AMINO PCC AMSC 2020: London by AMSA-Indonesia

AMINO | PCC AMSC 2020: LONDON

AMINO | AMSC 2020: LONDON

AMINO | PCC AMSC 2020: LONDON

AMINO | AMSC 2020: LONDON

FOREWORD

Christina Wunardi Secretary of Academic AMSA-Indonesia 2019/2020

AMSA National Competition Archive, or AMINO, is an archive of all academic works submitted by AMSA-Indonesia 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 PreConference Competition Asian Medical Students’ Conference (PCC AMSC). AMINO aims to provide thorough overview of AMSA-Indonesia’s national competitions to all member of AMSA-Indonesia. On the third volume, all qualified works that was submitted to PCC AMSC 2020: London have been compiled and are expected to draw forth inspiration and motivation in creating academic works in field of Scientific Paper, Scientific Poser, and White Paper and Video. I would like to thank and express my sincere appreciation to all the participants of PCC AMSC 2020: London, the Academic Team, Executive Boards of AMSA-Indonesia 2019/2020, and other parties that have contributed to the creation of this archive. Hopefully, the release of AMSA International Competition Archive can enhance and intensify the academic enthusiasm and interest of all members of AMSA-Indonesia. “Enhancing Collaboration, Influencing Community” Viva AMSA!

AMINO | PCC AMSC 2020: LONDON

TESTIMONY

AMINO | AMSC 2020: LONDON

Nikolaus Tobian AMSA-Universitas Katolik Indonesia Atma Jaya 1st Winner of Scientific Paper Category

AMSA is the third organization I have joined during college. I realize that being a part of AMSA can accommodate many opportunities for me to improve even more, so I decided to become an AMSA member in my second year. Getting more experiences is one of the definite reasons I participated in this scientific competition. Entering a competition does not indicate you have to win that competition, yet you need to focus more on the process you have been through. Another reason why I joined PCC is that it can give me an opportunity to participate in an international conference. I think that communication between members will always be the key to success. Dedication and perseverance are also other factors that are also essential. COVID-19 pandemic has made me mostly free, so I was thinking to spend my free time by creating literature, and by chance, PCC AMSA was open for registration. A friend of mine also invited me to join PCC together so instead of looking for other competitions, participating in PCC is a better option for me, because there are friends who also interested in joining PCC. Honestly, Iâ&#x20AC;&#x2122;m the only junior in our group, and I thought I couldnâ&#x20AC;&#x2122;t do well compare to them. Nevertheless, they still teach me a lot about the systematic review. Therefore, I can contribute more than I thought

AMINO | PCC AMSC 2020: LONDON

Annisa Nur Insani AMSA-Universitas Pembangunan Nasional “Veteran” Jakarta 1st Winner of Scientific Poster Category

I think we can all agree that AMSA has given us so many opportunities in every aspect of its philosophies. Personally, AMSA has been the place for me to explore and to maximize my full potential. I’m very grateful to be a part of this family, joining AMSA was indeed one of the best decisions that I made in medical school! To be honest, my team and I didn’t expect much other than to gain new experiences and knowledge. Having learned all the theories and lessons, we knew that the only way we can really learn more is to put it into practice! Hopefully, this experience can be the start for us to explore more and participate in other competitions. I think eagerness and persistence are the key. Don’t be afraid to seek help from those who have experiences in this field. Look for advice from your teachers and fellows, it is really good to have a fresh pair of eyes when revising your work. Teamwork is also very vital for the whole process. At first, the four of us hesitated to join the competition because we were too focused on what could go wrong. But we realized that the thought of failing was not as scary as the regret of not trying! During the process, we went through a phase of trial and error, but I think that was where we learned the most. Needless to say, the process is the most important part.

AMINO | AMSC 2020: LONDON

Richard Pinarto AMSA-Universitas Hasanuddin 1st Winner White Paper and Video Category

AMSA is the right choice for me to develop my academic capabilities, social realization, and connection between medical students both in my university and other university. Being one member of AMSA-Unhas, I have started to find out the wider medical world. I have also participated in some national events before and as far as I know we can say that AMSA is like a complete “supermarket”. Everything you want, you will get it in AMSA. Starting from relation, knowledge, and of course action. Before join PCC AMSC 2020, I also joined and submitted a work in PCC EAMSC 2020. Unfortunately, my team haven’t had a chance to win there. So, I thought that “why I don’t give it a try in PCC AMSC 2020 too?”. To be honest, experience is what matter. Even if I win or lose, I just want to give the best, applicating more and more what I have just learned before. The opportunity for joining in PCC AMSC 2020 is my time to hone my ability to write a paper and make a videography. Truly, sometimes it takes a time to start writing, you should do a deep research and set a reasonable and achievable goals. Finding an expert or past competitor and learn from them is also another way to compete in the competition. Last but not least, prepare your mental. In some ways, it’s the most important part because if you’re not mentally sound, you won’t have the presence of mind to focus on the competition. We should have a commitment to get the work done and ambition to win the competition. Join the pre-conference competition of AMSA is a very perky way to participate in AMSA International Events. I have so many new knowledges and experiences from the competition. At first, it was very hard for me to find the idea and started to write, but with a short training from AMSA-Unhas about how to make a good paper and amazing videography, I and my team finally have a courage to give it a shot. Sincerely, this project was taking time, but the process is the important one. Because I and my team believe that every second of making this work is an enormous experience. It’s time for you to start now, VIVA AMSA!!!

AMINO | PCC AMSC 2020: LONDON

AMINO | AMSC 2020: LONDON TABLE OF CONTENTS

SCIENTIFIC PAPER...............................................................................................1 1st Winner The Potential of MicroRNA (miRNA) as a Novel Diagnostic Biomarker for Mild Traumatic Brain Injury: A Systematic Review................................................................................3 2nd Winner Antioxidants Supplementation as a Potential Therapy on Improving Neurobehavioural Status in Post Traumatic Brain Injury (TBI) Patients : A Systematic Review and Meta-Analysis...............................................................................................30 3rd Winner The Prognostic Value Of S100b Level As A Promising Biomarker Of Early Prognosis In Patients With Traumatic Brain Injury: A Systematic Review and Meta Analysis Of Cohort Studies................................................................................................63 The Importances of Promt Pre Hospital Care in Society to Raise Awareness of Accident Among Elderly People and Brainstorm For the Solution to the Problems of Accident to Improve Pre-Hospital Care by Societ...............................................................................93 The Role of Psychological Intervention on Mental Health Outcome in Post-Traumatic Stress Disorder Patients: A Systematic Review..............110 Injury Severity Score (ISS) Per Admission as a Predictor for Length of Hospital Stay in Multiple Trauma Adult Patients...................................................................127 Systematic Review of the Quality of Life after Traumatic Brain Injury.......136 Thromboelastography (TEG) as a Guiding Tool for Blood Transfusion in Patients With Trauma-Induced Coagulopathy: A Systematic Review.......................145 The Efficacy of Blood Transfusion in Damage Control Resuscitation (DCR) As a Non Invasive Life Saving Procedure for Severely Hemorrhagic Patients..........................162 The Contribution of Emergency Thoracotomy to the Survival Rate of Blunt Cardiac Injury Patients: A Systematic Review........................................................................174 Systematic Review of Effect of Interpersonal Psychodynamic Therapy for Women with Childhood Sexual Abuse Post-traumatic Stress Disorder............................ 183 Effectiveness of Trauma and Injury Severity Score (TRISS), Revised Trauma Score (RTS), and Injury Severity Score (ISS) in Predicting Mortality of Multiple Trauma in Adult Patients: A Systematic Review........................................................................................194

AMINO | PCC AMSC 2020: LONDON The Effect of Cognitive Behavioral Therapy on Reducing Symptoms of Post Traumatic Stress Disorder in Adults: A Systematic Review..............................................................210 Comparative Study of Thoracic Endovascular Aortic Repair (TEVAR) and Open Surgery (OS) as Interventions for Patients with Blunt Thoracic Aortic Injury (BTAI): A Systematic Review and Meta-Analysis.....................................................................................................222 The Relevance Of Traumatic Spinal Cord Injury In Military Veterans With Mental Health Disorder And Government Support: A Systematic Review ........................240 Systematic Review on The Prevalence of Bipolar Disorder in Traumatic Brain Injury Patient as The Leading Cause of Psychiatric Disorder ..................................................258 Effectiveness of Extracorporeal Shockwave Therapy in Acute and Chronic Soft Tissue Wound Healing: A Systematic Review ........................................................................269 Understanding The Factor Of Ambulance Delay And Ambulance Crash To Find A Breakthrough For Enhancing Ambulance Efficiency: A Systemic Review ........................286 Handling Trauma in Elderly Patient ...............................................................304 Wound Dressings Comparison in Pain Infliction for Second-degree Pediatric Burn : A Systematic Review ...........................................................................................315

SCIENTIFIC POSTER........................................................................................341 1st Winner CSF Biomarkers to Predict Injury Severity and Predicting Neurological Recovery In Human Traumatic Spinal Cord Injury...........................................................................343 2nd Winner Knowledge, Attitude, and Practice of First Aid in Road Traffic Accidents Settings Among Online Motorcycle Drivers in Surabaya: A Cross-Sectional Study ...........................344 3rd Winner Indonesian Communityâ&#x20AC;&#x2122;s Healthcare Seeking Behaviors Related to Bone Fracture: The Importance of Having BPJS Health Insurance and Choosing Orthopaedic Medical Treatment over Traditional Bonesetter ............................................................................345 REBOA (Rescucitative Endovascular Balloon Occlusion of the Aorta) as a Novel Pre-Hospital Method in NCTH (Non Compressible Pelvic Trauma Hemorrhage): A Systematic Review 346 The Effect of Therapeutic Hypothermia in Traumatic Brain Injury Management :A Systematic Review ...............................................................................................................347

AMINO | AMSC 2020: LONDON Danger of Lateness in Handling and Advantages of Initial Handling of Trauma Jellyfish Stings ....................................................................................348 The Effectiveness of Topical Sucralfate versus Sulfadiazine in Partial Thickness Burn Healing ..................................................................349 The Efficacy of Honey as a Treatment of Diabetic Foot Ulcer: A Systematic Review ...............................................350 Prehospital Management: Limb Fracture Treatment in Traffic Accident ............................................................................................351 Radionuclide Pet Signal as a Modality in Chronic Traumatic Encephalopathy Early Detection ..............................352 Systematic Review on The Prevalence of Bipolar Disorder in Traumatic Brain Injury Patient as The Leading Cause of Psychiatric Disorder ..................................................353 Relationship Time Transportation and Transportation Home Hospital with Complication and Prognosis in Patient Injuries Head Medium to Heavy .................................354 Diagnostic Performance of Glial Fibrillary Acidic Protein as A Biomarker for Mild Traumatic Brain Injury among Children: A Systematic Review and Meta-Analysis of Cohort Studies .............................................................355 Evaluation of Ambulance Emergency Call Services in Pre-Hospital Care: A Systematic Review .......................................................................................356 Bioresorbable Polymer-based and Allograft Scaffold Augmentation in Massive Rotator Cuff Tears: A Systematic Review of Clinical Trials ...............................................357 Hyperglycemia on Admission Related Mortality in Patients with Severe Traumatic Brain Injury: A Systematic Review & Meta-Analysis ..............................................................358 Clover Flower Honey and Binahong (Anredera codifolia) Positive Effects to Wound Healing Parameters .......................................................................................................359 Tranexamic Acid Novel Usage as Antifibrinolytics Agent in Preventing Head Injury-related Death and Disability from Traumatic Brain Injury Patients. ...................................360 Mortality Rate in Trauma Patients Following Massive Transfusion with High Plasma to PRBC Ratio: A Systematic Review & Meta-Analysis ................................................361 Diagnostic Performance of Glial Fibrillary Acidic Protein as A Biomarker for Mild Traumatic Brain Injury Patient: A Systematic Review and Meta-Analysis ....................362

AMINO | PCC AMSC 2020: LONDON WHITE PAPER AND VIDEO...........................................................................363 1st Winner Innovation Towards Emergency Medical System With M-Bulance Application Involving Emergency Button To Minimize Road Trauma Death In Indonesia...........365 2nd Winner Be Aware, Don Play With Fire: First Aid Treatment Of Bruns To Mitigate Adverse Effects Due To The Wrong Handling In Community ..............................................................375 3rd Winner Lifesaving Lesson Since the Beginning: Inclusion of CPR in Indonesian Education System ....................................................................382

Improving Pre-hospital Trauma Care System in Asia ..................................388 Everlasting Anguish ..........................................................................................400

AMINO | AMSC 2020: LONDON

AMINO | PCC AMSC 2020: LONDON

The Potential of MicroRNA (miRNA) as a Novel Diagnostic Biomarker for Mild Traumatic Brain Injury: A Systematic Review Ghea Mangkuliguna1a, Rexel Kuatama1, Nikolaus Tobian1, Yulian Prastisia1 1

Undergraduate Medical Program, School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia a

mangkuligunaVG1402@yahoo.com

ABSTRACT Introduction: Mild traumatic brain injury (mTBI) accounts for at least 80% of all cases of traumatic brain injury. Even though the majority of patients with mTBI recovers immediately, however, around 10-20% of patients will develop long-term cognitive and behavioural alterations which results in postconcussive syndrome and chronic traumatic encephalopathy (CTE). Current diagnostic techniques, such as Computed Tomography (CT) and Magnetic Resonance Imaging (MRI), yield obvious drawbacks in identifying micro-lesions/bleeds commonly occurred in mTBI patients. Protein biomarkers, such as S-100β, GFAP, and UCH-L1, are not very useful for mTBI patients with no detectable brain lesions. Therefore, it is necessary to develop new markers that can be used to accurately distinguish mTBI patients from healthy persons as early as possible. Recently, microRNAs (miRNAs) have shown altered expression in humans’ blood, saliva, and CSF can be molecular signature in distinguishing patients with mTBI and normal healthy people, hence miRNAs are promising diagnostic biomarkers for mTBI. Objective: This study will investigate the potential of miRNA as a diagnostic biomarker for mild TBI. Materials and Method: This systematic review is reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. Literature search is carried out in electronic databases, such as PubMed, ScienceDirect, and ProQuest. The outcome is evaluated by using summary receiver operating characteristics (sROC) curve that will calculate diagnostic accuracy in the form of areas under the curve (AUC) for each miRNA. The quality of each study is assessed using Quality Assessment of Diagnostic Accuracy Studies – 2 (QUADAS 2). Key Findings: Twelve studies were included in the meta-analysis. Among all of the miRNAs found in patients serum/plasma, miR-425-5p, miR-502, and miR-93 show the highest AUCs of 1, meaning the miRNAs are excellent in diagnosing mTBI. miR-92a has the highest diagnostic accuracy (AUC=0.860) when miRNA level is assessed from the CSF. Meanwhile, the combination of miR-10b-5p, miR-30b5p, miR-3678-3p, miR-455-5p, miR-5694, miR-6809-3p, and miR-92a-3p has shown diagnostic accuracy of 0.890 when patients’ saliva is used to detect miRNAs. Another study using miRNAs from brain-derived extracellular vesicles from plasma yields AUC value of 0.900 by using the combination of miR-129–5p and miR-9–5p. Overall, this study reveals that miRNAs have very good to excellent diagnostic accuracy in distinguishing patients with mTBI and healthy people. Conclusion: This systematic review provides qualitative evidence suggesting miRNA as a potential diagnostic biomarker for mTBI. Keywords: diagnostic biomarker; microRNA; mild traumatic brain injury; systematic review

The Potential of MicroRNA (miRNA) as a Novel Diagnostic Biomarker for Mild Traumatic Brain Injury: A Systematic Review

Author: Ghea Mangkuliguna Rexel Kuatama Nikolaus Tobian Yulian Prastisia

School of Medicine and Health Science Atma Jaya Catholic University of Indonesia Asian Medical Studentsâ&#x20AC;&#x2122; Association-Indonesia 2020

Currently, Computed Tomography (CT)

Introduction Traumatic brain injury (TBI) is defined

scanning and Magnetic Resonance Imaging

as acquired brain injury resulting from an

(MRI) are mainly used to detect the extent of

external physical force which damages the

brain damage. However, CT-scan is not

brain (Hyder et al., 2007). It is a major cause of

sensitive enough to detect brain injuries in

long-lasting

trauma-related

mTBI because of the absence of lesions and

deaths worldwide (Dewan et al., 2018; Maas et

micro-bleeds in almost all mTBI patients. A

al., 2017). The spectrum of disease ranges from

more advanced imaging techniques, MRI, is

mild to severe, with mild traumatic brain injury

proven to be more sensitive than CT-scan,

(mTBI)

also known as concussion accounts

however the implementation of this technique

for at least 80% of the cases (LaRocca et al.,

is often limited due to the high cost and low

2019; Omalu, 2014; Yan et al., 2019; Yang et

availability (Bhomia et al., 2016; Delouche et

al., 2016).

al., 2016; Levin & Diaz-Arrastia, 2015;

disability

and

Even though the majority of patients

Maegele et al., 2017; Qin et al., 2018; Shin et

with mTBI recovers immediately, however,

al., 2017; Yan et al., 2019). Several protein

around 10-20% of patients will develop long-

markers found in blood, urine, cerebrospinal

term cognitive and behavioural alterations

fluid (CSF), or saliva, such as S-100 calcium

which results in post-concussive syndrome and

binding protein (S-100 ), Glial Fibrillary

chronic

(CTE)

Acidic Protein (GFAP) and Ubiquitin C-

(Bhomia et al., 2016; Omalu, 2014; Pogoda et

Terminal Hydrolase-L1 (UCH-L1), have been

al., 2012; Yan et al., 2019; Yang et al., 2016).

proposed to be diagnostic biomarkers in severe

The overlying mechanism is thought to be the

traumatic brain injury (sTBI). However, it is

induction of percussive and/or rotational injury

reported that these protein biomarkers have

to the brain. This process leads to parenchymal

relatively low sensitivity in detecting mTBI

bruising and subarachnoid bleeding which

patients with no detectable brain lesions, and

eventually cause cell deaths and diffuse axonal

thus are not approved for clinical use (Adrian et

injury that persist for years (Johnson et al., 2013;

al., 2016; Bhomia et al., 2016; Papa et al., 2015;

LaRocca et al., 2019). Correctly diagnosing

Qin et al., 2018; Thelin et al., 2017; Yang et al.,

mTBI has become a challenge because no

2016; Zetterberg & Blennow, 2016). Therefore,

initial injuries or lesions are detected using

it is necessary to develop new markers that can

neuroimaging techniques, while at the same

be used to accurately distinguish mTBI patients

time the condition becomes more progressive

from healthy persons as early as possible.

traumatic

encephalopathy

Recently, researchers have shifted their

across time. Therefore, early and accurate diagnosis of mTBI is particularly important for

focus

identifying

those with greater risk of repetitive mTBI, such

molecules that play a role in regulating both

as athletes, military personnel and children

physiological and pathological processes in

(LaRocca et al., 2019; Yan et al., 2019).

central

nervous

small

system

endogenous

(CNS)

disease, 2

including TBI (Ji et al., 2018; Martinez &

Type of Studies

Peplow, 2017). This molecule, known as

Randomized-controlled trials, cross-

microRNA (miRNA), belongs to a novel class

sectional, cohort, and case-control studies are

of small non-coding RNAs ranging from 17 to

included. Review, case report, case series, and

25 nucleotides in length (Flynt & Lai, 2008;

conference

LaRocca et al., 2019; Qin et al., 2018; Yan et

commentaries/editorials

al., 2019; Yang et al., 2016). Accumulating

Laboratories and non-human studies are not

evidences have shown that altered expression of

included

miRNA in h mans blood, sali a, and CSF can

unavailable full-text, languages other than

be molecular signature in distinguishing

English, and irrelevant topics are also omitted.

abstracts,

well.

book are

Lastly,

sections, excluded.

articles

with

patients with mTBI and normal healthy people (Bhomia et al., 2016; Di Pietro et al., 2017,

Participants

2018; Hicks et al., 2018; J. Ko et al., 2018; Jina

All patients with/without symptoms of

Ko et al., 2019; LaRocca et al., 2019; Papa et

concussion or mTBI are included for this study.

al., 2019; Qin et al., 2018; Redell et al., 2010;

There is no limitation for age, gender, races,

Yan et al., 2019; Yang et al., 2016). This

and history of treatment.

findings also suggested that brain-specific miRNAs related to the pathological processes

Index Test

of TBI are released to the peripheral biofluids,

Studies evaluating miRNA altered

hence miRNAs are promising diagnostic

expression in biofluids to distinguish between

biomarkers for mTBI. This systematic review

normal healthy people (no evidence of any

will investigate the potential of miRNA as a

diseases) from those with mTBI in clinical

diagnostic biomarker for mild TBI.

setting.

Materials and Method

Target Condition Studies include all cases of concussion or mTBI with/without clinical symptoms

Study Registration and Methodology This systematic review is reported

observed. Imaging modality, such as CT-scan,

following the Preferred Reporting Items for

shows no abnormality in the patients head.

Systematic

Glasgow Coma Scale (GCS) shows value

Reviews

and

Meta-Analyses

ranging from 13-15 indicating there is no to

(PRISMA) criteria (Moher et al., 2009).

mild neurological injury (Heather et al., 2013; Irimia et al., 2017; Teasdale et al., 2014).

Eligibility Criteria The following criteria are considered for

s dies

eligibili :

Reference Standard

s d ,

The reference standard is a clinical

participants, index test, target condition, and

examination

reference standards.

performed

qualified 3

Quality Assessment

professionals by comparing miRNA expression in normal and mTBI.

Each study are assessed for their quality by using Quality Assessment of

Data Sources and Search

Diagnostic Accuracy Studies 2 (QUADAS 2).

Literature search is carried out with

This tool consists of 4 key domains: patient

multiple electronic databases, such as PubMed,

selection, index test, reference standard, and

ScienceDirect, and ProQuest. No time and

flow and timing. Each domain is evaluated for

language restriction is applied. The keywords

risk of bias, and the first 3 domains are also

used are presented in Table 1.

evaluated for concern regarding applicability to the research question (Whiting et al., 2011). Any discrepancies will be resolved by

Study Selection Articles

are

discussion among the review team.

identified using the

keywords described above. After removing duplicates using EndNote program, retrieved

Results

articles are screened based on their titles and Search Results

abstracts. Thereafter, potentially eligible fulltext articles are thoroughly assessed using the eligibility criteria described

above.

Search in electronic database yielded

Any

4484 studies. Screening through titles and

emerging discrepancies will be resolved by

abstracts found 867 articles, 55 of which met

consensus among the review team. The planned

the inclusion criteria. A total of 12 studies were

procedure is illustrated in Figure 1.

included in the systematic review at last (Bhomia et al., 2016; Di Pietro et al., 2017,

Data Extraction

2018; Hicks et al., 2018; J. Ko et al., 2018; Jina

The following data is extracted from

Ko et al., 2019; LaRocca et al., 2019; Papa et

the included studies: first author, publication

al., 2019; Qin et al., 2018; Redell et al., 2010;

year, region, study design, age, gender, sample

Yan et al., 2019; Yang et al., 2016). Search

size, sample sources, sample collection timing,

flowchart and selection methods used this meta-

RNA

analysis was summarized in Figure 1.

profiling

platform,

and

miRNA

dysregulation. The outcome is evaluated by using

summary

receiver

Characteristics of Included Studies

operating

characteristics (sROC) curve that will calculate

Twelve

studies

evaluated

the

diagnostic accuracy in the form of areas under

diagnostic accuracy of miRNA when used in

the curve (AUC) for each miRNA. Test

patients with mTBI (Bhomia et al., 2016; Di

accuracy is defined based on the corresponding

Pietro et al., 2017, 2018; Hicks et al., 2018; J.

AUC: <0.5 (not useful), 0.5-0.6 (bad), 0.6-0.7

Ko et al., 2018; Jina Ko et al., 2019; LaRocca

(sufficient), 0.7-0.8 (good), 0.8-0.9 (very good),

et al., 2019; Papa et al., 2019; Qin et al., 2018;

and 0.9-1.0 (excellent).

Redell et al., 2010; Yan et al., 2019; Yang et al., 4 7

2016). Two studies assessed the accuracy of

The Potential of MicroRNAs to Distinguish

miRNA in distinguishing mTBI from sTBI (Di

Patients with Mild Traumatic Brain Injury from

Pietro et al., 2017; Yan et al., 2019). Most of the

Healthy People

included studies are conducted in United States,

Twelve

studies

evaluated

the

followed by China and United Kingdom. The

diagnostic

type of studies included are case control (1

distinguishing mTBI patients from normal

study) and cohort (11 studies). Two studies

healthy people. The sources of miRNA come

used adolescents as study population, while the

from the serum/plasma, CSF, saliva, and brain-

rest of the studies used ad l s population. Most

derived extracellular vesicle from plasma.

accuracy

miRNA

study subjects mainly comprises of male. Seven

The earliest study evaluating the

studies used miRNA derived from blood

diagnostic accuracy of circulating miRNAs was

plasma/serum, 2 studies from CSF, 3 studies

conducted by Redell et al. in 2010. This study

from saliva, and 2 studies from brain-derived

was using 11 mTBI patients and 8 healthy

extracellular vesicle from plasma. Almost all of

controls. The key findings of this study

the included studies used Polymerase Chain

included: (1) The significant elevation of miR-

Reaction (PCR) as method of miRNA profiling,

16 and miR-92a in plasma of mTBI patients;

followed by Next Generation Sequencing

and (2) The ability of miR-16 and miR-92a to

(NGS), Microarray, and TaqMan Low Density

distinguish

Array (TLDA). Gathered data from 899

controls with a diagnostic accuracy of 0.82 and

subjects (351 of normal, 437 of mTBI, and 111

0.78, respectively (Redell et al., 2010). miR-

92a is further assessed in a study conducted by

sTBI)

Characteristics

were of

analyzed included

together. studies

are

mTBI

patients

from

healthy

Papa et al. in 2019. This study included 23

presented in Table 2.

mTBI samples from football players and 30

Table 3 shows methodological quality

non-athlete control subjects. Contrary to the

assessment of included studies according to

study by Redell et al., miR-92a showed higher

QUADAS-2. Most of the included studies show

AUC of 0.92 and is categorized as having

unclear risk of bias regarding patient selection

excellent diagnostic accuracy. miR-195 also

as the studies do not clearly explain how the

achieved the same result, followed by miR-30d,

samples are recruited. Two of the studies have

miR-505, miR-151-5p, and miR-362-3p. All of

high risk of bias of patient selection. One study

these miRNAs are significantly upregulated in

is using case-control design, while another is

mTBI subjects (Papa et al., 2019).

using controlled-non-randomized method in

Qin

al.

demonstrated

altered

recruiting study samples. Regarding index tests,

miRNAs expression of mTBI patients in a study

reference standard, and flow and timing, all of

that included 75 subjects. Six miRNAs that

the included studies have low risk of bias and

were identified: miR-762, miR-3665, miR-

applicability concerns.

2861, miR-4669, miR-3195, miR-855, and 0.765. The diagnostic accuracy of these 5 8

miRNAs ranged from 0.765 to 0.921 with miR-

evidence that brain-specific miRNA in CSF

762 being the highest (Qin et al., 2018). Other

could be found in peripheral bloodstream

study by Di Pietro et al. using 90 adults revealed

suggesting its clinical use as diagnostic

that 2 miRNAs that were significantly

biomarker.

downregulated in patients with mTBI as early

successfully identified and had been proven to

as 0-1 hour post injury. miR-425 and miR-502

be significantly upregulated in mTBI. These

have become ideal candidates for mTBI

were the miRNAs reported in the study: miR-

biomarkers for having excellent diagnostic

92a, miR-451, miR-505, miR-195, miR-486,

accuracy as shown in AUC equals to 1.

miR-362-5p, miR-20a, miR-30d, miR-328, and

Moreover, miR-425 has also shown promise as

miR-151 with AUC ranging from 0.66 to 0.92.

a predictive biomarker when 6-month outcome

miR-92a has shown the highest AUC score,

is assessed during 0-1 hour after injury (Di

indicating that this miRNA has excellent

Pietro et al., 2017).

diagnostic accuracy (Bhomia et al., 2016). A

There

were

miRNAs

In a study conducted by Yan et al., 7

similar finding is reported by Hicks et al whose

miRNAs, including miR-103a-3p, miR-219a-

study is using adolescents with mean age of

5p, miR-302d-3p, miR-422a, miR-518f-3p,

14Âą3. A combination of miRNAs (miR-182-5p,

miR-520d-3p, and miR-627, were significantly

miR-221-3p, mir-26b-5p, miR-320c, miR-29c-

upregulated in 81 mTBI patients compared with

3p, miR-30e-5p) gave an AUC of 0.860,

their expression in 82 age/sex-matched controls.

indicating very good diagnostic accuracy in

The AUC ranged from 0.747 to 0.847 (Yan et

distinguishing mTBI from normal healthy

al., 2019). Similar findings are reported by

people. Additionally, several miRNAs from

Yang et al whose study included 76 TBI

this study were associated with medical

patients and 38 healthy controls. Three

characteristics in clinical setting. There was

miRNAs found in the serum

miR-93, miR-

inverse correlation between miR-26b-5p levels

had been proven their

with medical reports of I ge ired a lo and I

ability in distinguishing TBI patients from

ge ired easil . A direc correla ion was also

healthy controls. The AUCs of miR-93, miR-

observed between the levels of miR-320c and

191, and miRNA-499 were 1.000, 0.727, and

I da dream oo m ch , I ge conf sed , has

0.801, respectively. In addition, these miRNAs

ro ble s s aining a en ion , as

were also predictive in determining patients

easil dis rac ed (Hicks et al., 2018).

191, and miRNA-499

outcome

ell as is

The same study conducted by Hicks et

the higher the expression level, the

al. also revealed that the same set of miRNAs

poorer the outcome (Yang et al., 2016). Bhomia et al. conducted a research on

could be fo nd in h mans sali a i h he same

identifying a panel of miRNAs that could be

diagnostic accuracy as in CSF (Hicks et al.,

found both in mTBI and sTBI patients. This

2018). Another study by LaRocca et al.

study used 15 mTBI and 8 control samples with

evaluated the diagnostic accuracy of miRNAs

mean age of 36Âą16. This study also provides

ad l s mar ial ar figh ers sali a samples. This 6 9

study included a total of 50 samples with mean

The Potential of MicroRNAs to Distinguish

age of 26.5Âą5.8. The combination of miR-10b-

Patients with Mild Traumatic Brain Injury from

5p, miR-30b-5p, miR-3678-3p, miR-455-5p,

Severe Traumatic Brain Injury

miR-5694, miR-6809-3p, and miR-92a-3p had shown

very

good

diagnostic

A study conducted by Di Pietro et al.

accuracy

analyze miRNA from blood serum at different

(AUC=0.890) and demonstrated quantitative

time points in 120 patients equally separated

associations with head impacts as well as

into mTBI, sTBI, extra-cranial injury, and

cognitive and balance measures. This miRNAs

healthy groups. The study reported that in

were also observed in mTBI patients serum and

mTBI patients, miR-425-5p and miR-502 were

had proven to give similar diagnostic accuracy

both significantly decreased at T0-T1h and T4-

(LaRocca et al., 2019). Other study by Di Pietro

12h compared to other groups. Both miRNA

et al. also evaluated the diagnostic utility of

went to normal level after 48 hours. In sTBI,

miRNAs in 22 athletes with concussion. There

miR-21 were found increased in T>4h while

were 5 miRNAs detected in the saliva that

miR-335 increased at all time points. All

significantly upregulated in concussed athletes.

biomarkers

These were the miRNAs reported: miR-27b-3p,

distinguishing mTBI or sTBI from healthy

let-7i-5p, miR-142-3p, miR-107, miR-135b-5p.

group. When comparing between mTBI and

The AUC ranged from 0.732 to 0.845 and the

sTBI group, AUC showed good to excellent

highest AUC was observed in let-7i-5p (Di

value ranging from 0.780-0.990. Furthermore,

Pietro et al., 2018).

miR-425-5p at T0-1h T4-12h and miR-21 at

showed

excellent

AUC

Ko et al. assessed the miRNAs from

T4-12h showed significant correlation with

brain-derived extracellular vesicle from plasma.

extended Glasgow Outcome Scale (GOS) 6

The first cohort study conducted in 2018 was

months post injury (Di Pietro et al., 2017).

using 60 subjects, while the second one in 2019

A similar study was also conducted by

was using 36 subjects. Two sets of miRNAs

Yan et al. Blood samples from 81 sTBI and

were identified and reported to be significantly

mTBI patients were analyzed for possible

altered in mTBI. The first set included miR-

miRNA biomarkers. Seven miRNA; miR-103a-

129-5p and miR-9-5p with AUC equals to 0.90,

3p, miR-219a-5p, miR-302d-3p, miR-422a,

while the second set included miR-203b-5p,

miR-518f-3p, miR-520d-3p and miR-627 were

miR-203a-3p, miR-206, and miR-185-5p with

found elevated in mTBI and sTBI compared to

AUC equals to 0.84 (J. Ko et al., 2018; Jina Ko

healthy groups with AUC ranging from 0.747-

et al., 2019).

0.853. Out of these mRNA, the levels of miR-

Summary of findings of this section is

219a-5p, miR-422a and miR-520d-3p were

presented in Table 4.

found to be significant in distinguishing mTBI and sTBI with AUC 0.643, 0.616, 0.593, respectively. miR-219a-5p also showed both correlation with Marshall classification in CT 7 10

findings and GOS score 6 months after (Yan et

secondary

lesions,

and

genetic

profile

al., 2019).

determine the evolution of SIRS. There are some stages noted after traumatic events: hyperinflammation, equilibrium state (decrease

Discussion MicroRNA is a non-coding sequence

of proinflammatory mediators and increase of

of RNA which generated around 19-24

anti-inflammatory mediators), and last anti-

nucleotides. It undergoes transcription of

inflammatory response syndrome (CARS)

protein encoding gene by polymerase II enzyme

(increased

and produces the primary form of microRNA

mediators). Depending on pathophysiological

(pri-microRNA). Then pri-microRNA will be

aspects, SIRS and CARS could progress into

transformed to be mature microRNA precursor

multiple

(pre-microRNA) by polyadenylation process.

Endothelial dysfunction is also responsible for

This process needs a polymerase III enzyme

inflammatory response. The activation of

and DiGeorge critical region 8 complex. Then

nuclear

the pre-microRNA will be transferred to

modulates vascular cell adhesion molecules and

cytoplasm and become double-stranded mature

proinflammatory

microRNA. There are two passages for

miRNAs are responsible for activation of NF-

microRNA to enter systemic circulation. First

kB pathway, and thus responsible for sepsis and

by active release which microRNA transported

inflammation experienced by patients.

concentration

organ

factor

inflammatory

dysfunction

(MODS).

transcription-kB cytokines

(NF-kB)

(Figure

2).

using microvesicle, exosomes, and high-

Laboratories studies revealed that the

density lipoproteins. Second by passive release

altered expression miRNAs induced neuronal

which microRNA released to the plasma during

cell deaths following TBI (Han et al., 2014; Li,

apoptosis in the form of apoptotic bodies.

Huang, Yin, et al., 2019; Li, Huang, Zhu, et al.,

miRNAs can be found in various types of fluids

2019; Sabirzhanov et al., 2016; Sun et al., 2017).

of the human body, such as saliva, tears, urine,

Later, in vivo studies demonstrated the link

cerebrospinal fluids, and many more, including

between miRNAs and pathological processes in

peritoneal fluid, breast milk and bronchial

TBI (Balakathiresan et al., 2012; Chandran et

lavage (Bedreag et al., 2015; Weber et al.,

al., 2017; Ge et al., 2014; Huang et al., 2018;

2010).

Liu et al., 2014; Lv et al., 2018; Redell et al., After a traumatic event, patients

2009; Sandhir et al., 2014; Sharma et al., 2014;

experienced systemic inflammatory response

Sun et al., 2018; Vuokila et al., 2018; Wang et

syndrome (SIRS). If there are excessive

al., 2020; Zhang et al., 2019). Taken together,

production of proinflammatory molecules,

these findings demonstrated the potential of

activation

miRNAs utility in clinical setting of TBI.

coagulation

cascade,

physiological

To the best of our knowledge, there is

imbalances, SIRS can develop into sepsis. The

no comprehensive study conducted until now

severity of a trauma and post-traumatic

that evaluate the ability of miRNAs to

hypermetabolism,

and

8 11

discriminate mTBI and normal healthy people.

combination of miR-129 5p and miR-9 5p.

This systematic review includes 12 studies to

Overall, this qualitative study reveals that

assess the diagnostic accuracy of miRNAs for

miRNAs have very good to excellent diagnostic

mTBI. Among all of the miRNAs found in

accuracy in distinguishing patients with mTBI

patients serum/plasma, miR-425-5p, miR-502,

and healthy people.

and miR-93 show the highest AUCs of 1, meaning the

miRNAs

are

excellent

Strengths and Limitations

diagnosing mTBI. In addition, miR-502 also

The current study has several strengths.

shows the most prominent accuracy when

This is the first systematic review investigating

differentiating

mild

TBI

the diagnostic accuracy of miRNAs in

(AUC=0.990).

miR-92a

highest

distinguishing patients with mTBI and normal

when

healthy people, as well as comparing the AUCs

miRNA level is assessed from the CSF. miR-

of severals miRNAs identified across included

92a can also be found in patients sera and have

studies. This paper also presents evidences that

higher

its

miRNAs expression in normal people, mTBI,

counterpart in CSF (AUC=0.920). Previous

and sTBI patients are significantly different,

study conducted by Redell et al. in 2010 shows

hence their potential role as a diagnostic

miR-92a with a much lower diagnostic

biomarker for mTBI. Finally, all of the included

accuracy of 0.780, even though miR-92a is

studies show low risk of bias and applicability

derived from patients sera. Other miRNAs

concerns in term of index test, reference

have also been detected both in patients sera

standard, and flow and timing.

diagnostic

accuracy

AUC

value

from has

severe the

(AUC=0.860)

compared

with

and CSF. Similar to the previous results,

The

current

study

has

several

miRNAs evaluated in serum show higher

limitations. First, a larger sample size is

diagnostic accuracy compared with the ones

required for this systematic review to be

detected in CSF, as shown in miR-195 (0.920

representative

vs 0.810), miR-30d (0.860 vs 0.750), and miR-

Included studies mostly originate in United

505 (0.830 vs 0.820). These events might be the

States, followed by China and United Kingdom.

result of different in methodology across

Second, the limited evidence available implies

studies as well as the sample being used.

that this systematic review must be interpreted

Meanwhile, the combination of miR-10b-5p,

with caution. Third, despite showing no

miR-30b-5p, miR-3678-3p, miR-455-5p, miR-

concerns in regards of applicability, this paper

5694, miR-6809-3p, and miR-92a-3p has

shows unclear risk of bias in term of patient

shown diagnostic accuracy of 0.890 when

selection. Almost all the included studies do not

patients saliva is used to detect miRNAs.

specifically address the methods of sample

Another study using miRNAs from brain-

recruitment.

worldwide

population.

derived extracellular vesicles from plasma yields AUC value of 0.900 by using the 9 12

Adrian, H., MĂĽrten, K., Salla, N., & Lasse, V.

Conclusion This systematic review revealed that

(2016). Biomarkers of Traumatic Brain

miRNAs expression are significantly altered in

Injury: Temporal Changes in Body

patients with mTBI. miRNAs found in

Fluids. Eneuro, 3(6), ENEURO.0294-

serum/plasma, CSF, saliva, and brain-derived

16.2016.

extracellular vesicles from plasma could be

https://doi.org/10.1523/ENEURO.029

molecular signatures in patients with mTBI

4-16.2016

whose injuries are not detectable with the

Balakathiresan, N., Bhomia, M., Chandran, R.,

current diagnostic techniques. This paper

Chavko, M., McCarron, R. M., &

reveals that miRNAs have very good to

Maheshwari, R. K. (2012). MicroRNA

excellent diagnostic accuracy in distinguishing

let-7i is a promising serum biomarker

patients with mTBI and healthy people. Hence,

for blast-induced traumatic brain injury.

this systematic review provides evidences for

Journal of Neurotrauma, 29(7), 1379

the use of miRNAs as a potential diagnostic

1387.

biomarker for mild traumatic brain injury.

PubMed.

https://doi.org/10.1089/neu.2011.2146 Bedreag, O. H., Rogobete, A. F., Dumache, R.,

Recommendation

Sarandan,

Further comprehensive studies should

M.,

Cradigati,

C.,

be done to investigate the extent of altered

Papurica, M., Craciunescu, M. C., Popa,

miRNAs expression in mTBI, as it would serve

D. M., Luca, L., Nartita, R., & Sandesc,

as a foundation for future research in mTBI

biomarker. Moreover, we recommend more

microRNAs as biomarkers in critically

studies done in Asian, European, Australian,

ill polytrauma patients. Biomarkers and

and

the

Genomic Medicine, 7(4), 131 138.

applicability of this diagnostic tool worldwide.

https://doi.org/10.1016/j.bgm.2015.11.

African

countries

confirm

(2015).

Use

circulating

002 Conflict of Interest

Bhomia, M., Balakathiresan, N., Wang, K.,

The author declares that there are no competing

Papa, L., & Maheshwari, R. (2016). A

interests in this study.

Panel of Serum MiRNA Biomarkers for the Diagnosis of Severe to Mild

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17 20

Appendix

Figure 1. PRISMA Flow Diagram

18 21

Figure 2. Mechanism of Injury Following Trauma (Bedreag et al., 2015)

19 22

Table 1. Search Keywords Databases Pubmed

Keywords ("MicroRNAs"[Mesh]

"MicroRNA"[Title/Abstract]

Articles

"MicroRNAs"[Title/Abstract]

"MicroRNAs"

[Title/Abstract]

207

"miRNA"[Title/Abstract] OR "miRNAs"[Title/Abstract] OR "non coding RNA"[Title/Abstract]) "Traumatic

Brain

AND

("Brain

Injuries,

Injury"[Title/Abstract]

Traumatic"[Mesh]

"Traumatic

OR Brain

Injuries"[Title/Abstract] OR "TBI"[Title/Abstract] OR "Mild Traumatic Brain Injury"[Title/Abstract] OR "Mild Traumatic Brain Injuries"[Title/Abstract] OR "mTBI"[Title/Abstract] OR "Traumatic Head Injury"[Title/Abstract] OR "Traumatic Head Injuries"[Title/Abstract] OR "Mild Traumatic Head Injury"[Title/Abstract] OR "Mild Traumatic Head Injuries"[Title/Abstract] OR "concussion"[Title/Abstract]) ScienceDirect

("microRNA" OR "microRNAs" OR "miRNA" OR "miRNAs" OR "non coding

1307

RNA") AND ("traumatic brain injury" OR "traumatic brain injuries" OR "TBI" OR "mild traumatic brain injury" OR "mild traumatic brain injuries" OR "mTBI" OR "traumatic head injury" OR "traumatic head injuries" OR "mild traumatic head injury" OR "mild traumatic head injuries" OR "concussion") ProQuest

("microRNA" OR "microRNAs" OR "miRNA" OR "miRNAs" OR "non coding

2970

20 23

Table 2. Characteristics of Included Studies

Author, Year

Bhomia et al., 2016

Di Pietro et al., 2017

Di Pietro et al., 2018

Region

United States

United Kingdom

Study Design

Cohort

Hicks et al., 2018

United States

Cohort

Ko et al., 2018

United States

Cohort

Age (MeanÂąSD)

mTBI: 36 (16)

sTBI: 38.5 (18.4) mTBI: 39.2 (23.9) N: 42 (15.8)

Concussion: 23.3 (3.4) N: 25.3 (2.6)

mTBI: 14 (3) N: 14 (3)

Gender

mTBI: M(14), F(1)

sTBI: M(21), F(9) mTBI: M(23), F(7) N: M(19), F(11)

Concussion: M(10),F(0) N: M(22),F(0)

mTBI: M(30), F(30) N: M(11), F(7) -

Sample Size

mTBI: 15 N: 8

sTBI: 30 mTBI: 30 N: 30

Concussion: 22 N: 10

mTBI: 60 N: 18

TBI: 28 N: 32

Sample Sources

CSF

Serum

Saliva

CSF, Saliva

Brain-derived extracellular

Sample Collection Timing

24 hr

0-1 hr, 4-12 hr

48-72 hr

Platform

TLDA/ RT-PCR

Microarray/ RT-PCR

14 days

NGS

1 hr, 1 day, 4 days, 14 days

NGS/ qPCR

AUC

miRNA Studied

mTBI*

miR-195

0.81

Upregulated

miR-30d

0.75

Upregulated

miR-451

0.82

Upregulated

miR-328

0.73

Upregulated

miR-92a

0.86

Upregulated

miR-486

0.81

Upregulated

miR-505

0.82

Upregulated

miR-362-5p

0.79

Upregulated

miR-151

0.66

Upregulated

miR-20a

0.78

Upregulated

miR-425-5p

0.911

Downregulated

miR-502

0.990

Downregulated

miR-27b-3p

0.755

Upregulated

sTBI

miRNA Dysregulation

let-7i-5p

0.845

Upregulated

miR-142-3p

0.791

Upregulated

miR-107

0.732

Upregulated

miR-135b-5p

0.755

Upregulated

Combined miR-182-5p miR-221-3p mir-26b-5p miR-320c miR-29c-3p miR-30e-5p miR-129 5p miR-9 5p

0.836

Upregulated Downregulated Downregulated Downregulated Downregulated Upregulated Upregulated Upregulated Upregulated

0.852

0.90

Ko et al., 2019

LaRocca et al., 2019

Papa et al., 2019

Qin et al., 2018

Redell et al., 2010

Yan et al., 2019

United States

China

United States

China

Cohort

Multiphase, case-control

mTBI: M(48),F(2)

26.5 (5.8)

mTBI: M(23), F(0) N: M(15), F(15)

mTBI: 21 N: 31

mTBI: 44.9 (10.9) N: 39.7 (9.3)

sTBI: 48.91 (13) mTBI: 47.47 (15.1) N: 49.22 (12.2)

mTBI: M(16),F(9) N: M(18),F(7)

sTBI: M(65),F(16) mTBI: M(57),F(24) N: M(67),F(15)

TBI: 16 N: 20

mTBI: 50 N: 50

mTBI: 23 N: 30

mTBI: 25 N: 25

mTBI: 11 N: 8

sTBI: 81 mTBI; 81 N: 82

vesicle from plasma Brain-derived extracellular vesicle from plasma

1 hr, 1 day, 4 days, 14 days

NGS

Serum, Saliva

Pre-fight: 1 hr Post-fight: 1530 minutes, 1 hr, 2-3 days, 1 week, 3+ weeks

NGS

Serum

Pre-season: 1 week prior to or in-season contact practices/com petition Post-season: 1 week after the last game of the season

Plasma

Serum

24 hr

Droplet digital PCR

Microarray/ RT-qPCR

TLDA/ RT-qPCR

miR-203b-5p miR-203a-3p miR-206 miR-185-5p miR-10b-5p miR-30b-5p miR-3678-3p miR-455-5p miR-5694 miR-6809-3p miR-92a-3p miR-195

0.92

Upregulated Upregulated Upregulated Upregulated Upregulated Upregulated Downregulated Downregulated Downregulated Downregulated Downregulated Upregulated

miR-92a

0.92

Upregulated

miR-30d

0.86

Upregulated

miR-505

0.83

Upregulated

miR-151-5p

0.81

Upregulated

miR-362-3p

0.75

Upregulated

miR-6867-5p

0.765

Upregulated

miR-3665

0.916

Upregulated

miR-328-5p

0.855

Upregulated

miR-762

0.921

Upregulated

miR-3195

0.859

Upregulated

miR-4669

0.894

Upregulated

miR-2861

0.898

Upregulated

miR-16

0.82

Upregulated

miR-92a

0.78

Upregulated

miR-103a-3p

0.807

0.574

Upregulated

miR-219a-5p

0.794

0.643

Upregulated

miR-302d-3p

0.798

0.581

Upregulated

miR-422a

0.795

0.616

Upregulated

miR-518f-3p

0.747

0.510

Upregulated

miR-520d-3p

0.847

0.593

Upregulated

0.84

0.89

Yang et al., 2016

China

Cohort

TBI: 48.5 (16.5) N: 46.6 (4.3)

TBI: M(59),F(17) N: M(29),F(9)

TBI: 76 N: 38

Serum

24 hr

RT-qPCR

miR-627

0.790

miR-93

0.560

Upregulated Upregulated

miR-191

0.742

Upregulated

miR-499

0.819

Upregulated

* : mTBI vs healthy control group : mTBI vs sTBI Abbreviation: CSF : Cerebrospinal Fluid F : Female M : Male miRNA : MicroRNA mTBI : Mild Traumatic Brain Injury N : Normal NGS : Next Generation Sequencing RT-qPCR : Reverse Transcriptase Quantitative Polymerase Chain Reaction SD : Standard Deviation sTBI : Severe Traumatic Brain Injury TLDA : TaqMan Low Density Array

Table 3. Quality Assessment of Included Studies

Study

RISK OF BIAS PATIENT SELECTION

Bhomia et al., 2016 Di Pietro et al., 2017 Di Pietro et al., 2018 Hicks et al., 2018 Ko et al., 2018 Ko et al., 2019 LaRocca et al., 2019

INDEX TEST

APPLICABILITY CONCERNS

REFERENCE STANDARD

FLOW AND TIMING

PATIENT SELECTION

INDEX TEST

REFERENCE STANDARD

? ? ? ? ? ? ?

