss. Thus, this will increase the mortality rate of the patient with sever haemorrhagic condition. The mortality rate associated with Acute Trauma Coagulopathy (ATC) is increasing along with ISS (Injury Severity Score) (Figure 1). Recent study that has been conducted by Holcomb JB et al found the evidence of the primary trial outcomes of mortality at 24 hours and 30 days were obtained on 100% and 99.4% of patients, respectively. No significant differences in mortality were detected at 24 hours (12.7% in 1:1:1 a

(22.4%

17.0% 26.1%,

1:1:2 c

;

c , 4.2% [95% CI, 9.6%

1.1%)

a 30

c , 3.7% [95% CI, 10.2%

2.7%). One of the main pillars of DCR is early and aggressive transfusion of blood products aiming for a ratio of PRBCs, FFP, and platelets that approximates 1:1:1. The pioneering data for a balanced ratio of PRBCs and FFPs came from military experience, where the survival of combat hospital patients receiving variable ratios of FFP:PRBC was studied One of the main pillars of DCR is early and aggressive transfusion of blood products aiming for a ratio of PRBCs, FFP, and platelets that approximates 1:1:1. The pioneering data for a balanced ratio of PRBCs and FFPs came from military experience, where the survival of combat hospital patients receiving variable ratios of FFP:PRBC was studied. In this retrospective study, the survival of patients receiving FFPs in a 1:8 ratio compared to PRBCs was dramatically higher than those receiving FFPs in a 1:1.4 ratio (92.5% vs 37%, p < 0.001).21

Pre-hospital Care or the first 20 minutes after injury has the goal to get the patient to the trauma center by Sc

while minimizing the fluid resuscitation and

preventing hypothermia. After succeeding the Pre-hospital Care the next goal at the emergency room is to mobilize promptly to interventional radiology suite (IR suite) then proceed to operating room (OR) if needed for less than 30 minutes while doing so we have to allow permissive hypotension and administer blood & blood products early to start massive transfusion protocol (MTP) with minimum fluid resuscitation. We then can start the

abbreviated surgical procedure for less than 90 minutes with the goals to control surgical bleeding and contamination by maintaining MTP and adding abdominal packing with temporary abdominal closure. The next step after the procedure is to do observation at the intensive care unit for 12-36 hours with the goals to resuscitate and reverse the lethal triad of trauma while supporting hemodynamic. Definitive surgical procedure will be done to make definitive surgical repair and serial primary abdominal closer after taking of the abdominal packing. Last step of this procedure is to decrease fluid overload to allow definitive abdominal closure and postoperative liberation from the ventilator in the intensive care stay. (Figures 2)

Worsening of hypotension and acidosis due to peripheral vasodilatation could be prevented by rewarming the torso before the extremities. There are three stages of body rewarming depending on the rate of of rewarming needed, and the severity of patient hypothermia : passive external rewarming, active external rewarming, and active internal core rewarming.7 Although the historic practice of

a c

recent studies has found results of aggressive fluid resuscitation conduce worsening in coagulopathy, thrombocytopenia, multiple organ failure and thus, the current evidence strongly suggest the minimization of intravenous fluid usage in haemorrhagic patients.8-13 Acting as the centre of DCR, permissive hypotension is a stage which delayed the initiation of fluid resuscitation and limit the volume of resuscitation fluids/blood products administered to the bleeding trauma patient by targeting a lower than normal blood pressure.6 The patient

a a a a

incidence and severity of dilutional coagulopathy7, avoiding the hypothetical

decreasing the c

effect, which occurs when the fresh and unstable clot sealing a vascular laceration is dislodged when the intravascular pressure increases14, and restricting the volume of resuscitative fluids relates to the amelioration of the inflammatory cascade, which is exacerbated in response to exogenous fluids administration. Balanced blood product administration in haemorrhagic patients has shown results of augmentation of coagulation factors, lower chance of exacerbation of dilutional coagulopathy, and less bleeding. Early administration of blood products in addition to packed red blood cells (PRBCs) can help prevent trauma-related coagulopathy once the patient is recognize to have massive haemorrhage. The aim is to give approximately 1:1:1 ratio of PRBC : FFP : Platelets.

And the last main pillar of DCR is massive blood transfusion which typically uses 10 or more PRBCs in the first 24 hours of injury. Massive transfusion protocol (MTP) ideally

created by joined efforts of the trauma, emergency room, and blood bank teams, and should clearly address the several critical steps whereas according to current evidence of a multicentre study of major trauma centres found that only 1.7% of admitted trauma patients require massive transfusion.15 The prompt activation of a MTP in a recognized patient needing massive transfusion not only leads to a more systematic, efficient, timely, and balanced delivery of blood and blood products, but can also result in overall less use of blood and improved patient outcomes and survival. (Figures 3)

Conclusion The successful resuscitation of the massively bleeding and unstable trauma patient will depend on effective trauma team leadership, identification of early traumarelated coagulopathy, sound decision-making in the emergency and operating rooms . DCR methods to resuscitate correcting coagulopathy and has shown to improve the chances of survival in the exsanguinating trauma patient by reversing the lethal trias of death (trauma) by including permissive hypotension, body rewarming, minimization of fluid resuscitation, and early balanced administration of blood and blood products.

Table and Figures : Table 1. Survival time of severe haemorrhage patient with Massive Transfusion (MT)

Figures 1. The mortality of patients with and without ATC on ER arrival according to the severity of injury as reflected by ISS.

Figures 2. Precentage mortality associated with low, medium, and high plasma to RBC ratio

Figures 3. DCR Algorithm INJURY

Pre-hospital Care (<20 minutes)

Emergency Room (<30 minutes)

Definitive Surgical

Intensive Care Unit (12-36 hours)

Abbreviated Surgical Procedure (<90 minutes)

Procedure (2-8 Days)

Intensive Care Unit Stay (2-8 Days)

References : 1. Chatrath V, Khetarpal R, Ahuja J. Fluid management in patients with trauma: Restrictive versus liberal approach. J Anaesthesiol Clin Pharmacol. 2015;31(3):308 316.

2. Indonesia Health Profile 2017. Ministry of Health Indonesia Republic. 2018 3. Eastridge, B. J., Holcomb, J. B. and Shackelford, S. (2019), Outcomes of traumatic hemorrhagic shock and the epidemiology of preventable death from injury. Transfusion, 59: 1423-1428. 4. Mizobata, Y. Damage control resuscitation: a practical approach for severely hemorrhagic patients and its effects on trauma surgery. j intensive care 5, 4 (2017) doi:10.1186/s40560-016-0197-5

5. Andrew P Cap, et al. Damage Control Resuscitation, Military Medicine, Volume 183, Issue suppl_2, 1 September 2018, Pages 36 43 6. H.M. A. Kaafarani, G. C. Velmahos. Damage Control Resuscitation In Trauma. doi : 10.1177/1457496914524388 7. Debas, HT, Gosselin, R, McCord, C: Chapter 67: Surgery. In: Jamison, DT, Breman, JG, Measham, AR (Eds) Disease Control Priorities in Developing Countries, 2nd ed. World Bank, Washington, DC, 2006, pp. 1245 1260. 8. Cotton, BA, Guy, JS, Morris, JA: The cellular, metabolic, and systemic consequences of aggressive fluid resuscitation strategies. Shock 2006;26(2):115 121. 9. Daugherty, EL, Liang, H, Taichman, D: Abdominal compartment syndrome is common in medical intensive care unit patients receiving large-volume resuscitation. J Intensive Care Med 2007;22(5):294 299. 10. O Ma a, MS, S a

, H, G

a b, IW: A prospective, randomized evaluation of intra-

abdominal pressures with crystalloid and colloid resuscitation in burn patients. J Trauma 2005;58(5):1011 1018. 11. Giannoudis, PV, Fogerty, S: Initial care of the severely injured patient: Predicting morbidity from sub-clinical findings and clinical proteomics. Injury 2007;38(3):261 262. 12. Klein, MB, Hayden, D, Elson, C: The association between fluid administration and outcome following major burn: A multicenter study. Ann Surg 2007;245(4):622 628.

13. Kasotakis, G, Sideris, A, Yang, Y: Aggressive early crystalloid resuscitation adversely

affects outcomes in adult blunt trauma patients: An analysis of the Glue Grant database. J Trauma Acute Care Surg 2013;74(5):1215 1221;discussion 1221 1222. 14. Evans, JA, van Wessem, KJ, McDougall, D: Epidemiology of traumatic deaths: Comprehensive population-based assessment. World J Surg 2010;34(1):158 163. 15. Como, JJ, Dutton, RP, Scalea, TM: Blood transfusion rates in the care of acute trauma. Transfusion 2004;44(6):809 813. 16. Tan, JN, Burke, PA, Agarwal, SK: A massive transfusion protocol incorporating a higher FFP/RBC ratio is associated with decreased use of recombinant activated factor VII in trauma patients. Am J Clin Pathol 2012;137(4):566 571. 17. Dente, CJ, Shaz, BH, Nicholas, JM: Improvements in early mortality and coagulopathy are sustained better in patients with blunt trauma after institution of a massive transfusion protocol in a civilian level I trauma center. J Trauma 2009;66(6):1616 1624. 18. Ball, CG, Dente, CJ, Shaz, B: The impact of a massive transfusion protocol (1:1:1) on major hepatic injuries: Does it increase abdominal wall closure rates? Can J Surg 2013;56(5):E128 E134. 19. Khan, S, Allard, S, Weaver, A: A major haemorrhage protocol improves the delivery of blood component therapy and reduces waste in trauma massive transfusion. Injury 2013;44(5):587 592. 20. Barelli S, Alberio L. The Role of Plasma Transfusion in Massive Bleeding: Protecting the Endothelial Glycocalyx?. Front Med (Lausanne). 2018;5:91. Published 2018 Apr 18 21. J Trauma. Brooke Army Medical Centre. 2007 Oct;63(4):805-13 22. Maegele M. Acute traumatic coagulopathy: Incidence, risk stratification and therapeutic options. World J Emerg Med. 2010;1(1):12â&#x20AC;&#x201C;21.

Indonesian Medical Students Training and Competition 2020

Group Counselling as Rehabilitation Care for Individual with Childhood Trauma Related to Neuroendocrine Response: A Literature Review Farida Aisyah

Abstract Introduction Trauma is experience as result of events happen in individual as emotionally or physically harmful also has lasting detrimental effect on the individual

f nc i ning and

physical, emotional, spiritual, and social. Trauma in children is unique because children can t verbalize their reaction toward dangerous event and lack of understanding traumatic event. Prevalence of child abuse happen to be 1 in 5 women and 1 in 13 men. Adult with childhood trauma tend to having smaller amygdala, hippocampus, mPFC, and higher secretion of cortisol which lead to many detrimental impact on decrease their quality of life. Group counselling could be solution for adult with childhood trauma related to neuroendocrine response. Materials and Methods This literature review used data by Tourigny et al, compared experimental group vs control group. Control group consist of 15 female without group counselling and experimental group consist 27 female having group counselling, both group have same variable trauma experience as child. Group counselling consist 6-8 participant with 2 therapist as leader, compose 20 weekly meeting for 2 hour with main focus relate disclosure to abuse. Measurement in this study using 2 wave, pre-test and post-test by questionnaire. Result and Discussion There is no significant difference between experimental group and control group related to eating disorder, self-harming, and father relationship cause of low frequency of these behaviour in early therapy. Other, show significant result in experimental group at level of PTSS, coping, relationship with mother, internalizing and externalizing behavioural problems, and empowerment because counselling focus on intrusive thought,

exercise on understanding cycles of sexual abuse, and consequences of sexual. Experimental group show less stressor than control group, which lead to good neuroendocrine response. Conclusion Group counselling show effective impact towards adult with childhood trauma related to neuroendocrine response. Keyword: Trauma, Children, Group Counselling, Neuroendocrine, Rehabilitation Care

Group Counselling as Rehabilitation Care for Individual

with Childhood Trauma Related to Neuroendocrine Response: A Literature Review

Author:

Farida Aisyah

Introduction Trauma defined by experience as result of event, series of events, or set of incidence happen in individual as emotionally or physically harmful or threatening also has lasting detrimental effect on the individual

f nc i ning and h ical, em i nal,

i i al

ell-being,

and social.1 There is a varied type of traumas including Natural and Human-Caused Trauma, natural trauma such as tornado and avalanche yet human-caused trauma divided into accident and technological catastrophes such as train derailment and structural collapse also into intentional act, such as homicides and suicides or sexual assault and abuse, other type of trauma are based on number of people effected by the event, divided into individual, group or mass trauma.1 Prevalence of trauma appeared to be 16.3-27.1% is Post-Traumatic Stress Disorder (PTSD) in case of 12 months post-injury, 24.0-24.6% is Acute Stress Disorder (ASD) for <1 week post injury, other study by World Health Organization (WHO) show trauma of unexpected death of loved one contribute 31.4%, direct exposure as witnessing death or fatal injury were 23.7%, muggings were 14.5%, life-threatening automobile accident were 14.0%, physical violence were 22.9%, intimate partner sexual violence were 14.0%, life-threating illness were 11.8%, and other trauma were 8.4%.2,3 Impact of trauma commonly chronic and hard to cope, such as nightmare, chronic stress, depression, isolation from society, sleep disorder, induced selfharm, hard to concentrate, and individual with trauma in their childhood have high recidivism to do maltreatment to other individual.4,5 With chronic impact, children in their growth and developmental years a long with traumatic event should have more consideration. Trauma happen in pediatric or early lifehood stress (ELS) not alone as they experience threated event by themselves also when child witnesses threated event. 6 Children trauma is unique because children in age range 0-6 years old can not verbalize their reaction toward dangerous event yet those threating event will create new fear in them resulting in re-enact the event,6,7 Lack of understanding traumatic event between the causative and the effect making children only believe of what they see and their own thought, other than those, children trauma is unique because children can not anticipate danger and how to safe themselves, they still depend on adult one. 7 Prevalence of childhood maltreatment by Devi et al show 59.1% were emotional abuse and 54% were physical neglect other prevalence by WHO show quarter of all adults reported having been physically abused as children also 1 in 5 women and 1 in 13 men reported having been sexually abused as child, common type of childhood trauma stressor such as domestic violence, emotional abuse, physical abuse, sexual abuse, internet harass, bullying,

natural disaster, interpersonal loss like parental mental illness, parental divorce, or parental death.8,9,10 Childhood trauma may result on intrusive thought of repetitive play or traumaspecific re-enactment(s) and compulsive rituals such as hearing voice saying threatening perpetrator/auditory hallucinations, high risk of personality disorder, alcohol dependence, and nicotine dependence in future, depression, and individual with childhood trauma tend to avoid society resulting in emotional numbing and diminished interest in other, lack of empathy, comorbid dysthymia, and increase risk of self-mutilation, past studies by Charney et al show childhood maltreatment effect as hyperarousal symptoms consist of difficulty to sleep and to concentrate, irritable mood or angry outburst, hypervigilance, and exaggerated startle response.11,12,13 Explanation about those effect correlate neuroendocrine system include hormone secretion and brain development with region of interest (ROIs) were hippocampus, amygdala, and mPFC (medial prefrontal gyrus and anterior cingulate gyrus).

14-20 As describe before, trauma effect commonly chronic hence if trauma happen in childhood era it will impact as long as their growth and development year. Brain development of adult with childhood trauma or maltreatment show significantly decrease volume of hippocampus, evidence about decrease volume of hippocampus more consistent in adult rather than in children with same trauma in their childhood era.14 Around hippocampus in medial temporal lobe, the amygdala, also has correlation with childhood trauma hence the finding about amygdala and childhood trauma are less consistent, some studies report bigger volume amygdala or smaller volume amygdala of adult with childhood trauma, some report also said there is no volume difference between individual with and without childhood trauma.

Volumetric increase in amygdala like dendritic arborisation in amygdala nuclei have been reported in adult with childhood trauma exposure yet structural neuroimaging related to amygdala volume in human have been ambiguous, nonetheless recent study by McEwen and Mehta et al show brain alteration in humans during initial episodes of major depression where amygdala tend to increase in volume and hyperactivity further this hyperactivity eventually shrinkage and become smaller amygdalae after repetitive depressive episodes.16,21,22

Figure 1. Correlation between Left Amygdala Volume with Cumulative Life Stress (Panel A) and with Behaviour Problems (Panel B)16 2 87

Other than amygdala, hippocampus development should counted to, hippocampus play main role as neurobiological stress system with protracted ontogeny and high glucocorticoid receptor making hippocampus exposed to the effect of trauma.23 Chronic trauma such childhood maltreatment associated with decreased grey matter volume in right hippocampus and has negative impact on normative pattern of development.14,23 Hippocampus is heterogeneous region as structure and function hence it is feasible that trauma affects certain structure of some hippocampus subregions, such as cornu ammonis (CA), dentate gyrus, etc.23 Later, mPFC also show reduction volume up to 7.2% in individual with childhood trauma.20

Figure 2. Left: Effect of Childhood Trauma on the Development Male Left CA4 Subregion; Right: mPFC Volume Related to Abuse F e enc 20,23

Figure 3. Media Prefrontal Cortex Region Showing 7.2% Reduction in Individual with Childhood Trauma (A: Sagital, B: Transversal, C: Planes)20 In neuroendocrine perspective, stress, trauma, or other form of threat has principle pathway which is hypothalamic-pituitary-adrenal (HPA) axis, stress induce hypothalamus to secrete corticotropin releasing hormone (CRH) and arginine vasopressin (AVP) which lead to secretion of adrenocorticotropic hormone (ACTH) by anterior pituitary, ACTH promote secretion of cortisol by adrenal gland, cortisol is necessary for survival hence if cortisol poorly regulated like in condition of chronic stress or trauma it can have destructive impact towards health, especially sympathetic activity, pro-inflammatory cytokine, high blood pressure, and high appetite.20,24,25 Neuroendocrine pathway discuss above explain about correlation between impact of childhood trauma with brain development (ROIs: hippocampus, amygdala, and mFCC) and endocrine system.

3 88

Great impact of childhood trauma in early adulthood life making health provider should take precaution in promotive, preventive, curative, and rehabilitative step. One of many solution of these issue was focus group discussion conseling as rehabilitation care in order to increase individual quality of life. Materials and Methods In this literature review data obtain using scientific database including PubMed, Elsevier, Google Scholar, and Research Gate using certain keyword such as f c maltreated children

c n elling in ad l

i h childh

di c

i n in

d a ma etc. From initial search

found 200 article related to keyword, articles obtain have no years range, and articles obtain in English only, hereinafter article were excluded based on abstract and title, finally article by Tourigny et al (2005) used in this literature review. Study by Tourigny et al compared between experimental group vs control group, participant of all group gather between September 1999 until May 2000, 44 participant were obtain hence 42 participant give their consent to join intervention while other did not. Later, 42 participant divided into experimental group consist of 27 teenage girls and control group with 15 adolescent girl, control group consist of individuals whom requested services hence did not receive treatment because they decided not to participate in group intervention, leaving group therapy in first few week, and they evaluated that group therapy is not suitable for them. Mean age of participant were 14.6 years old, 33% participant found to be living in a foster family, 31% living with both of parent, and 26% with their mother only. Trauma experience from both group consist of sexual trauma include 62% penetration as in anal, vaginal, or oral with 69% cases happen at least once a week and 31% cases involved used of physical abuse, in view of perpetrator 15% participant abuse by more than one perpetrator, 82% perpetrator were adult, 39% were immediate family, and 36% were extended family member. Control group and experimental group any significant statistically difference related abuse variable except for abuse episode show higher in control group rather than in experimental group.26 Measurement in Tourigny et al study using 2 waves measurement (pre-test and post-test) questionnaires which completed by participant except Sexual Abuse Rating Scale (SARS) whose completed by practitioner, first questionnaire about socio-demographic including number and rank in family and second questionnaire is SARS consist 21 yes/no item which describe abuse-related variable. The measurement outcome were: 1) Trauma Symptoms checklist for children, related to PTSD, higher score related to higher frequency of symptoms;

Youth Self-Report and Profile, higher score related to higher behaviour problems; 3) Ways of Coping Questionnaire, higher score related to higher frequency of use of the given coping strategy; 4) Empowerment, higher score related to higher empowerment; 5) Children Attributions and Perception Scale, higher score related to higher negative attributions and perceptions; 6) Self-Injurious Behaviour Questionnaire: and 7) Child Mother (CAM) and Child

A i de

a d he

A i ude toward the Father (CAF), higher score related to higher

negative relationship.26 Group intervention practiced in this study is closed-group treatment with 6-8 participant each group lead by 2 therapist (man and woman), compose 20 weekly meeting last for 2 hour each, include group discussion, personal stories, and collective exercise or lectures. Main theme relate to the disclosure of abuse.26 Results and Discussion People have natural tendency to gather in group for mutual beneficial purpose, this natural tendency can be used as rehabilitation care in form of group counselling in individual with childhood trauma.27 Group counselling involves individual who have difficulties they wish to resolve that are of a personal, educational, social, or vocational nature with therapist as leader of the group in order to establish rapport and develop a trusting relationship which will help individual address the behaviour, feeling, and thought that are generated by the trauma experience.27,28 In this present study, using data by Tourigny et al, show in Figure 4, at the end of group counselling found to be there is no significant difference between experimental group and control group related to eating issue disorder, self-harming behaviour, and adolescent/father relationship might cause of low frequency of these behaviour in early therapy.26 Other, show significant result in experimental group at level of PTSS, attribution, coping strategies, internalizing and externalizing behavioural problems, and empowerment, these aspect show improvement count to group intervention theme with focus on intrusive thought and flashback, exercise on understanding cycles of sexual abuse, and consequences of sexual abuse for positive coping strategies, participant appears to use social support to cope which generally more positive than escape-avoidance coping strategies.26 Significant score also appear on relationship with mother while no score change in relationship with father in experimental group, while in control group there is no change at all this linked to negative towards mother whom do not protect them from abuse, and for self-destructive behaviour reduction does not reach significance level.26 5

Figure 4. Efficacy of the group intervention for teenage with sexual abuse trauma26

6 91

Group counselling for rehabilitation care for individual with childhood trauma also done by Thompson et al in group counselling with student with domestic violence trauma as target counselling having result as group counselling is most efficient ways in which school mental health professional can promote the growth and development of student exposed to domestic violence trauma.29 Other study done by Layne et al with target counselling was children with postwar trauma yielded reduced psychological distress and positive association between distress reduction and psychosocial adaptation.30 Group interview for pediatric health search are valuable means of eliciting children

n health-related matter about given an appropriate

research question.31 Good result of group counselling for individual with childhood trauma may result in good response of neuroendocrine system. Group counselling show low stress level on participant, low stress level will have good effect on neuroendocrine system because of low stressor obtain. Conclusion Group counselling show effective outcome in individual with childhood maltreatment related to it is neuroendocrine system hence this literature review have limitation such as: 1) Only one article used in this literature; 2) There is no gender related because all participant were female only; 3) Trauma discussed orientate on sexual abuse trauma only; and 4) Small amount literature which discussed about group counselling related to neuroendocrine response. Overall there is still need further study about group counselling as rehabilitation care in individual with childhood trauma related to their neuroendocrine system.

References Substance Abuse and Mental Health Services Administration, Trauma and Justice Strategic Initiative. SAMHSA

king defini i n f a ma and g idance f

a ma-

informed approach. Rockville, MD: Substance Abuse and Mental Health Services Administration; 2012. Ronald C. Kessler, Sergio Aguilar-Gaxiola, Jordi Alonso, Corina Benjet ,Evelyn J. Bromet, GraĂ§a Cardoso , Louisa Degenhardt, Giovanni de Girolamo,Rumyana V. Dinolova, Finola Ferry, Silvia Florescu, Oye Gureje, Josep MariaHaro, Yueqin Huang, Elie G. Karam, Norito Kawakami, Sing Lee, Jean-PierreLepine, Daphna Levinson, Fernando Navarro-Mateu, Beth-Ellen Pennell,Marina Piazza, JosĂŠ Posada-Villa, Kate M. Scott, Dan J. Stein, Margreet TenHave, Yolanda Torres, Maria Carmen Viana, Maria V. Petukhova, Nancy A.Sampson, Alan M. Zaslavsky & Karestan C. KoenenOn behalf of the WHOWorld Mental Health Survey Collaborators. (2017). Trauma and PTSD in the WHO World Health Mental Health Surveys. European Journal of Psychotraumatology, 8(5). Robbin H. Ophuis, Branko F. Olij, Suzanne Polinder, and Juanita A. Haagsma. (2018). Prevalence of post-traumatic stress disorder, acute stress disorder and depression following violence related injury treated at the emergency department: a systematic review. British Medical Centered Psychiatry, 18:311. Zahrotul Uyun. (2016). Kekerasan Seksual Pada Anak: Stres Pasca Trauma. Proceeding Seminar Nasional, 228-238. Dongdong Li, Chi Meng Chu, Joseph Teck Ling Goh, Irene Y. H. Ng, and Gerald Zeng. (2015). Impact of Childhood Maltreatment On Recidivism In Youth Offenders. International Association for Correctional and Forensic Psychology, 42(10):990-1007.

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Mythily Subramaniam. (2019). The prevalence of childhood trauma in psychiatric outpatients. Annals of General Psychiatry, 18:15. Benjamin E. Saunders and Zachary W. Adams. (2014). Epidemiology of Traumatic Experiences in Childhood. Child Adolesc Psychiatr Clin N Am, 23(2):167-184. World Health Organization. (2016). Child Maltreatment. Retrieved from WHO: https://www.who.int/news-room/fact-sheets/detail/child-maltreatment

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November 2019. Jeffrey G. Johnson, Patricia Cohen, Jocelyn Brown, Elizabeth M. Smailes, David P. Bernstein. (2000). Childhood Maltreatment Increases Risk for Personality Disorders During Early Adulthood. Arch Gen Psychiatry, 56:600-606. Michael D. De Bellis. (2001). Developmental traumatology: The psychobiological development of maltreated children and its implications for research, treatment, and policy. Development and Psychopathology, 13:539-564. Stephanie J. Lewis, Louise Arseneault, Avshalom Capsi, Helen L. Fisher, Timothy Matthews, Terrie E. Moffitt, Candice L. Odgers, Daniel Stahl, Jin Ying Teng, and Andrea Danese. (2019). The epidemiology of trauma and post-traumatic stress disorder in a representative cohort of young people in England and Wales. Lancet Psychiatry, 6:247-256. Gwendolyn M. Lawson, Joshua S. Camins, Laura Wisse, Jue Wu, Jeffrey T. Duda, Philip A. Cook, James C. Gee, and Martha J. Farah. (2017). Childhood socioeconomic status and childhood maltreatment: Distinct associations with brain structure. PLoS ONE, 12(4). Pechtel P, Lyons-Ruth K, Anderson C.M, and Teucher M.H. (2014). Sensitive periods of amygdala development: the role of maltreatment in preadolescence. Neuroimage, 15(97):236-244. Jamie L. Hanson, Brendon M. Nacewicz, Matthew J. Sutterer, Amelia A. Cayo, Stacey Schaefer, Karen D. Rudolph, Elizabeth A. Shurtcliff, Seth D. Pollak, and Richard J. Davidson. (2015). Behaviour Problems After Early Life Stress: Contributions of the Hippocampus and Amygdala. Biological Psychiatry, 77(4):314-323.

Erin E. Edmiston, Fei Wang, Carolyn M. Mazure, Joanne Guiney, Rajita Sinha, Linda C. Mayes, and Hilary P. Blumberg. (2011). Corticostriatal-limbic Gray Matter Morphology in Adolescents with Self-Reported Exposure to Childhood Maltreatment. Arch Pediatric Adolescent Medicine, 165(12):1069-1077.

Katie A. McLaughlin, Margaret A. Sheridan, Warren Winter, Nathan A. Fox, Charles Zaenah, and Charles A. Nelson. (2014). Widespread reductions in cortical thickness following severe early-life deprivation: A neurodevelopmental pathway to ADHD. Biol Psychiatry, 76(8):629-638. Margaret A. Sheridan, Nathan A. Fox, Charles H. Zeanah, Katie A. McLaughlin, and Charles A. Nelson. (2012). Variation in neural development as a result of exposure to institutional early in childhood. PNAS, 109(32):12927-12932. Anne-Laura van Harmelen, Marie-Jose van Tol, Nic J.A. van der Wee, Dick J. Veltman, Andre Aleman, Philip Spinhoven, Mark A. van Buchem, Frans G. Zitman, Brenda W.

H. Penninx, and Bernet M. Elzinga. (2010). Reduced Medial Prefrontal Cortex Volume in Adults Reporting Childhood Emotional Maltreatment. Biological Psychiatry, 68(9):832-838. Bruce S. McEwen. (2005). Glucocorticoids, depression, and mood disorders: structural remodelling in the brain. Metabolism Clinical and Experimental, 54(1):20-23.

Mehta M.A, Golembo N.I, Nosarti C, Colvert E, Mota A, Williams S. C, Rutter M, SonugaBarke E. J. (2009). Amygdala, hippocampal and corpus callosum size following severe early institutional deprivation: the English and Romanian Adoptees study pilot. Journal Children Psychology Psychiatry, 50(8):943-951. Sarah Whittle, Julian G. Simmons, Sylke Hendriksma, Nandita Vijayakumar, Michele Byrne, Meg Dennison, and Nicholas B. Allen. (2016). Childhood maltreatment, psychopathology, and the development of hippocampal subregions during adolescence.

Amanda R. Tarullo and Megan R. Gunnar. (2006). Child maltreatment and the developing HPA axis. Hormones and Behaviour, 50:632-639. Bruce S. McEwen. (2008). Central effects of stress hormones in health and disease: understanding the protective and damaging effects of stress and stress mediators. European Journal of Pharmacology, 7(583):174-185. Marc Tourigny, Martine Hebert, Pascale Senechal, Isabelle Daigneault, and Ann C. Simoneau. (2005). Efficacy of a Group Therapy for Sexually Abused Adolescent Group. Journal of Child Sexual Abuse, 14(4):71-93. Samuel T. Gladding. (1994). Effective Group Counselling. Washington: ERIC Digest, pp.175. Anthony J. Urquiza and Cynthia Winn. (2000). Treatment for Abused and Neglected Children: Infancy to Age 18. USA: U.S Department of Health and Human Services,

Administration for Children and Families, Administration on Children, Youth and Families, National Center on Child Abuse and Neglect. E. Heather Thompson and Shannon Trice-Black. (2012). School-Based Group Interventions for Children Exposed to Domestic Violence. Journal of Family Violence, 27:233-241. Christopher M. Layne, William R. Saltzman, Nadezda Savjak, Tatjana Popovic, Mirjana Music, Nermin Djapo, Robert S. Pynoos, Berina Arslanagic, Mary Black, Elvira Durakovic, Nihada Campara, and Ryan Houston. (2001). Trauma/Grief-Focused Group Psychotherapy: SchoolBased Postwar Intervention With Traumatized Bosnian Adolescents. Group Dynamic: Theory, Research, and Practice, 5(4):277-290.