Papa et al., 2018 Qin et al., 2018 Redell et al., 2010

? ?

Yan et al., 2019 Yang et al., 2016

? Low Risk

High Risk

? Unclear Risk

Table 4. MicroRNAs to Distinguish Mild Traumatic Brain Injury from Normal Healthy People Sources

MicroRNAs

AUC

Dysregulation

References

miR-425-5p

1.000

Downregulated

Di Pietro et al., 2017

miR-502

1.000

Downregulated

Di Pietro et al., 2017

miR-93

1.000

Upregulated

Yang et al., 2016

miR-762

0.921

Upregulated

Qin et al., 2018

miR-195

0.920

Upregulated

Papa et al., 2019

miR-92a

0.920

Upregulated

Papa et al., 2019

miR-3665

0.916

Upregulated

Qin et al., 2018

miR-2861

0.898

Upregulated

Qin et al., 2018

miR-4669

0.894

Upregulated

Qin et al., 2018

Set (miR-10b-5p, miR-30b-5p, miR3678-3p, miR-4555p, miR-5694, miR-

Upregulated/

0.890

Downregulated

LaRocca et al., 2019

6809-3p, miR-92a3p)

Serum/Plasma

miR-30d

0.860

Upregulated

Papa et al., 2019

miR-3195

0.859

Upregulated

Qin et al., 2018

miR-328-5p

0.855

Upregulated

Qin et al., 2018

miR-520d-3p

0.847

Upregulated

Yan et al., 2019

miR-505

0.830

Upregulated

Papa et al., 2019

miR-16

0.820

Downregulated

Redell et al., 2010

miR-499

0.819

Upregulated

Yang et al., 2016

miR-151-5p

0.810

Upregulated

Papa et al., 2019

miR-103a-3p

0.807

Upregulated

Yan et al., 2019

miR-302d-3p

0.798

Upregulated

Yan et al., 2019

miR-422a

0.795

Upregulated

Yan et al., 2019

miR-219a-5p

0.794

Upregulated

Yan et al., 2019

miR-627

0.790

Upregulated

Yan et al., 2019

miR-92a

0.780

Upregulated

Redell et al., 2010

miR-6867-5p

0.765

Upregulated

Qin et al., 2018

miR-362-3p

0.750

Upregulated

Papa et al., 2019

miR-518f-3p

0.747

Upregulated

Yan et al., 2019

miR-191

0.742

Upregulated

Yang et al., 2016

miR-92a

0.860

Upregulated

Bhomia et al., 2016

0.852

Upregulated

Hicks et al., 2018

miR-451

0.820

Upregulated

Bhomia et al., 2016

miR-505

0.820

Upregulated

Bhomia et al., 2016

Set (miR-182-5p, miR-221-3p, mirCSF

26b-5p, miR-320c, miR-29c-3p, miR30e-5p)

miR-195

0.810

Upregulated

Bhomia et al., 2016

miR-486

0.810

Upregulated

Bhomia et al., 2016

miR-362-5p

0.790

Upregulated

Bhomia et al., 2016

miR-20a

0.780

Upregulated

Bhomia et al., 2016

miR-30d

0.750

Upregulated

Bhomia et al., 2016

miR-328

0.730

Upregulated

Bhomia et al., 2016

miR-151

0.660

Upregulated

Bhomia et al., 2016

Set (miR-10b-5p, miR-30b-5p, miR3678-3p, miR-4555p, miR-5694, miR-

Upregulated/

0.890

Downregulated

LaRocca et al., 2019

6809-3p, miR-92a3p) Set (miR-182-5p, miR-221-3p, mir26b-5p, miR-320c, Saliva

0.852

Upregulated

Hicks et al., 2018

0.845

Upregulated

Di Pietro et al., 2018

0.836

Upregulated

Di Pietro et al., 2018

miR-142-3p

0.791

Upregulated

Di Pietro et al., 2018

miR-27b-3p

0.755

Upregulated

Di Pietro et al., 2018

miR-135b-5p

0.755

Upregulated

Di Pietro et al., 2018

miR-107

0.732

Upregulated

Di Pietro et al., 2018

0.90

Upregulated

Ko et al., 2018

0.84

Upregulated

Ko et al., 2019

miR-29c-3p, miR30e-5p) let-7i-5p Set (miR-27b-3p, let-7i-5p, miR-1423p, miR-107, miR135b-5p)

Brain-derived extracellular vesicle from plasma

Set (miR-129 5p, miR-9 5p) Set (miR-203b-5p, miR-203a-3p, miR206, miR-185-5p)

Antioxidants Supplementation as a Potential Therapy on Improving Neurobehavioural Status in Post Traumatic Brain Injury (TBI) Patients : A Systematic Review and Meta-Analysis Nathanael Ibot David 1*, William Wiradinata 1, Shafa Maulida 1, Tania Isabella Waspodo 1 1

Faculty of Medicine, Brawijaya University, Malang, Indonesia *nathanaelibot@gmail.com; +62 81286928218

ABSTRACT Introduction: Traumatic brain injury (TBI) is an event occuring predominantly in young adults, impairing the quality of life (QoL) among survivors. The presence of oxidative stress caused by a buildup of free radicals in TBI patients leads to brain cell damage and subsequent secondary brain injury. Antioxidants’ ability to scavenge free radicals theoritically could prevent damage propagation and improve neurological outcome. The objective of this review study is to evaluate the efficacy of antioxidants in preventing neurological sequelae in post TBI patients. Methodology: Authors conducted this review study based on PRISMA guidelines. Studies were searched using electronic databases with the keywords “Traumatic Brain Injury”, “Antioxidant”, and “Neurobehaviour”, ranging from the year 2006-2020. Studies included assessed the efficacy of antioxidant usage in post TBI patients in order to prevent neurological sequelae. Studies including pediatric population were excluded. Bias among studies were evaluated using Cochrane-risk-of-bias tool. Statistical analysis were done using the Mantel-Haenzel method and random effects model. Results: The utilization of antioxidants in post TBI patient compared to placebo regarded an odds ratio (OR) of 1.24 (95% confidence intervals (CI) 0.88 to 1.75, P = 0.22). The utilization of late treatment was significantly better compared to early treatment. Treatments conducted on mild-to-moderate TBI patients and with multiple doses yielded better results compared to severe TBI and single dose treatment. Conclusion: The application of antioxidants in post TBI patients could reduce neurological sequelae. Antioxidants with BBB crossing properties are to be preferred due to its ability to act directly on the injury. Further research is needed in order to evaluate and represent a wider population base. Keywords: antioxidants, neurobehavioural, traumatic brain injury

I. INTRODUCTION

capable of theoretically preventing tissue damage

Traumatic brain injury (TBI) is defined as a

propagation

and

improving

neurological outcomes (Razmkon et al.,

blow or a penetrating head injury to the

2011).

head that results in the disruption of normal brain functions (American Association of

So far, the treatment for TBI solely focuses

Neurological Surgeons, 2020). According

to a study conducted by the United States

neuroprotective aspect of TBI management.

of America, TBI is a major cause of death

For more than 30 years, various attempts

induced by injury (Popescu et al., 2015).

have been made in efforts to discover

Approximately over 50% of TBI cases are

effective and harmless compounds. In the

related to motor vehicle accidents (MVA).

last two decades, every stage 2 and 3

TBI predominantly occurs among young

clinical trials have failed, with 130 drugs

adults, significantly impairing the quality

found to be effective in animal studies, yet

of life (QoL) among survivors. The

insignificant in clinical trials. Because of

reduction of patients’ QoL was a byproduct

its safety and neuroprotective capability,

of secondary brain injury, manifested as a

antioxidants

neurobehavioural sequelae (Béavogui et al,

prospective

2015 and Aminmansour et al., 2012).

(Aminmansour et al., 2012).

In the pathogenesis of TBI, free radicals

To examine the effect of antioxidants

plays an important role. Free radicals are

supplementation

highly

generated

neurobehavioural impairment related to

physiologically during cellular respiration

TBI, we reviewed randomized controlled

and

trials

reactive

molecules,

metabolism,

and

execessive

handling

that

injuries,

are

forgoing

regarded

choice

assessed

the

therapy

reducing

efficacy

accumulation of free radicals leads to

antioxidants supplementation on : (1)

oxidative stress that damages the cells

reducing

around it (Kehrer & Klotz, 2015).

Therefore, the presence of oxidative stress

antioxidants supplementation; (2) acute

is a potential contributor to acute central

clinical setting compared with late clinical

nervous system (CNS) injuries, causing

setting; and (3) its ability to cross the blood

damage to brain cells, leading towards

brain barrier (BBB).

subsequent

secondary

brain

neurobehavioural to

TBI

compared

sequelae with

injury

(Ramzkon et al., 2011). In order to

II. METHODS

counteract this event, antioxidants are

Authors conducted this systematic review

needed for its ability to scavenge free

was conducted according to the PRISMA

radicals. This is supported through the

statement’s flow diagram and checklist to

results of studies where antioxidants are

improve the quality of the review (Liberati

preventing TBI induced neurobehavioural

et al., 2009). Items deemed essential for

sequelae in acute clinical setting compared

transparent reporting of a systematic

with late clinical setting; (3) preventing

review such as title, introduction, methods,

TBI induced neurobehavioural sequelae

result, and discussion were included in the

based on its ability to cross the BBB.

checklist. d. 1. Eligibility

Criteria

for

Human

This review included any randomized

Clinical Trials a.

Types of studies

controlled trials (RCT) using antioxidant

Types of participants

therapy versus placebo in treating TBI

This review includes all studies that

published in English from the year

involved both males and female aged 18

2006-2020. Studies outside the publication

years old diagnosed with TBI. Working

range of 2006-2020 and not published in

diagnosis of TBI was based on clinical

English were excluded.

findings,

including

neurobehavioural

sequelae symptoms reported by a physician.

2. Eligibility Criteria for Animal Studies

Studies that included patients below 18

Authors included animal studies published

years old and assessed non-trauma related

in English from years 2010-2020. Studies

brain injury were excluded.

conducted in RCT, with antioxidants as intervention

Types of interventions

TBI

evaluated

with

neurobehavioural tests were included.

Intervention of interest included any

Studies not published in English and

pharmacological agents with antioxidant

outside

properties

2010-2020 were excluded.

such

vitamins,

the

publication

range

N-acetylcysteine, enzogenol, melatonin, dexanabinol (HU-211), and progesterone,

3. Search Strategy

administered at any dose, by any route, for

The authors searched through electronic

any duration, and at any time after trauma.

literature using databases and search engines such as PubMed, Cochrane,

Types of outcome measures

Science Direct, Scopus, Researchgate, and

The outcomes of interest included, but not

Google Scholar from the year 2006-2020.

limited to the role of antioxidants in : (1)

Keywords used in the search were :

preventing TBI induced neurobehavioural

(“Traumatic Brain Injury” OR “TBI”)

sequelae measured with Glasgow Outcome

AND (“Antioxidant”) AND (“Vitamins*”

Scale (GOS) or Glasgow Outcome Scale

Extended

(“Neurobehaviour”)

(GOS-E)

neurobehavioural

assesment

another test;

(2)

Outcome

“Supplements*”) Scale*”

AND OR

AND (“Glasgow

“GOS*”

“Glasgow Outcome Scale Extended*” OR

form of interventions, and measured

“GOS-E*”) AND (“Free radical*” OR

outcomes. The researchers analyzed and

“Oxidant*”)

(“Randomized

summarized the outcomes of studies

Controlled Trial*” OR “RCT*”). The

included with emphasis of statistical results

wildcard term (*) was applied to increase

from RCTs reported.

AND

the sensitivity of the search strategy. The studies included were original research that evaluated the effect of antioxidants on

5. Risk of Bias Assessment

neurobehavioral

The quality of this study was assessed by

reviewers

four reviewers with the same portion by

evaluated the journals independently and

using Cochrane-risk-of-bias tool. Bias

discrepancies between the four authors

assessed

were resolved by discussion.

generation (selection bias), allocation

post-TBI

statusimprovement

patients.

Four

include

random

sequence

Table 1. Dichotomization of GOS (Glasgow Outcome Scale) and GOS-E (Glasgow Outcome Scale Extended) score (Osler, 2014 and Bao et al., 2014)

4. Data Extraction and Analysis Eligible studies were reviewed and the

concealment (selection bias), blinding of

following data were extracted : author’s

participants and personnel (performance

name, year of publication, the place where

and detection bias), incomplete outcome

the study was performed, study design,

data (attrition bias), and selective reporting

number of samples,sample characteristics,

(reporting bias). Disagreements between

the reviewers were resolved through

statistical method with 95% confidence

discussion.

intervals (CI). Random effects model were used because of variance in substance used

6. Statistical Analysis Meta-analysis

were

across studies. P â&#x2030;¤ 0.05 was considered conducted

using

statistically significant. Bias in studies used

Review Manager 5.3. Data across studies

in the meta-analysis were evaluated

were dichotomized into two categories.

visually using a funnel plot.

Evaluation based on GOS levels (see Table 1.) were dichotomized into favorable (4-5)

III.RESULTS

and unfavorable (1-3) (Bao et al., 2014).

1. Study Identification and Selection

Mantel-Haenzel method were used as the

Figure 1. Flowchart of study identification and selection based on PRISMA

After conducting a search of studies on

Based on data collected from 4 studies,

various databases, a total of 267 studies

authors evaluated the effect of antioxidants

were found, consisting of 127 human

usage compared to placebo in reducing the

studies and 140 animal studies. Studies that

potential

included pediatric patients in the study

related to TBI. Data obtained through

were excluded, numbering 39 studies.

meta-analysis indicate that the usage of

Another 210 studies were excluded from

antioxidants is close to significance in

both human and animal studies due to

decreasing the potential neurobehavioural

limited presentations of findings and weak

sequelae related to TBI assessed from

methodology. Finally, 8 human studies

dichotomized GOS levels at the end of

were included in qualitative analysis with 5

treatment (odds ratio (OR) = 1.24, 95%

of them included in quantitative analysis

confidence intervals (CI) 0.88 to 1.75, P =

and 10 animal studies were included in

0.22;

qualitative analysis. Authors reached full

heterogeneity

agreement for inclusion of studies included

conditions (P = 0.33, I2 = 13.0%).

in this review (see Figure 1.)

Qualitative observations based on the

neurobehavioural

see

Figure

2.).

showed

sequelae

Tests

for

insignificant

funnel plot resulted showed that data collected has a low risk of reporting bias

2. Risk of Bias Assessment

(see Figure 3.).

Authors examined the studies acquired using the Cochrane Risk of Bias tool for

5. Meta-analysis of Secondary Outcome

both human studies and animal studies. The risk for bias in both human and animal

Authors performed an analysis on the

studies are mostly in the low and unclear

effectiveness of antioxidants between early

risk of bias category (see Table 4. see

and late treatment for TBI patients. The

Table 5.)

analysis was carried out on 5 trials based on the mortality rate between the two groups. Through a meta-analysis of 4 trials reporting early treatment, the results were

3. Study Characteristics

found to be close to significant (risk ratio

Authors summarized the characteristics

(RR) = 0.97, 95% confidence intervals (CI)

and properties of each study included (see

0.85 to 1.09, P = 0.58; see Figure 4.). Tests

appendix 1 and appendix 2)

for heterogeneity showed insignificant conditions (P = 0.55, I2 = 0%). Based on the funnel plot that has been made on early

4. Meta-analysis of Primary Outcome

treatment data, qualitative observations are

Table 2. Table of Human study synthesis data

Table 2. (cont.) Table of Human study synthesis data

Table 3. Table of Animal study synthesis data

Table 3. (cont.) Table of Animal study synthesis data

Table 4. Risk of bias table of human studies (authorsâ&#x20AC;&#x2122; judgements of studies about each risk of bias item)

Table 5. Risk of bias table of Animal studies (authorsâ&#x20AC;&#x2122; judgements of studies about each risk of bias item)

made and the results found that the data

95% confidence intervals (CI) 0.43 to 2.19,

collected is at a low risk of reporting bias

P = 0.93; see Figure 6.). Heterogeneity test

(see Figure 5). Furthermore, data collected

cannot be done because it is only

from 1 study with with late treatment

represented by 1 study. Furthermore, a

showed significant results (risk ratio (RR)

meta-analysis of 4 trials with inpatient TBI

= 0.39, 95% confidence intervals (CI) 0.17

patients found near significant results (risk

to 0.91, P = 0.03; see Figure 4.).

ratio (RR) = 1.01, 95% confidence

Heterogeneity test cannot be done because

intervals (CI) 0.84 to 1.21, P = 0.95; see

it is only represented by 1 study.

Figure 6.). Tests for heterogeneity showed

Comparing the risk ratios (RR) obtained,

less significant conditions (P = 0.37, I2 =

late treatment was found to be more

7%).Qualitative observations based on the

effective compared to early treatment in

funnel plot resulted showed that the data on

preventing mortality in TBI patients.

inpatient TBI patients has some risk of reporting bias (see Figure 7.). Comparing the risk ratios (RR) obtained, no significant

3. Tertiary Outcome

difference were found between inpatient

Authors summarized the properties of each

and outpatient care in preventing potential

antioxidants

mortality in TBI patients.

included

the

study

regarding the ability to cross the BBB from various

literatures.

All

antioxidants

included in the study but vitamin C is

Progesterone

Vs.

Progesterone (placebo)

capable of crossing the BBB due to its need to be in the form of DHA to cross BBB (see

Authors compared patients treated with

Table 6.).

progesterone

Inpatient

patients

without

progesterone (placebo). A total of 2 studies

4. Subgroup Analysis a.

that evaluated this comparison were found. Compared

Data

obtained

from

the

results

meta-analysis discovered that progesterone

Outpatient Treatment

treatment were significantly effective in

Authors also conducted an analysis on

preventing

the effectiveness of TBI patient care

neurobehavioral

sequelae

related to TBI compared to placebo

between inpatient and outpatient care. The

through the comparison of mortality rate at

analysis was carried out on 5 studies based

the end of treatment (risk ratio (RR) = 0.45,

on the mortality rate between the two

95% confidence intervals (CI) 0.24 to 0.87,

groups. Data collected from 1 study with

P = 0.02; see Figure 8.). Tests for

outpatient TBI patients obtained results

heterogeneity showed

nearing significant (risk ratio (RR) = 0.97,

less

conditions (P = 0.81, I2 = 0%).

significant

Figure 2. Meta-analysis of Primary outcome (Forest Plot)

Figure 3. Meta-analysis of Primary outcome (Funnel Plot)

Figure 4. Meta-analysis of Secondary outcome (Forest Plot)

A. Early setting B. Late setting

Figure 5. Meta-analysis of Secondary outcome (Funnel Plot)

c. Single

Dose

Compared

severe. Data collected from 1 study with

Multiple Dose Treatment

mild to moderate TBI subject conditions obtained significant results (risk ratio (RR)

Next, authors compared patients treated

= 0.48, 95% confidence intervals (CI) 0.28

with single dose compared to multiple

to 0.81, P = 0.006; see Figure 10.).

doses of treatment. A total of 3 trials gave

Heterogeneity test cannot be done because

and multiple dose treatment and 2 trials

it is only represented by 1 study.

gave single dose treatment. Data obtained

Furthermore, from the data collected from

through meta-analysis of single dose

4 trials with severe TBI subject conditions

treatments found near significant results

based

(risk ratio (RR) = 0.98, 95% confidence

heterogeneity

Data obtained from meta-analysis of obtained

results

through

near-significant

heterogeneity

Figure

9.).

showed

Tests

insignificant

observations were made on the data evaluating severe TBI using a funnel plot and it were determined to have some risk of

confidence intervals (CI) 0.45 to 1.06, P = see

showed

conditions (P = 0.37, I2 = 7%). Qualitative

meta-analysis (risk ratio (RR) = 0.69, 95% 0.09;

near

P = 0.95; see Figure 10.). Tests for

insignificant conditions (P = 0.97, I2 = 0%). treatments

found

95% confidence intervals (CI) 0.84 to 1.21,

Figure 9.). Tests for heterogeneity showed

dose

meta-analysis

significant results (risk ratio (RR) = 1.01,

intervals (CI) 0.86 to 1.12, P = 0.77; see

multiple

reporting bias (see Figure 11.). Comparing

for

the risk ratios (RR) obtained, antioxidants

insignificant

usage on mild to moderate TBI leads to

conditions (P = 0.27, I2 = 21%). Comparing

better prognosis compared to severe TBI

the risk ratios (RR) obtained, treatment

patients in preventing neurobehavioral

conducted in multiple doses is more

sequelae related to TBI through the

effective than single dose in preventing

comparison of mortality rate at the end of

neurobehavioral sequelae related to TBI

treatment.

through the comparison of mortality rate at the end of treatment.

IV. DISCUSSION TBI is one of the most frequently met case

d. Mild

Moderate

in hospitals and clinical settings. Data

TBI

shows that the causes of TBI are numerous

Compared to Severe TBI

and varying (Puvanachandra & Hyder,

Authors performed data analysis on 5 studies

order

determine

2008). Some of the causes attributable to

the

TBI are traffic accidents, accident falls,

effectiveness of antioxidants in preventing

blast injury, and others. Based on the data

neurobehavioral sequelae based on the TBI

analysis from studies selected by authors,

classification of mild to moderate, and

traffic accidents are the leading cause of

Table 6. List of antioxidant substances in ability to cross Blood-Brain Barrier (BBB)

TBI, being responsible for 58% of TBI

et al., 2011, antioxidants are theoritically

cases from a total of 1540 cases. Other

possessing the capability in preventing the

causes are accountable for 20% of TBI

propagation of tissue damage, leading to

cases, followed by accidental falls at 7% of

improvements in neurological outcome.

TBI cases, and blast injury at 5% of TBI

According to the analysis of 8 studies that

cases (see Figure 13.). Therefore, the risk

conducted human clinical trials and 10

and occurence of traffic accidents must be

studies

reduced in order to lessen the incidence rate

concluded that antioxidants usage in

of TBI.

post-TBI

with

minimizing

Based on the data obtained from Razmkon

animal

patients the

Figure 6. Meta-analysis of inpatient compared to outpatient treatment (Forest Plot)

are

trials,

authors

functional occurence

in of

neurobehavioural sequelae. From

the

results

trials. This is also reinforced by animal

obtained

studies from Hua et al., 2012 and Tang et

through

al., 2013, where favorable outcomes were

meta-analysis on 4 studies (Maas et al.,

found in the usage of progesterone and

2006; Wright et al., 2007; Razmkon et al.,

vitamin D combination (combined therapy).

2011; and Aminmansour et al., 2012) by

Other antioxidant substances that are

the evaluation of dichotomized GOS levels,

considered as effective are dexanabinol,

antioxidants are 1.24 times more effective

progesterone (monotherapy), and vitamin

compared to placebo see Figure 2. This

E (Îą-Tocopherol).

finding is also supported by clinical improvement in patients that according to

Contrary to other substances, the utilization

studies by Hoffer et al., 2013 and Grima et

of vitamin C (ascorbic acid) shown

al., 2018 are initially experiencing various

insignificant

symptoms, such as balance dysfunction,

potential of neurobehavioural sequelae.

effect

reducing

However, according to a

the

study by

Razmkon et al., 2011, the application of high dose vitamin C (HD Vit. C) yielded much better results compared to low dose vitamin C (LD Vit. C). This finding could be identified based on the progression of perilesional edema see Figure 12. Beside the antioxidant substances that had already been tested in human clinical trials, Figure 7. Meta-analysis of

there are some known to be effective in

inpatient treatment

animal studies, such as nicotinamide;

(Funnel Plot)

confusion, headache, sensorineural hearing loss,

impaired

memory,

and

sleep

calcitriol;

vitamin

hydrogen

rich

B12

saline;

(cobalamine); and

omega-3

polyunsaturated fatty acids (Omega-3

disturbances, into only experiencing 1

PUFA).

symptom or even complete recovery by the

Based

from

those

findings,

substances mentioned above could possess

end of treatment period, evaluated by

potential to be developed in further human

neurobehavioural tests.

studies.

According to the data from Aminmansour

Other than the efficacy of antioxidants in

et al., 2011, the application of antioxidants

preventing neurobehavioural sequelae in

in the form of progesterone and vitamin D

post-TBI patients, authors also assessed the

combination (combined therapy) achieved

comparison

the highest effectivity in human clinical

between

antioxidants

Figure 8. Meta-analysis of progesterone vs. no progesteron (Forest Plot)

supplementation in early and late setting.

neuropsychological outcome. Based on the

Early setting being within 24 hours of

forest plot used in meta-analysis, the study

injury and late setting being more than 24

conducted by Wright et al., 2007 stands out

hours post injury. Through analysis from 4

from the rest by having a risk reduction of

studies (Maas et al., 2006; Wright et al.,

57% on patients treated in early setting compared to placebo. It should be known

2007; Razmkon et al., 2011; and Lee et al.,

that variance on the studiesâ&#x20AC;&#x2122; results could

2019) reporting treatment in early setting

be caused by the lack of sample involved.

and 1 study (Aminmansour et al., 2012) reporting treatment in late setting. Based on

In the management of brain injuries, it

the analysis done by evaluating mortality in

should be understood that a substanceâ&#x20AC;&#x2122;s

patients (risk ratio (RR) = 0.97, 95%

ability to cross the BBB is of importance.

confidence intervals (CI) 0.85 to 1.09, P =

The structural complexities of the BBB,

0.58)

treatments

acting as a filter to any substances that

conducted in early setting, where this

attempts to penetrate it, would be of some

indicates that there is no significant

hindrance

difference in patients treated in acute

medications on acting. Therefore, in the

setting. Opposing the acute setting (risk

therapy of TBI, a substance that could

ratio (RR) = 0.39, 95% confidence

penetrate the BBB would be preferred. See

intervals (CI) 0.17 to 0.91, P = 0.03) were

Table 6.

were

obtained

found in patients treated in late setting.

for

some

substances

According to the analysis of 8 human

This finding shows a 61% decrease in risk

clinical trials involving various substances,

with patients treated in the late setting

some of them were able to penetrate the

compared to placebo.

BBB. Antioxidants that could go past the

However, there exists a discrepancy

BBB are NAC (Katz et al., 2015),

between authorsâ&#x20AC;&#x2122; analysis compared to a

melatonin (Johns,

study by Hoffer et al., 2013. In the study

(Kalueff et al., 2006), vitamin E (Ferri et

done by Hoffer et al., 2013, the use of

al., 2015), progesterone (Banks, 2012),

N-acetylcysteine (NAC) in the time range

dexanabinol (Maas et al., 2006), and

of 24 hours (early setting) resulted in sole

enzogenol (Rashno et al., 2020). However,

benefit of neurological outcome but not on

vitamin C could not pass the BBB in order

2011), vitamin D

Figure 9. Meta-analysis of Single Dose Compared to Multiple

Dose Treatment (Forest Plot & Funnel Plot) C. Multiple Dose D. Single Dose

to function before being converted into

significant difference in patients with

DHA (Camarena & Wang, 2016).

severe TBI. On the other hand, through a study (Wright et al., 2007) evaluating

In order to complement and improve the

patients with mild to moderate TBI, authors

effectiveness of antioxidants in TBI

obtained (risk ratio (RR) = 0.48, 95%

patients, Authors analyzed the comparison

confidence intervals (CI) 0.28 to 0.81, P =

of patient prognosis using mortality data

0.006).Through the results, it could be

based on the severity of TBI. Based on the

comprehended that there a 52% risk

results of meta-analysis from 4 studies

reduction in patients with mild to moderate

(Maas et al., 2006; Wright et al., 2007;

TBI compared to placebo. In the data

Razmkon et al., 2011; and Aminmansour et

evaluating patients with severe TBI, there

al., 2012) evaluating patients with severe

is little to no difference compared to

TBI, authors obtained (risk ratio (RR) =

placebo. Based on these findings, authors

1.01, 95% confidence intervals (CI) 0.84 to

conclude that patients with mild to

1.21, P = 0.95).Through the results, it could be

comprehended

that

there

moderate TBI will have better prognosis

compared to those with severe TBI.

Figure 10. Meta-analysis of Mild to Moderate

TBI compared to Severe TBI (Forest Plot) A. Multiple Dose B. Single Dose

Figure 11. Meta-analysis of Mild to Moderate TBI compared to Severe TBI (Funnel Plot)

Based on the data available from studies

and Aminmansour et al., 2012) evaluating

selected,

issue

multiple dose treatment, authors obtained

regarding the management of TBI patients

(risk ratio (RR) = 0.69, 95% confidence

where 6 studies (Wright et al., 2007;

intervals

Razmkon et al., 2011; Aminmansour et al.,

0.09).Through the results, it could be

2012; Hoffer et al., 2013; Theadom et al.,

comprehended that there is a 31% risk

2013; and Grima et al., 2018) utilized

reduction on patients treated with multiple

multiple dose treatment and another 2

dose compared to placebo. On the other

studies (Maas et al., 2006 and Lee et al.,

hand, based on the results of meta-analysis

2019) that used single dose treatment in

from 2 studies (Maas et al., 2006 and Lee et

TBI patients. Therefore, authors analyzed

al., 2019) evaluating single dose treatment,

the comparison of patient prognosis using

authors obtained (risk ratio (RR) = 0.98, 95%

mortality data between single dose and

confidence intervals (CI) 0.86 to 1.12, P =

multiple dose treatment. Based on the

0.77).Through the results, it could be

results of meta-analysis from 3 studies

comprehended that there a 3% risk

(Wright et al., 2007; Razmkon et al., 2011;

reduction in patients treated with single

authors

assessed

(CI)

0.45

1.06,

dose treatment compared to placebo.

utilization of

progesterone

could be

Multiple dose treatment are to be preferred

considered in post TBI patients for the sake

due to the greater risk reduction compared to the little to no difference in single dose treatment. So, multiple dose treatment of antioxidants is more effective in the management of TBI patients. Supported by the abundance of samples and involvement of 3 research centres, authors are interested in analyzing the comparison of prognosis in the application of the antioxidant progesterone. Analysis was

performed

Figure 12. Evolution of perilesional edema during first

using mortality data

7 days after trauma (Razmkon et al., 2011)

between progesterone usage and no use of progesterone (placebo). Based on the

of achieving better neurological outcome.

results of meta-analysis from 2 studies

However,

(Wright et al., 2007 and Aminmansour et

progesterone, the potential of hormone

al., 2012), authors obtained (risk ratio (RR)

disturbances and the occurance of adverse

= 0.45, 95% confidence intervals (CI) 0.24

effects must be considered thoroughly. As

to 0.87, P = 0.02)Through the results, it

of this moment, adverse effects relating to

could be comprehended that there is a 55%

the usage of progesterone in TBI patients

risk reduction on patients treated with

couldn't be determined due to the lack of

progesterone compared to placebo. Based

study participants to provide adequate

on the analysis result and in accordance to

evidence of the occurances of adverse

the findings by donald & david, 2010, the

effects.

long

term

usage

Beside the effectivity of antioxidant usage in post TBI patients, authors also evaluated the importance of determining treatment form on TBI patients based on the results of corresponding treatment. authors analyzed the comparison of patient prognosis using mortality data between inpatient care and outpatient care. Based on the results of meta-analysis from 4 studies (Maas et al., Figure 13. Epidemiology of Traumatic Brain Injury

2006; Wright et al., 2007; Razmkon et al.,

(TBI)

2011; and Aminmansour et al., 2012)

evaluating inpatient care, authors obtained

authors included studies published within

(risk ratio (RR) = 1.01, 95% confidence

2005-2020.

intervals (CI) 0.84 to 1.21, P = 0.95) and

VI.CONCLUSIONS

from 1 study that evaluated outpatient care,

authors obtained (risk ratio (RR) = 0.97, 95%

this

systematic

meta-analysis,

confidence intervals (CI) 0.43 to 2.19, P =

results

review

and

shown

that

antioxidants supplementation could reduce

0.93). Through the results, it could be

neurobehavioural sequelae in post TBI

comprehended that there wasn’t any

patients.

significant change on patient prognosis in

Antioxidants

supplementation

displayed fine efficacy especially in

both inpatient and outpatient care.

preventing continuing damage in head

V.LIMITATION

injury. In the management of TBI patients,

In this systematic review and meta-analysis,

treatments in late setting are to be advised

all of the studies included are utilizing the

compared to early setting, regarding the

same study design, which is RCTs.

effectivity of recovery. Next, regarding

However, there exists a problem where the

enhancing

samples

medication,

included

within each

study

the

effectivity

antioxidants

of with

TBI BBB

couldn’t represent the wide population.

crossing properties are to be preferred in

This leads to an acceptable internal validity,

order to work directly on the centre of the

but also external validity inadequacy.

injury.

Some of the studies included also didn’t clearly

state

complicating

the the

data process

explicitly, of

data

VII.RECOMMENDATIONS

homogenization, such as the processing of

Based on author’s readings on available

GOS and GOS-E data from 4 out of 8

studies, Aloe vera could be one potential

human

that,

source for exogenic antioxidant. Exogenic

mortality data that wasn’t explicitly

antioxidants could sourced from consumed

explained forced authors to calculate it

food and supplementations (Santos al et.,

manually using the data presented within

2019).

the study. Undoubtedly, this leads to some

substances discovered, one of them that has

degree of information and selection bias. It

been known to be non-hazardous through

should be brought to attention that the

toxicology testing is polyphenols. Through

amount of studies exploring the use of

many studies, analysis of commonly

antioxidants in post TBI patients are

bioactive substances contained within

relatively scarce. This predicament gave

regularly consumed herbal plants yielded a

rise to the expansion of study inclusion

result that declared Aloe vera as a rich and

criteria based on publication year, where

abundant source of the bioactive substance

clinical

trials.

Besides

Among

many

antioxidant

polyphenol (HÄ&#x2122;Ĺ&#x203A; et al., 2016). Due to its

usage of antioxidants in TBI management.

availibility and economic pricing, Aloe

Future human clinical trials needs to be

vera supplementation could be a solid

conducted in a large scale, multicentre

choice in managing TBI. There needs to be

approach in order to achieve data adequacy

further research with a wider scope on the

and external validity.

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APPENDIX

Appendix 1. Table summary of the characteristics and properties of Human studies

Appendix 1. (cont.) Table summary of the characteristics and properties of Human studies

Appendix 2. 1. (cont.) Table summary Table summary of the characteristics of the characteristics and properties and properties of Animal of studies studies

Appendix 2. (cont.) Table summary of the characteristics and properties of Animal studies

THE PROGNOSTIC VALUE OF S100B LEVEL AS A PROMISING BIOMARKER OF EARLY PROGNOSIS IN PATIENTS WITH TRAUMATIC BRAIN INJURY: A SYSTEMATIC REVIEW AND META ANALYSIS OF COHORT STUDIES Ayers Gilberth Ivano Kalaij*, Michael Sugiyanto**, Valencia Hadinata***and Ugiadam Farhan Firmansyah**** * **

Second Year Medical Student, AMSA-UI (kalaijayers@gmail.com)

Second Year Medical Student, AMSA-UI (michael.sugiyanto@yahoo.co.id)

*** Second Year Medical Student, AMSA-UI (valenciahadinata@gmail.com) **** Third Year Medical Student, AMSA-UI (ugiadamfarhan@yahoo.co.id)

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 Indonesia, the most prevalent cause of TBI is road traffic injury. The mortality rate of road traffic injury in Indonesia is around 26%. 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 cohort studies found by database searching systematically using previously determined inclusion, such as moderate to severe traumatic brain injury patients, have outcome predictors, and have serum S100B data, and exclusion criteria, such as pediatric patients. This review was arranged based on PRISMA guideline. Results: Our meta-analysis yields a significant difference of S100B serum level among unfavourable (GOS 1-3) compared to favourable (GOS >3) group with the p value for the overall effect test (z=5.92) is p <0.00001. Even though, it consists of considerable heterogeneity studies. Hence, it implies that patients with high S100B serum level tend to have low Glasgow Outcome Score (GOS), vice versa. Discussion: This study review uses individual participant-level data in objective of examining the prognostic value of S100B protein serum level concentration in predicting the outcome of moderate and severe traumatic brain injury which included a total of 9 studies in our systematic review. The studies were conducted in various countries. The mean difference revealed that the result of this meta-analysis is most likely unfavourable in align with 1.80 mean difference which means that S100B serum level concentrations were found higher in unfavourable groups. Conclusion: This review has proven that S100B has a significant correlation with the outcome of traumatic brain injury patients. Higher serum level of S100B indicates unfavourable prognosis. 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 PROMISING BIOMARKER OF EARLY PROGNOSIS IN PATIENTS WITH TRAUMATIC BRAIN INJURY: A SYSTEMATIC REVIEW AND META ANALYSIS OF COHORT STUDIES Scientific Paper

Ayers Gilberth Ivano Kalaij Michael Sugiyanto Valencia Hadinata Ugiadam Farhan Firmansyah AMSA-UI 2020

Scientific Paper Competition PCC AMSC 2020 THE PROGNOSTIC VALUE OF S100B LEVEL AS A PROMISING BIOMARKER OF EARLY PROGNOSIS IN PATIENTS WITH TRAUMATIC BRAIN INJURY: A SYSTEMATIC REVIEW AND META ANALYSIS OF COHORT STUDIES Ayers Gilberth Ivano Kalaij*, Michael Sugiyanto**, Valencia Hadinata***and Ugiadam Farhan Firmansyah**** * **

Second Year Medical Student, AMSA-UI (kalaijayers@gmail.com)

Second Year Medical Student, AMSA-UI (michael.sugiyanto@yahoo.co.id)

*** Second Year Medical Student, AMSA-UI (valenciahadinata@gmail.com) **** Third Year Medical Student, AMSA-UI (ugiadamfarhan@yahoo.co.id)

Introduction In recent years, traumatic brain

traumatic brain injury will die while 50%

injury (TBI) is a major phenomenon which

of them will be moderately disabled

often leads into severe damage injury. It is

(Myburgh et al., 2008; Thornhill et al.,

also

heterogeneous

2000). Despite recent improvement in

pathological disease state considering the

management of TBI patients in intensive

report that it affect all ages (Hammond et

care and standardized care guideline

al., 2001; Pickett, Ardern, & Brison,

development, mortality and morbidity in

2001). Overall, according to recent study,

these patients remains high. The objective

around sixty-nine million cases of TBI

of TBI treatment is to reduce the extent of

across the world every year (Dewan et al.,

secondary brain-damage following the

2019).

primary effects (Park et al., 2009)

considered

The post prevalent cause of TBI in

Early prediction of prognosis in

Indonesia is road traffic accident. In 2013,

TBI is currently based on demographic,

the number of road traffic accidents in

clinical

Indonesia was 100.106. In the same year,

including age, initial Glasgow Coma Scale

26.416 people died because of road traffic

(GCS) score, pupillary response, vital

accident, which means the mortality rate

signs, significant non-cranial injuries, and

of road traffic injury is around 26%

computed

(Traffic Corps Indonesian National Police,

however,

2014). The injury grade varies in range,

predictions

from mild with low mortality rate until

regarding

severe with life-threatening lesion (Park,

assessment compared to other diagnosis

Kim, Yoon, Cho, & Kim, 2009). About

methods, especially in traumatic injury

30% of patients admitted after severe

(Baer, Carson, & Evans, 2013; Susie

and

radiological

tomography these have the

(CT)

clinical several lack

features,

indices; outcome

limitations neurologic

Zoltewicz et al., 2012). Therefore, plenty

Measurements of using S-100 protein are

studies

and

also not widely used in clinical practice

and are not considered standard of care

TBI-

(Kochanek et al., 2008; Kövesdi et al.,

regarding

diagnostic

prognostic

method,

developing

assays

associated

biomarkers

especially measuring accurately

and

2010).

specifically has been conducted recently

Therefore, evaluation of the prognostic

(Susie Zoltewicz et al., 2012).

value of this biomarker after moderate or

Over the last 20 years, studies of

severe TBI could be a breakthrough in

biochemical markers of brain damage as

early prediction of prognosis. Thus, this

potential tools for prognostic evaluation

systematic review aims to evaluate the

have been increasing (Gonçalves, Concli

feasibility and prognostic value of S100B

Leite, & Nardin, 2008; Kochanek et al.,

in patients with moderate or severe

2008; Kövesdi et al., 2010; Papa et al.,

traumatic brain injury. Studies and reviews

2008; Zitnay et al., 2008). Concentrations

like this are needed due to the urgency and

of S-100

subunit of a

its potency in early prognosis. Through

calcium binding protein present mainly in

this endeavour, the results of this review is

glial

(Zimmer,

hoped to help improve guidelines of

Cornwall, Landar, & Song, 1995), are

advanced trauma care systems considering

being studied because of the increase of

this biomarker as an early prognostic

this substance in human blood and

biomarker, thereby achieving the goals of

cerebrospinal

reducing

protein, the

and

Schwann

cells

fluid in

brain

damage

mortality

(Kuzumi, Vuylsteke, Guo, & Menon,

associated with TBI.

2000; Pelinka, Bahrami, Szalay, Umar, &

Methods

Redl,

2003).

Even

though

evidence

and

morbidity

This systematic review and meta-

suggesting a potential clinical role of S-

analysis

100

the

Preferred Reporting Items for Systematic

protein and

Reviews and Meta-Analyses (PRISMA)

short, mid, and long term outcome of

protocol. The protocol can be accessed

prognosis is remains unclear in TBI

through http://www.prisma-statement.org/.

patients (Pelinka et al., 2003; Zitnay et al.,

This protocol consists of identification,

2008). Lack of sufficient discriminative

screening, eligibility test, and inclusion of

capacity

studies which was conducted through

protein

biomarker,

association between S-100

inform

clinical

decision

reported

making also indicated that other type of

PRISMA

prognostic

(PRISMA, 2015).

indicators

are

needed.

Statements’

following

flow

the

diagram

Type of studies

Reference standard

Prospective cohort studies that met

The reference standard is the

the criteria were included in this review.

clinical

Prospective cohort studies were used for

qualified professionals by assessing S100B

this review as its outcome is more

protein level serum concentrations using

compatible to identify and follow-up the

any Immunoassay. The studies included

association between S100B concentrations

must also have at least one follow-up in

and the clinical outcome, which requires

duration of time using GOS.

period of time. Review, retrospective

Information sources and search strategy

cohort, cross-sectional, case report, case series,

case-control,

performed

The literature search was done with

conference

multiple electronic databases, such as

abstract were excluded studies. Studies

PubMed, Wiley, Cochrane, ScienceDirect,

with unavailable full-text, language than

and Scopus. The keywords used were

other english, and irrelevant topics are also

((S100B[Title/Abstract]) AND ((traumatic

our exclusion criteria to ensure the

brain

relevancy of this study.

trauma[Title/Abstract]))

Participants

(((outcome[Title/Abstract])

All

patients

and

examination

diagnosed

with

injury[Title/Abstract])

brain AND

mortality[Title/Abstract])

OR OR

glasgow

moderate and severe traumatic brain injury

outcome score[Title/Abstract]). Limitation

(TBI) are included for this study. Patients

in the literature search was the availability

under the age of 18 were excluded from

of full-text articles. No limitation regarding

this review. There are no limitations for

time is applied. Database searches were

gender, races, domicile, and history of

done up to March 18, 2020.

treatment.

Study selection

Index Test

Studies were identified using the

Studies evaluating the Glasgow

keywords

described

above.

Duplicate

Outcome Scale and/or mortality rate

removal of the database search was

prognosis of S100B in moderate and severe

performed using EndNote X9 software;

traumatic brain injury were included.

whereas retrieved studies were screened of

Studies measuring mean serum level of

their titles and abstracts. Screening of

concentration of S100B were included in

potentially eliglible full-text studies are

meta-analysis to ensure the quantitative

done due to criteria of accessibility. The

analysis homogeneity.

planned procedure was summarized in

with a total score of 22. Studies with higher

Figure 1.

STROBE score indicates better quality of studies which shown that the study has lower risk of bias (STROBE, 2009). The quality

assessment

was

done

collaboratively by three reviewers until consensus was reached. Subsequently, funnel plot was used as a visual indication of publication bias. An asymmetrical shape indicates the presence of publication bias. Additional sensitivity analysis was conducted through Duval and Tweedieâ&#x20AC;&#x2122;s trim-and-fill analysis which are specific for situations that the

Figure 1. Literature search strategy

heterogeneity is too large. These methods was conducted in order to re-ensure the

Data collection process

pooled effect size after removing any

First author, publication year, study

studies to minimize the publication bias

design, study location, data analysis, time

(Higgins J, 2008).

to follow-up, study population, severity scale, assay tools, evaluation time, and

Operational definitions

outcome GOS and S200B Serum level at

The variable included in the study

first S100B assessment was extracted from

was the moderate TBI, severe TBI,

the included studies.

favourable

Quality assessment included

Strengthening observational

was the

studies

asssesed reporting in

unfavourable

outcomes, and mortality. Moderate TBI

The quality assessment of each study

outcomes,

were defined as patients with Glasgow

using

Coma Scale (GCS) from 9 up to 13,

whereas severe TBI were defined as

epidemiology

patients with GCS â&#x2030;¤8. (Kellerman, 2016)

(STROBE) statement checklist designed

Moreover,

for Cohort Studies. This tool consists of

Favourable

patients

were

defined as patients with GOS 4-5, while

quality and risk of bias assessment based

unfavourable patients were defines as

on every section of the included studies

patients with GOS 1-3 (Rainey, 2009)

including title and abstract, introduction,

which often leads to death.

methods, result, discussion, and fundings

included studies. If the p-value of the chisquared test results is <0.1, then the null Summary of measures and data analysis

hypothesis that the inclusion study is

The results of the study were stated

homogeneous is rejected. Thresholds for

as favourable and unfavourable using

the interpretation of I2 referred to Cochrane

standard mean difference ( p<0.05). All

Handbook for Systematic Reviews of

forms of statistical tests of this study were

Interventions is as follows: 0% to 40%

carried

Manager

considered as not important; 30% to 60%

(RevMan) v5.3. Risk ratio (RR) with a

represent moderate heterogeneity; 50% to

95% confidence interval and p-value below

90% represent substantial heterogeneity;

0.05

the

75% to 100% considered as strong

effectiveness of the TEVAR intervention in

heterogeneity. The importance of the

reducing

patients

observed value of I2 depends on (i)

compared to open surgery. If OR <1,

magnitude and direction of effects and (ii)

TEVAR has a significant effect in reducing

strength of evidence for heterogeneity (e.g.

the death rate of BTAI patients compared

p-value from the chi-squared test, or a

to those who receive open surgery.

conďŹ dence interval for I2 (Higgins J, 2008).

out

was

using

used

mortality

Review

to in

determine BTAI

Determination of the size of the impact is carried out by the fixed-effect method

Results

(FEM) or random-effect method (REM),

Search result and study selection

depending on the homogeneity of the

A preliminary search obtained 375

included studies. Both REM and FEM will

articles. 37 duplicate articles were removed

give identical results when there is no

and screening by authors regarding the title

heterogeneity among the studies. Where

and abstract of were done resulting in 338

there is heterogeneity, confidence intervals

studies. Author excluded some literatures

for the average intervention effect will be

with reason including other study design

more extensive if the random-effects

than prospective cohort, irrelevant study

method is used rather than a fixed-effect

population, irrelevant study outcomes, and

method, and the corresponding claims of

incompatible languages. Finally, full text

statistical

was retrieved for 21 papers and 9 studies

significance

will

conservative (Higgins J, 2008).

were included for qualitative synthesis of

The Cochraneâ&#x20AC;&#x2122;s chi-squared test

systematic review; however, only 6 studies

and the Higgins I statistical test were used

were included in quantitative synthesis of

to evaluate the heterogeneity of the

meta-analysis. The literature searching

difference

between

unfavourable

and

result was summarized in Figure 1.

favourable groups. Therefore, this implies that patients with high S100B serum level

Included study characteristics

tend to have low Glasgow Outcome Score

Several studies were included in

(GOS), vice versa. The forest plot and

our systematic review and meta-analysis

funnel plot is presented in Figure 4 in the

based on our literature searching with

appendix. Moreover, Duval and Tweedieâ&#x20AC;&#x2122;s

certain inclusion and exclusion factors. We

trim-and-fill analysis revealed that one

found 9 eligible studies for systematic

study is an outlier study (Kellerman, 2016).

review

qualitative

analysis.

extracted 5 studies for meta-analysis.

Discussion

Those were included because each study

Summary of main results

consists of sufficient data for quantitative

This study review uses individual

analysis, such as S100B serum level for

participant-level

unfavourable and favourable groups. The

examining the prognostic value of S100B

rest 4 studies were not included due to lack

protein

predicting the outcome of moderate and

data

and

different

outcome

serum

data

in objective of

level

severe

described in table of characteristics shown

included a total of 9 studies in our

in Appendix 1.

systematic

Meta-analysis

conducted in various countries. The mean

review. The

which

studies were

difference revealed that the result of this

significant difference of S100B serum level

meta-analysis is most likely unfavourable

among unfavourable (GOS 1-3) compared

in align with 1.80 mean difference which

to favourable (GOS >3) group. Although,

means

our

concentrations

consists

yields

injury

study

meta-analysis

brain

measurement. Included studies were all

Our

traumatic

concentration

studies

with

that

S100B were

serum

found

level

higher

considerable heterogeneity. Those studies

unfavourable groups. Overall, S100B level

showed that the tau-square test was 0.46,

is proven as a good predictor in predicting

the chi-square test was 34.45, the degree of

the outcome as the high concentration in

freedom was 5, and the I-square test was

serum

85%. Those are indicating significant

unfavourable outcomes in patients with

heterogeneity

TBI.

value for the overall effect test (z=5.92) is

Gold

p <0.00001 which shows a significant

traumatic brain injury

studies.

Nevertheless,

level

Standard

significantly

the

prognosis

Presently, computed tomography

parameter and has led to confusion among

(CT scan) is the gold standard in regards to

clinicians.

(Maas,

2005)

That

prognosing traumatic brain injury patients.

pathological

CT scan uses computer processed X-ray

continuously occur up to the first 48 hours

measurements from various angles to

after the trauma. This calls for repeated CT

produce sectional images of a specific area

scans during that critical hour, all the while

in the human body. Any abnormalities

CT scan is relatively expensive to perform.

found in the head region, be it tumors,

A study by Stenberg et al. demonstrated

calcifications, infarctions, or bone traumas

that

can be clearly visualized by the CT scan. It

scanned by CT increased by 50% from

is also relatively easy to perform aside

initial CT scan after trauma to 24 hours

from the clear visualization it provides. In

after trauma. This further proves that

daily clinical practice, CT scan results from

prognosis of TBI cannot be predicted by

TBI patients is classified based on Marshall

only performing CT scans once or even

classification. Injury features that are

twice. (Stenberg, 2017)

intracranial

severely

injured

aside, changes

patients

group

differentiated in the Marshall classification are presence or absence of intracranial

Advantages of the S100B protein

abnormalities, presence or absence of mass

The S100B protein is relatively

lesions, shifting of basal cisterns, and

easy to handle and reliable in analysis. This

planned evacuation of mass lesions. (Maas,

is because the S100B protein is very stable

2005)

and unaffected by temperature changes, Marshall classification, however,

storing,

freeze-thaw

cycles,

the

wasnâ&#x20AC;&#x2122;t initially designed for prognostic

properties of a useful biomarker for clinical

purposes based on several reasons. The

use. Another important property of the

Marshall classification cannot differentiate

S100B protein is its resistance towards

the type of mass lesion on the patient. The

hemolysis, making it a very significant and

type of mass lesion is important to be

competent

differentiated

(Beaudeux, 2000; Raabe,2003)

because

patients

with

epidural generally have better prognosis

S100B protein assessment options

and subdural or intracranial hematoma. On the

contrary,

Marshall

biomarker in acute cases.

The

classification

Immunosorbent

Enzyme-Linked Assay

(ELISA)

differentiates between evacuated and non-

currently named as the gold standard in

evacuated mass lesions. Many argued that

assessing S100B protein levels in the

it should not be included as a CT scan

serum. However, several other options are

available,

such

automated

luminometric

LIAISON-mat

S100

the

quantitative

There are some limitations of our

immunoassay

study. First, the studies selected for our

system

and

the

meta analysis are very heterogeneous

electrochemiluminescence immunoassay or

indicating the needs of more studies to be

widely known as the Elecsys S100B kit.

done. This may be caused by variations in

Clinically speaking, the LIAISON-mat

S100B concentration assay method and

S100 system and the Elecsys S100B kit are

follow up time among those studies. Also,

the most frequently used assays. The

our systematic review and meta analysis

LIAISON system is meant to screen S100B

only includes studies written in english

protein levels in cases of melanoma or

which may present limitations.

other malignant tumors. However, it is not designed for quick analysis, making it a

Conclusion

less time-efficient assay. The Elecsys

conclusion,

this

systematic

system is a much quicker option, with only

review and meta-analysis has proven that

approximately 18 minutes to run a serum

S100B protein level serum concentrations

sample. The ELISA kit is the most widely

were significantly higher in unfavourable

manufactured kit which makes it the most

prognosis groups of patients diagnosed

reachable kit in most clinical settings.

with moderate or severe TBI. Thus, It may

However, ELISA assays generally take up

be a promising predicting tool for early

to 4-6 hours long to run a serum sample.

prognosis of the patients itself; however,

The ELISA kit may also result in high

further research should be done due to our

inter-assay and intra-assay coefficients of

findings.

variation (CV) if compared with other clinical assays. Another alternative to the

Recommendation

ELISA kit which has attracted quite a big

We recommend a study with a

attention is the Electrochemiluminescent

larger sample and more homogeneous

Immunoassay (ECLIA). The ECLIA has a

settings

wide dynamic detection rate and low

considering the heterogeneity of this study.

background noise. (Thelin, 2016; Smit,

Further implications regarding this novel

2005) The cut-off value of serum S100B

method to predict the outcome of TBI

concentration in predicting unfavorable

patients should be considered by the

outcome and mortality in TBI can be seen

government, especially in Indonesia where

in Table 2 and Table 3. ( Stefanovi , 2017)

Road Traffic-Induced TBI occurs often.

Limitations of the review

which

needs

done

Acknowledgement

Gordillo-Escobar,

We have nothing to declare.

Rodríguez,

E.,

A.,

RodríguezEnamorado-

Enamorado, J., Revuelto-Rey, J., … Conflict of Interest

Vilches-Arenas, A. (2013). S100B

We declare that we have no competing

protein

intention for completing this review.

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APPENDIX 1. Table of characteristics 2. Figures and Funnel-Forest Plot

Study

Study design

Location

Kellerman, 2016

Prospective Cohort

Erlangen, Germany

Stefanovic, 2017

Prospective Cohort

Belgrade, Serbia

Goyal, 2013

Prospective Cohort

Vos, 2010

Data Analysis

Time to Followup

Study Population Mean Age

Number of Patients

MannWithney-U test, Pearson, and Wilcoxon MannWhitney U test

6 months

63.1 ± 15.9

14 days

40.2 ± 13.8

130

Pittsburgh, Pennsylvania

Pearson's correlation

6 months

37,1 ± 1,8

Prospective Cohort

Nijmegen, the Netherlands

Univariate logistic regression analysis

6 months

50.75 ± 12.17

Rainey, 2009

Prospective Cohort

Manchester, UK

3 months

41 ± 11.67

100

Guerrero, 2013

Prospective Cohort

Seville, Spain

MannWhitney U test Spearman correlation

≥ 24 hour post admission

52 ± 15.3

140

Pelinka, 2004

Prospective Cohort

Austria

MannWhitney U test

3 months

Median 39 (2855)

Wiesmann, 2010

Prospective Cohort

Muenchen, Germany

MannWhitney U test, Spearman

6 months

43.8 ± 20.5

Severity scales

Assay

Evaluation Time

GCS 912 (n=4); GCS below 8 (n=53) Median GCS 9, mean ISS 34,2 ± 15,9 Median GCS 6, mean ISS 34,8 ± 1,2 Median GCS 3, median ISS 25 (5-75) Median ISS 25, no GCS Range GCS 3-8

ElectroChemiluminescence Immunoassay

at 6 months

ElectroChemiluminescence Immunoassay

at 14 days

0.93 ± 0.724

0.48 ± 0.107

16.59

Enzyme-Linked Immunosorbent Assay

at 6 months

3.29 ± 0.75

2.04 ± 0.44

18.74

2-site Luminometric Immunoassays

at 6 months

0.94 ± 0.62

0.315 ± 0.15

15.44

Enzyme-Linked Immunosorbent Assay ElectroChemiluminescence Immunoassay

at 14 days

1.4 ± 0.42

19.77

at 24 hours

Death 16

N/A

0.5475 ± 0.1625 N/A

Median ISS 25, Median GCS 6 No ISS, Median GCS 7.7 ± 4.1

Monoclonal Immunoluminometric Assay

at 3 months

Death 33

N/A

20.14

Assay

at 14 days

1.65 ± 1

0.7 ± 0.5

19.27

Outcome Unfavourable Favourable (GOS 1-3) (GOS > 3) N S100B N S100B Serum Serum Level Level (ng/mL) (ng/mL) 17 0.28 ± 40 0.13 ± 0.065 0.025

STROBE Score

13.19

17.22

Bohmer, 2010

Cohort

Porto Alegre, Brazil

MannWhitney U test and Pearson test

3 days

29 Âą 13

No ISS, GCS 6 Âą 1

Enzyme-Linked Immunosorbent Assay

at 3 days

Death 5

N/A

Appendix 1. Study Characteristics

Table 2. Cut-off value of S100B protein in the diagnosis of unfavorable outcome after TBI

Figure 2. Marshall Classification in tree structure

Table 3. Cut-off value of S100B protein in the prediction of mortality after TBI

Figure 4. The forest plot (upper) and the funnel plot (lower) of our systematic review

STROBE Statement

Checklist of items that should be included in reports of cohort studies

Study: Kellerman, 2016

Title and abstract

Item No 1

(a) Indica e he

Recommendation de ign i h a commonl ed erm in he i le or he ab rac

(b) Provide in the abstract an informative and balanced summary of what was done and what was found (v) Introduction Background/rationale

Explain the scientific background and rationale for the investigation being reported (v)

Objectives

State specific objectives, including any prespecified hypotheses (v)

Methods Study design

Present key elements of study design early in the paper

Setting

Describe the setting, locations, and relevant dates, including periods of recruitment, exposure, follow-up, and data collection (v)

Participants

(a) Give the eligibility criteria, and the sources and methods of selection of participants. Describe methods of follow-up (v) (b) For matched studies, give matching criteria and number of exposed and unexposed (v)

Variables

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

Data sources/ measurement

For each variable of interest, give sources of data and details of methods of assessment (measurement). Describe comparability of assessment methods if there is more than one group

Bias

Describe any efforts to address potential sources of bias

Study size

Explain how the study size was arrived at (v)

Quantitative variables

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

Statistical methods

(a) Describe all statistical methods, including those used to control for confounding (v) (b) Describe any methods used to examine subgroups and interactions (c) Explain how missing data were addressed (d) If applicable, explain how loss to follow-up was addressed (e) Describe any sensitivity analyses

Results Participants

13*

(a) Report numbers of individuals at each stage of study eg numbers potentially eligible, examined for eligibility, confirmed eligible, included in the study, completing follow-up, and analysed (v) (b) Give reasons for non-participation at each stage (c) Consider use of a flow diagram

Descriptive data

14*

(a) Give characteristics of study participants (eg demographic, clinical, social) and information on exposures and potential confounders (v) (b) Indicate number of participants with missing data for each variable of interest (c) Summarise follow-up time (eg, average and total amount) (v)

Outcome data

15*

Report numbers of outcome events or summary measures over time (v)

Main results

(a) Give unadjusted estimates and, if applicable, confounder-adjusted estimates and their precision (eg, 95% confidence interval). Make clear which confounders were 1

adjusted for and why they were included (b) Report category boundaries when continuous variables were categorized (v) (c) If relevant, consider translating estimates of relative risk into absolute risk for a meaningful time period Other analyses

Report other analyses done

eg analyses of subgroups and interactions, and

sensitivity analyses Discussion Key results

Summarise key results with reference to study objectives (v)

Limitations

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

Interpretation

Give a cautious overall interpretation of results considering objectives, limitations, multiplicity of analyses, results from similar studies, and other relevant evidence (v)

Generalisability

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

Other information Funding

Give the source of funding and the role of the funders for the present study and, if applicable, for the original study on which the present article is based

*Give information separately for exposed and unexposed groups.

Study: Stefanovic, 2017

Title and abstract

Item No 1

(a) Indica e he (v)

Recommendation de ign i h a commonl ed erm in he i le or he ab rac

(b) Provide in the abstract an informative and balanced summary of what was done and what was found (v) Introduction Background/rationale

Explain the scientific background and rationale for the investigation being reported (v)

Objectives

State specific objectives, including any prespecified hypotheses (v)

Methods Study design

Present key elements of study design early in the paper (v)

Setting

Describe the setting, locations, and relevant dates, including periods of recruitment, exposure, follow-up, and data collection (v)

Participants

Variables

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

Data sources/ measurement

For each variable of interest, give sources of data and details of methods of assessment (measurement). Describe comparability of assessment methods if there is more than one group

Bias

Describe any efforts to address potential sources of bias

Study size

Explain how the study size was arrived at (v)

Quantitative variables

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

Statistical methods

(a) Describe all statistical methods, including those used to control for confounding 2

(v) (b) Describe any methods used to examine subgroups and interactions (v) (c) Explain how missing data were addressed (d) If applicable, explain how loss to follow-up was addressed (e) Describe any sensitivity analyses (v) Results Participants

13*

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

eg numbers potentially

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

14*

Outcome data

15*

Report numbers of outcome events or summary measures over time (v)

Main results

(a) Give unadjusted estimates and, if applicable, confounder-adjusted estimates and their precision (eg, 95% confidence interval). Make clear which confounders were adjusted for and why they were included (v) (b) Report category boundaries when continuous variables were categorized (v) (c) If relevant, consider translating estimates of relative risk into absolute risk for a meaningful time period

Other analyses

Report other analyses done sensitivity analyses (v)

eg analyses of subgroups and interactions, and

Discussion Key results

Summarise key results with reference to study objectives (v)

Limitations

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

Interpretation

Give a cautious overall interpretation of results considering objectives, limitations, multiplicity of analyses, results from similar studies, and other relevant evidence (v)

Generalisability

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

Other information Funding

Give the source of funding and the role of the funders for the present study and, if applicable, for the original study on which the present article is based

*Give information separately for exposed and unexposed groups.

Study: Guerrero, 2013

Title and abstract

Item No 1

(a) Indica e he (v)

Recommendation de ign i h a commonl ed term in the title or the abstract

(b) Provide in the abstract an informative and balanced summary of what was done and what was found (v) Introduction Background/rationale

Explain the scientific background and rationale for the investigation being reported (v) 3

Objectives

State specific objectives, including any prespecified hypotheses (v)

Methods Study design

Present key elements of study design early in the paper (v)

Setting

Describe the setting, locations, and relevant dates, including periods of recruitment, exposure, follow-up, and data collection (v)

Participants

Variables

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

Data sources/

measurement

For each variable of interest, give sources of data and details of methods of assessment (measurement). Describe comparability of assessment methods if there is more than one group (v)

Bias

Describe any efforts to address potential sources of bias

Study size

Explain how the study size was arrived at (v)

Quantitative variables

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

Statistical methods

Results Participants

13*

Descriptive data

14*

Outcome data

15*

Report numbers of outcome events or summary measures over time (v)

Main results

(a) Give unadjusted estimates and, if applicable, confounder-adjusted estimates and their precision (eg, 95% confidence interval). Make clear which confounders were adjusted for and why they were included (v) (b) Report category boundaries when continuous variables were categorized (c) If relevant, consider translating estimates of relative risk into absolute risk for a meaningful time period

Other analyses

Report other analyses done

eg analyses of subgroups and interactions, and

sensitivity analyses (v) Discussion Key results

Summarise key results with reference to study objectives (v)

Limitations

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

Interpretation

Give a cautious overall interpretation of results considering objectives, limitations, 4

multiplicity of analyses, results from similar studies, and other relevant evidence (v) Generalisability

Discuss the generalisability (external validity) of the study results

Other information Funding

Give the source of funding and the role of the funders for the present study and, if applicable, for the original study on which the present article is based

*Give information separately for exposed and unexposed groups.

Study: Vos, 2010

Title and abstract

Item No 1

(a) Indica e he

Recommendation de ign i h a commonl ed erm in he i le or he ab rac

(v) (b) Provide in the abstract an informative and balanced summary of what was done and what was found (v) Introduction Background/rationale

Objectives

State specific objectives, including any prespecified hypotheses (v)

Methods Study design

Present key elements of study design early in the paper (v)

Setting

Describe the setting, locations, and relevant dates, including periods of recruitment, exposure, follow-up, and data collection (v)

Participants

(a) Give the eligibility criteria, and the sources and methods of selection of participants. Describe methods of follow-up (v)

Explain the scientific background and rationale for the investigation being reported (v)

(b) For matched studies, give matching criteria and number of exposed and unexposed Variables

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

Data sources/

For each variable of interest, give sources of data and details of methods of

measurement

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

Bias

Describe any efforts to address potential sources of bias

Study size

Explain how the study size was arrived at (v)

Quantitative variables

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

Statistical methods

(a) Describe all statistical methods, including those used to control for confounding (b) Describe any methods used to examine subgroups and interactions (c) Explain how missing data were addressed (d) If applicable, explain how loss to follow-up was addressed (e) Describe any sensitivity analyses

Results Participants

13*

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

Descriptive data

14*

(a) Give characteristics of study participants (eg demographic, clinical, social) and 5

information on exposures and potential confounders (v) (b) Indicate number of participants with missing data for each variable of interest (c) Summarise follow-up time (eg, average and total amount) (v) Outcome data

15*

Report numbers of outcome events or summary measures over time (v)

Main results

(a) Give unadjusted estimates and, if applicable, confounder-adjusted estimates and their precision (eg, 95% confidence interval). Make clear which confounders were adjusted for and why they were included (v) (b) Report category boundaries when continuous variables were categorized (c) If relevant, consider translating estimates of relative risk into absolute risk for a meaningful time period

Other analyses

Report other analyses done

eg analyses of subgroups and interactions, and

sensitivity analyses Discussion Key results

Summarise key results with reference to study objectives (v)

Limitations

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

Interpretation

Give a cautious overall interpretation of results considering objectives, limitations,

Generalisability

Discuss the generalisability (external validity) of the study results

Other information Funding

Give the source of funding and the role of the funders for the present study and, if applicable, for the original study on which the present article is based

multiplicity of analyses, results from similar studies, and other relevant evidence (v)

*Give information separately for exposed and unexposed groups.

Study: Goyal

Title and abstract

Item No 1

(a) Indica e he (v)

Recommendation design with a commonly used term in the title or the abstract

(b) Provide in the abstract an informative and balanced summary of what was done and what was found (v) Introduction Background/rationale

Explain the scientific background and rationale for the investigation being reported (v)

Objectives

State specific objectives, including any prespecified hypotheses (v)

Methods Study design

Present key elements of study design early in the paper (v)

Setting

Describe the setting, locations, and relevant dates, including periods of recruitment, exposure, follow-up, and data collection (v)

Participants

Variables

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

Data sources/ measurement

For each variable of interest, give sources of data and details of methods of assessment (measurement). Describe comparability of assessment methods if there is 6

more than one group (v) Bias

Describe any efforts to address potential sources of bias

Study size

Explain how the study size was arrived at (v)

Quantitative variables

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

Statistical methods

(a) Describe all statistical methods, including those used to control for confounding (v) (b) Describe any methods used to examine subgroups and interactions (v) (c) Explain how missing data were addressed (v) (d) If applicable, explain how loss to follow-up was addressed (v) (e) Describe any sensitivity analyses (v)

Results Participants

13*

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

eg numbers potentially

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

14*

(a) Give characteristics of study participants (eg demographic, clinical, social) and information on exposures and potential confounders (v) (b) Indicate number of participants with missing data for each variable of interest (v) (c) Summarise follow-up time (eg, average and total amount) (v)

Outcome data

15*

Report numbers of outcome events or summary measures over time (v)

Main results

Other analyses

Report other analyses done sensitivity analyses (v)

eg analyses of subgroups and interactions, and

Discussion Key results

Summarise key results with reference to study objectives (v)

Limitations

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

Interpretation

Give a cautious overall interpretation of results considering objectives, limitations, multiplicity of analyses, results from similar studies, and other relevant evidence (v)

Generalisability

Discuss the generalisability (external validity) of the study results

Other information Funding

Give the source of funding and the role of the funders for the present study and, if applicable, for the original study on which the present article is based

*Give information separately for exposed and unexposed groups.

Study: Rainey, 2009

Title and abstract

Item No 1

(a) Indica e he

Recommendation de ign i h a commonl ed erm in he i le or he ab rac

(b) Provide in the abstract an informative and balanced summary of what was done 7

and what was found (v) Introduction Background/rationale

Explain the scientific background and rationale for the investigation being reported (v)

Objectives

State specific objectives, including any prespecified hypotheses (v)

Methods Study design

Present key elements of study design early in the paper (v)

Setting

Describe the setting, locations, and relevant dates, including periods of recruitment, exposure, follow-up, and data collection (v)

Participants

Variables

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

Data sources/ measurement

For each variable of interest, give sources of data and details of methods of assessment (measurement). Describe comparability of assessment methods if there is more than one group (v)

Bias

Describe any efforts to address potential sources of bias (v)

Study size

Explain how the study size was arrived at (v)

Quantitative variables

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

Statistical methods

Results Participants

13*

Descriptive data

14*

(a) Give characteristics of study participants (eg demographic, clinical, social) and information on exposures and potential confounders (v) (b) Indicate number of participants with missing data for each variable of interest (v) (c) Summarise follow-up time (eg, average and total amount) (v)

Outcome data

15*

Report numbers of outcome events or summary measures over time (v)

Main results

(a) Give unadjusted estimates and, if applicable, confounder-adjusted estimates and their precision (eg, 95% confidence interval). Make clear which confounders were adjusted for and why they were included (b) Report category boundaries when continuous variables were categorized (c) If relevant, consider translating estimates of relative risk into absolute risk for a meaningful time period

Other analyses

Report other analyses done sensitivity analyses (v)

Discussion 8

eg analyses of subgroups and interactions, and

Key results

Summarise key results with reference to study objectives (v)

Limitations

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

Interpretation

Give a cautious overall interpretation of results considering objectives, limitations, multiplicity of analyses, results from similar studies, and other relevant evidence (v)

Generalisability

Discuss the generalisability (external validity) of the study results

Other information Funding

Give the source of funding and the role of the funders for the present study and, if applicable, for the original study on which the present article is based (v)

*Give information separately for exposed and unexposed groups.

Study: Pelinka, 2004

Title and abstract

Item No 1

(a) Indica e he

Recommendation de ign i h a commonl ed erm in he i le or he ab rac

(b) Provide in the abstract an informative and balanced summary of what was done and what was found (v) Introduction Background/rationale

Explain the scientific background and rationale for the investigation being reported (v)

Objectives

State specific objectives, including any prespecified hypotheses (v)

Methods Study design

Present key elements of study design early in the paper (v)

Setting

Describe the setting, locations, and relevant dates, including periods of recruitment, exposure, follow-up, and data collection (v)

Participants

Variables

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

Data sources/ measurement

For each variable of interest, give sources of data and details of methods of assessment (measurement). Describe comparability of assessment methods if there is more than one group (v)

Bias

Describe any efforts to address potential sources of bias (v)

Study size

Explain how the study size was arrived at (v)

Quantitative variables

Explain how quantitative variables were handled in the analyses. If applicable,

Statistical methods

describe which groupings were chosen and why (v) (a) Describe all statistical methods, including those used to control for confounding (v) (b) Describe any methods used to examine subgroups and interactions (v) (c) Explain how missing data were addressed (v) (d) If applicable, explain how loss to follow-up was addressed (v) (e) Describe any sensitivity analyses (v) Results Participants

13*

(a) Report numbers of individuals at each stage of study eg numbers potentially eligible, examined for eligibility, confirmed eligible, included in the study, 9

completing follow-up, and analysed (v) (b) Give reasons for non-participation at each stage (v) (c) Consider use of a flow diagram (v) Descriptive data

14*

(a) Give characteristics of study participants (eg demographic, clinical, social) and information on exposures and potential confounders (v) (b) Indicate number of participants with missing data for each variable of interest (v) (c) Summarise follow-up time (eg, average and total amount) (v)

Outcome data

15*

Report numbers of outcome events or summary measures over time (v)

Main results

Other analyses

Report other analyses done sensitivity analyses (v)

eg analyses of subgroups and interactions, and

Discussion Key results

Summarise key results with reference to study objectives (v)

Limitations

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

Interpretation

Give a cautious overall interpretation of results considering objectives, limitations, multiplicity of analyses, results from similar studies, and other relevant evidence (v)

Generalisability

Discuss the generalisability (external validity) of the study results

Other information Funding

Give the source of funding and the role of the funders for the present study and, if applicable, for the original study on which the present article is based (v)

*Give information separately for exposed and unexposed groups.

Study: Wiesmann, 2010

Title and abstract

Item No 1

(a) Indica e he (v)

Recommendation de ign i h a commonl ed erm in he i le or he ab rac

(b) Provide in the abstract an informative and balanced summary of what was done and what was found (v) Introduction Background/rationale

Explain the scientific background and rationale for the investigation being reported (v)

Objectives

State specific objectives, including any prespecified hypotheses (v)

Methods Study design

Present key elements of study design early in the paper (v)

Setting

Describe the setting, locations, and relevant dates, including periods of recruitment, exposure, follow-up, and data collection (v)

Participants

Variables

Data sources/

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

measurement

For each variable of interest, give sources of data and details of methods of assessment (measurement). Describe comparability of assessment methods if there is more than one group (v)

Bias

Describe any efforts to address potential sources of bias

Study size

Explain how the study size was arrived at (v)

Quantitative variables

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

Statistical methods

Results Participants

13*

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

eg numbers potentially

14*

(a) Give characteristics of study participants (eg demographic, clinical, social) and information on exposures and potential confounders (v) (b) Indicate number of participants with missing data for each variable of interest (v) (c) Summarise follow-up time (eg, average and total amount) (v)

Outcome data

15*

Report numbers of outcome events or summary measures over time (v)

Main results

Other analyses

Report other analyses done eg analyses of subgroups and interactions, and sensitivity analyses (v)

Discussion Key results

Summarise key results with reference to study objectives (v)

Limitations

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

Interpretation

Give a cautious overall interpretation of results considering objectives, limitations, multiplicity of analyses, results from similar studies, and other relevant evidence (v)

Generalisability

Discuss the generalisability (external validity) of the study results

Other information Funding

Give the source of funding and the role of the funders for the present study and, if applicable, for the original study on which the present article is based (v)

*Give information separately for exposed and unexposed groups.

Study: Bohmer, 2010

Title and abstract

Item No 1

(a) Indica e he

Recommendation de ign i h a commonl ed erm in he title or the abstract

(v) (b) Provide in the abstract an informative and balanced summary of what was done and what was found (v) Introduction Background/rationale

Explain the scientific background and rationale for the investigation being reported (v)

Objectives

State specific objectives, including any prespecified hypotheses (v)

Methods Study design

Present key elements of study design early in the paper (v)

Setting

Describe the setting, locations, and relevant dates, including periods of recruitment, exposure, follow-up, and data collection (v)

Participants

Variables

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

Data sources/ measurement

For each variable of interest, give sources of data and details of methods of assessment (measurement). Describe comparability of assessment methods if there is more than one group (v)

Bias

Describe any efforts to 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 (v)

Statistical methods

Results Participants

13*

Descriptive data

14*

(a) Give characteristics of study participants (eg demographic, clinical, social) and information on exposures and potential confounders (v) (b) Indicate number of participants with missing data for each variable of interest (v) (c) Summarise follow-up time (eg, average and total amount) (v)

Outcome data

15*

Report numbers of outcome events or summary measures over time (v)

Main results

(b) Report category boundaries when continuous variables were categorized (v) (c) If relevant, consider translating estimates of relative risk into absolute risk for a meaningful time period (v) Other analyses

Report other analyses done

eg analyses of subgroups and interactions, and

sensitivity analyses (v) Discussion Key results

Summarise key results with reference to study objectives (v)

Limitations

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

Interpretation

Give a cautious overall interpretation of results considering objectives, limitations, multiplicity of analyses, results from similar studies, and other relevant evidence (v)

Generalisability

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

Other information Funding

Give the source of funding and the role of the funders for the present study and, if applicable, for the original study on which the present article is based (v)

*Give information separately for exposed and unexposed groups. Note: An Explanation and Elaboration article discusses each checklist item and gives methodological background and published examples of transparent reporting. The STROBE checklist is best used in conjunction with this article (freely available on the Web sites of PLoS Medicine at http://www.plosmedicine.org/, Annals of Internal Medicine at http://www.annals.org/, and Epidemiology at http://www.epidem.com/). Information on the STROBE Initiative is available at http://www.strobe-statement.org.

The Importances of Promt Pre Hospital Care in Society to Raise Awareness of Accident Among Elderly People and Brainstorm For the Solution to the Problems of Accident to Improve Pre-Hospital Care by Society Author: Arini Elfi Saâ&#x20AC;&#x2122;adah Harahap, Hasna Maharani, Neysa Triana. AMSA-Batam University ABSTRACT Background: The development of accident cases is the largest cause of death in almost every population in the world, especially in populations with developing country status and low-income countries. This also widely recorded as countries with a fairly high population of elderly people, particularly those aged over 65. where at their social status, there are still many parents who suffer injuries due to accidents such as vehicles, pedestrians, and other factors that can increase the number of deaths caused by accidents each year. this is certainly a concern that is quite important in the world of health to be able to cope with the risk factors for traffic accidents that occur. As we know that, in handling Pre Hospital, the community is the first person who is the most important factor, this is because the community is the most frequent subject and the first person to face this case in their environment. therefore, our aim in this review is to provide education to the community to minimize accident cases in the elderly. accident and their consequences are significant concerns for older adults, caregivers, and health care providers. Identification of accident risk is crucial for appropriate referral to preventive interventions. accident are multifactorial; no single measure is an accurate diagnostic tool. There is limited information on which history question, self-report measure, or performance-based measure, or combination of measures, best predicts future accidents. Objective: To systematically identify the various preventing possibility of elder people from an accident by educating society. Methods: The systematic review was facilitated through the use of a structured template, a companion explanatory piece, and a grading and methodological scoring system based on published criteria for critical appraisal. A reference librarian did two PubMed searches using the following: strategy, intervention, prevent, accident, trauma, road traffic injury, old, aging, and elder crash.

- Conclusion: Conclusion and recommendations The results presented in this paper show a positive effect of exercise on injurious falls, including the most severe falls and those that result in medical careâ&#x20AC;&#x201D;that is, those with the greatest consequences for peopleâ&#x20AC;&#x2122;s health and use of resources. These results should provide useful additional evidence for healthcare providers to encourage participation in exercise fall prevention programs, and further justification for decision-makers to provide funding for those programs.

The Importance of Prompt Pre Hospital Care in Society to Raise Awareness of Accident Among Elderly People and Brainstorm For the Solution to the Problems of Accident to Improve Pre-Hospital Care by Society Author: Arini Elfi Saâ&#x20AC;&#x2122;adah Harahap, Hasna Maharani, Neysa Triana. AMSA-Batam University ABSTRACT Background: The development of accident cases is the largest cause of death in almost every population in the world, especially in populations with developing country status and low-income countries. This also widely recorded as countries with a fairly high population of elderly people, particularly those aged over 65. where at their social status, there are still many parents who suffer injuries due to accidents such as vehicles, pedestrians, and other factors that can increase the number of deaths caused by accidents each year. this is certainly a concern that is quite important in the world of health to be able to cope with the risk factors for traffic accidents that occur. As we know that, in handling Pre Hospital, the community is the first person who is the most important factor, this is because the community is the most frequent subject and the first person to face this case in their environment. therefore, our aim in this review is to provide education to the community to minimize accident cases in the elderly. accident and their consequences are significant concerns for older adults, caregivers, and health care providers. Identification of accident risk is crucial for appropriate referral to preventive interventions. accident are multifactorial; no single measure is an accurate diagnostic tool. There is limited information on which history question, self-report measure, or performance-based measure, or combination of measures, best predicts future accidents. Objective: To systematically identify the various preventing possibility of elder people from an accident by educating society. Methods: The systematic review was facilitated through the use of a structured template, a companion explanatory piece, and a grading and methodological scoring system based on published criteria for critical appraisal. A reference librarian did two PubMed searches using the following: strategy, intervention, prevent, accident, trauma, road traffic injury, old, aging, and elder crash. - Conclusion: Conclusion and recommendations The results presented in this paper show a positive effect of exercise on injurious falls, including the most severe falls and those that result in medical careâ&#x20AC;&#x201D;that is, those with the greatest consequences for peopleâ&#x20AC;&#x2122;s health and

use of resources. These results should provide useful additional evidence for healthcare providers to encourage participation in exercise fall prevention programs, and further justification for decision-makers to provide funding for those programs. A. INTRODUCTIONS number of aged people, age-related

Accident related injuries are common,

problems also increase.

result in considerable healthcare utilization, and are a major cause of long term pain and

As many as one-third of older adults

functional impairment among older adults.

accident at least once over a year. The

They also increase considerably the risk of

accident can be related to Traffic Injuries,

discharge to a nursing home and have a high

injuries causing by some disease, fall, and

economic cost.

fear of falling who have contributed to restricted activity as a strategy to reduce

The development of human societies has usually been accompanied by an

perceived risk of subsequent in it all.

increase in the level of life expectancy and

Resultant secondary deconditioning may

an increase in the number of elderly people.

increase the risk of the accident.

Existing reports suggest that during the past

accident-related injuries (eg, hip fractures

50 years the number of aged people is

and head injury) contribute to increasing

tripled and it is estimated to be tripled again

care costs for older adults.

in the upcoming 50 years. In 1950 there was

Accident risk-reduction programs have

200 million elderly all around the world.

received significant funding in public health

According to UN investigations in 2000,

initiatives and also awareness of the society.

over 600 million elderly people lived in the

Nonetheless, accurately identifying those

world which approximately compromises

requiring intervention to reduce accident

10% of the global population. This number

risk is challenging not just for health

will be doubled in 2025. The rate of aging

professionals but also for the community as

population growth is 1.9 % that is higher

the first hand to stay for care to older adults.

when compared to 1.2% of global population growth.

Susceptibility to accident results from an interaction of multiple factors: reduced

The rate of population aging in middle

efficacy of postural responses, diminished

and lower-income countries is more rapid

sensory acuity, impaired musculoskeletal,

than the developed. It is predicted that up to

neuromuscular, and/or cardiopulmonary

the year 2025 over 80% of global elderly

systems, deconditioning associated with

people will come by countries with low and

inactivity, depression and low balance

middle income. With the increase in the

self-efficacy, polypharmacy, and a host of

environmental factors. The multifactorial

â&#x20AC;&#x153;diagnosticâ&#x20AC;? tool(s) to examine the clientâ&#x20AC;&#x2122;s

nature of fall risk complicates the

risk of falling. But, from this review that

identification of those most at risk.

will give some prevention of how to make

Consequently, fall risk assessment tools are

the step of accident cases decreased. From

as plentiful as contributing factors

covered knowledge in society. Those steps are used to combine role from health care

( Table 1 ). Given the number of tests and

services and community from a medical

measures available

field like simple ways for airway, breathing

for fall risk assessment, so that clinicians

and circulation, simple fracture first

will select the best

handling, and other material include prehospital trauma life support.

Table 1. Additional Measures Identified During Review of Retrieved Articles Included

Excluded

History questions

Self-report measures

Age > 80 y (yes/no)

Balance Effifi Cacy Scale

Alcohol use (yes/no)

Community Balance and Mobility Scale

Ambulatory assistive device (AD) use (yes/no)

Demura Fall Risk Assessment

Dependence in activities of daily living

Fall Assessment and Intervention

(yes/no)

Record

History of previous falls (yes/no)

Falls Behavioral Scale for Old People

Nocturia/urgency/incontinence (yes/no)

Fall Risk Assessment Tool for Older People

Polypharmacy (yes/no)

Fall Risk Assessment Tool

Psychoactive medication use (yes/no)

Falls Assessment Risk and

Self-reported depression (yes/no)

Management Tool

Self-Reported difficulty walking

Fall risk by exposure

Self-reported fear of falling (yes/no)

Fall Risk Questionnaire

Self-reported imbalance (yes/no)

Fear of Falling Avoidance

Self-reported physical activity/exercise

Questionnaire

Self-reported health status

Gait Effifi Cacy Scale

Self-reported pain

Goal Attainment Scale

Self-report measures

Hauser Ambulation Index

Balance Self-Perception Test

Hendrich II Fall Risk Model

Falls Risk Assessment Questionnaire

Home Falls and Accidents Screening Tool

Longitudinal Study of Aging Physical Activity Questionnaire

21-item Fall Risk Index

Older Adults Resources and Services

Performance-based measures

(OARS) ADL scale

Alternate Step Test

Self-Rated Health Questionnaire

Body mass index

Subjective Ratings of Specififi c Tasks

Cadence

Short Orientation Memory Concentration Test

Figure-8 Walking Test Grip strength

Sickness Impact Profile le (SIP)

Get up and go (untimed) Lateral Reach Test Lateral Reach Test

B. METHODS Method is an essential first step of our work was to group definitions of injurious falls found in the studies selected for this review into more homogeneous categories to allow pooling of data. This systematic review was conducted following the PRISMA guidelines.11 Search strategy and study selection We searched PubMed to identify relevant studies published in peer-reviewed journals from inception to July 2015. We also selected references in relevant reviews for screening. Independently screened the titles, abstracts, and full text of identified papers to determine their eligibility for inclusion (see supplementary file).

Discrepancies were resolved by discussion. Inclusion criteria were randomized controlled trials of fall interventions in adult, published in English, targeting community-dwelling adults aged over 65 years, and providing quantitative data on injurious falls, serious falls, fall-related injuries, or fall induced fractures. We included studies where exercise was compared with no intervention (usual activity or usual care) or a placebo control intervention (for example, general health education classes, social visits, or a low-intensity exercise program not designed to modify the risk of falling). We excluded studies in which exercise was part of a multifactorial program such that participants received other interventions (for example, visual treatment) in addition to exercise, and when participants were selected for a specific characteristic that greatly affected the risk of falling but was not correctable by exercise (such as severe visual impairment). Data extraction and quality assessment We used a form designed for this review to extract data on study and intervention characteristics, quality assessment, and outcomes (see supplementary file). The taxonomy for fall prevention interventions developed by the Prevention of Falls Network Europe (ProFaNE) was used to describe the characteristics of the interventions provided (for example, participantsâ&#x20AC;&#x2122; selection criteria, type of exercises, and intervention procedures). This tool uses internationally agreed criteria to evaluate systematically the content and format of fall prevention interventions. We also extracted the definitions and methods used to collect falls and to classify fall-related injuries, as well as the number, rate, or risk ratio of injurious falls and any available data on the nature of the injuries. We contacted authors of included articles to obtain more detailed data on the outcomes of injurious falls (for example, if authors reported the number of participants with an injurious fall but not the total number of injurious falls, or data on falls resulting in fractures but not data on other injurious falls). After reviewing the case definitions used in the selected studies, we sought to group definitions of injurious falls into more homogeneous categories to allow results to be compared across studies and the data to be pooled. The ProFaNE group recently proposed a standardized classification of injurious falls to be used in future randomized controlled trials. As a foundation for developing a retrospective classification of the definitions of injurious falls found in the studies selected for this review, we used the ProFaNE classification along with the standardized classification of Campbell and Robertson, which is the classification most often used in published trials of these interventions. We also recorded any reports of adverse effects associated with interventions. We followed the recommendations of the Cochrane Collaboration to assess the risk of bias in the following domains: random sequence generation (selection bias), allocation concealment (selection bias), blinding of the assessment of falls and injurious falls (detection bias), and incomplete outcome data (attrition bias). We also assessed bias in the recall of falls owing to unreliable methods of ascertainment, using the criteria developed for the Cochrane review of fall prevention trials. The methods used to confirm serious injurious falls were also

100

examined: we judged self-reports from participants to be at a high risk of bias, whereas we considered the use of medical records or radiography reports (for fractures) to be at low risk. Two authors (FEK, PDM) independently assessed the risks of bias and extracted data. The disagreement was resolved by consensus or adjudication by a third party. Statistical analysis The rate ratio of injurious falls was the outcome of interest. If the rate ratio was not presented in the article, we calculated it from the ratio of the total number of injurious falls divided by the total length of time falls were monitored (person-years) in the two comparison groups. In cases where data were available only for people who had completed the study, or where the trial authors had stated there were no losses to follow-up, we assumed that these participants had been followed up for the maximum possible period. We estimated the standard error of the rate ratio by using the formula given in the Cochrane handbook. We used the generic inverse variance method in Review Manager (RevMan) to group the trial results and we compiled forest plots for each category of injurious falls. To allow for variability among the participants, type of exercise intervention, and outcome definitions we used a random-effect model. We report the pooled rate ratios for each injurious fall outcome, along with 95% confidence intervals. We also explored the possible impact of risk of bias on statistically significant pooled estimates of exercise effect by removing studies of a poorer quality—that is, those for which the risk of bias was unclear for at least three of the quality components considered, or the risk was at least unclear for one category and high for another. Classification of injurious falls The definition and classification of injurious falls varied substantially and most trials did not provide a reference for their definition. Injurious falls usually included diverse consequences, ranging from relatively minor injuries such as bruises or abrasions to fractures or other serious injuries requiring hospital admission. Most often the definition referred to either the presence of symptoms or the use of medical care. In other cases, injurious falls meant simply any self-reported physical consequence of a fall, without any details. Some definitions specifically required the use of medical care, by using non-specific terms such as “fall for which medical care was sought,” “falls requiring medical care/medical attention,” or “medical consultations/visits.” When serious injuries were distinguished or specifically reported, their definition was more homogeneous across studies. Such injuries usually included fractures, severe soft tissue injuries requiring suturing, or other injuries leading to hospital admission. Some studies reported only fractures. Based on our review of case definitions used in the 17 studies, we distinguished four categories of injurious falls: those resulting in any reported consequences, including specific symptoms (ranging from bruises and cuts to more serious injuries such as fractures) or medical care; those resulting in medical care; those resulting in serious injuries such as fractures, head trauma, soft tissue injury requiring suturing, or any other injury requiring admission to hospital; and

101

those resulting in fractures. These categories represent increasingly specific subgroups of all injurious falls, which can also be considered to correspond to increasing levels of severity (except for those resulting in fracture, which is simply a specific type of serious injury).In each selected article (as a direct quotation), the category or categories of injurious falls in which it was classified for this review, and the rate ratio used in the corresponding analysis. For two studies, the rate ratio could not be calculated because the authors provided only the number of participants who had an injurious fall (rather than the number of such falls). In these cases, we used the ratio of the risk of at least one injurious fall in both groups instead. Of note, the outcomes of injurious fall in those studies were severe injuries and fractures, two relatively rare outcomes, so that the risk ratio was likely to be close to the rate ratio. Prospective daily calendars returned monthly are the preferred method for recording falls,16 and most of the trials used this method. However, only six of the 11 trials that reported data on serious injuries used medical records to confirm the injury. C. RESULTS RTIs compromised 23.6% of total injuries among the elderly. The most frequent injuries were about Car accidents (51.4%). Pedestrian injuries composed 48.1 % of the RTIs. Head and neck (32.1%) were the most injured body parts. There was a significant difference between elderly and non-elderly people in terms of RTIs Associated mortality (Odd=2.57[1.2-5.4CI95%]). Overall 25 main domains of intervention and 73 subordinate Domains were extracted in five categories (human, road and environment, tools and cars, medical, legal and political issues). D. DISCUSSION Discussion This systematic review provides evidence that fall prevention exercise programs for older people not only reduce the rates of falls but also prevent injuries resulting from falls in older community-dwelling people. The protective effect seems most pronounced for the most severe fall-related injuries: the estimated reduction is 37% for all injurious falls, 43% for severe injurious falls, and 61% for falls resulting in fractures. Many of the risk factors for falls and fall induced injuries are similar. These factors are correctable by well-designed exercise programs, even in the very old and frail. All exercise programs that have proved to be effective for fall prevention (and all trials included in this review) emphasize balance training, and there is now ample evidence that this type of program improves balance ability. However, most programs are multicomponentâ&#x20AC;&#x201D;that is, also include other types of exercise such as gait and functional training, strengthening exercises, flexibility, and endurance. There is evidence that these types of interventions can improve reaction time, gait, muscle strength, coordination, and overall physical functioning as well as cognitive

102

functions, especially executive function. It is therefore thought that exercise prevents injurious falls not only by improving balance and decreasing the risk of falling but also by improving cognitive functioning,41 and the speed and effectiveness of protective reflexes (such as quickly extending an arm or grabbing nearby objects) or the energy absorbing capacity of soft tissues (such as muscles), thereby diminishing the force of impact on the body. Hence, for any given initial energy of a fall, improved protective responses should decrease the severity of the resulting trauma, which may explain why the estimated protective effect of exercise is stronger for severe injurious falls than for all injurious falls, the latter including severe but also minor and moderate injuries. Although exercise reduces the severity of the injury, the pooled effect of exercise on reducing all injurious falls (37%) was larger than the effect of exercise on falls resulting in medical care (30%) (which are presumably more severe). However, medical care-seeking behavior is influenced by the type and availability of care and sociodemographic characteristics as well as by other personal factors such as personality, pain tolerance, and anxiety. Accordingly, the mere fact that medical care was sought does not necessarily imply that an injury was more severe, although this is probably less true when different categories of injurious falls are examined within the same population. Of the 10 studies included in the analysis of all injurious falls, five also contributed to the analysis of falls resulting in medical care, and three also contributed to the analysis of severe injurious falls. Within these studies, the point estimate of the effect of exercise decreased from all injurious falls to falls resulting in medical care for all studies but one, and from falls resulting in medical care to severe injurious falls for all studies. These results support the argument that exercise reduces the severity of the injuries caused by falls. Other risk factors are specific to the risk of trauma during a fall, and correction of these factors by exercise may also help explain the larger protective effect of exercise on serious injuries such as fractures. In particular, low bone mass is a major determinant of the risk of fracture once a fall begins. In three of the five trials included in the analysis of fall-related fractures, the intervention was specifically designed to improve bone mass and hence included high-intensity impact exercise in addition to balance, gait, and functional exercises. It resulted in a significant positive effect on bone mass at bone sites that varied with the study. However, these interventions were tested in women who were on average less than 75 years of age and did not have specific risk factors for falling. Hence, they may not be appropriate for older people aged more than 75 years, who are at the highest risk of falls and fractures, especially hip fractures. The large estimated pooled effect of more moderate-intensity exercise training on serious injuries found in this meta-analysis suggests that reducing the risk of falling and improving protective responses during a fall are important and feasible means of preventing fractures and other serious injuries in elderly people, as others have emphasized. This finding is especially important because large epidemiological studies have shown that most fractures in the

103

population occur in people at moderate “bone risk” for their age. Hence, while prescription of antiosteoporotic drug treatments is currently recommended for older people with low bone mass, who are at the highest risk of fracture, additional effective strategies that can be proposed to larger segments of the elderly population will be necessary to significantly reduce the burden of fractures in this population. Fall prevention exercise training seems to be one such strategy. E.CONCLUSIONS AND RECOMMENDATIONS Conclusion and recommendations are the results presented in this paper show a positive effect of exercise on injurious falls, including the most severe falls and those that result in medical care—that is, those with the greatest consequences for people’s health and use of resources. These results should provide useful additional evidence for healthcare providers to encourage participation in exercise fall prevention programs, and further justification for decision-makers to provide funding for those programs. Systematic reporting of falls and injuries should be implemented in future randomized controlled trials, where the different levels of severity of the injury should be standardized and defined in advance, to improve the comparison between studies and subsequently the accuracy of pooled estimates for each category of falls. Future trials should also aim to deal with some of the limitations of published studies, in particular by providing data on other important outcomes (physical and cognitive functional capacities, psychological outcomes, and quality of life) and a thorough description of the implementation process. consequences of falls in the older population: injuries, healthcare costs, and long-term reduced quality of life. J Trauma 2011;71:748-53.