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Systematic Review of Effect of Extracorporeal Shock Wave Therapy for Burn Patients Michele Indrawan, Herbert Deji, Angeline Tancherla Introduction: Burn is damage to the skin which can be caused by fire/flame, scalds. In Indonesia, burn is ranked 6th for unintentional injuries in 2014 with mortality rate of 34% and annually causing approximately 195,000 deaths. All degree of burn can be healed, but deep partial-thickness and full-thickness burn cause scarring to occur which can be minimized by plastic surgery and physical therapy measures. Extracorporeal shock wave therapy (ESWT) is a method, tested as a potential way of injuries management in burn patients. ESWT were less prominent as an option for burn scar management due to the lack of knowledge and systematised study oriented in ESWT efficacy for burn scar treatment. On that account, this sytematic review was carried out to evaluate the further efficacy of Extracorporeal Shock Wave Therapy in burn patients. Materials and Methods: Data are collected from Online Resources that has an Open Access, such as Pubmed, Google Scholar, and Science Direct. Systematic analysis is done using PICO and MeSH terminology. Results and Discussions: This systematic review analyses 7 studies, which consists of 2 experimental studies and 5 randomized clinical trials. The studies evaluated the healing, scar size and appearance, itching or pruritus, mobility, and pain in 254 burn patients after ESWT by using VAS, VSS, NRS, 5-D Itch Scale, Leuven Itch Scale, measurement of scar appearance, mobility, size in mm, and completion of epithelization time. All these studies informed that groups with usage of ESWT in their treatment have superior reduction of pain, itching or pruritus, better scar appearance and size, more mobility on burned area, and faster healing time. Conclusion: All of the studies that we have analysed had found that ESWT is effective in the process of treatment for burn patients. Extracorporeal shock wave therapy is a method proficient in treating post burn scar pain and appearance, itching or pruritus, improve movement on burned area, and reduction of epithelization time. Keyword: Extracorporeal shock wave therapy, burn

Systematic Review of Effect of Extracorporeal Shock Wave Therapy for Burn Patients

Michele Indrawan1, Herbert Deji1, Angeline Tancherla1 1

Faculty of Medicine, Pelita Harapan University, Tangerang, Banten, Indonesia

Systematic Review of Effect of Extracorporeal Shock Wave Therapy for Burn Patients Michele Indrawan1, Herbert Deji1, Angeline Tancherla1 1

Faculty of Medicine, Pelita Harapan University, Tangerang, Banten, Indonesia

Introduction: Burn is damage to the skin which can be caused by fire/flame, scalds. In Indonesia, burn is ranked 6th for unintentional injuries in 2014 with mortality rate of 34% and annually causing approximately 195,000 deaths. All degree of burn can be healed, but deep partial-thickness and full-thickness burn cause scarring to occur which can be minimized by plastic surgery and physical therapy measures. Extracorporeal shock wave therapy (ESWT) is a method, tested as a potential way of injuries management in burn patients. ESWT were less prominent as an option for burn scar management due to the lack of knowledge and systematised study oriented in ESWT efficacy for burn scar treatment. On that account, this sytematic review was carried out to evaluate the further efficacy of Extracorporeal Shock Wave Therapy in burn patients. Materials and Methods: Data are collected from Online Resources that has an Open Access, such as Pubmed, Google Scholar, and Science Direct. Systematic analysis is done using PICO and MeSH terminology. Conclusion: All of the studies that we have analysed had found that ESWT is effective in the process of treatment for burn patients. Extracorporeal shock wave therapy is a method proficient in treating post burn scar pain and appearance, itching or pruritus, improve movement on burned area, and reduction of epithelization time. Keyword: Extracorporeal shock wave therapy, burn

Systematic Review of Effect of Extracorporeal Shock Wave Therapy for Burn Patients Michele Indrawan1, Herbert Deji1, Angeline Tancherla1 1Faculty of Medicine, Pelita Harapan University, Tangerang, Banten, Indonesia Introduction: Burn is damage to the skin which can be caused by fire/flame, scalds, hot objects, electrical, and chemical. The severity of the burn depends on several factors such as the location, temperature, and duration which will be assessed based on how deep the damage is. Superficial (first degree) which affects only the epidermis of the skin with no blister, pink to red in color, and it is fairly painful. Superficial partial thickness (second degree) which affects the superficial dermis, appears wet and red, accompanied by blister, and pain is quite severe. Deep partial-thickness (second degree) which affects the deeper dermis, appears yellow or white, dry, and there is minimal sensation of pain. Full-thickness (third degree) which affects the skin and subcutaneous structure, appears white or black or brown, dry, with minimal to no sensation of pain.1 Burn injury mapping also include damage coverage; expressed in total body surface area (TBSA) involved.2 In Indonesia, burn is ranked 6th for unintentional injuries in 2014 with mortality rate of 34% and annually causing approximately 195,000 deaths.3 All degree of burn can be healed, but deep partial-thickness and full-thickness burn cause scarring to occur which can be minimized by plastic surgery and physical therapy measures. Although elimination of said scar cannot be done completely.4 Shockwaves are three dimensional waves of pressure which cause increases in pressure within nanoseconds. Positive pressure impulses rapidly rising from 5 to 120 MPa in 5ns, then decrease to negative values of -20 MPa. Extracorporeal shock wave therapy (ESWT) was first used to break apart kidney stones invasively. Follow up study revealed ESWT was capable of treating painful plantar fasciitis, chronic calcifying tendinitis, and improve cerebral palsy muscle spasticity. 5,6 The goal of treatments in patients with burn injuries is to manage pain and scars as well as acceleration in wound re-epithelialization. Extracorporeal shock wave therapy (ESWT) is a method, tested as a potential way of injuries management in burn patients. 7 Extracorporeal Shock Wave Therapy were less prominent as an option for burn scar management due to the lack of knowledge and systematised study oriented in ESWT efficacy for burn scar treatment, leaving a gap of knowledge in 1) whether ESWT provide a clinical improvement in burn scar management, 2) what are the effects of ESWT, and 3) how helpful is ESWT in burn therapy.

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On that account, this systematic review was carried out to evaluate the further efficacy of Extracorporeal Shock Wave Therapy in burn patients. Methods: To report our systematic review, we used PRISMA statement as a basis, which consists of evidence-based set of 27 items to report in systematic reviews.8 Data are collected from Online Resources that has an Open Access, such as Pubmed, Google Scholar, and Science Direct. Systematic analysis is done using PICO. MeSH terminology for P (Population) is B E

ea S

Patients a d Ad c

Wa e T e a

. MeSH terminology for I (Intervention) is

OR S

Wa e . MeSH e

(Comparison) is N/A. MeSH terminology for O (Outcome) is Hea Appearance OR Mobility OR Pain . T e e ea c

OR Sca S e OR Sca

e on for this systematic review is: Ca

Extracorporeal Shock Wave Therapy (ESWT) effectively treat burn injuries? . I c criteria are: prognostic studies, burn injury, population: adult (ages 18-80 years old), outcome: healing, scar size and appearance, mobility and pain. Exclusion criteria are: literature review, systematic review, meta-analysis, case report, animal study, and population: children. In order to reduce bias, we will check for the validity of the studies that fulfill the inclusion and exclusion criteria. After ensuring the validity of the studies, the data will be analyzed.

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Results and Discussion: Using PICO approach, searching is done through online database, and we acquired 7 articles that will be analysed. The selection process is shown in the diagram below. B Pa e a d Ad AND E ac ea S c Wave Therapy OR Shock Wave AND Hea OR Sca Size OR Scar Appearance OR Mobility OR Pain

PubMED (33)

Science Direct (84)

Google Scholar (81)

Inclusion Criteria: • Prognostic study • Burn injury • Population: adult (1880 years old) • Outcome: healing, scar size and appearance, mobility, itching, pruritus, and pain Exclusion Criteria: • Literature review • Systematic review • Meta-analysis • Case report • Animal- study • Population: children

10 Filtering double literature 8 Relevant Study 7

Figure 1 Information flowchart through the different phases of the systematic review

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Table 1 Summary of studies on extracorporeal shock wave therapy in burn patients Authors

Study

Year

Object/injury

Parameter

Results

Taheri et al.9

Prospective

2018

Burn scars in

100 impulses per cm2,

Improving pain, itching, and appearance

extremities

E = 0.1 j/mm2 energy, 4 Hz frequency, 6

of burn scar (decreased VAS and VSS

sessions

treatment. Following 3 months after

experimental

score) after treatment and 1 month after

treatment, no changes in pain relief and itching, but better scar appearance

Fioramonti et

Experimental

2012

al.10

Ottoman et al.

Prospective

2012

randomized clinical trial

Burn scars

100 impulses per cm2,

Improved VAS score, scar appearance

contractures in

E = 0.037 mJ / mm2 /

(scars appeared more pliable, and

extremities, face, trunk

cm , 4 Hz frequency, 12 sessions

color mismatch was less evident) and

Reepithelization

100 impulses per cm2,

Patients with ESWT showed

of Superficial Second-Degree

-2.12

E = 0.1 mJ/ mm , 1 session

movement after treatment.

significantly reduced mean time to complete (≥95%) second-degree burn

Burn Wounds

wound epithelialization (9.6 ± 1.7 vs. 12.5 ± 2.2 days; P < 0.0005) compared to the control group without ESWT.

Cho et al.7

Randomized clinical trial

2016

Burn scars

100 impulses per cm2,

Scar pain was reduced more

E = 0.05-0.15 mJ/

significantly. NRS score

mm , 4 Hz frequency, 3 sessions

significantly decreased (7.80±1.54 to

Burn scars

2500 3000 impulses

Patients in study group experience

contractures, hyperthropic

per 10-15 minutes, 12 sessions

42.55% of improvement in scar

Zaghloul et

Randomized

al.12

clinical trial

2016

3.80±2.35 points, P<0.001)

thickness, result was higher compared to 12.15% of improvement in control

scars, or keloids

group. A significant improvement was also seen in results obtained using VSS in both groups. Samhan, AT, Abdelhalim, NM

Randomized clinical trial

2019

Burn scars in upper and lower extremities

100 impulses per cm2,

Study group patients showed more

E = 0.05-0.20

prominent result than placebo group in

mJ/mm , 4 Hz frequency, 4 sessions.

pain reduction with NRS median 7 (6-

10) in pre-treatment and median 2 (04) post-treatment.

Joo et al.

Prospective

2017

Burn pruritus

randomized clinical trial

100 impulses per cm , E = 0.05-0.20 mJ/mm2, 4 Hz frequency, 3 sessions.

Results measured in 3 scales (NRS, 5-D Itch Scale, and Leuven Itch Scale) indicated a better improvement in post burn skin pruritus of patients in experimental group compared to control group.

Note: VAS : Visual Analog Scale VSS : Vancouver Scar Scale ESWT : Extracorporeal Shock Wave Therapy NRS : Numerical Rating Scale

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According to a prospective study by Taheri et al, ESWT improves pain, itching, and appearance of burn scar (decreased Visual Analog Scale (for pain and itching) and Vancouver Scar Score) after treatment and 1 month after treatment. However, 3 months after treatment, there were not significant changes in pain relief and itching, but better scar appearance. 9 Table 2 Different mean scores of visual analog scale (pain and itching) and Vancouver Scar Scale at different times of evaluation

experimental

study

Table 3 Demographic data and VAS score of Patients

Fioramonti et al found that there is an improved VAS score after ESWT treatment for burn patients (scar appearance improved 3 points for three patients (18.75%), 2 points for eight patients (50%), 1 point for two patients (12.5%), and 0 points for three patients (18.75%)). The scars appeared more pliable, and color mismatch was less evident.

There is also improved movement after ESWT treatment on burn patients.10 Ottoman et al mentioned that patients

Figure 2 Mean number of days from burn to ≥95% epithelialization

with ESWT showed a significantly reduced ea

e e ( 95%)

degree burn wound epithelialization (9.6 ± 1.7 vs. 12.5 ± 2.2 days; P<0.0005) compared to the control group without ESWT.11

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In a study conducted by Cho et al., ESWT was performed around primary treatment site three times with more significant result in scar pain reduction (NRS score 7.80±1.54 to 3.80±2.35 points, P<0.001) when compared to control group (NRS score 7.30±1.30 to 5.55±1.50 points, P<0.001).7 Table 4 Prehomogeneity test of the preliminary assessment

Statistical analysis of results in a study carried out by Zaghloul et al. showed a more significant improvement in scar thickness in study group (42.55%; 6.72 ± 1.62 mm to 3.86 ± 0.73 mm; p=0.0001) compared control group (12.15%; 6.58 ± 1.43 mm to 5.78 ± 1.17 mm; p=0.0001). Another outcome measured in this study was VSS score which also showed a significant improvement in study group (48.57%; 8.75 ± 1.71 to 4.5 ± 1.73; P=0.0001) compared to control group (14.04%; 8.9 ± 1.61 to 7.65 ± 1.78; P=0.0001).12 Table 5 Scar thickness mean value in mm for pre- and post-treatment of study and control group

Table 6 VSS mean score pre- and post-treatment of study and control group

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Samhan, AF and Abdelhalim, NM study showed lower NRS value in study group (pre-treatment median=7, ranging from 6-10 and post-treatment median=2, ranging from 0-4 with P<0.001) which means better treatment result compared to NRS value in placebo group (pre-treatment median=7, ranging from 6-9 and post-treatment median=6, ranging from 6-9 with P=0.173).13 Table 7 Numerical Rating Scale (NRS) changes for pain and pruritus between study group and the placebo group pre- and post-treatment

To assess the effect of treatment, Joo et al measured post burn skin pruritus in both experimental and control group in 3 different scales (NRS, 5-D Itch Scale, and Leuven Itch Scale). Results in all scales indicate that ESWT significantly reduced severity and disturbances in the experimental group (NRS score 6.30 1.29 to 3.57 2.09; p<0.001) compared to control group (NRS score 6.78 1.32 to 5.35 2.31; p=0.002). 14 Table 8 The changes in numerical rating scale (NRS), 5-D pruritus scale, Leuven Itch Scale

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Conclusion: From the 7 studies that we have analysed, we found that extracorporeal shock wave therapy is a method proficient in treating post burn scar pain and appearance, itching or pruritus, improve movement on burned area, and reduction of epithelization time.

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References: 1.

Warby R, Maani C V. Burns Classification [Internet]. StatPearls. 2019 [cited 2019 Nov 29]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/30969595

Schaefer TJ, Szymanski KD. Burns, Evaluation And Management [Internet]. StatPearls. 2018 [cited 2019 Nov 29]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28613492

Wardhana A, Basuki A, Prameswara ADH, Rizkita DN, Andarie AA, Canintika AF. The epidemiology of burns in Indonesia

a efe a b

ce e f

2013

2015. Burn Open. 2017 Oct;1(2):67 73. 4.

Goel A, Shrivastava P. Post-burn scars and scar contractures. Vol. 43, Indian Journal of Plastic Surgery. 2010.

Notarnicola A, Moretti B. The biological effects of extracorporeal shock wave therapy (eswt) on tendon tissue. Vol. 2, Muscles, Ligaments and Tendons Journal. 2012. p. 33 7.

Kim HJ, Park J-W, Nam K. Effect of extracorporeal shock wave therapy on muscle spasticity in patients with cerebral palsy: meta-analysis and systematic review. Eur J Phys Rehabil Med. 2019;

Cho YS, Joo SY, Cui H, Cho SR, Yim H, Seo CH. Effect of extracorporeal shock wave therapy on scar pain in burn patients: A prospective, randomized, single-blind, placebo-controlled study. Med (United States). 2016 Aug 1;95(32).

Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med [Internet]. 2009 Jul 21 [cited 2019 Nov 16];6(7):e1000097. Available from: https://dx.plos.org/10.1371/journal.pmed.1000097

Taheri P, Khosrawi S, Mazaheri M, Parsa M, Mokhtarian A. Effect of extracorporeal shock wave therapy on improving burn scar in patients with burnt extremities in Isfahan, Iran. J Res Med Sci [Internet]. 2018 [cited 2019 Nov 16];23(1):81. Available from: http://www.jmsjournal.net/text.asp?2018/23/1/81/242091

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Fioramonti P, Cigna E, Onesti MG, Fino P, Fallico N, Scuderi N. Extracorporeal shock wave therapy for the management of burn scars. Dermatologic Surg. 2012 May;38(5):778 82.

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Ottomann C, Stojadinovic A, Lavin PT, Gannon FH, Heggeness MH, Thiele R, et al. Prospective randomized phase II trial of accelerated reepithelialization of superficial

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second-degree burn wounds using extracorporeal shock wave therapy. Ann Surg. 2012 Jan;255(1):23 9. 12.

Zaghloul MS, Khalaf MM, Thabet WN, Asham HN. Effect of Extracorporeal Shock Wave Therapy on Post Burn Scars.

13.

Samhan AF, Abdelhalim NM. Impacts of low-energy extracorporeal shockwave therapy on pain, pruritus, and health-related quality of life in patients with burn: A randomized placebo-controlled study. Burns [Internet]. 2019 Aug [cited 2019 Dec 4];45(5):1094 101. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0305417918310222

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Joo SY, Cho YS, Seo CH. The clinical utility of extracorporeal shock wave therapy for burn pruritus: A prospective, randomized, single-blind study. Burns. 2018 May 1;44(3):612 9.

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Systematic Review of The Effectiveness of Pharmacological Treatment for Post Traumatic Stress Disorder Diagnosed Patients Compared to Placebo Jonathan Juniard Anurantha, Johan Wibowo, Nadia Khoirunnisa Heryadi

ABSTRACT Introduction: Post Traumatic Stress Disorder (PTSD) is a chronic psychiatric disorder which causes someone to re-experience past traumatic events such as war, natural disaster, a violent personal assault that affects his/her personality for a long period usually longer than a monthÂš. In research published by Cambridge UniversityÂ˛, it is stated that a low level of serotonin is related to the prevalence of PTSD and thus serotonergic agents such as sertraline can be used to possibly reduce the symptoms of PTSD. Sertraline is a type of antidepressant that fall under the class selective serotonin reuptake inhibitor(SSRI)Âł. We wanted to evaluate the effectiveness of the sertraline compared to the placebo group in a PTSD patient. Material and Methods: In our systematic review, we collected our data from an online journal which includes Pubmed and Google Scholar. Systematic Analysis approaches were used in this study, for example, the PICO method. Result and Discussion: By using the inclusion and exclusion criteria, we have found 5 articles that were relevant. Panahi et al, Davidson et al, Austin et al, Brady et al stated in their studies that there were significant improvements and consistent numeric advantages of sertraline compared with placebo. There s onl 1 s d , cond c ed b Friedman e al, which stated that there were no significant differences between sertraline and placebo. Conclusion: In conclusion, the use of sertraline is effective and safe in reducing symptoms of PTSD. As there are only 1 out of 5 studies that state that there is no significant differences and effect given by sertraline compared with placebo.

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Systematic Review of The Effectiveness of Pharmacological Treatment for Post

Traumatic Stress Disorder Diagnosed Patients Compared to Placebo

Jonathan Juniard Anurantha, Johan Wibowo, Nadia Khoirunnisa Heryadi

111

hich stated that

there were no significant differences between sertraline and placebo. Conclusion: In conclusion, the use of sertraline is effective and safe in reducing symptoms of PTSD. As there are only 1 out of 5 studies that state that there is no significant differences and effect given by sertraline compared with placebo.

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Introduction Post Traumatic Stress Disorder (PTSD) is a chronic psychiatric disorder which causes someone to re-experience past traumatic events such as war, natural disaster, a violent personal assault that affects his/her personality for a long period usually longer than a month¹. PTSD is associated with a chronic course and debilitating symptoms. According to the Diagnostic and Statistical Manual of Mental Disorders- fifth edition (DSM-5), there are several criteria to diagnose PTSD, one of which is that the traumatic event must involve a person to directly exposed to the event. PTSD symptoms usually develop during the first month after the traumatic event but in a minority of cases, this period is usually can occur in months or even years. These symptoms of PTSD include (1) re-experiencing in the form of a nightmare, flashback, repetitive distressing image or sensation, and physical sensation; (2) avoidance and emotional numbing by trying to avoid a certain place, people or activity; and (3) Hyperarousal or anxious that can lead someone to irritability, angry outburst, difficulty sleeping, and difficulty in concentrating In research published by Cambridge University², it is stated that a low level of serotonin is related to the prevalence of PTSD and thus serotonergic agents such as sertraline can be used to possibly reduce the symptoms of PTSD. serotonin(5-HT) is a type of neurotransmitter which is usually found in the brain, bowel, and blood platelets. It helps regulate cognitive, appetite, sleep cycle, and is a key role in mood balancing. and thus as the result of the research conducted by Cambridge University shows that the treatment of PTSD is usually involving 5-HT Pathway. Sertraline is a type of antidepressant that fall under the class selective serotonin reuptake inhibitor(SSRI)³. Sertraline works by slowing the reabsorption of serotonin in the brain. Normally serotonin in the brain gets absorb quickly after sending a signal however the SSRI works by slowing that absorption so the serotonin can send more signals to the neurons which can improve mood. In this Systematic Review, We wanted to evaluate the effectiveness of the sertraline compared to the placebo group in a PTSD patient to see whether the sertraline is effective to help reduce the symptoms.

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Methods In our systematic review, we collected our data from an online journal which includes Pubmed and Google Scholar. Systematic Analysis approaches were used in this study, for example, the PICO method and MeSH terminology. For the People or Population(P) we used ad lt . For inter ention(I) the terminolog

Sertraline

the terminology Placebo . And for the o tcome(O),

as sed. For Comparison(C)

e sed

e sed s mptom red ction . And the

Hypothesis in this systematic review is Is sertraline effecti e and safe for PTSD patients compared to placebo? . The incl sion criteria sed in this s stematic re ie

are a randomi ed

controlled trial, post-traumatic stress disorder, sertraline, placebo-controlled, adult population. The exclusion criteria are meta-analysis, a systematic review, animal study, and children. Results and Discussion: Using the PICO method or approach, we have gathered and selected 5 articles to be analyzed. The diagram below shows the process of selection.

114

Authors

Study

Year

Subject

Result

Friedman et al ⁴.

Randomized

2007

DSM-III-R diagnosis of

No significant

PTSD and scored 50 or higher on CAPS-2 at the end of a 1-week placebo run-in period participated

between sertraline and placebo on any of the primary or secondary efficacy measures at the endpoint.

Panahi et al ⁵.

Randomized

Controlled Trial

2011

Controlled Trial Davidson et al ⁶.

Randomized

Brady et al ⁸.

Randomized

the Responders in the sertraline

Iran-Iraq war who met DSM-IV criteria 2001

Controlled Trial Austin et al ⁷.

Iranian veterans

Outpatients

group were significantly higher than in the placebo group

with

a Significantly

DSM-III-R diagnosis of moderate-to-severe PTSD 2002

differences

improvement slopes for sertraline compared with placebo on the CAPS-2

Outpatients aged 18 years A

Controlled Trial

and older with DSM-III-R criteria

Randomized 2000 Controlled Trial

Outpatients with DSM-3R diagnosis PTSD and a CAPS-2

steeper

consistent

numeric

advantage for sertraline compared with placebo across the primary outcome measures

a Sertraline treatment yielded of significantly greater improvement than placebo on 3 of the 4 primary outcome measures

Note : PTSD : Post-Traumatic Stress Disorder DSM

: Diagnostic and Statistical Manual of Mental Disorders

DSM-R : Diagnostic and Statistical Manual of Mental Disorders, Revised CAPS:Clinician-Administered PTSD Scale

According to the study by Friedman et al, conducted in 169 subjects which were assigned randomly to the sertraline group (n=86) and placebo group (n=83). The study shows no statistical significance between the result of the sertraline group and the placebo group. As the mean baseline CAPS severity score and standard deviation for sertraline and placebo group were 72.1(19.1) and 73.8(3.1) respectively and the endpoint for each group CAPS were -13.1 ± 3.0 and -15.4 ± 3.1 which shows no significant difference. The same trends go for the total impact of event scale(IES) the result for both groups is shows relatively the same results, sertraline

115

group(-8.7 ± 1.8) and placebo group (-8.1 ± 1.9). For the clinical global impression-severity of illness scale(CGI-S), there are no significant differences again between the sertraline group(-0.5

0.1) and placebo group(-0.6 ± 0.1). And for the clinical global impressions-improvement scale(CGI-I) the results once again show no difference between 2 groups(3.0 ± 0.2). These results show that sertraline might not be efficacious at the endpoint. One interpretation from Friedman et al studies is stated in the discussion of their journal which suggests that sertraline might only be effective for PTSD patients with civilian trauma. Panahi et al. stated in their study that, with a total of seventy-male Iranian Iran-Iraq veteran outpatients, which were randomly assigned to a double-blind treatment of sertraline (n=35) and placebo (n=35) and amongst these, 62 people completed the study (n=32 and 30 in the sertraline and placebo groups, respectively). On the per-protocol analysis (PPA), the mean reduction of IES-R total score was found to be significantly higher in sertraline than the placebo

group ( – 24.8±2.0 v. – 20.4±2.2; t=

-8.3,p<0.001). There was also a similar trend for all

three IES-R subscales: re-experiencing/intrusion (-– 9.1±1.3 v. –7.6±1.2; z= –4.4, p<0.001), avoidance/numbing (–8.8±1.1 v. –7.2±1.5, z= –4.0, p<0.001) and hyperarousal (–6.9±0.8 v. –5.6±0.7, z= –5.6, p<0.001) symptoms. Using PPA, the mean reduction in the CGI-S score by the end of the trial was found to be signi cantly greater in the sertraline than in the placebo group (–1.0±0.7 v. –0.5±0.7; z= –2.9, p=0.003). Similarly, treatment with sertraline was associated with a signi cantly lower CGI-I score at endpoint compared to placebo (2.7±0.7 v. 3.4±0.7, z= –3.4, p=0.001). Responder rates also turned out to be higher in the sertraline group when CGI-I (sertraline: 44%; placebo: 13%; p=0.008) and IES-R (sertraline: 100%; placebo: 80%; p=0.01) based criteria were applied alone. The results of the study show a significant efficacy for sertraline in all three efficacy measures: IES-R, CGI-I, and CGI-S scales. There was also a greater reduction in the mean score of each defined clusters of DSM-IV of the IES-R subscales, which was associated with sertraline. The study conducted by Davidson JRT et al, 208 subjects, consisting of male and female outpatients who met the DSM-III-R criteria and they were among the ages of 18 years and older, were randomly assigned to sertraline or placebo. The baseline PTSD symptoms of subjects were then rated by investigators using CAPS-2 and the Clinical Global Impression-Severity Scale (CGI-S), while efficacy and safety that was consisted of primary outcome rated by CAPS-2 and

116

Impact of Event Scale (IES), CGI-S and CGI-Improvement (CGI-I) scales. The secondary outcome which was rated by CAPS-2, 17 item Davidson Trauma Scale (DTS), which were administered at every visit while, the Hamilton Depression Rating Scale (HAM-D), the Hamilton Anxiety Rating Scale (HAM-A), Pittsburgh Sleep Quality Index which were administered at baseline and study endpoint only. The results for efficacy show that the benefit of sertraline on the 2 PTSD severity scales (CAPS-2 and IES) was confirmed by global (CGI) measures as well as the DTS scale. There is significance (x2 = 8.48, P= .004) more sertraline treated subjects were 1 classified as responders at endpoint compared with placebo subjects and it was also observed a

significantly steeper improvement in using sertraline compared with placebo on both measures

(t = -2.96, P = .003 for CAPS-2, and t = -3.45, P<.001 for DTS) and additional mixed-effect 1379 1377 analysis were also found significantly steeper improvement slopes in favour of sertraline for the IES ( t1375= -2.26, P = .02) and for the CGI-I score (t1178= -3.62, P<0.001) and for CGI-S (t1380=

-4.40, P<.001). As for the results in social functioning measured by the global rating on CAPS-2 showed significantly greater improvement on sertraline (2.6±0.8 to 1.2±1.1) which was compared to placebo (2.7±0.9 to 1.7±1.1; t = 2.48; P=.01), but there were no significant differences between sertraline and placebo found on either HAM-A or HAM-D at the end of the study. This study provides evidence of a safe, well-tolerated, significantly effective treatment of sertraline compared with placebo for this long-abandoned public health problem. According to Austin et al. study, out of the 42 patients who were screened and signed informed consent forms, 23 patients randomized to sertraline (83% male, age [mean ± SD]: 41± 6 years) and 19 patients randomized to placebo (95% male, age: 38 9 years). Those with randomized to sertraline has a significant outcome than those with randomized to placebo, although the effect of sertraline only achieved significance (p = 0.05) on the Clinical Global Impression 1 (see Fig.1).

117

Fig. 1. Patients meeting three responder criteria: Comparison of outcome for sertraline vs. placebo (completer analysis). CAPS-2, Clinician-Administered PTSD total severity score; CGI-I, Clinical Global Impression Improvement Score.

In the study conducted by Brady et al., a total of 187 patients are randomly assigned to sertraline (n=94) or placebo (n=93) that ages ranged from 18 to 69 years, with 45% of the sample being younger than 45 years. Sertraline has a significantly greater efficacy than placebo at the study endpoint on 3 out of 4 primary outcome measures. A significant (p = 0.02) treatment efficacy result on CAPS-2 treated with sertraline. A significant (p = 0.01) result is also found on CGI-S with sertraline. Efficacy measures of CGI-I have a significant (p = 0.04) outcome with sertraline. A significant (p = 0.003) advantage is found for sertraline compared with placebo on the Davidson PTSD Scale. Conclusion: We can conclude from the 5 studies that we have analyzed, sertraline has a high efficacy and significant improvement compared with placebo when it comes to reducing symptoms of PTSD, this can also be seen out of the 5 studies we have analyzed, only 1 that stated that there was no significant difference between sertraline and placebo.

118

References: American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-IV-TR. Washington, DC: American Psychiatric Association, 2000. Connor K, Davidson J. The Role of Serotonin in Posttraumatic Stress Disorder: Neurobiology and Pharmacotherapy. CNS Spectrums. 1998;3(S2):42-51. K S. An evidence-based review of the clinical use of sertraline in mood and anxiety disorders. - PubMed NCBI [Internet]. Ncbi.nlm.nih.gov. 2019 [cited 28 November 2019]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/21456103#:~:targetText=An%20evidence%2Dbased%20r eview%20of%20the%20clinical%20use%20of,in%20mood%20and%20anxiety%20disorders.&ta rgetText=In%20adults%20and%20in%20pediatric,and%20has%20low%20fatal%20toxicity. Friedman MJ e. Randomized, double-blind comparison of sertraline and placebo for

posttraumatic stress disorder in a Department of Veterans Affairs setting. - PubMed - NCBI [Internet]. Ncbi.nlm.nih.gov. 2019 [cited 27 November 2019]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/17503980 Panahi Y e. A randomized, double-blind, placebo-controlled trial on the efficacy and tolerability of sertraline in Iranian veterans with post-traumatic stress ... - PubMed - NCBI [Internet]. Ncbi.nlm.nih.gov. 2019 [cited 30 November 2019]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/21349225 Davidson JRT, Rothbaum BO, van der Kolk BA, Sikes CR, Farfel GM. Multicenter, Double-blind Comparison of Sertraline and Placebo in the Treatment of Posttraumatic Stress Disorder. Arch Gen Psychiatry. 2001;58(5):485 492. doi: https://doi.org/10.1001/archpsyc.58.5.485 Austin; Double-Blind Placebo-Controlled Pilot Study of Sertraline in Military Veterans With Posttraumatic Stress Disorder [Internet]. Insights.ovid.com. 2002 [cited 27 November 2019]. Available from: https://insights.ovid.com/clinicalpsychopharmacology/jcps/2002/04/000/double-blind-placebo-c ontrolled-pilotstudy/13/00004714 Brady K, Pearlstein T, Asnis GM, et al. Efficacy and Safety of Sertraline Treatment of Posttraumatic Stress Disorder: A Randomized Controlled Trial. JAMA. 2000;283(14):1837 1844. doi:https://doi.org/10.1001/jama.283.14.1837

119

Assessment of Factors Associated with Unfavourable Prognosis of Traumatic Brain Injury Patients in Asian Countries as a Comprehensive Consideration for Trauma Care after Road traffic Injury: A Systematic Review of Cohort Studies Michelle Imanuelly, Elizabeth Marcella, Ayers Gilberth Ivano Kalaij ABSTRACT Introduction Traumatic brain injury (TBI) is a

silen

epidemic ,

he main ca se of

hospitalization, death, and disability more than any other traumatic insult in the world. Surprisingly, TBI burden study in Asia is the highest compared to all other global regions due to TBI-related outcomes as a result of falls (77%) and other intentional injuries. Currently, no study has comprehensively reviewed the factors related to TBI prognostic specifically in Asian settings, though such review is desperately needed considering the high Road Traffic Injury (RTI) induced TBI prevalence in Asian population. Objective To assess comprehensive set of predictive TBI prognostic indicators in Asian Methods A systematic review was conducted through PubMed, Scopus, and CENTRAL, searching for cohort studies which analyse factors contributing to related with unfavourable prognosis of TBI Patients in Asia. Studies selected were then assessed for bias risk with STROBE s cri eria. Results The search yielded seven studies with a total of 1,940 subjects, consisting 6 cohort studies. Sociodemographic factors and clinical factors are two categories of factors associated with unfavourable prognosis of traumatic brain injury patients in Asian countries. The most consistent factors are age, GCS Score, and neurological comorbidity. Conclusions To conclude, the factors associated with unfavourable prognosis of traumatic brain injury patients in Asian countries are Age, Gender, Glasgow Coma Scale (GCS), neurological comorbidity, pH bleeding, pH respiratory distress, raised intracranial pressure (ICP), hypotension/ blood pressure, heart rate, hypoxia, and motor response. Future evaluation of current triage criteria in ED is hoped to establish the updated triage system in clinical setting, thereby helping to reduce the unfavourable prognosis of TBI patients in Asian countries. Keyword: traumatic brain injury, unfavourable outcome, Asia

120

Michelle Imanuelly, Elizabeth Marcella, Ayers Gilberth Ivano Kalaij

121

INTRODUCTION

TBI mainly caused by falls and RTI and it

Traumatic brain injury (TBI) is a

will become the main cause of death and

silent epidemic that are more deadly than

disability worldwide by 2020.3,5-6 The

any other traumatic insult in the world.1-3

majority of cases are due to road traffic

According to recent study, sixty-nine

injury (60%), falls (approximately 20-

million individuals across the world are

25%) and violence (10%).5-7 This indicates

estimated to sustain a TBI every year.1

TBI needs a comprehensive solution in

Surprisingly, compared to all other global

trauma care considering factors associated

regions, according to the TBI burden study

with the TBI prognosis, which will

in Asia, Asia has the highest-percentage of

determine the patients future outcome. In Asian countries, which are

TBI-related outcomes as a result of falls (77%) and other intentional injuries.

dominated

Specifically,

injuries are becoming the main cause of

recorded as the greatest overall burden of

mortality and morbidity.6,8 Moreover, rare

diseases region.3 Several studies have been

disabilities related with TBI, are associated

conducted to determine the significant

with the health care system problems

factors that contribute to outcomes after

where knowledge of the epidemiological

TBI indicating the fact that TBI preventive

profile of TBI and prevention development

methods need to be more effective.

measures are excessively important, for

However, researches have shown that TBI

instance in the limited resources setting.3

still requires long-term care in health

Especially, in Indonesia, averagely there

system,

causes

are at least three people who died due to

neurotrauma. Therefore, several factors

road traffic injury-induce TBI every

need to be addressed in specific settings in

hour.7,9 The high percentage of RTI that

order to suit in an effective method to

happened each year presents a higher risk

conquer this problem.4

of TBI to happen due to severe accidental

the

Southeast

because

often

Asian

developing

countries,

TBI is mainly due to RTI.7,9

TBI is a close matter in all countries

Currently,

trauma care problems. Referred to an injury

the

comprehensive

survey by the Hong Kong Department of

identification of reliable TBI prognosis

Health in 2008, all injuries among children

indicators is critical to both medical

were mainly caused by falls while in a

professionals and patients. From the

productive age group mainly caused by road

medical professional perspective, these

traffic injury (RTI).5-6 Furthermore, it was

factors could be used as an evaluation of

reported that severe

chance of survival or recovery in order to

122

solute comprehensively in trauma care

Scopus, MEDLINE and Cochrane Library

plan10 and would help as a basis of

databases up to 2 December 2019 using the

immediate neurological triage criteria in

following keywords or terms: (TBI OR

emergency department to help them

"traumatic brain injury" OR "head trauma"

making decisions of treatments based on

OR "head injury ) AND (unfavourable OR

the patients prognosis and produced a

bad) AND (prognosis OR outcome) AND

favourable outcome. For the patients, the

predictor AND (factor OR "risk factors" OR

prognostic information plays important

"factors associated ) AND (mortality OR

role in counselling in a critical scenario,

survival OR "disability and functional

addressing factors related to TBI prognosis

status ) AND Asia. Moreover, additional

could be a breakthrough in making the

records were identified through manual

treatment more effective.10

search, similar articles suggestion, and

knowledge,

references cited in previous studies of

currently no study has comprehensively

factors associated with outcomes in patients

reviewed the factors related to TBI

with TBI. We limited our literature search to

prognostic specifically in Asian settings,

studies with English or Bahasa Indonesia

though such review is desperately needed

language, as these were the languages which

considering the high RTI induced TBI

are compatible with the authors.

the

authors

prevalence in Asian population. Thus, this systematic

review

aims

Inclusion and exclusion criteria of studies

assess

Studies were screened according to

comprehensive set of TBI prognostic

the eligibility for inclusion as follows: (1)

indicators TBI patients in Asia. Through

studies of factors associated to TBI with

this endeavor, hopefully, the results of this

extractable outcomes, (2) cohort studies,

review can help to improve guidelines of

and (3) conducted in Asian countries.

advanced trauma care systems and triage

Subsequently, our exclusion criteria were:

for emergency in Asian population, as an

irretrievable

integral part of reducing mortality and

full-text

articles,

(2)

inappropriate study types or design, and (3)

morbidity associated to TBI.

published in 2000 and above to ensure the

METHODS

relevancy of the studies in today situation.