Reference: 1 Rubenstein LZ. Falls in older people: epidemiology, risk factors and strategies for prevention. Age Ageing 2006;35(suppl 2):ii37-41.

5 Gill TM, Murphy TE, Gahbauer EA, Allore HG. Association of injurious falls with disability outcomes and nursing home admissions in community-living older persons. Am J Epidemiol 2013;178:418-25.

2 Stevens JA, Mack KA, Paulozzi LJ, Ballesteros MF. Self-reported falls and fall-related injuries among persons aged ≥65 years—United States, 2006. J Safety Res 2008;39:345-9.

6 Davis JC, Robertson MC, Ashe MC, Liu-Ambrose T, Khan KM, Marra CA. International comparison of cost of falls in older adults living in the community: a systematic review. Osteoporos Int 2010;21:1295-306.

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The Role of Psychological Intervention on Mental Health Outcome in Post-Traumatic Stress Disorder Patients: A Systematic Review Dyta Ghezhanny1, Jessica Anastasia1, Angeline Tancherla1, Felix Wijovi 1

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

Introduction: Trauma (either physical or emotional) can be defined as a deeply distressing experience that may lead to psychological problems, such as Post-Traumatic Stress Disorder (PTSD). Several studies suggest that early psychotherapy may help prevent the development of psychiatric symptoms. The effectiveness of psychotherapy in trauma patients with PTSD diagnosis is not fully understood. A better understanding of psychological interventions and their efficacy can guide the development of interventions aimed at preventing and ameliorating the negative psychological sequelae of trauma. The main objectives of this systematic review are to review the current literature on CBT, performed within 1 year of the injury, in adult trauma patients, and to determine their long-term effects on psychiatric symptoms and diagnoses. Materials and Methods: For our systematic review, we collected our data from online resources which includes PubMed, Google Scholar, and Science Direct, using combinations of keywords related to patient population, intervention, and outcomes. Studies that fulfill the inclusion and exclusion criteria will be analyzed. Conclusion: In our qualitative analysis, there is only 1 out of 11 studies stating that the psychological interventions do not differ in the improvement of mental health outcomes between the CBT group and control group. Other studies suggest that CBT reduces the PTSD symptoms and improve the mental health outcomes of the participants, which include anxiety, depression, quality of life, and overall functioning. Keyword: Post-traumatic Stress Disorder, Psychological Intervention, Cognitive Behavioral Therapy

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

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The Role of Psychological Intervention on Mental Health Outcome in Post-Traumatic Stress Disorder Patients: A Systematic Review Dyta Ghezhanny1, Jessica Anastasia1, Felix Wjovi1, Angeline Tancherla1 1

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

Introduction: Trauma (either physical or emotional) can be defined as a deeply distressing experience and may lead to psychological problems. The emotional nature of the trauma itself, in addition with a long stay at the hospital and recovery period (for physical trauma patients), drives trauma patients to be prone to psychiatric sequelae. After severe traumatic event, some patients may develop psychiatric disorders, which one of them includes Post-Traumatic Stress Disorder (PTSD). Several studies suggest that early psychotherapy or pharmacotherapy may help prevent the development of psychiatric symptoms. (Zatzick et al., 2004) Several studies which includes several systematic reviews and meta-analyses have evaluated the effects of early psychological interventions on outcomes in trauma patients with PTSD (Giummarra, Lennox, Dali, Costa, & Gabbe, 2018; Kornør et al., 2008) and its long-term effects. (Kline, Cooper, Rytwinksi, & Feeny, 2018) With respect to PSTD, specifically, a systematic-review of randomized controlled trials (RCTs) in trauma patients demonstrated that psychotherapy interventions (in this case Cognitive Behavioral Therapy) in patients diagnosed with PTSD based on DSM-IV have significantly reduced PTSD symptoms. (Kline et al., 2018) The effectiveness of psychotherapy in trauma patients with PTSD diagnosis is not fully understood and extended. Furthermore, there are several psychological interventions offered, including cognitive behaviour therapy (CBT), pharmacotherapy, and collaborative care (CC); however, no specific intervention has been demonstrated to be superior than the others.(Roberts et al., 2019) The main objectives of this systematic review are to review the current literature on CBT, performed within 1 year of the injury, in adult trauma patients, and to determine their long-term effects on psychiatric symptoms and diagnoses. We hypothesized that CBT may reduce the incidence of PTSD, anxiety, and depression in adult trauma survivors. A better understanding of psychological interventions and their efficacy can guide the development of interventions aimed to prevent and ameliorate the negative psychological sequelae of trauma. Methods: For our systematic review, we collected our data from online resources which includes PubMed, Google Scholar, and Science Direct, using combinations of keywords related to patient population, intervention, and outcomes, which are: “CBT”, “PTSD”, “outcomes”, “depression”, “anxiety”, “quality of life”. The studies that we included are only RCTs with participants, aged 18-70 years old, who were

112

diagnosed with PTSD. The psychotherapy intervention must be Cognitive Behavior Therapy (CBT) with more than one session, and the outcome assessed are incidence and severity of psychiatric consequences (e.g. PTSD, depression, and anxiety), social and psychological dimensions, and quality of life. The studies must be in English or Indonesian language and published after year 2010. Studies with patient reported opinions or outcomes through non-standardized questionnaire were excluded. We also excluded other main outcomes of intervention, such as number of hospital readmission, duration of admission, hospital cost, etc. If there were varied time of outcome measurements among the patients, the study will be excluded. Hypothesis question for this systematic review is â&#x20AC;&#x153;what is the effect of Cognitive Behavioral Therapy for patients with Posttraumatic Stress Disorder?â&#x20AC;?. 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 analyzed. The variables that we obtained from the analyzed studies are study characteristics and design, sample size, patient demographics, inclusion and exclusion criteria, intervention details (i.e., duration and total numbers of sessions, when the first session started, and who did the session), follow-up times, and primary or secondary outcomes.

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Results and Discussion: Using PICO approach, searching is done through online database, and we acquired 11 articles that will be analysed. The selection process is shown in the diagram below.

Total citations obtained from databases (PubMed, Science Direct, Google Scholar) n = 288

Inclusion Criteria & Exclusion Criteria

n = 22 Filtering double literature

n = 18 Relevant study n = 11

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

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Table 1 Inclusion and Exclusion Criteria Publication Type

Study Type Case Definition

Inclusion Criteria Original research in peer-reviewed journal

Exclusion Criteria Unpublished manuscripts, abstracts or lectures, dissertations, books and book chapters, editorials, online articles, letters to the editor or opinion pieces, and poster or conference presentations Randomized control trial Case reports, case series, meta-analysis, animal study, cross-sectional, case-control studies, retrospective studies, cohort Patients diagnosed with Posttraumatic Stress Disorder 1. Studies that include patients with pregnancy complications, paediatric, (PTSD) according to Diagnostic and Statistical Manual adolescence patients (<18 years of age) of Mental Disorders (DSM) -IV or V, or Clinician Administered PTSD Scale (CAPS) whether exposed to physical trauma or emotional trauma

Study Outcome

Incidence and severity of psychiatric consequences (e.g. PTSD, depression, and anxiety), social and psychological dimensions, quality of life

Intervention Type

Cognitive Behavioural Therapy (CBT)

Study Population

Adults (18-70 Years Old)

Publication Period Publication Language

â&#x2030;Ľ year 2010 English, Indonesian

1. Patient Reported opinions or outcomes through non-standardized questionnaire 2. Other main outcomes (i.e. number of hospital readmission, duration of admission, hospital cost, etc.) 3. Varied time of outcome measurements among the patients 1. Single session intervention 2. The intervention starts â&#x2030;Ľ 1 year after injury 3. Does not target psychiatric symptoms or disorders or long-term outcomes (functional status, QoL, etc.) 4. Internet or telephone based psychological therapy Children (< 18 years old) or elderly (>70 years old) < year 2010 Non-English, Non-Indonesian and not translated into either English or Indonesian

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Table 2 Summary of studies on psychological intervention in traumatic patients No

Authors (year)

Study

Country

design

(number of centre)

Inclusion Criteria (IC)/ Exclusion

Mean age

Criteria (EC), Mechanism of PTSD

Male/

Intervention (I) (type,

Follow-up

Primary (P) and

Female

Duration and Total

Time (Month)

Secondary (S)

(P), Additional Information (AI)

Number of Sessions,

Outcomes

When Started 1st

Measured

Session), Who did the

(Measurement

Session (i.e.,

Tools)

Findings

Psychologist, etc.) 1

Mueser et al. (2015)

RCT

USA (5)

(Mueser et al., 2015)

IC: Diagnosed based on DSM IV,

CBT, 1.5 hrs per session

post-treatment,

P: PTSD (CAPS)

Cognitive

significant function limitations within

for 9-13 total session, 2

6-month, 12-

S: Borderline

restructuring has a

the past 3-6 months, diagnosis of severe

weeks to 1 months after

month post

personality disorder

significant impact

PTSD, based on CAPS, schizophrenia

diagnosis, by clinicians

intervention

(SCID-II),

in the CBT

psychiatric

programme,

treatment for PTSD.

symptoms

reducing PTSD

EC: Hospital admission or suicide

(PANSS), Quality

symptoms and

attempt in the past 3 months, or

of Life (QOLI),

improving

substance dependence within the past 3

Overall functioning

functioning in

months.

(GAF)

people with severe

version,

interested

43.775

63/138

receiving

P: PTSD in severe mental injuries

mental illness

patients AI: N/A 2

Brunet et al. (2013)

RCT

Canada (2)

IC: Experienced a life-threatening

36.33

40/44

Dyadic CBT intervention

3 months

P: PTSD (IESR)

Decrease in PTSD

S: PTSD (CAPS)

symptoms at

(Brunet, Des Groseilliers,

event that elicited a peritraumatic

(1st: 90 min 2 week after

Cordova, & Ruzek, 2013)

reaction of fear, helplessness, or horror

trauma; 2nd: 75 min 2

follow-up, not

in the last 10 days

week

statistically

EC: Doesnâ&#x20AC;&#x2122;t speak either English or

after 1st session), 2

significant

French, history of suspect or

sessions, within 1 months

between groups

confirmed TBI, lifetime diagnosis pf

after exposure, by clinical

psychosis, substance or alcohol

psychologist

dependence, bipolar, mental retardation, clinically depressed, were taking psycho-tropic medication at the onset of the study, were injured to the extent that they could not participate in the study, live outside Montreal metropolitan area, did not have

116

significant other to bring to the therapy session, did not make appointment with the therapist within 30 days P: MVA, NSA, Occupational and Leisure Accident AI: N/A 3

Steel et al. (2016) (Steel et

RCT

UK (multi)

al., 2017)

O'Donnell ML et al. (2012)

RCT

(O’Donnell et al., 2012)

IC: 18-65 years old, had stable living

CBT, 1 hour per session for

Post-treatment,

P: PTSD (CAPS)

The current trial did

arrangements, met Diagnostic and

42.25

38/23

12-16 session of CBT by

6 months

S: Psychosis

not demonstrate any

Statistical Manual of Mental Disorders,

trainee clinical psychologist

symptoms (PANSS)

effect in favour of

fourth edition (DSM-IV) (American

CBT. Cognitive

Psychiatric Association, 2000) criteria for

restructuring

schizophrenia, schizo-affective disorder

programmes may

or schizophreniform disorder, met DSM-

require further

IV criteria for PTSD

adaptation to

EC: Organic impairment or insufficient

promote emotional

command of English.

processing of

P: Schizophrenia, schizo-affective

traumatic memories

disorder or schizophreniform disorder

within people

with PTSD

diagnosed with a

AI: N/A

psychotic disorder

Australia

IC: admitted to hospital for >24 h after

(1)

trauma, 18–70 years old

36.1

28/18

4 x 90 min sessions of CBT then 6x 90 min session if

1 year

EC: Moderate or severe TBI, psychotic

increased anxiety/

or suicidal

depression at 3 month,

symptoms in CBT

P: Motor Vehicle Accident, NSA

within 1 month after

group.

AI: Included some patients with pre-

exposure by clinical

existing psychiatric condition, mild TBI,

psychologist

P: PTSD (CAPS), Depression (BDI), Anxiety (HADS-A)

Decrease in PTSD, anxiety, and depression

and SA 5

Skogstad L. et al. (2015) (Skogstad, Hem, Sandvik, & Ekeberg, 2015)

RCT

Norway (1)

IC: 18–65 years old, GCS ≥ 11, acute

39.3

35/50

1-6 session(s) of CBT which lasting for 1 hr for

physical injury, PTSD with IES ≥ 20

each session, within 1

EC: IES < 20, incarcerated, self-inflicted

month after exposure and

injury, serious psychiatric, and/or SA

done by nurses

P: MVA, NSA, fall AI: Included some patients with previous psychiatric disorder

117

1 year

P: PTSD (IESR), Depression (HADSD), Anxiety (HADS-A)

Significant reduction in PTSD, depression, or anxiety symptoms in intervention group

Levi et al. (2015) (Levi,

RCT

Israel (1)

Bar-Haim, Kreiss, & Fruchter, 2016)

Markowitz et al. (2015)

RCT

USA (1)

(Markowitz et al., 2015)

IC: Treatment-seeking veterans,

32.1

243/0

8-12 months

P: PTSD (CAPS)

Significant

diagnosed with chronic combat-related

sessions, by 12 therapists

S: PTSD

symptom reduction

PTSD

(psychiatrists,

Questionnaire,

for CBT and PDT;

EC: Receiving another treatment which

clinical psychologists and

Depression

no significant

includes pharmacotherapy or group

social workers) with

(MADRS), Function

difference between

therapy

extensive experience in

(POAMS)

treatment

P: War or combat-related PTSD

PTSD diagnosis and

AI: All male

treatment

IC: 18–65 years old, had primary DSM-

39.94

29/49

IV diagnosis of chronic PTSD and CAPS score ≥50 (at least moderate PTSD severity) EC: comprised psychotic disorders,

24 once-weekly CBT

interventions

10 weekly 90-minute

Week 7 and

sessions (900 minutes) of

week 14

P: PTSD (CAPS)

Significant and comparable pre–

CBT by Study therapists,

post- treatment

psychologists or

symptom

psychiatrists

improvement in CBT and IPT

bipolar disorder, unstable medical

14 weekly 50-minute

groups but CBT

condition

sessions (700 minutes) of

group showed more

substance dependence, active suicidal

IPT by Study therapists,

rapid improvement

ideation antisocial, schizotypal, or

psychologists or

schizoid personality disorder, prior non-

psychiatrists

response to ≥8 weeks of study therapy ongoing psychiatric treatment including pharmacotherapy P: PTSD AI: N/A 8

Wu KK et al. (2012) (Wu,

RCT

Li, & Cho, 2014)

Hongkong,

IC: ≥ 18 years old, MVA survivor ,

P: PTSD (IESR),

CBT group had a

China (1)

PTSD

36/17

4 x 1.5 h weekly CBT sessions within 1-3 months

6 months

Depression (HADS-

greater decrease in

EC: Pre-existing major psychiatric

after exposure done by

D), Anxiety (HADS-

anxiety at 3 and 6-

disorder, cognitive deficit

psychologist

month, there was

P: MVA

only a decrease in

AI: N/A

depress-ion at 6month, and no change in PTSD symptoms at 3 and 6-month

Nacasch et al. (2011) (Nacasch et al., 2011)

RCT

Israel (1)

IC: Patient had to be diagnosed with

P: PTSD symptoms

The severity of

PTSD related to combat or terror, and the

34.25

120 minutes 1x per week by

(PSS-I)

PTSD after

traumatic event must have occurred at

5 therapists (2 psychiatrists,

S: Depression (BDI),

treatment was lower

least 3 months before diagnosis AND had

2 master's degree

Anxiety (STAI-S),

in the intervention

PTCI

group compared to

to have a score of 25 or more on the

118

26/0

9 to 15 sessions of 90 to

12 months

PTSD Symptoms-Interview Version

psychologists, 1 masterâ&#x20AC;&#x2122;s

the control group (p

(PSS-I), If treated with medication,

degree social worker)

< 0.01)

patients had to be on a stable regimen for at least 3 months prior to their pretreatment evaluation EC: Current active substance dependence, current psychotic symptoms, bipolar disorder, severe dissociative disorder, patients deemed at high risk for suicidal behaviour P: combat or terror-related PTSD AI: All Male 10

Shalev AY et al. (2016)

RCT

Israel (1)

(Shalev et al., 2016)

IC: 18â&#x20AC;&#x201C;70 years old, trauma within 7

P: PTSD (CAPS)

Significant decrease

days

39.1

106/125

12 weeks. 15 hours sessions/ week of PE or

36 months

S: PTSD (PSSR),

in PTSD and

EC: > 7 days of hospital stay,

CBT within 1 month after

Depression (BDI)

depression

unconscious at time of ED, admission,

exposure by psychologist

prevalence and

medical/surgical condition that interfered

symptoms between

with ability to participate in study

1 and 5-month in PE

P: MVA, work, terrorist

and CBT groups. No

AI : N/A

difference in PTSD and depress-ion prevalence and symptoms at 3 years.

Dunne et al. (2012) (Dunne, Kenardy, & Sterling, 2012)

RCT

Australia

IC: had chronic WAD grade II or III

P: PTSD (SCID)

Clinically

(1)

(range, 3mo to 5 y, M = 28.5 months) and

32.54

of individually delivered

S: PTSD symptom

significant

met the diagnostic criteria for current

TF-CBT by single graduate

severity (PDS),

reductions in PTSD

MVC-related PTSD.

psychologist with

Anxiety and

symptoms were

EC: Cervical spine fractures, serious

postgraduate clinical

Depression (DASS)

found in the TF-

head injury or burns, previous history of

training and 12 months of

CBT group

neck pain or headaches requiring

prior experience delivering

compared with the

treatment, insufficient comprehension of

TF-CBT interventions by

waitlist at post-

English to complete measures, if they

single graduate

assessment, with

were receiving current treatment for a

psychologist with

further gains noted

major psychiatric disorder (i.e.

postgraduate clinical

at the follow-up.

psychological or pharmacological

training and 12 months of

treatment)

prior experience delivering

P: Whiplash-associated disorders

TF-CBT interventions

AI: N/A

119

13/13

10 weekly 1-hour sessions

6 months

Notes BDI: Beck's Depression Inventory CAPS : Clinically Administered PTSD Scale

PDS: Post-traumatic Stress Diagnostic Scale

CBT: Cognitive Behavioral Therapy

POAMS: Psychotherapy Outcome Assessment and Monitoring System

DASS: Depression Anxiety Stress Scale

PSS-I: Post-traumatic Stress Disorder Symptom Scale

GAF: Global Assessment of Functioning

PSSR: PTSD Symptoms Scale- Revised

GCS: Glasgow Coma Scale

PTSD: Post-traumatic Stress Disorder

HADS-A: Hospital Anxiety and Depression Scale-Anxiety

QOLI: Quality of Life Inventory

HADS-D: Hospital Anxiety and Depression Scale-Depression

RCT: Randomized Controlled Trial

IES: Impact of Event Scale

SA: Sexual Assaults

IESR: Impact of Event Scale - Revised

SCID: Structured Clinical Interview for DSM

IPT: Interpersonal Psychotherapy

SCID-II : Structured Clinical Interview for DSM-II

MADRS: Montgomery–Åsberg Depression Rating Scale

STAI-S: State-Trait Anxiety Inventory-State Anxiety

MVA: Motor Vehicle Accidents

TBI: Traumatic Brain Injury

NSA: Non-sexual Assaults

TF-CBT: Trauma-focused Cognitive Behavioural Therapy

PANSS : Positive and Negative Syndrome Scale

WAD: Whiplash-associated Disease

120

The study by Mueser et al consists of participants who were diagnosed with PTSD and severe mental illness, with 104 participants in a 12-16 session CBT group and 87 participants in brief group (3 session breath retraining and education). At post-treatment follow-up in CBT group, the total CAPS (Clinician Administered PTSD Scale) score had significantly reduced from baseline (post-treatment=63.55; baseline=86.06, p=0.01). At 6 months and 12 months follow-up, the total CAPS score of CBT group slightly decreased from post-treatment (63.23 and 60.62 respectively, p=0.01). PCTI (post-traumatic cognitions inventory), Positive and Negative Syndrome Scale, Beck Depression and Anxiety inventory, Global Assessment of Functioning, Quality of Life, and Social Functioning were also recorded at post-treatment, 6 months, and 12 months follow-up. CBT group had improved symptoms and overall functioning, and better outcomes than brief group. (Mueser et al., 2015) In the RCT by Brunet et al, 90 trauma-exposed participants were recruited, and 44 of them were assigned to dyadic CBT intervention for 2 sessions. Post-intervention follow-up at 3rd month showed significant decrease in IES-R (Impact of Event Scale-Revised) score, and it is lower than control group (p=0.04). Secondary outcome was assessed using CAPS. In spite of a significant between-group symptom reduction, a Chi-square analysis showed no significant difference in the number of participants with a CAPS PTSD diagnosis at the post-treatment in the control group (8/32) compared to that of the intervention group (5/34), x2(1, N = 66)=1.10, p = 0.36). (Brunet et al., 2013) According to Steel et al, 61 participants were assigned to different intervention groups, 30 into CBT groups and 31 into control groups. At post-treatment and 6 month follow-up, both the CBT and control groups showed a significant decrease of PTSD symptoms on CAPS (CBT: F = 4.41, p < 0.01; Control: F = 8.51, p < 0.01), but there was no significant difference between the intervention and control groups in the primary outcome of PTSD symptoms on the CAPS-S at the end of treatment (p > 0.1, between-group d = −0.26, 95% CI −0.84 to 0.32), or in the secondary outcome of the positive symptoms on PANSS positive (p > 0.1, between-group d = 0.32, 95% CI −0.26 to 0.91). (Steel et al., 2017) Based on the RCT by O’Donnell ML et al, 24 PTSD patients who were assigned to CBT group had lower CAPS score at 6-month and 12-month follow-up (pre-treatment = 56.61; 6-month follow-up = 31.95; 12-month follow-up = 25.26, p < 0.05). Secondary outcomes that were assessed include depression on BDI (Beck Depression Inventory), and anxiety on HADS-A (Hospital Anxiety and Depression Scale). BDI scores of CBT group at follow-up had decreased significantly (pre-treatment = 30.13; 6-month follow-up = 12.24; 12-month follow-up = 7.84, p < 0.05). HADS-A scores were decreased in CBT group at followup (pre-treatment = 30.13; 6-month follow-up = 12.24; 12-month follow-up = 13.95, p < 0.05). A significant difference of outcomes (CAPS, BDI, HADS-A) was observed between CBT group and control group. (O’Donnell et al., 2012)

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In the RCT conducted by Skogstad et al, 85 participants with PTSD were randomly assigned to CBT group (n = 35) and control group (n = 50). At 3-month follow-up, the IES scores were significantly reduced in both groups (CBT = 41.1-28.6, p < 0.001 vs. control = 35.4-26.2, p < 0.001), but not significantly different between groups. Baseline IES score was a significant predictor of IES scores at 3 (β = 0.4, P < 0.05) and 12 months (β = 0.3, P < 0.05), whereas overall daily functioning at 3 months predicted IES scores at 12 months (β = -0.5, P < 0.001). Patients receiving intervention became significantly more optimistic during the year and had an increase in overall daily functioning from 3 to 12 months (p < 0.001). Patients declining intervention were more pessimistic and had lower daily functioning. (Skogstad et al., 2015) Levi et al reported that there were no differences in symptom levels between CBT group (n = 95) and control group (n = 148) of participants who were diagnosed with chronic combat-related PTSD at any of the assessment points, and none of the interaction effects were significant, which indicates the equal efficacy for both interventions. The three ANOVAs relating to the CAPS, PTSD Questionnaire and MADRS depression scores revealed main effects of Time, Fs(2, 416) =57.91, 49.61 and 42.97, respectively, ps<0.001, pointing to significant reductions in clinician-rated and patient-reported PTSD symptoms and depression symptoms following treatment, and a retention of treatment gains at follow-up. (Levi et al., 2016) According to the RCT by Markowitz et al, 3 interventions (Interpersonal Psychotherapy, CBT, and Relaxation Therapy) done on 110 PTSD patients had large within-group pre/post effect sizes (d=1.32–1.88). Response rates (>30% CAPS improvement) were: Interpersonal Psychotherapy 63%, CBT 47%, and Relaxation Therapy 38%. Interpersonal psychotherapy and CBT CAPS outcome differed by 5.5 points. Interpersonal Psychotherapy and CBT improved quality of life and social functioning more than Relaxation Therapy (p = 0.010). (Markowitz et al., 2015) Wu, et.al. study indicates that there were significant improvements in the measures of anxiety, depression, and PTSD symptoms over time. Participants treated with B-CBT showed greater reductions in anxiety at 3-month and 6-month followups, and in depression at 6-month follow-up. The results show that the B-CBT participants were significantly younger than SHP participants. At 1week after MVC, the IES-R hyperarousal score of the B-CBT participants was higher than that of SHP participants at p= 0.006. At 1 month after the MVC, the participants assigned to the B-CBT condition had a higher IES-R score for hyperarousal at p= 0.001, a higher

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Figure 1. Change of HADS subscale scores from 1-month to 6-month. B-CBT = Brief Cognitive Behavioural Therapy. SHP = Selfhelp Program

HADS-A score at p= 0.007, and a higher HADS-D score at p=0.12. No significant difference was found for any of the other variables. There was no differential effect on PTSD symptoms measured by IES-R. (Wu et al., 2014) In their study, Nacasch, et. al. PTSD symptoms severity is significantly decline in patients who received Psychological intervention therapy which includes CBT for long period, compared to patients who received TAU Treatment (control group) (F1,24 = 35.3 P < .001). Similar results have emerged in measures of depression and state and trait anxiety. Furthermore, a significant change from pre-treatment to followup was found for CBT group (F1,14 = 80.5, P < .0001), but not for the control group (F1,10.3 = 0.6, P = .44). (Nacasch et al., 2011) Shalev et.al. reported in their study that cognitive therapy significantly reduced PTSD and PTSD symptoms between 1 and 5 months of therapy after exposure (mean of CAPS total scores [95% CI] at 1 month: prolonged exposure = 73.59 [68.21-78.96] and cognitive therapy = 71.78 [66.92-78.93]; mean CAPS total scores [95% CI] at 5 months: prolonged exposure = 28.59 [21.89-35.29] and cognitive therapy = 29.48 [21.32-37.95], P < 0.001). However at 3 years after exposure, the study groups had similar levels of PTSD symptoms (mean CAPS total scores [95% CI]: prolonged exposure = 31.51 [20.25-42.78]; cognitive therapy = 32.08 [20.74-43.42]; SSRI = 34.31 [16.54-52.07]; placebo = 32.13 [20.15-44.12]; and no intervention = 30.59 [19.40-41.78]), similar prevalence of PTSD (28.6%-46.2%), and similar secondary outcomes. (Shalev et al., 2016) In addition, Dunne et.al also states clinically significant reductions in PTSD symptoms were found in the TF-CBT group compared with the waitlist at post- assessment, with further gains noted at the followup. The treatment of PTSD was also associated with clinically significant improvements in neck disability, physical, emotional, and social functioning and physiological reactivity to trauma cues, whereas limited changes were found in sensory pain thresholds. There were also no differences found between the treatment and waitlist groups with regard to medication use, specifically simple analgesics (84.6% and 76.9%, respectively; w2 (1)=0.25, P=0.62) and antidepressants (38.5% in each group). (Dunne et al., 2012) Our analysis is limited by the internal validity of the scoring systems we examined, as well as individual patient characteristic. We were also unable to control for the socioeconomic status of the participants which may be the major confounding factor of those studies. Our inclusion criteria of having a mixed causal of PTSD also prevent us from analyzing the effect of various etiologies on the interventions and outcome of interest. In addition, there may also be varied spectrum of disease severity across studies. There may have variability among studies with respect to the intervention methodology, such as therapy initiation time, number, duration of the session, intervention provider, and follow up periods. Some studies with shorter follow-up periods may produce more inaccurate results on the impact of the intervention on symptoms and limit the ability to interpret long-term effects.

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Conclusion In our qualitative analysis, there is only 1 out of 11 studies stating that the psychological interventions do not differ in the improvement of mental health outcomes between the CBT group and control group. Other studies suggest that CBT reduces the PTSD symptoms and improve the mental health outcomes of the participants, which include anxiety, depression, quality of life, and overall functioning. Through this systematic review, we hope that this could aid in the development of interventions aimed to prevent and ameliorate the negative psychological sequelae of trauma.

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References: Brunet, A., Des Groseilliers, I. B., Cordova, M. J., & Ruzek, J. I. (2013). Randomized controlled trial of a brief dyadic cognitivebehavioral intervention designed to prevent PTSD. European Journal of Psychotraumatology, 4, 1–12. https://doi.org/10.3402/ejpt.v4i0.21572 Dunne, R. L., Kenardy, J., & Sterling, M. (2012). A randomized controlled trial of cognitive-behavioral therapy for the treatment of PTSD in the context of chronic whiplash. Clinical Journal of Pain, 28, 755–765. https://doi.org/10.1097/AJP.0b013e318243e16b Giummarra, M. J., Lennox, A., Dali, G., Costa, B., & Gabbe, B. J. (2018). Early psychological interventions for posttraumatic stress, depression and anxiety after traumatic injury: A systematic review and meta-analysis. Clinical Psychology Review, 62, 11–36. https://doi.org/10.1016/j.cpr.2018.05.001 Kline, A. C., Cooper, A. A., Rytwinksi, N. K., & Feeny, N. C. (2018). Long-term efficacy of psychotherapy for posttraumatic stress disorder: A meta-analysis of randomized controlled trials. Clinical Psychology Review, 59(September 2017), 30–40. https://doi.org/10.1016/j.cpr.2017.10.009 Kornør, H., Winje, D., Ekeberg, Ø., Weisæth, L., Kirkehei, I., Johansen, K., & Steiro, A. (2008). Early trauma-focused cognitive-behavioural therapy to prevent chronic post-traumatic stress disorder and related symptoms: A systematic review and meta-analysis. BMC Psychiatry, 8, 1–8. https://doi.org/10.1186/1471-244X-8-81 Levi, O., Bar-Haim, Y., Kreiss, Y., & Fruchter, E. (2016). Cognitive-Behavioural Therapy and Psychodynamic Psychotherapy in the Treatment of Combat-Related Post-Traumatic Stress Disorder: A Comparative Effectiveness Study. Clinical Psychology & Psychotherapy, 23, 298–307. https://doi.org/10.1002/cpp.1969 Markowitz, J. C., Petkova, E., Neria, Y., Van Meter, P. E., Zhao, Y., Hembree, E., … Marshall, R. D. (2015). Is Exposure Necessary? A Randomized Clinical Trial of interpersonal Psychotherapy for PTSD. American Jounal of Psychiatry, 172, 430–440. Mueser, K. T., Gottlieb, J. D., Xie, H., Lu, W., Yanos, P. T., Rosenberg, S. D., … McHugo, G. J. (2015). Evaluation of cognitive restructuring for post-traumatic stress disorder in people with severe mental illness. British Journal of Psychiatry, 206, 501–508. https://doi.org/10.1192/bjp.bp.114.147926 Nacasch, N., Foa, E. B., Huppert, J. D., Tzur, D., Fostick, L., Dinstein, Y., … Zohar, J. (2011). Prolonged exposure therapy for combat- and terror-related posttraumatic stress disorder: A randomized control comparison with treatment as usual. Journal of Clinical Psychiatry, 72, 1174–1180. https://doi.org/10.4088/JCP.09m05682blu O’Donnell, M. L., Lau, W., Tipping, S., Holmes, A. C. N., Ellen, S., Judson, R., … Forbes, D. (2012).

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Stepped early psychological intervention for posttraumatic stress disorder, other anxiety disorders, and depression following serious injury. Journal of Traumatic Stress, 25, 125–133. https://doi.org/10.1002/jts.21677 Roberts, N. P., Kitchiner, N. J., Kenardy, J., Robertson, L., Lewis, C., & Bisson, J. I. (2019). Multiple session early psychological interventions for the prevention of post-traumatic stress disorder. Cochrane Database of Systematic Reviews, 2019(8). https://doi.org/10.1002/14651858.CD006869.pub3 Shalev, A. Y., Ankri, Y., Gilad, M., Israeli-Shalev, Y., Adessky, R., Qian, M., & Freedman, S. (2016). Long-Term Outcome of Early Interventions to prevent Posttraumatic Stress Disorder. The Journal of Clinical Psychiatry, 77. Skogstad, L., Hem, E., Sandvik, L., & Ekeberg, O. (2015). Nurse-Led Psychological Intervention After Physical Traumas: A Randomized Controlled Trial. Journal of Clinical Medicine Research, 7, 339– 347. https://doi.org/10.14740/jocmr2082w Steel, C., Hardy, A., Smith, B., Wykes, T., Rose, S., Enright, S., … Mueser, K. T. (2017). Cognitivebehaviour therapy for post-traumatic stress in schizophrenia. A randomized controlled trial. Psychological Medicine, 47, 43–51. https://doi.org/10.1017/S0033291716002117 Wu, K. K., Li, F. W., & Cho, V. W. (2014). A randomized controlled trial of the effectiveness of briefCBT for patients with symptoms of posttraumatic stress following a motor vehicle crash. Behavioural and Cognitive Psychotherapy, 42, 31–47. https://doi.org/10.1017/S1352465812000859 Zatzick, D., Roy-Byrne, P., Russo, J., Rivara, F., Droesch, R. A., Wagner, A., … Katon, W. (2004). A Randomized Effectiveness Trial of Stepped Collaborative Care for Acutely Injured Trauma Survivors. Archives of General Psychiatry, 61, 498–506. https://doi.org/10.1001/archpsyc.61.5.498

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Injury Severity Score (ISS) Per Admission as a Predictor for Length of Hospital Stay in Multiple Trauma Adult Patients Anthony Yusuf 1, Angeline Tancherla1, Felix Wijovi1 1

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

Introduction Trauma is one of the main health problems in the world that causes disability and even death in all age groups. In order to increase survival rate of the patients, it is important for traumatic patients to receive appropriate medical care, including proper triage, surgery and hospital stay. The initial assessment is critical. It involves a physical evaluation, and also may include the use of imaging tools to determine the types of injuries accurately and to formulate a course of treatment. The Injury Severity Score (ISS) is an established medical score to assess trauma severity. It correlates with mortality, morbidity and hospitalization time after trauma. However, there is limited information (only 1 study) about the ISS in predicting outcome of multiple trauma patients in Indonesia. We aim to analyse the use of ISS index in predicting the length of hospital stay in adult multiple trauma patients in Indonesia. Material and Methods This is a cross sectional study which is based on multiple trauma patients who were admitted in emergency department of Siloam General Hospital between January 2020 - April 2020. All participants were multiple trauma patients older than 18 years old and younger than 70 years old. The required data was derived from the hospital information system to obtain the ISS score for predicting the multiple trauma patient's length of hospital stay. Patient who have psychological trauma, nonmultiple trauma, predisposing conditions (diabetes mellitus, hypertension, kidney failure, chronic lung disease, and neoplasm), or with ventilator usage are excluded from this study. In addition, children (< 18 years old) or elderly (>70 years old) also excluded. Conclusion Through this study, we obtained the predictive equation of length of stay: Length of Hospital Stay (days) = -0.317 + 0.530 (ISS score per admission) Âą 4 days. However, there are some limitations in this study. This study could not predict the mortality of the patients and is only limited to multiple trauma patient. In addition, this study is only limited to one centre. The specificity and sensitivity has not been determined. We strongly suggest for future study to develop this equation with other factors considered and included. Keywords: Multiple trauma, ISS, predictor, hospital stay

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Injury Severity Score (ISS) Per Admission as a Predictor for Length of Hospital Stay in Multiple Trauma Adult Patients Anthony Yusuf 1, Angeline Tancherla1, Felix Wijovi1 1

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

128

Injury Severity Score (ISS) Per Admission as a Predictor for Length of Hospital Stay in Multiple Trauma Adult Patients Anthony Yusuf 1, Angeline Tancherla1, Felix Wijovi1 1

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

Introduction: Trauma is one of the main health problems in the world that causes disability and even death in all age groups. It is estimated that by 2020, trauma will reach the third cause of death worldwide, following cardiovascular and pulmonary disease. There are many causes of major trauma, blunt and penetrating, including falls, motor vehicle collisions, stabbing wounds, and gunshot wounds. Depending on the severity of injury, quickness of management and transportation to an appropriate medical facility or trauma centre may be necessary to prevent mortality and morbidity. Common complications of trauma include haemorrhage, respiratory failure, renal failure, sepsis, and multiorgan failure. These complications will result in the increased risk of mortality. In traumatic brain injury setting, it may further cause a disruption of nerve functions (especially central nervous system) which may affect both motor and sensory function, cognitive or mental function, and may lead to death. In order to increase survival rate of the patients, it is important for traumatic patients to receive appropriate medical care, including proper triage, surgery and hospital stay. The initial assessment is critical, and involves a physical evaluation and also may include the use of imaging tools to determine the types of injuries accurately and to formulate a course of treatment. During admission, there are several trauma scoring systems such as anatomic, physiologic and combined scores that could be used to evaluate patientâ&#x20AC;&#x2122;s condition and severity of trauma. Physiological scores describe changes due to a trauma and translated by changes in vital signs and consciousness. On the other hand, anatomical scores describe all the injuries recorded by clinical examination, imaging, surgery or autopsy. They are used to stratify trauma patients and measure lesion severity. Scores that include both anatomical and physiological criteria (mixed scores) are useful for patientâ&#x20AC;&#x2122;s prognosis. Some of the trauma scoring systems that are widely used are ISS (Injury Severity Score) and NISS (New Injury Severity Score) which are anatomical scoring, RTS (Revised Trauma Score) which is a physiologic scoring, and TRISS (Trauma Injury Severity Score) which is a combined scoring. The Injury Severity Score (ISS) is an established medical score to assess trauma severity. It correlates with mortality, morbidity and hospitalization time after trauma. However, there is limited information (only 1 study) about the ISS in predicting outcome of multiple trauma patients in Indonesia, especially regarding the correlation of ISS and length of stay in multiple trauma patients. Therefore, through this study, we aim to analyse the use of ISS index in predicting the length of hospital stay in adult multiple trauma patients in Indonesia.

129

Methods: Study design and setting This is a cross sectional study which is based on multiple trauma patients who were admitted in emergency department of Siloam General Hospital between January 2020 - April 2020. The data collected were: demographic characteristics (age, sex), injury (type of injury, mechanism of injury, location of injury, mode of transport), and patients’ length of hospital stay. Data were collected anonymously to respect the ethical consideration. Participants All participants were multiple trauma patients older than 18 years old but younger than 70 years old, who were referred to emergency department of Siloam General Hospital in Tangerang in the months of January 2020 - April 2020. However, patients who had passed away during our study were excluded. Patients with an existing predisposition condition (such as diabetes, hypertension, etc.) or ventilator usage will also be excluded. Data gathering The required data was derived from the hospital information system to get the ISS score for predicting the multiple trauma patient's length of hospital stay. The scores of ISS is derived from the Abbreviated Injury Scale (AIS). The ISS score is gathered in the emergency room together with the health care professionals in charge at the time. Statistical analysis The ability of ISS score in predicting hospitalization was evaluated by Kolmogorov-smirnov normality test. It is used to determine whether the data gathered are normal or not. Non-parametric correlation test of both variables is used with a confidence interval of 95%. Linear regression test was used to know the relationship between two variables and to get the predictor formula. All statistical analysis was performed by SPSS (ver. 25). The significant level was considered at 0.05. Hypothesis question for study is “Can an ISS score predict the length of hospital in multiple trauma adult patients?”.

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Table 1 Inclusion and Exclusion Criteria Inclusion Criteria

Exclusion Criteria

Case

Patients diagnosed with multiple

1. Psychological trauma patients

Definition

physical trauma patients with

2. Non-multiple trauma patients

various causes

3. Predisposing conditions (Diabetes melitus, hypertension, kidney failure, chronic lung disease, and neoplasm) 4. Ventilator usage

Study

Length of Hospital Stay

Outcome Study

Adults (18-70 Years Old)

Children (< 18 years old) or elderly (>70

Population

years old)

Results and Discussion We gathered data of 50 patients with a mean age of 38.54 (19-58) years old. From the 50 patients, 40 (80%) patients are males and 10 (20%) are females. Most common mechanism of injury was caused by the blunt object (58.8%), followed by sharp object (31.4%), and burning objects (7.8%). Ziglar et al had also reported that blunt trauma is the most common mechanism of trauma. The number of male patients in this study was 4 times more than the number of female patients. This might be due to the active working of male population, who travelled more frequently, and drive motor vehicle more commonly than female population. The proportion was similar with Pakistan population according to a study by Chaudri et al. In Singapore, male to female polytrauma patient ratio was smaller, which is 2.8:1. The spearman correlation is used due to abnormal data gathered in this study (<0.05). The correlation between ISS score per-admission and the length of hospital stay is defined by r-value of 0.835 with the p-value of 0.0005, which means both variables are strongly and positively correlated. It means the greater ISS score will be followed by the increasing length of hospital stay. Based on the statistics, data are significant between the ISS Score and length of hospital stay. According to Shu et al, the ISS was significantly correlated with ICU stay and LOS (length of stay). The ICU stay and LOS in patients with extremely severe trauma (ISSâ&#x2030;Ľ25) who underwent surgery were significantly longer than any other group. In addition, the ICU stay and LOS increased by 0.496 and 0.656 days per incremental increase in ISS. Andre et al reported that the correlation between ISS score and LOS is r2 = 0.249, p = 0.0008. A study by Watts et al, that included elderly trauma patients (aged > 65 years old), showed that the total hospital LOS increased with increasing ISS, with statistical significance decreasing at the highest levels of ISS, which shows that ISS had limited correlation with hospital LOS in elderly trauma patients.

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From the linear regression test, we get the determination coefficient (R2) from the 'model summary' table which is 0.698. The p-value from the 'ANOVA' table which is 0.0005 and that means the simple regression test is fit with the data gathered. The regression line equation can be seen in the 'coefficient' table in the column 'B'.

The regression equation to predict the length of hospital stay based on the ISS score is defined by the pre-existing formula Y = a + bX. Based on the analysis result, the coefficient (intercept value or a-value) equal to -0.317 while b-value is 0.530. Thus, the regression equation is: Length of hospital stay (days) = -0.317 + 0.530 * (ISS score per admission) With that equation, length of hospital stay in multiple trauma patients can be predicted if we know the ISS score per admission of the patients. The p-value is 0.0005 which means there is a linear correlation between the ISS score and the length of hospital stay. Based on the b-value= 0.530, we can conclude that the length of hospital stay will increased by 0.530 day if the ISS score is increased by 1. To sum up the result, attached is the result of correlation and regression analysis of both variables. Variable

ISS Score

0.835

0.698

Linear equation Length of stay = -0.317 + 0.530 * (ISS score per admission)

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p-value 0.0005

This regression prediction cannot result an exact number of the outcome and thus the prediction is also based on the 'Standard Error of The Estimate (SEE)' in the 'Model Summary' table to predict the error of the equation which valued 1.937. Therefore, dependent variable variation is defined as Z * SEE. Z score calculated based on the Z table with the confidence interval of 95% and thus the Z Score is 1.96 and we get this calculation 1.96 * 1.937 = ± 3.8 » ± 4 days In addition to the prediction equation, we get this new equation to get the prediction of the length of hospital stay and the error added. Length of hospital stay (days) = -0.317 + 0.530 * (ISS score per admission) ± 4 days Below is the prediction graph on this study.

The limitation of this study is the sensitivity and specificity of the equation is not determined and thus the equation need to be validated in the future study. Aside from that, we do not know whether it can be applied in single trauma, since the result may differ between types of trauma. In addition, it does not contain data of trauma patients of other hospitals and is not population based. We urge for future researches to improve the equation in order to predict the death of patients by considering other factors that can affect the hospital stay.

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Conclusion The ISS scoring system may become a predictive score to determine the length of hospital stay in multiple-trauma patient. The length of hospital stay will increased by 0.530 day if the ISS score is increased by 1. The result of this study, we can get the predictive formula of length of stay is as follow: Length of hospital stay (days) = -0.317 + 0.530 (ISS score per admission) Âą 4 days. However, there are some limitations in this study. This study could not predict the mortality of the patients and is only limited to be applied in multiple trauma patient. In addition, this study is only limited to one centre, and the specificity and sensitivity is not determined. We strongly suggest for future studies to develop this equation with other factors considered and included.