Search strategy

Cohort studies were used for this review as

This systematic review of cohort

its outcome is more compatible to identify

studies is conducted based on PRISMA

and follow-up the association between

statement. We searched through PubMed,

factors and TBI prognosis, which requires a

123

period of time. Details of study search

Risk of bias assessment details was

strategy are shown in Figure 1.

provided in Appendix.

Data extraction and risk of bias

RESULTS

assessment

Study selection

Afterwards, data were extracted from

The process of literature searching

our selected articles by two reviewers using

and selection is illustrated in Figure 1.

standardized

were

Initially, searches from PubMed, Scopus,

independently checked and assured by the

MEDLINE and Cochrane Library yielded a

third reviewer. There were no multiple

total of 593 records. The additional records

publications

were identified from manual search (n=11).

duplicates were also removed in the prior

From that, there were 604 total records

process, therefore the identical data will only

retrieved. Duplicates were removed, titles

be extracted once. Extraction of study

and abstracts were screened, and full-text

characteristics include author and year of

articles were then assessed for eligibility.

publication, study design and settings, study

Twenty-eight studies were further excluded

population and sample size, predictors, and

due to irrelevant study types, inappropriate

outcomes

location,

forms.

Then

identical

study

they

studies,

expressed

language

restrictions,

not

percentage, adjusted odds ratio, or beta or

discussing factors related to TBI prognosis,

weld for each factor. Moreover, articles were

and irrelevant outcomes. This resulted in a

also assessed in terms of quality and bias

final of 6 cohort studies to be included in

assessment after data extraction of every

qualitative synthesis.

included studies by

using

the

STROBE s

(Strengthening

the

criteria

Reporting

Observational Studies in Epidemiology). This criteria uses a checklist in which the study is judged using the 22 checklist items guided in the STROBE guideline. Each checklist was created to ensure high-quality

presentation

each

conducted

observational studies. Quality assessment was

done

collaboratively

three

Figure 1. Diagram flow of literature search

reviewers until consensus were reached.

strategy

124

All studies included was valid due

According

various

studies

to the multivariate statistical analysis

included in the table above, the factors

method used in the studies shown by

associated with unfavourable prognosis of

adjusted risk ratio (aRR) provided in the

traumatic brain injury patients in Asian

study. All the variable was operationally

countries can be divided into 2 main

defined in the Table 1.

factors: sociodemographic factors such as age; and clinical factors such as Glasgow

Table 1. Operational Definition Variable

Definition

Hyperthermia

Abnormally high temperature13

Hypoxia

Condition in which the tissues are starved of

Coma body

comorbidity,

brain,

spinal

said studies can be improved because

the

although they were internally validated, they

cord,

muscles, or nerves prior

had not yet been ready to be released for

to arrival on ED 10.14

external

produce the best treatment and outcome of a health care.12 Furthermore, the method of

cohort studies which varied across Asia.

estimating prognosis should be standardized,

were

clearly reported, user-friendly, and can be

significantly related to TBI unfavourable provided

some

individual patient is needed in order to

patients. All 6 included studies were

prognosis,

reliable to predict the prognosis of an

this review included a total of 1,673

which

due

Specifically, in patient cares, a model that

this review are shown in Table 2. Overall,

factors

purposes

inconsistencies and lack of external validity.

Study characteristics included in

were

motor response. Unfortunately, the quality of

Study characteristics and outcomes

Outcomes

deficit,

blood pressure, heart rate, hypoxia, and

a body area due to weaker function of

neurological

intracranial pressure (ICP), hypotension/

Patients with Abnormal / neurological function of

Neurological deficit

(GCS),

bleeding, pH respiratory distress, raised

oxygen 13 Neurological comorbidity

Scale

clinically practical.15,16

percentage,

Therefore,

adjusted odds ratio, beta score, or wald

each

comprehensively

score with their corresponding p-values.

study

explained

should prognostic

models mechanisms and how it can be

Results of quality assessment based on

applicable in a clinical setting. Moreover,

STROBE s criteria were given in the

we strongly recommend that future studies

appendix part on the last part of this paper.

that follow can be further explained by elaborating the prognosis of each patient and

DISCUSSION Analysis of the study

possibly score the prognosis so that this

125

can be applied in a clinical setting,

which are usually more susceptible to RTI;

especially as an indicator for even there

however, this study is not valid due to the

has not yet been a standardized test up to

cross-sectional design which are not

this date.

followed by further follow-up. Despite, in

From the studies, we can conclude

TBI prognosis measurement, we conclude

the most consistent factors correlating with

that older patients is more susceptible for

unfavourable prognosis of traumatic brain

TBI prognosis.

injury patients, which are age12,14,16,17, GCS12,13,16,17,,

and

Moreover, higher admission GCS

neurological

motor score is associated with lower in-

comorbidity12,13,14,17, shown by four out of

hospital mortality and vice versa, lower

six studies which agreed that all these three

admission GCS motor score is associated

factors significantly can be a predictor of

with higher in-hospital mortality. This is

unfavourable prognosis in TBI patients.

obvious as the GCS measures the severity of

Older patients appeared to have worse

injury which is not a surprising important

prognosis

predictor

compared

younger

ones.

prognosis

TBI

Specifically, patients over 65 years have a

patients.12,13,16,17 Therefore, as this review

significantly lower survival rate after TBI as

mentioned, GCS should be continuously

they are advancing in age due to the fact that

assessed

brain aged physiologically and have a higher

emergency department. Furthermore, based

incidence

subdural

on studies reviewed above, GCS motor

hematoma.18 Furthermore, older patients

score12-13,16,17,19 on arrival is the significant

have decreased capacity for brain repair, and

predictor of TBI prognosis which will need

systemic complications are more frequent.19

more attention by the ED doctors in the

This should be a strong consideration that all

future due to the fact that it has strong

older trauma patients, especially traumatic

correlation to TBI prognosis compared to

brain injury patients, with minor fall or slip

other GCS which are not mentioned by most

injury should be triaged to the main ED

studies such as GCS eye and verbal.

injury-induced

immediately and assessed rapidly and

even

after

stabilization

after

Four out of six studies also agree

continuously. However, speaking of the

that

cause of TBI, a study from Ziaeirad18 in Iran

discharge outcomes was higher in patients

suggest

with

neurological

susceptible to TBI, this is due to the fact that

such

in RTI, mostly the TBI patients are using

intracranial hematoma, which one study

motor vehicles

measure it using Charlson comorbidity

that

younger

men

are

126

the

likelihood

diffuse

unfavourable

comorbidity12,13,14,17, axonal

injury

and

index (CCI)17. This could be due to the fact

hematoma/hemorrhage

that more complications produce more bad

edema.20

cerebral

prognosis and also that cerebral blood flow

Minor factors such as pH bleeding13,

plays an important role in providing

pH respiratory distress13, hyperthermia16, or

adequate cerebral oxygen supply.17,20 Factors

hypoxia16 was also found to be predictors of

like raised ICP, blood pressure appears to be

unfavourable prognosis in TBI patients in

connected to after TBI pathophysiological

Asia. Patients with pH bleeding, pH

process as they may disrupt the cerebral

respiratory

blood flow. Several studies believe that

hypoxia

raised ICP is significantly associated with

outcome.

unfavourable outcomes and was significant

considered one of the most important

independent

predictors of 6-month functional disability

predictor

for

unfavourable

outcome. Three out of six studies11,12,14 were

distress, also

had

Motor

hyperthermia, more

unfavourable

response

severe

TBI

was

also

patients.

also in agreement that systolic blood pressure was also one of the most important

b. Limitation of the study

predictors of 6-month functional disability.

This study is not without limitation due

Moreover, patients with hypotension will

to the exclusion of inaccessible full-text

most likely develop unfavourable outcome/

articles and studies with incompatible

prognosis. Two out of six studies12,14 show

language. Moreover, the lack of study

that heart rate was one of the predictors for

Asian settings may also present limitation.

bad prognosis in TBI patients. Although these are purely observational predictors, it

c. Future Application and Research

is necessary for early identification.15,19

The result of the above systematic review can be further applied to formulate factors

Furthermore, studies12,16,17 have also

contribute to prognosis of patients with

shown that pupillary reflex can be used as

traumatic brain injury in Asian settings

one of the indicators for prognosis. Patients

which will be invaluable in triage criteria,

with bilaterally abnormal pupillary response

care

and size patients have more unfavourable

prognostication, resource use and patient and

outcome than the bilaterally normal and

counselling. Especially, in Asian settings

unilaterally abnormal pupillary response and

which are very susceptible to TBI due to the

size. An abnormal pupillary response or

fact that Asia has high prevalence of RTI

reflex is often indicative of increasing ICP

which often induced TBI. This study would

due to progression of an

provide an modification to objective

127

and

discharge

planning,

injury

guide for trauma team to evaluate current

factors and clinical factors. The following

triage criteria in emergency department (ED)

factors were significantly associated with

and establish the updated triage system in

unfavourable outcomes in TBI patients in

clinical settings. For instance, for the

Asia: age, Glasgow Coma Scale (GCS),

geriatric trauma patients which can fail to

and

meet standard physiological criteria for

bleeding, pH respiratory distress, raised

trauma team activation which leads to

intracranial pressure (ICP), hypotension/

longer-wait areas meanwhile age plays

blood pressure, heart rate, hypoxia, and

important role in TBI bad prognosis.

motor response. Age, GCS score, and

Consideration of clinical settings in ED is

neurological comorbidity are among the

also important. Through this systematic

most consistent factors associated with

review, we suggest that ED doctors should

increased risk of unfavourable prognosis

do GCS motor initial and neurological

in TBI patients. Most of the predictor

comorbidity history assessment as the first

studies were not well validated or not

matter

sufficiently report validation information.

before

doing

other

predictors

neurological

comorbidity,

assessment such as heart rate and other

We hope that the results of this

factors. Intracranial pressure and heart rate

systematic review could serve to improve

are also crucial to be tested, but are not as

clinical applications and improvements of

prioritize as GCS motor initial compared to

guidelines

other GCS score. Therefore, older patients

systems and triage for emergency in Asian

considering patients age which even only

population through better measurements in

experienced minor fall injury should be

clinical settings considering prognostic

triage to the main ED more frequently than

associated factors at the ED. GCS motor

what is done in the practice. Furthermore,

initial

following this review, we strongly suggest

comorbidity history is the first matter that

that more researches on the topic can be

ED has to look up to. Then, other advance

done and published in Asia in order to

follow-up

explore more applicable predicting factors,

Pressure and heart rate needs to be done.

as there are only few studies and predictive

The implementation of such evaluation of

factors

current triage criteria in ED is hoped to

currently

known.

advanced

assessment

establish

and

assessment

the

trauma

updated

care

neurological

Intracranial

triage

system,

thereby helping to reduce the unfavourable

CONCLUSION

prognosis of TBI patients in Asian

To conclude, the factors related to TBI

countries.

prognosis in Asia are sociodemographic

128

REFERENCES Dewan M, Rattani A, Gupta S, Baticulon R, Hung Y, Punchak M et al. Estimating the global incidence of traumatic brain injury. Journal of Neurosurgery. 2019;130(4):1080-1097. Zia N, Mehmood A, Namaganda R, Ssenyonjo H, Kobusingye O, Hyder A. Causes and outcomes of traumatic brain injuries in Uganda: analysis from a pilot hospital registry. Trauma Surgery & Acute Care Open. 2019;4(1):e000259. [Internet]. Tbimedlegal.com. 2019 [cited 3 December 2019]. Available from: http://www.tbimedlegal.com/sitebuildercontent/sitebuilderfiles/TBIinASIA.pdf WHO | Neurotrauma [Internet]. Who.int. 2019 [cited 3 December 2019]. Available from: https://www.who.int/violence_injury_prevention/road_traffic/activities/neurotrauma/e n/ Ellis Hon K, Huang S, Sang Poon W, Ming Cheung H, Ip P, Zee B. Mortality And Morbidity of Severe Traumatic Brain Injuries; A Pediatric Intensive Care Unit Experience Over 15 Years. Bulletin of Emergency and Trauma. 2019;7(3):256-262.

Shekhar C, Gupta L, Premsagar I, Kishore J, Sinha M. An epidemiological study of traumatic brain injury cases in a trauma centre of New Delhi (India). Journal of Emergencies, Trauma, and Shock. 2015;8(3):131. KOMINFO P. Rata-rata Tiga Orang Meninggal Setiap Jam Akibat Kecelakaan Jalan [Internet]. Website Resmi Kementerian Komunikasi dan Informatika RI. 2019 [cited 2 December 2019]. Available from: https://kominfo.go.id/index.php/content/detail/10368/rata-rata-tiga-orang-meninggalsetiap-jam-akibat-kecelakaan-jalan/0/artikel_gpr Park J, Kim S, Yoon S, Cho K, Kim S. Risk Factors Predicting Unfavourable Neurological Outcome during the Early Period after Traumatic Brain Injury. Journal of Korean Neurosurgical Society. 2009;45(2):90. [Internet]. Kesmas.kemkes.go.id. 2019 [cited 2 December 2019]. Available from: http://www.kesmas.kemkes.go.id/assets/upload/dir_519d41d8cd98f00/files/Hasilriskesdas-2018_1274.pdf Xu X, Liu W, Yang X, Li L. Evaluation of models that predict short-term outcome after traumatic brain injury. Brain Injury. 2007;21(6):575-582.

129

Lee E, Hung Y, Wang L, Chung K, Chen H. Factors Influencing the Functional Outcome of Patients with Acute Epidural Hematomas. The Journal of Trauma: Injury, Infection, and Critical Care. 1998;45(5):946-952. Park J, Kim S, Yoon S, Cho K, Kim S. Risk Factors Predicting Unfavourable Neurological Outcome during the Early Period after Traumatic Brain Injury. Journal of Korean Neurosurgical Society. 2009;45(2):90. Ram K, VaraPrasad K, Krishna M, Kannan N, Sundar V, Joseph M et al. Prehospital Factors Associated with Discharge Outcomes: Baseline Data from the Andhra Pradesh Traumatic Brain Injury Project. World Neurosurgery: X. 2019;2:100020. Oh H, Seo W, Lee S, Song H. Comparisons of the Prognostic Predictors of Traumatic Brain Injury According to Admission Glasgow Coma Scale Scores-Based on 1- and 6-month Assessments. Journal of Korean Academy of Nursing. 2006;36(4):621.

McHugh G, Engel D, Butcher I, Steyerberg E, Lu J, Mushkudiani N et al. Prognostic Value of Secondary Insults in Traumatic Brain Injury: Results from The IMPACT Study. Journal of Neurotrauma. 2007;24(2):287-293. Jiang J, Gao G, Li W, Yu M, Zhu C. Early Indicators of Prognosis in 846 Cases of Severe Traumatic Brain Injury. Journal of Neurotrauma. 2002;19(7):869-874. Okazaki T, Hifumi T, Kawakita K, Nakashima R, Matsumoto A, Shishido H et al. Association Between Comorbidities, Nutritional Status, and Anticlotting Drugs and Neurologic Outcomes in Geriatric Patients with Traumatic Brain Injury. World Neurosurgery. 2016;93:336-340. Alimohammadi N, Ziaeirad M, Irajpour A, Aminmansour B. Association between Outcome of severe traumatic brain injury and demographic, clinical, injury-related variables of patients. Iranian Journal of Nursing and Midwifery Research. 2018;23(3):211. Perel P, Edwards P, Wentz R, Roberts I. Systematic review of prognostic models in traumatic brain injury. BMC Medical Informatics and Decision Making. 2006;6(1).

Adoni A, McNett M. The Pupillary Response in Traumatic Brain Injury. Journal of Trauma Nursing. 2007;14(4):191-196.

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APPENDIX Table 2. Study characteristics Author and Year

Study Design

(STROBE â&#x20AC;&#x2122;s score)

Study Population

Predictor

Predicted Outcome

and Location

Ram et

Cohort

447 adult

GCS on

Higher admission GCS

al13,

Prospective (

patients with

arrival

motor score is associated

2019

May to

TBI in King

with lower in-hospital

(19.14/2 October

George

prognosis and mortality

Hospital, India

(GCS score motor 5: aRR,

2017), data obtained from

0.39; 95% CI: 0.26-0.58,

medical

p<0.05; GCS score motor 6:

records

aRR, 0.34; 95% CI: 0.210.55, p<0.05) Neurological

The likelihood of

Injury

unfavourable discharge

comorbidity

outcomes was higher in patients with diffuse axonal injury (aRR 2.39; 95% CI=1.80-3.18, p<0.05), intracerebral hemorrhage/contusion (aRR 2.40; 95% CI=1.80-3.10, p<0.05), and intraventricular hemorrhage (aRR 1.63; 95% CI=1.13-2.33, p<0.05) which was identified using initial CT scan.

131

PH bleeding

Patients with PH bleeding had more unfavourable outcome (aRR 1.60; 95% CI=1.18-2.17, p<0.05)

PH respiratory distress was

respiratory

associated with unfavourable

distress

discharge outcomes (aRR 1.23; 95% CI=1.00-1.51, p<0.05)

Lee et

Cohort

43 pediatric

Raised ICP

ICP was raised

al11,

Retrospective

TBI patients in

2019

(June 2011 to

the National

patients and 70.6% had

(20.67/2 January

University

unfavourable outcome.

2017), data

Hospital of

Raised ICP was significantly

obtained from

Singapore

associated with unfavourable

intraoperatively in 17

patients

outcomes and was significant

medical

independent predictor for

records

unfavourable outcome (odds ratio [OR] = 35.6, 95% CI = 2.6â&#x20AC;&#x201C;493.5, p<0.05) Hypotension

Hypotension was significantly associated with unfavourable outcomes in 83.3% of 12 patients with hypotension and was significant independent predictor for unfavourable outcome (odds ratio [OR] = 26.1, 95% CI 2.2â&#x20AC;&#x201C;311.8, p<0.05)

132

Okazaki et al17,

Cohort Retrospective

2016

(January 1,

(19.40/2 2008 to 2)

October 31,

Patients â&#x2030;Ľ65 with severe

Charlson comorbidity

TBI in Kagawa index (CCI) University

CCI was one of an independent predictors of unfavourable neurological outcomes in elderly patients

Hospital

with TBI (Adjusted OR =

2015), data

1.91, 95% CI = 1.21-3.29,

obtained from

p<0.05).

medical records Age

Age was one of an independent predictors of unfavourable neurological outcomes in elderly patients with TBI (Adjusted OR = 1.16, 95% CI = 1.07-1.28, p<0.05).

GCS on

GCS was one of an

arrival

independent predictors of unfavourable neurological outcomes in elderly patients with TBI (Adjusted OR = 0.56, 95% CI = 0.40-0.72, p<0.05).

Pupillary

Unilateral pupil dilatation

response

was significantly higher in the favourable group compared to the favourable group, (p<0.05)

Neurological

Neurological deficits occurs

deficit

more frequent in the unfavourable group

133

compared to the favourable (unfavourable group= 59.5%-64.3%; favourable group= 23.1-25.3%, , p<0.05) Park et

Cohort

115 TBI

Age

Age was independent risk

al9,

Prospective

Patients in

factors for poor prognosis.

2009

(December

Korea

The number of patients aged

(18.40/2 2004 to

â&#x2030;Ľ35 years was significantly

March 2006),

higher in the unfavourable

data obtained

group compared to the

from initial

favourable group (The

clinic-

favourable group for TBI

radiological

patients was 46.8-47.3 years

data.

and the unfavourable group was 57.7-59.5 years, p<0.05). GCS on

Mean initial GCS scores was

arrival

independent risk factors for poor prognosis. The mean Initial GCs score are significantly higher in the favourable group compared to the unfavourable one. (Favourable group: 12.012.2; Unfavourable group: 7.2-7.8)

Pupillary

Unilateral pupil dilatation

response

was significantly higher in the favourable group

134

compared to the favourable group Neurological

Neurological deficits occurs

deficit

more frequent in the unfavourable group compared to the favourable (unfavourable group= 59.5%-64.3%; favourable group= 23.1-25.3%)

Systolic

Systolic blood pressure was

blood

one of the most important

pressure

predictors of 1-month functional disability in severe TBI patients. (beta = -0.30, t = -2.13, p = 0.02, one-tailed test). sBP also was one of the most important predictors of 6-month functional disability in severe TBI patients. ( beta = -0.50, t = -3.52, p = 0.00, one- tailed test)

Heart rate

Heart rate was one of the most important predictors of 6-month functional disability in severe TBI patients (beta = -0.23, t = -1.66, p = 0.05, one-tailed test)

Motor

Motor response was one of

response

the most important predictors of 6-month functional disability in severe TBI

135

patients (beta = 0.24, t = 1.80, p = 0.04, one-tailed test). Oh HS

Cohort

82 TBI patients Age

Age was one of the best

et al14,

Prospective

in Neurological

predictors of 1-month

2006

(1- and 6-

Intensive Care

functional disability in severe

(16.94/2 months

Unit at a

TBI patients (beta = 0.56, t =

period), data

university

4.06, p = 0.00, one-tailed

obtained from

hospital

test), and one of the best

medical

predictors of 6-month

records

functional disability in severe TBI patients (beta = 0.45, t = 3.21, p = 0.00, one-tailed test) Intracranial

Intracranial hematoma was

hematoma

one of the most important predictors of 1-month functional disability in severe TBI patients (beta = 0.37, t = 2.88, p = 0.00, one-tailed test) and one of the most important predictors of 6month functional disability in severe TBI patients (beta = 0.32, t = 2.45, p = 0.01, onetailed test).

Systolic

Systolic blood pressure was

blood

one of the most important

pressure

predictors of 1-month functional disability in severe TBI patients. (beta = -0.30, t

136

= -2.13, p = 0.02, one-tailed test). sBP also was one of the most important predictors of 6-month functional disability in severe TBI patients. ( beta = -0.50, t = -3.52, p<0.05, one- tailed test) Heart rate

Heart rate was one of the most important predictors of 6-month functional disability in severe TBI patients (beta = -0.23, t = -1.66, p<0.05, onetailed test)

Motor response

Motor response was one of the most important predictors of 6-month functional disability in severe TBI patients (beta = 0.24, t = 1.80, p<0.05, one-tailed test).

Jiang et

Cohort

846 Patients in

GCS on

After 1 year injury, patients

al16,

Retrospective

China

arrival

with lower GCS score

2002

(January

showed more unfavourable

(17.20/2 1991-

prognosis than the higher

December

ones. (Good Recovery: 8 =

1998), data

39.88%; 7=37.61%;

obtained from

6=32.16%; 5=21.69%;

medical

4=16.18%; 3=6.98%,

records

p<0.05).

137

Age

The prognosis of aged patients was much more unfavourable than that of the young ones (Good Recovery: Age <16 = 53.76%; 1750=31.33%; 51-65=19.05%; >66=9.28%, p<0.05).

Pupillary

The prognosis of patients

response

with bilaterally abnormal pupillary response and size patients have more unfavourable outcome than the bilaterally normal and unilaterally abnormal pupillary response and size (Good Recovery: bilateral normal = 53.13%; unilateral abnormal = 20.99%; bilateral abnormal = 11.23%, p<0.05)

Hyperthermia The prognosis of patients with hyperthermia within 72 hours post injury was much more unfavourable than that of patients without hyperthermia (Good Recovery: <37oC = 35.53%; 37-39oC = 33.43%; >39oC = 24.17%, p<0.05). Hypoxia

The prognosis of patients with hypoxia was much unfavourable than patients

138

without hypoxia (Good Recovery: <60 mmHg = 10.11%; 60-80 mmHg = 25.84%; >80 mmHg = 38.57%, p<0.05). High ICP

The prognosis of patients with high ICP was much worse than of patients without high ICP (Good Recovery: <20 mmHg = 29.36%; 20-40 mmHg = 19.42%; >40 mmHg = 9.57%, p<0.05).

Notes: GCS, Glasgow Coma Scale; TBI, traumatic brain injury; ICP, intracranial pressure; PH, blood pH; aRR, adjusted risk ratio

Table 3. Studies quality assessment based on STROBE s criteria

Title and abstract

Ite m

Recommendati

(a) Indicate the study s design

Ram et al

Lee et al

Oka zaki

Park et al

et al

Oh HS

Jiang et al

et al

Yes

with a commonly used term in the title or the abstract (b) Provide in the abstract an informative and

139

balanced summary of what was done and what was found Introduction Background/ rationale

2 Explain the scientific

Yes

background and rationale for the investigation being reported Objectives

3 State specific objectives, including any prespecified hypotheses

Methods Study design

4 Present key elements of study design early in the paper

Setting

5 Describe the setting, locations, and relevant dates, including periods of recruitment, exposure,

140

follow-up, and data collection Participants

(a) Cohort

Yes

study Give the eligibility criteria, and the sources and methods of selection of participants. Describe methods of follow-up Case-control study Give the eligibility criteria, and the sources and methods of case ascertainment and control selection. Give the rationale for the choice of cases and controls Cross-sectional study Give the eligibility criteria, and the sources and methods of

141

Yes

selection of participants (b) Cohort study For

N/A

Yes

N/A

Yes

matched studies, give matching criteria and number of exposed and unexposed Case-control study For Yes matched studies, give matching criteria and the number of controls per case Variables

7 Clearly define all outcomes, exposures, predictors, potential confounders, and effect modifiers. Give diagnostic criteria, if applicable

Data sources/ measurement

8* For each variable of interest, give sources of data

142

and details of methods of assessment (measurement). Describe comparability of assessment methods if there is more than one group Bias

Describe any efforts to

Yes

address potential sources of bias Study size

Explain how the study size was arrived at

Quantitative variables

Explain how quantitative variables were handled in the analyses. If applicable, describe which groupings were chosen and why

Statistical methods

(a) Describe all statistical methods, including those used to control for confounding

143

(b) Describe any methods used to

Yes

examine subgroups and interactions (c) Explain how missing data were addressed (d) Cohort study If applicable, explain how loss to followup was addressed Case-control study If applicable, explain how matching of cases and controls was addressed Cross-sectional study If applicable, describe analytical methods taking account of sampling strategy

144

(e) Describe any sensitivity

Yes

analyses Results Participants

13* (a) Report numbers of individuals at each stage of study

e.g.

numbers potentially eligible, examined for eligibility, confirmed eligible, included in the study, completing follow-up, and analysed (b) Give reasons for nonparticipation at each stage (c) Consider use of a flow diagram Descriptive data

14* (a) Give characteristics of study participants (e.g.

145

demographic, clinical, social) and information on exposures and potential confounders (b) Indicate number of

Yes

N/A

participants with missing data for each variable of interest (c) Cohort study Summarise follow-up time (e.g., average and total amount) Outcome data

15* Cohort study Report numbers of outcome events or summary measures over time Case-control studyâ&#x20AC;&#x201D;Report numbers in each exposure category, or summary

146

measures of exposure Cross-sectional studyâ&#x20AC;&#x201D;Report

N/A

Yes

numbers of outcome events or summary measures Main results

16 (a) Give unadjusted estimates and, if applicable, confounderadjusted estimates and their precision (e.g., 95% confidence interval). Make clear which confounders were adjusted for and why they were included (b) Report category boundaries when continuous variables were categorized

147

N/A

Yes

translating estimates of relative risk into absolute risk for a meaningful time period Other analyses

17 Report other analyses done e.g. analyses of subgroups and interactions, and sensitivity analyses

Discussion Key results

18 Summarise key results with reference to study objectives

Limitations

19 Discuss limitations of the study, taking into account sources of potential bias or imprecision. Discuss both direction and magnitude of any potential bias

148

Interpretation

20 Give a cautious overall

Yes

interpretation of results considering objectives, limitations, multiplicity of analyses, results from similar studies, and other relevant evidence Generalisabil ity

21 Discuss the generalisability (external validity) of the study results

Other information Funding

22 Give the source of funding and

Yes

Yes No

the role of the funders for the present study and, if applicable, for the original study on which the present article is based TOTAL 19.14 20.67

149

19.40

18.40

16.94

17.20

Handling Trauma in Elderly Patient Marito Lenni Tin Sianipar and Chatrine Angelica Dwi Christy AMSA-Universitas Kristen Indonesia Introduction Trauma is the seventh leading cause of death in older adults. Trauma can occur in any age-groups. The elderly suffer the same injuries that young people suffer; However, due to various age-related processes, the elderly suffer more severe consequences from this injury. Death and morbidity due to injury can be influenced by many factors including age, physical condition, and comorbidity. Management of elderly trauma patients can present several unique challenges compared to young patients. Methods Search strategies and criteria for selecting articles Systematic literature study searches were conducted with a database in Pubmed, Google for articles published between 2011 and 2018. We use the following terms in the search field: “Trauma AND Handling and “Trauma AND Elderly . Search results are downloaded into a personal database. The results from the four databases are then cited and combined. Results All 926 eligible patients were included in the analyses: 344 MT-HI patients and 582 minor trauma without head injury. After six months, the functional decline was similar in both groups: 10.8% and 11.9%, respectively (RR = 0.79 [95% CI: 0.55–1.14]). The proportion of patients with mild cognitive disabilities was also similar: 21.7% and 22.8%, respectively (RR

= 0.91 [95% CI: 0.71–1.18]). Furthermore, for the group of patients with an MT-HI, the functional outcome was not statistically different with or without the presence of a co-injury (RR = 1.35 [95% CI: 0.71–2.59]). Conclusion This study did not demonstrate that the occurrence of an MT-HI is associated with a worse functional or cognitive prognosis than other minor injuries without a head injury in an elderly population, six months after injury. Keyword: Injury, Trauma, Elderly, Management

150

Handling Trauma in Elderly Patient Name of author:

1. Marito Lenni Tin Sianipar

2. Chatrine Angelica Dwi Christy ABSTRACT Introduction: Trauma is the seventh leading cause of death in older adults. Injuries among the elderly are a common occurrence. As you age, the elderly will become a prominent part of the trauma patient. The elderly suffer the same injuries that young people experience; However, due to various age-related processes, the elderly suffer more severe consequences from this injury. 2Trauma is a disease process that attacks all age groups. Death and morbidity due to injury can be influenced by many factors including age, physical condition, and comorbidity. Management of elderly trauma patients can present several unique challenges compared to young patients. The most dangerous is craniofacial trauma associated with high mortality, but the most common is hip fracture. Methods: Search strategies and criteria for selecting articles Systematic literature study searches were conducted with a database in Pubmed, Google for articles published between 2011 and 2018. We use the following terms in the search field: Trauma AND Handling and Trauma AND Elderly. Search results are downloaded into a personal database. The results from the four databases are then cited and combined. Results: All 926 eligible patients were included in the analyses: 344 MT-HI patients and 582 minor trauma without head injury. After six months, the functional decline was similar in both groups: 10.8% and 11.9%, respectively (RR = 0.79 [95% CI: 0.55 1.14]). The proportion of patients with mild cognitive disabilities was also similar: 21.7% and 22.8%, respectively (RR

= 0.91 [95% CI: 0.71 1.18]). Furthermore, for the group of patients with an MT-HI, the functional outcome was not statistically different with or without the presence of a co-injury (RR = 1.35 [95% CI: 0.71 2.59]). Conclusion: This study did not demonstrate that the occurence of an MT-HI is associated with a worse functional or cognitive prognosis than other minor injuries without a head injury in an elderly population, six months after injury. Keyword: Injury, Trauma, Elderly, Management

151

HANDLING TRAUMA IN ELDERLY PATIENT

Authors:

Marito Lenni Tin Sianipar Chatrine Angelica Dwi Christy AMSA-Universitas Kristen Indonesia

Asian Medical Students Associa ion-Indonesia (AMSA-Indonesia)

2019

152

Introduction Trauma is the seventh leading cause of death in older adults.1 Injuries among the elderly

are a common occurrence. As people get older, the elderly will become a prominent part of the trauma patient. The elderly suffer the same injuries that young people experience; However, due to various age-related processes, the elderly suffer more severe consequences from this injury.2 Trauma is a disease process that attacks all age groups. Death and morbidity due to injury can be influenced by many factors including age, physical condition, and comorbidity. Management of elderly trauma patients can present several unique challenges compared to young patients. The most dangerous is craniofacial trauma associated with high mortality, but the most common is hip fracture.2,3,4 Elderly trauma patients are very susceptible to the adverse effects of red blood cells (PRBC). Elderly intensive care unit (ICU) patients are more often transfused than younger counterparts because they can disproportionately experience immunosuppressive effects and increased mortality associated with blood transfusions.4 Elderly trauma patients will have lower levels of incoming hemoglobin, higher transfusion rates, and worse outcomes than younger trauma patients when controlling the severity of injuries, comorbid conditions, and blood loss ..5 Massive transfusion protocol (MTP) is used to sensitize patients with hemorrhagic shock. When MTP is activated, survival for outpatients in elderly trauma patients is comparable to younger patients.6 Management of elderly trauma patients presents unique challenges. The incidence of elderly major trauma in Victoria is increasing, with now 36.4% of adult major trauma presentations associated with patients aged 65 years or more in 2014-2015.7 Physiological patients who can determine their recovery from traumatic injuries than at only their chronological age. Co-morbid clinical conditions can fundamentally determine the healing of elderly patients and even survival after Major and even Minor Trauma. Be aware that even in situations where there are no life-threatening injuries, patients can die from limited physiological reserves.2,3,4,8 Their results suggested that patients 50 89 years of age, particularly those with mTBI, were significantly more dependent compared to younger patients, as measured with the Independent Living Scale (ILS) at one-year post-injury. More recently, Sirois et al. and the CETI (the Canadian Emergency Departments Team Initiative) evaluated functional decline in older patients after different types of minor trauma, including MT-HI,9 and found that approximately 18% of their population had a functional decline at six months. Furthermore, older adults often sustain more than one injury in the same event.10 Leong et al. studied the effect of a co-injury (injury to another part of the body) with

153

an mTBI in young patients and found that their functional outcome was significantly worse than those without a co-injury.11

II.