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References Beuran, M., Negoi, I., PÄ&#x192;un, S., Runcanu, A., Gaspar, B., & Vartic, M. (2012). Trauma scores: a review of the literature. Chirurgia (Bucharest, Romania: 1990), 107(3), 291-297. Braunschneider, G. (1994). Complications of Trauma. JAMA: The Journal Of The American Medical Association, 272(20), 1626. doi: 10.1001/jama.1994.03520200084046 Chaudhry, N., Naqi, S., & Qureshi, A. (2012). Effectiveness of TRISS to Evaluate Trauma Care in a Developing Country. Emergency Medicine: Open Access, 02(07). doi: 10.4172/21657548.1000124 Krug E.G., Sharma G.K., Lozano R. The global burden of injuries. (2000). American Journal Of Public Health, 90(4), 523-526. doi: 10.2105/ajph.90.4.523 Lavoie, A., Moore, L., LeSage, N., Liberman, M., & Sampalis, J. (2005). The Injury Severity Score or the New Injury Severity Score for predicting intensive care unit admission and hospital length of stay?. Injury, 36(4), 477-483. doi: 10.1016/j.injury.2004.09.039 Leong, M., Mujumdar, S., Raman, L., Lim, Y., Chao, T., & Anantharaman, V. (2003). Injury Related Deaths in Singapore. Hong Kong Journal Of Emergency Medicine, 10(2), 88-96. doi: 10.1177/102490790301000205 Orhon, R., Eren, S., Karadayi, S., Korkmaz, I., Coskun, A., Eren, M., & Katrancioglu, N. (2014). Comparison Of Trauma Scores For Predicting Mortality And Morbidity On Trauma Patients. Turkish Journal Of Trauma And Emergency Surgery, 20(4), 258-264. doi: 10.5505/tjtes.2014.22725 Patil, A., Srinivasarangan, M., Javali, R., LNU, K., LNU, S., & LNU, S. (2019). Comparison of Injury Severity Score, New Injury Severity Score, Revised Trauma Score and Trauma and Injury Severity Score for Mortality Prediction in Elderly Trauma Patients. Indian Journal Of Critical Care Medicine, 23(2), 73-77. doi: 10.5005/jp-journals-10071-23120 Shu-Ting, Y., Shih-Fang, H., Jen-Lung, C., Chih-Jung, W., Yan-Shen, S., Jeremy, Y. (2015). Correlation of Injury Severity Score and Average Length of Stay. Health Care Current Reviews 2016, 4:2, 315-330. doi: 10.6174%2fJHM2015.16(4).315 The top 10 causes of death. (2020). Retrieved 27 March 2020, from https://www.who.int/newsroom/fact-sheets/detail/the-top-10-causes-of-death

135

Systematic Review of the Quality of Life after Traumatic Brain Injury Adella Calista1, Dhea Zulrahmania Hermanto1, Penradee Piyarat1 1Faculty

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

Introduction: Traumatic Brain Injury (TBI) by American Association of Neurological Surgeons is defined as a blow to the head or a penetrating head injury that disrupts the normal function of the brain. TBI can result when the head suddenly and violently hits an object or when an object pierces the skull and enters brain tissue. Symptoms of a TBI can be mild, moderate or severe, depending on the extent of damage to the brain.1 It is often known as a major cause of death and disability and impairs health-related quality of life. It can affect their ability to think and memorize, physical function, emotional and feelings, also their sleep schedule. But, some symptoms might not be seen right away after the injury, it can take weeks a dm

e ha

he e

le d

eall

derstand the un-normal pattern that they have.

Material 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 incl di g PICO A al i . F I e e i a d

(I). F cial

T a ma ic B ai I j

C m ai

(C), e

he P ed he cla

me al heal h . A d f

la i f

(P), e Im

he O c me (O),

ed ad l . We did eme e

h ical f

ed Q ality of Life after

Result and Discussion: By utilizing the PICO method, without using the intervention. We have acquired 3 longitudinal cohort studies that we have already analyzed. The studies that we will be using by Kathleen F. Pagulayan et al., Xue-Bin Hu et al., Mau-Roung Lin et al.. We found that from the 3 studies stated that Traumatic Brain Injury (TBI) takes longer improvement in psychosocial or mental health as opposed to physical function. Conclusion: In conclusion, from 3 studies that we have already analyzed, we found that the studies by Kathleen F. Pagulayan et al., Xue-Bin Hu et al., Mau-Roung Lin et al. have given the statement that Traumatic Brain Injury (TBI) takes longer improvement in psychosocial or mental health as opposed to physical function. We can conclude that TBI that physical function is the first domain that recover after Traumatic Brain Injury in a short term of time (months) and followed by another domain that are related psychosocial with their mental health years after. We may conclude that physical

2 136

function is easier to improve by daily practice rather than psychosocial and mental health because the patients need more time to adjust after the trauma.

Keyword: Traumatic brain injury, longitudinal cohort, quality of life

3 137

Systematic Review of the Quality of Life after Traumatic Brain Injury Adella Calista1, Dhea Zulrahmania Hermanto1, Penradee Piyarat 1 1

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

1 138

Systematic Review of the Quality of Life after Traumatic Brain Injury

Adella Calista1, Dhea Zulrahmania Hermanto1, Penradee Piyarat1 1

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

Introduction: Traumatic Brain Injury (TBI) by American Association of Neurological Surgeons is defined as a blow to the head or a penetrating head injury that disrupts the normal function of the brain. TBI can result when the head suddenly and violently hits an object or when an object pierces the skull and enters brain tissue. Symptoms of a TBI can be mild, moderate or severe, depending on the extent of damage to the brain. 1 It is often known as a major cause of death and disability and impairs health-related quality of life. Perceived health-related functioning in both physical and psychosocial domains may change over time because recovery from TBI is a complex and lengthy process. Some symptoms would appear when someone is recovering from TBI, it can affect their ability to think and memorize, physical function, emotional and feelings, also their sleep schedule. But, some symptoms might not be seen right away after the injury, it can take weeks a dm

e ha

he e

le d

eall

a d he

-normal pattern that they have.

Traumatic Brain Injury can be measured by several methods, one of the most popular one is Traumatic Brain Injury-Quality of Life (TBI-QOL). In TBI-QOL and another measurement, mostly they divided the classes into several big domains, such as physical health (mobility, headache pain), emotional health, cognitive health, and social health. The concept of quality of life broadly encompasses how an individual measures the g d e

f m l i le a ec

f hei life. The e e al a i

i cl de

e em i al eactions

to life occurrences, disposition, sense of life fulfilment and satisfaction, and satisfaction with work and personal relationships2. I a

he li e a

e, he e m

ali

f life i al

efe ed

ell-bei g .

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 hi

d i cl di g PICO A al i . F

I e e i f

a d

(I). F ch

C m ai cial

(C),

he P e

la i

(P), e

ed he cla

me al heal h . A d f

ed ad l . We did Im

eme

he O c me (O),

be e

ea h ical

ed Q ali

f 4

139

Life af e T a ma ic B ai I j

. The h

he i i

ema ic e ie

improvement in patient quality of life between their physical function and psychosocial? Is he e a

diffe e ?

The inclusion criteria used in this study is a longitudinal cohort study, with these key factors: Traumatic Brain Injury, Quality of Life, Adult Population, Physical Function, Psychosocial, Mental Health. The methods that are excluded are case report studies, literature reviews, and animal study.

5 140

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.

((("Physical") AND "Psychosocial") AND "Quality of life") AND ("Traumatic brain injury" OR "TBI")

PubMED (56)

Google Scholar (224)

Science Direct (652) Inclusion Criteria: Traumatic brain injury Quality of life Population: adult Outcome: Physical and psychosocial related quality of life Longitudinal cohort study

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

10 Filtering double literature 5 Relevant Study 3

Figure 1 Information flowchart through the differ phases of the systematic review 6 141

Table 1 Summary of studies on quality of life after TBI Authors

Study

Year Subject

Result

Kathleen et al

Longitudinal Cohort

2016 Patients with severe TBI, general trauma, and healthy friend controls

Severe TBI patients improve their physical domain disability for months, but it takes longer for their cognitive, emotional, and communication abilities to recover.

Xue-Bin Hu

Longitudinal Cohort

2011 Patients with moderate-tosevere TBI

Significant improvement of HRQoL in four physical health domains and two mental health domains. It takes longer for another two mental health domains to recover.

MauRoung Lin

Longitudinal Cohort

2010 Patients with Traumatic Brain Injury with followup assessments at 6 and 12 month after injury.

Improvement scores on the WHOQOL-BREF domains including physical capacity, changes in environment, physiologic well-being improved except for social and communication relationships in 6 months after injury.

A study by Kathleen F. Pagulayan et al for 1 month to 3 to 5 years longitudinal cohort study with shows that 133 adolescents and adults with complicated mild to severe TBI who completed the outcome measure. In this study, the chosen subjects were compared with the friend healthy controls. The TBI adolescents and adults patients were randomized, placebocontrolled, dium in preventing post-traumatic seizures, and its neurobehavioral side effects. The subject must be at least 14 years old at the time of injury a d c

ha e a hi

f a

brain injury or neurologic situation. The measurement in this study is using both Brain Injury Severity Indices which includes GCS right after the injury and TFCs and HRQOL measures. HRQOL measurement includes 136 items that assess functioning in 12 domains, includes psychosocial factor score (social interaction, alertness behavior, communication, and emotional behavior subscales) and physical factor score (ambulation, body care and movement, and mobility subscales. Thus, 5 subscales (sleep and rest, home management, work, recreation and pastimes, eating) are not included in either of the factor scores but do contribute to the total score. The result of this longitudinal study show that TBI is associated with most aspect of everyday life, there was substantial improvement from 1 to 6 months, especially in the physical domains for subjects who had sustained complicated mild or moderate TBIs and recovered enough to take the SIP at 1 month after injury . In contrast, recovery in psychosocial domains 7 142

including cognitive, and emotional improvement were smaller and not really significant, when it was compared with the friend healthy controls, this situation most related to the injury and its consequences. A study conducted by Xue-Bin Hu et al to measure health-related-quality-of-life (HRQoL) after 2 years after Traumatic Brain Injury (TBI), total 358 adult patients in Wuhan Trauma Center with moderate-to-severe TBI based of Glasgow Coma Scale and followed up for 2 years with HRQol measurement. There are certain exclusions for the subject criteria, patients with blood alcohol level exceeding 199mgdL -1, patients with spinal cord injury, and those with mild TBI were excluded based on the Glasgow Coma Scale score 13-15 within 24 hours. The mean age of patients who were followed up at admission wa 32.7 (1.2) years. Traffic accidents, falls, and assaults were the major causes of injuries. Results of HRQoL assessment at discharges, 6 months, 1 year and 2 years after discharge of the 312 survivors are listed. All eight domains: (1) physical function, (2) role function, (3) bodily pain, (4) general health, (5) vitality, (6) social function, (7) role emotional, (8) mental health. The improvement in 6 months shows that all four physical health domains have improved and two mental health domains also improve. The other two mental health domains improve after 1 to 2 years after discharge. Based on Mau-Roung Lin et al study, the measure and track the health-related quality of life (HRQL) at discharge and at 6 and 12 months after traumatic brain injury (TBI) and examine factors associated with changes in each HRQL domain. There are 158 participants in the initial assessment, and 147 and 146, respectively, completed the follow up assessments at 6 and 12 months after injury. The measurement in this study use the brief version of the World Health Organization Quality of Life (WHOQOL-BREF) with 4 domains of physical capacity, psychological well being, social relationships, and environment. Scores on all WHOQOLBREF domains except social relationships greatly improved over the first 6 months and showed continued improvement at 12 months after injury. The domain scores of the WHOQOL-BREF at discharge were significantly associated with the preinjury HRQL level, marital status, alcohol consumption at the time of injury, GOS level, cognition, ADLs, social support, and depressive status. Conclusion: Based on 3 studies that we have already analyzed, the study by Kathleen F et al, XueBin Hu et al, Mau-Rong et al stated that physical function is the first domain that recover after 8 143

Traumatic Brain Injury in a short term of time (months) and followed by another domain that are related psychosocial with their mental health years after. For this reason, we may conclude that physical function is easier to improve by daily practice rather than psychosocial and mental health because the patients need more time to adjust after the trauma. References: 1. Traumatic Brain Injury - Causes, Symptoms and Treatments (2020) Received 23rd of March 2020, from https://www.aans.org/en/Patients/Neurosurgical-Conditions-andTreatments/Traumatic-Brain-Injury 1. E

al f P ch l g - Quality of Life (2013) Received 23rd of March 2020

from https://pdfs.semanticscholar.org/e6d3/548eb9a7243f4cac2772cd3577b106596975.pdf 2. Kathleen F. Pagulayan,PhD, Nancy R. Temkin, PhD, Joan Machamer, Ma, Sureyya S. Dikmen, PhD. (2006). A Longitudinal Study of Health-Related Quality of Life After Traumatic

Brain

Injury.

Retrieved

24th

March

2020

from

https://www.ncbi.nlm.nih.gov/pubmed/16635622 3. Xue-Bin Hu, Zhe Feng, Yu-Cong Fan, Zhi-Yong Xiong, and Qi-Wei Huang. (2011). Health-related quality-of-life after traumatic brain injury: A 2-year follow-up study in Wuhan, China. Retrieved 24th of March 2020 from https://www.ncbi.nlm.nih.gov/pubmed/22360524 4. Mau-Roung Lin, PhD, Wen-Ta Chiu, MD, PhD, Yi-Ju Chen, MS, Wen-Yu Yu, MD, Sheng-Jean Huang, MD, Ming-Dar Tsai, MD. (2010). Longitudinal Changes in the Health Related Quality of Life During the First Year After Traumatic Brain Injury. Retrieved 24th of March 2020 from https://www.ncbi.nlm.nih.gov/pubmed/20298842

9 144

Thromboelastography (TEG) as a Guiding Tool for Blood Transfusion in Patients With Trauma-Induced Coagulopathy: A Systematic Review Aleyda Zahratunany I., Dita Widirahmayanti, Fatimah Az Zahra, Yessica Chelsea Horax

ABSTRACT Introduction Traumatic injury has been identified as potential risk factors of death. Coagulopathy is part of the iad of dea h coagulopathy,

hich

e en ed b majo

a ma ic a ien . Ma i e an f ion, one of he a

is known to bring on severe complications and a high rate of mortality among

traumatic patients. Several studies demonstrated that Thromboelastography (TEG) can help to improve transfusion treatment and strategies by choosing selective blood products which can diminish the transfusion impact of patients with trauma-induced coagulopathy. Methods The systematic review was conducted using PRISMA principles to improve the quality of reporting. Studies were conducted through four online databases (ProQuest, ScienceDirect, SpringerLink, and PUBMED) he a

and

i h ke

an f ion

Th omboela og a h o iden if

ele an

(TEG) ,

a ma ind ced coag lo a h ,

die f om he ea 2010-2020. A total of 662

studies were identified and analyzed to finally shortlisted to six studies included to review phase. These studies were assessed for its quality using STROBE for observational studies or CONSORT statement checklist for clinical trial studies. Result In this study, we included 6 eligible a icle and e cl ded 116

die ha didn mee o

incl ion

criteria. Assessment of studies collected was performed using STROBE checklist for observational studies or CONSORT. Five studies are observational studies (highest score of 20.622). Another study is an experimental study (score of 21 of 25). A total of 694 participants (mean age = 47.49) were included in all six studies (5 in Denmark and 1 in USA). The intervention group of these studies used TEG to analyze the blood sample. Transfusion therapy were done based on the result of TEG analysis. The measured outcomes are total transfusion of blood product (PRC, FFP, or PC) mortality rate, survival rate, and hospital length of stay. Conclusion Thromboelastography (TEG) should be considered as a recommended tool for guiding transfusion therapy in trauma-induced coagulopathy which can reduce total number of blood transfused, duration

145

of hospitalized, mortality rate, and healthcare cost. Future research should have longer duration and larger sample using standardized protocol to explore more beneficial effects in TIC therapy.

Keywords : Thromboelastography, TEG, Trauma-Induced Coagulopathy, TIC, Blood Transfusion, Therapy

146

Thromboelastography (TEG) as a Guiding Tool for Blood Transfusion in Patients With Trauma-Induced Coagulopathy: A Systematic Review Scientific Paper

Author(s) Aleyda Zahratunany I. Dita Widirahmayanti Fatimah Az Zahra Yessica Chelsea Horax

Faculty of Medicine Universitas Brawijaya 2020

147

INTRODUCTION Trauma remains a leading cause of death and permanent disability in adults despite advances in systematic approaches including prevention, resuscitation, surgical management, and critical care. Trauma-related death and disability have also been suggested to have a big impact on global productivity. Bleeding accounts for 30 40% of all trauma-related deaths and typically occurs within hours after injury. Although the mortality of trauma patients requiring massive transfusion exceeds 50%, at least 10% of deaths after traumatic injury are potentially preventable, and 15% of those are due to hemorrhage; many of these deaths occur within the first few hours of definitive care, with coagulopathy playing a crucial role (Kushimoto, 2017). Coagulopathy is seen in 25 35% of trauma patients and become a common contributor to hemorrhagic death. In fact, it is thought to be responsible for half of the hemorrhagic deaths in trauma patients who receive mass transfusions (Vernon, 2019). The updated European guidelines addressing one of the management of bleeding and coagulopathy following major trauma is transfusion (Spahn et al.,2013). However, after massive transfusion therapy may increase in several complications (Sniecinski et al.,2011). Hence indications of administration of transfusion in each patient must be due the indication considered given the impact that can result from transfusion therapy. Improvements in transfusion treatment and strategies are associated with better outcome. Early therapeutic intervention does improve coagulation tests, reduce the need for transfusion of RBC, FFP, and platelets, reduce the incidence of posttraumatic multi-organ failure, shorten length of hospital stay and may improve survival. Therefore, complete and rapid monitoring of blood coagulation and fibrinolysis using viscoelastic methods like TEG may facilitate a more accurate targeting of therapy (Spahn et al.,2013). Thromboelastography (TEG) has been used in cardiovascular surgery and liver transplantation, and more recently, has been applied to trauma (Veigas et al., 2016). It was developed in 1947 for use specifically in research; and more recently, it has become a tool to identify and treat coagulation abnormalities. It provides more complete picture of coagulation status, taking into account more factors involved in clotting process, including platelet function and temperature. It is most useful for detection of trauma and surgery-related dilutional coagulopathy. Moreover, TEG is valuable in optimizing targeted therapy, especially transfusion with specific coagulation factors. Multiple studies have found that using a transfusion algorithm based on a TEG tracing decreases the amount of blood product transfused which in effect decrease the total treatment cost and strain on blood bank resources. Its initial result which is available within minutes could lead to early treatment and good prognosis of trauma-induced coagulopathy (Collins and Hewer, 2016).

148

With the aim to assess whether TEG is an effective tool for guiding trauma-induced coagulopathy therapy, the writers reviewed systematically studies that assessed TEG as a guiding tool for therapy in patients with trauma-induced coagulopathy. METHODS A Systematic Review ab

Thromboelastography (TEG) as a guiding tool for blood transfusion in

patients with trauma-induced coagulopathy was carried out using PRISMA Statement rules. In order to find relevant journals and articles for this systematic review, studies search were conducted using search engines ScienceDirect, PUBMED, ProQuest, and SpringerLink database with keywords Th

b ea

g a h (TEG) ,

a i d ced c ag

ah ,

he a

a d

a f i

criterion papers published in 2010 to 2020 and related in humans. To assess the quality of included papers, Consolidated Standards of Reporting Trials (CONSORT) statement checklist for randomized clinical trials study and Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement checklist for observational studies were used. From the initial search, 662 studies were identified. 498 studies were then excluded because of uncoressponding topics. Another 158 studies were later excluded because of conducted on non-Trauma Induced Coagulopathy (n=66), discussing other aspect besides management therapy and transfusion using TEG (n=35), using other viscoelastic assay besides TEG (n=22), using different study design (n=12), and studies subject were pediatrics (n=13), geriatrics (n=1) and non-human (n=9). Eventually, we obtained 6 studies that fulfilled the criterion of this systematic review. Initial search result through database searching (n=662)

Studies excluded based on uncorresponding topics (n=498)

Records after uncorresponding topics removed

Full-text-articles excluded : Non-Trauma Induced Coagulopathy (n=66) Discussing other aspect besides management therapy and transfusion using TEG (n=35) Using other viscoelastic assay besides TEG (n=22) Using different study design (n=12) Studies subject were : o Pediatrics (n=13) o Geriatrics (n=1) o Non-human (n=9)

(n=163)

Full text articles assessed for eligibility (n=6)

Figure 1. Flowchart of Systematic Review

149

RESULT 1. Study search result A total of 662 articles were retrieved from four search engines (ScienceDirect, PUBMED, ProQuest, and SpringerLink database). Full text of 6 articles were assessed for eligibility after exclusion of 116 studies. Those studies were excluded because they discussed non-trauma-induced coagulopathy (n=66) or other aspect (n=35), used another viscoelastic assay (n=22) or study design (n=12), or different criteria of sample (n=9). The inclusion criteria include having patients more than 18 years old who had trauma-induced coagulopathy as the samples, using TEG as a guiding tool for TIC therapy, and published in the last ten years. Finally, only 6 studies which met all inclusion criteria were analyzed. 2. Quality Assessment Assessment of studies collected was performed using STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) checklist for observational studies or CONSORT (Consolidated Standars of Reporting Trials) checklist for experimental studies to assure their quality. Five studies are observational studies, which obtain the highest score of 20.622. Another study is an experimental study with the score of 21 of 25. 3. Characteristic of included Studies The study design characteristics are shown in Table 1. Out of six studies assessed, five were conducted in United States and the other was conducted in Denmark. A total of 694 participants were included in all six studies. The mean age of participants was 47.49 years. 4. Intervention characteristic The intervention group of these studies used TEG to analyze the blood sample. Transfusion therapy were done based on the result of TEG analysis. Some studies compared the TEG utilization with traditional coagulation test as a guiding tool for trauma-induced coagulopathy therapy. 5. Outcomes The measured outcomes are total transfusion of blood product (PRC, FFP, or PC) mortality rate, survival rate, and hospital length of stay. The detailed outcomes of every studies are shown in Table 1.

150

Authors

Study

Participant

Intervention

Outcome

Design

Score

Reference

(CONSORT / STROBE)

Mohame

Cohort

134 patients

Staff trauma

For the first 24h of treatment, patient

20.6 of 22

Mohamed, M.,

d et al.

studies (16

meeting Class I

surgeons were

with TEG guided resuscitation had

(STROBE)

Majeske, K.,

months)

trauma activation

educated on

lower packed red blood cells (3.60

Sachwani, G. R.,

were divided into

identification of

units/patient, p = 0.0022) and fresh

Kennedy, K., Salib,

2 groups: patients

TEG tracings and

frozen plasma (2.13 units/patient, p =

M., & McCann, M.

prior to TEG

interpretation of

0.474), but higher jumbo pack

(2017). The impact

implementation

TEG values.

platelets utilization (1.45 units/patient,

of early

(n=87) and

Rapid

p = 0476) compared to the patients

thromboelastograph

patients with TEG

thromboelastograph

prior to thromboelastography

y directed therapy in

guided trauma

y assay was

implementation

trauma

resuscitation

obtained as part of

Patients in the post-TEG group were

resuscitation. Scandi

(n=47).

the initial trauma

found to have a mean hospital length

navian journal of

work-up panel.

of stay 10 days shorter (p = 0.0011)

trauma,

R-TEG test result

and ICU length of stay 7 days

resuscitation and

were interpreted on

shorter(p = 0.0059) than the preTEG

emergency

a computer within 5

group

medicine, 25(1), 99.

min of laboratory

The mortality rate was significantly

receiving blood

lower in patients <30 years in the post

sample.

TEG group (42.5% VS 14.29%)

Blood product

151

usage was compared for three time periods: first 4h, the next 20h, and first 24h Johansso n et al.

Cohort study

182 patients were

Patient admitted to

One-fourth of the patients received

17.1 of 22

Johansson, P. I.,

included (75%

the trauma center

RBCs, plasma, or PLTs within 2

(STROBE)

SĂ¸rensen, A. M.,

males, median age

have blood sampled

hours from admission to the

Larsen, C. F.,

43 years).

for TEG analysis

Trauma Center

WindelĂ¸v, N. A.,

performed within 10

75% patients transfused within 24

Stensballe, J.,

minutes and displayed

hours received respective blood

Perner, A., ... &

in real time on a

product within the first 2 hours.

Ostrowski, S. R.

computer screen.

Median number of transfused

(2013). Low

During resuscitation,

blood product at 2 hours was 5

hemorrhage e a ed

blood samples for

units of RBC, 5 units of FFP, and

mortality in trauma

TEG are analyzed

2 units of PC.

patients in a L evel I

every 30 minutes.

trauma center

Hemostatic

employing

resuscitation with

transfusion packages

blood products and

and early

hemostatic agents

thromboelastograph

were done accordance

di ec ed

with the result of the

hemostatic

152

TEG analysis.

resuscitation with plasma and platelets. Transfusio n, 53(12), 30883099.

Unruh,

Retrospectiv

81 trauma patients

Period I represented a

In this study, there were a 52.4% reduction

16/22

Unruh, M., Reyes,

et.al.,

e review

who underwent

time in which patient

in the volume of red blood cells transfused

(STROBE)

J., Helmer, S. D., &

MTP activation in

coagulability was

after TEG-directed was impemented.

Haan, J. M. (2019).

American College

assessed and blood

Utilizing TEG, the clinicians transfused

An evaluation of

of Surgeons from

product utilizationwas

significantly fewer patients with Fresh

blood product

January 1, 2014-

guided using

Frozen Plasma (from 70.6% to 3.0%) and

utilization rates with

December 31,

traditional

platelets (from 67.6% to 30.3%).

massive transfusion

2014 (Period I)

coagulation test and

There were no significant difference in the

protocol: Before and

and July 1 2015-

comprised control

length of hospital stay for MTP with or

after

June 30, 2014

groups. Period II

without TEG (12.5 and 13 days).

thromboelastograph

(Period II).

represented the period

Reduction of mortality was found in the

y (TEG) use in

There were 20 and

in which TEG was

used of TEG, which in 44.1% in MTP

trauma. The

47 patients in

fully implemented as

without TEG and 33.3% with TEG.

American Journal of

period I and II,

the standard for

Surgery, 218(6),

respectively.

assessment for

1175-1180.

2019

coagulopathy and comprised comparison group.

153

Eduardo

Randomized

Injured

Gonzales

Clinical

, et al.

Trial

(2016)

patients

Patients

were

TEG group had a significant improvement

(at least 18 years

randomized

with

in survival at 28 days and at 6 hours from (CONSORT)

Moore, E.,

of age) that fulfill

weekly alternation of

injury while using less plasma and

Moore, H.,

platelets in the early phase of resuscitation

Chapman, M.,

criteria for MTP 2

treatment

20.5/25

(Massive

modalities,

Transfusion

example,

patients

deaths (36.4%); TEG: 11 deaths (19.6%)).

Ghasabyan, A. et

Protocols)

enrolled during weeks

Moreover, the CCA group had more

al. (2016). Goal-

activation

in 1 and 3 were in the

plasma and platelets transfused during the

directed

Emergency

CCA group, and those

first 4 and 2 hours of resuscitation that can

Hemostatic

Departement

enrolled during weeks

lead to unnecessary use of blood products,

Resuscitation of

arrival during a 3- 2 and 4 in the TEG

especially because the same ratio of blood

Trauma-induced

year

products is given to every patient and at

Coagulopathy. A

were

every time point in the MTP. In addition,

nnals Of

2014. These study

performed on platelet

patients in the TEG group had more ICU-

Surgery, 263(6),

participant

poor plasma collected

free days and ventilator-free days than

1051-1059.

vacuum

those in the CCA group (TEG: 16 and 18

https://doi.org/10.

2 tubes, while TEG was

days; CCA: 8,5 and 13 days, respectively).

1097/sla.0000000

period group.

ending July 30, CCA

(n=111) devided

were into

groups:

for compared with the CCA group (CCA: 20

Gonzalez, E.,

Patients group

citrated

Chin, T., &

MTP performed on whole

guided by CCA blood

collected

000001608

(n=55) and MTP vacuum tubes with no goal-directed

by anticoagulant.

TEG (n=56) Jeffry L.

Prospective

68 patients at risk

The patient's whole

In this study, only one patient in the TEG

154

17.6/22

Kashuk, J., Moore,

Kashuk,

study

for trauma-

blood sample will be

group died of coagulopathy compared to

et al.

induced

examined by TEG in

seven in the pre-TEG group. This proves

Johnson, J., Pezold,

(2011)

coagulopathy that

pre-TEG group and in

that real-time assessment of coagulation

M., & Lawrence, J.

admitted to

r-TEG group, 10 mL

function using TEG might lead to

et al. (2011). Initial

American College

of r-TEG solution

increased analysis of clot function and

experiences with

of Surgeons

(consisting of 8%

improved management. r-TEG differs

point-of-care rapid

before (Pre-TEG)

kaolin, human

from standard TEG because the addition of

thrombelastography

and after (TEG)

recombinant tissue

tissue factor greatly accelerates the clotting

for management of

implementation of

factor, phospholipids,

mechanism resulting in the visualization of

life-threatening

r-TEG as an

buffers, and

the early phase in examination within

postinjury

additional tool for

stabilizers) was added

seconds.

coagulopathy. Trans

monitoring

to 0.35 mL of

coagulation status that received 6 or

a ie

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(STROBE)

E., Wohlauer, M.,

fusion, 52(1), 23-33. d

https://doi.org/10.11

sample.

11/j.1537-

more units of

2995.2011.03264.x

blood within the first 6 hours after injury. Hota, S

retrospective

118 patients

Patients will be

The final results showed that patients

16/22

Hota, S., Ng, M.,

et al

chart

traumatic brain

divided based on

with moderate injuries (MAX AIS

(STROBE)

Hilliard, D., &

(2019)

review

injury while on

MAX AIS Head

Head score 2 or 3) who received TEG

Burgess, J. (2019).

antithrombotis (44

Score, patients with

had higher mortality (8.7%) than

Thromboelastogram-

to 94 years) that

moderate injuries and

patients who did not received TEG

Guided

155

will be divided

patients with severe

(3.8%). Patients with severe injuries

Resuscitation for

into 2 groups,

injuries. All patients

(MAX AIS Head score 4 or 5) who

Patients with

those who

will be compared

received TEG had lower mortality

Traumatic Brain

received a TEG

between those who

(28.5%) than patients who did not

Injury on Novel

on arrival and

received TEG and

received TEG (31.6%)

Anticoagulants. The

those who did not.

those who did not

TEG guided reversal in patients with

American Surgeon,

receive TEG, the

TBI allows for a more efficient

85(8), 861-864

result will be seen

utilization of blood products without a

mortality between the

significant change in overall mortality.

whole group and compare the overall utilization of blood products. Table 1. Study Design and Characteristics

156

DISCUSSION Tromboelastography (TEG) is a visco-elastic test that monitors the thrombodynamic properties of blood as a clot is formed (Gonzales et al, 2016). Prior studies have established that it provides more comprehensive description of global hemostatic functional aspect as it could trace more specific coagulation disturbance, allowing more targeted blood component replacement approach. TEG may serve as a useful and cost-effective tool in patients with TIC or those requiring massive blood transfusion. (Holcomb et al., 2012). Our systematic review on six studies shows that TEG as a guiding tool for transfusion therapy in TIC could reduce total transfusion of blood products, mortality rate due to coagulopathy, hospital length of stay, and predict total blood product that would be used for therapy and survival rate. It is also more cost-effective than traditional coagulation test due to the decrease of hospital length of stay and total transfusion. It is important to perform blood transfusion quickly and appropriately as well as obtain immediate hemostasis for the treatment of hemorrhagic shock that accounts for 90% of incidents of traumatic shock. Viscoelastic assays such as TEG is a coagulation test that can better represent TIC and enable the clinician with data for critical decision making. TEG's greatest application in trauma care is in the guidance of massive transfusion protocols. TEG analysis can be performed on whole blood with no anticoagulant (native), whole blood collected into sodium citrate 3.2% (0.109 mol/L) (9 volumes blood to 1 volume anticoagulant) and whole blood collected into heparin (>14.5 IU heparin/milliliter of blood sample). There has been growing interest in the effects of citrate on thrombelastographic profiles, and whether citrate can introduce variation to interpretation of results. Studies on healthy volunteers performing serial TEG assays at different time points from collection show that citrated samples produce variable results when the assay is performed within 5 minutes from sample collection but stabilize thereafter for up to 2 hours (Gonzalez, et al, 2017; Phillips et al, 2017). Similar to other studies, this study showed using viscoelastic tests for trauma patietns corresponded to an overall reduction in the use of packed red blood cells and fresh frozen plasma during the first 24 hours of resuscitation. In addition, this study showed using viscoelastic tests corresponded to a significant reduction in both hospital and intensive care unit length of stay (Mohamed, et al, 2017). Patient with trauma-induce coagulopathy that had an MTP guided by TEG had improved mortality compared to Conventional Coagulation Assays (CCA). Gonzales et al (2017) published a study that The TEG guided MTP group had a survival advantage over the CCA group which mortality of TEG group was 19% compared to 36% in the CCA group. Another study shows that Mortality rate was higher in Conventional Coagulation Assays (40%) than TEG (6%, p < 0.017), because there is no parameter of clot degradation (Fibrinolysis/LY30) in conventional test which associated with increased mortality (Sumislawski, 2019). Correspondingly to another study result shows that The

157

mortality rate was significantly lower in patients under 30 years in the postTEG group (14.29%), then in preTEG group (42.5%) (Mohamed, 2017). These several studies indicate that delayed or inadequate diagnosis of coagulopathy in trauma patient may lead to an excessive and improperly balanced transfusion of blood components with increased mortality. Two studies demonstrate a significant reduction in ICU length of stay in the intervention group. Study written by Mohamed et al. (2017) shows that patient in TEG group have a mean hospital length of stay 10 days shorter and ICU length of stay 7 days shorter than the control group. Another study written by Gonzales et al (2016) shows that patient in TEG group had more ICU-free days and ventilator-free days than those in control group. Similar to our result, study by Redfern, et al. (2019) demonstrated 1.3 day decrease in length of stay in hospital after TEG implementation (11.26 versus 9.95) assumedly due in part to the lower rate of reoperation. When exploring ways to drive down healthcare costs, evaluation of length of stay becomes important. Decreased length of stay would lead to healthcare cost reduction. Based on the effectiveness of TEG, Hota Salini et al. (2019) showed that patients with moderate injuries (MAX AIS Head score 2 or 3) who received TEG had higher mortality (8.7%) than patients who did not receive TEG (3.8%). However, patients who received TEG with severe injuries (MAX AIS Head score 4 or 5) had lower mortality (28.5%) than patients who did not receive TEG (31.6%). A study written by Subramanian et al. (2014) demonstrated that in emergency trauma situations, immediate corrective measures need to be taken based on coagulation parameters and conventional coagulation tests may cause delay, TEG can give highly specific and rapid results depicting the underlying coagulopathy. Massive transfusion therapy frequently occur as complicating in severe bleeding (Sniecinski et al.,2011). TEG is helpful for early detection and treatment of coagulopathic bleeding that may reduce the number of complications and mortality after transfusion therapy. TEG helps to choose the selective use of blood products so that it can reduce the risks induced by transfusion and also reduced medical costs without a decrease inpatient care, as well as a decreased chance of future need for transfusions and less recovery time in critical care units. Thromboelastography potentially to prevent coagulopathy and promote effective control of bleeding in the presence of coagulopathy (Brazzel el at.,2013). LIMITATION The limitation of TEG is not widely used as recommended guiding tool for transfusion therapy. Moreover, this systematic review has also limitation. There were only one randomize clinical trials and six observational studies that discuss about the effectiveness of management therapy and transfusion using TEG in trauma-induced coagulopathy patients. Hence, the result of our review may lead to bias and difficult to generelize to other trauma. Another limitation are relatively small sample

158

size and few eligible study were found due to specific inclusion criteria that may also affect the result of this systematic review.

CONCLUSION According to the evidence shown in studies reviewed, thromboelastography (TEG) should be considered as a recommended tool for guiding transfusion therapy in trauma-induced coagulopathy. This systematic review has shown that this intervention may help to reduce total number of blood product used for transfusion, length of stay in ICU or hospital and mortality rate due to coagulopathy. In addition, it may predict total number of blood product that would be used for therapy and also survival rate of patients with TIC. Another advantage is reduced healthcare cost due to decreased length of stay and total transfusion. However, the effect of this intervention should be further explored in future studies. Studies with longer duration and larger sample using standardized protocol may well demonstrate beneficial effects in TIC therapy.

159

REFERENCES Brazzel, Charice,C.R.N.A., D.N.P. (2013). Thromboelastography-guided transfusion therapy in the trauma

patient. AANA

Journal, 81(2),

127-32.

Retrieved

from

https://e-

resources.perpusnas.go.id:2076/docview/1440816473?accountid=25704 Gonzalez, E., Moore, E. E., & Moore, H. B. (2017). Management of Trauma-Induced Coagulopathy with

Thrombelastography. Critical

care

clinics, 33(1),

119 134.

https://doi.org/10.1016/j.ccc.2016.09.002 Gonzalez, E., Moore, E., Moore, H., Chapman, M., Chin, T., & Ghasabyan, A. et al. (2016). Goaldirected Hemostatic Resuscitation of Trauma-induced Coagulopathy. Annals Of Surgery, 263(6), 1051-1059. https://doi.org/10.1097/sla.0000000000001608 Holcomb, J. B., Minei, K. M., Scerbo, M. L., Radwan, Z. A., Wade, C. E., Kozar, R. A., et al. (2012). Admission Rapid Thrombelastography Can Replace Conventional Coagulation Tests in the Emergency

Department.

Annals

Surgery,

256(3),

476 486.

doi:

10.1097/sla.0b013e3182658180 Hota, S., Ng, M., Hilliard, D., & Burgess, J. (2019). Thromboelastogram-Guided Resuscitation for Patients with Traumatic Brain Injury on Novel Anticoagulants. The American Surgeon, 85(8), 861-864 Johansson, P. I., SĂ¸rensen, A. M., Larsen, C. F., WindelĂ¸v, N. A., Stensballe, J., Perner, A., ... & Ostrowski, S. R. (2013). Low hemorrhage e a ed a

a ce e

i g

a f i

ackage

ai a d ea

a a ie

b ea

i a L e e I g a h di ec ed

hemostatic resuscitation with plasma and platelets. Transfusion, 53(12), 3088-3099. Kashuk, J., Moore, E., Wohlauer, M., Johnson, J., Pezold, M., & Lawrence, J. et al. (2011). Initial experiences with point-of-care rapid thrombelastography for management of life-threatening postinjury

coagulopathy. Transfusion, 52(1),

23-33.

https://doi.org/10.1111/j.1537-

2995.2011.03264.x Kushimoto, S., Kudo, D., & Kawazoe, Y. (2017). Acute traumatic coagulopathy and trauma-induced coagulopathy: an overview. Journal of Intensive Care, 5(1), 6. Mohamed, M., Majeske, K., Sachwani, G. R., Kennedy, K., Salib, M., & McCann, M. (2017). The impact of early thromboelastography directed therapy in trauma resuscitation. Scandinavian journal of trauma, resuscitation and emergency medicine, 25(1), 99. Redfern, R. E., Fleming, K., March, R. L., Bobulski, N., Kuehne, M., Chen, J. T., & Moront, M. (2019).

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Transfusion in Cardiac

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Surgery:

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Postoperative Outcomes. The Annals of Thoracic Surgery, 107(5), 1313 1318. doi: 10.1016/j.athoracsur.2019.01.018 Shawn Collins, D. N. P., & Ian Hewer, M. S. N. (2016). Thromboelastography: clinical application, interpretation, and transfusion management. AANA journal, 84(2), 129. Sniecinski, R. M., & Levy, J. H. (2011). Bleeding and management of coagulopathy. The Journal of Thoracic and Cardiovascular Surgery, 142(3), 662–667. doi:10.1016/j.jtcvs.2011.03.015 Spahn, D. R., Bouillon, B., Cerny, V., Coats, T. J., Duranteau, J., Fernández-M

d ja , E.,

Rossaint, R. (2013). Management of bleeding and coagulopathy following major trauma: an updated European guideline. Critical Care, 17(2), R76. doi:10.1186/cc12685 Subramanian, A., Albert, V., Agrawal, D., Saxena, R., & Pandey, R. M. (2014). Evaluation of the utility of thromboelastography in a tertiary trauma care centre. ISRN Hematology, doi:http://eresources.perpusnas.go.id:2129/10.1155/2014/849626 S

i a

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b i h, L. Z., S e e , G. R., N

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Cohen, M. J. (2019). Discrepancies between Conventional and Viscoelastic Assays in Identifying

Trauma-Induced

Coagulopathy.

The

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Surgery. doi:10.1016/j.amjsurg.2019.01.014 Unruh, M., Reyes, J., Helmer, S. D., & Haan, J. M. (2019). An evaluation of blood product utilization rates with massive transfusion protocol: Before and after thromboelastography (TEG) use in trauma. The American Journal of Surgery, 218(6), 1175-1180. Veigas, P. V., Callum, J., Rizoli, S., Nascimento, B., & da Luz, L. T. (2016). A systematic review on the rotational thrombelastometry (ROTEM®) values for the diagnosis of coagulopathy, prediction and guidance of blood transfusion and prediction of mortality in trauma patients. Scandinavian journal of trauma, resuscitation and emergency medicine, 24(1), 114. Vernon, T., Morgan, M., & Morrison, C. (2019). Bad blood: A coagulopathy associated with trauma and massive transfusion review. Acute medicine & surgery, 6(3), 215-222.

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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 Pardede1, Bethaniel Roy Matthew1 1Faculty

of Medicine, Universitas Kristen Indonesia 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 â&#x20AC;&#x153;massive transfusion protocolâ&#x20AC;? with 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.

162

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 2020

163

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. E 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 thir who die days or weeks after 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

164

50% ,

25%

30%

2 6

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 S

NCBI

resuscitation , published 2005-2019 and related to this topic.

165

Resuscitation ,

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 ca 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%

1:1:1

17.0%

1.1%) or at 30 days (22.4%

1:1:2

;

26.1%,

;

, 4.2% 95% CI, 9.6% , 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

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

166

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 3) 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 hypothermia : passive external rewarming, active external rewarming, and active internal core rewarming.7 A

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 T

decreasing the

incidence and severity of dilutional coagulopathy7, 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. Although in the past many reviewers have used 10 or more units of RBCs as a threshold .

23-28,

the condition of balanced blood

product administration performed by DCR ratio 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.

167

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 trauma-related 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.

168

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

169

Figures 3. DCR Algorithm INJURY

Pre-hospital Care (<20 minutes)

Emergency Room (<30 minutes)

Definitive Surgical Procedure (2-8 Days)

Intensive Care Unit (12-36 hours)

Abbreviated Surgical Procedure (<90 minutes)

Intensive Care Unit Stay (2-8 Days)

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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.

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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):12 21. 23. Lim RC, Olcott C, Robinson AJ, Blaisdell FW. Platelet response and coagulation changes following massive blood replacement. J Trauma 1973;13:577-82. 24. Wudel JH, Morris JA, Yates K, et al. Massive transfusion: outcome in blunt trauma patients. J Trauma 1991;31:1-7. 25. Stainsby D, MacLennan S, Hamilton PJ. Management of massive blood loss: a template guideline. Br J Anaesth 2000;85:487-91. 26. Phillips TF, Soulier G, Wilson RF. Outcome of massive transfusion exceeding two blood volumes in trauma and emergency surgery. J Trauma 1987;27:903-10.

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27. Velmahos GC, Chan L, Chan M, et al. Is there a limit to massive blood transfusion after severe trauma? Arch Surg 1998;133:947-52. 28. Hakala P, Hiippala S, Syrjala M, Randell T. Massive blood transfusion exceeding 50 units of plasma poor red cells or whole blood: the survival rate and the occurrence of leukopenia and acidosis. Injury 1999;30:619-22.

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The Contribution of Emergency Thoracotomy to the Survival Rate of Blunt Cardiac Injury Patients: A Systematic Review Audrey Hamdoyo1 1

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

Introduction: Blunt cardiac injury (BCI) surrounds various injuries such as contusion, chamber rupture, and acute valvular disorders. As there is no accepted gold standard diagnostic test in addition to the little consensus on how to define BCI, it limits research and understanding of it. Given a lack of uniformity and specificity to define this injury, treatment algorithms remain ambiguous. When a critical BCI patient is deemed in need of a surgery, emergency thoracotomy (ET) is performed. ET can be performed immediately at the site of trauma or in the emergency department (ED) or operating room (OR). It is potentially lifesaving when performed on trauma patients in extrimis. Thus, this systematic review was carried out to evaluate the contribution of emergency thoracotomy to the survival rate of blunt cardiac injury patients. Methodology: Data are collected from online resources including Pubmed, Google Scholar, and Science Direct. Systematic Analysis approaches were used in this study including Pico Analysis and MeSH terminology. Result & Discussion: Using PICO approach, searching is done through online database, and we acquired 3 articles that will be analyzed. Studies conducted by Segalini et al., Moore et al., and Mancini et al. will be used. Out of all studies, only Mancini e al.

100% m

ali

n BCI a ien

underwent ET. Conclusions: It can be concluded that ET may contribute in the decreasing rate of mortality in BCI patients. Out of the three studies analyzed, only one study had 100% mortality in BCI patients who went through ET. Keywords: blunt cardiac injury, emergency thoracotomy, resuscitative thoracotomy, survival, mortality

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The Contribution of Emergency Thoracotomy to the Survival Rate of Blunt Cardiac Injury Patients: A Systematic Review Audrey Hamdoyo1 1

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

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Introduction The earliest reports of blunt cardiac injury (BCI) date back to the seventeenth century; however, the first successful management was 4 centuries later (Warburg E., 1940). There is no accepted gold standard diagnostic test of BCI. Given a lack of uniformity and specificity to define this injury, BCI treatment algorithms remain ambiguous. There are six types of blunt cardiac injury: myocardial rupture, pericardial rupture, septal injury, valvular injury, myocardial contusion, and commotio cordis. Blunt myocardial rupture is the development of a laceration in the walls of the atria, ventricles, or papillary muscles caused by a blunt trauma (Huis in t Veld, Craft, & Hood, 2018). Pseudoaneurysm may develop if the myocardium is blocked by an intact pericardium and development of thrombus, making it prone to possible spontaneous rupture after the patient has survived the acute trauma (Marcolini & Keegan, 2015). Pericardial injury includes pericardial laceration, rupture, or pneumopericardium, typically resulting in pericarditis with consequent effusion and tamponade (Huis in t Veld, Craft, & Hood, 2018; Marcolini & Keegan, 2015). Pericardial rupture caused by blunt trauma is rare, and most cases are discovered postmortem. Septal injury is a form of myocardial injury, it may occur because of a mechanical rupture or a delayed inflammatory response. Valvular injury caused by blunt trauma is relatively uncommon, mostly due to papillary muscle rupture. Injuries to specific valves are cycle specific. The spectrum of clinical presentations of myocardial contusion classification is broad and ranges widely. For some physicians, myocardial contusion represents mild cardiac biomarker elevation following cardiac trauma, whereas for others, the diagnosis suggests significant myocardial dysfunction. Commotio cordis is the Latin term for agitation to the heart, often provoked by blunt trauma to the chest in the form of a fast-moving projectile. It is the third most common cause of sudden cardiac death in young athletes after hypertrophic cardiomyopathy and congenital coronary abnormalities (Huis in t Veld, Craft, & Hood, 2018). When a critical BCI patient is deemed in need of a surgery, emergency thoracotomy (ET) is performed (Gao et al., 2020). The goal of ET is to control any thoracic or abdominal hemorrhage, relief possible cardiac tamponade, deliver immediate repair of cardiac injuries, restore cardiac output and circulation, control any major thoracic vascular or pulmonary hilar injuries, and to perform internal defibrillation in patients with ventricular fibrillation cardiac arrest. Classic indications for ET include BCI patients going into cardiac arrest prior to hospital arrival, upon arrival, or under an operative procedure. An extended indication is BCI patients with cardiac arrest prior to arrival at the hospital (Pust & Namias, 2016). ET is potentially lifesaving when performed on trauma patients in extrimis (Yoong, Heng, Mathur, Lim, & Goo, 2018).

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Previous studies on BCI and ET were lacking with most journals fragmented, making the contribution of ET to the survival rate of BCI patients ambiguous at best. Thus, this systematic review is constructed to evaluate the contribution of ET to the survival rate of BCI patients.

Methodology To report this systematic review, data from online resources including from Pubmed, Google Scholars, and Science Direct are gathered. Systematic Analysis approaches used in this study are Pico Analysis and MeSH terminology. MeSH terminology for P (population) are blunt cardiac injury patients adults , MeSH terminology for I (intervention) is

and

emergency thoracotomy OR resuscitative

thoracotomy . MeSH terminology for C (comparison) is N/A. MeSH terminology for O (outcome) is survival OR mortality . The research question to this systematic review is: Can emergency thoracotomy influence the survival rate in blunt cardiac injury patients? Inclusion criteria are: prognostic studies, blunt cardiac injury, population: adult (ages 18-80 years old), outcome: survival. Exclusion criteria are: literature review, systematic review, meta-analysis, case report, animal study, penetrating cardiac injury, and population: children. In order to reduce bias, validity of the studies that fulfill the inclusion and exclusion criteria will be checked before the data is analyzed.

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Results and Discussion Using PICO approach, searching is done through online database, and we acquired 3 articles that will be analyzed. The selection process is shown in the diagram below.

"Blunt Cardiac Injury Patients and Adults" AND "Emergency Thoracotomy OR Resuscitative Thoracotomy" AND "Survival OR Mortality"

PubMed (17)

Science Direct (33)

Google Scholar (187)

Inclusion criteria: • Prognostic studies • Blunt cardiac injury • Population: adult (18-80 years old) • Outcome: survival Exclusion criteria: • Literature review • Systematic review • Meta-analysis • Case report • Animal study • Penetrating cardiac injury • Population: children

22 Filtering double literature 22

Relevant Study 3

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

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Table 1. Summary of studies on survival rate in BCI patients who went through emergency thoracotomy Authors

Study

Year

Subject

Result A generally increased survival rate

Segalini et al.

Retrospective

2018

Adult patients who received ET

after the adoption of a more liberal policy. Patients with BT surpassed survival

Moore et al.

Prospective observational 2016

Adult patients who received EDT rates in penetrating injuries over the last five years.

Mancini et al.

Retrospective

2017

Adult patients who received ET

No survivors in the BT group.

Note : BT : blunt trauma EDT : emergency department thoracotomy ET : emergency thoracotomy

Segalini et al. divided an eight-year period into two sections; 2010-2012 and 2013-2017. The two Table 2. The outcomes after ET during the period between January 1st, 2010 and December 31st, 2012, before the adoption of the more liberal policy

periods were divided based on the release of a more liberal policy at Bologna Maggiore Hospital Trauma Center. Over the study period, 27 patients who received ET were identified, males accounted for 74% (n=20) and females 26% (n=7). 13 (48.1%) ETs were

performed

the

emergency

department (ED) and 14 (51.9%) in the trauma operating room (OR) for those patients with profound and refractory shock but not yet in cardiac arrest. There were 21 (77.8%) BT patients who underwent ET. ERT: emergency room thoracotomy ICU: intensive care unit

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During the first period, there were four early survivors (40%), in which two of them are BT patients (Table 2). After the adoption of a more liberal policy for ET in 2013, one BT patient (5.8%) survived ET, one (5.8%). During this second period, there were eight (47%) early survivors, in which four of them are BT patients (Table 3). Among the survivors during the period between 2013 and 2017, one BT patient was in hemodynamic extremis. Table 3. The outcomes after ET during the period between January 1st, 2010 and December 31st, 2012, before the adoption of the more liberal policy

ERT: emergency room thoracotomy ICU: intensive care unit

According to Moore et al., survival rate of BT patients who underwent EDT surpassed the survival rate of penetrating injury patients during the period of 2010-2014 (Table 4). Table 4. Trends in Emergency Department Thoracotomy outcomes over time

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Based on Mancini et al., out of 22 patients who went through resuscitative thoracotomy (RT), 12 patients were BT patients. The outcome of the RT includes no survivors among the BT patients.

Conclusions From the systematic analysis, it can be concluded that ET may contribute in the decreasing rate of mortality in BCI patients. Out of the three studies analyzed, only one study had 100% mortality in BCI patients who went through ET.

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References Gao, J.M., Du, D.Y., Kong, L.W., Yang, J., Li, H., Wei, G.B., for

Blunt

Cardiac

Injury:

Experience

Liu, C.-P. (2020). Emergency Surgery

Cases.

World

Journal

Surgery.

https://doi.org/10.1007/s00268-020-05369-6 Huis in t Veld, M. A., Craft, C. A., & Hood, R. E. (2018). Blunt Cardiac Trauma Review. Cardiology Clinics, 36, 183 191. https://doi.org/10.1016/j.ccl.2017.08.010 Marcolini, E. G., & Keegan, J. (2015). Blunt Cardiac Injury. Emergency Medicine Clinics of North America, 33, 519 527. https://doi.org/10.1016/j.emc.2015.04.003 Moore, H. B., Moore, E. E., Burlew, C. C., Biffl, W. L., Pieracci, F. M., Barnett, C. C.,

Sauaia, A.

(2016). Establishing Benchmarks for Resuscitation of Traumatic Circulatory Arrest: Success-to-Rescue and Survival among 1,708 Patients. Journal of the American College of Surgeons, 223(1), 42 50. https://doi.org/10.1016/j.jamcollsurg.2016.04.013 Pust, G. D., & Namias, N. (2016). Resuscitative thoracotomy. International Journal of Surgery, 33, 202 208. https://doi.org/10.1016/j.ijsu.2016.04.006 Segalini, E., Di Donato, L., Birindelli, A., Piccinini, A., Casati, A.,

Tugnoli, G. (2018). Outcomes

and indications for emergency thoracotomy after adoption of a more liberal policy in a western European level 1 trauma centre: 8-year experience. Updates in Surgery. https://doi.org/10.1007/s13304-018-0607-4 Warburg E. (1940), Myocardial and pericardial lesions due to non-penetrating injury. British heart journal, 2, 271 80. http://dx.doi.org/10.1136/hrt.2.4.271 Yoong, I. R. W., Heng, G., Mathur, S., Lim, W. W., & Goo, T. T. (2018). Outcomes of emergency thoracotomy for trauma in a general hospital in Singapore. Asian Cardiovascular and Thoracic Annals, 26(4), 285 289. https://doi.org/10.1177/0218492318772221

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Systematic Review of Effect of Interpersonal Psychodynamic Therapy for Women with Childhood Sexual Abuse Post-traumatic Stress Disorder Beatrix Liony Frandi1 , Caesaria Honoris Wijaya1 , Gabriella Hilary Tumiwa1 , Marsja Ruthfanny Hutapea1 1 Faculty of Medicine, Pelita Harapan University, Tangerang, Banten, Indonesia ABSTRACT Introduction: Interpersonal Psychodynamic Therapy is a type of psychological treatment designed to investigate problems that relate to personal difficulties after experiencing a traumatic event. Childhood Sexual Abuse (CSA) is a serious problem that leads to long-term psychological distress. The prevalence of children sexual abuse PTSD is estimated at 20% of women and 10% of men. It is associated with symptomatic distress, poor interpersonal functioning, and low self esteem. Materials and Methods: For our systematic review, we collect our data from online resources which includes PubMed, Google Scholars, and Science Direct. Results and Discussion: Using the inclusion and exclusion criteria, we found 3 relevant articles. Talbot et al., Bleiberg et al., Harkness et al. had stated that traumatized women with CSA have an improvement with Interpersonal Psychotherapy. Only one of study states that there is no difference in EFs control between children with PTSD and children without PTSD. Conclusion: We can conclude that over 4 studies we had analyzed, only 1 study states that IPT is less effective than other psychotherapy for women with CSA who suffered from PTSD, depressive, and other symptoms. Keyword: Interpersonal Psychodynamic Therapy, Post-Traumatic Stress Disorder, Women, Childhood Sexual Abuse

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1 184

Introduction Child sexual abuse (CSA) includes a wide range of sexual behaviors that take place between a child and an older child or adult. These sexual behaviors are intended to erotically arouse the older person, generally without consideration for the reactions or choices of the child and without consideration for the effects of the behavior upon the child.1 One of the long-term effects of CSA is post-traumatic stress disorder (PTSD), and the women who reported multiple abusive episodes which involved sexual intercourse had increased symptoms of PTSD.2 PTSD is a mental health problem that some people develop after experiencing or witnessing a life-threatening event, like combat, a natural disaster, a car accident, or sexual assault. It's normal to have upsetting memories, feel on edge, or have trouble sleeping after this type of event. If symptoms last more than a few months, it may be PTSD.3 It is important for anyone with PTSD to be treated by a mental health professional who is c PTSD. T a a a c a ( a a ), ca , b . Everyone is different, and PTSD affects people differently, so a treatment that works for one person may not work for another. People with PTSD need to work with a mental health professional to find the best treatment for their symptoms.4 Psychodynamic Interpersonal Therapy (PIT) is a type of psychological treatment designed to help people with a range of different problems. The therapy takes the form of an in-depth conversation b (c a a ), c c c a a resolved. The goal of the conversation is for the client to get a better understanding of their difficulties with feelings and relationships, so that they can manage their personal problems more effectively. The expectation is that this will lead to an improvement in their psychological symptoms as well. To do this, a c a c c a a c a experience during therapy sessions, including their feelings about the therapist. This can be difficult at first, but many people find that it becomes easier over time.5 The current study of the effectiveness of psychodynamic therapy explored differential rates of change in treatment between CSA survivors and non CSA survivors6 (price2004). Women with CSA survivors reported increased problems related to general social adjustment, relation with their mother, parenting attitudes and abilities, and relation with children compared with a sample with no abuse history7 (callahan2004). A number of studies have supported the effectiveness of group therapy with adult survivors of CSA. Moreover, recent group outcome studies have also reported positive results in reduced symptomatic distress, enhanced self-esteem, and increased level of functioning. Thus, we execute a systematic review to perform the effectiveness of psychodynamic group therapy for women CSA survivors.

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Materials and Methods For our systematic review, we collect our data from online resources which includes PubMed, Google Scholars, Psychiatric Services, and Science Direct. Systematic analysis is done using PICO. M SH P (P a ) c a ab . M SH I (I ) a c a . M SH C (C a ) N/A . MeSH terminology O (O c ) c a and improvements . T ac a c : D a c a c a ab c a PTSD ? .I c c a a : PTSD symptoms, other depressive disorders, comparison of study, RCT, pilot study, population: woman with CSA, intervention: interpersonal psychotherapy, outcome: decrease symptoms and improvements. Exclusion criteria are : systematic review, working alliance or treatment group, prediction of treatment, brief report, literature review, meta analysis, symptoms without PTSD dan depression. 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.

3 186

Results and Discussion Using PICO approach, searching is done through an online database, and we acquired 4 articles that will be analyzed. The selection process is shown in the diagram below.

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

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Figure 2 Effects of interventions on symptoms severity, shame, and functioning among 70 women with a sexual abuse history who received treatment for major depression8 (Talbot et al) Talbot et al conducted a pilot study in a CMHC Trauma history was assessed with the Childhood Trauma Questionnaire-Short Form, a self-report measure of lifetime trauma experiences. PTSD symptoms were measured with the Modified PTSD Symptom Scale-Self Report which shows a score reflecting the frequency and severity of PTSD symptoms. Seventy patients were randomly assigned to interpersonal psychotherapy (N=37) or to usual care (N=33). The results indicate that depressive symptoms, PTSD symptoms, and shame show improvements over time than in usual care. On the family unit subscale of Social Adjustment Self-Care Report (data not demonstrated), the advantage of the treatment for interpersonal psychotherapy appeared significantly (Ď&#x2021;2=3.93, df=1, 5 188

=.05). C a a a c a a -adjusted effect sizes which range from small to big work on advantage for interpersonal psychotherapy at 36 weeks12 (Cohen, J.). The results show suggestion that interpersonal psychotherapy was beneficial with advantages as well over the usual psychotherapy in a CMHC in giving better treatment arrangement and retention, a greater improvement in psychiatric symptoms, and better functioning within the family.

Figure 3 Scores at Baseline and After 14 Weeks of Interpersonal Psychotherapy for 14 Subjects With Posttraumatic Stress Disorder9 (Bleiberg et al) Bleiberg et al did a pilot study of IPT for PTSD. Over 25 subjects that were eligible for study evaluation, 14 subjects meeting study inclusion criteria enrolled. The measurement for the outcome were 17-item total Clinician Administered PTSD Scale, th 24-item Hamilton Depression Rating Scale, the Posttraumatic Stress Scale-Self Report Version, the Beck Depression Inventory, the State-Trait Anger Experience Inventory, and the Social Adjustment Scale-Self Report Version. Eleven women and three men of a mean age of 33.1 years were treated as participants. Those participant precipitating traumas ranged from childhood sexual and physical abuse to armed mugging or rape in adulthood. The results show that interpersonal psychotherapy was well tolerated. At the termination, 12 of 13 subjects rated no longer met diagnostic criteria for PTSD on the Clinician-Administered PTSD scale. On the Posttraumatic Stress Scale, fourteen subjects reported declines in PTSD symptoms across all three symptoms clusters (Reexperiencing, Avoidance, and Hyperarousal, all 0.001) a c sizes. Hamilton Depression Rating Scale (N=14), Beck Depression Rating Scale (N=12), and StateTrait Anger Experience Inventory (N=13 for state and N=11 for trait) show that depressive symptoms improved. Interpersonal psychotherapy showed excellent retention and high response and remission rates and may help patients who have developed PTSD but refuse exposure-based treatment or pharmacotherapy. Some subjects reported that unprompted and after their interpersonal functioning and symptoms had improved. This condition may motivate patient self-exposure to further master the trauma.

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Figure 4 IPT for Depressed Women With Sexual Abuse Histories: Scores at Baseline and 10, 24, and 36 Weeks on Measures of Depression, Psychological Functioning, and Social Functioning8 (Talbot et al) Talbot et al compared IPT and usual care psychotherapy in a CMHC. Over 151 women who were screened for study eligibility, 32 eligible women who did agree to be contacted for an evaluation with some measurements: Trauma Questionnaire, Traumatic Life Events Questionnaire, Beck Depression Inventory-II, Hamilton Rating Scale for Depression, Medical Outcome Survey-36, and Social Adjustment Scale. The results, only 25 study participants who were studied and who had a mean age 31. Sixteen women were prescribed antidepressants either prior to or during. Twenty-two women (88%) suffered from chronic or recurrent depression. Seventeen women (68%) had three or more Axis 1 diagnoses and the most common one is PTSD. All women reported childhood sexual abuse on the Childhood Trauma Questionnaire. As an outcome, even though the numbers of participants in each assessment decreased from pretreatment (N= 25) to week 36 (N=13), women experienced a significant decline in depression based on HRSD (Hamilton Rating Scale for Depression) and BDI-II (Beck Depression Inventory). Mental health functioning on the SF-36 (health assessment) also showed improvement. Women treated in a CMHC who had major depression and childhood sexual abuse histories had several common characteristics: chronic depression, multiple comorbid psychiatric disorders and traumatic experiences in adulthood. The results showed that study participants became less depressed and had improved mental health functioning following treatment.

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Figure 5 Relation of child maltreatment to response status by treatment group in the (a) full randomized sample (n=203) and (b) case-complete sample (n=112), IPT interpersonal therapy; CBT=cognitive behavioral therapy; ADM=antidepressant medication10 (Harkness et al) Harkness et al did a study to compare response between Cognitive-behavioral therapy (CBT), interpersonal psychotherapy (IPT), and antidepressant medication (ADM) for childhood maltreatment victims, which all of them shown great efficacy compared with placebo in several RCTs of unipolar major depressive disorders. The study participants met DSM-VI criteria for MDD (Major Depressive Disorder), with age interval from 18 to 60, had moderate to severe symptoms level with minimum score of 16 on Hamilton Rating Scale for Depression, were free from ADM, without electroconvulsive therapy in the past 6 months, did not have a concurrent medical illness, had ebough education with 8 years of education as the minimum, and were fluent in reading English. The diagrams showed that IPT had a lower response rate compared to CBT and ADM, with highest response rate in ADM. According to study of adult MDD Patients who report high levels of avoidant and ambivalent attachment fare significantly more poorly in IPT than in CBT11 (McBride et al., 2006). Thus, maltreated patients in this study may have failed to respond in IPT.

8 191

Conclusion In conclusion, our systematic review mostly shows interpersonal psychotherapy (IPT) have various impacts for reducing PTSD, depressive, and other symptoms for women with childhood sexual abuse (CSA), as well as improvement in social functioning for instance in family and society. Over 4 studies we had analyzed, only 1 study states that IPT is less effective than other psychotherapy for women with CSA who suffered from PTSD, depressive, and other symptoms.

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References: 1. Whealin, J. & Barnett, E. (2018, August 20). Child Sexual Abuse. U.S. Department of Veterans Affairs. Available from: https://www.ptsd.va.gov/professional/treat/type/sexual_abuse_child.asp 2. Briggs, L., & Joyce, P. R. (1997). What determines post-traumatic stress disorder symptomatology for survivors of childhood sexual abuse? Child Abuse & Neglect, 21(6), 575 582. doi:10.1016/s0145-2134(97)00014-8 3. U.S. Department of Veterans Affairs. (2020, March 12). PTSD: National Center for PTSD. Available from: https://www.ptsd.va.gov/ 4. National Institute of Mental Health. (n.d.). Post-Traumatic Stress Disorder. Available from: https://www.nimh.nih.gov/health/publications/post-traumatic-stress-disorder-ptsd/index.shtml 5. Greater Manchester Mental Health NHS Foundation Trust. (n.d.). Psychodynamic Interpersonal Therapy. Available from: https://www.gmmh.nhs.uk/psychodynamicinterpersonal-therapy/ 6. Price, J. L., Hilsenroth M. J., Callahan K. L., Jackson P. A. P., & Bonge D. (2004). A pilot study of psychodynamic psychotherapy for adult survivors of childhood sexual abuse. Clinical Psychology Psychotherapy, 11, 378-391. doi:10.1002/cpp.421 7. Callahan, K. L., Price, J. L., & Hilsenroth M. J. (2004). A review of interpersonalpsychodynamic group psychotherapy outcomes for adult survivors of childhood sexual abuse. Int J Group Psychother, 54(4), 491-519. doi:10.1521/ijgp.54.4.491.42770 8. Ta b N. L., C Y., O Ha a M. W., S a S., Wa E. A., Ga b S. A., Wa A., & T X. (2005). Interpersonal psychotherapy for depressed women with sexual abuse histories: a pilot study in a community mental health center. J Nerv Ment Dis, 193(12), 847-50. doi:10.1097/01.nmd.0000188987.07734.22 9. Bleiberg, K. L. & Markowitz, J. C. A pilot study of interpersonal psychotherapy for posttraumatic stress disorder. Am J Psychiatry, 162(1), 181-3. doi:10.1176/appi.ajp.162.1.181 10. Harkness, K. L., Bagby, R. M., & Kennedy, S. H. (2012). Childhood maltreatment and differential treatment response and recurrence in adult major depressive disorder. Journal of Consulting and Clinical Psychology 2012, 80(3), 342 353. doi:10.1037/a0027665 11. McBride, C., Atkinson, L., Quilty, L. C., & Bagby, R. M. (2006). Attachment as moderator of treatment outcome in major depression: A randomized control trial of interpersonal psychotherapy versus cognitive behavior therapy. Journal of Consulting and Clinical Psychology, 74(6), 1041 1054. doi:10.1037/0022-006X.74.6.1041 12. Cohen, J. : Statistical Power Analysis for the Social Sciences. Hillsdale, NJ, Erlbaum, 1988 Google Scholar

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Effectiveness of Trauma and Injury Severity Score (TRISS), Revised Trauma Score (RTS), and Injury Severity Score (ISS) in Predicting Mortality of Multiple Trauma in Adult Patients: A Systematic Review Billy Susanto1, Yoriska1, Elizabeth Marcella1, Angeline Tancherla1 1

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

Introduction: Trauma is a sudden severe injury that is usually caused by a violent attack or an accident. It could lead to a minor, serious, and life-threatening condition. In the management of trauma, several scoring systems are available to predict the outcome of the patients. The most commonly used trauma scoring systems are Revised Trauma Score (RTS), Injury Severity Score (ISS), and Trauma and Injury Severity Score (TRISS) scoring system. Each trauma scoring system has different abilities and effectiveness in predicting the outcome, especially the mortality of trauma patients. Therefore, finding the most effective trauma scoring system to be used in evaluating trauma patients, especially in multiple trauma, is important to help identify and improve the outcome. The main objectives of this systematic review is focused on the comparison of the effectiveness between trauma scoring systems in predicting mortality in multiple trauma patients. Materials and Methods: Our systematic review is done by collecting data from online resources which includes PubMed, Science Direct, and Google Scholar. Combination of keywords that was used for searching are related to patient population, scoring, and outcomes. Data will be analyzed from studies that fulfil the inclusion and exclusion criteria. Conclusion: Based on our systematic review, 7 out of 10 studies show that TRISS is superior than RTS and ISS in predicting mortality of multiple trauma in adult patients. Only one study suggests that RTS is better than TRISS and ISS in scoring for multiple trauma patients in the AE. Another study reports that the best trauma scoring system in VT patients is ISS. An additional study claims that RTS is comparable to TRISS in mortality prediction. Keyword: RTS, ISS, TRISS, Mortality

194

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

195

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

Introduction: Trauma is a sudden severe injury that is usually caused by a violent attack or an accident. It could lead to a minor, serious, and life-threatening condition. In the management of trauma, several scoring systems are available to predict the outcome of the patients. Trauma scoring systems are appropriate to be used in two situations, in the field before the patient reaches the hospital and during the arrival of the patient at the emergency room. Even though trauma scoring systems are not the key elements of management of trauma, it is still an essential part in triage decision and in identifying patients with unexpected outcomes. By using trauma scores, the mortality rate caused by trauma could be minimized due to improvement of the trauma care triage that saves the time in treating trauma patient. In other words, trauma scores help in the effectiveness in treating trauma patients. The most commonly used trauma scoring systems are Revised Trauma Score (RTS), Injury Severity Score (ISS), and Trauma and Injury Severity Score (TRISS) scoring system. However, each trauma scoring system has different abilities and effectiveness in predicting the outcome, especially the mortality of trauma patients. Therefore, finding the most effective trauma scoring system to be used in evaluating trauma patients, especially in multiple trauma, is important to help identify and improve the outcome. The main objectives of this systematic review is focused on the comparison of the effectiveness between trauma scoring systems in predicting mortality in multiple trauma patients. Methods: Our systematic review is done by collecting data from online resources which includes PubMed, Science Direct, and Google Scholar. Combination of keywords that was used for searching are related to patient population, scoring, and outcomes, which are: “traumatic patients”, “RTS”, “ISS”, “TRISS”, and “mortality”. The inclusion criteria are cross sectional studies, prospective studies, retrospective studies, or cohort studies, consisting of traumatic patients aged

196

15-80 years old. The patients must assessed using the following scoring systems: RTS, ISS, and TRISS; and the outcome assessment is the mortality of the patients. The language of the studies should be in English or Indonesian language, and published after year 2010. The exclusion criteria are case reports, case series, meta-analysis, literature reviews and systematic reviews, that assess other outcomes other from mortality of patients, and do not include the three scoring systems (RTS, ISS, TRISS). Hypothesis question for this systematic review is â&#x20AC;&#x153;How effective is RTS, ISS, and TRISS in predicting mortality in traumatic patients?â&#x20AC;?. The validity of the studies will be examined to reduce the risk of bias before analyzing the data. Variables obtained for this systematic review are study characteristics and design, sample size, patient demographics, inclusion and exclusion criteria, types of scoring systems, and mortality rate of patients.

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Results and Discussion: Using PICO approach, searching is done through online database, and we acquired 9 articles that will be analysed. The selection process is shown in the diagram below. Total citations obtained from databases (PubMed, Science Direct, Google Scholar) n = 430

Inclusion Criteria: • Prognostic study • Cross sectional studies • Prospective studies • Retrospective studies • Cohort studies • Year: > 2010 • Population: adult traumatic patients (15-80 years old) • Scoring: RTS, ISS, TRISS • Outcome: mortality Exclusion Criteria: • Literature review • Systematic review • Meta-analysis • Case report • Animal-study • Population: children

178

Relevant Study

16 Filtering double literature

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

198

Table 1 Summary of studies on the Effectiveness of Trauma and Injury Severity Score (TRISS), Revised Trauma Score (RTS), and Injury Severity Score (ISS) in Predicting Mortality of Traumatic Patients Authors Jung et al.

Study Cohort

Year 2016

Object/injury 7,120 trauma patients

Demography Korean

Parameter ISS, RTS, TRISS

Results The AUCs of ISS, RTS, and TRISS were 0.866, 0.894, and 0.942 respectively, and the prediction ability of the TRISS was significantly better than the others (p < 0.001, respectively). The cut-off value of the TRISS was 0.9082, with a sensitivity of 81.9% and specificity of 92.0%; mortality was predicted with an accuracy of 91.2%; its positive predictive value was the highest at 46.8%.

Conclusion The result suggest that the TRISS is the best prediction model of trauma outcomes in the current Korean population.

Yadollahi

Retrospective Cohort Study

2017

849 trauma patients

South of Iran

ISS, RTS, TRISS

For each unit increase in GCS, risk of death decreased by about 40% (OR = 0.63, 95% CI: 0.59–0.67). For each unit increase in ISS, risk of death increased by 10% (OR = 1.11%, 95% CI: 1.08–1.14) and for each unit increase in TRISS, there was 18% decrease in the risk of fatality (OR = 0.82, 95% CI: 0.71–0.88).

The TRISS indicator is better predictor of traumatic death than other indicators.

Singh et al.

Analytic Descriptive Study with Retrospective Cohort Design

2011

1000 trauma patients

Ludhiana, Punjab, India

ISS, RTS, TRISS

The RTS ranged from 2.746 to 7.8408. There was a graded increase in mortality with decreasing RTS score. There was a graded increase in mortality with increasing ISS scores. The TRISS index also revealed similar probability of survival as expected from above values. Definitive analysis of TRISS revealed Z values of 3.95, W 5.345, and M +0.967.

Comparison of RTS, ISS and TRISS showed that ISS gave the poorest gain in information, while RTS and TRISS were comparable.

199

YousefzadehChabok et al.

CrossSectional Study

2016

352 trauma patients

Iran

ISS, RTS, TRISS

Mean ISS was higher for patients who did not survive. Mean of TRISS and RTS scores in survivors was higher than nonsurvivors and difference in all 3 scores was statistically significant (p<0.001). Best cut-off points for predicting mortality in trauma patients in RTS, ISS, and TRISS systems were ≤6, ≥13.5, and ≤2, with sensitivity of 99%, 84%, and 95% and specificity of 62%, 62%, and 72%, respectively.

TRISS was the strongest predictor of mortality in trauma patients as result of combination of both anatomical and physiological parameters.

Jassy et al.

CrossSectional Study

2016

37 trauma patients

Manado, Indonesia

ISS, RTS, TRISS

RTS is the recommended scoring for multitrauma patients in the AE. RTS and ISS can be used as mortality predictor in multirauma patients.

Yadollahi et al.

Prospective Cohort Study and Systematical Random Sampling

2020

1410 trauma patients.

Iran

ISS, RTS, TRISS

RTS has a mortality rate of 81,92%. ISS has a score of ≥ 25. One of the weaknesses for TRISS is that in calculating TRISS, coeficient is used according to trauma type (blunt or penetrating). In the case of multitrauma, it is often caused by a complex mechanism consisting of a mix between blunt trauma and penetrating trauma, therefore the chosen coefficient can’t be accurate. TRISS, ISS, and RTS have the ability to correctly diagnose death up to 73.45%, and also they can correctly diagnose survival up to 96.71% of cases. The findings reveal the areas under the ROC curves as 0.93, 0.80, 0.75, and 0.85 for the trauma indices of TRISS, ISS and RTS, respectively. Needless to say, these results indicated the higher ability of TRISS in predicting trauma outcomes. The findings regarding the ROC curve denoted to a higher level of sensitivity in TRISS and RTS. Also, TRISS had the highest

200

TRISS, RTS, and ISS were all very effective approaches for evaluating prognosis, mortality and probable complications in trauma patients; thus, these systems of injury evaluation and scoring are recommended to facilitate treatment. Finally, TRISS was selected as the most efficient scale for predicting mortality.

sensitivity and specificity for scores higher than 96.15. Loh et al.

Retrospective Cohort Study

2010

100 trauma patients

New York

ISS, RTS, TRISS

All three systems failed to accurately predict mortality in the VT group (14.3% [ISS], 4% [RTS], and 18.9% [TRISS] vs 24% [actual]). The TRISS scoring systems was the most accurate in predicting mortality in the VT patients but still underestimated the actual mortality. The ISS and TRISS systems were reasonably accurate in predicting mortality in NVT patients (15.6%, 9.6%, and 15.8% vs 11.8%).

The ISS was the best of the three systems tested with an AUC of 0.870, which makes it an adequate, but not superb, trauma scoring system for VT patients with multitrauma injury. The TRISS had AUCs of 0.786, indicating that this study is not ideal for use in vascular trauma patients.

Saad et al.

CrossSectional

2016

84 trauma patients

Ismailia, Egypt

ISS, RTS, TRISS

The mortality rates between the studied patients were 11.9% in comparison to 88.1% discharged alive. TRISS showed better sensitivity when compared to RTS & ISS with low false negative rate when compared to both of them. Comparable performances of the RTS, ISS, and TRISS showed RTS as the poorest index, while TRISS was the best.

TRISS showed high specificity and good sensitivity and the negative values are indicative of higher mortality observed in our study than predicted by TRISS and this may be lake of resources and man power or it may be due to delay of arrival of the patients. TRISS showed better sensitivity when compared to RTS and ISS with low false negative value when compared to both of them.

Javali et al.

Prospective Observational Study

2019

200 trauma patients

Mysuru, India

ISS, RTS, TRISS

Mean age of patients was 66.35 years. Most common mechanism of injury was road traffic accident (94.0%) with mortality of 17.0%. The predictive

TRISS was the strongest predictor of mortality in elderly trauma patients when compared to the ISS and RTS.

201

accuracies of the ISS, RTS and TRISS were compared using ROC curves for the prediction of mortality. Best cutoff points for predicting mortality in elderly trauma patient using TRISS system was a score of 91.6 (sensitivity 97%, specificity of 88%, area under ROC curve 0.972), for ISS best cutoff point was at 15(91%, 89%, 0.963) and for RTS it was 7.108 (97%, 80%, 0.947). There were statistical differences among ISS, RTS and TRISS in terms of area under the ROC curve (p <0.0001).

Notes : AE = Accident and Emergency AUC = Area Under The ROC Curve CI = Confidence Interval ISS = Injury Severity Score NISS = New Injury Severity Score NVT = Non-Vascular Trauma

OR = Odds Ratio PTS = Physiologic Trauma Score ROC = Receiver Operating Characteristic RTS = Revised Trauma Score TRISS = Trauma And Injury Severity Score VT = Vascular Trauma

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According to Jung et al in a cohort study of 7,120

Scoring system

AUC

95% CI

trauma patients with a mean age of 48.85 ± 19.25 years old,

ISS

0.866

0.851-0.881

the mean values of ISS, RTS, and TRISS (survival

RTS

0.894

0.877-0.910

TRISS

0.942

0.932-0.953

probability) were 11.6 ± 10.4, 7.34 ± 1.53, and 0.92 ± 0.19 respectively. The AUCs (area under the receiver operating characteristics curve) for the predictive ability of the ISS, RTS, and TRISS were 0.866, 0.894, and 0.942 respectively. The ability in predicting mortality of TRISS

Table 2 Areas under the ROC curve for the predictive ability of each injury severity scoring system ROC: receiver operating characteristic AUC: area under the receiver operating characteristic curve CI: confidence interval

is significantly better than ISS (p<0.001) and RTS (p<0.001), and the cut-off value of TRISS was 0.9082, with a sensitivity of 81.9% and specificity of 92.0%; mortality was predicted with an accuracy of 91.2%; its positive predictive value was the highest at 46.8%. In a retrospective cohort study by Yadollahi et al that consists of 849 traumatic patients with a mean age of 39.27 ± 18.52 years, it is reported that for each unit increase in ISS, risk of death increased by 10% (OR = 1.11%, 95% CI: 1.08-1.14. p<0.001). For each unit increase in RTS, there was 80% reduction in the risk of death (OR = 0.2, 95% CI: 0.15-0.26, p<0.001). For each unit increase in TRISS, there was 18% decrease in the risk of fatality (OR = 0.82, 95% CI: 0.71-0.88, p<0.001), which indicates a statistically significant relationship. From the result, we can observe that the increase in the ISS index increases the risk of death in trauma patients, but the increase in the RTS and TRISS scoring system reduces the risk of death in trauma patients. It was also found that the TRISS index is a better predictor of mortality for traumatic patients than other indicators (RTS and ISS). In the analytic descriptive study with retrospective

RTS

ISS

TRISS

cohort design, Singh et al had evaluated performance of

0.96

RTS, ISS and TRISS as predictors of mortality using the

0.041

0.039

0.049

0.49

0.41

0.56

PER method (the misclassification rate, the information gain and the relative information gain). Comparison of RTS, ISS and TRISS by the PER method showed that ISS gave the poorest gain in information (E=0.039), while RTS

Table 3 Comparison of Predictive Performance by PER Method P: a priori survival rate E: information gain R: relative information gain

(E-0.041) and TRISS (0.049) were comparable. Comparable performances of the RTS, ISS, and TRISS again showed ISS as the poorest index, while the results of RTS and TRISS were comparable.

203

Scoring system

AUC

95% CI

ISS

0.76

0.68-0.85

RTS

0.87

0.79-0.94

TRISS

0.94

0.90-0.98

Table 4 Comparison of area under ROC curve for trauma scoring systems

A cross-sectional study by Yousefzadeh-Chabok et al in 2016 with 352 trauma patients in Iran concluded that mean ISS was higher for patients who did not survive. Meanwhile, mean of TRISS and RTS scores in survivors was higher than non-survivors. The difference in all 3 scores was statistically significant (p<0.001). The best cut-off points for predicting mortality in trauma patients in RTS, ISS, and TRISS systems were ≤6, ≥13.5, and ≤2, with sensitivity of 99%, 84%, and 95% and specificity of 62%,62%, and 72% respectively. From this study, it was concluded that TRISS was the strongest predictor of mortality in trauma patients as result of combination of both anatomical and physiological parameters. On a cross-sectional study in 2016 by Jassy et al held in Manado, Indonesia with 37 trauma patients as the participant of the study, showed that RTS has a mortality rate of 81,92%. It also showed that ISS has a score of ≥ 25. This study explained that coefficient that is used according to trauma type (blunt or penetrating) in calculating TRISS is one of the weaknesses for TRISS. In the case of multi trauma, it is often caused by a complex mechanism consisting of a mix between blunt trauma and penetrating trauma. Threfore, the chosen coefficient can’t be accurate. This crossssectional study by Jassy et al concluded that RTS is the recommended scoring for multitrauma patients in the AE, and RTS and ISS can be used as mortality predictor in multitrauma patients.

204

According to a Prospective Cohort

Scoring system

AUC

95% CI

Study and Systematical Random Sampling

ISS

0.80

7.38

3.91-13.93

done on 1410 trauma patients by Yadollahi et

RTS

0.75

6.04

2-13.7

al, TRISS, ISS, and RTS have the ability to

TRISS

0.93

3.09

1.39-6.88

correctly diagnose death up to 73.45%, and also they can correctly diagnose survival up to 96.71% of cases. The findings reveal the areas

Table 5 Areas under the ROC curve for the predictive ability of each injury severity scoring system OR: odds ratio AUC: area under the receiver operating characteristic curve CI: confidence interval

under the ROC curves as 0.93, 0.80, 0.75, and 0.85 for the trauma indices of TRISS, ISS and RTS, respectively. Needless to say, these results indicated the higher ability of TRISS in predicting trauma outcomes. The findings regarding the ROC curve denoted to a higher level of sensitivity in TRISS and RTS. Also, TRISS had the highest sensitivity and specificity for scores higher than 96.15. Hence, TRISS, RTS, and ISS were all very effective approaches for evaluating prognosis, mortality and probable complications in trauma patients; thus, these systems of injury evaluation and scoring are recommended to facilitate treatment. Finally, TRISS was selected as the most efficient scale for predicting mortality. In a retrospective cohort study done on 100 trauma

Scoring system

AUC

95% CI

patients by Loh et al, RTS, ISS, and TRISS failed to

ISS

0.870

0.746-0.993

accurately predict mortality in the VT group (14.3% [ISS],

RTS

0.618

0.432-0.805

4% [RTS], and 18.9% [TRISS] vs 24% [actual]). The

TRISS

0.786

0.641-0.932

TRISS scoring systems was the most accurate in predicting

Table 6 Receiver operator characteristic curves C-statistics (AUC) for trauma scoring patients.

mortality in the VT patients but still underestimated the

actual mortality. The ISS and TRISS systems were reasonably accurate in predicting mortality in NVT patients (15.6%, 9.6%, and 15.8% vs 11.8%). The ISS was the best of the three systems tested with an AUC of 0.870, which makes it an adequate, but not superb, trauma scoring system for VT patients. The TRISS had AUCs of 0.786, indicating that this study is not ideal for use in vascular trauma patients.

205

Based on Saad et al cross-sectional descriptive study done on 84 trauma patients that attended Emergency Department at Suez Canal

Comparative

University Hospital, the mortality rates between

Performance of

studied were 11.9% in comparison to 88.1% discharged alive. TRISS showed better sensitivity

RTS

ISS

TRISS

Specificity

100%

Three Indices

when compared to RTS and ISS with low false

Sensitivity

20%

30%

60%

False Negative Rate

80%

70%

40%

negative rate when compared to both of them.

False Positive Rate

Comparable performances of the RTS, ISS, and TRISS showed RTS as the poorest index, while

Table 7 Comparison between RTS, ISS, and TRISS regarding specificity, sensitivity, false negative, and false positive rate.

TRISS was the best. In a prospective observational study made by Javali et al. on 200 elderly trauma patients with 66.35 years old as the mean age of patient and most common injury mechanism was road traffic accident (94.0%) with mortality of 17.0%. The predictive accuracies of the ISS, RTS, and TRISS were compared using receiver operator characteristic (ROC) curves for the prediction of mortality. Best cutoff points for predicting mortality in elderly trauma patient using TRISS system was a score of 91.6 (sensitivity 97%, specificity of 88%, area under ROC curve 0.972); for ISS best cutoff point was at 15 (91%, 89%, 0.963) and for RTS, it was 7.108 (97%, 80%, 0.947). There were statistical differences among ISS, RTS, and TRISS in terms of area under the ROC curve (p <0.0001). Youden

Scores

Cutoff

Sensitivity

Specificity

PPV

NPV

AUC

ISS

>15

91.18%

89.76%

64.6%

98.0%

0.963

0.8094

<0.0001

RTS

â&#x2030;¤7.108

97.06%

80.12%

50.0%

99.3%

0.947

0.7718

<0.0001

TRISS

â&#x2030;¤91.6

97.06%

87.95%

62.3%

99.3%

0.972

0.8510

<0.0001

Index

Table 8 Comparison of the assessment scores in predicting outcome

206

P Value

Conclusion: Based on our systematic review, 6 out of 9 studies show that TRISS is superior than RTS and ISS in predicting mortality of multiple trauma in adult patients. Only one study suggests that RTS is better than TRISS and ISS in scoring for multiple trauma patients in the AE. Another study reports that the best trauma scoring system in VT patients is ISS. An additional study claims that RTS is comparable to TRISS in mortality prediction. To conclude, we hope that the result of this systematic review could help to improve assessment of multiple trauma patients and evaluation of patientâ&#x20AC;&#x2122;s prognosis. Therefore, medical professionals would be able to enhance the management of patients to improve prognosis.

207

References: Jassy S, Heber B, Laurens T. (2016). 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. doi: 10.35790/jbm.8.2.2016.12699 Jung, K., Lee, J., Park, R., Yoon, D., Jung, S., & Kim, Y. et al. (2016). The Best Prediction Model for Trauma Outcomes of the Current Korean Population: a Comparative Study of Three Injury Severity Scoring Systems. The Korean Journal Of Critical Care Medicine, 31(3), 221-228. doi: 10.4266/kjccm.2016.00486 Loh, S., Rockman, C., Chung, C., Maldonado, T., Adelman, M., Pachter, H., & Mussa, F. (2010). Existing Trauma and Critical Care Scoring Systems Underestimate Mortality Among Vascular Trauma Patients. Journal Of Vascular Surgery, 51(4), 1072-1073. doi: 10.1016/j.jvs.2010.01.017 Singh, J., Gupta, G., Garg, R., & Gupta, A. (2011). Evaluation of trauma and prediction of outcome using TRISS method. Journal of emergencies, trauma, and shock, 4(4), 446– 449. https://doi.org/10.4103/0974-2700.86626 Yadollahi, M., Kashkooe, A., Rezaiee, R., Jamali, K., & Niakan, M. (2020). A Comparative Study of Injury Severity Scales as Predictors of Mortality in Trauma Patients: Which Scale Is the Best?. Bulletin Of Emergency And Trauma, 8(1), 27-33. doi: 10.29252/beat080105 Yadollahi, M. (2019). A study of mortality risk factors among trauma referrals to trauma center, Shiraz, Iran, 2017. Chinese Journal Of Traumatology, 22(4), 212-218. doi: 10.1016/j.cjtee.2019.01.012 Yousefzadeh-Chabok, Hosseinpour M, Kouchakinejad-Eramsadati L, Ranjbar F, Malekpouri R, Razzaghi A, Mohtasham-Amiri Z. (2016). Comparison of Revised Trauma Score, Injury Severity Score and Trauma and Injury Severity Score for mortality prediction in elderly trauma patients. Ulus Travma Acil Cerrahi Derg 2016;22(6):536–540 doi: 10.5505/tjtes.2016.93288 Saad, S., Abo-Zied, A., Siam, W., & El-Ghoul, Y. (2016). Assessment of the use of TRISS scoring system in polytraumatized patients in Suez Canal university hospital, Ismailia, Egypt. International Surgery Journal, 1524–1527. doi: 10.18203/2349-2902.isj20162740 Javali, R. H., Krishnamoorthy, Patil, A., Srinivasarangan, M., Suraj, & Sriharsha (2019).

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Comparison of Injury Severity Score, New Injury Severity Score, Revised Trauma Score and Trauma and Injury Severity Score for Mortality Prediction in Elderly Trauma Patients. Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine, 23(2), 73â&#x20AC;&#x201C;77. https://doi.org/10.5005/jpjournals-10071-23120

209

e a ic e ie

eh d

ch a PICO

a al e da a ha

e ga he ed. O

he i a e Ca

Cognitive Behavior Therapy Reduce Symptoms of Post Traumatic Stress Disorder i Ad l

i h he

inclusion criteria are post Traumatic Stress Disorder, Clinical Trials, Randomized Controlled Trials and Adult population. Exclusion Criteria are Systematic review, Meta-Analyses, Literature review, Children population. Results and Discussion: Using the inclusion and exclusion criteria, we found 6 relevant articles. J. Ponsford, Kim T. Mueser, Michelle C. Acousta had stated that cognitive behavioral therapy was effective in reducing PTSD symptoms. Two other studies conducted by C. Steel and Sverre Urnes Johnson had found that cognitive behavioral therapy had no significant effect in reducing PTSD symptoms. One other journal that conducted by Kim T. Mueser revealed that CBT helped improve cognitive ability, however did not suppress the PTSD symptoms exhibited. Conclusion: After reviewing 6 relevant journals, it was revealed that 3 of them showed significance of CBT in reducing PTSD symptoms, while the remaining showed no relation between the two. Therefore, it has been concluded that further research is required to establish the effectiveness of CBT to reduce symptoms of PTSD in adults. Keyword: Post-traumatic stress disorder, cognitive behavioral therapy, adult

210

211

The Effect of Cognitive Behavioral Therapy on Reducing Symptoms of Post Traumatic Stress Disorder in Adults: A Systematic Review Chandni Kumar1, Dion Ravinder Theodeus S1, Ida Bagus Ram K.P.M1, Mario Sutanto1 1 Faculty of Medicine, Pelita Harapan University, Tangerang, Banten, Indonesia Introduction Post Traumatic Stress Disorder (PTSD) is a mental disorder that may develop after exposure to a traumatic event. About 3% of the adult population can have PTSD at any given time, with a lifetime prevalence of 1.9%-8.8%. The diagnosis of PTSD requires the fulfilment of criteria set by Diagnostic and Statistical Manual of Mental Disorders - fifth edition (DSM-5). According to DSM-5, the traumatic event must involve exposure to actual or threatened death, serious injury or sexual violation. Common symptoms of PTSD include persistent intrusive recollections, avoidance of stimuli related to the trauma, negative alterations in cognitions and mood, and hyperarousal. Cognitive Behavioral Therapy (CBT) is a form of psychological intervention commonly used in treatment of PTSD. It is a structured and goal-oriented form of therapy, where the patient and therapist work in collaboration in order to modify the patient s pattern of thinking and behavioral patterns in an attempt to bring about beneficial psychological changes as well as alleviate symptoms of PTSD (3). Many researches have proven the efficacy of Cognitive Behavioral Therapy in dealing with psychological issues, allowing CBT to dominate international guidelines for psychological treatments, and making it the first-line treatment for many psychological disorders as noted by the National Institute for Health and Care Excellence s Guidelines and American Psychological Association. (4) Much research has been conducted to examine the effectiveness of CBT in tackling psychological issues such as depression, anxiety and even schizophrenia. However, little studies have examined the effectiveness of CBT in treatment of PTSD, which by itself already covers a range of psychological and emotional changes, instead of focusing on only one disorder. Previous studies associated with PTSD and its treatment using CBT were rather incomplete, and often examined effectiveness of CBT in patients with PTSD as well as other psychological disorders. Therefore, this systematic review has been carried out to evaluate the relationship between PTSD and CBT in adults. Methods The data we use in the systematic reviews are collected from Pubmed and Science direct. Systematic analysis approach is used in this study such as PICO method was used, P (Population) is used for “Adult Post-traumatic stress disorder Patient” , I (intervention) is used for “Cognitive Behavior Therapy”, C (comparison) is used for N/A, O (Outcome) is used for “Cognitive Behavior Therapy Efficiency on PTSD Patient Recovery”. The research question in our systematic review are “Can

212

Cognitive Behavior Therapy Reduce Symptoms of Post Traumatic Stress Disorder in Adultsâ&#x20AC;?. The inclusion criteria in this Systematic review are Post Traumatic Stress Disorder, Clinical Trials, Randomized Controlled Trials and Adult population. Exclusion Criteria are Systematic review, MetaAnalyses, Literature review, Children population.

213

Result and Discussion Using the PICO method without applying the interventions, we have acquired 8 articles that will be analyzed. The diagram below shows the selection process of the articles.

(((ptsd) AND cbt) AND adults) NOT children

PubMED (260)

Inclusion Criteria: Post Traumatic Stress Disorder / PTSD Clinical Trials Randomized Controlled Trials Population : Adult

Science direct (27)

Exclusion Criteria: Systemic Review Meta-analyses Literature review Population : Children

28 Filtering double literature 19 Relevant Study 6 Figure. 1 Information flowchart through the different phases of the systematic review

214

Table. 1 Summary of studies of Cognitive Behavioral Therapy on reducing symptoms PTSD

Authors

Study

Randomized Controlled Trials

C. Steel5

J. Ponsford

Kim T. Mueser7

Kim T. Mueser8

Randomized Controlled Trials

Year

Subject

Result

2016

Adult diagnosed with schizophrenia and exhibiting posttraumatic stress symptoms

There was no significant difference between treatment with CBT and treatment as usual.

2015

Adult had an anxiety disorder comorbid with depressive disorder

Adapted CBT has a significant effect in reducing Anxiety and depression.

2015

People with severe mental illness and PTSD

CBT treatment has greater improvement than the brief treatment in PTSD. Both groups improving on other outcomes and effects maintained 1-year posttreatment.

2017

People with severe mental illness and PTSD

CBT treatment helps PTSD patients who are exposed to CBT would perform better cognitive functions and learning but still exhibits PTSD symptoms

There is no significant difference between CBT and MCT after 1 year follow up. CBT had larger gains from post-treatment to oneyear follow-up.