Methods Search strategies and criteria for selecting articles Systematic literature study searches

were conducted with a database in Pubmed, Google for articles published between 2011 and 2018. We use the following terms in the search field: Trauma AND Handling and Trauma AND Elderly. Search results are downloaded into a personal database. The results from the four databases are then cited and combined. III.

Results A total of 926 patients were included in the analysis, 344 in the MT-HI group and 582

in the group without head injury (Figure 1). Table 1 describes the characteristics of the participants and highlights some differences between the two groups. Patients with MT-HI were older than those without head injury. Also, falls from their height were the leading cause of trauma in both groups but a greater proportion was found in the MT-HI group. A greater proportion of patients with a pain level > 7/10 was identified in the without head injury group. Two important differences were found: patients from the without head injury group needed more help after their injury and they also had a greater proportion of consultation delays (time between injury and presentation at the ED) of 48 hours and more. 9 Six months after trauma, 10.8% of patients in the MT-HI group had a functional decline compared to 11.9% in the without head injury group (RR= 0.79 [95% CI 0.55 1.14]), which was not statistically significant (Table 2). The proportion of participants who had mild cognitive impairment was similar in the two groups both at baseline (RR = 1.01 [95% CI 0.84 1.30]) and at six months post-injury (RR = 0.91 [0.71 1.18]). Surprisingly, at six months, the proportion of patients who had a cognitive impairment was lower than at baseline in both groups, 21.7% v. 35%, and 22.8% v. 33% respectively (p < 0.001). The presence of a co-injury did not have a significant impact on functional decline in the MT-HI group (RR = 1.35 [95% CI 0.70 2.59]) (Table 3). 9 We performed a subgroup analysis comparing mTBI patients, as defined by the WHO criteria, to patients with injuries other than mTBI (Table 4). The proportion of patients who had a functional decline was 11.7% in the mTBI group v. 11.4% in the group without mTBI (RR = 0.90 [95% CI 0.58 1.39]). We found no significant difference in cognitive outcomes at

154

six months between these two subgroups (20.4% v. 22.9%, RR = 0.82 [95% CI 0.59 1.13]). Sensitivity analyses with different cut-offs for the OARS scale did not show different results (data not shown). 9 IV.

Discussion To our knowledge, this is the first prospective study aiming to compare the functional

prognosis of older adults after an MT-HI with those who sustained a minor trauma without a head injury. Our study included elderly patients from a large Canadian multicenter cohort, and standardized validated scales were used to assess outcomes. Our results showed that functional and cognitive decline was similar in both groups. So we can expect a similar prognosis regardless of the nature of the injury. 9 Our initial hypothesis was that a minor trauma involving a head injury (MT-HI) could have a more significant impact on functional outcome than a minor trauma without a head injury. However, there were no differences between the two groups six months after the trauma. Surprisingly, the cognitive status at six months improved relative to baseline for all patients, which correlates with results of a previous study.10

A hypothesis that could explain this finding is that the tests were done after the actual injury and their results might not represent the real baseline cognitive status of participants before the trauma. Also, it has been shown that a short visit to the ED has repercussions on the cognitive status (recognized as delirium) of elderly patients.11-15 Given the results of this study, interventions that reduce the impact of injury on functional status are likely to affect the risk of injury recurrence. Such interventions might focus on the aggressive management of the elderly patient who experienced trauma in the rehabilitation setting. Research16 supports the contention that more aggressive rehabilitation management planning can be effective in returning patients to a preinjury level of functioning. Fall injury prevention programs are also likely to provide insight as to effective interventions to reduce recurrent injuries in general. Several studies have evaluated interventions focused on improving mobility and physical fitness, identifying (and modifying) environmental and personal safety risks, and modifying psychotropic drug use. The growing consensus in this literature is that multifactorial interventions are likely to be most successful in reducing the risk of initial and recurrent falls. It is suggested that patients at risk of falls based on known risk factors17

155

Conclusion Older independent adults with minor trauma involving a head injury do not seem to

have worse functional or cognitive decline than those without head injury. In our MT-HI group, the presence of a concomitant injury did not seem to be associated with an increased risk of functional decline after six months. Although we observed a similar prognosis regardless of the nature of the injury, 11% of our cohort of independent older adults had a significant functional decline following their minor traumatic injury. Accordingly, further research should focus on finding a way to effectively screen for patients who are at higher risk of functional decline.9

156

VI.

References 1. Cutugno, Christine L. PhD, RN. The 'Graying' of Trauma Care: Addressing Traumatic Injury in Older Adults. American Journal of Nursing. Vol 111. Number 11. November 2011. P 40-8. 2. RS, H. (2015). Elderly trauma. crit care nurse, 298-299. 3. FLORIO, M. G., MURABITO, L. M., VISALLI, C., & PERGOLIZZI, F. P. (2018). Trauma in elderly patients: a study of prevalence, comorbidities and gender differences. IL GIORNALE DI CHIRURGIA, 35-40. 4. Loftus, T. J., Brakenridge, S. c., Murphy, T. W., & Nguyen, L. L. (2018). Anemia and blood transfusion in elderly trauma patients. J Surg Res, 288-293. 5. Murry, S, J., Zaw, & A, A. (2018). Activation of massive transfusion for elderly trauma patients. THE AMERICAN SURGEON. 6. Santora TA, Schinco MA, Trooskin SZ. Management of Trauma in The Elderly Patient. Surgical Clinics of North America. Vol 74. Issue 1. February 1994. P 163-86. 7. Florio GM, Murabito LM. Trauma in Elderly Patient:A Study of Prevalence, Comorbidities and Gender Differences. G Chir. 2018. P 35-40. 8. Ouellet MC, Sirois MJ, Beaulieu-Bonneau S, et al. Is cognitive function a concern in independent elderly adults discharged home from the emergency department in Canada after a minor injury? J Am Geriatr Soc 2014;62(11): 2130-5. 9. Brousseau AA, Emond M. Comparison of Functional Outcomes in Elderly Who Have Sustained A Minor Trauma with or without Head Injury: A Prospective Multicenter Cohort Study. CJEM. 2017. P 329-37. 10. Cutugno, Christine L. PhD, RN. The 'Graying' of Trauma Care: Addressing Traumatic Injury in Older Adults. American Journal of Nursing. Vol 111. Number 11. November 2011. P 40-8. 11. Santora TA, Schinco MA, Trooskin SZ. Management of Trauma in The Elderly Patient. Surgical Clinics of North America. Vol 74. Issue 1. February 1994. P 163-86. 12. Brousseau AA, Emond M. Comparison of Functional Outcomes in Elderly Who Have Sustained A Minor Trauma with or without Head Injury: A Prospective Multicenter Cohort Study. CJEM. 2017. P 329-37. 13. Cutugno, Christine L. PhD, RN. The 'Graying' of Trauma Care: Addressing Traumatic Injury in Older Adults. American Journal of Nursing. Vol 111. Number 11. November 2011. P 40-8.

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14. Brousseau AA, Emond M. Comparison of Functional Outcomes in Elderly Who Have Sustained A Minor Trauma with or without Head Injury: A Prospective Multicenter Cohort Study. CJEM. 2017. P 329-37. 15. Sirois MJ, Emond M, Ouellet MC, et al. Cumulative incidence of functional decline after minor injuries in previously independent older Canadian individuals in the emergency department. J Am Geriatr Soc 2013;61(10): 1661-8. 16. Ouellet MC, Sirois MJ, Beaulieu-Bonneau S, et al. Is cognitive function a concern in independent elderly adults discharged home from the emergency department in Canada after a minor injury? J Am Geriatr Soc 2014;62(11): 2130-5. 17. Kennedy M, Enander RA, Tadiri SP, et al. Delirium risk prediction, healthcare use and mortality of elderly adults in the emergency department. J Am Geriatr Soc 2014;62

(3):462-9.

158

VII.

Table and Figures

159

160

Protective Effect of Erythropoietin in Traumatic Brain Injury Jonathan Vincent Lee* Johanna Valentina* Tharriel Jeremia* ABSTRACT

Introduction Between 2009 and 2013, there are 1178 cases of traumatic brain injury (TBI) in Indonesia each year. This calls for new methods to improve the outcome of TBI, one of those is by the usage of erythropoietin (EPO). Earlier researches in mice found that EPO possesses beneficial effects. However, the effect in human is not certain.

Aim This systematic review aims to determine the benefit of EPO usage on TBI patients.

Materials and Methods Search was done in Cochrane, Google Scholar, and Science Direct. PICO a ed a analytical design method, and all literature will be filtered using inclusion and exclusion criteria. Risk of Bias 2 tool was used to determine the risk of bias for each research.

Result and Discussion There were 9.920 journals from Cochrane, Google Scholar, and Science Direct. After filtered with inclusion and exclusion criteria, 5 literatures were taken to be analyzed. Claudia S. Robertson, MD; et al: there are no significant advantage by using EPO in TBI (95% CI, 0.184 to 0.44 , P < .001) Skrifvars MB,et.al: there are significant improvement in TBI patients with EPO (95% confidence interval, 2.9-17%; p = 0.007). R. Nirula, et al (2010): there are no reduction of neuronal cell death by using EPO in TBI (P = 0.89). Nichol, Alistair. Et.al: the effect of EPO in patients remain uncertain (RR 0路68 ,95% CI 0路44 1路03 p=0路07) . Talving, Et,Al: they demonstrated a significantly lower in-hospital mortality in comparison to controls groups (7.9% vs 24.2% (OR: 0.27; 95% CI = 0.12-0.62; P = 0.001).

161

Conclusion Some contradicting experiments disproved the benefits of EPO. However, most of the researches can be optimized further due to the limitations. Therefore, we strongly suggest that most of the researches be optimized further for more accurate results. Keywords: Erythropoietin, Traumatic Brain Injury.

162

Protective Effect of Erythropoietin in Traumatic Brain Injury: A Systematic Review

Scientific Paper

Author(s): Jonathan Vincent Lee Johanna Valentina Tharriel Jeremia

163

Protective Effect of Erythropoietin in Traumatic Brain Injury: A Systematic Review Jonathan Vincent Lee* Johanna Valentina* Tharriel Jeremia*

INTRODUCTION Traumatic Brain Injury Traumatic brain injury (TBI) is damage to the brain that is caused by a sudden trauma. TBI occurs due to an impact or head injury. Based on the research conducted by Rosyidi et.al, in Indonesia, between the year of 2009 and 2013, it was found that there were 1178 cases of brain injury patients each year. Half of all TBI cases were from motor vehicle accidents. 1

Symptoms of TBI vary from mild, moderate, or severe, depending on the damage to the brain. Sometimes people called mild brain injury as c c

. Pa ie

i d TBI

remain conscious or may experience loss of consciousness. Other symptoms of mild TBI include headache, nausea, confusion, blurred vision, ringing in the ears, dizziness, and tiredness.2 Patients with moderate or severe TBI may experience the same symptoms, but they may have a headache that gets worse or does not go away, repeated vomiting or nausea, convulsions or seizures, slurred speech, inability to awaken from sleep, dilated pupils, and loss of coordination. The worst TBI can lead to permanent brain damage or death.2 TBI may cause problems with various brain function. The types of these problems depend on where the brain was injured. The problems include difficulty learning, trouble talking, difficulty with social situations, depression, and loss of the sense of taste. A large body of epidemiological studies has shown that having a history of previous TBI is associated with the development of numerous types of dementia later in life. Other recent studies showed that TBI is linked to other types of neurodegeneration such as Lewy Body accumulation and Parkinsonism.3,4 A variety of treatments can help promote recovery from the physical, emotional, and cognitive problems TBI may cause. The types of treatments depend on the severity of the injury and its specific location in the brain. Mild TBI may not require specific treatment other than rest. However, it is important to follow a health care provider i

164

ee e ,

so patients can return to normal activities gradually. Patients with concussion might need to reduce heavy activities or might need to rest between periods of such activities to let the brain rest. In addition, alcohol and other drugs can make the recovery process become slower and increase the chances of re-injury. In most of emergency cases, the treatment focuses on stabilizing the patient and promoting survival. The treatment may include ensuring adequate oxygen flow to the brain, controlling blood pressure, and preventing further injury to the head or neck. Once the patient is stable, other types of care for TBI and its effects can begin. Surgery may be done in emergency treatment to reduce additional damage to brain tissue. 5,6 Erythropoietin Human Erythropoietin (EPO) is an acidic glycoprotein hormone produced by the peritubular cells of the kidney which is crucial in the production of Red Blood Cell (RBC). It has 165 amino acid residues chain that form four antiparallel -helices,

-sheets, and two intra-

chain disulfide bridges (Cys7-Cys161, Cys29-Cys33). The carbohydrate portion comprises three N-glycans (at Asn24, Asn38, and Asn83) and one O-glycan (at Ser126).7 EPO stimulates proliferation and differentiation of RBC in the red bone marrow, known as erythropoiesis. Once erythropoiesis is done, mature RBC will be released into the blood. EPO secretion will stop if the oxygen supply to the kidney is fulfilled. Decreased oxygen supply to the kidney will stimulate the secretion of EPO into the blood. 7 EPO stimulates red blood cell production by binding and activating a high affinity receptor (EpoR) that is expressed predominantly on the surface of immature erythroid cells. Signal transduction through EpoR is initiated by ligand binding which cause dimerization of EpoR monomers. The predominant pathway activated by EpoR is the Jak/STAT signaling cascade. Activated EpoR cause tyrosine phosphorylation of several intracellular proteins. Jak2 protein tyrosine kinase associated with EpoR and serving as mediator of Epo-responsive signal transduction. The EpoR contains eight tyrosine residues, upon phosphorylation, several of these serve as docking sites for intracellular signaling molecules, including the transcription factors STAT5A and STAT5B, the p85 subunit of phosphoinositol 3'-kinase (PI3K), the cytokine suppressor CIS and the phosphatase SHP-1. 7

165

Image 1.1 EPO Receptor binding Watowich S. The Erythropoietin Receptor: Journal of Investigative Medicine. 2011;59(7):1067-1072.

Jak2 appears to interact directly with STAT5A and STAT5B, indicating it can serve as a scaffold for signal protein activation in addition to its enzymatic role in EpoR signal transduction. Recruitment of signaling molecules in proximity to Jak2 in the EpoR complex enables their tyrosine phosphorylation, which is an important step in subsequent activation of their respective signaling cascades. STAT5A and STAT5B proteins are predominant signal transducers for EpoR. These proteins are activated within seconds of EPO binding and accumulate in the nucleus to mediate Epo-responsive gene transcription for erythropoiesis. EPO production depends on the rate of Epo Gene in Chromosome 7. EPO have Hypoxia-Response Element (HRE) that activated by Hypoxia-Inducible Transcription Factors (HIFs). The main activator of EPO is HIF-2. 7

166

MATERIALS AND METHODS Search is done in Cochrane, Google Scholar, and Science direct using E Ta

a ic B ai I j

, a d TBI

d, e

i g i 9,920 j

ie i , EPO ,

a , he d

ica e a e

removed, and the journals are further excluded according to year, population and research types leaving only 5 valid journals. Risk of bias tool 2 (ROB 2) is used to determine the risk of bias for each research. RESULT AND DISCUSSION Erythropoietin have long been regarded as possessing protective effects, especially regarding traumatic brain injury. Experiments in mice and rats prove that erythropoietin possess neuroprotective effects; research done by Grasso et Al. proves that usage of EPO improves recovery, reduces blood brain barrier breakdown, and reduces injury volume significantly. 8 However, it remains to be seen whether erythropoietin does have a positive effect to reduce damage from traumatic brain injuries. This is found by several conflicting researches. One research done by Talving et.al, in which 267 patients were included in a retrospective study, out of the 89 people that is given Epo Stimulating Agent, only 7 (7.9%) patients whose condition worsened, compared to the 43 (24.2%) patients in the control group. (OR: 0.27; 95% CI = 0.12-0.62; P = 0.001). 9 In a randomized controlled trial done by Skifvars et al. in which 603 TBI patients were included in the research, out of the 301 patients with Injury Severity Score (ISS) of over 6, 147 patients were given EPO and 154 patients were given placebo. Only 10 (6.8%) of the patients in the treatment group died compared to 26 (17%) of patients in the placebo group (risk reduction, 0.1 ; 95% confidence interval, 2.9-17%; p = 0.007).10 These researches proves that EPO possess a benefit to patients with TBI On the other hand, research done by Claudia S et.al, out of 200 patients with closed head injury, 102 patients were given EPO using two different doses, unfortunately, both of the doses does not improve the outcome of the patients (first dosing regimen: 17/35 [29.8%; 95% CI, 0.184 to 0.44 ], P < .001), second dosing regimen: 17/57 [48.6%; 95% CI, 0.31 to 0.66]

Also, According to Nichol et.al, out of 596 patients which were enrolled to a study, in which 302 of the patients were given EPO, and 294 were given placebo, the population with

167

EPO does not improve 6 months mortality rate (RR 0·68 ,95% CI 0·44 1·03 p=0·07), or decrease neurological dysfunction ([RR] 0·99,95% CI 0·83 1·18, p=0·90).11 Another research done by Nirula et.al, which measures the Baseline and daily serum S100B and Neuron Specific Enolase (NSE) founds that out of patients which were given epo, the severity of TBI was worse compared of placebo patients, in which the value of NSE (P = 0.89) or S100 B (P = 0.53) does not improve.12 These researches proves that there are no significant advantage by using EPO in traumatic brain injuries, with no differing recovery rate, reduction of damage, or improved outcome. Thus, it seems that most research trends towards the conclusion that EPO provides no beneficial effects. Yet, there are aspects we need to consider, one of those are the limitations of the research. Traumatic brain injury is a complex injury which correlates to many, if not all, of systems, which results in a hugely heterogeneous range of disability. A question rises regarding the dosage, intervention time, and the assessment of EPO, an area where most of the researches can be refined in. 13 As an example, within the research done by Nichol et.al, the recruitment period of 24 hours did not corroborate with the research done by Ponce et.al which shows that EPO possesses beneficial effect to acute traumatic brain injuries.14 Another part of the conundrum are the dosages given; most of the patient does not receive the optimal dosage of EPO due to safety concerns. This leads to a conclusion that none of the researches truly covers the scope of TBI as well as the full benefits of EPO that comes with the optimal dosage and timing. CONCLUSION Experiments using EPO in mice proved that there is potential for protective effects of EPO in traumatic brain injury. Even though most clinical research in humans find that EPO usage fails to produce a significant protective effect in traumatic brain injury, yet most of the research fails to define the value of EPO in the optimal conditions. This can be caused due to difficulty and limitations of EPO and the complexity of traumatic brain injuries within human populations. Thus, further clinical research with refined and specified goals, method and outcome is needed to have a definitive conclusion regarding this matter.

168

REFERENCES Traumatic Brain Injury | TBI | MedlinePlus . Medlineplus.gov. 2019 Traumatic Brain Injury Information Page | National Institute of Neurological Disorders and Stroke . Ninds.nih.gov. 2019 What are the possible effects of TBI? . https://www.nichd.nih.gov/. 2019 What are the treatments for TBI? . https://www.nichd.nih.gov/. 2019 Ramos-Cejudo, J., Wisniewski, T., Marmar, C., Zetterberg, H., Blennow, K., de Leon, M. and Fossati, S. (2018). Traumatic Brain Injury and Alzheimer's Disease: The Cerebrovascular Link. EBioMedicine, 28, pp.21-30. Chen G, Shi J, Hang C, Xie W, Liu J, Liu X. Inhibitory effect on cerebral inflammatory agents that accompany traumatic brain injury in a rat model: A potential neuroprotective mechanism of recombinant human erythropoietin (rhEPO). Neuroscience Letters . 2007 Jelkmann W. Physiology and Pharmacology of Erythropoietin. Transfusion Medicine and Hemotherapy . 2013;40(5):302-309. Grasso G, Sfacteria A, Meli F, Fodale V, Buemi M, Iacopino D. Neuroprotection by erythropoietin administration after experimental traumatic brain injury. Brain Research . 2007 ;1182:99-105.7 Talving P, Lustenberger T, Kobayashi L, Inaba K, Barmparas G, SchnĂźriger B et al.Erythropoiesis Stimulating Agent Administration Improves Survival After Severe Traumatic Brain Injury. Annals of Surgery . 2010 ;251(1):1-4. Skrifvars MB e. Erythropoietin in patients with traumatic brain injury and extracranial injury-A post hoc analysis of the erythropoietin traumatic brain injury trial. - PubMed - NCBI . Ncbi.nlm.nih.gov. 2019 Robertson C, Hannay H, Yamal J, Gopinath S, Goodman J, Tilley B et al. Effect of Erythropoietin and Transfusion Threshold on Neurological Recovery After Traumatic Brain Injury. JAMA ;312(1):36. Nichol A, French C, Little L, Haddad S, Presneill J, Arabi Y et al. Erythropoietin in traumatic brain injury (EPO-TBI): a double-blind randomised controlled trial. The Lancet . 2015 ;386(10012):2499-2506. Nirula R, Diaz-Arrastia R, Brasel K, Weigelt J, Waxman K. Safety and Efficacy of Erythropoietin in Traumatic Brain Injury Patients: A Pilot Randomized Trial. Critical Care Research and Practice. 2010 ;2010:1-5.

169

D, Maa A. EPO i

a ic b ai i j

i e

The Lancet . 2015;386(10012):2452-2454. Ponce L, Navarro J, Ahmed O, Robertson C. Erythropoietin neuroprotection with traumatic brain injury. Pathophysiology.;20(1):31-38. Watowich S. The Erythropoietin Receptor: Journal of Investigative Medicine. 2011;59(7):1067-1072.

170

TABLES AND FIGURES Table 1.1 Journal Assessment Journal

Author

Effect

Population

of Claudia S. Robertson, 200

Erythropoietin and Transfusion Threshold on Neurological Recovery After Traumatic Brain Injury A Randomized Clinical Trial

Conclusion

patients Among patients

MD; H. Julia (erythropoietin, Hannay, PhD; JosĂŠ- = 102; Miguel Yamal, PhD; aceb , = 98) et al

Limitation 1.

with closed head injury, neither the administration of erythropoietin nor maintaining hemoglobin 2. concentration of at least 10 g/dL resulted in improved neurological outcome at 6 months.

Erythropoietin

Skrifvars MB, Bailey

in patients with M, French traumatic brain Presneill J,et.al. injury and extracranial injury-A post hoc analysis of the erythropoietin traumatic brain injury trial

Safety

603

included In this post hoc

C, patients (1 147 EPOtreated patients and 154 placebo-treated patients )

and R. Nirula, R. Diaz-

Efficacy of Arrastia, K. Brasel, et Erythropoietin al. in Traumatic Brain Injury Patients: A Pilot

16 patients (11

The

Risk of Bias trial

was Low

conducted at only 2 clinical sites, which could limit the ability to generalize the results Enrollment under the Exception From Informed Consent was not allowed in the early months of the study, and it was difficult to recruit patients within the 6hour window. the trial was on clinical hold for approximately 1 year due to safety concerns about the initial erythropoietin dosage regimen.

The primary

was not designed to study the effect of EPO in TBI within patients with coexisting extracranial injuries at various levels of severity.

This

The small

171

Probably Done

trial Low

analysis, EPO administration was associated with a potential differential improvement in 6-month mortality in TBI patients with more severe extracranial injury. These findings need confirmation in future clinical and experimental studies.

in EPO group, 5 preliminary in Placebo analysis did not Group). demonstrate a reduction in neuronal cell death as

I e iga and clinical personnel caring for the patient were blinded to the study drug (erythropoietin or placebo) for each patient, but not to the transfusion threshold assignment. Personnel conducting outcome assessments were blinded to both drug treatment assignment and transfusion threshold. The clinical personnel were not provided with the outcome assessments .

Pa ie were randomized to receive either weekly doses of 40,000 IU of epoetin alfa (Eprex JanssenCilag Pty Ltd, Titusville, NJ) or placebo (0.9% sodium chloride) up to three doses or until intensive care unit (ICU) discharge. Probably Done

sample Low

size leads to a disproportionately greater degree of head injury in the EPO group relative to the placebo group.

a ie were randomized to receive EPO (40,000 Units IV) or placebo

Randomized

determined

Trial

serum markers when EPO was administered at a dose of 40,000 units within 6 hours of injury. Secondary outcomes of death, length of stay and Glascow outcome scores also did not differ with the treatment.

Erythropoietin

Nichol,Alistair.

596

French, Craig. Little, Lorraine, Et.Al.

(302 in the erythropoietin group and 294 in the placebo group).

in traumatic brain injury (EPO-TBI): a double-blind randomised controlled trial

Erythropoiesis

Talving,

Peep,

Stimulating Lustenberger, Agent Thomas. Kobayashi, Administration Leslie. Et,Al. Improves Survival After Severe Traumatic Brain Injury: A Matched Case Control Study

patients Erythropoietin

267 Patients,

did not reduce the number of patients with severe neurological dysfunction (GOS-E level 1 4) or increase the incidence of deep venous thrombosis of the lower limbs. The effect of erythropoietin on mortality remains uncertain.

The

within 6 hours of the time of injury. Probably Done

Our study has some limitations. It was powered to detect a 24% relative risk reduction of the proportion of patients with a GOSE of 4 or lower; therefore, we cannot exclude a smaller risk reduction. We chose a 24-h time window for the initiation of erythropoietin treatment; whether or not earlier administration of the drug affects outcome remains uncertain.

ESA+ The patients

(89 Patients patients given ESA, 178 experienced Not given ESA) protracted hospital length of stay and comparable surgical intensive care unit free days, they demonstrated a significantly lower inhospital mortality in comparison to controls at 7.9% versus 24.2%, respectively.

172

administered

Low T further minimise bias, we published the statistical analysis plan and did all planned analyses before unmasking of assignments . Probably done

were Low

not randomized to receive ESA, but were given ESA at the discretion of the attending physician due We attempted to compensate for this lack of randomization by matching our controls as closely as possible to ESA cases by using 2:1 control to case matching. The second potential limitation of our study is the changing pattern of ESA administration over the study period.

i hi the first 30 days after hospital admission, 2 matched control patients without ESA administration (ESA) were randomly selected from the pool of controls using a random number table Probably Done

Fig 1.1 Exclusion Figure

9920 journals assessed

909 duplicate journals removed

Inclusion: Population: TBI Patients Clinical Research Exclusion Literature Review Meta Analysis Animal Study Population: Spinal Injury Patients Case Report

9011 Journals

5 Journals

173

Excluded 5491 were done in mice 3515 were Spinal Injury Patients

Systematic Review of the Effect of Post-traumatic Stress Disorder Symptoms on Executive Functions in Children Angeline Tancherla, Felix Wijovi, Jessica Anastasia Introduction: Post-traumatic stress disorder (PTSD) is a chronic psychological disorder that may develop after exposure to a traumatic event. The lifetime prevalence of PTSD is estimated at 8.3%. It is associated with a chronic course and debilitating symptoms. Many researches have been conducted related to EFs (Executive Functions) in adults who are exposed to trauma. However, there are relatively little research has discussed EFs among children who are exposed to trauma. Thus, we carried out our systematic review to evaluate the relationship between PTSD and EFs in children. Materials and Methods: For our systematic review, we collect our data from online resources which includes Pubmed, Google Scholars, and Science Direct. Systematic Analysis approaches were used in this study including Pico Analysis and MeSH terminology. Results and Discussion: Using the inclusion and exclusion criteria, we found 7 relevant articles. Park et al., Samuelson et al., Li et al., MacDonald et al., DePrince et al., Yasik et al. had stated that traumatized children with PTSD have impaired executive functions. Only 1 study conducted by Yang et al. had found that there is no significant difference on EFs control between children with PTSD and children without PTSD. Conclusion: We can conclude that PTSD may cause the declining of EFs in children. Only 1 out of 7 study states that there is no difference in EFs control between children with PTSD and children without PTSD.

Keyword: Post-traumatic stress disorder, executive functions, children

174

Keyword: Post-traumatic stress disorder, executive functions, children

2 Systematic Review of the Effect of Post-traumatic Stress Disorder Symptoms on Executive Functions in Children Angeline Tancherla, Felix Wijovi, Jessica Anastasia 175

Introduction Post-traumatic stress disorder (PTSD) is a chronic psychological disorder that may develop after exposure to a traumatic event and is associated with a chronic course and debilitating symptoms. The lifetime prevalence of PTSD is estimated at 8.3%. According to Diagnostic and Statistical Manual of Mental Disorders- fifth edition (DSM-5), the traumatic event must involve exposure to actual or threatened death, serious injury, or sexual violence and is more likely occur after more severe types of trauma, such as rape, military combat, and childhood abuse.1 PTSD is characterized by four clusters of symptoms: (1) re-experiencing symptoms (e.g., recurrent intrusive memories, traumatic nightmares, and flashbacks); (2) avoidance symptoms (e.g., avoiding trauma-related thoughts and feelings and/or objects, people, or places associated with the trauma); (3) negative changes in cognitions and mood (e.g., distorted beliefs about oneself or the world, persistent shame or guilt, emotional numbing, feelings of alienation, inability to recall key details of the trauma); and (4) alterations in arousal or reactivity symptoms (e.g., irritability, hypervigilance, reckless behaviour, sleep disturbance, difficulty concentrating).2 The term of executive functions (EFs; also called as executive control or cognitive control) refers to mental processes that involves the goal-directed activities and are comprised of such diverse abilities which includes directing attention, manipulating information in working memory, and self-monitoring.3 Many researches have been conducted related to EFs in adults who are exposed to trauma. However, there are relatively little research has discussed EFs among children who are exposed to trauma. Neurophysiological evidence has demonstrated that the brain's frontal lobes and striatal regions are the primary region involved in executive functioning.4 Accordingly, the development of EFs is thought to coincide with growth spurts in the maturation of the frontal cortex that occur between birth and 2nd, 7th, 9th years, during adolescence, and into the third decade of life. Therefore, developmental factors should be considered in examining EFs associated with trauma exposure. Findings in adults related to trauma and EFs may not generalise to youth who are still undergoing cortical development. In addition, since EFs are 3

176

central to many of the developmental tasks children has, the study of EFs and trauma exposure in children is particularly important.5 Previous studies on PTSD and EFs were fragmented and incomplete; in addition, no evidence-based study has examined the association between PTSD and EFs in children who still undergoing cortical development. Thus, we carried out our systematic review to evaluate the relationship between PTSD and EFs in children. Methods: For our systematic review, we collect our data from online resources which includes Pubmed, Google Scholars, and Science Direct. Systematic Analysis approaches were used in this study including Pico Analysis and MeSH terminology. For P (Population), Paediatric

a M SH

. M SH

I (I

)

while for C (Comparison) also N/A. MeSH terminology for outcome is E Impairment OR Executive Function Decline . H Ca

-traumatic stress disorder affect children

OR N/A,

F a ? I

criteria are prognostic studies, PTSD, EFs impairment, population: children, outcome: declining of executive functions. Exclusion criteria are literature review, systematic review, meta-analysis, case report, animal study, and population: adult. In order to reduce bias, we will check for the validity of the studies that fulfil the inclusion and exclusion criteria. After ensuring the validity of the studies, the data will be analysed.

4 177

Results and Discussion: Using PICO approach, searching is done through online database, and we acquired 7 articles that will be analyzed. The selection process is shown in the diagram below. (("Child"[Mesh] OR "Pediatric") AND ("Stress Disorders, Post-Traumatic/complications"[Mesh] AND "Executive Function"[Mesh])

PubMED (7)

Google Scholar (132)

Science Direct (21) Inclusion Criteria: • Prognostic study • PTSD • EFs impairment • Population: children • Outcome: declining of executive functions Exclusion Criteria:

• Literature review • Systematic review • Meta-analysis • Case report • Animal study • Population: children

Filtering double literature 8

Relevant Study 7

Figure 1 Information flowchart through the different phases of the systematic review

5 178

Table 1 Summary of studies on executive function in children with PTSD Authors

Park et al.6

Study

Year

Cohort

2013

Subject

Results

Traumatized

Traumatized children with marked PTSD symptoms performed more poorly on measures of interference control

preadolescent

compared to those children without marked PTSD

children

symptoms.