Treatment with CBT have better improvement than TAU in PTSD outcomes

Sverre Urnes Johnson9

Randomized Controlled Trials

2017

Patient with a primary diagnosis of Post Traumatic Disorder, Social Phobia or Panic disorder, with and without Agoraphobia

Michelle C. Acousta10

Randomized Controlled Trials

2018

Veterans with PTSD

215

Note : PTSD = Post Traumatic Stress Disorder CBT = Cognitive Behavioral Therapy TAU = Treatment as Usual MCT = Metacognitive Therapy

In a randomized control study by C. Steel which involves a total of 61 participants that is diagnosed with schizophrenia and exhibiting post-traumatic stress symptoms. Those randomized to treatment were offered up to 16 sessions of cognitive-behaviour therapy (CBT, including psychoeducation, breathing training and cognitive restructuring) over a 6-month period, with the control group offered routine clinical services. T However, even though both the control group and treatment experience a significant decrease in post traumatic syndrome over time, the current trial did not demonstrate any effect in favour of CBT over TAU, this contrast the Mueser et al study which reports that cognitive restructuring intervention is effective for samples suffering from a range of severe mental health problems. It is important to consider that of those agreeing to partake in the study may be patients who are a help-seeking sub group and do not represent a wider clinical group exhibiting the same symptoms, not only that but the current study also includes individuals who are suffering from post traumatic stress symptoms but does not exhibit a fully diagnosed level of PTSD this does not line up with Mueser et al sample requirement which indicates that the treatment is effective in those individuals within the severe subgroup. It could also be because the symptoms of PTSD fluctuate over time. It could be that the proportion of the current sample may have entered the clinical trial at a more severe cyclical presentation and would experience a subsequent drop whether or not they are given exposure. The paper states that ructuring programmes may require further adaptation to promote emotional processing of traumatic memories within people diagnosed with a psychotic disorder. According to J. Ponsford Randomized Controlled Trials which samples adults of whom had an anxiety disorder comorbid with depressive disorder suggested that adapted CBT has a significant effect in reducing anxiety and depression. Using intention-to-treat analyses, random-effects regressions controlling for baseline scores revealed that Adapted CBT groups (MI + CBT and NDC + CBT) showed significantly greater reduction in anxiety on the Hospital Anxiety and Depression Scale [95% confidence interval (CI) -2.07 to -0.06] and depression on the Depression Anxiety and Stress Scale (95% CI -5.61 to -0.12) (primary outcomes), and greater gains in psychosocial functioning on Sydney Psychosocial Reintegration Scale (95% CI 0.04-3.69) (secondary outcome) over 30 weeks post-baseline relative to WC. The group receiving MI + CBT did not show greater gains than the group receiving NDC + CBT.

216

Kim T. Mueser s (2015) Randomized Controlled Trials suggested that CBT treatment has greater improvement than the brief treatment in PTSD. Both groups improving on other outcomes and effects maintained 1-year post-treatment. The samples for this experiment was people with severe mental illness and PTSD. 01 people with severe mental illness and PTSD were randomised to 12- to 16-session CBT or a 3-session brief treatment programme (breathing retraining and education). The primary outcome was PTSD symptom severity. Secondary outcomes were PTSD diagnosis, other symptoms, functioning and quality of life. Engagement in both programmes was high, with 88/97 (91%) participants in the brief group and 92/104 (89%) participants in the CBT group completing at least one session. Among engaged participants, 83/88 (94%) were exposed to the brief programme by completing at least two sessions, and 67/92 (73%) were exposed to CBT by completing at least six sessions. There were no site differences in rates of engagement for either programme, or rates of exposure to the brief programme. However, there were site differences in rates of exposure to the CBT programme ( 2 = 15.84, d.f. = 4, P = 0.003), with participants in the three partial hospital programmes having higher rates of exposThe analyses of the other outcomes indicated significant group effects, with the CBT group improving more than the brief group on overall functioning (GAF) and social functioning (CAPS) but not the other variables. However, there were significant groupĂ&#x2014;time interactions for social functioning and post-traumatic cognitions (PTCI), with the CBT group improving more than the brief group at posttreatment, and the brief group catching up by 12-months post-treatment. There were also significant time effects for depression (BDI-II) with both groups improving from post-treatment to the follow-up assessments. Participants in both interventions tended to improve from baseline to the follow-up assessments on all of the secondary outcomes.ure (68%, 85%, 100%) than participants in the two outpatient programmes (47%, 49%). Kim T. Mueser s (2017) randomized control trial suggested that CBT treatment helps PTSD patients who are exposed to CBT would perform better cognitive functions and learning but still exhibits PTSD symptoms. This study was conducted with a total of 54 participants were randomized to the CBT program, of whom 49 (91%) completed the neurocognitive evaluation. Among the 49 participants who were randomized to the CBT program and who completed the neurocognitive battery at baseline, 40 (81.6%) were exposed to the program (i.e., completed > 6 sessions). The 2 analyses and t-tests comparing the 9 participants who were not exposed to the program with the 40 participants who were exposed on the demographic and baseline clinical and cognitive variables indicated one significant difference. Participants with a lifetime substance use disorder were less likely to be exposed to the program (9/14 or 64.3%) than those without such a disorder (3/34 or 91.2%), 2 = 5.16, df=1, N = 48, p = 0.016. Among the 40 participants who were exposed to the CBT program, the average rate of homework completion was 50% (range: 0â&#x20AC;&#x201C;92%.) However, PTSD symptoms are still present in participants. Sverre Urnes Johnson11conducted a randomized clinical trial and concluded that there is no significant difference between CBT and MCT after 1 year follow up. CBT had larger gains from post-

217

treatment to one-year follow-up. The subjects of this randomized clinical trial are patient with a primary diagnosis of Post Traumatic Disorder, Social Phobia or Panic disorder, with and without Agoraphobia, 75 samples were then used after filtering 130. The patients did not differ on key variables at pretreatment, including number of diagnoses, former treatment, use of medications, age and gender (p > 0.05 for all variables). Further, no significant pre-treatment differences between conditions emerged on the outcome variables (p > 0.05 for all variables; see supplementary material B). The sample analysed included 74 patients, of whom 72 were Norwegians (Caucasian), 1 was African and 1 was Asian. The mean age was 42.0 (SD= 12.8), mean duration of illness was 16.1 years (SD= 11.8), 45 (60.8%) were female and 29 (39.2%) were male, 39 (52.7%) lived alone. Only 9 (12.2%) had a university degree, while the majority had only upper secondary school 28 (37.8%). The number of diagnoses was reduced from pre- to post-treatment and maintained at one-year follow-up with no significant differences between the treatment groups. The results replicate and extend previous work on the effect of CBT on comorbid symptoms and diagnosis for anxiety disorders (Norton et al., 2013; Tsao, Lewin & Craske, 1998). The results did not support our hypothesis that working on transdiagnostic processes, such as worry and rumination (MCT), would lead to larger effects on comorbid symptoms and diagnoses. However, MCT reduced personality-problems more then CBT, indicating a possible broader effect of MCT on comorbid personality problems, a result that needs further investigation. Meanwhile, Michelle C. Acousta1 Randomized Controlled Trials which draws samples from veterans with PTSD which concludes that The current study demonstrated that a web-based CBT intervention was effective in reducing heavy drinking among OEF/OIF/OND veterans with symptomatic PTSD and hazardous substance use. The impact of the intervention on heavy drinking was mediated by intervening increases in social support, self-efficacy, coping, and hope for the future during the 12-week intervention period. These findings indicate that a web-based, self-management intervention may be useful for engaging and providing treatment to difficult to reach veterans with behavioral health and substance use needs. This type of web-based intervention could be made easily accessible to the many thousands of veterans who need treatment, but are reluctant or unable to receive traditional mental health or substance use treatment. Future research is needed to investigate if adding professional support to web-based treatments may boost their effectiveness in treating PTSD and to determine which aspects of the current treatment are essential to generate the desired improvements in PTSD and substance use outcomes.

Conclusion: From the systematic review conducted, it can be concluded that the effectiveness of CBT as a solution to reduce PTSD symptoms in adults continues to remain unclear. From the 6 journals reviewed, 2 showed no significant effectiveness of CBT. One journal revealed that CBT helped improve cognitive ability, however did not suppress the PTSD symptoms exhibited. The 3 remaining journals we examined

218

revealed the relevance and effectiveness of CBT in reducing PTSD symptoms quite well. Therefore, it can be established that CBT may be helpful in reducing PTSD symptoms, however further research may be required to build on the idea of CBT as an effective first-line treatment for reducing PTSD symptoms in adults.

219

References: 1. Bisson J. I. (2010). Post-traumatic stress disorder. BMJ clinical evidence, 2010, 1005. 2. Bisson, J. I., Cosgrove, S., Lewis, C., & Robert, N. P. (2015). Post-traumatic stress disorder. BMJ (Clinical research ed.), 351, h6161. https://doi.org/10.1136/bmj.h6161 3. Chand, S.P., Kuckel, D.P., Huecker, M.R., Cognitive Behavior Therapy (CBT) [Updated 2020 Feb 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470241/ 4. Davi, D., Cristea, I., & Hofmann, S.G. (2018). Why Cognitive Behavioral Therapy Is the Current

Gold

Standard

Psychotherapy.

Frontiers

psychiatry,

https://doi.org/10.3389/fpsyt.2018.00004 5. Kanady, J. C., Talbot, L. S., Maguen, S., Straus, L. D., Richards, A., Ruoff, L., Metzler, T. J., & Neylan, T. C. (2018). Cognitive Behavioral Therapy for Insomnia Reduces Fear of Sleep in Individuals With Posttraumatic Stress Disorder. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 14(7), 1193–1203. https://doi.org/10.5664/jcsm.7224 6. Ponsford, J., Lee, N. K., Wong, D., McKay, A., Haines, K., Alway, Y., Downing, M., et al. (2016). Efficacy of motivational interviewing and cognitive behavioral therapy for anxiety and depression symptoms following traumatic brain injury. Psychological Medicine, 46(5), 1079– 1090. Cambridge University Press 7. Mueser, K. T., Gottlieb, J. D., Xie, H., Lu, W., Yanos, P. T., Rosenberg, S. D., Silverstein, S. M., Duva, S. M., Minsky, S., Wolfe, R. S., & McHugo, G. J. (2015). Evaluation of cognitive restructuring for post-traumatic stress disorder in people with severe mental illness. The British journal

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https://doi.org/10.1192/bjp.bp.114.147926 8. Mueser, K. T., McGurk, S. R., Xie, H., Bolton, E. E., Jankowski, M. K., Lu, W., Rosenberg, S. D., & Wolfe, R. (2018). Neuropsychological predictors of response to cognitive behavioral therapy for posttraumatic stress disorder in persons with severe mental illness. Psychiatry research, 259, 110–116. https://doi.org/10.1016/j.psychres.2017.10.016 9. Urnes, S., Ho, A., Nordahl, H. M., & Wampold, B. E. (2017). Metacognitive therapy versus disorder-speci fi c CBT for comorbid anxiety disorders : A randomized controlled trial ☆, 50(3370), 103–112. https://doi.org/10.1016/j.janxdis.2017.06.004

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10. Acosta, M. C., Possemato, K., Maisto, S. A., Marsch, L. A., Barrie, K., Lantinga, L., Fong, C., Xie, H., Grabinski, M., & Rosenblum, A. (2017). Web-Delivered CBT Reduces Heavy Drinking in OEF-OIF Veterans in Primary Care With Symptomatic Substance Use and PTSD. Behavior therapy, 48(2), 262â&#x20AC;&#x201C;276. https://doi.org/10.1016/j.beth.2016.09.001

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Comparative Study of Thoracic Endovascular Aortic Repair (TEVAR) and Open Surgery (OS) as Interventions for Patients with Blunt Thoracic Aortic Injury (BTAI): A Systematic Review and Meta-Analysis Clarissa Felicia1*, Puspa Gracella Tambunan1, Ayers Gilberth Ivano Kalaij2 Medical Undergraduate Study Program, Faculty of Medicine, Tarumanagara University 1 Medical Undergraduate Study Program, Faculty of Medicine, University of Indonesia2 Asian Medical Studentsâ&#x20AC;&#x2122; Association Indonesia *ichafelicia99@gmail.com ABSTRACT

Background: Blunt thoracic aortic injury (BTAI) is the second most common cause of death in trauma patients. More than 80% of BTAI cases were caused by motor vehicle accidents with 85% of all adults and children dying at the site. The annual incidence of traffic accidents in Indonesia is very high, and so is the risk of BTAI. Given the high incidence of mortality in patients presenting with BTAI, the use procedures with the lowest associated mortality risk are desperately needed. TEVAR was found as a rapid-developing and dominant surgical approach in BTAI, with substantial perioperative morbidity and mortality benefits over the open surgery. Our study aims to assess comprehensive comparison to reveal the level of TEVAR efficiency compared to open surgery as a treatment for BTAI patients, especially in reducing the risk of mortality. Methods: We conducted a systematic review and meta-analysis of cohort studies in the BTAI survival populations. The study was obtained from five databases (n = 615), screened and assessed with the Newcastle-Ottawa Scale (NOS) for the Cohort Study and all studies that met the eligibility criteria were included (n = 8). Hereinafter, it is assessed for the full text and synthesized for analysis. Results: Among the 1251 patients with BTAIs, 604 underwent thoracic aortic repair (TEVAR) and 647 underwent open surgery (OS). The TEVAR group had 44 cases of fatality whereas the OS group had 108 cases. A pooled study analysis (n = 1251) from 2008-2019 showed a significant effect (P <0.00001) of TEVAR as an intervention on BTAI compared to open surgery. The results suggested that TEVAR interventions on BTAI patients reduced the risk of death compared to patients who received open surgery (pooled OR = 0.33; 95% CI: 0.22-0.49; I2 = 0%). Conclusions: Previous findings stating TEVAR reduce the risk of death in BTAI compared to OS confirmed in this study. A randomized control trial can be carried out as future research. The study can

222

be focused on the long-term success, endurance, and complications of TEVAR that are used to treat BTAI. Key findings: thoracic endovascular aortic repair, TEVAR, open surgery, open repair, blunt thoracic aortic injury

223

Comparative Study of Thoracic Endovascular Aortic Repair (TEVAR) and Open Surgery (OS) as Interventions for Patients with Blunt Thoracic Aortic Injury (BTAI): A Systematic Review and Meta-Analysis

Authors: Clarissa Felicia Puspa Gracella Tambunan Ayers Gilberth Ivano Kalaij

Faculty of Medicine Tarumanagara University A ia Medical S de

A 2020

224

cia i

I d

e ia

popular clamp and sew technique in the past

INTRODUCTION

was preferred rarely due to the high incidence Blunt thoracic aortic injury (BTAI)

of paraplegia. Research data also show that

remains the second most common cause of

open surgery of traumatic aortic injuries is

death in trauma patients. It is potentially lethal

associated with up to 41% mortality rate

and

severe

(Hasjim BJ, et al., 2019, pp. 150-157); whereas

multisystem injury (Yamaguchi S, et al., 2018,

thoracic endovascular aortic repair (TEVAR)

pp. 1008). These injuries most commonly occur

was found as a rapid-developing and dominant

at the highest or most significant point of strain

surgical approach in BTAI, with substantial

between relatively mobile and fixed segments

perioperative morbidity and mortality benefits

of the aorta. The pre-hospital mortality rate is

over the open aortic repair. Given the multi-

70-80 % and for those who safely arrive at the

organ nature of the injuries in most patients

hospital, 50% will die within 24 hours without

with BTAI, TEVAR has quickly replaced open

definitive treatment. This significant mortality

repair as the treatment of choice for most

rate is related to the high incidence (40%) of

anatomically suitable patients with BTAI (Fox

severe associated injuries (Yamaguchi S, et al.,

N, et al., 2014, pp. 136-146).

often

associated

with

the

2018, pp. 1008).

Given the high incidence of mortality

Every year, at least 1 million new cars

in patients presenting with BTAI, the use

and around 6 million new motorbikes hit the

procedures with the lowest associated mortality

road in Indonesia and are followed by a few

risk are desperately needed. Previous studies

number of road accidents. The fact that

have demonstrated that endovascular repair of

incidence of traffic accidents in Indonesia every

BTAI significantly reduces mortality compared

year is as large as the population in the city of

to those receiving open repair treatment. Since

Bukittinggi, West Sumatra, Indonesia means

the recognition of TEVAR in 2005, the views

that traffic accidents in Indonesia cause the

on BTAI have changed considerably. Studies

same disadvantages as the impact of disasters in

have found that the mortality rate of BTAI

one area. An average of 287 accidents per day

decreased due to the use of TEVAR compared

in 2016, killing 25,589 people and injuring a

to open repair. In assessing the mortality of

further 22,939, according to data from the

open and endovascular repairs, studies have

National Police. In 2017, the number decreased

demonstrated TEVAR to be the superior option

slightly to 98,414 accidents, killing 24,213 and

compared to open surgery (Eklbuli A, et al.,

injuring 16,410 (Rahman R, 2018). Over 80%

2019, pp. 179-182); however, according to the

of BTAIs occur after a motor vehicle accident

2014 ESC Guidelines on diagnosis and for

with 85% of all adults and children dying on

treatment of aortic disease, the use of TEVAR

site (Hasjim BJ, et al., 2019, pp. 150-157).

for BTAI is still in class IIa (must be

BTAI was traditionally treated with an

considered) and level C (consensus of opinion

open surgical (OS) approach. Recently, the

of experts and / or small studies) which 2 225

indicates the need of a higher level of evidence

The study eligibility was determined

which hopefully can be provided through this

according to the following criteria, including

meta-analysis (ESC, 2014).

the type of study, participants, index text, and

Within our best knowledge, this

reference standards. All homogeneous cohort

systematic review and meta-analysis is the first

studies that met the criteria were included in

review to assess comprehensive comparison

this review. Cross-sectional, case-control,

between TEVAR and OS in a modern setting.

review, case report, case series, and conference

Current world health conditions have more

abstract were excluded studies. Cohort studies

complicated patients than ever before, so a

were used due to lack of randomized control

systematic review and meta-analysis that is

trials (RCTs) of this topic and ethical

more relevant to the current BTAI problem

considerations. Included studies must have a

need to be made. We hope that this systematic

full-text version, written in English and contain

review and meta-analysis can be applied to

topics that are relevant to the purpose of the

improve

regarding

review. Samples consist of all patients

traumatic aortic injury in Indonesia (PERKI,

diagnosed with blunt thoracic aortic injury

2016). Therefore, this study aims to reveal the

(BTAI). There are no limitations in age, gender,

level of TEVAR efficiency compared to open

race, and domicile. The study must evaluate

surgery as a treatment for BTAI patients,

mortality rates between BTAI patients who

especially in reducing the risk of mortality.

received thoracic endovascular aortic repair

existing

guidelines

(TEVAR) and those who underwent open surgery to be included in this study. The reference standard is the clinical literature that

MATERIALS AND METHODS

describes endovascular repair outcomes and This systematic review and meta-

compares them with open surgery, and also

analysis were conducted based on the Preferred

calculates

Reporting Items for Systematic Reviews and

possible to determine the odds ratio of two

Meta-Analyses (PRISMA) protocol which can

treatment mortality rates.

accessed

through

or provides data that makes it

http://www.prisma-

statement.org/. This protocol consists of a four-

Information sources and search strategy

phased flow diagram and checklist of 27 items

The literature search was performed

relating to the substance of systematic review

with multiple electronic databases, such as

and meta-analysis, including the title, abstract,

PubMed, Wiley, ScienceDirect, OvidSP and

introduction, methods, results, discussion, and

Cochrane. The keywords used in the pursuit

funding (PRISMA, 2015).

were (((((thoracic endovascular repair) OR TEVAR) AND open surgery) OR open repair)

Study eligibility criteria

AND blunt thoracic aortic injury. Limitation in the literature search was the availability of full3 226

text articles. Database searches were carried out

accessibility. The planned procedure was

up to March 14, 2020.

illustrated in Figure 1.

Study selection

Data collection process

Literatures was identified using the

The following data was extracted from

keywords described in the previous section.

the included studies: first author, publication

Following the database search, duplicate

year, study design, study location, follow-up

removal was performed using EndNote X9

duration, patient characteristics (age and

software. Screening of titles and abstracts of

gender), study population, injury severity score

studies was carried out according to criteria of

(ISS) of each intervention, and number of

Figure 1. Study Diagram Flow 4 227

deaths per total patient who received treatment

thoracic endovascular aortic repair (TEVAR)

at each intervention.

and open surgery. The variables of this study were defined in Table 1.

Quality assessment The quality assessment of each study included

was

examined

following

Variable

The

Definition

Newcastle-Ottawa Scale (NOS) for Cohort A procedure to treat

Studies. NOS is a 'star system' that has been

an aneurysm (a

developed in which a study is judged on three

weak, bulging area)

broad perspectives: the selection of the study

in the upper part of

groups; the comparability of the groups; and the

the aorta. It is

assessment of the outcome of interest for cohort studies respectively (OHRI, 2000). The quality

Thoracic

of individual studies was assessed by two

endovascular aortic

reviewers and then independently checked by a

repair (TEVAR)

third reviewer. Based on the result of the

considered as a minimally invasive surgery and its utilization is carried out with a device

assessment, studies with lesser bias and higher

called a stent-graft

quality will be taken more into consideration in

that is used to

qualitative analysis, however no primary

reinforce the

included study was excluded.

aneurysm. (Tintoiu,

Funnel plot is used as a visual

2018, pp. 541-548).

indication of publication bias. Some factors such as the study size, academic rank and sex

Cutting through the

of primary investigators were not consistently

skin or mucous

associated with the probability of publication or

membrane and any

were not possible to assess separately for

Open approach

other body layers

clinical trials. Additional analysis in the form of

(open surgery)

necessary to expose

D al a d T eedie

the site of the

i -and-fill analysis was

conducted to re-calculate the pooled effect size

procedure (Barta A,

after removing any studies which may

2009, pp. 78-80).

introduce publication bias (i.e., small studies

The number of

with large effect sizes from the positive size of

deaths in a given

the funnel plot) (Higgins J, 2008, pp. 279-281).

Mortality rates

area or period, or from a particular cause (Wise RP, et

Operational definitions

al., 1988, pp. 268-

The variable sought in the study was the death rate of BTAI patients who received

5 228

273); calculated by

corresponding claims of statistical significance

the odds ratio which

will be more conservative (Higgins J, 2008, pp.

compares the relative

266-267). The C ch a e

odds of death in each

chi-squared test and

group (mortality due

the Higgins I2 statistical test were used to

to TEVAR

evaluate the heterogeneity of the included

intervention vs open

studies. If the p-value of the chi-squared test

surgery

results is <0.1, then the null hypothesis that the

intervention).

inclusion study is homogeneous is rejected. Thresholds for the interpretation of I2 referred to Cochrane Handbook for Systematic Reviews

Table 1. Operational Definitions

of Interventions is as follows: 0% to 40% considered as not important; 30% to 60%

Summary measures and data analysis The results of the study were stated as

represent moderate heterogeneity; 50% to 90%

odds ratio (p<0,05; CI 95%). All forms of

represent substantial heterogeneity; 75% to

statistical tests of this study were carried out

100% considered as strong heterogeneity. The

using Review Manager (RevMan) v5.3.

importance of the observed value of I2 depends on (i) magnitude and direction of effects and (ii) strength of evidence for heterogeneity (e.g. p-

Synthesis of the result

value from the chi-

Odds ratio (OR) with a 95% confidence

a ed e ,

de ce

interval for I2) (Higgins J, 2008, pp. 277-278).

interval and p-value below 0.05 was used to determine the effectiveness of the TEVAR

RESULTS

intervention in reducing mortality in BTAI patients compared to open surgery. If OR <1,

Search result and study selection

TEVAR has a significant effect in reducing the death rate of BTAI patients compared to those

Search results from databases yielded

who receive open surgery. Determination of the

615 studies. Two hundred fifty-nine studies

size of the impact is carried out by the fixed-

were obtained after the duplication was

effect method (FEM) or random-effect method

removed. Title and abstract screening excluded

(REM), depending on the homogeneity of the

245 studies and 14 studies were identified with

included studies. Both REM and FEM will give

full-text access available. Inclusion criteria

identical results when there is no heterogeneity

were met by 8 out of 14 studies (4 studies

among

discussed irrelevant outcomes and 2 studies

heterogeneity, confidence intervals for the

were irrelevant study type) and total of 8 studies

average intervention effect will be more

were

extensive if the random-effects method is used

(Demetriades D, et al., 2008; Jonker FHW, et

rather than a fixed-effect method, and the

al., 2010; Patel HJ, et al., 2011; Cho JW, et al.,

the

studies.

Where

there

included

the

meta-analysis

6 229

2012; Azizzadeh A, et al., 2013; Chen SW, et

The results of methodology quality

al., 2015; Elkbuli A, et al., 2019; Hasjim BJ, et

assessment according to The Newcastle-Ottawa

al., 2019). The study selection diagram flow

Scale (NOS) for the Cohort study are shown in

chart is summarized in Figure 1.

Appendix 2. There are 4 of 8 studies (Patel HJ, et al., 2011; Cho JW, et al., 2012; Azizzadeh A,

I cl ded

die cha ac e i ic

et al., 2013; Elkbuli A, et al., 2019)

A total of 8 included studies evaluating mortality

events

small size of samples and insignificant

meta-analysis.

outcomes. Whereas the other 4 studies have low

Information on death, non-death, and total

risks for selection biases (Demetriades D, et al.,

participants numbers were recorded in all

2008; Jonker FHW, et al., 2010; Chen SW, et

studies (Demetriades D, et al., 2008; Jonker

al., 2015; Hasjim BJ, et al., 2019). Only 1 study

FHW, et al., 2010; Patel HJ, et al., 2011; Cho

(Jonker FHW, et al., 2010) did not report

JW, et al., 2012; Azizzadeh A, et al., 2013;

additional factors in the form of pre-operative

Chen SW, et al., 2015; Elkbuli A, et al., 2019;

injury severity score (ISS). The overall studies

Hasjim BJ, et al., 2019). Preoperative injury

(Demetriades D, et al., 2008; Jonker FHW, et

severity scores (ISS) were stated in 7 of 8

al., 2010; Patel HJ, et al., 2011; Cho JW, et al.,

studies.

2012; Azizzadeh A, et al., 2013; Chen SW, et

interventions

TEVAR

for

this

and

underrepresented this meta-analysis because of

P-value of the chi-squared test = 0.96,

al., 2015; Elkbuli A, et al., 2019; Hasjim BJ, et

meaning that the null hypothesis stated the

al., 2019) classified as good quality refer to the

homogeneous

were

threshold for converting the Newcastle-Ottawa

accepted. I2 = 0% indicates the heterogeneity of

scale to Agency for Healthcare Research and

studies

Quality (AHRQ) standards: good (3 or 4 stars

participants

included

negligible. from

studies

There were 1251 were

in selection domain AND 1 or 2 stars in

combined and analyzed in this study. BTAI

comparability domain AND 2 or 3 stars in

screenings were performed with computed

outcome domain); fair (2 stars in selection

tomography (CT) in all included 8 studies

domain AND 1 or 2 stars in comparability

(Demetriades D, et al., 2008; Jonker FHW, et

domain AND 2 or 3 stars in outcome domain);

al., 2010; Patel HJ, et al., 2011; Cho JW, et al.,

poor (0 or 1 star in selection domain OR 0 stars

2012; Azizzadeh A, et al., 2013; Chen SW, et

in comparability domain OR 0 or 1 stars in

al., 2015; Elkbuli A, et al., 2019; Hasjim BJ, et

outcome/exposure domain); however, there are

al., 2019). One study (Azizzadeh A, et al.,

limitations that allow for risk of selection and

2013)

computed

reporting bias from this study because we

tomographic angiography (CTA) to ensure the

included merely retrospective nonrandomized

diagnosis. The characteristics of each study

comparative studies, given the difficulty of

included in this meta-analysis are presented in

finding randomized controlled trials focusing

Appendix 1.

on this topic.

added

2008-2019

additional

who

7 230

Figure 2. Forest Plot Meta-analysis TEVAR interventions reduce mortality rates in BTAI patients compared to open surgery Evaluation of 8 studies (Demetriades D, et al., 2008; Jonker FHW, et al., 2010; Patel HJ, et al., 2011; Cho JW, et al., 2012; Azizzadeh A, et al., 2013; Chen SW, et al., 2015; Elkbuli A, et al., 2019; Hasjim BJ, et al., 2019) revealed that TEVAR was effective in reducing the mortality rate in BTAI patients. A Figure 3. Funnel Plot

pooled study analysis (n = 1251) from 20082019 showed a significant effect (P<0.00001) of TEVAR as an intervention on BTAI

DISCUSSIONS

compared to open surgery. Figure 2 discloses the forest plot for the association between TEVAR intervention and mortality in all ages

Traumatic aortic injury is a severe

BTAI patients over OS. The association

complication of the accidents associated with

obtained is significant, with pooled OR = 0.33;

rapid

95% CI: 0.22-0.49; I2 = 0% (P<0.00001). The

vehicle crushes. In the past, the only available

funnel plot (Figure 3) showed no publication

open surgical repair was associated with

bias was found in this study and heterogeneity

marked mortality and morbidity. Introduction

was considered insignificant. Duval and

T eedie

significantly the management in this particular

i -and-fill analysis identified no

deceleration,

endovascular

predominantly

methods

has

motor

changed

group of patients. The early and mid-term

outlier studies.

results of these novel and minimally invasive 8 231

procedures with stent graft implantation are

a significant advantage in the trauma setting

very pledging. Thus, recently, they have

where BTAI can be managed rapidly, without

become the methods of choice in the treatment

additional blood loss (Riesenman PJ, 2007, pp.

of individuals with traumatic aortic injuries

934 940). Beyond the commonly-encountered

(Tintoiu, 2018, pp. 541-548).

perioperative complications, the repair of

Previous studies have found TEVAR to

BTAIs

may

lead

such as

specific

be the superior option compared to open

complications,

paraplegia,

stent

surgery, particularly in reducing mortality rate

endoleaks, even stroke which represent the

of BTAIs (Eklbuli A, et al., 2019, pp. 179-182).

most common complications of OS and

The present meta-analysis of all comparative

TEVAR respectively. Nevertheless, TEVAR

studies of TEVAR over OS for BTAI to date

has associated with significantly lower rates of

demonstrated a statistically significant benefit

stroke compared to OS (0.85% vs. 5.3%) and

of TEVAR over OS for mortality (pooled OR =

paraplegia is substantially more common after

0.33; 95% CI: 0.22-0.49; I2 = 0%). These

OS than after TEVAR (5.6%-7% vs. 0-1%);

results interpret that the incidence of death in

most likely due to clamping and prolonged

TEVAR is 0.67 times lesser than those who

hypotension and extension of aortic trauma in

underwent OR. Thus, it can be concluded that

the former as well as the short segment of aorta

all studies have shown TEVAR as a more

stented in the latter and its relation to the blood

advantageous intervention for BTAI compared

supply of the spinal cord (Challoumas D, 2015,

to OS.

pp. 69-72; Tang GL, 2008, pp. 671-675). The It was reported that OS has an odds

occurrence of postoperative complications,

ratio of 3 times higher than complications or

including acute renal failure and postoperative

death in hospital (Azzizadeh A, et al., 2013, pp.

infections was also lower in the TEVAR group

108-14). A patient undergoing TEVAR can

(Chen SW, et al., 2015, pp. 1559-66).

simply undergo an isolated endovascular repair,

The highest weighted study in this

while a patient undergoing an open surgery

meta-analysis was Hasjim BJ, et al., 2019 with

requires additional exploratory procedures and

33.6% and followed by Demetriades D, et al.,

temporizing measures. This contributes to the

2008 in second place with 22.4%. Hasjim BJ, et

patient's death rate due to the difference in

al., 2019 discussed comparative study based on

timing of intervention. A study states that the

national trends related to the selection of

average time needed for an intervention is 50%

TEVAR over OS for BTAI patients in adult

shorter in TEVAR compared to OS (Romagnoli

pediatric

AN, 2019, pp. 4-5).

Demetriades examined adult BTAI patients

(mean

age

years),

while

Compared to open surgical repair,

(mean age 40.2 Âą 18.7 years). These studies

endovascular management of BTAI has a

imply that current meta-analysis represents

reduced operative time, estimated blood loss,

BTAI patients from various ages. Eleven years

and volume of blood transfused. This represents

of publication span (2008-2011) proves that 9 232

from the beginning until now, TEVAR versus

reached health facilities in remote areas. Only a

OS for BTAI is still a topic that needs further

few large cities provide this intervention option,

development following the latest settings.

because health workers and equipment needed

There are variations in the outcomes of

cannot be provided in rural areas. Departing

included studies. The lowest OR is shown by

from this situation, our study is expected to

Chen SW, et al., 2015 (0.19; 95% CI: 0.04-

clarify the existing guidelines, so that in the

0.81) and the highest OR (0.64; 95% CI: 0.16-

future the provision of human resources and

2.61) is reached by Elkbuli A., et al., 2019.

equipment needed for TEVAR procedures can

Heterogeneity in the study was shown

be distributed more evenly to all regions of

by the forest plot and considered as negligible

Indonesia, including rural areas (PERKI, 2016;

with a statistic of I = 0% and p-value of the chi-

Commission Vascular HBTKV, 2018).

squared test = 0.96. This elucidates the homogeneity of the review in which all studies

Strengths and limitations of the study

use the same study design and there are similar

This systematic review and meta-

results in all included studies that TEVAR

analysis has several strengths. This study is the

considerably reduces mortality in BTAIs over

first systematic review and meta-analysis that

OS. Furthermore, the symmetrical funnel plot

assesses comprehensive comparison between

in Figure 3 proves homogeneity and low

TEVAR and OS in a modern setting based on

publication bias in this study.

current world's health condition. There is no

The risk of bias examined using The

publication bias observed from the study,

Newcastle-Ottawa Scale (NOS) for the Cohort

evidenced by the results of the symmetrical

study as stated previously is summarized in

funnel plot. Heterogeneity was considered

Appendix 2. According to our assumptions,

absent or ignored in the comparative study of

selection bias could be found due to uneven

the mortality outcome of TEVAR versus open

sample size across studies.

surgery intervention.

Based on the result of this study,

The main limitation of our study is to

TEVAR has been proven to be a superior option

include merely retrospective nonrandomized

compared to open surgery. Nonetheless, the use

comparative studies that allow selection biases

of TEVAR in Indonesia itself is still very

for outcomes in favor of TEVAR. A larger

minimal. According to the Clinical Practice

sample size with wider coverage area is needed

Guidelines and Clinical Pathways issued by

to calculate OR that can represent a worldwide

PERKI, TEVAR and open correction surgery

population. The samples in the included studies

were both the recommended treatment options

came from Asia (South Korea and Taiwan) and

for BTAI, but there is no clear statement which

the United States. The same type of study has

is more recommended. This procedure has been

never been carried out on a sample from

found and recognized as a superior option

Indonesia, whereas the incidence of traffic

compared to open surgery, but has not yet

accidents which caused 80% of BTAIs in 10 233

Indonesia is quite high, approximately the same

guidelines in clinical practice and encourage

as the population of the city of Bukittinggi

the emergence of new research in this field

(Rahman R, 2018). The limited amount of

from Indonesia.

related literature available means that this metaanalysis

must

carefully

examined.

Acknowledgement

Nevertheless, this study yields better evidence

We have nothing to declare.

for the comparison of TEVAR versus OS given the difficulty of recommending prospective

Conflict of interest

randomized control trials that have never been

We declare that we have no competing

conducted.

intention for completing this review.

CONCLUSION

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13 236

APPENDICES

Appendix 1. Characteristics of Included Studies No

Author and Publication Year

Study Desig n

Demetriades D, 2008

Cohort

Jonker FHW 2010

Cohort

Patel HJ, 2011

Cohort

Cho JW, 2012

Cohort

Azizzadeh A, 2013

Cohort

Study Locati on

Follow-up duration

Patient Characteristics

Study Population TEVAR OS

Age: Mean 40.2±18.7 years

United States

26 months

United States

2000-2007

United States

1992-2010

South Korea

August 2003-March 2012 (104 months)

United States

April 2002June 2010

Results (p<0,05; CI 95%) OR

Study included in Meta-analysis

125

39.4±11. 3

38.9±11 .8

0.826

0.25 [0.10, 0.61]

yes

261

0.31 [0.11, 0.90]

yes

39.8±16. 6

39.5±13 .2

0.9

0.40 [0.02, 7.51]

yes

31.14 (mean)

26.27 (mean)

0.231

0.25 [0.01, 6.11]

yes

36.68 (mean)

37.96 (mean)

0.51

0.42 [0.08, 2.30]

yes

Gender: Male 146 Female 47 Age: Mean 39.3±18 years Gender: Male 261 Female 67 Age: Mean 39.0±18.1 years Gender: Male 80 Female 29 Age: Mean 41.94 years Gender: Male 12 Female 6 Age: Mean 36.4 years

Injury Severity Score TEVAR OS P

237

Chen SW, 2015

Elkbuli A, 2019

Hasjim BJ, 2019

Cohort

Taiwan

United States

January 2003February 2014

2016 (a single year retrospectiv e study)

January 2007December 2015

Gender: Male 74 Female 32 Age: Mean 37.9±17.1 years Gender: Male 57 Female 6 Age: Mean TEVAR 41.2 Mean OR 35.9

41.3± 13.7

40.1± 13.3

0.75

0.19 [0.04, 0.81]

yes

172

103

0.64 [0.16, 2.61]

yes

124

38.0 (mean)

0.73

0.37 [0.19, 0.71]

yes

Gender: Male 206 Female 70 Age: Median 16 years Gender: Male 106 Female 53

TEVAR, thoracic endovascular aortic repair; OS, open surgery; ns, not significant; nr, not reported; P, p-value

238

Representativeness Selection of the OS intervention cohort Ascertainment of TEVAR intervention Demonstration that outcome of interest was not present at start of study Age, sex, marital status

Demetriades D, 2008

* * * * *

Jonker FHW 2010

* * * * *

Patel HJ, 2011

* * * *

Cho JW, 2012

* * *

Azizzadeh A, 2013

* *

Chen SW, 2015

Hasjim BJ, 2019 Adequacy of follow-up of cohorts

Follow-up was long enough for outcomes to occur

Elkbuli A, 2019 Assessment of outcome

Additional factors

Appendix 2. The Newcastle-Ottawa Scale (NOS) for Cohort Study Assessment Selection Comparability Outcome

* * * *

* * *

* * * *

* * * * *

* * * * * *

* * * * * * *

* * * * * * * *

239

AMSC 2020 The Relevance Of Traumatic Spinal Cord Injury In Military Veterans With Mental Health Disorder And Government Support: A Systematic Review Farida Aisyah1, Az Zachra1, Ellen Josephine1 1

Second Year of Medical Student, Medical Department, Medical Faculty [corresponding email: azzachras@student.uns.ac.id] Abstract

Introduction Traumatic Spinal Cord Injury (tSCI) is a condition which spinal cord was damaged because of trauma. The incidence of tSCI is approximated to be 36 to 72 cases per million population. Military veterans has the highest level of traumatic spinal cord injury risk compared to other professions. Material and Method This systematic review was carried out using PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) and study search were conducted using PubMed, Google Scholar and ScienceDirect database. The twelve selected studies were appraised using CEBM appraisal tools (Centre for Evidence-Based Medicine). Result Result is completed by cross-sectional and cohort study from 30 up to 8000 veterans per study. Major tSCI happen because explosion, vehicle-related accident, gunshot, and falling from high altitude. Prevalence tSCI in thoracic have highest prevalence followed by lumbar, cervical, and sacral. Furthermore, prevalence of complete tSCI is higher than incomplete tSCI. Military veterans with tSCI show more severe mental disorders such as anxiety, PTSD, psychoses, and bipolar disorders acoompanied with alcohol and substance abuse. Therefore, government support is only relevant in the form of medical facilities and service such as rehabilitation service and medical intervention. Discussion Military veterans have higher risks of PTSD because in war they witness traumatic events. These traumatic events decrease the quality of life of a military veteran, especially those with tSCI because they become more dependent due to the motoric and/or sensory lesion, limited expectancy of life, and even the psychological condition

240

that can lead to severe mental health disorders. For government support, relevance obtain because military veterans have a very high prevalence of being unemployed because of their age or their inability to remain full function due to their motor and/or sensoric injuries therefore military veteran needs assistance towards free medical services and financial support. Conclusion There is a correlation between military veteran with tSCI and higher risks of mental health disorders but the relevance between military veteran with tSCI and government support is not determined yet. Recommendation Further research is needed relating to the relevance of military veterans with traumatic spinal cord injury with mental health diseorder and government support in order to improve the system that has been implemented and improve patientâ&#x20AC;&#x2122;s quality of life especially in the African, Australian, European and Asian continent. Keyword: Military Veteran, Traumatic Spinal Cord Injury, Mental Health, Government Support, Relevance

241

The Relevance Of Traumatic Spinal Cord Injury In Military Veterans With Mental Health Disorder And Government Support: A Systematic Review

Arranged by

Farida Aisyah

(G0018071)

Az Zachra Sanati K

(G0018039)

Ellen Josephine Handoko

(G0018062)

FACULTY OF MEDICINE UNIVERSITY OF SEBELAS MARET 2020

242

Introduction In days of the twenty-one century, trauma care keeps develops both in developing a d de e

ed c

ie , i c di g

a ca e f

i a c d i j

(O Rei

et al,

2014). Spinal Cord Injury (SCI) defined as attenuate neurological conditions with a vast i

a ie

ci ec

a d a huge impact on the health care system

(Alizadeh et al, 2019). Spinal cord injury could be devastating condition because spinal cord injury often strikes all of sudden and the outcome of SCI are commonly either elimination of social life or premature mortality (WHO, 2013a). Yet it is still challenging to diagnose SCI, this following injuries could be appraised for possible damage to SCI, such as: 1) Head injuries, especially in facialias region; 2) Pelvic fractures; 3) Piercing injuries in spine or around spine; and 4) Injuries from work, particularly from falling from heights, this following condition need supporting examination using MRI, CT-Scan, and USG to establish the diagnosis of SCI (NIH, 2016; Scholtes et al, 2012). Pathophysiology of SCI start with primer mechanical damage with commonly consist of spinal cord compression which extend post beat later bleeding start in early period which continues with interruption of blood flow, this interruption cause damage in gray matter, reducing of myelin thickness, oedema, and macrophages that lead to deterioration of nerve transmission, hereafter hours or days, secondary mechanical damage start due to lack of energy because impaired perfusion on cell level and ischemia, for traumatic SCI ischemia begins immediately aftershock happened and will worse for first 3 hours also happen for 24 hours long, damage not only happen in spinal cord but also in local injuries around spinal cord, example neuron in descending pathway which lead to pathological chain of atrophy to necrosis or apoptosis, pathophysiology of secondary damage of SCI is most crucial for implementing advanced therapies on patient with SCI (Yilmaz et al, 2014). Even though clinical management of SCI do undoubtedly enhance by its prognosis, traumatic paraplegia and tetraplegia still remain incurable (Scholtes et al, 2012). Differentiate on its location, SCI could happen on cervical spinal cord injury (C1C8); Thoracic spinal cord injury (T1-T12); Lumbar spinal cord injury (L1-L5); and Sacral spinal cord injury (S1-S5), this causal categories of SCI may result as incomplete SCI, means spinal cord do not lose all the ability to convey impulses to brain or convey majority impulses marked by inappropriate function of sensory and motoric below the level of injury (Reeve Foundation, 2020). Based on the etiology, spinal cord injury could also caused by non-traumatic causes such as cancer, inflammation or infection, and disk

1 243

degeneration of the spine. Another source said that spinal cord injury may stem from traumatic experiences such as sudden accident: gunshot, falling, traumatic blow or other out of blue accident (Scholtes et al, 2012; Reeve Foundation, 2020).

Figure 1. MRI Of Spinal Cord Injury On L1 Fracture (Labajo et al, 2018) The spinal cord that was damaged by trauma is called traumatic spinal cord injury (tSCI). The incidence of tSCI is approximated to be 36 to 72 cases of traumatic spinal cord injury per million population, another study also claims the incidence and prevalence of tSCI in range of 10.4 and 83 per million inhabitants per year and 223-755 per million inhabitants respectively followed by epidemiology study show majority case affect young adult (average age: 29 years), meanwhile in this last three decades, elderly subjects have increased (average age: 45 years). This calculated incidence does not involve a victim who dies at the accident scene (van Middendorp et al, 2011; Kirshblum et al, 2002; Scholtes et al, 2012). Already explained before, most cases of tSCI happen because of sudden action and based on its etiology, army is a profession that has the highest level of traumatic spinal cord injury risk compared to other professions. This statement supported by several prevalence traumatic spinal cord injury in military veterans. Prevalence and incidence of gunshot-induced spine injures among US Army were 0.26% with 55% on fatal state. Data from American Civil War expose spinal injuries estimated to be 1.2% in the Korea War, 1% in the Vietnam War and Gulf War, and 6% in the Panama War. Afghanistan and Iraq war result on 11.1% combatants with spinal injuries which ensuing army with traumatic spinal cord injuries correspond to disable condition and discharge from military service followed by financial burden as much as $3.6 trillion USD and this number will add up to at least 1.2 trillion USD in 2053 (Furlan et al, 2019; Furlan et al,

2 244

2017). Globally, 11% military veterans were injuries include as traumatic spinal cord injury with chronic pain. Operation Iraqi Freedom and Operation Enduring Freedom also Department of Veterans Affairs (AF) estimates probably 450 newly traumatic spinal cord injured veteran enroll at rehabilitation spinal cord injury annually (Fyffe et al, 2019). Despite having low prevalence and incident compare to other traumatic health problems, traumatic spinal cord injury was crucial for soldier worldwide because they have a high risk for tSCI than other professions. The impact of tSCI itself can influence social life, economic status, mental and physical condition of patient. Thus will also affecting a ie

fa i

because they will experience a decrease in quality of life (Fyffe et al,

2019; Ullrich et al, 2008). The reasons why prevalence show 15% of individuals with tSCI are military veterans are veteran tend to experience a higher number of socioeconomic and lifestyle risk factor for pain, veteran also more likely to be old, male, job free, heavy drinker, low income, smoker, single, and less educated than nowadays generation this reason result as veteran have more comorbid medical condition (Ullrich et al, 2008). High prevalence of tSCI in military veterans followed by great lifestyle risk factors by veterans itself making an impact of tSCI are more alarming in veterans. Additional clinical manifestations of tSCI in military veterans are deep vein thrombosis, urinary tract infection, muscle spasms, osteoporosis, pressure ulcers, chronic pain, and respiratory complication. The worst case is the patient has become dependent on caregivers and unavoidable need of assistive technology to aid mobility, communication or even self-care, with tremendous price of assistive technology. This result in neither patients and families having poor economic condition or being unable to purchase the equipment, yet society also give negative attitude and physical barrier towards patient making them have no job and exclude from community. Data showed adult with traumatic spinal cord injuries have global unemployment rate more than 60% pursued by 20-30% of them show clinically significant sign of depression with the deteriorating state of overall health (WHO, 2013b; Ullrich et al, 2008). Related with tSCI in military veterans and mental health, overall 40% of veterans with SCI at least have been diagnosed with one mental disorder, most common is depressive disorder by 19%, posttraumatic stress disorder (PTSD) as much as 12%, followed by substance or alcohol use disorder by 11%, adjustment disorder by 6.8%, pain disorder by 4.5%, personality disorder by 3.0% and other mental health problems include schizophrenia, bipolar, sleep disorder, and sexual disorder in veterans with SCI lean to be higher than the general

3 245

population (McDonald et al, 2017). This prejudice impact related to the mental health of traumatic spinal cord injury in military veterans not silenced by health practitioners under government support, especially when the reason why military veterans suffering is because they fought for their nation. In this systematic review with title, the relevance of traumatic spinal cord injury in military veterans with mental health disorder and government support aims to evaluate is it already relevant or not between government assistance to military veterans with traumatic spinal cord injury followed by it is an impact which is their mental condition also aim to giving solution if the relevance is not found through a point of view of medical professionals, medical student, and community. Materials and Methods The systematic review with the title the relevance of traumatic spinal cord injury in military veterans with mental health disorder and government support was carried out using PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses). Studies search were conducted using PubMed, Google Scholar, and ScienceDirect database with keyword military veteran, traumatic spinal cord injury, mental health, and government support. Inclusion criteria were paper publish only in English, literature have eleven years range since it was published, and qualified literature were deals with traumatic spinal cord injury in military veterans by evaluating whether the literature also looks at the mental health disorder of sufferers and whether the literature discusses support from the government for sufferers to see if there is any relevance among traumatic spinal cord injury in military veterans with mental health disorder and government support. The selected studies were appraised using CEBM appraisal tools (Centre for Evidence-Based Medicine). Journal searching takes time from April to March 2020, from initial search obtained 1,597 studies from selected database, journal selection processes through assessment on title and topic, assessment on abstract, assessment on eligibility, and full test assessment also devoted to inclusion and exclusion criteria. After the journal selection process, obtained 8 qualified literature for this systematic review. Selection of journal shown in Figure 2.