Children with Samuelson et al7

Crosssectional

2010

Children with PTSD exhibited slower and less effective

current full or partial PTSD and witnessing IPV

Li et al.8

Cross-

Earthquake 2015

sectional

Yang et al.9

MacDonald et al.

DePrince et al.11

Cohort

2013

Crosssectional

2015

Cross-

2009

learning, heightened sensitivity to interference, and impaired effect of rehearsal on memory acquisition on the CVLT-C. Individuals in higher symptom groups showed more trauma

trauma exposed children

exposure and lower quality of life.

Earthquake

Children and adolescents with PTSD performed similar to controls in executive function at 4-months after the

trauma exposed

earthquake. Both PTSD and control groups improved

children

significantly in similar domains of cognition during the following 8 months.

Children with PTSD

Impairment in executive functioning may be a correlate of PTSD symptoms in some children

Trauma exposed

Familial trauma (relative to non-familial and no trauma exposure) was associated with poorer performance on an

sectional

children

EF composite (composed of working memory, inhibition, auditory attention, and processing speed tasks).

Yasik et al.12

Cross-

2007

Trauma exposed

Youth with PTSD evidenced significantly lower scores on the WRAML General Memory, Verbal Memory, and

sectional

children

Learning indices compared with nontraumatized control subjects

Note: PTSD: Post-traumatic Stress Disorder IPV: Intimate Partner Violence CVLT-C: California Verbal Learning Test, Children E EFs: Executive Functions WRAML: Wide Range Assessment of Memory and Learning

6 179

According to Park et al., out of 215 subjects of children who are exposed to trauma, there are 26 children with marked PTSD symptoms (UCLA CPTSD-RI (Child Post-traumatic Stress Disorder Reaction Index) score >25, high-risk group). Those high-risk group children had lower neuropsychological scores in flanker interference [94.66, p < 0.001], working memory [94.03, p = 0.046], and in total composite score [96.19, p = 0.030] compared to control group and low-risk group.6 In a cross-sectional study by Samuelson et al., there are 27 children exposed to IPV (intimate partner violence) with PTSD, who scored lower in CVLT-C (California Verbal Learning Test, Children

) T a 1 5 [mean = 44.48] compared to children without

PTSD [mean = 53.94].7 In the study conducted by Li et al., probable PTSD diagnosis was inferred using the DSM-IV diagnostic algorithm of at least one re-experiencing, three avoidance/numbing and two arousal symptoms endorsed at the level of 2 or higher (scale range: 0-4), and 12.1% (n = 1,629) of the trauma-exposed students met the diagnostic criteria. The average score for DEX-S was 20.0 (SD = 13.0; range: 0-80), and the mean level of impairments in quality of life Figure 2 Profile plot for the ten sum scores of PTSD and executive was 21.5 (SD = 14.0; range: 0-92). Individuals in the extremely high symptom group showed the most

function (Li et al).8

IN=Intrusion; AV=Avoidance; NUM=Numbing; DA=Dysphoric arousal; BI=Inhibition; GDB=Goal-directed behaviour; EM=Executive memory; LOA=Lack of awareness; AGI=Agitation

severe PTSD symptoms and executive deficits while those in the low symptom group showed the least. The severity of PTSD and dysexecutive symptoms tightly cohered within each class and none of the classes showed predominant PTSD or executive dysfunction symptoms. the ilustration of the results is displayed in figure 2.8 According to Yang et al, no significant differences were found in neuropsychological testing between the PTSD group and the controls in any measure at 4- and 12- months after trauma exposure. Both PTSD group and control group improved in similar domains of executive function: the ROCFT immediate and delayed memories and TMT-A and -B (p = 0.6, p = 0.5, p = 0.6, p = 0.2 respectively).9

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Figure 2 Neuropsychological scores in PTSD and control group (Yang et al). 9 PTSD=Post-traumatic Stress Disorder; ROCFT=Rey-Osterrieth Complex Figure Test; TMT=Trail Making Test.

Macdonalds et al. stated in their study that trauma-related memories, may additionally affect to decline in executive functions, as the content of the traumatic memory or resultant physiological arousal may distract the child from focusing on an academic and social task including communication. There is empirical support for the deleterious impact of reexperiencing symptoms on cognitive functioning in adults, suggesting that there may be a specific relationship between this cluster of PTSD symptoms and executive functioning deficits, which may extend to children. PTSD symptoms was significantly correlated with executive functioning as measured by Trail Making Test, (log of) B

A (r = 0.34; p = 0.01). PTSD

symptoms were associated at the trend level with failure to maintain set on the Wisconsin Card Sorting Test (r = 0.27; p = 0.062).10 A study by DePrince et al. found that children with familial-trauma exposure have poorer performance in executive function tests compared to children who are not exposed to any trauma. The executive function tests are working memory composite (Trauma-exposure group zscores = -0.26 vs. 0.11), inhibition composite (Trauma-exposure group z-scores = -0.25 vs. 0.18), interference control: Stroop (Trauma-exposure group z-scores = -0.09 vs. 0.14), auditory attention: Brief Test of Attention (Trauma-exposure group z-scores = -0.24 vs. 0.03), processing speed: Symbol Search (z-scores = -0.27 vs. 0.16) and total composite (z-scores = - 0.25 vs. 0.12).11 Based on Yasik et al. study, there are significant differences between the groups with regard to gender X2 (2, n = 131) 6.73, p =0.05 and ethnicity X 2 (8, n=131) 20.04, p =0.05. An ANOVA identified significant group differences for SES, F(2,128) 8.51, p=0.001. Post hoc

8 181

tests determined that the PTSD group had significantly lower SES ratings than the traumatised PTSD negatives, t (91) 3.93, p=0.001, and non-traumatised control subjects, t (69) 3.46, p= 0.01. ratings of the PTSD negatives and the non-traumatised control subjects were not significantly different. The mean number of traumas reported by the PTSD group (M=1.83, SD =0.97) was significantly greater than the mean number of traumas reported by the traumatised PTSD negatives (M=1.32, SD=0.59), F(1,88) 9.41, p=0.01. Among the PTSD group, 41.4% reported exposure to a single traumatic event, 44.8% reported exposure to two traumatic events, and 13.8% reported exposure to more than two traumatic events. With reference to the traumatised PTSD negatives, 74.2% reported exposure to a single traumatic event, 19.3% reported exposure to two traumatic events, and 6.5% reported exposure to more than two traumatic events. In contrast, the mean number of months since trauma for the PTSD group (M=7.92, SD=10.80) was not significantly different from the mean time since trauma for the traumatised PTSD negatives (M=5.52, SD=10.20), F(1,88) 1.09, p=0.05. Similarly, the mean age at traumatisation for the PTSD group (M=13.57, SD=3.15) was not significantly different from the traumatised PTSD negative group (M=12.77, SD=3.20), F(1,88) 1.25, p=0.05.12 Conclusion: From systematic analysis we done, we can conclude that PTSD may cause the declining of EFs in children. From the 7 studies we had analysed, only 1 study states that there is no difference in EFs control between children with PTSD and children without PTSD.

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References: Kilpatrick DG, Ressnick HS, Melissa EM, Miller MW, Keyes KM, Friedman MJ. National Estimates of Exposure to Traumatic Events and PTSD Prevalence Using DSM-IV and DSM-5 Criteria. J Trauma Stress. 2013;26:537 47. Lancaster C, Teeters J, Gros D, Back S. Posttraumatic Stress Disorder: Overview of EvidenceBased Assessment and Treatment. J Clin Med. 2016;5:105. Billard C. Executive Function. ANAE - Approch Neuropsychol des Apprentissages chez l E a . 2017;29:13 5. Leh SE, Petrides M, Strafella AP. The neural circuitry of executive functions in healthy subjects and parkinson

a . N

]. 2010;35(1):70

85.

Available from: http://dx.doi.org/10.1038/npp.2009.88 E M, C P, M D, A B, J C. Place and posttraumatic stress disorder. J Trauma Stress. 2016;29:293 300. Park S, Kim BN, Choi NH, Ryu J, McDermott B, Cobham V, et al. The effect of persistent posttraumatic stress disorder symptoms on executive functions in preadolescent children witnessing a single incident of death. Anxiety, Stress Coping. 2014;27:241 52. Samuelson KW, Krueger CE, Burnett C, Wilson CK. Neuropsychological functioning in children with posttraumatic stress disorder. Child Neuropsychol. 2010;16(2):119 33.

Li G, Wang L, Cao C, Fang R, Cao X, Chen C, et al. Posttraumatic Stress Disorder and executive dysfunction among children and adolescents: A Latent Profile Analysis. Int J Clin Heal Psychol. 2019;19:228 36. Yang R, Xiang YT, Shuai L, Qian Y, Lai KYC, Ungvari GS, et al. Executive function in children and adolescents with posttraumatic stress disorder 4 and 12 months after the Sichuan earthquake in China. J Child Psychol Psychiatry Allied Discip. 2014;55:31 8.

MacDonald HZ, Ellis BH, Pulsifer MB, Lyons M. Executive Functioning in Children with Posttraumatic Stress Disorder Symptoms. J Child Adolesc Trauma. 2015;8:1 11. DePrince AP, Weinzierl KM, Combs MD. Executive function performance and trauma exposure in a community sample of children. Child Abus Negl. 2009;33:353 61. Yasik AE, Saigh PA, Oberfield RA, Halamandaris P V. Posttraumatic Stress Disorder: Memory and Learning Performance in Children and Adolescents. Biol Psychiatry. 2007;61:382 8.

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The Effectiveness of Phytochemical Constituents in Moringa Leaves (Moringa Oleifera Lam) on the Wound Healing Processs Winalda Eka Santi, Marlin, Lestari Eka Putri Wanti

Abstract Introduction Wound healing is regeneration of cellular and anatomic continuity of tissue. Herbal medicines are providing natural healing because they have Antimicrobial, Antioxidant properties, and provide effective healing. This paper will discus about the healing potential of Moringa olifera. Moringa leaves have phytochemical properties related to the wound healing process. The purpose of this paper was to investigate the effectiveness of Moringa leaves on the wound healing process. It is helpful for research and development of new formulations for wound healing. Materials and Methods Literature searching was conducted with databases in PubMed, IJBCP, JSTOR, Science Alert, Science Direct and JIDMR, restricting published studies in the years of no later than 2010. We used the following words in search field : ( Moringa Lea es OR Moringa Oleifera Lam) AND Wo nd Healing . The search res lts were downloaded into a personal database. Results and Discussion The article of Ph toe tract in o nd healing mentioned that moringa leafs containing ph tochemical constituents which are essential for the wound healing. The properties of its phytochemicals, such as flavonoid and phenolic acids were related to the anti-inflammatory, antioxidant and antibacterial activities. Invivo articles that mentioned evaluation of aqueous leaves extract of Moringa olifera lam for wound healing mentioned that aqueous leaf extract of Moringa olifera investigated and concluded that it possess high wound healing activity. Conclusion In conclusion, Moringa olifera leaves having greater potential to facilitate and accelerate wound healing because Moringa olifera having rich amount of flavonoids, tannins and anthocyanin these constituents are potential to facilitate the anti-oxidant, anti inflammatory and anti-bacterial properties so it more helpful in therapeutic practices and research to develop new wound healing formulations for human use.

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Indonesian Medical Studentâ&#x20AC;&#x2122;s Training & Competition (IMSTC) 2020

The Effectiveness of Phytochemical Constituents in Moringa Leaves (Moringa Oleifera Lam) on the Wound Healing Process

Authors : Winalda Eka Santi Marlin Lestari Eka Putri Wanti

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G1A118049 G1A118007 G1A117028

The Effectiveness of Phytochemical Constituents in Moringa Leaves (Moringa Oleifera Lam) on the Wound Healing Process Winalda Eka Santi, Marlin, Lestari Eka Putri Wanti I.

Introduction Moringa olifera is a small fast growing tree, it belongs to moringaceae family. The main origin of the

Moringa olifera is reported that in south Himalayas and North West region of India. In English it is known as Horseradish tree, Drumstick tree.1 This plant has been widely consumed in many rural and urban areas of developing countries, such as countries in the African and Asian continents, due to its benefits in medicine and nutritional contents.2 Many of whose parts are consumed for both nutritional as well as medicinal values world wide. The people called Moringa plants as the miracle tree because of its remarkable healing properties on various diseases and some chronic diseases.3-4 Moringa leaves, fruits, flower, seed and braches have there on medicinal properties it good for human growth and development.1 And also its all parts is used for the treatment of various disease like Inflammatory bowel disease, Crohnâ&#x20AC;&#x2122;s disease5 and other immunological disorders like arthritis, ulcerative colitis, asthma, allergy etc.6 The moringa leaves possess several properties, its main principle are growth enhancing properties, antitumor, antiepileptic, antispasmodic, antioxidant, antiinflammatory, anti-ulcer, antihypertensive antimicrobial, anti-helminthic, analgesic activity, antipyretic, diuretic and cholesterol lowering activity, also anti hepatoprotective activities.7 Moringa leaves contain aspartic acid, glutamic acid, glycine, threonine, alanine, valine, leucine, isoleucine, histidine, lysine, phenylalanine, tryptophan, cysteine, and methionine.8 Moringa leaves having good wound healing property and leaves were used for rubbed against temple can relive headache, to stop bleeding from cuts and wounds.9 Caceres et al. reported the antimicrobial activity of the Moringa leaves and roots in an in-vitro study using the disc-diffusion method. Moringa oleifera as an antibiotic is identified by the pterygospermin content, with the bioactive phytochemical of glucosinolate 4 alphaL-rhamnosyloxy benzyl isothiocyanate.8 Also, the anti-inflammatory properties are identified by pterygospermin and moringinine alkaloid content which can cause blood vessels constriction. Moringa leaves also contains other substances such as proteins, fats, carbohydrates, minerals, vitamins, and essential amino acids.3,10 The wound is a loss of tissue continuity, which will be followed by the wound healing process begins with the scar tissue formation.11 Wound may occur due to chemical, immunological, physical and microbiological attack to the tissue leading to cellular disruption of tissue is occurring. 12 Wound healing is a complex and dynamic process it restores normal functions of damaged tissue, which divided into three phases: the inflammatory phase, the proliferation, and the remodelling phase.11 Wound healing is a form of response from the connective tissue. The initial phase of this process involves an acute inflammatory phase followed by the synthesis of collagen and other extracellular macromolecules which then form scars or scar tissue. 13 Appropriate wound healing methods are essential for a sustained recovery of damaged anatomical. 186

Many factors are affecting the wound healing period, such as age, nutrition, immunosuppression status, systemic interference, and the extrinsic factors such as medication and treatment. Many ways can be done in the wound care management, for example by giving antiseptic substances. However, side effects often arise in the use of chemical substances, so finding the alternative herbal remedies with relatively small side effects is necessary.14 There are number of plants are used for the treatment of wound healing.12 About 400 years ago India and china written their knowledge about the plant remedies is called as herbals. Herbal medicines are act on the body; their action is depending on the presence of constituents present in the plant. Herbal plants are providing stamina, support the action of digestive system, enhance the absorption, improving blood flow to the body, eliminate the toxins, maintain the infections and heal the injury.15 Research the effect of herbal ingredients on wound healing has been done, various herbal ingredients such as betel quid extract,14 propolis,16 turmeric liquid extract,17 brotowali extract (Tinospura crispa).18 Exploration, cultivation, and research of herbal remedies are developing, such as the Moringa plants (Moringa Oleifera Lam.).19 This study was aimed to determine the effectiveness of Moringa leaves extract gel on the wound healing. II.

Materials and Methods Literature searching was conducted with databases in PubMed, IJBCP, JSTOR, Science Alert, Science

Direct and JIDMR, restricting published studies in the years of no later than 2010. We used the following words in search field : (“Moringa Leaves” OR “Moringa Oleifera Lam) AND “Wound Healing”. The search results were downloaded into a personal database. The inclusion criteria used in this literature searching were following : (1) study was published in the years of no later than 2010, (2) study was written in English, (3) study was fully accessible, and (4) study was correlated to the aim of this paper. The articles which did not meet the criteria were excluded. III.

Results and Discussion

Pathophysiology of Wound Healing Acute wounds are a common health problem, with 11 million people affected and approximately 300,000 people hospitalized yearly in the United States. Typically, acute wound healing is a well-organized process leading to predictable tissue repair where platelets, keratinocytes, immune surveillance cells, microvascular cells, and fibroblasts play key roles in the restoration of tissue integrity. The wound repair process can be divided into 4 temporarily and spatially overlapping phases: coagulation, inflammation, formation of granulation tissue (proliferative phase), and remodeling or scar formation phase.20 [Figure ] During the process of healing reactive oxygen species are produced at the site of wound and it active against the invading bacteria and also impaired wound healing is occurring due to increasing the concentration of reactive oxygen species. Oxidative stress has important role in the tissue damage during the process of healing. Oxidative stress is due to imbalance between the granulation of reactive oxygen species and endogenous antioxidant.21

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Oxidative stress can be reducing by using the anti-oxidant property having drugs or medicinal plants. Herbal plant provides natural way of wound repairing. Moringa leaves having antimicrobial and anti-oxidant property which essential for wound healing and Moringa olifera contains 92 nutrient and 46 types of antioxidant. Various types of vitamins are also present such as vitamin A (Beta carotene), vitamin B1 (Thiamine), vitamin B2 (Riboflavin), vitamin B3 (Niacin), vitamin B6 (Phyrodixine), vitamin B7 (Biotin), vitamin C (Ascorbic acid), vitamin D (Cholecalciferol), vitamin E (Tocopherol) and vitamin K.22 Also it contains high content of carotenoids, the sulphur containing amino acids methionine and cysteine flavonoids, tannins, alkaloids, triterpinoids, saponins, anthraquinone glycoside, proteins, carbohydrates, cardiac glycosides etc. These constituents are support the healing process, enhancing the angiogenesis and flow of blood at the wound site.23 Phytochemical Constituents in Moringa Oleifera Moringa Oleifera consists of anti-inflammatory, anti-spasmodic, anti-hipertensive, anti-cancer, antioxidant, anti-oxidant, anti-pyretic, anti-ulcer, anti-epileptic, diuretic, cholesterol lowering, renal, anti-diabetic, and anti hepatoprotective activities. Many article reported that the leaves contains phytochemical constituent having principle activities.7 Susanto, E et al reported that the gel base is a fat-based HPMC that can keep the right humidity of the wound area. In the ointment with a concentration of 4% Moringa leaves extract, the basic composition of the ointment and extract are in accordance with the required moisture, thus increasing the cell growth. In the ointment with a concentration of 4% Moringa leaves extract, the salve’s basic content is higher, thus increasing the moisture, and the cell growth will be more excessive compared to the HPMC, povidone iodine and 2% Moringa leaves extract salves. The results of this study showed that the ethanolic extract of Moringa leaves helps to accelerate the wound healing on the rat’s palate. It is hoped that the ethanolic extract of Moringa leaves gel can be used as a herbal remedy that can be used safely for the wound healing. This gel may be used to accelerate the healing of the palatal lesions in the procedure of obtaining a donor of connective tissue graft from the palate as an action in the periodontal surgery treatment.8 The article of “Phytoextract in wound healing” mentioned that moringa leafs containing phytochemical constituents which are essential for the wound healing. At the site of injury these are activated the platelet, macrophage, neutrophils, and fibroblast. Any infections are in the wound site healing become impaired and increasing the ROS damage the tissue. Main constituents present in leafs such as flavonoids, quionescinammic acid, saponin, tannins, triterpinoids, anthocyanin etc and also there structures are mentioned Phytoextract in wound healing by Prasanta K G and Anjali G done like some research work on it in that they come to know that is many constituent in that extract like that. And also specific functions and actions of flavonoids, tannins, quinones, anthocyanin, saponins are explained. These compounds have been shown to be an effective antioxidants, antimicrobial, and anti-carcinogenic agents. 24-25 [Table] Invivo articles that mentioned the importance of moringa olifera leaves for wound healing. Evaluation of aqueous leaves extract of Moringa olifera lam for wound healing by B S Rathi, S L Bodhankar and A M 188

Baheti mentioned that aqueous leaf extract of Moringa olifera investigated and concluded that it possess high wound healing activity. The extract was studied at doses level of 300mg/kg body weight using different type of wound like incision, excision, and dead space wound. The contribution of healing is depending on the different types of wound. And they observed that significant increase in wound closure rate, skin breaking strength, granuloma breaking strength, granuloma dry weight and decrease in scar area. And also observed that prohealing activity of leaves due to increased collagen deposition as well as better alignments and maturation.26 Effect of ethanolic extract of leaves of moringa olifera lam on acetic acid induced colitis in albino rats by Swarnamoni Das and Lalit Kanodia. In this article shows that experiment done by using 4 set of albino rat. Acute toxicity study was done and it shows that it improves the colon architecture by antioxidant enzyme, mainly catalase and superoxide dismutase. The leaves contain high amount of flavonoids it having anti-oxidant property and protective action against the oxidative stress induced cellular damage.27 Experimental project Moringa leaves extract compare with povidone-iodine application on Sprague Dawley rats, aged 2 - 3 months, weighing 250-300 grams. As much as sixteen rats were divided into four groups; group I was applied with 2% Moringa leaves extract gel; group II with 4% Moringa leaves extract gel; group III with 10% povidone-iodine; and group IV with 4% HPMC gel (vehicle only). Each group consisted of 15 rats, analysed on five periods, from day 0, 3, 7, 10, and 14 (with three rats in each analysing period). The wound was made on the palate using a 4 mm diameter biopsy punch. The measurement of the wound area diameter on day 0, 3, 7, 10, and 14, resulted in quantitative data analysed statistically. The fastest wound contraction was seen in the group with application of 4% Moringa leaves extract. In this group, decreasing of the wound area on day 3 reached 1 mm thus made the wound diameter became 3 mm wide. In the group with application of 2% Moringa leaves extract, decreasing of the wound area on day 3 reached 0.7 mm thus made the wound diameter became 3.33 mm wide; while in the group with application of povidoneiodine and HPMC, decreasing of the wound area on day 3 only reached 0.5 mm thus made the wound diameter became 3.5 mm. The highest decrease was seen in the group with application of 4% Moringa leaves extract, followed with the 2% Moringa leaves extract application group, povidone-iodine application, and HPMC application respectively.28 From the observed value of the wound healing process, it was assumed that the groups with Moringa leaves extract application showed better and faster healing than the control groups. Moringa plants have been practically used in the medicinal field for decades to heal various acute and chronic conditions. The properties of its phytochemicals, such as flavonoid and phenolic acids were related to the anti-inflammatory, antioxidant and antibacterial activities.29 In a study conducted by Singh et al. in 2012, the antimicrobial activity of Moringa oleifera was examined using the main model of Kirby-Bauer disc diffusion method, in which as much as 50% ethanolic extract of Moringa leaves successfully showed low antibacterial activity. Even at higher concentrations, the extract displayed only mild inhibitory activity, and no activity at all towards the Pseudomonas.30 Peixoto et al. in 2011 reported that the aqueous and ethanolic extract of Moringa leaves indicated a promising potential as a 189

treatment for certain bacterial infection. The aqueous and ethanolic extracts of Moringa leaves have antibacterial potential properties, with higher inhibitory effects on gram-positive species (Staphylococcus aureus and Enterococcus faecalis) over gramnegative species (Escherichia coli, Salmonella, Pseudomonas aeruginosa, Vibrio parahaemolyticus, and Aeromonas caviae).31 Further, Waterman et al. reported that both Moringa leaves concentration and isothiocyanates decreased the gene expression and production of inflammatory markers in RAW macrophages. The Moringa leaves extract stimulated both cellular and humoral immune responses in cyclophosphamide-induced immunodeficient rats, by increasing the white blood cells, the percentage of neutrophils, and serum immunoglobulins.30 In addition, quercetin may have been involved in the reduction of the inflammatory process by inhibiting the action of neutral factor kappa-beta (NF-k_) and subsequent NF-kB-dependent downstream events and inflammation.32 IV.

Conclusion

In conclusion, it is proven in numerous cases that Moring olifera possesses a wide range of medicinal and therapeutic properties. Fot instance, in this paper it views the effectiveness of Moringa olifera leaves in wound healing process. Moringa olifera leaves having greater potential to facilitate and accelerate wound healing because Moringa olifera having rich amount of flavonoids, tannins and anthocyanin these constituents are potential to facilitate the anti-oxidant, anti inflammatory and anti-bacterial properties so it more helpful in therapeutic practices and research to develop new wound healing formulations for human use. It is good for human health because it is herbal in nature and side effects are very less. Moringa olifera providing good healing effect in different types of wound also it could be promoting natural anti-bacterial agents with potential applications in pharmaceutical industry.

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References 1. Foidl N, Makkar HPS and Becker K, The potential of moringa olifera for agricultural and industrial uses, Moringa News, 2015, www.moringanews.org/actes/foidl_en.doc. 2. Eyarefe OD, Idowu A, Afolabi JM. Healing potentials of oral Moringa oleifera leaves extract and tetracycline on methicillin resistant Staphylococcus aureus infected wounds of Wistar rats. Niger J Physiol Sci 2015; 30: 73-8. 2. 3. Razis AFA, Ibrahim MD, Kntayya SB. Health benefits of Moringa oleifera. Asian Pac J Cancer Prev 2014; 15: 8571-6. 4. 4. Spandana U, Srikanth P, Chand G, Babu A. A Review on Miracle tree: Moringa oleifera. J Pharmacogn Phytochem 2016; 5: 189-91. 5. Swarnamoni D and Lalit K, Effect of ethanolic extract of leaves of moringa olifera lam. On accetic acid induced colitis albino rats, Asian Journal of Pharmaceutical and Clinical Research, 5, 2012, 110-114. 6. Switi BG, Krishna M, Kavitha JR, Moringaolifera leaves: Immunomodulation in wistar albino rats, International Journal of Pharmacy and Pharmaceutical Sciences, 3, 2011, 426-430. 7. Jayaprakash R and Anupriy. A Review of Healing Potential of Moringa olifera Leaves in Wound. International Journal of Pharmaceutical Sciences Review and Research, 43(1). 2017. 42-48. 8. Susanto, E. et al. The Effectiveness of Ethanolic Extract of Moringa Leaves (Moringa Oleifera Lam.) Gel on the Wound Healing Process of the Ratâ&#x20AC;&#x2122;s Palate. Journal of International Dental and Medical Research, 12. 2019. 504-509. 9. Olufunmilayo EA, Adelodum LK, Akintomiwa OF, Moringaoliferalam(moringaceae) grow in Nigeria: In vitro antisickling activity on deoxygenated erythrocyte cells, Journal of Pharmacy and Bioallied Science, 4, 2012, 118122. 10. Kou X, Li B, Olayanju JB, Drake JM, Chen N. Nutraceutical or Pharmacological Potential of Moringa oleifera Lam. Nutrients 2018; 10: 343. 11. Adhiarto W, Mangundjaja S, Yusuf M, Pontjo B. Comparison of the effect of Collagen (amino acid) and Amnion (proteinase inhibitor) on the wound healing of soft tissues. Padjadjaran J Dent 2010 ; 22: 17-23. 12. Prafulla S, Bhargav B, Chirag P and Vidya S, An overview of medicinal plants as wound healers, Journal of Applied Pharmaceutical Science, 2, 2012, 143-150. 13. Charde RM, Dhongade HJ, Charde MS, Kasture AV. Evaluation of antioxidant, wound healing and anti-inflammatory activity of ethanolic extract of leaves of Ficus religiosa. Int J Pharm Sci Res. 2010; 1: 73-82. 14. Pambayun R, Utami DP, Santoso B, Widowati TW, Dewi SR. Antiseptic Effect of Betel Quid Extract on Lip Mucosal Wound of male Wistar (Rattus novergicus) Rats. J Int Den Med Res. 2018 May 1;11(2): 621-7. 191

15. Sudhakar LS, medicinal plants and their role in the wound healing and regeneration.www.hilagric.ac in/edu/covas/vpharma/winterschool/Lecture/22Wound Healing and Regeneration.pdf. 16. Moraes LT, Trevilatto PC, Grégio AM, Machado MÂ, de Lima AA. Quantitative Analysıs of Mature and Immature Collagens During Oral Wound Healing in Rats Treated by Brazilian Propolis. J Int Den Med Res. 2011;4(3):106-10. 15. 17. Meizarini A, Siswandono YA. The role of TLR2, NF- B, TNFα as an inflammation markers of wound dressing combination of zinc oxide with turmeric liquid extract. J Int Dent Med Res 2016; 9 (3): 173.-7. 16. 18. Arundina I, Diyatri I, Budhy TI, Jit FY. The Effect of Brotowali Stem Extract (Tinospora Crispa) Towards Increasing Number of Lymphocytes in the Healing Process of Traumatic Ulcer on Diabetic Wistar Rat. J Int Den Med Res. 2017;10(3):975-80. 19. Amjad MS, Qureshi H, Arshad M, Chaudhari SK, Masood M. The incredible queen of green&58; Nutritive value and therapeutic potential of Moringa oleifera Lam. J Coast Life Med. 2015; 3: 744-51. 20. Demidova-Rice, Tatiana N et al. “Acute and impaired wound healing: pathophysiology and current methods for drug delivery, part 1: normal and chronic wounds: biology, causes, and approaches to care.” Advances in skin & wound care vol. 25,7 (2012): 304-14. 21. Heather LO, David K, Loulse F and MarleF , Basic principles of wound healing, Wound care Canada, 9, 4-12. 22. Aggarwal S and Sardana S, Medicinal plants with wound healing and antioxidant activity: An update. International Journal of Pharmaceutical innovations, 3, 2013, 30-40. 23. Kassa B and Mesay S, Phytochemical constituents and physiochemical properties of medicinal plant(Moringaolifera) Around blue hora, Chemistry and material Research, 6, 2014, 61-71 24. Jennifer A and Anchana D, A study on phytochemical screening and anti-bacterial activity of moringaolifera, International Journal of Research in Applied Natural and social science, 2, 2014, 169176. 25. Prasanta KG and Anjali G, Phyto-extracts in wound healing, Journal of pharmacy and pharmaceutical science, 16, 2013, 760-820. 26. Roopalatha UC, Vijay M, Phytochemical analysis of successive reextract of the leaves moringaolifera lam, International Journal of pharmacy and Pharmaceutical science, 5, 2013, 629-634. 27. Razis AFA, et al. Health Benefits of Moringa OLeifera. Asian Pac J Cancer Prev, 15 (20). 2014. 85718576. 28. Susanto A, Muhaimina RK , Amaliya , Sutjiatmo AB. The Effectiveness of Ethanolic Extract of Moringa Leaves (Moringa Oleifera Lam) Gel on the Wound Healing Process of the Rat’s Palate. Journal of International Dental and Medical Research. Volume .12. Number 2. 2019 29. Mbikay M. Therapeutic potential of Moringa oleifera leaves in chronic hyperglycemia and dyslipidemia: A review. Front Pharmacol 2012; 3: 24. 30. Singh GP, Sharma SK. Antimicrobial evaluation of leaf extract of Moringa oleifera Lam. Int Res J Pharm. 2012; 3: 1-4. 23. 192

31. Peixoto JR, Silva GC, Costa RA, de Sousa Fontenelle JR, Vieira GH, Filho AA, dos Fernandes Vieira RH. In vitro antibacterial effect of aqueous and ethanolic Moringa leaf extracts. Asian Pac J Trop Med 2011; 4: 201-4. 32. Das N, Sikder K, Ghosh S, Fromenty B, Dey S. Moringa oleifera Lam. leaf extract prevents early liver injury and restores antioxidant status in mice fed with high-fat diet. Indian J Exp Biol 2012; 50: 404-12.

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VI.

Tables and Figures

Figure : Wound Healing Process

Table : Phytochemical Screening Result of the Moringa Olifera Leaves

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Efficacy of Chitosan Wound Healing Potential as a Wound Dressing on Treating Acute Wound: a Systematic Review of Case Control Studies Michelle Gracella, Kennedy Artahsasta Gonbei, Muhammad Kholis Dzaky

Background : The trauma or other injuries always lead to varying degrees of damage and skin defects. Recent progress in wound management is mainly in terms of physiologic support of healing. Because infections delay healing and worsen scar formation, skin generally needs to be covered with a dressing immediately after it is damaged. Although several wound dressings materials have been developed, the problem of wound management is far from being solved. This big challenge of wound treatment for a faster wound healing and reducing the incidence of bacterial infection require an ideal wound dressing material Chitin, chitosan, and their oligomers have been found to promote wound healing. Chitosan, derived from natural resources, the structural element in the exoskeleton of crutaceans (crabs, shrimps, etc), and available abundantly, is considered as a promising material for tissue regeneration. Method : This study using journals that earnt scientific sources : PubMed. The search using certain criteria to ensure the eligibility and reliable on this study. After several assessment, we got 5 journals (n=5) as material of this study. We also gathered view grey literature to provide all data that is needed for better understanding on the study. Result : From 5 journals, Chitosan show variety result macroscopic. Chitosan dressing also use with various content containing, from synthetical to neutral element. But all of the result show a satisfying result, either in vitro or in vivo trial. Conclusion : Chitosan is has shown a well result of it effects on re-epithelization and also as anti-microbial. Both of them is something that we really require to dressing an acute wound such in injury and trauma cases. But not just that, in an acute and severe cases such burn wound, chitosan also shows a good result as wound dressing. Not to mention, chitosan can be applied in many forms of dressing and content any kind of material, from synthesis to natural element, without any effect on its biocompatibility and biodegradability. This shows how ideal chitosan as wound dressing. Keywords : Chitosan, wound dressing

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Efficacy of Chitosan Wound Healing Potential as a Wound Dressing on Treating Acute Wound: a Systematic Review of Case Control Studies

Author : Michelle Gracella Kennedy Artahsasta Gonbei Muhammad Kholis Dzaky

FACULTY OF MEDICINE AND HEALTH SCIENCE 2019/2020

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healing. In addition, it should be easily available,

Introduction

inexpensive, non-allergic, and should also have Wound repairing is a complex process involving

hemostatic and analgesic properties.7

an integrate response by many different cell types

Chitin, chitosan, and their oligomers have been

and growth factors to achieve rapid restoration of

found to promote wound healing. Chitosan,

skin integrity and protective function after

derived from natural resources, the structural

injury. 1 Wound repair is a well highly coordinated

element in the exoskeleton of crutaceans (crabs,

process that involves a series of overlapping

shrimps, etc), and available abundantly, is

phases: the inflammatory phase (re-establishment

considered as a promising material for tissue

of homeostasis and local inflammation), the

regeneration. The features of chitosan for using in

proliferative phase (granulation, contraction of

wound

tissue and beginning of epithelialization) and

property to accelerate wound. 5,8,9 Moreover,

healed, which also this phase decides the strength and appearance of tissue after healing. 2,3,4 The trauma or other injuries always lead to

membrane

stimulates

its

in terms of physiologic support of healing.

cells

indicate that the

and

chitosan

migration

promotes

cellular

major

repeating unit,

which forms

polysaccharide with a chemical structure of (1,4)-

Because infections delay healing and worsen scar

2-amino-2-deoxy-b-D-glucan.9

formation, skin generally needs to be covered

Furthermore, chitosan can easily be processed into

with a dressing immediately after it is damaged.5,6

membranes,

Although several wound dressings materials have of

findings

organization. Chitosan contains aminoglucose as

Recent progress in wound management is mainly

problem

histological inflammatory

varying degrees of damage and skin defects.

the

biocompatibility,

enhancement, anti-inflectional activity and with

epithelium forms and the wound is considered

developed,

include

biodegradability, hemostatic activity, penetration-

ultimately the remodeling phase, the new

been

healing

gels,

nanofibers,

beads,

nanoparticles, scaffolds, and sponges for wound

wound

dressing

management is far from being solved. This big

applications.

addition

biocompatibility and biodegradability, chitosan is

challenge of wound treatment for a faster wound

also characterized by its nontoxic nature. In

healing and reducing the incidence of bacterial

reality, it has been considered to be a highly

infection require an ideal wound dressing

promising

material that should have specific requirements

physiologically

active

functional

biomaterial, often incorporated in biopharma or

such as: maintaining a moist environment and

nutraceutical preparations. Chitosan enhances the

electrolyte balance at the wound interface,

transport of polar drugs across epithelial surfaces,

allowing gaseous exchange, removing excess of

and is biocompatible and biodegradable. Purified

exudates, possessing antimicrobial properties for

chitosan

infection control, and promoting faster wound

available

for

biomedical

aipplications.5,9 Based on this, in this study we

197

Figure 1 Chitosan chemical stucture9

would want to study more about chitosan wound

2015-2019), (3) Paper that is written in English,

healing potential as a wound dressing material on

(4) a free access paper, (5) a control case study,

treating acute wound on several case control study.

(6) the wound on the clinical case is a acute wound (not a chronic wound case such on diabetic, but a

Material and Method

wound by excision to present a basic wound, or burn wound). Further, we assessed according the

Study Design

title, we take studies with relevant title. Then, we

This study is a systematic review of publications

do a full text assessment on each of them and

relating to case control study of chitosan

extract them to few selected papers that we

application as wound dressing. In addition, a

consider relevant to our study. In final, we

grey-literature manual search was conducted to

concluded 6 literatures to be used in this study. To

identify existing competency sets published on other

professional

entities,

performed

be clearer, we put the selection process in

Diagram 1.

additional references. Data Collection

Result

The search was conducted on few reliable search engine and sources, PubMed. The search was

The Selected Studies will be explained in table 1.

restricted to title, abstract, and key words and

By the result, we provide the characterization of

search themes were combined using the Boolean

the study on diagram 2. Further explanation will

operator AND and OR.

be in discussion.

TI = (*Chitosan*) AND TI= (*Wound*) AND TI = (*Healing*) Data Selection For, initial search the inclusion criteria used in this review are (1) Studies that put chitosan as topic, (2) Studies that written in the last five years (

198

199

2nd assessment (n=6)

Appraisal on the wound healing potential of Melaleuca alternifolia and Rosmarinus officinalis L. essential oil-loaded chitosan topical Preparations Preparation, Characterization and Wound Healing Effects of New Membranes Based on Chitosan, Hyaluronic Acid and Arginine Derivatives

Rola M. Labib, et al

Andreea-Teodora Iacob, et

Malaysia

Ahmad S. Halim, et al superficial wounds

Efficacy of chitosan derivative films versus hydrocolloid dressing on

Brazil

Romania

Egypt

Elaine Pereira dos Santos, et al Chitosan/Essential Oils Formulations for Potential Use as Wound Dressing: Physical and Antimicrobial Properties

Title

Country

Text assessment: Suitable ith this stud s aim

â&#x20AC;˘ Screening and Elegibility : Duplicates, Exlusion because of Title and abstract

Author

Table 1 Description of the Literature

(n = 26)

1st assesment

â&#x20AC;˘ Identification

Diagram 1 Systematic review conducted in this paper

(n = 191)

Initial Search Result with the criteria

2018

2017

2018

2019

Year

Human

method)

(agar diffusion

In Vitro

In Vivo - Rat

Rat

In Vivo -

Method

200

in vivo (n=5)

rat (n=4)

Diagram 2 Characteristic of the studies

human (n=1)

Trial on (in vivo)

its natural antioxidant effect

China

2019

Synthesis/manufactured (n=2)

Natural (n=3)

content of the dressing

A novel curcumin-loaded composite dressing facilitates wound healing due to

in vitro (n-=1)

Trial method

Yong Zhao, et al

(in vivo) Rat

Melaleuca alternifolia) under magnetic stirring for

Discussion

more 3 h at 45

Dressing preparation

Ahmad S. Halim, et al use a This dressing was

From the first study, by Rola, et al., selected essential

oils

(Melaleuca

alternifolia

5 C.10

manufactured and supplied by SIRIM Malaysia.

and

Their pilot plant in Sepang (SIRIM incubation

Rosmarinus officinalis L. essential oil) were added

centre) is a GMP-compliant facility. Preparation of

drop wise onto the viscous solution, with

film was produced as described by Ujang and

continuous stirring, in order to reach 10% v/v oil

colleagues (2014-in press).11

concentration within the formulation, and stirred for 1h .Dose selection for essential oils was

Last, Yong Zhao, et al, use a cyclodextrin (CD)

performed as previous report, where 10% v/v gave

Curcumin (Cur) complex that was prepared with a

better wound-healing outcomes in comparison with

self-assembly method by mixing CD and Cur at a

other lower concentrations and demonstrated

molar ratio of 1:1 as the content of Chitosan-

favorable anti-bacterial and wound-healing effects.

Alginate sponge as the dressing.12

Then,

film-forming

From these studies, we can see that 2 of them are

solutions were ultrasonically treated for 10 min to

use a synthesis content. One of them are

expel air bubbles.3

manufactured and being marketed. But the one

essential

oil-impregnated

from Andreea-Teodora use Arginine Deratives.

In the second study conducted by Andreea-Teodora Iacob, et al., the Synthesis of Arginine Derivatives

There are also a lot of other things that has been

are use as a contain of Chitosan

used as content beside of it, like a metal for

Arginine

instance. There are studies that use silver (Ag),

Derivatives (CS-ArgD) Membranes.7

Gold (Au), and Titanium (TiO2) as content too.6,13

In Elaine Pereira dos Santos, et al. research,

But the most common and most of research use is a

Chitosan (0.7 g) was dissolved in 70 mL of 1%

using of natural content for the dressing. Curcumin

(v/v) lactic acid solution under continuous stirring for 2 h at 45

is an active component from turmeric. Two of the

5 C. After this period, the chitosan

study that use in this review (from Rola M. Labib,

solution (CS-S) obtained was poured into Petri

et al and Elaine Pereira dos Santos, et al.) also use

dishes, dried in an o en at 40 C for 30 h to

essential oil such from Melaleuca alternifolia,

evaporate the solvent and to obtain the chitosan

Rosmarinus officinalis L., Eugenia caryophyllata or

films (CS-F). For chitosan/essential oils emulsions

Syzygium

preparation, the chitosan solution was mixed with

aromaticum

and

Melaleuca

alternifolia.3,10

1% and 3% (v/v) of CEO and MEO (CEO: Clove essential from Eugenia caryophyllata or Syzygium

But

aromaticum; MEO: melaleuca essential oil from

wound dressing without any content. A high

201

there is also study that use Chitosan as the

molecular of Chitosan alone has proven have an effective effect on the wound closure.2 Effectiveness of Chitosan Study by Rola et al., concluded that the incorporation of tea tree and rosemary essential oils

Figure 3Wound site after 5th and15th day, first row is picture from the control group (without treatment), second row is the group that treated with Chitosan dressing

in chitosan-based preparations in appropriate combination could efficiently promote different stages of wound healing. In addition, it decreased

Elaine Pereira dos Santos, et al. study show that the

oxidative stress in the wound area.3

CEO (Clove essential from Eugenia caryophyllata or Syzygium aromaticum) had the highest inhibition against the three strains studied. As regards the films properties, the coloration of the films was affected by the type and concentration of bioactives used. At higher EOs concentration, the chitosan/CEO films showed an intense yellowish coloration. In general, all chitosan/Eos (essentials oil) films presented good transparency in visible light besides flexibility, mechanical resistance

Figure 2 Wound site after treatment : A is negative control group (left being wounded), B is positive control group that treated with a market drug, and C is trated with Chitosan and mixture of the esential oil

when touched, smaller thicknesses than the dermis, and higher wettability than chitosan films, in both distilled water and PBS. Tensile properties,

Almost the same result also found in the study by

including elongation at break, increased with EOs

Andreea-Teodora, as the result from the 15th day,

incorporation due to the lubricant characteristics of

the macroscopic evaluation from the wound site

the EOs in addition to the interactions developed

show a well re-epithelization than the control

between chitosan and EOs, which were also

group.7

confirmed by FTIR. The EOs droplets were well distributed along the surface of the films in SEM data. The results suggest that chitosan films incorporated with these essential oils could be employed for wound-healing applications, and both of them show an antibacterial activity.10

202

On study by Ahmad S. Salim et al., a total of 244

that a film dressing manufactured from a

patients were enrolled in this randomised control

deacetylated chitosan bioderivative is equivalent

trial study from May until October 2012. Of

to hydrocolloid in terms of epithelisation,

these, 121 (49.6%) received chitosan derivative

oedema, and ease of removal. The chitosan

film (treatment group) and 123 (50.4%) received

derivative film, however, produced less odour

hydrocolloid (control group) dressings. This

and exudate. These attributes represent attractive

prospective randomised controlled study showed

aspects of this new dressing.11

Table 2 Comparison of mean wound epithelization over time between chitosan group and control group

And last, Yong Zhao et al, CA-CD-Cur

reepithelialization, CA-CD-Cur treated wounds

accelerated cutaneous wound healing in rats,

showed more collagen deposition and better

CA-CD-Cur treated wounds showed advanced

collagen-fiber alignment.12

Figure 4 Woud site progress of control group (first row), Chitosan only group (second row), Chitosan-Curcumin group (third row), and Chitosan-Curcumin-Cyclodextrin group (fourth row

203

Figure 5 Microscopic evaluation show a good re-epithelization

But, to prove Chitosan effectiveness, here we also

but in a high molecular weight Chitosan. The

show result by research conducted by Ibrahim A.

result show a good re epithelization too, even

Alsarra, In this research, they only use Chitosan,

with a chitosan dressing alone.2

Figure 6 a wound site of control group, chitosan group, and market drug group, respectively

Also, there study from that conclude dermal burn

wound contraction, and accelerates the wound

healing experiments using rabbit model have

closure and healing process. Thus, the fucoidan-

shown that the application of fucoidan-chitosan

chitosan film may be a promising new dressing

film onto an open burn wound induces significant

for wound occlusion and tissue repairing.1

204

Figure 7 A wound site treated with chitosan-fucoidan, fucoidan only, chitosan only, and control group, respectively

Result Refferences

Chitosan is has shown a well result of it effects

1. Sezer AD, et al. Chitosan film

on re-epithelization and also as anti-microbial.

containing fucoidan as a wound dressing

Both of them is something that we really require

for dermal burn healing: preparation and

to dressing an acute wound such in injury and

in vitro/in vivo evaluation. AAPS

trauma cases. But not just that, in an acute and

PharmSciTech. 2007

severe cases such burn wound, chitosan also

2. Ibrahim A. Alsarra. Chitosan topical gel

shows a good result as wound dressing. Not to

formulation in the management of burn

mention, chitosan can be applied in many forms

wounds. International Journal of

of dressing and content any kind of material, from

Biological Macromolecule. Vol 45.

synthesis to natural element, without any effect

2007

on its biocompatibility and biodegradability.

3. Labib, Rola, M, et al. Appraisal on the

This shows how ideal chitosan as wound

wound healing potential of Melaleuca

dressing, we highly recommended to start a

alternifolia and Rosmarinus officinalis

further study to make a compatible chitosan

L. essential oil-loaded chitosan topical

dressing form to use as a first aid on trauma

preparations. PLOS. 2019

wound for wide use.

4. Nguyen, V.C, et al. Curcumin-Loaded Chitosan/Gelatin Composite Sponge for Wound Healing Application.

205

2018

International Journal of Polymer

12. Zhao, Y. A novel curcumin-loaded

Science.2007 5. Mingxian Liu, et al. The Improvement

composite dressing facilitates wound

of Hemostatic and Wound Healing

healing due to its natural antioxidant

Property of Chitosan by Halloysite

effect. Drug Design, Development and

Nanotubes. RSC Advance. 2014

Therapy 2019:13 3269 3280

6. Mohandas, A, et al. Chitosan based

13. Peng C.C, et al. Composite nano-

metallic nanocomposite scaffolds as

titanium oxide-chitosan artificial skin

antimicrobial wound dressing. Bioactive

exhibits strong wound-healing effect-an

Material. 2018

approach with anti-inflammatory and bactericidal kinetics. Macromol

7. Andreea-Teodora Iacob, et al.

Biosci.2008

Preparation, Characterization and Wound Healing Effects of New Membranes Based on Chitosan, Hyaluronic Acid and Arginine Derivatives. MDPI. 2018 8. Azad A.K. et al. Chitosan membrane as a wound-healing dressing: characterization and clinical application. J Biomed Mater Res B Appl Biomater. 2004 9. Muzarelli, et al. Chitin nanofibrils/chitosan glycolate composites as wound medicaments. Carbohydrate Polymer. Vol.70. 2007 10. Santos. E. Chitosan/Essential Oils Formulations for Potential Use as Wound Dressing: Physical and Antimicrobial Properties. Materials. 2019 11. Halim A. et al. Efficacy of chitosan derivative films versus hydrocolloid dressing on superficial wounds. Journal of Taibah University Medical Science.

206

Indah, Denok, Triyan 1

The Effectiveness of Glial Fibrillary Acidic Protein (GFAP) and Ubiquitin C-Terminal Hydrolase -L1 (UCTH-L1) as Traumatic Brain Injury (TBI) biomarker in Patients with CT Negative proved by MRI Positive Indah Rahmadani Siin, Denok Maretta Haq, Triyan Ihza Mahendra Traumatic brain injury (TBI) is defined as a traumatically-induced structural brain injury or physiological disruption of brain function caused by an external force. Yet, mTBI is often overlooked by clinical teams, as it is not easily identified in the acute setting. The injuries sustained by patients with mTBI are often seen as not severe b clinical staff,

may be falsely reassured by negative CT imaging. Consequently, patients with mTBI are often discharged from the ED with basic written instructions, and little in the way of treatment. The assessment of patients with suspected TBI often relies upon neurological imaging such as CT scanning and magnetic resonance imaging (MRI). However, CT has a low sensitivity for mTBI and exposes the patient to a significant dose of radiation. Conversely, MRI can provide information on the extent of cerebral parenchymal injury, but its availability in the acute setting is limited. This paper was carried out a systematic review of GFAP and UCTH-L1 as a blood biomarkers of Traumatic Brain Injury (TBI) for the rapid diagnosed if the CT showed negative value but patients clinically indicated TBI. PRISMA statement rule was used to select the proper journal for being reviewed. Blood biomarker known for its uninvasive which is safer than the contrast or radiation CT or MRI have. A study conducted in USA use prototype immunoassay on the i-STAT platform show how within 15 minutes you may got the result of GFAP and UCTH-L1 serum analysis. A clinical trial showed thata the best way to have a blood biomarker examination in this Traumataic Brain Injury case is within 24 hours. Study showed that GFAP may diagnosed the patients with CT negative lack of TBI that actually suffer from mild TBI which is this kind of patient have the strong indication to do MRI test, and rapidly may go through the further management of TBI. This effective procedure is usefull to prevent unnecessary MRI radiation, and prevent undetectable TBI to prevent disability to untreated TBI.

207

Indah, Denok, Triyan 1

Indah Rahmadani Siin Denok Maretta Haq Triyan Ihza Mahendra

208

Indah, Denok, Triyan 2

Introduction Traumatic brain injury (TBI) is defined as a traumatically-induced structural brain injury or physiological disruption of brain function caused by an external force. Brain injuries can be classified into mild, moderate, and severe categories. Symptoms of mTBI can include headache, nausea, tinnitus, hypersensitivity to light, confusion and other cognitive disturbances. 1 Head injury is one of the commonest reasons for emergency department (ED) attendance worldwide. Yet, mTBI is often overlooked by clinical teams, as it is not easily identified in he ac e e ing. The inj ie

ained b pa ien

i h mTBI a e of en een a

no e e e

by clinical staff, who may be falsely reassured by negative CT imaging. Consequently, patients with mTBI are often discharged from the ED with basic written instructions, and little in the way of treatment.1 The assessment of patients with suspected TBI often relies upon neurological imaging such as CT scanning and magnetic resonance imaging (MRI). However, CT has a low sensitivity for mTBI and exposes the patient to a significant dose of radiation. Conversely, MRI can provide information on the extent of cerebral parenchymal injury, but its availability in the acute setting is limited.1 Therefore, the biomarker can diagnose TBI on CT-: Ubiquitin C-terminal hydrolase-L1 (UCH-L1) (Neuronal cell body injury markers): UCH-L1 is a protein that mainly resides in the neuronal cell body cytoplasm. It was one of the few TBI biomarker candidates identified based on recent proteomic studies.2,3 We reason that UCH-L1 is a functional biomarker and serves as a barometer of neuronal cell body injury. UCH-L1 was first found to be released into CSF and serum among severe TBI patients.4,5,6 Glial fibrillary acidic protein (GFAP)( Astroglial biomarkers): astroglial GFAP is emerging as the most robust TBI biomarker GFAP biomarker levels are elevated within 3 to 34 h in CSF and serum/plasma following severe TBI [46,52-55] and in serum and plasma samples after moderate to mTBI [56]. GFAP as a biomarker, in the form of either the GFAP intact protein (50kDa) or as breakdown products (GFAP-BDPs; 44-38 kDa) are predominantly released from injured brain tissue into biofluid such as cerebrospinal fluid and serum/plasma shortly followingTBI.7,8,13

209

Indah, Denok, Triyan 3

It has been suggested that UCH-L1 together with GFAP form the foundation of a biomarker panel representing the two dominant cell types in the brain.14 Material and methods This paper was carried out a systematic review of Glial Fibrillary Acidic Protein (GFAP) and Ubiquitin C Terminal Hydrolase-L1 (UCTH-L1) as a blood biomarkers of Traumatic Brain Injury (TBI) for the rapid diagnosed if the CT showed negative value but patients clinically indicated TBI. PRISMA statement rule was used to select the proper journal for being reviewed. Studies search were conducted using search engine Science Direct and PUBMED da aba e

i h ke

o d GFAP and UCTH-L1 and TBI bioma ke . The incl ion c i e ia

are 1) paper published in 2015 until 2019 2) written in english 3) use GFAP and UCTH-L1 as blood biomarker in TBI cases only 4) for clinical trial showed patient with CT negative. From the search we identified 185 studies. From 185, 179 then being excluded because they were not related to topic (n=157), and by full paper reading studies are not found or irrelevant (n=22). Finally 6 studies remained suitable to fulfill the criteria of this systematic review.

Records identified through database searching n= 185 Records excluded Unrelated to topic n= 143 Duplicates n= 14 Records identified after unrelated to topic and duplicates removed Full text excluded

n= 28

Studies not found n= 18 Irrelevant to search n= 4 Studies suitable for further reviewed n= 6

210

Indah, Denok, Triyan 4

Result From the study fulfill our criteria we synthesis the data to show how the Glial Fibrillary Acidic Protein (GFAP) and Ubiquitin C-Terminal Hydrolase -L1 (UCTH-L1) as blood biomarker may influenced the rapid and precise to diagnose a Traumatic Brain Injury (TBI). We assessed data about CT status of the clinical trial Standard biomarker measurement Accuracy of Glial Fibrillary Acidic Protein (GFAP) and Ubiquitin C-Terminal Hydrolase -L1 (UCTH-L1) in diagnosed or prognosis predictor within 24 hours Optimal of GFAP and UCTH-L1 volume to sampling Studies centered U. S. Army Medical Research and Material Command (USAMRMC) Office of Research Protections (ORP) Human Research Protection Office (HRPO) Department of Defense. Department of defense

Study Design planned secondary analysis of a prospective, multi-center, observational clinical trial

CT Status

TBI explored Ct the abnormal diagnostic performance of the blood protein biomarkers GFAP and UCH-L1 for the early diagnosis of TBI during the first week after the injury.

Biomarker meassurment ELISA assay

Proteomic analyses were conducted at Randox Laboratories Ltd (Crumlin, County Antrim, United Kingdom) with Randox Biochip technology, which is a solid-state device

211

Findings

Ref

[16] GFAP, and UCH-L1 were predictive of acute intracranial lesions on CT and the need for neurosurgical intervention One previous study in patients with mTBI found early serum GFAP concentration, but not S-100 , a correlated with return to work at 6 months. Diagnostic threshold levels 35 pg/ml for GFAP and 40-170 pg/ml for UCH-L1 [14] Glial fibrillary acidic protein (GFAP) is a specific blood biomarker of astroglial injury Ubiquitin C-terminal hydrolase-L1 (UCHL1) is involved in either adding or removing ubiquitin from proteins targeted for metabolism, abnormal proteins, and proteins damaged by oxidation.

Indah, Denok, Triyan 5

Human Research Protection Office Department of defense

Trauma centres in the USA

designed to show therapeutic with ct - but biomarker show TBI

Ct Negative

Prospective cohort study that enrolled patients with TBI who had a clinically indicated head CT scan within 24 h of injury at 18 level 1

CT negative

containing an array of discrete test regions of immobilized antibodies specific to different cerebral immunoassays ELISA or similar immunoassays

Prototype immunoassay on the i-STAT (Abbott, Abbott Park, IL, USA) point-of-care platform

212

UCH-L1 together with [7] GFAP form the foundation of a biomarker panel representing the two dominant cell types in the brain. GFAP is emerging as the most robust TBI biomarker. GFAP biomarker levels are elevated within 3 to 34 h in CSF. [17] plasma GFAP biomarker concentrations in the acute phase after head trauma identified patients with a suspected TBI and normal head CT who had detectable pathology on MRI, confirming the diagnosis of TBI. 27% of patients with a normal CT had positive findings on an MRI, demonstrating the diagnostic utility of GFAP prototype assay in development that provided GFAP concentrations over a dynamic range of 0 50 000 pg/mL. Unlike conven tional ELISA analysis, plasma GFAP concentrations can be

Indah, Denok, Triyan 6

quantified in as little as 15 min patients with GFAP concentrations more than 20 pg/mL (upper limit for orthopaedic trauma controls) but less than 140 pg/mL (lower limit for patients with negative CT and positive MRI) might have occult injury not visible on structural MRI Discussion Based on this systematic review we found that Glial Fibrillary Acidic Protein (GFAP) and Ubiquitin C-Terminal Hydrolase -L1 (UCTH-L1) as Traumatic Brain Injury (TBI) blood biomarker is a solution to help rapid diagnosed and may predict the prognosis of the patient. In diagnostic TBI, CT scan remain the main procedure to use, but eventually CT scan may show negative result but after MRI patient proved to had Traumatic Brain Injury that may absence by CT scan evaluation. Whereas MRI is the last weapon to used due to the radiation and we also need to realize that not all trauma center have MRI. Tha why finding a novel blod biomarker is essential for further diagnosis finding. Blood biomarker known for its uninvasive which is safer than the contrast or radiation CT or MRI have. A study conducted in USA use prototype immunoassay on the i-STAT (Abbott, Abbott Park, IL, USA) point-of-care platform show how within 15 minutes you may got the result of GFAP and UCTH-L1 serum analysis. Which is a rapid way compared to a conventional immunoassay well-known ELISA assay. GFAP compared to UCTH-L1 showed that GFAP have higher specificity while UCTH-L1 have higher sensitivity. Diagnostic threshold levels for GFAP 35 pg/ml and UCH-L140-170 pg/ml. Based on the clinical trial we also known that GFAP serum level may increased within 3 until 34 hours in CSF, which is usefull for us to know the better way to do the examination. Another clinical trial showed thata the best way to have a blood biomarker examination in this Traumataic Brain Injury case is within 24 hours.

Conclusion Glial Fibrillary Acidic Protein (GFAP) and Ubiquitin C-Terminal Hydrolase -L1 (UCTH-L1) is effective to help Traumatic Brain Injury (TBI) diagnostic and predict the prognostic. The examination of multi blood biomarker is recommended to conduct every possibility each biomarker may work in response to TBI. Some study based on cohort prospective clinical trial showed that GFAP may diagnosed the patients with CT negative

213

Indah, Denok, Triyan 7

lack of TBI that actually suffer from mild TBI which is this kind of patient have the strong indication to do MRI test, and rapidly may go through the further management of TBI. This effective procedure is usefull to prevent unnecessary MRI radiation, and prevent undetectable TBI to prevent disability to untreated TBI.

214

Indah, Denok, Triyan 8

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Indah, Denok, Triyan 9

traumatic brain injury: results from the prospective transforming research and clinical knowledge in traumatic brain injury study. J. Neurotrauma. 30(17), 1490 1497 (2013). 13. Yang Z, Wang KKW. Glial fibrillary acidic protein: from intermediate filament assembly and gliosis to neurobiomarker. Trends in neurosciences. 38(6), 364 374 (2015). 14. Welch RD, Ayaz SI, Lewis LM, et al. Ability of Serum Glial Fibrillary Acidic Protein, Ubiquitin C-Terminal Hydrolase-L1, and S100B To Differentiate Normal and Abnormal Head Computed Tomography Findings in Patients with Suspected Mild or Moderate Traumatic Brain Injury. J. Neurotrauma. 33(2), 203 214 (2016). 15. Tate CM, Wang KKW, Eonta S, et al. Serum brain biomarker level, neurocognitive performance, and self-reported symptom changes in soldiers repeatedly exposed to low-level blast: a breacher pilot study. J. Neurotrauma. 30(19), 1620 1630 (2013). 16 Lawrence M. Lewi, Derek Schloemann, Linda Papa, Robert Fucetol. Utility Of Serum Biomarkers In The Diagnosis and Stratification Of Mild Traumatic Brain Injury. 2017 John K Yue, Esther L Yuh, Frederick K Korley, Ethan A Winkler, Xiaoying Sun, Ross C Puffer, Hansen Deng, et all. Association between plasma GFAP concentrations and MRI abnormalities in patients with CT-negative traumatic brain injury in the TRACK-TBI cohort: a prospective multicentre study. Published Online August 23, 2019 available on http://dx.doi.org/10.1016/. Department of Neurological and Department of Radiology, University of California San Francisco, San Francisco, CA, USA; Brain and Spinal Injury Center, Zuckerberg San Francisco General Hospital, San Francisco, CA, USA.

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The Use of Telemedicine to Ensure a Successful Traumatology Treatment Author: 1.) Mohammad Fahmi Akbar 2.) Muhammad Asmawi Alamsyah

a new

technology called telemedicine. Telemedicine can make it possible for a doctor to do a treatment of a trauma injury without even have to do it directly (face-to-face) with the patient of the said trauma. As time follows by along with the advancement of technology, telemedicine can be used as an effective and efficient care for traumatic patient and save lives of many people worldwide.

Materials and Methods The literature review method were used to review three literatures as follows An overview of telemedicine for trauma and emergency management (literature review and case report evaluation) The application of telemedicine for trauma and emergency in the ICU (systematic review) A cohort study for the usage of telemedicine in treating certain amount of severely injured rural trauma patients (observational cohort study)

217

Results and Discussion The following were the results of the research that has been done for all the three topics stated above in their respective orders: The development and utilization of telemedicine has occurred in high income areas and countries throughout the world. Although the application seems to be highly concentrated in the high income and crowded areas, the usage of telemedicine has offered specialty care to resource poor settings on a global level. For the most part, tele-ICUs have positive impacts on mortality and length of stay which the key revolves around communication, data review, and teamwork. Emergency departmentâ&#x20AC;&#x201C;based telemedicine consultation is requested for the most severely injured rural trauma patients, especially with those with penetrating trauma, burns, and abnormal presenting vital signs.

Conclusion Telemedicine has been proved to be effective for the treatment of physical traumatic injuries. There is still some problems and setbacks regarding the application of this technology especially in the rural areas. As for Indonesia, the practice of telemedicine still need some time to be developed in order to be used in its full extend. Further development and empowerment in natural and human resources were required. Future work should better educate how telemedicine impacts timeliness of care, diagnostic and therapeutic interventions, length-of-stay, hospital costs, and clinical outcomes. With major countries have the same issues of dealing with the lack of financial resources, uneven population growth, and most importantly limited number of healthcare professionals, the telemedicine technology has paved a way to a better and more promising healthcare system.

218

The U e f Telemedicine En e a S cce f l T a ma l g T ea men Mohammad Fahmi Akbar Muhammad Asmawi Alamsyah How the innovation in the technology of telemedicine can provide and ensure a successful treatment of physical trauma injuries, especially in the rural areas.

2019

219

Introduction Trauma injuries both physically and mentally is one of the major cause of death and disability in the world, especially in the developed countries. One of which is Indonesia. With many concerns regarding trauma injury these days, especially the one caused by traffic accident or road traffic accident in Indonesia, the treatment of trauma injury has become something crucial to know and skilled for in order to make sure that life can be saved and no life is wasted. Trauma physical injuries can be considered an emergency situation and need to be treated as soon as possible with moderate to extreme care depending on the situation. As showed through the data of Badan Pusat Statistik (BPS), there were currently around as much as one hundred thousand number of road traffic accident in Indonesia for one year (2017) (Fig.1) (1). According to the Riset Kesehatan Dasar (Riskesdas) done by Badan Penelitian dan Pengembangan Kesehatan in 2018, the prevalence number of trauma injuries that occurred from 2007 to 2018 has been increased (Fig 2-5)(5). One of the recent innovation in technology of medicine is the application of a new technology called telemedicine. Telemedicine can make it possible for a doctor to do a treatment of a trauma injury without even have to do it directly (face-to-face) with the patient of the said trauma. This innovation can help saving lives of many people with physical trauma injuries, especially in a place with limited access to healthcare such as rural areas, villages, etc. Those places can be easily found scattered in the region of Indonesia. As time follows by along with the advancement of technology, telemedicine can be used as an effective and efficient care for traumatic patient and save lives of many people worldwide. With many researches that has been done regarding this certain issues about trauma and the correlation of telemedicine effectiveness, knowledge of whether the usage of it is useful or not has become something important for all of us to know. This scientific paper will provide you with some credible and reliable resource of researches regarding this specific issue to raise awareness and give descriptive view of a positive outlook for the future of medicine and healthcare. Although, it canâ&#x20AC;&#x2122;t be ignored that there must be some minor setbacks in the application of this technology which will be provided in the conclusion section below, this can also leave a room for improvement and innovation to make this technology practically better and

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applicative for the future usage. The innovation in turned could be used practically for the developed countries in the future.

Materials and Methods In order to provide a reliable and credible research, there were around three literature that were reviewed as the material of this scientific paper. The source of the said literature will be provided in the references section below. The following is the list of topics that were discussed in the literature provided: An overview of telemedicine for trauma and emergency management (literature review and case report evaluation)(4) The application of telemedicine for trauma and emergency in the ICU (systematic review)(2) A cohort study for the usage of telemedicine in treating certain amount of severely injured rural trauma patients (observational cohort study)(3) With those topics stated, the study used some methods such as literature or systematic review, case report evaluation, and observational cohort study. The method of literature review of those three literatures and topics were used for this scientific paper.

Results and Discussion The development and utilization of telemedicine has occurred in high income areas and countries throughout the world. Although the application seems to be highly concentrated in the high income and crowded areas, the usage of telemedicine has offered specialty care to resource poor settings on a global level with the utilization of remote and internet-based system. telemedicine has emerged as a bridge between pre-hospital, community based and tertiary care allowing specialty care previously outside the scope of local healthcare (Tab.1).

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From initial treatment of orthopedic and neurosurgical injuries to tube thoracostomies and EFAST assessment, telemedicine has the capability to provide expert guided mentoring of timely life-saving procedures. As for the limitation of the usage in rural areas, continued advancement in the future may provide a reliable solution for this issue(4). For the most part, tele-ICUs have positive impacts on mortality and length of stay which the key revolves around communication, data review, and teamwork(1). Emergency departmentâ&#x20AC;&#x201C; based telemedicine consultation is requested for the most severely injured rural trauma patients, especially with those with penetrating trauma, burns, and abnormal presenting vital signs. Future work should evaluate how telemedicine impacts the timeliness of care and specific care interventions(2). We realized that all of the data that has been used here were the data from USA medicine and healthcare system. We believed this to be a good standard of comparison if this technology were going to be applied effectively in Indonesia.

Conclusion Telemedicine has been proved to be effective for the treatment of physical traumatic injuries. The innovation of the technology provide an efficient and reliable healthcare system to treat this specific injury in a fast and precise way. Although it may seems to be used and utilized in high income areas, this has to be expected considering the amount of time and cost for the utilization of this technology. There is still some problems and setbacks regarding the application of this technology especially in the rural areas. Making the concentration of the application seems to be focused in the high income area. Continued advancement may be the key to provide solution for this problem. With major countries have the same issues of dealing with the lack of financial resources, uneven population growth, and most importantly limited number of healthcare professionals, the telemedicine technology has paved a way to a better and more promising healthcare system. As for the developed countries itself, especially Indonesia, the practice of telemedicine still need some time to be developed in order to be used in its full extend. Further development

222

and empowerment in natural and human resources were required. Future work should better educate how telemedicine impacts timeliness of care, diagnostic and therapeutic interventions, length-of-stay, hospital costs, and clinical outcomes.

References

1. Badan Pusat Statistik (BPS) 2018

[cited

Jumlah Kecelakaan Lalu Lintas (1992-2017) [Internet]. December

2019].

Available

from

https://databoks.katadata.co.id/datapublish/2018/09/21/sepanjang-2017-terjadi-98-ribukali-kecelakaan-lalu-lintas

2. Becker C, Scurlock C. Telemedicine for Trauma and Emergency: the eICU. Curr Trauma Rep [Internet]. 2016 [cited 3 December 2019]; 2: 132-137. Available from https://link.springer.com/article/10.1007/s40719-016-0054-y 3. Bell A, Chrischilles EA, Harland KK, Mohr NM, Shane DM, Ward MM. Emergency Department Telemedicine is Used for More Severely Injured Rural Trauma Patients, but Does Not Decrease Transfer: A Cohort Study. Academic Emergency Medicine [Internet]. 2017 [cited 4 December 2019]; 24(2); 177-185. Available from https://www.ncbi.nlm.nih.gov/pubmed/28187248 4. Latifi

Lombardo

Prabhakaran

Telemedicine

for

Trauma

and

EmergencyManagement: an Overview. Curr Trauma Rep [Internet]. 2016 [cited 3 December

2019];

115-123.

Available

from

https://link.springer.com/article/10.1007/s40719-016-0050-2 5. Badan Penelitian dan Pengembangan Kesehatan 2018. Hasil Utama RISKESDAS 2018 [Internet]. Jakarta: Kemenkes RI; 2018. Available from

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Appendix: Table and Figures

Authors iPhone-based teleradiology for the diagnosis of acute cervicodorsal spine trauma Can J Neurol Sci 2010

Title/journal

Descriptive program evaluation of the French Mobile Neurosurgical Unit (MNSU) to support remote military medicosurgical units

Retrospective study of 74 cases of suspected cervicodorsal spine fracture

Methods

From 2001 to 2009, 15 Mobile Neurosurgical Unit (MNSU) missions were performed for 16 patients. Injuries included 2 craniocerebral wounds, 7 closed head trauma cases, 5 cases of spinal trauma, and 2 spontaneous intracranial hemorrhage cases. In 5 of the 16 cases, neurosurgical intervention was provided on site A cell-phone-based multimedia messaging service is feasible and accurate in transferring a comprehensive impression to consultant

High sensitivity and accuracy of detecting vertebral body fractures (80 and 97 %) and posterior element fractures (75 and 80 %)

Summary

This system is accurate in diagnosis of cervicodorsal trauma and allows rapid, remote, and secure visualization of medical imaging without storing patient data The MNSU can be deployed for timely treatment when a short delay time in neurosurgical management is acceptable

Conclusion

Modi, et al. (Canada) [15]

The French mobile neurosurgical unit Neurosurg Focus 2010

Case report evaluating telemedicine to transfer images of patients to the consultant physician

Summary of selected studies on the use of telemedicine for trauma and emergency medicine patients internationally

Dulou, et al. (France) [28]

Cell-phone-based multimedia messaging service (MMS) and burn injuries Burns 2009

Literature review of articles on the role of telemedicine in accident and emergency care

Table 1

Knobloch, et al. (Germany) [29]

A review of the role of telemedicine in the accident and emergency department J Telemed Telecare 2009

Review of 39 articles using telemedicine in emergency medicine. Communication equipment included radio links, telephone, e-mail, and mobile wireless video conferencing devices

Description of program framework

Review of 2 cases with unfavorable outcomes related to failure to activate a teleradiology system

1024 neurosurgical cases (945 patients) between 1995 and 2000. Analysis showed 67 % of cases did not require transport and admission to a neurosurgical center and the associated potential cost savings 3 normal volunteers and 20 acute clinical examinations were performed using an existing internet link to direct or observe EFAST

The use of cell-phone-based MMS photo and video transmission facilitates immediate decision making irrespective of geographical location of the consultant All devices were found to transfer information effectively but success was at times limited to technical failure of the technology and staff confidence using the technology Pilot project for telemedicine framework in trauma network in Germany There is a risk for adverse outcomes when teleradiology is excluded from the management of patients in an emergency setting A teleradiology system enables rapid and reliable TC in neurosurgery patients with trauma, stroke, and intracerebral hematoma at low cost Remote real-time guidance or observation of an EFAST using telesonography appeared feasible. Technical challenges included initiating US audio and video communications, Keane (United Kingdom) [30]

Telematics in acute trauma care Stud Health Technol Inform 2009

Retrospective case review of an analog image transfer system for CT and MRI images from 7 referring hospitals in Germany

Description of a pilot project integrating telemedicine into a trauma network Case review of 2 mortality cases due to failure to obtain accurate radiologic diagnosis Teleradiology in neurosurgery: Experience in 1024 cases J Telemed Telecare 2008

Emergency radiology without the radiologist: The forensic perspective Radiol Med 2009

Kreutzer, et al. (Germany) [33]

Case series evaluating the use of telesonography protocols during trauma resuscitations

Juhra, et al. (Germany) [31] Di Paolo, et al. (Italy) [32]

Dyer, et al. (Canada) [34]

The clinical and technical evaluation of a remote telementored telesonography system during the acute resuscitation and transfer of the injured patient

224

123

Curr Trauma Rep (2016) 2:115â&#x20AC;&#x201C;

Figure 1 – Number of Road Traffic Accident in Indonesia (1992-2017) (Statistic Indonesia - Badan Pusat Statistik (BPS), 2018)

Figure 2 – Proportion of Injury that Disturb Everyday Activity According to Province, 2007-2018

225

Figure 3 – Trauma Injury Prevalence Based on Charateristic

Figure 4 – Proportion of the Location of Trauma of Injury, 2018

226

Figure 5 â&#x20AC;&#x201C; Proportion of Trauma Injury Caused by Road Traffic Acciden

227

I d e ia Medica S de

T ai i g a d C

eii

(IMSTC) 2020

Extract of Onion (Allium cepa L.) as Antimicrobial and Antioxidant Agent: The Alternative Solution for Contact Lens-related Corneal Ulcer Moh. Iqbal Irsyad Al Zaman, Muhammad Irsyad Amien, Siti Aminah Daeng Ndiko, Izza Amalia Putri.

Abstract Introduction: A corneal ulcer or ulcerative keratitis is a pathological condition of the cornea characterized by suppurative infiltrates accompanied by corneal defect, corneal tissue discontinuity can occur from the epithelium to the stroma. The prevalence of corneal turbidity due to corneal ulcers in Indonesia was 5.5% of all corneal opacities due to other eye diseases with the highest prevalence found in Bali (11.0%), followed by DI Yogyakarta (10.2%) and South Sulawesi (9.4%). One of causes of eye trauma is wrong habit of using contact lens. Contact lens cause many changes in the eye, including reduces oxygen transmissibility, changes in tear film, and infection may develop in contact lens users. Material and Methods: This study method is using a literature review which is to compile based on online databases s ch as Researchga e , P bMed , ncbi , Sciencedirec , ile online librar , and reposi or Ulcer ,

Con ac Lens ,

Onion ,

nej . The ke

Fla onoid ,

ords ha

e sed

An io idan , and

ere Corneal

An imicroba . The

inclusion criterias that we use are (1) the study was no later than 2009, (2) was truthworthy, and (3) correlated with the aim of this study. Result and Discussion: Onion s flavonoids are proven to have antimicrobial abilities against types of gram-positive bacteria such as Staphylococcus aureus, and Streptococcus mutans, and types of gram-negative bacteria such as Helicobacter pylori, Poryphomonas gingivalis, and Pseudomonas aeruginosa. Onion s fla onoids also ha e an io idan ac i i

hat has

proven by many resources. Flavonoids work as antioxidants by donating hydrogen atoms and an electron to hydroxyl and peroxyl to stabilize it. The hydroxyl configuration of the aromatic B ring in flavonoids has an important role in binding ROS. Conclusion: Quercetin in onion (Allium cepa L.) has antimicrobial and antioxidant that could improve corneal wound healing in corneal ulcer induced by contact lens. Keywords: corneal ulcer, contact lens, onion, flavonoid, antioxidant, antimicroba

228

I d e ia Medica S de

T ai i g a d C

eii

(IMSTC) 2020

Extract of Onion (Allium cepa L.) as Antimicrobial and Antioxidant Agent: The Alternative Solution for Contact Lens-related Corneal Ulcer Created by: 1. Moh. Iqbal Irsyad Al Zaman 2. Muhammad Irsyad Amien 3. Siti Aminah Daeng Ndiko 4. Izza Amalia Putri

229

Introduction A corneal ulcer or ulcerative keratitis is a pathological condition of the cornea characterized by suppurative infiltrates accompanied by corneal defect from the epithelium to the stroma. Extensive corneal ulcers require prompt and precise treatment to prevent ulcer expansion and complications in the form of descemetocele, perforation, endophthalmitis, even blindness[1]. Turbidity in the cornea is the third leading cause of blindness in the world after cataracts and glaucoma. In Indonesia, corneal opacification has a fairly high prevalence of eye disorders. The results of Riset Kesehatan Dasar (RISKESDAS) 2013 showed that the prevalence of corneal turbidity due to corneal ulcers in Indonesia was 5.5% of all corneal opacities due to other eye diseases with the highest prevalence found in Bali (11.0%), followed by DI Yogyakarta (10.2%) and South Sulawesi (9.4%)[2]. A corneal ulcer can be caused by infection and non-infection. Infection can be caused by bacteria, fungi, viruses, and acanthamoeba. While non-infectious causes include chemicals both acidic and alcalic, radiation or temperature, Sjogren's syndrome, vitamin A deficiency, use of eye drops corticosteroid drugs and trauma[3]. One of causes of eye trauma is wrong habit of using contact lens. Contact lens was invented to correct vision in vision problems including myopia (near-sightedness), hypermetropia (far-sightedness), and astigmatism (both near and farsightedness)[4]. Approximately, more than 85 million people use contact lens worldwide[5]. Contact lens cause many changes in the eye, including reduces oxygen transmissibility, changes in tear film, and infection may develop in contact lens users[6]. Contact lens has capacity to change tear biochemistry on the cornea surface if its too close to cornea or changes in tear exchange (tear mixing) between pre-contact lens and post-contact lens compartement during blinking. The changes in ocular surface biochemistry not only could reduce defenses against microbes because of lack of ability to remove microbes from post-contact lens, but also changes the homeostasis in ocular surface, such as epithelial injury induced by post-contact lens tear film due to hypoxic epithelial cells[7]. Bacterial colonization on the contact lens will lead to corneal infection or keratitis and formation of ulcer[5].The most common bacteria associated with microbial keratitis in contact lens users are Staphylococcus and Pseudomonas species[8]. In bacterial corneal infections, bacterial toxins that penetrate the corneal epithelium into the stroma will activate macrophages which will then activate various pro-inflammatory cytokines namely interleukin-1 (IL-1), interleukin-6 (IL-6), and TNF-

230

which subsequently affects several growth factor enzymes such as TGF- 1, FGF and PDGF as well as the extracellular matrix in the stroma. TGF- 1 i a er impor an growth factor in regulating MMP expression, especially MMP-9 and other collagenases which will stimulate MAPK signaling pathways and JNK-dependent fibronectinmediated that will affect activated keratocytes (activated keratocyte) thereby reducing proliferation and differentiation of keratocytes into myofibroblasts in corneal wound healing[9]. Quick and appropriate treatment is needed to prevent ulcers widespread, namely by eradicating the causes of corneal ulcers and also preventing tissue damage due to enzymes and toxins released by bacteria. Eradication of bacteria can be done by giving broad-spectrum antibiotics topically, such as fluoroquinolone or the antibiotic combination if monotherapy is not effective in treating infections[10]. If inflammation occur in the cornea, macrophages will clease debris and trigger cell apoptosis by expressing various mediators. Mediators for angiogenesis like VEGFA, VEGF-C, and VEGF-D will increase during inflammation. [11]. At present, using herb plants as treatment in disease began to develop. One of plants that is often used is onion plants (Allium sp.). Onion is famous as a medicinal plant because it is rich in flavonoids, namely flavonolsquercetin. A study says that quercetin has the ability as an anti-inflammatory, anticancer, antiallergic, antioxidant, and cardioprotective agent[12]. Besides, quercetin can also inhibit Vascular Endothelial Growth Factor (VEGF) in inducing choroidal angiogenesis and retinal in vitro [13]. Onion (Allium cepa L.) was chosen because it contains more quercetin than garlic (Allium sativum) viz at 54-286 mg / kg. Meanwhile, garlic (Allium sativum) has a quercetin content of 1.7 mg / kg

[14]

. Due to higher quercetin content, we use onion

(Allium cepa L.) as an alternative treatment for contact lens-related corneal ulcer. II. Materials and Methods This study method is using a literature review which is to compile based on online databases ob ained hro gh earch engine ncbi , Sciencedirec , ha

ere

An io idan , and

ch a

Re earchga e , P bMed ,

ile online librar , and repo i or Corneal Ulcer ,

Con ac

An imicroba . The a hor

eligibility of the sources.

231

Len ,

nej . The ke Onion ,

ere independen l

ord

Fla onoid , checked he

The inclusion criterias that we use are (1) the study was no later than 2009, (2) was trustworthy, and (3) correlated with the aim of this study. The studies which not meet the criterias were excluded. III. Result and Discussion 1. Corneal Wound Healing Corneal wound healing is a complex process that aims to maintain the integrity and health of the corneal surface epithelium so that the transparency of the cornea and our vision is maintained. Anatomically Corneal wound healing can be divided into 3 stages: (1) Lag Phase, a quiescent time to prepare the wound healing (2) Active migration/reepithelization of superficial cell sheets to cover the denuded surface (3) Proliferation, stratification, and differentiation[15]. There are several growth factors/cytokines that play an important role in the mechanism of corneal wound healing, namely (1) epidermal growth factor family, (2) hepatocyte growth factor / HGF, (3) keratinocyte growth factor / KGF, (4) Insulin-like growth factors / IGFs, (5) transforming growth factor-beta (TGF-b) and etc[16]. 2. Onion (Allium cepa L.) Onion is one of Indonesia's agricultural products. Onions have the following taxonomy : Kingdom

: Plantae

Subkingdom : Tracheobionta Super division : Spermatophyta Division

: Liliopoda

Subclass

: Liliales

Order

: Liliaceae

Genus

: Allium

Species

: Allium cepa L.

Onion is known as a plant that has a lot of potential for use in the medical field because of its phytochemical content which has anti-inflammatory, antioxidant and antimicrobial pharmacological effects[17]. The phytochemical which contained in onion are mainly saponin, quercetin, and anthocyanin[18]. Quercetin is one type of flavonoid in onions with the highest concentration of the entire flavonoid concentration, which is 80%-90%[19]. In addition, onion flavonoids also contain many active ingredients, such as allicin, essential oils (dipropyl disulfide, methyl

232

metantiosulfonate), minerals (potassium, phosphorus, calcium, manganese, sodium, sulfur, iron, zinc, copper, and selenium in small amounts ), vitamins (Vit C, folic acid, Vit E) and amino acids (glutamic acid, arginine, lysine, glycine)[20]. 3. Flavonoid Flavonoids are secondary metabolites that can be easily found in food and plants except for algae. Flavonoids are derivatives of polyphenol compounds which cause flavonoids to have polar properties so they can easily penetrate the peptidoglycan membrane. Flavonoids have a chemical chain composed of two substituted benzene rings connected by one three-carbon aliphatic chain (C6-C3C6)[18]. Flavonoids have a diversity that is determined by the location of the hydroxyl group on the carbon atom which is arranged using a numbering system. There are flavonoid compounds in the form of aglycones only and some are in the form of glycosides (aglycones and sugars). Flavonoids also bind to sulfate groups called flavonoid sulfates and some are bound to other flavonoids called biflavonoids[21]. Quercetin is one type of flavonoid in onions. Quercetin levels in onions are 300 mg / dl[18] or 13.27 mg / 100 g[21]. Most quercetin found in onions is glycosides (bound to glucose groups) or ether. The quercetin that found in onions mostly present in conjugated form as quercetin 4Â´-O- -glycopyranoside, quercetin 3, 4Â´-O- diglycopyranoside, andquercetin3,7, 4Â´-O- -triglycopyranoside[18].

Figure 1 Chemical stucture of quercetin[18] 4. Antimicrobial Activity Many studies have proven that flavonoids have antimicrobial effects. Flavonoids are proven to have antimicrobial abilities against gram-positive bacteria such as Staphylococcus aureus, and Streptococcus mutans, gram-negative bacteria such as Helicobacter pylori, Poryphomonas gingivalis[18], and Pseudomonas aeruginosa[12]. Meanwhile, gram-negative bacteria are more resistant than gram-

233

positive bacteria. Flavonoids have three antimicrobial pathways, namely: (1) directly kill the bacteria, (2) synergistically activate the antibiotics, and (3) attenuate the bacterial pathogenicity[17]. In a previous study, the tests of the quercetin effectivity on gram-positive and gram-negative bacteria showed significant results in which gram-negative bacteria were more resistant. Quercetin gives results of IZ (inhibition zone) 15.0 Âą1.0 mm, MIC (minimal inhibitory concentration) 40 mg on Staphylococcus aureus and IZ 11.8 mm Âą1.0, MIC 100 mg on Pseudomonas aeruginosa[12].

In other study, it was

mentioned that the minimum inhibitory concentration (KHM) of onion extract against Staphylococcus aureus in vitro studies with the turbidimetry method, and UV-Vis spectrophotometry was at a concentration of 1.56%[22]. Table 1 The concentration of onion extract on the diameter area inhibits the growth of Pseudomonas aeruginosa[20] Sampel

Pseudomonas aeroginosa

Onion extract 100%

(+)d=0, 75 cm

Onion extract 80%

(+)d=0, 65 cm

Onion extract 60%

(+)d=0,45 cm

Onion extract 40%

(+)d=0,35 cm

d: diameter of inhibitory area 5. Antioxidant Activity Flavonoids in onions have been shown to have antioxidant activity that can prevent contact between Reactive Oxygen Species and cells and tissues. Onion skin has a lot of quercetin, quercetin glycoside, and other oxidative products which have an active role as antioxidants for non-enzymatic lipid peroxidation and oxidation of lowdensity lipoproteins (LDL) [18]. Based on previous studies, quercetin is known to have six mechanisms of actions as antioxidants, namely: (1) Anti-oxidative action, (2) direct radical scavenging action, (3) inducible nitric oxide synthetase inhibitory

234

action, (4) xanthine oxidase inhibitory action, (5) modulation of gene expression, and (6) interaction with other enzyme systems[21]. Flavonoids work as antioxidants by donating hydrogen atoms and an electron to hydroxyl and peroxyl to stabilize it. The hydroxyl configuration of the aromatic B ring in flavonoids has an important role in binding ROS. While the heterocyclic rings on flavonoids function to initiate the conjugation between free 3-OH and aromatic rings. Besides, flavonoids can process metal chelating properties, while quercetin itself has the ability to iron-stabilize and iron-chelating attributes that play a role in stopping the formation of free radicals[18].

Figure 2 Inhibition of tert-butylhydroperoxide-induced lipid peroxidation by flavonoids. 6. FLAVONOID EXTRACTION Onion extract is made using maceration method with 96% ethanol as solvent. 4 kg of onions are peeled and washed thoroughly, and cut into small pieces. Onion pieces are put in room temperatur with good air ventilation till dry. Dried onion pieces are mashed with a blender. The maceration process is carried out 2 times, first mixed with 96% ethanol with a ratio of ethanol: simplicia that is 1: 4. After that, allowed to stand for 2 days and filtered using filter-paper so that the result of maceration of filtrate I. The result of maceration of filtrate I was mixed again with 96% ethanol and allowed to stand for 2 days. Then filtered again using filter paper and obtained the results of the maceration of filtrate 2. Then the results of the maceration of filtrate 2 obtained were evaporated from the remaining solvent using a vacuum rotary evaporator for 3 hours at 40ยบC. After that, the pure extract of the onion is put into the oven for 2 hours at 40ยบC, then put in a sterile sealed bottle and stored in the refrigerator[22].

235

IV. Conclussion Quercetin in onion (Allium cepa L.) has antimicrobial and antioxidant that could improve corneal wound healing in corneal ulcer induced by contact lens. Based on previous research on contact lens-related corneal ulcer, contact lens may cause corneal abrasion. Corneal abrasion can lead to corneal ulcer because contact lens increase bacterial colonization. Most bacteria found in contact lens-related corneal ulcer are Pseudomonas sp. And Staphyloccocus sp. Based on literature we found, Quercetin as antimicrobes is effective in gram positive bacteria, like Staphyloccocussp. and gram negative bacteria like Pseudomonas sp. Nevertheless, antimicrobial activity in gram negative is not as strong as gram positive.

236

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Dyavaiah M, Phaniendra A and Sudarshan SJ. Microbial Keratitis in Contact Lens Wearers. JSM Ophthalmology. 2015;3(3): 1036.

Samantha L. Wilson, Alicia J. El Haj, Ying Yang. Control of Scar Tissue Formation in the Cornea: Strategies in Clinical and Corneal Tissue Engineering. J. Funct. Biomater. 2012;3:642-687.

10. Asyifa Hilda Hapsari. Efek Ekstrak Bawang Bombay (Allium Cepa L.) Terhadap Neovaskularisasi Kornea Pada Kelinci Model Ulkus Kornea Staphylococcus Aureus [skripsi]. Jember: Fakultas Kedokteran Universitas Jember; 2018. 11. Bukowiecki, A., D. Hos, C. Cursiefen, and S. A. Eming. Wound-healing studies in cornea and skin: Parallels, differences and opportunities. International Journal of Molecular Sciences. 2017;18(6): 1257. 12. Santas, J., M. P. Almajano, dan R. Carbo. Antimicrobial and antioxidant activity of crude onion (Allium cepa L.) extracts. International Journal of Food Science and Technology. 2010;45: 403-409.

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13. Li, F., Y. Bai, M. Zhao, L. Huang, S. Li, X. Li, dan Y. Chen. Quercetin inhibits vascular endothelial growth factor-induced choroidal and retinal angiogenesis in vitro. Ophthalmic Research. 2015;53(3): 109-116. 14. Lim, T. K. Edible Medicinal and Non Medicinal Plants Volume 9 Modified Stems, Roots, Bulbs. Dordrecht, Heidelberg, New York, London: Springer. 2015. 15. Liu C.Y., Kao W.W.Y. Corneal Epithelial Wound Healing. Progress in Molecular Biology and Translational Science .. 2015 Aug; 134(5): 61-71 16. Ljubimov A.V., Saghizadeh M. Progress in Retinal and Eye Research. Progress in Retinal and Eye Research. 2015 July 18; 49:17-45 17. Xie Y., Yang W., Tang F., Chen X., and Ren L. Antibacterial Activities of Flavonoids : Structure-Activity Relationship and Mechanism. Currnt Medical Chemistry.2015 June 18;22(1):132-148 18. Pareek S., Sagar N.A, and Kumar V. Onion (Allium cepa L.). In Fruit and Vegetable Phytochemicals : Chemistry and Human Health . 2nd eds. 2018;2:1145-1161 19. Rodrigues, A. S., Almeida D. P. F., Gandara J. S., and Gregorio M. R. P. Onions: A Source

Flavonoids.

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https://www.intechopen.com/books/flavonoids-from-biosynthesis-to-human health/onions-a-source-of-flavonoids. 20. Wuryanti. W, and Murnah. M. Uji Ekstrak Bawang Bombay Terhadap Anti Bakteri Gram Negatif Pseudomonas aeruginosa dengan Metode Difusi Cakram. Jurnal Sains dan Matematika. 2012;17(3): 151-158. 21. Baghel S.S., Shrivastava N., Baghel R.S., Agrawal P., and Rajput S. A Review of Quercetin : Antoxidant and Anticancer Properties. World Journ of Pharmacy and Pharmaceutical Science. 2016 Jan 18;1(1):146-160 22. Permata,D.A.A., Waworuntu O.A., and Mintjelungan C. Uji Konsentrasi Hambat Minimum (KMH) Ekstrak Bawang Bombay Allium cepa, L. terhadap Pertumbuhan Staphylococcus aureus. Pharmacon. 2016 Nov 4; 5(4):52-60

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Author: Alfiani Zukhruful Fitri Rifa i. Rizqi Apsari Fairuz Kamila

Asian Medical Student s Association Indonesia (AMSA-Indonesia) 2019

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ABSTRACT Traumatic brain injuries (TBIs) induces structural injuries and/or physiological disruptions of brain function as a result of an external force, leading to temporary or even permanent impairment of the central nervous system and increase the morbidity and mortality rate. Secondary of TBI can not be ignored because has many impact on neuronal damage and loss. The most frequent case which happened are excessive oxidative stress and calcium release after brain injury. Although some traditional antioxidants have been clinically approved, the efficacy is far from statifactory due to their low ROS-scavenging efficiency, instability, toxicity, or inadequate penetration of bloodâ&#x20AC;&#x201C;brain barrier. Moreover, combination of Nanozyme based-bandage with Pt/CeO2 atom catalysis with electrospinning nanofibers Ntype voltage gated calcium channel blocker (SNX-185) is predicted to be as promising as a potential novel to reduce secondary injury of TBI. Therefore, the duo could cut down morbidity and mortality rate because of TBI in the future with noninvasive way. Keywords: Traumatic brain injury, nanozymes, antioxidant, reactive oxygen nitrogen species (RONS), Calcium Channel Blocker, SNX-185, and Electrospinning nanofiber

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Author: Alfiani Zukhruful Fitri Rifa’i. Rizqi Apsari Fairuz Kamila

Asian Medical Student’s Association Indonesia (AMSA-Indonesia) 2019

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Combination of Nanozyme-based Bandage with Pt/CeO2 Atom Catalysis and Electrospinning Nanofibers N-Type Voltage-gated Calcium Channel Blocker (SNX-185): A Potential Novel Way to Reduce Secondary Injury of Traumatic Brain Injury Alfiani Zukhruful Fitri Rifaâ&#x20AC;&#x2122;i. Rizqi Apsari Fairuz Kamila Introduction Traumatic brain injuries (TBIs) are induced structural injuries and/or physiological disruptions of brain function as a result of an external force, leading to temporary or even permanent impairment of the central nervous system and causing morbidity and mortality1. The exact number of head injuries incidence is difficult to determine due to various factors, for example some of the fatal cases never reach the hospital. Based on Riskesdas 2018 traumatic brain injury accounts for 11,9% proportion of body part affected in motor vehicle crashes other than all of the other body parts2. One of the major causes of secondary injury from a TBI is an overproduction of Reactive Oxygen Nitrogen Species3,4. Experimental and clinical studies have emphasized the importance of generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) as occurring in the early post-traumatic stages of the injury process5. Oxidative stress (OS) leads to irreversible neuronal membrane damage, resulting in a pattern of secondary injury mechanisms ultimately leading to dysfunction and cell death 6. Recent studies have shown evidence that neuroinflammation associated with TBI can also contribute to posttraumatic neurodegeneration3,7 The body naturally produces endogenous antioxidants, such as superoxide dismutase and glutathione molecules, to inhibit these increases in ROS production. However, if the TBI produces more ROS than the antioxidants, lipid peroxidation, DNA and protein damage8. To eliminate these excessive amount of ROS, antioxidant is needed. One of the biggest disadvantages of traditional antioxidant bandage is that it can lose efficacy after long-term exposure at room temperature due to limited electron-donating ability9. Regarding this case, a nanozyme-based bandage using single-atom Pt/CeO2 with a persistent catalytic activity is studied to find an alternate noninvasive treatment of neurotrauma in brain injury.

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Materials and methods The search strategy for this literature review was compile based journal sources through search engine such as NCBI-Pubmed, Research Gate, and Google Scholar online instruments. Keywords used are traumatic brain injury, nanozymes, antioxidant, and reactive oxygen nitrogen species (RONS), Calcium Channel Blocker, SNX-185, Electrospinning nanofiber with filters used are 10 years from publication date. From the search results, the journal is selected with 40 literatures are valid and reliable to our discussion. Level of evidence this literature review is Level 2A determined based on classification under license of Oxford Centre for Evidence-based Medicine Level of Evidence10. Results and Discussion Reactive Oxygen Nitrogen Species (RONS) Timely Removal is Essential Due to Irreversible Brain Damage An estimated 5.3 million traumatic brain injury (TBI) survivors are currently suffering long-term or life-long motor deficits11. However, currently there are no effective neuroprotective treatments12 because their effectiveness may be limited. In TBI, primary injury occurs at the time of trauma and the direct result is deformation of the brain tissue and disruption of normal brain function. Secondary injury is extensive and lasting damage such as neuroinflammation with excessive oxidtive stress which is believed as the main cause of neuron loss13. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) with unpaired electrons triggered by inflammation are among the most important elements for TBI 4. Mitochondrial ROS production contributes to innate immune activation after cellular damage and stress14. Toxicity of ROS to biomolecules causes activation of microglia and astrocytes. As a result, inflammatory and neurotoxic factors are released and trigger more oxidative stress, hence causing a chronic neuroinflammatory response13.

Fig. 1. Time course of measured secondary injury events in the mouse CCI model of TBI.

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In humans, post-mortem studies have shown microglial activation can be present up to 17 years after TBI. This suggests that TBI triggers a chronic inflammatory response particularly in subcortical regions15. Therefore, timely removal of harmful ROS is essential for neuron protection. Traditional Antioxidant Has Limitation and Drawbacks for Tackling Oxidative Stress Damage in Traumatic Brain Injury Cell-based therapy has been shown to reduce neuroinflammation and improve functional recovery after TBI16. Studies with multiple antioxidant agents have demonstrated effectiveness in decreasing the secondary brain injury, which is a principal focus of current TBI research17,18,19. In addition to these ROS producers, there is also an antioxidant system in the body that can scavenge ROS. When the balance of redox is disturbed, then lead to oxidative stress, resulting in the damage of many macromolecules (e.g., DNA, protein, and lipid) which cause inflammation and many neurological diseases4. Traditional ROS regulators, such as some natural enzymes and assemblies based on them, have not been well applied in brain diseases due to their low ROS-scavenging efficiency, instability, toxicity, or inadequate penetration of bloodâ&#x20AC;&#x201C;brain barrier20. For example, traditional intravenous administration of organic enzymes has shown great potentials in brain diseases21,22 but toxicity remains a major concern for clinical translation23. Thus, nanotechnology can maximize the therapeutic efficacy while minimizing the side effects24. Nanozymes, stable inorganic nanomaterials that possess intrinsic enzymemimic activities, have efficient ability to alleviate oxidative stress in the central nervous system. Compared with traditional antioxidants, these nanozymes have advantages of stable structure, adjustable activity, and diverse functions20. RONS Scavenging Activity in Enzyme-mimetic Properties of single-atom Pt/CeO2 in Elimination of Excessive Oxidative Stress As explained earlier, nanozymes have enzyme-mimetic activity mainly contain SODlike (Superoxide Dismutase) or catalase-like activities, which can effectively remove ROS accumulated in the body20. After TBI, an assembly of oxidative stress markers (RONS) are produced in the brain, while antioxidant defense enzymes decrease (GSH, ratio GSH/GSSG, GPx, SOD, CAT)25. Both of CeO2 and Pt have SOD-like and catalase-activity26,27. In otherwords, nanozymes

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have been reported to possess multiple antioxidative enzyme-like activities under the same condition and show effective neuroprotective effects20.

Fig. 2. (a) POD-like activity after 48 h; (b) The optimal doping ratio of Pt/CeO2 is â&#x2C6;ź15% in POD, (c) CAT-like activity of Pt/CeO2 showed a 9.2 times higher; (d) SOD-like activity, of Pt/CeO2 are 4 times higher; (e) GPx-like activity, (f) Pt/CeO2 catalysis endows multiantioxidant scavenging activities The above in vitro preliminary results to treat TBI noninvasively using the singleatom

28,29

Pt/CeO2 bandage that exhibit significantly catalytic activity over that of Pt/C

catalysts and ultrasmall Pt clusters30. Nanozyme-Based Bandage with Single-Atom Catalysis and Nanofibers Calcium Channel Blocker with for Traumatic Brain Injury Nanozymes with catalytic activities provide a potential solution for treatment of CNS and ROS related diseases31,32 The catalytic CeO2 and redox metal oxides have shown protective effects against brain injuries through scavenging ROS33,34.

Fig. 3. Concept of Using the Nanozyme-Based Bandage with Single-Atom Catalysis

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The procedure for the bandage fabrication use hydrophilic polyacrylonitrile fiber that has been activated. It then immerged into the specific nanozyme solution for 30 min. After being vacuum-dried and annealed for 1 h, fiber loaded with nanozyme was attached to the medical tape for further wound application23.

Fig. 4. (a) Single-atom Pt/CeO2 nanozymes were used as the multienzyme catalytic layer, whereas the flexible carbon fiber served as the substrate layer, (b) Nanozyme activity, (c) Design of the nanozyme-based bandage of single-atom Pt/CeO2 at (111) facets Moreover, this nanozyme-based bandage can protect neurons by clearing ROS and reducing inflammation in the neuron. Compared with previous IV injection routes for nanozymes the bandage can be an alternative solution for TBI noninvasive treatment via rational design at the single-atom level without side effects23.

Fig. 5. Time-course wound healing processes with/without using nanozyme-based bandage

Fig. 6. In vivo treatment of nanozyme bandage. (a) H2O2 generation and (b) GSSG activity (c) Immunofluorescence images for astrocyte and microglia

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The nanozyme-based bandage was attached to the injured brain area of TBI mice. The wound size and area were both significantly reduced to the healthy levels after receiving bandage treatment, whereas the untreated mice only showed a partial recovery (â&#x2C6;ź50%)23. Brain injuries also mediate both expression of inflammatory cytokines and recruitment of astrocytes and microglia in the injured area, but the nanozyme-based bandage alleviates levels of inflammatory factors and activation of astrocytes and microglia, leading to a decrease in overall neuroinflammation23. Both in vitro and in vivo results show that the nanozyme-based bandage can decrease indicators of oxidative stress and inflammation responses of neuron cells and improve impaired neurocognition. It has a promising frontier for noninvasive treatment of TBI using nanozymes for single-atom catalysis. Nanofibers N-Type Voltage-gated Calcium Channel Blocker (SNX-185) with Electrospinning Technique for Traumatic Brain Injury Calcium ions (Ca2+) are essential in the regulation of many cellular systems Disruption of calcium regulation, specifically prolonged periods of elevated cytosolic free calcium, can be catastrophic for the cell leading to chronic dysfunction or death.

Fig. 7. Patoghenesis of Traumatic Brain Injury N-type VGCCs play a critical role in many developmental and pathological events in neurons, and have been studied in models TBI35,36. N-type channels are found on the soma, dendrites, and axons of neurons throughout the brain37. Pre-clinical studies carried out in vivo in animal models of TBI report that selective blockade of N-type VGCCs results in decreased calcium accumulation in areas of TBI, preservation of mitochondrial function, and improved behavioral outcome when administered after TBI in rats35.

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SNX-185 is a synthetic version with highly selective N-type VGCC blocker that demonstrates improved bioavailability and more prolonged persistence in brain tissue than SNX-11135. These data suggest that SNX-185 treatment, even when delayed for hours after initial insult, may be effective in preventing or reducing calcium-related secondary injuries that occur clinically over many hours or days after injury35. Secondary insults such as ischemia and hypoxia often occur after human TBI 35. Several techniques have been reported to produce nanofibers such as pressurized gyration technique, self assembly, phase separation and freeze drying 38,20. However, all of these techniques are not ideal for wound dressingâ&#x20AC;&#x2122;s fabrication as this techniques would fail in providing adequate diffusion of oxygen and nutrients into cells resulting in failure of cells migration, proliferation and compensation. On a contrary situation, electrospinning technique was reported to overcome all of the previously mentioned drawbacks through producing well controlled ultrafine nanofibers mimicking the extracellular matrices in human body39. In addition, electrospinning is a costeffective, ecofriendly and facile technique40.

Fig. 8. A schematic representation of SNX-185 Nanofibers Conclusion Combination of Nanozyme-based Bandage with Pt/CeO2 Atom Catalysis and Electrospinning Nanofibers N-Type Voltage-gated Calcium Channel Blocker (SNX-185) can reduce secondary injury caused by Traumatic Brain Injury. It has relation with RONS scavenging activity in enzyme mimetic properties by Pt/CeO2 to eliminate the excessive oxidative stress. In other hands, electrospinning nanofibers SNX-185 is the most likely promising concept because other blockade mechanism of calcium channel has a lot of limitation and drawbacks. The combination between both elements have no spesific drug interaction effect. Larger multi-center studies and research for the duo should be furthermore conducted to get more scientific evidence. References

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Treatments of Blunt Cardiac Injury and How Mortality Rates Could be Reduced Catherine Kamaladevi, David Christiadi, Miriam Angeli Islamyah, Jerrick Lo Abednego (A Team)

Abstract Introduction Blunt cardiac injury (BCI) refers to injury sustained due to blunt trauma to the heart which is more common than penetrating injuries. Missed diagnoses and high mortality are major concerns in this injury. [2] Although an increasing number of cases have been diagnosed during the past few years, due to better equipment, the mortality rate is still high and majority of patients pass away before they arrive in the emergency department. [3] This is why blunt cardiac injury goes on mostly underdiagnosed. Methods We produced a literature review based on journals obtained on the PUBMED library. We queried blunt cardiac injury in the PUBMED library, and revealed 1361 articles by the time of writing. Articles are chosen based on correspondence to our thought process. Result and discussion Despite blunt cardiac injury being a difficult condition to diagnose, a few diagnostic measures can be taken to reduce misdiagnoses, such as the use of cardiac markers troponin I, serum NTproBNP, echocardiography and transesophageal echocardiography. The use of NT-proBNP as an adjunct assessment to other diagnostic test such as troponins, ECG, chest x-ray and echocardiogram should be done for BCC in trauma diagnosis. [20] TEE can be the best method for patients who suffered polytrauma and frequently connected to life support devices. [19] Conclusion We conclude that underdiagnoses of blunt cardiac injury occurs due to the inability of clinicians to recognize the importance of diagnosing (or excluding the diagnosis of) blunt cardiac injury.

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Although the current technology available as instruments for blunt cardiac injury are sufficient, the lack of suspicion from clinicians cause the diagnosis of blunt cardiac injury to be underdiagnosed.

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IMSTC 2020 Treatments of Blunt Cardiac Injury and How Mortality Rates Could be Reduced

Authors: Catherine Kamaladevi David Christiadi Miriam Angeli Islamyah Jerrick Lo Abednego (A Team)

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Treatments of Blunt Cardiac Injury and How Mortality Rates Could be Reduced Catherine Kamaladevi, David Christiadi, Miriam Angeli Islamyah, Jerrick Lo Abednego (A Team)

Abstract Introduction Blunt cardiac injury (BCI) refers to injury sustained due to blunt trauma to the heart which is more common than penetrating injuries. Missed diagnoses and high mortality are major concerns in this injury. [2] Although an increasing number of cases have been diagnosed during the past few years, due to better equipment, the mortality rate is still high and majority of patients pass away before they arrive in the emergency department. [3] This is why blunt cardiac injury goes on mostly underdiagnosed. Methods We produced a literature review based on journals obtained on the PUBMED library. We queried blunt cardiac injury in the PUBMED library, and revealed 1361 articles by the time of writing. Articles are chosen based on correspondence to our thought process. Result and discussion Despite blunt cardiac injury being a difficult condition to diagnose, a few diagnostic measures can be taken to reduce misdiagnoses, such as the use of cardiac markers troponin I, serum NT-proBNP, echocardiography and transesophageal echocardiography. The use of NT-proBNP as an adjunct assessment to other diagnostic test such as troponins, ECG, chest x-ray and echocardiogram should be done for BCC in trauma diagnosis. [20] TEE can be the best method for patients who suffered polytrauma and frequently connected to life support devices. [19]

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Conclusion We conclude that underdiagnoses of blunt cardiac injury occurs due to the inability of clinicians to recognize the importance of diagnosing (or excluding the diagnosis of) blunt cardiac injury. Although the current technology available as instruments for blunt cardiac injury are sufficient, the lack of suspicion from clinicians cause the diagnosis of blunt cardiac injury to be underdiagnosed.

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Introduction And always with a heart contusion arise both doubt and much confusion: a quote by Burchell in 1935 still stands true today. [1] Blunt cardiac injury (BCI) refers to injury sustained due to blunt trauma to the heart which is more common than penetrating injuries. Missed diagnoses and high mortality are major concerns in this injury. [2] Blunt injury to the heart ranges from subtle alterations in functions and electrical conduction (concussion) to myocardial contusion, and in the worst case, death. The term myocardial contusion, however, is generally used to denote the whole spectrum of cardiac pathology from non-penetrating trauma. Although an increasing number of cases have been diagnosed during the past few years, due to better equipment, the mortality rate is still high and majority of patients pass away before they arrive in the emergency department. [3] The symptoms of cardiac contusion are variable and frequently unnoticed by the anxious and often multiply traumatized patients whose cardiac symptoms are overshadowed by musculoskeletal injuries.[4] This is why blunt cardiac injury goes on mostly underdiagnosed. Multiple case and autopsy studies have revealed that the most common cause of blunt cardiac injury is motor vehicle accidents. Below are the studies reviewed and their specific percentages, arranged from the most recent year published.

Study

MVC (%)

Turan et al. 2010. Cardiac injuries caused by blunt trauma.

56%

Teixeira et al. 2009. Blunt thoracic aortic injuries: an autopsy study

49,7%

Teixeira et al. 2008. Blunt cardiac trauma: lessons learned from the medical examiner 57,4%

As we review further, it has come to our attention that we had not found any data regarding blunt cardiac injury from Indonesia. It is interesting as the most common mechanism for blunt cardiac

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injury is MVC, and the amount of motor vehicle collisions in Indonesia is high. According to Korlantas Polri, from 31st December 2018 to 31st March 2019, are 28,272 in which 5,918 passed away. [5] This would mean if one were to conduct a data study of BCI in Indonesia, there would be an abundance of information. However, we also understand that blunt cardiac injury is a difficult diagnosis. To this date, it is beyond our knowledge if a study on blunt cardiac injury performed in Indonesia have been done before.

Objective To present recent developments in the understanding of treatments and diagnosis for blunt cardiac injury, and suggest better treatments so that mortality rates could be reduced.

Method We produced a literature review based on journals obtained on the PUBMED library. We queried blunt cardiac injury in the PUBMED library, and revealed 1361 articles by the time of writing. Articles are chosen based on correspondence to our thought process. Articles are then filtered through its clinical significance to our paper. For example, when looking for statistics, only those of autopsy studies in the various decades are taken to produce a trend. Although we understand that only papers of the past 5 years are the most reliable, we realized that blunt cardiac injury has only few data studies. Hence, we decided that including papers of the past 30 years is acceptable to compare. Articles are chosen and filtered by early November to midNovember 2019.

Discussion Epidemiology In the United States, trauma ranks as the fourth leading cause of death. [6] 25% of trauma-related

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deaths are associated with thoracic injuries. [7] Determining the incidence of cardiac injury after blunt chest injury is difficult due to the absence of clear diagnostic guidelines to direct management. [6] The incidence of blunt cardiac injury according to CDC is approximately 30,000 cases per year. Based on a case report, following blunt chest trauma, the incidence of cardiac injury ranges between 8% to 86%. [2] A study obtained data from the National Trauma Data Bank (NTDB) from January 2007 to December 2015 and concluded that from 4,571,161 adult patients, 0.3% had BCI. Most patients involved were male (67.9%) and had an average age of 48.8 years. The mortality rate for patients with BCI is identified to be 19.1%. [8] The largest causative mechanism for blunt cardiac injury is motor vehicle collision (72%) and auto versus pedestrian (16%). From 93.7% of patients with blunt cardiac rupture who were alive upon arrival to the hospital, only 10.8% survived. Patients who survived to discharge from the hospital were younger. [9] Aortic rupture is present in 24% of people. Death in the scene is more consistent with patients with thoracic aortic injury than those without injury. [10] The incidence of cardiac injury is lower in pediatric, varying between 15-20%. The survival time may vary in patients with BCI. In 56% patients, the survival time is recorded to be less than 24 hours, whilst in 44% patients, the survival time is more than 24 hours. [3] Cardiac trauma in children occur more often in boys, predominantly due to motor vehicle versus pedestrian accidents. Deaths from blunt myocardial injury came from child abuse rather than automobile trauma. [11] Although pediatric cardiac injuries caused by motor vehicle collision are more common than by firearm injury, more deaths from cardiac injury in pediatrics occur in firearm injury. Rib trauma are associated with blunt cardiac injury. [4] Mechanism The mechanism of cardiac injury involves a sequence of events beginning with direct impact to the chest wall with transmission of the kinetic force to the patient, causing compression of the heart between the sternum and the spine. This results in a change of the inertia of the viscera and the momentum of the blood column. Cardiac injury has been reported after deceleration from velocities of less than 20 mph. Another mechanism of injury to the heart without direct chest trauma is seen during cases of abdominal and lower extremity trauma. In such cases, upward displacement of the viscera can result in cardiac injury, a phenomenon known as the Hydraulic Ram Effect . Cardiac injury also may be caused by severe changes in atmospheric pressure surrounding the patient, as is commonly seen in cases of explosion victims. Other mechanisms of

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cardiac injury after blunt chest trauma include hypotension, anemia secondary to acute bleeding, hypoxia complicating lung injury, and increased intracranial pressure with head injury leading to elevated epinephrine levels (acute catecholamine storm), causing beta receptor desensitization, coronary vasoconstriction, and myocardial necrosis. [12, 13] Diagnosis Blunt cardiac injury is a difficult condition to diagnose, especially because it is a heterogeneous category of multiple specific injuries. Patients may come with unspecified symptoms as they may also have other injuries from a traumatic accident which masks the specific symptoms of BCI. The physical examination is often also nonspecific, although clinical findings such as ecchymosis, chest tenderness, flail chest and crepitus are markers for a high risk mechanism of injury.[14] If patients still experience chest pains after an inconclusive physical examination, EKG can be done to further screen for BCI. Many sources support the notion that EKG results can safely be trusted to differentiate malignant cardiovascular course from those that aren t. Blunt cardiac injury EKG picture could be shown as sinus tachycardia, arrhythmias, and ST segments changes.[15] Although an EKG could safely exclude emergent cases from those that could be handled therapeutically, the results are also said to be biased towards the right ventricle only. As most of the waves source from the right ventricle, problem areas in other cardiac chambers cannot be viewed well. There have been attempts to use specialized types of ECG to improve the predictive value of this modality, because the right ventricle is believed to be the more likely injured cardiac chamber in BCI.[17] From laboratory test, CK-MB, CK-MB/CK total ratio, CK-MB mass, and CK-MB mass/CK total ratio was not useful in detecting myocardial damage after blunt chest trauma, based on Swaanenburg's research. Although CKMB-isoenzyme measurement is currently a recommended bio-chemical test for the detection of myocardial damage, it is less accurate in patients with chest trauma. As CKMB is present in a myocardial muscle and in skeletal muscle, CKMB from both types of tissue is released and causes blood values to be elevated in response to the injury.[17] Recently, the cardiac markers troponin I (cTnI) and troponin T (cTnT) have become another

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laboratory test for cardiac markers. Troponin I and T form a complex that regulates the calciummodulated interaction of actin and myosin in striated muscle.[17] To be more specific, cardiac troponin I (cTnI) is a cardiac regulatory protein found only in cardiac tissue, elevations have high sensitivity for detecting myocardial injury, the elevations of cTnI persist for 4 to 7 days in plasma, providing a convenient time frame for identifying myocardial injury. The excellent diagnostic sensitivity of cTnI for cardiac injury is because of the large amount of cTnI in myocardium, which is many times greater than concentration of CKMB. Measuring the concentration in serum of cTnI is harder and less costly than using echocardiography as a routine screening test to detect cardiac injury after blunt chest trauma.[18] Based on a study results, Transesophageal echocardiography (TEE) more preferred to use than Transthoracic echocardiography (TTE) due to TEE can predictably provide stable high-quality tomographic images of the heart and thoracic aorta in nearly all patients. TEE can be used with less difficulties and resulted with important information to help on developing treatment for the patient. The study also get another function of TEE which could detect or exclude aortic dissection with high sensitivity and specificity. TEE can be the best method for patients who suffered polytrauma and frequently connected to life support devices.[19] Another study revealed they identified a significant increase from serum NT-proBNP level during the first 5 hours after Blunt Cardiac Contusion from the BCC group as one of the laboratory tests. If the BNP values increased above from the thresholds, it could means an abnormality of heart function. The early increased of NT-proBNP level may be explained by the direct myocardial cell damage caused by BCC. The use of NT-proBNP as an adjunct assessment to other diagnostic test such as troponins, ECG, chest x-ray and echocardiogram should be done for BCC in trauma diagnosis.[20] Myocardial contusion is one of the most common but ambiguous, cardiac diagnoses which made after patients experienced a blunt chest trauma. Some clinicians may apply the label of myocardial contusion to all patients who experiencing chest soreness with elevation of serum cardiac biomarkers after a blunt chest trauma, the diagnosis of subclinical Myocardial Contusion itself can

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be done with echocardiography, gated cardiac radionuclide angiography (MUGA), or myocardial perfusion imaging but similarly may not affect outcome in stable patients.[21] Clinical Presentations Blunt cardiac injury could present itself variously, from cardiac concussion to cardiac contusion. However, as cardiac contusion is a more common form of presentation of cardiac injury, it is mostly used to represent blunt cardiac injury as a term overall. Myocardial contusion, histologically, is characterized by intramyocardial hemorrhage, edema and necrosis of myocardial muscle cells. [13] This is similar to findings in myocardial infarction. The distinction between them is that in contusion, there is a visible boundary between normal and contused tissue, while in infarction there is a gradual transition from the normal to infarcted tissue. The area of injury is only determined by the force in which the contusion were dissipated. There is no effect on coronary artery flow, unlike in myocardial infarction. Macroscopically, superficial areas of hemorrhage in the epicardium extend in a pyramidal fashion and transmurally.[22] The healing patterns of myocardial infarction and myocardial contusion are different too. Myocardial infarction heals in a generalized fibrotic manner, while myocardial contusion heals with patchy and irregular fibrosis.[23] Myocardial concussion, from myocardial contusion, is distinguished by its lack of myocardial cellular damage, assessed both histopathologically and chemically. There is no CPK released in the myocardium. This does not exclude their risks for developing arrhythmias, though, as the damage is still present. Concussion usually occur due to a blow to the sternum, while contusion from trauma to any thoracic site.[4] A study by Richard C Frazee in 1986 suggests that the diagnosis for contusion and concussion is made based on 2-DE results. If 2-DE is normal, then the diagnosis is to be cardiac concussion, and release of the patient is confidently done. Although, there is no other study that analyses the use of 2-DE for blunt cardiac injury. Other complications that might occur together with cardiac contusions and concussions include, cardiac rupture, valvular injuries, pericardial involvement, vascular injuries and dysrhythmias.

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Treatments Any therapeutic management present for blunt cardiac injury results from treatments of its complications. As myocardial contusion usually occur with arrhythmias and pump failure, management is usually done in the ICU. However, when the diagnosis of myocardial contusion can be safely set aside (ex: when ECG doesn t indicate myocardial contusion), home medications while the patients are to be discharged can be safely done. Treatment of arrhythmias in patients with blunt cardiac injury can be done through antiarrhythmic protocols. As arrhythmias usually appear 24 hours after blunt cardiac injury, afterwards, diagnosis can be safely ruled out. [28] Intravenous thrombi can also appear as a consequence of myocardial contusion. This has been repeatedly demonstrated through the help of TEE. The management for thrombi is still controversial. The setting of trauma contraindicates the use of anticoagulants to combat thrombus. It could worsen the area of contusion-necrosis, promote intramural bleeding, or instigate tamponade by permitting bleeding in the pericardium. However, patients with intramural thrombosis is suggested to be given prophylaxis heparinization whenever beneficial. Management for cardiac output depression is done through intra-venous balloon and heparinization. Contraindications for heparinization include low-output cardiac failure. The success rates for cardiac output increase is 12,5% plus minus 3,2% .[22] Whenever heparin isn t favored, the low molecular weight dextran is used for its antiplatelet effect.

Conclusion Constructing a diagnostic criteria for blunt cardiac injury remains difficult. We conclude that underdiagnoses of blunt cardiac injury occurs due to the inability of clinicians to recognize the importance of diagnosing (or excluding the diagnosis of) blunt cardiac injury. Although the current technology available as instruments for blunt cardiac injury are sufficient, the lack of suspicion from clinicians cause the diagnosis of blunt cardiac injury to be underdiagnosed. Clinicians should be more aware of the workups needed for blunt cardiac injury, to prevent underdiagnoses that causes complicated symptoms of patients, which increases the risks of death. Technology present are sufficient, as long as the knowledge of the physicians are enough.

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Treatment of Spinal Cord Injury and Complication Prevention Using Stem Cell Methods

Author(s) Sahda Alfreda Putri Naziha Abdullah Zarkasih Bianda Astari Warman

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Abstract Background: Spinal cord injury (SCI) is a devastating disease with a frequency of occurrence of 12.1-57.8 cases per million. About 57.1 % individuals with spinal cord injury are employed before their injury, but this number decreased to 11.8% the next year. A key element in restoring function after a spinal cord injury through cell transplantation will be the replacement of damaged neural tissue (neurons, oligodendrocytes) to re-establish connections between central and peripheral nervous system. Stem cell transplantation is a promising and attractive cell-based treatment modality for repairing the damaged central nervous system, including SCI Materials and methods: We use database form PubMed, Proquest, Google Scholar, and Science Direct to conduct this literature review. While screening the title, abstract and full text eligibility there are 6 journals that meet the full criteria include prevent complication and treatment of Spinal cord injury Results and discussion: A lot of basic research and clinical trials has already been tried using stem cell therapy. It can significantly reduces neurological disability as the complication of SCI, using mononuclear cell preparations (MCPs) combine with granulocyte-macrophage colony-stimulating factor (GM-CSF), one of stem cell methods. Breast Milk Stem CellConditioned Medium (BMSC-CM) are shown to improves motoric and sensoric functions, also reduces production of proinflamatory cytokines. Therefore, BMSC-SM reduces apoptosis after SCI. Conclusion: As stated above, using stem cell methods for treatment and prevent complication of SCI show a good impact in improvement quality of life. However, further studies about stem cell-based treatment are needed to discover the most efficient way of stem cell administration into the injured spinal cord, also the side effects that follow. Thus, we still need more applied level of animal experimentation and translation into human clinical trials to know more about the effectivity of stem cell Keywords: Spinal Cord Injury, Stem Cell, Prevention, Complication

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Treatment of Spinal Cord Injury and Complication Prevention Using Stem Cell Methods

Author(s) Sahda Alfreda Putri Naziha Abdullah Zarkasih Bianda Astari Warman

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Introduction Spinal cord injury (SCI) is a devastating disease with a frequency of occurrence of 12.157.8 cases per million.(1) Based on several regional studies in United States, the incidence of spinal cord injury is estimated roughly 12,000 to 20,000 cases per year. (2) SCI can be caused by motor vehicle crash (41.1%), falls (26.7 %), violent acts (15.1%), sports (7.6%), and other (8.6%), including medical and surgical causes. Falls are the most common cause of SCI for eldery with age older than 60 years. The cervical level is the most commonly injured (54.1%) compared to thoracic, lumbal, and sacral levels. (3) SCI is a serious disease with high social economic cost associated with the significant disability and associated health expenses it causes.(1) The limitations on daily activities of spinal cord injury patient are depends on the location and completeness of the injury. The higher the level of the effected spinal cord, the more assistance needed for the patient to do their daily activities, otherwise patient with spinal cord injury level T1 or below generaly more independent in their activities. About 57.1 % individuals with spinal cord injury are employed before their injury, but this number decreased to 11.8% the next year.(4) This shows how spinal cord injury could effect ones capability to work. Acute and long-term secondary medical complications are common in patients with SCI. however, chronic complication especially further negatively impact on patientsâ&#x20AC;&#x2122; functional independence and quality of life. therefore, prevention, early diagnosis and treatment of chronic secondary complications in patients with SCI is critical for limiting these compications, improving survival, community participation and health-related quality of life.(7) Frequent complications of cervical and high thoracic SCI are neurogenic shock, bradyarrhythmias, hypotension, ectopic beats, abnormal temperature control and disturbance of sweating, vasodilatation and autonomic dysreflexia. Due to physical inactivity and altered haemostasis, patients with SCI have a higher risk of venous thromboembolism and pressure ulcers. The psychological stress associated with SCI may lead to anxiety and depression.(8) Goals in the management of SCI-patients include minimizing the primary neurological damage, and preventing secondary cord injury due to hypoperfusion, ischemia, and apoptotic, biochemical and inflammatory changes. After a traumatic SCI, the number of complications during the acute phase hospitalization, depends on the timing of surgery, with less complications when surgery is performed soon after the injury. In the Trauma Audit and Research Network database, the percentages of neurogenic shock was 19.3% in cervical injuries. In thoracic and lumbar injuries the reported incidence was 7.0% and 3.0%, respectively.(9)

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Screening

Identification

Materials and methods

Initial search results from Pubmed and EBSCOhost (50) Irrelevant titles excluded (30) Title screening of authenticity and duplication (20)

Eligibility

Abstracts screened (20)

Full-text assessed for eligibility (10)

Included

Full-text article excluded: (6)

Full-text eligible case-control articles included in review (6)

We used some databases to conduct this literative review such as: PubMed, Proquest, Google Scholar, and Science Direct. The following search terms used in all five databases are “spinal cord injury” “treatment” “stem cell”. We identify 50 papers through the initial finding, after screening the title, abstract and full text eligibility there are 6 papers that meet the full criteria.

Results and discussion Primary SCI refers to the neural elements damage at the time of trauma, such as shear force to axon or blood vessels and results to irreversible injury. Secondary SCI refers to the body’s response to the primary injury. A host cellular cascades has been identified to occurs immediately after injury and may persist for the next months to years, these will exacerbate the underlying injury and prevent neurologic recovery.(5) Current SCI treatment focus on stabilization of the spinal column to prevent further damage, supportive management to prevent secondary injury, and measures to enhance cord perfusion. Acute care for these patients can be provided in the intensive care unit (ICU), an intermediated care unit, or a surgical unit of a hospital, depending on the stability of the patient’s vital sign, the injured spinal level snd severity, also other associated injuries.(3) Early

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surgical decompression is playing an increasing role in the treatment of acute SCI. In terms of safety, the treating surgeon must balance the potential benefits of early surgery versus the risk. The benefits include relieving cord compression and therefore limiting secondary injury. The risks include aggravating secondary injury by hypotensive episodes or blood loss. (5) Pharmacologic agents such as methylprednisolone are controversial but have purported benefits in improving neurologic function in some patients. (3) Based on a study of 169 adults, urinary tract infections (62%), autonomic dysreflexia (43%), and pressure ulcers (41%) are common complications in the first year after inpatient rehabilitation for SCI. These complications are often recurrent, and more likely affect people with higher impairment levels.(6) Gray and white matter damage after SCI leads to partial or complete motor, sensory, or autonomic deficit in parts of the body distal to the lesion site. In accordance, the most devastating of all SCIs are injuries of the cervical spine, accompanied by high-grade dysfunction of the central nervous system (CNS).(10) In the past, treatment of spinal cord injury seemed frustrating and hopeless because of the remarkable morbidity and mortality and restricted therapeutic options. The traditional approach to SCI has been to limit the secondary injury that follows trauma more than to repair damage which is much more difficult. Treatments might target the cellular and matrix changes that occur at the injury site, the regenerative perikaryal responses that occur in injured neurons or the reactions of neuronal and non-neuronal cells located beyond the lesion, especially neutrophils and microglia.(11) Interventions that have been combined with transplants to promote repair and/or recovery include the application of neurotrophic or growth factors, pharmacological agents that mimic the action of neurotransmitters, agents that interfere with inhibitors of growing axons and physical rehabilitation and training. Most treatments are devoted to cure acute injury, whereas chronic injury is a more challenging. A key element in restoring function after a spinal cord injury through cell transplantation will be the replacement of damaged neural tissue (neurons, oligodendrocytes) to re-establish connections between central and peripheral nervous system. There are two types of bone marrow stem cell, hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs), which are known to differentiate into hematopoietic and mesenchymal cell lineages. (11) For clinical transplantation, HSCs and MSCs represent attractive cell sources as they can be easily and reproducibly isolated from bone marrow aspirates and reintroduced into patients as autografts. One research found successful results were obtained with different cell types: embryonic stem cells, adult neural stem cells, fetal tissue, myelin producing cells and mesenchymal stem cells (MSCs). (12) Stem cell transplantation is a promising and attractive cell-based treatment modality for repairing the damaged central nervous system, including SCI. Many studies have successfully applied stem cell-based therapy in animal models of SCI and they have achieved functional recovery. (13) Among a variety of types of stem cells, of particular interest is the availability of adult stem cells as a source for cell transplantation. Unlike embryonal or fetal origin stem cells, using adult stem cells avoids ethical and moral problems as well as teratogenic and oncogenic risks. Some groups have especially focused on the potential of human umbilical cord blood (hUCB) derived-stem cells as a graft source for various intractable neurological disorders. (14) However, SCI has been less dealt with as a target disease for stem cell research, using hUCB derived-stem cells, as compared to other neurodegenerative diseases such as stroke. This may be in part because SCI has an impact on specific types of cells and tissue, including oligodendrocytes and axons. Therefore, the following review discusses the past and recent

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findings on specific stem cell properties and the therapeutic potential of hUCB as a safe, feasible and effective cellular source for transplantation in patients with SCI. Despite all above-described successful cell-therapy experiments, it should be noted that under physiological conditions, allogeneic cell transplantation, independently of cell type, will be associated with immunological rejection unless proper immune suppression is provided. (15) Therefore, to circumvent this problem of immunological rejection, MSCs, nonhematopoeitic stem cells residing in the bone marrow, have received much attention nowadays. Indeed, such MSCs can be cultured relatively easily out of a bone marrow aspirate and have shown in vitro trans-differentiation potential into neural cells. After transplantation into brain and spinal cord, differentiation of MSCs into cells with neuronal and astrocyte characteristics was reported. Transplantation in demyelinated spinal cord resulted in proper remyelination, associated with enhanced conduction velocity, suggesting that cell transplantation might cause an influence through integration and/or differentiation of transplanted cells, but also by a possible paracrine effect, which can alter the local environment allowing for endogenous regeneration.

Conclusion As stated above, using stem cell methods for treatment and prevent complication of SCI show a good impact in improvement quality of life. However, further studies about stem cellbased treatment are needed to discover the most efficient way of stem cell administration into the injured spinal cord, also the side effects that follow. Thus, we still need more applied level of animal experimentation and translation into human clinical trials to know more about the effectivity of stem cell Table and figures Author and Year

Topic

Outcome

Gazdic M, Stem Cells Therapy for Results of preclinical studies indicate that application of stem cell-derived progenitors et al. 2018 Spinal Cord Injury significantly reduces neurological disability in most severe SCIs Tsai MJ, et al. 2018

Attenuating Spinal Cord Injury by Conditioned Medium from Bone Marrow Mesenchymal Stem Cells

The study confirmed the neurite promoting and neuroprotective effect of Mesechymal Stem Cell (MSC) co-cultures, and similar effect occurred when MSC-CM was added to spinal cord neuronglial culture. The beneficial effect of MSC were possibly derivided from itâ&#x20AC;&#x2122;s released fraction. Supporting the neurological improvement, the axons were significantly preserved in SCI rat models with MSC-CM treatment. Thus, MSC-CM

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treatment could promotes spinal cord repair and recovery, via activation of autophagy and enhancement of survival-related proteins. Haghighi BM, et al. 2019

The Therapeutic Potential of Conditioned Medium from Human Breast Milk Stem Cells in Treating Spinal Cord Injury

Sun Kyu Oh, et al. 2016

Current Concept of Stem Cell Therapy for Spinal Cord Injury: A Review

Stem cell therapy in SCI provides a clue to solve the challenges which modern medicine cannot treat. A lot of basic research and clinical trials has already been tried using stem cell therapy and promising results have been also reported. If stem cell therapy in SCI is established, it will have a great progression on other incurable degenerative central nervous system disorders.

Wright KT, et al. 2011

Concise Review: Bone Marrow for the Treatment of Spinal Cord Injury: Mechanisms and Clinical Applications

Based on animal studies, transplanted mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) might induce tissue protection/ repair. In clinical trials, patients with SCI both acute and chronic injected by mononuclear cell preparations (MCPs) combined with granulocytemacriphage colony-stimulating factor (GM-CSF) show neurological and functional improvement, also improvement in quality of life

Ronsyn MW, et al. Can cell therapy heal a spinal cord injury? 2008

Intrathecal administration of Breast Milk Stem Cell- Conditioned Medium (BMSC-CM) provides therapeutic effects in rats with SCI. BMSC-CM are shown to improves motoric and sensoric functions, also reduces production of proinflamatory cytokines. Therefore, BMSC-SM reduces apoptosis after SCI.

Although current therapeutic approaches for spinal cord injury are mainly focused on prevention and treatment of secondary complications, animal research has provided multiple successful strategies to follow to cure and not just to care for spinal cord injury. However, application of these promising therapeutic approaches will need much more research, both on the basic level to clear out the exact pathophysiological mechanism of secondary damage and endogenous regeneration, as well as on a more applied level of animal experimentation and translation into human clinical trials.

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