4 246

Initial Search Result (n = 1,597) Studies Excluded on title and topic (n = 1,094)

Studies after screened on title and topic (n = 503)

Studies Excluded on abstract (n = 376)

Studies after screened on abstract (n = 127)

Studies Excluded on eligibility (n = 113)

Studies after screened on eligbility (n = 14)

Studies Excluded full-text assessment

(n = 6) Studies included (n = 8)

Figure 2. Studies Selection Chart

Result From eight qualified journals discuss about traumatic spinal cord injury in military veterans, including etiology, location, and type of tSCI also connect the discussion with a mental health disorder, whether it is diagnosed, emotion disturbance or any substance abuse, and government support, whether about finance, facilities, medical personnel, food, and other assistance that can improve the q a i

f a ie

ife to seek

relevance of military veteran with tSCI with mental health disorder and government support. Summary of selected studies shown in Table 1.

5 247

Table 1. Summary Of Studies Related To tSCI In Military Veterans Associated With Mental Health Disorder And Government Support Authors (Year)

Saadat et al (2010)

McDonald et al (2017)

Lehman et al (2012)

Galvin et al (2014)

Study Design

Cross-sectional study

Retrospective cohort study

39 veterans in Tehran, Iran

280 veterans in USA

31 veteran of the US army in

30 veteran from US or North

Iraq and Afghanistan war

Atlantic Treaty Organization of

Military Veterans

the Afghanistan Wars Based on etiology shrapnel High wound

(34.3%),

Cord Injury (tSCI)

C1-C4 Low lumbar L3-L5 (59.4%), Lumbar 2 or higher (65%) and

bullets (26.1%), low tetraplegia C5- upper lumbar T12-L2 (37.5%), Lumbar 3 or lower (37%).

(22.9%), mines (5.7%), falls C8 (32.5%) and paraplegia

upper and lower lumbar T12-L3 Based on etiologic, blast (70%),

(8.9%) and rest is other

(3.1%). With complete lower

(41.4%) with majority result

causes. For location, cervical from Traumatic Spinal

tetraplegia

injury

(56.4%)

traumatic

accident

dan which not explained further

lumbar

(16.7%),

gunshot

(10%),

fall

(7%),

incomplete vehicle-related accident (7), and

lower lumbar (33.3%), and rest

thoracic/lumbar (43.6%) with

have no neurologic deficit along

100% all participant having

with complete upper lumbar

motor lesion

(10.5%),

incomplete

unknown (7%)

lower

upper lumber (57.9%), and rest have

neurologic

deficit.

Based on etiology, improvised explosive device (25%), vehiclerelated

accident

(34.4%),

6 248

helicopter (9.4%),

(21.9%), fall

gunshot

(6.3%),

and

unknown (3.1%)

Veteran with SCI having 40% of all participant have Not explained

Not

limited observation time

severe

emotional minimum one mental health

Mental

disturbance

Health

mental health-related quality depressive disorder (19%),

Disorder

and

poorer

life by 62.3 mean score

disorder

explained

because

diagnosed,

posttraumatic stress disorder

(12%),

and substance or

alcohol use disorder (11%)

Giving veteran access to free Facilitated in the form of

Provide

health

different echelons of medical protective equipment, vehicle

rehabilitation

insurance,

Government

Support

care

such

as department

services,

veterans

affairs and no further explain

bedsore

management,

wheelchair,

veterans

care,

with

five Giving

progressively technology,

stabilization of life and limb-

surgical

additional

capabilities

transported to higher echelons.

test,

and

physical laboratory

access

medical care consisting of initial

available

and

personal

increasing medical diagnostic,

special center for annual examination

veteran

patients

are threatening aeromedical

Veteran also receive definitive deferment

wounds,

rapid

evacuation, of

and

definitive

800 US dollars per month to

surgery or medical management

treatment to facilities later in

pay nurse and approximately

at Echelon IV or Echelon V evacuation chain. This form of

7 249

1200 US dollars monthly salary for

veteran

hospital

support

living

show

successful

result, can be seen from combat

expenses

casualties surviving their initial wounds and evacuated to a medical

facility

have

survivability exceeding 90%

Table 1. continue Authors (Year)

Guzelkucu et al (2016)

Javadi et al (2014)

Blair et al (2012)

Banerjea et al (2009)

Study Design

Retrospective cohort study

45 Turkish Armed Forces

1984 Iranian veteran of the

598 veterans in Globar War on

8338 veteran in USA

Rehabilitation Center

Iraq-Iran War

Terrorism

Military Veterans

Cervical (17.8%), thoracic Cervical (11.0%), thoracic (51.1%), Traumatic Spinal Cord Injury (tSCI)

and

lumbar (63.3%),

(31.1%). With complete SCI and

lumbar

sacral

Cervical

(15.2%),

Thoracic

(23.8%), (28.1%),

Lumbar

(40.8%), tetraplegia

(1.9%).

With Sacral (10.9%), and other (5%).

(64.5%) and the rest is complete SCI (91.2%) and Complete

SCI

incomplete.

(48.1%0,

further etiology

There

explanation

no incomplete

about further

(8.8%).

explanation

etiology

No incomplete about

unknown (6.7%). etiology,

explosion

vehicle-related

Paraplegia further

(52.9%) (54.8)

and

explanation

with

about

(45.2%), etiology and location and

Based on (56.2%), accidents

8 250

(29.3%), gunshot (14.9%), fall (7.4), dan unknown (4.8%) Not explained

Anxiety disorder: reaction to Veteran severe stress and adjustment

Mental

Health

Disorder

e v

disorder

(2.6%),

depressive

disorder (up to 13.61%). explanation about the diagnose

disorder

(26.7%),

psychoses

Veteran with SCI reported

(5.3%),

PTSD

(6.3%),

having a higher level of

schizophrenia (3.2%), alcohol

psychological condition than

abuse

the general population

(8.0%),

Provide management of SCI Veteran

n e

devastating Anxiety disorder (9.8%), bipolar

mental state with no further

(9.0%), and

drug

abuse

tobacco

abuse

(18.9%)

a c

having

in the form of Government Support

medical structured

intervention such as surgery

government,

having

well- Ensuring the supply of the Provide medical care and other

support giving

from foodstuffs and medical needs

services in the Veteran Health

them

Administration

consistent access to medical care and education related to self-care following SCI

9 251

Result complete by cross-sectional and cohort study with several veterans from 30 until up to 8,000 per study. The majority of military veteran is from the USA, Iran, and lastly from Turkey, they were veteran from the Afghanistan war, Global War on Terrorism, and the majority is ex-soldier from Iraq-Iran war. Based on etiology, majority traumatic SCI happen because explosion, vehicle-related accident, gunshot, and falls respectively from higher to lower value yet based on location, prevalence tSCI in thoracic have highest number followed by lumbar, cervical, and sacral in sequence based on the highest prevalence furthermore prevalence of complete tSCI is higher than incomplete tSCI. Mental health disorder relevance on a military veteran with tSCI found to be high in depressive disorder followed by the second high and so on is anxiety, PTSD, psychoses, and bipolar disorder accompanied with alcohol and substance abuse, summed up mental health condition in military veteran with tSCI show more severe mental disturbance and longer devastating phase than general population result as poorer mental health-related quality life however the relevance of mental health disorder did not explained in 3 out of 8 selected journal. Further, the relevance of government support in military veteran with tSCI shown in large quantities in the form of medical facilities and service, such as rehabilitation service, wheelchair and other personal health assistance equipment, annual examination, and medical intervention, forth only one literature shown government support in form of fresh money, insurance, food, or education about tSCI. Discussion Military veteran is getting less attention nowadays, this situation getting worse too because their health condition also affects their quality of life. In the case of military veteran with tSCI, their condition have compelling relevance with their mental health condition and their health outcome also dependency on government support on their sustainability of life. First, a discussion started in the relevance to the mental health condition, we should take note that soldiers leaving for the battlefield were voluntary and intentionally, especially for military veteran ex-Iran and Iraq war, those military veteran have hope in having ideal society after the war ended yet after 8 years of Iran and Iraq war, the social norm is different and have evolved so they were confronted with a social norm which far from an ideal society they expected as if their self-sacrificed have no impact make them have emotion disturbance such as anger, fear, sadness, shame and make them have poorer social functioning, they also going through and witnessing a traumatic event in a warzone thereby increasing the risk of PTSD, another sudden

10 252

traumatic event in a result of tSCI making the veteran quality of life decrease, high chances to be more dependent on others because of motoric or/and sensory lesion, and dissatisfication with work along to consistent of getting unemployed induce poorer economic status and less education, moreover trauma can cause loss of hope, a limited expectation of life, fear that life will end abruptly, and outright destructive those factors resulting on lack of close peronal relationship and poorer mental health condition which lead to a severe mental health disorder, this pathophysiologic way about military veteran whom having poorer mental health state after traumatic event on spinal cord called a

a ic i a i ie

(Saadat et al, 2010; Kleber, 2019; Furlan et al, 2017; SAMHSA,

2014; Schwarzbold et al, 2008; Smith et al, 2008). Lastly, yes, there is compelling relevance between a military veteran with tSCI and mental health disorder to wit military veteran with tSCI have a higher risk of having a mental disorder. Second discussion talk about relevance to government support, a veteran with tSCI have great prevalence of being unemployed because of age and their incapability yet the disability that occurs to them is not their fault but the risk of fighting for the country thus it is a common occurrence that the country bears the risk by providing various form of assistance. A veteran of the military with tSCI in some country serve with high technology of personal equipment to assist their daily needs, they also receive assistance through medical service at no charge and financial support through insurance which is not obtained by the veteran military without tSCI and the general population, even some of the military veteran with tSCI still having government support after they retire, but this data about government assistance only exist in a big country with a vast number of soldier, such as Afghanistan, Iran, Iraq, and the USA while in other countries there is no data about government assistance and the result of government support are not explained in all further studies, only the things that are carried out without being explained whether the support taken are effective or not, so it cannot be determined whether the relevance is between a military veteran with tSCI and government support in where a military veteran with tSCI have more government support than the general population and military veteran without tSCI (Schoenfeld et al, 2013a; Schoenfeld et al, 2013b). Limitation about this systematic review is the lack of journals that discuss relating to military veteran with tSCI with both about mental health disorder and government support, as well as the narrow scope of research on the relevance of government support

11 253

Conclusion There is compelling relevance between military veteran with tSCI related to mental health, yet can not be determined whether there is relevance between military veteran with tSCI related to government support. Recommendation Further research is needed relating to the relevance of military veterans with traumatic spinal cord injury with mental health disorder and government support in order i

e he

ha ha bee i

e e ed a d i

e a ie

f ife.

Besides, we also recommend doing more study about the relevance of military veterans with traumatic spinal cord injury with government support especially in the continent of Africa, Australia, Europe, and Asia. Reference Alizadeh Arsalan, Dyck M. Scott, and Karimi-Abdolrezaee. (2019). Traumatic Spinal Cord Injury: An Overview of Pathophysiology, Models and Acute Injury Mechanisms. Frontiers, 10(282). Banerjea R, Findley P. A, Smith B, Findley T, and Sambamoorthi U. (2009). Cooccurring medical and mental illness and substance use disorder among veteran clinic users with spinal cord injury patients with complexities. Spinal cord, 47:789-795. Blair A. James, Patzkowski C. Jeanne, Schoenfeld J. Andrew, Rivera D. C. Jessica, Grenier S. Eric, Lehman A. Ronald Jr, Hsu R. Joseph, and the Skeletal Trauma Research Consortium. (2012). Spinal Column Injuries Among Americans in the Global War on Terrorism. The Journal Of Bone And Joint Surgery, 94(18):135. Furlan C. Julio, Gulasingam Sivakumar, Craven B. Catahrine. (2017). The Health Economics of the spinal cord injury or disease among veterans of war: A Systematic Review. The Academy of Spinal Cord Injury Professionals, 40(6):649-664. Furlan C. Julio, Gulasingam Sivakumar, Craven B. Catahrine. (2019). Epidemiology of War-Related Spinal Cord Injury Among Combatants: A Systematic Review. Global Spine Journal, 9(5):545-558.

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Fyffe C. Denise, Williams Joyce, Tobin Paul, and Gibson-Gill Carol. (2019). Spinal Cord I j

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Patterns: Protocol for a Qualitative Study. JMIR Res Protoc, 8(10). Galvin W. J, Freedman A. B, Schoenfeld J. A, Cap P. A., and Mok J. M. (2014).Morbidity of early spine surgery in the multiply injured patient. Arch Orthop Trauma Surg, 134:1211-1217. Guzelkucuk U, Demir Y, Kesikburun S, Aras B, Yavuz F, Yasar E, dan Yilmas B. (2016). Spinal cord injury resulting from gunshot wounds: a comparative study with non-gunshot causes. International Spinal Cord Society, 54:737-741. Javadi M, Hafezi-Nejad Nima, Vaccaro Alexander, and Rahimi-Movaghar Vafa. (2014). Medical Complications and Patient Outcomes in Iranian Veterans with Spinal Cord Injury. Adv Clin Exp Med, 23(2):269-275. Kirshblum C. Steven, Groah L. Suzanne, McKinley O. William, Gittler S. Michelle, and Stiens A. Steven. (2002). Spinal Cord Injury Medicine: 1. Etiology, Classification, and Acute Medical Management. Arch Phys Med Rehabil, 83(1):50-57. Kleber J. Rolf. (2019). Trauma and Public Mental Health: A Focused Review. Frontiers in Psychiatry, 10(451). Labajo H. Guadalajara, Leon M. Arellano, Vaquero J. Crespo, Walverde I. Nunez, and D. Garcia-Olmo. (2018). Objective demonstration on improvement of neurogenic bowel dysfunction in a case of spinal cord injury following stem cell therapy. Journal of Surgical Case Report, 11:1-4. Lehman A. Ronald, Paik Haines, Eckel T. Tobin, Helgeson, Cooper B. Patrick, and Bellabarba Carlo. (2012). Low lumbar burst fractures: a unique fracture mechanism sustained in our current overseas conflicts. The Spine Journal, 12:784-790. McDonald D. Scott, Mickens N. Melody, Goldberg-Looney D. Lisa, Mutcler J. Brian, Ellwod S. Michael, and Castillo A. Teodoro. (2017). Mental disorder prevalence among U.S. Department of Veterans Affairs outpatients with spinal cord injuries. The Journal of Spinal Cord Medicine, 41(1):1-12.

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National Institutes of Health. (2016). How is it diagnosed?. US: Eunice Kennedy Shriver National Institutes of Child Health and Human Development. Access on https://www.nichd.nih.gov/health/topics/spinalinjury/conditioninfo/diagnosed, March 2020 O Rei

Da id, K i g T, a d Tai N. (2014). Fie d T a

a Ca e I The 21 st Century.

Journal of the Royal Army Medical Corps, 154(4):257-264. Reeve Foundation. (2020). Spinal cord injury types. Short Hills: Christopher & Dana Reeve

Foundation.

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https://www.christopherreeve.org/ko/international/top-paralysis-topics-inkorean/spinal-cord-injury-types, March 2020. Saadar Soheil, Javadi Masoud, Divshali S. Baharak, Tavakoli H. Amir, Ghodsi M. Seyed, Montazeri Ali, dan Rahimi-Movaghar Vafa. (2010). Health-related quality of life among individuals with long-standing spinal cord injury: a comparative study of veterans and non-veterans. BioMed Central Public Health, 10:6. Schoenfeld J. Andrew, Dunn C. John, and Belmont J. Philip. (2013a). Pelvic, spinal and extremity wounds among combat-specific personnel serving in Iraq and Afghanistan (2003-2011): A new paradigm in military musculoskeletal medicine. International Journal of Care Injured, 44:1866-1870 Schoenfeld J. Andrew, Laughlin D. Matthew, McCriskin J. Brendan, Bader O. Julia, Waterman R. Brian, and Belmont J. Philip. (2013b). Spinal Injuries in United States Military Personnel Deployed to Iraq and Afghanistan. Spine, 38(20):17701778. Scholtes F, Martin Didier, and Brook Gray. (2012). Spinal cord injury and its treatment: current management and experimental perspectives. Advances and technical standards in neurosurgery, 29-56. Schwarzbold Marcelo, Diaz Alexandre, Martins T. Evandro, Rufino Armanda, Amante N. Lucia, Thais E. Maria, Quevedo Joao, Hohl Alexandre, Linhares N. Marcelo, and Walz Roger. (2008). Psychiatric disorders and traumatic brain injury. Neuropsychiatric Disease and Treatment, 4(4):797-816.

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Smith M. Bridget, Weaver M. Frances, and Lavela Sherri. (2008). Health-related quality of life for veterans with spinal cord injury. Spinal Cord, 48:507-512. Substance Abuse and Mental Health Services Administration Center for Substance Abuse Treatment (SAMHSA). (2014). A Treatment Improvement Protocol TraumaInformed Care In Behavioral Health Services. USA: Department Of Health And Human Services. Ullrich M. Philip, Jensen P. Mark, Loeser D. John, Cardenas D. Diana, and Meaver M. Frances. (2008). Pain among veterans with spinal cord injury. J Rehabil Res Dev, 45(6):793-800. van Midden dorp J. Joost, Goss Ben, Urquhart Susan, Atresh Sridhar, Williams P. Richard, and Schuetz Michael. (2011). Diagnosis and Prognosis of Traumatic Spinal Cord Injury. Journal of Global Spine, 1:1-8. World Health Organization. (2013a). International Perspectives on Spinal Cord Injury. Malta: WHO. World Health Organization. (2013b). Spinal Cord Injury. WHO. Yilmaz Tevfik, Turan Yahya, and Keles Aysenur. (2014). Pathophysiology of the spinal cord injury. Journal of Clinical and Experimental Investigations, 5(1):131-136.

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Effectiveness of Extracorporeal Shockwave Therapy in Acute and Chronic Soft Tissue Wound Healing: A Systematic Review 1

Johanna Valentina Michele Indrawan1 Michelle Imanuelly1 Vanessa1 1

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

Introduction Wounds are an injury to the living tissue which can be an important cause to morbidity and mortality to everyone around the world. Wounds are classified into acute and chronic. In acute wound healing usually occurs during a short period, meanwhile in chronic wounds, healing does not occur within the expected period of time. Wounds are prevalent with diabetes melitus, arteriosclerosis, infections, and venous ulcers. This calls for new methods to improve the outcome of wound healing, and one of them is the usage of extracorporeal shockwave therapy (ESWT). Aim This systematic review aims to determine the efficacy of ESWT in acute and chronic soft tissue wound healing. Materials and Methods Search was done through Online Resources that have Open Access, such as Pubmed, Google Scholar, and ScienceDirect. PICO was used as an analytical design method and all literatures will be filtered using exclusion and inclusion criteria. Result and Discussion There were 27.966 journals from Pubmed, Google Scholar, and ScienceDirect. After filtered with exclusion and inclusion criteria, 7 literatures were taken to be analyzed. Ottoman, et al: shows a significant acceleration (P = 0.0001). Schaden, et al: shows a complete wound re epithelialization of 75% of patients with complicated, nonhealing, acute, and chronic wounds (wound size: <10 cm2 (P < 0.01; OR = 0.36; 95% CI, 0.16 to 0.80)) and (duration: <1 mo (P < 0.001; OR =0.25; 95% CI, 0.11 to 0.55)). Saggini, et al: 50% of the patients achieve complete wound healing after 6 sessions of shockwave therapy (P < 0.001). Zaghloul, et al: shows improvement in scar thickness (42.55%; 6.72 ± 1.62 mm to 3.86 ± 0.73 mm; P = 0.0001). Moretti, et al: re epithelialization and healing time in patients increase (re epithelialization: mean±DS; 2.97 ± 0.34 mm2/die vs 1.30 ± 0.26 mm2/die, healing time: mean±DS; 60.8 ± 4.7 days vs 82.2 ± 3.7 days). Fioramonti, et al: shows a significant improvement of scar contractures or hypertrophic scar, colour appeared to be more similar with the surrounding skin, the textures are less firm and thinner. Cho, et al: shows a specific difference in scar pain reduction (7.80 ± 1.54 to 3.80 ± 2.35 points, P < 0.001). Conclusion Most of the research shows that ESWT is effective in the treatment for acute and chronic soft tissue wound healing.

269

Keyword: extracorporeal shock wave therapy, chronic wound, acute wound, soft tissue wound.

270

Effectiveness of Extracorporeal Shockwave Therapy in Acute and Chronic Soft Tissue Wound Healing: A Systematic Review Johanna Valentina1 Michele Indrawan1 Michelle Imanuelly1 Vanessa1 1

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

271

Effectiveness of Extracorporeal Shockwave Therapy in Acute and Chronic Soft Tissue Wound Healing: A Systematic Review 1

Johanna Valentina Michele Indrawan1 Michelle Imanuelly1 Vanessa1 1

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

INTRODUCTION Shockwave Therapy Extracorporeal Shock wave therapy is a potential therapeutic treatment that plays a role in treating severe wounds.1 In chronic wound healing it is proved that Extracorporeal Shock wave therapy results in a significant positive effect. ESWT regulates blood perfusion in injuries, decreases pro-inflammatory response and improves tissue regeneration.2 ESWT also promotes epithelization which is defined as the process of migration and replication of epithelial cells across the skin edges in response to growth factors after several wound healing processes, it gives improvement and promotes physiological tissue growing.3 Shock wave therapy conducts its mechanism by the formation of cavitation bubbles that evoke distinct biological tissue and cell responses. I

ec a

a d c

helps in increasing

mechanosensitive feedback responses resulting in vasodilation, increased microcirculation, induction of neo-angiogenesis, immunomodulatory action that helps reducing inflammation rate and acceleration of stem cells for tissue growth. Extracorporeal shock wave therapy has been proven to treat severe soft tissue and bone injuries also complex conditions that are in high risk of being chronic due to persistent inflammation. The goal of this treatment is to convert chronic inflammation condition into a desirable acute state, hinder vicious inflammatory cycles and promote tissue regrowth mechanism of the body4. Wound Healing Wound healing is a normal biological process in our body which occurs after the programmed phase: hemostasis, inflammation, proliferation, and remodelling.5 Wound healing consists of regeneration and tissue repair processes to restore damaged tissue. In adult, optimal wound healing involves series of event, such as rapid homeostasis, appropriate inflammation, mesenchymal cell differentiation, proliferation, and migration to the wound site, angiogenesis, re-growth of epithelial tissue, and proper synthesis, cross-linking, and alignment of collagen to provide strength to the healing tissue. 6 The first phase of wound healing is the forming of blood clot around the wounded area. Hemostasis begins with vasoconstriction and fibrin clot formation. This process is affected by some factors, including transforming growth factor (TGF- ),

a e e -derived-growth-factor (PDGF), fibroblast-growth-factor

(FGF), and epidermal-growth-factor (EGF). The inflammatory phase is characterized by infiltration of

272

neutrophil to the site of the wound due to the chemotaxis gradient. Macrophages and T lymphocytes also migrate to the wounded area. Neutrophil plays a role in removing microbes and cellular debris. Macrophages will release cytokines which will promote inflammatory response. T lymphocytes will also migrate to the wounded area to regulate wound healing, especially to maintain the integrity of the tissue, remove pathogens, and regulate inflammation. The proliferative phase is characterized by epithelial migration and proliferation. Some cells that play a role in this phase are fibroblast and endothelial cells. Fibroblasts will produce collagen within the wounded area. Fibroblasts will also produce glycosaminoglycans and proteoglycans which are major components of extracellular matrix (ECM). The proliferation and synthesis of ECM will lead to the remodelling phase which form new capillaries and normal tissue to heal the wound. MATERIALS AND METHODS PRISMA statement is used as a basis to report our systematic review which consists of evidence-based sets. Search is done through Pubmed, Google Scholar, and ScienceDirect using the following keywords e

: e

d , e

27.966

a e

, c

a , af e f e ed

d , ac e

e c

a d

S c Wa e T e a

S c Wa e. MeSH e

terminology for O (Outc

a d c

d a e

'' a d Ad

. MeSH e

e a c e e c

e? I c

e-e : Ca E

e a ac

c e a ae

P (P

I (I e e C (C

a )

e 7

)

a d ca

ea S c Wa e T e a c

c e a, e

valid journals. Systemic analysis is done using PICO. MeSH e a dC

d , a d

Ac e

N/A. MeSH e. T e e ea c

effec

ea ac e

d e , acute and chronic injuries,

population: adult (ages 18-80 years old), outcome: skin re-epithelialization, tissue growth and scar size. Exclusion criteria are: literature review, systematic review, case report, animal study and population: children. In order to minimize bias, we will check for the validity of the studies that suits the inclusion and exclusion criteria. After ensuring the validity of the studies, the data will be analyzed.

273

RESULTS AND DISCUSSION Using the PICO approach, search is done through an online database, and we acquired 5 articles that will be analyzed . The selection process is shown in the diagram below

274

In a prospective randomized trial conducted by Ottoman, et al, acceleration in skin re epithelialization on graft donor site was assessed by randomizing 28 subjects with acute traumatic wounds and burns which require skin grafting into a control and study group. Patients in the experiment group (n=13) who received defocused Extracorporeal Shockwave Therapy (ESWT; 100 impulses/cm2, at 0.1mJ/mm2) once after skin harvest, show a significant acceleration (P=0.0001) in mean times needed to complete graft donor site epithelialization (13.9 Âą 2.0 days) compared to patients in control group (n=15) on standard topical therapy (non adherent silicone mesh) and antiseptic gel (polyhexanide/octenidine) on graft donor site without ESWT (16.7 Âą 2.0 days) . A study carried out by Schaden, et al showed a complete wound re epithelialization in 75% (n=156) of patients in their level IIb study of patients (n=208) with complicated, nonhealing, acute and chronic heterogeneous soft-tissue wounds. Patients were prospectively enrolled to receive standard debridement prior to ESWT (100 to 1000 shocks/cm2 at 0.1mJ/mm2; according to wound size, every 1 to 2 weeks over mean three treatments) and moist dressings. The study analyses multivariate outcome; wound size (<10 cm2 (P < 0.01; OR = 0.36; 95% CI, 0.16 to 0.80)) and duration (<1 mo (P < 0.001; OR =0.25; 95% CI, 0.11 to 0.55)) as independent predictors of complete healing. Statistical analyses were not done to assess the difference of healing rate based on cause of wound. Although small wounds (<10 cm2 ) with short duration (<1 month old) were associated with rapid complete epithelialization, unfocused shockwave treatment was proven effective in achieving complete wound re epithelialization in larger wounds (>10 cm2 ).

275

276

In a level IIIb study conducted by Saggini, et al, 30 consecutive patients were treated with focused ESWT with low energy flux density (100 impulses/cm2 at 0.037mJ/mm2 ) every two weeks, aiming for complete wound healing (specific parameter for healed wound was not specified). 50% of the patients (n=16) in the experimental group achieved complete wound healing within 6 sessions of shockwave therapy. Patients with unhealed wound experienced statistically significant improvements (p<0.01) shown in decreased amount of exudate, increased percentage of granulation tissue compared to fibrin/necrotic tissue (varying 5-45%) and decrease in wound size (decreased in ulcer dimension and surface area) after four to six sessions of ESWT. Significant decrease in pain was also reported in the experimental group (p<0.001) compared to patients in the control group (n=10) in standard regular dressings only.

Zaghloul, et al aim to investigate the effect of Extracorporeal Shockwave Therapy in post burn hypertrophic scar by conducting a controlled randomized study (n=40). The control group (Group B) received traditional physical therapy program (deep friction massage and stretching exercise), while patients in experimental group (Group A) received the same traditional physical therapy program with 12 ESWT sessions. ESWT was administered on an outpatient basis; the treatment region was covered with 2500 to 3000 impulses twice a week for 6 weeks. Statistical analysis showed significant improvement in scar thickness and Vancouver Scar Score (vascularity, pigmentation, pliability, and height). Improvement in scar thickness were measured in millimeter (mm) by comparing patients experimental group (42.55%; 6.72 Âą 1.62 mm to 3.86 Âą 0.73 mm; p=0.0001) compared control group

277

(12.15%; 6.58 ± 1.43 mm to 5.78 ± 1.17 mm; p=0.0001). Decrease in Vancouver Scar Scale mean score also indicate a significant change between both groups (48.57%; 8.75 ± 1.71 to 4.5 ± 1.73; P=0.0001 vs 14.04%; 8.9 ± 1.61 to 7.65 ± 1.78; P=0.0001).

Moretti et al carried out a randomized, prospective, controlled study by randomizing patients affected by neuropathic diabetic foot ulcer (n=30) into two equal control and study groups. Aiming for wound re epithelialization, the study was done by giving essentials foot ulcers care, debridement, adequate pressure relief, and standard treatment on infection with or without ESWT. Patients in both groups were followed for 20 consecutive weeks, proportion of ulcers that healed in the study and control group were 53.33% and 33.33% respectively. Both index of re epithelialization (mean±DS; 2.97 ± 0.34 mm2/die vs 1.30 ± 0.26 mm2/die) and healing time (mean±DS; 60.8 ± 4.7 days vs 82.2 ± 3.7 days) were increased in the ESWT group and differences were statistically significant. According to Fioramonti et al, ESWT was effective in treating postburn pathologic scar, shown as a significant improvement of scar contractures or hypertrophic scar in 16 patients who underwent 12 sessions of shockwave treatment (twice per week, for 6 weeks). Patients were followed every two weeks for two months. At the end of the study period, patients reported that scars felt to be less stiff, color appeared to be more similar to surrounding skin, texture less firm and thinner (no specific scale was used to compare this change). Visual analog scale was used to quantify scar improvement (0 =

278

poor to 10 = excellent), final score was derived from the evaluation of factors such as scar thickness, pliability, pigmentation, and acceptability; observer comfort; and movement impairment.

A study conducted by Cho et al, shows that Extracorporeal Shock Wave Therapy was done 3 times which shows a specific difference in the scar pain reduction ( NRS score 7.80 ±1.54 to 3.80±2.35 points, p<0.001 ) compared to the control group ( NRS score 7.30±1.30 to 5.55±1.50 points, p<0.001). There is also a significant difference in the Nirschl pain phase system value ( NRS score ( NRS score 6.35±1.31 to 4.40±1.21, p<0.001 ) compared to control group ( NRS score 6.35±0.75 to 5.40±1.05, p<0.002 ). Pain threshold is also measured by 3 times therapy which shows ( NRS score 1.20±0.54 to 2.60±0.73, p<0.001 ) compared to the control group ( NRS score 1.41±0.75 to 2,03±0.72, p<0.001). Based on the data, the study shows that Extracorporeal Shock Wave therapy shows great reduction in scar pain and also higher pain relief due to Extracorporeal Shock Wave therapy that induces vascularization for tissue regeneration. There are improvements measured by rodes and mauley measurement.

279

Prehomogenity test of the Preliminary assessment

Control group (n=20)

ESWT group (n=20)

P-value

NRS

7.30±1.30

7.80±1.54

0.316*

Pain Threshold

1.41±0.75

1.20±0.54

0.328*

Nirschl Pain phase

6.35±0.75

6.35±1.31

0.339*

Poor

13 (65)

17 (85)

Fair

7 (35)

3 (15)

Good

0 (0)

Excellent

0 (0)

system value

280

CONCLUSION Most of the research proved that there is an efficacy of ESWT in the wound healing process of acute and chronic soft tissue. In literature that we are currently studying, ESWT has a great potential and promising effect in the outcome of acute and chronic wounds. ESWT which is used to treat wounds is not considered as destructive. The shockwave has induced biological responses to stimulate the repair and regeneration of soft tissue. Although the mechanism of shockwave which can induce biological response is still under research, but it has shown that it stimulates factors affecting the healing cascade, such as cytokines and chemokines. ESWT efficacy and safety show that shockwave can be an innovative treatment for acute and chronic wounds. Besides ESWT is easy to perform, it also saves time and does not require anesthetics. ESWT may be a valid alternative treatment for patients with problematic wound conditions. However, some studies only have several numbers of patients as subjects. Thus, further clinical research with sufficient number of subjects is needed to confirm and develop the promising outcome regarding this matter.

281

REFERENCES 1. Davis, T., Stojadinovic, A., Anam, K., Amare, M., Naik, S., & Peoples, G. et al. (2009). Extracorporeal shock wave therapy suppresses the early proinflammatory immune response to a severe cutaneous burn injury. International Wound Journal, 6(1), 11-21. doi: 10.1111/j.1742481x.2008.00540.x 2. Kuo, Y., Wang, C., Wang, F., Chiang, Y., & Wang, C. (2009). Extracorporeal shock-wave therapy enhanced wound healing via increasing topical blood perfusion and tissue regeneration in a rat model of STZ-induced diabetes. Wound Repair And Regeneration, 17(4), 522-530. doi: 10.1111/j.1524-475x.2009.00504.x 3. Garner, W. (2009). Shock Wave Therapy for Acute and Chronic Soft Tissue Wounds: a Feasibility Study. Yearbook Of Plastic And Aesthetic Surgery, 2009, 197-198. doi: 10.1016/s1535-1513(08)79073-8 4. Zissler, A., Stoiber, W., Pittner, S., & SĂ¤nger, A. (2018). Extracorporeal Shock Wave Therapy in Acute Injury Care: A Systematic Review. Rehabilitation Process And Outcome, 7, 117957271876513. doi: 10.1177/1179572718765138 5. Guo, S., & Dipietro, L. (2010). Factors Affecting Wound Healing. Journal of Dental Research, 89(3), 219 229. doi: 10.1177/0022034509359125 6.

Gonzalez, A. C. D. O., Costa, T. F., Andrade, Z. D. A., & Medrado, A. R. A. P. (2016). Wound healing - A literature review. Anais Brasileiros De Dermatologia, 91(5), 614 620. doi: 10.1590/abd1806-4841.20164741

7. Ottomann, C., Hartmann, B., Tyler, J., Maier, H., Thiele, R., Schaden, W., & Stojadinovic, A. (2010). Prospective Randomized Trial of Accelerated Re-epithelialization of Skin Graft Donor Sites Using Extracorporeal Shock Wave Therapy. Journal of the American College of Surgeons, 211(3), 361 367. doi: 10.1016/j.jamcollsurg.2010.05.012 8. Sc ade , W., T e e, R., K

, C., P c , M., N

a , A., A

e , C. E.,

ad ovic, A.

(2007). Shock Wave Therapy for Acute and Chronic Soft Tissue Wounds: A Feasibility Study. Journal of Surgical Research, 143(1), 1 12. doi: 10.1016/j.jss.2007.01.009 9. Saggini, R., Figus, A., Troccola, A., Cocco, V., Saggini, A., & Scuderi, N. (2008). Extracorporeal Shock Wave Therapy for Management of Chronic Ulcers in the Lower Extremities.

Ultrasound

Medicine

Biology,

34(8),

1261 1271.

doi:

10.1016/j.ultrasmedbio.2008.01.010 10. Zaghloul, M., Khalaf, M., Thabet, W., & Asham, H. (2016). Retrieved 29 March 2020, from https://scholar.cu.edu.eg/?q=mahmoud_zaghloul/files/78-85v9n3pt.pdf 11. Moretti, B., Notarnicola, A., Maggio, G., Moretti, L., Pascone, M., Tafuri, S., & Patella, V. (2009). The management of neuropathic ulcers of the foot in diabetes by shock wave therapy. BMC Musculoskeletal Disorders, 10(1). doi: 10.1186/1471-2474-10-54

282

12. Fioramonti, P., Cigna, E., Onesti, M., Fino, P., Fallico, N., & Scuderi, N. (2012). Extracorporeal Shock Wave Therapy for the Management of Burn Scars. Dermatologic Surgery, 38(5), 778782. doi: 10.1111/j.1524-4725.2012.02355.x 13. Cho, Y., Joo, S., Cui, H., Cho, S., Yim, H., & Seo, C. (2016). Effect of extracorporeal shock wave therapy

on scar

pain in burn patients.

10.1097/md.0000000000004575

283

Medicine,

95(32),

e4575.

doi:

TABLES AND FIGURES

Author and

Study Design

Object/Injury

Parameter

Result

Year

Ottoman, et

Prospective

Acute traumatic

100

Shows a significant

al7, 2010

randomized

wounds and

impulses/cm2,

acceleration

clinical trial

burn

at 0.1mJ/mm2-,

(P=0.0001)

1 session.

in mean times needed to complete graft donor site epithelization (13.9 Âą 2.0 days).

Schaden, et

Prospective

Complicated,

al8, 2007

clinical trial

nonhealing,

100 to 1000

Complete wound re-

shocks/cm2 at

epithelialization in

acute and

0.1mJ/mm ;

75% patients in IIb

chronic

according to

level study of patients.

heterogeneous

wound size,

soft-tissue

every 1 to 2

wounds

weeks over means three treatments.

Saggini, et al9, 2008

Randomized

Chronic

controlled

posttraumatic, venous, and diabetic ulcers

100

Complete wound

impulses/cm2 at healing and patients 0.037mJ/mm2,

with unhealed wounds

6 sessions.

statistically have significant improvements (p<0.01).

284

Zaghloul, et

Randomized

Burn scars

al , 2016

2500-3000

Significant

impulses with

improvement in scar

average time

thickness and

10-15

Vancouver Scar Score

minutes,12

(vascularity,

sessions.

pigmentation, pliability, and height).

Moretti, et 11

al , 2009

Fioramonti, et

Prospective

Neuropathic

randomized

diabetic foot

controlled Experimental

al12, 2012

100

All treated scars have 2

impulses/cm at

a more acceptable

ulcer

0.03mJ/mm2.

appearance.

Postburn

12 sessions.

Scars are less stiff,

pathologic scar

colour appeared to be more similar to surrounding skin, texture less firm and thinner.

Cho et al13, 2016

Randomized

Burn scars

100

Scar pain was reduced 2

clinical trial

285

impulses/cm at

more significantly.

0.05-0.15

NRS score

mJ/mm2 , 4 Hz

significantly decreased

frequency, 3

(7.80 Âą 1.54 to 3.80 Âą

sessions

2.35 points, P<0.001)

UNDERSTANDING THE FACTOR OF AMBULANCE DELAY AND AMBULANCE CRASH TO FIND A BREAKTHROUGH FOR ENHANCING AMBULANCE EFFICIENCY: A SYSTEMIC REVIEW Authors: Ketut Shri Satya Wiwekananda

(21269)

Rizqiko Pandai Hamukti

(21286)

Ketut Shri Satya Yogananda

(21270)

Kadek Egadia Calisto

(21268)

AMSA-Universitas Gadjah Mada Introduction Trauma is one of the most contributors to the number of deaths worldwide. Injury trauma patients need medical treatment as fast as possible. More than 20% of patients needing emergency treatment have died on their way to the hospital because of ambulance delays. Beside that, The National Highway Traffic Safety Administration (NHTSA) shows there are an estimated 4500 ambulance crashes per year with 37% of them resulting in injuries. Ambulance delay and ambulance crash are problems that must be suppressed to improve patientâ&#x20AC;&#x2122;s survival during trips to the hospital. Therefore, this systematic review is aimed at finding the main factor that causes ambulance crashes and ambulance delays; and discuss the correlation of both factors. So, researchers can find the right solution to overcome these problems for the next project.

Method To get a study of the factors that cause ambulance delay and factors that cause ambulance crashes, researchers used 9 databases. Researchers used 2 different keywords to search for these two topics. The study will be included in this systematic review if it discusses the ambulance on land; discuss the factors that cause ambulance delay and ambulance crashes; written in english; using cross-sectional methods, cohort studies, and qualitative studies; and published no later than 20 years ago. Researchers conducted a risk of bias assessment using Joanna Briggs Institute's critical appraisal tools. Researchers used descriptive statistical data analysis methods. Researchers took the 3 factors that most influenced the ambulance delay and ambulance crash from each journal, then combined the factors obtained. That way, it can be seen what factors most influence the ambulance delay and ambulance crash.

286

Key Findings Researchers received 7 journals regarding the ambulance delay factor and 6 journals regarding the factor of ambulance crash. The main factor that causes ambulance delay is traffic congestion. Meanwhile, the main factor causing ambulance crash is intersection. The factors that cause the ambulance delay and the factors that cause the ambulance crash are actually related. Traffic congestion often occurs especially at intersection. So that, intersections have a significant effect on ambulance delay and also ambulance crashes. To overcome this problem, researchers offer the latest breakthroughs namely additional ambulance caution lamp on intersection. When an ambulance arrives, the additional ambulance caution lamp located in the direction of the ambulance will show a green color and red color will appear on additional ambulance caution lamp in other direction of road.

287

PCC AMSC 2020

UNDERSTANDING THE FACTOR OF AMBULANCE DELAY AND AMBULANCE CRASH TO FIND A BREAKTHROUGH FOR ENHANCING AMBULANCE EFFICIENCY: A SYSTEMIC REVIEW

Authors: Ketut Shri Satya Wiwekananda (21269) Rizqiko Pandai Hamukti

(21286)

Ketut Shri Satya Yogananda

(21270)

Kadek Egadia Calisto

(21268)

AMSA-UNIVERSITAS GADJAH MADA 2020

288

INTRODUCTION

hospital. Response time is the time between an emergency call is made to the ambulance station

Trauma is one of the most contributors to the

and the time an ambulance arrives at the scene for

number of deaths worldwide. Globally, in 2014,

assistance. A shorter response time is known to

trauma caused more than 5 million deaths

greatly improve survival (Zahra Farahgol, 2017).

worldwide and has a prevalence of 9% to the total world's deaths, nearly 1.7 times the number of

However, with the crucial roles of EMS to

deaths caused by HIV / AIDS, tuberculosis, and

provide assistance to patients, there are many

malaria combined (Who, 2015). In the United

problems that make EMS cannot provide

States, trauma becomes number one caused death

assistance as fast as possible to the patient

in people with age between 1-44 years old in 2017

because of the ambulance delay. Ambulance

(Cdc.gov, 2017). In addition, trauma is also

delay gives a significant effect to worsen the

caused by either fatal or non-fatal injury to

injury remained by the patients. More than 20%

casualties. Annually, it is estimated that there are

of patients needing emergency treatment have

30 million cases of non-fatal injuries and 240,000

died on their way to the hospital because of delays

cases

2017).

due to traffic jams and uncooperative motorists

Approximately 90% of global injury-related

(Panyaarvudh, 2017). Besides that, there are

deaths occur in low- and middle-income

many cases of traffic accidents that involve

countries, which places a large burden on

ambulances in it. The National Highway Traffic

developing countries, which lack trauma care

Safety Administration (NHTSA) shows there are

resources (Hamidreza Abbasi, 2017). Statistics

an estimated 4500 ambulance crashes per year

for Road Traffic Injuries (RTIs) also show that

with 37% of them resulting in injuries (Smith,

the estimated 90% of RTIs occur in low and

2015).

fatal

injuries

(Cdc.gov,

middle-income countries (Patel A, 2017).

Ambulance delay and ambulance crash are

Injury trauma patients need medical treatment as

problems that must be suppressed to improve

fast as possible. Pre-Hospital Emergency Medical

patient s survival during trips to the hospital.

Services (EMS) is the first level of treatment

Factors causing these problems must be clarified

provided to patients suffering from life-

to facilitate actions that can be taken to overcome

threatening conditions by emergency medical

the problem. Therefore, this systematic review is

technicians (EMT) and paramedics before being

aimed at finding the main factor that causes

submitted to the hospital. EMS seeks to reduce

ambulance crashes and ambulance delays; and

response time because the longer time for patients

discuss the correlation of both factors. So,

to get medical treatment is correlated with the

researchers can find the right solution to

higher number of deaths occurring out of

overcome these problems for the next project.

289

MATERIALS AND METHOD

time limit due to the limited articles that discuss this topic. The study will be excluded if the full

Authors conduct a systemic review based on

text of the study is inaccessible; discuss about air

PRISMA Statement s flow diagram and checklist

ambulance or water ambulance, only focused on

to improve the reporting quality of the result. The

1 factor and focus on discussing prehospital

PRISMA Statement consist of 27 item checklist

treatment in patients.

and 4 step flow diagrams (Moher, et al., 2009).

Risk of Bias Assessment

This study is focused on two topics regarding the factors that affect ambulance delay and factors

To ensure the validity of the study, 2 reviewers

that affect ambulance crashes.

evaluate each study independently and compare

Search Strategy

the results of the evaluation. Researchers evaluate the journals using a critical appraisal checklist

To find both topics in this study, we use these databases: ASCE

Pubmed,

Library,

Scopus,

Clinical

from the Joanna Briggs Institute's critical

Sciencedirect, Key,

appraisal tools. Journals that have high validity

EBSCO,

will be included in this systematic review.

Cambridge, Taylor & Franncis, dan ProQuest. The keywords that we use to find articles that

Data Extraction and Analysis Strategy

discuss factors that cause ambulance delays are:

Researchers took data from the

(factor OR cause) AND ( ambulance response time OR ambulance dela

consisting of the place where the research was

OR emergenc

conducted, the date the study was conducted, the

response time OR pre-hospital response time ).

method, the number of research subjects

The keywords we use to find articles that discuss

involved, and the results of the research.

factors causing ambulance crashes are: (factor

Researchers conducted data analysis using

OR cause OR characteristic) AND ("ambulance crashes"

"ambulance

accidents"

journals

descriptive statistical methods. To summarize the

results of each journal, researchers took the 3

"emergency medical vehicle collisions").

most important factors about ambulance delays

Study Selection

and ambulance crashes based on the obtained study. After that, researchers combine the 3 most

The study will be included in this systematic

preferred

review if it discusses the ambulance on land;

factors

from

each

journal

and

interpreted in graphical form. That way,

discuss the factors that cause ambulance delay

researchers can find out what is the most

and ambulance crashes; written in english; using

important factors of ambulance delays and

cross-sectional methods, cohort studies, and

ambulance crashes

qualitative studies; and published no later than 20 years ago. Researchers impose a considerable

290

RESULT

Factor of Ambulance Delay

Risk of Bias Assessment

Study Characteristic

Systematic assessments of biases in the included

Seven studies have been obtained that are

studies were carried out using Joanna Briggs

accessed in full text. Of the 7 studies that have

Institute's critical assessment tools to ensure their

been accessed, 4 studies conducted in developed

validity. A total of thirteen studies consisting of

countries, 3 studies conducted in developing

three types of research methods, namely cohort,

countries. All studies discuss the factors that

qualitative, and cross-sectional with respectively

cause ambulance delay, with 2 studies using

8, 3, and 2 studies. The assessment of each study

qualitative methods to determine the factors that

is carried out using appraisal tools that are

cause ambulance delay, 2 studies using cohort

appropriate to the research method. The results of

studies to look for factors that cause ambulance

the study assessment show that all studies are

delay, and 3 studies using cross sectional search

included as high quality. Table.1

table.3 shows

for causal factors ambulance delay. There were

appraisal results on studies using Joanna Briggs

123 respondents for the qualitative study, 49,798

Institute's Critical assessment tools.

patients used in the cohort studies, and 149 patients used in the cross-sectional study.

Study Search Result

Outcome

The literature search and selection process are illustrated in figure 1. We retrieved 620 articles

In a study conducted by Patel et al (2017), Traffic

from 9 databases and other sources (manual

conditions are the main cause of ambulance

search and bibliography from another study).

delay, followed by bad location and lack of

Full-text of 13 articles were assessed for

personel. In a study conducted by Noorani et al

eligibility after the exclusion of duplicated 25

(2014) which influence ambulance delay are

studies. We excluded 575 studies because they

traffic conditions, transportation availability, and

published before 2000 (n=207), did not use

distance of travel. In another study, Dimitriou,

suitable

not

Efthymiou, & Antoniou (2018) also stated that

correlated to the topic (n=247), or were not fully

traffic jams and congestion in urban areas and the

accessible (n=3). From that, 13 studies were

lack of cooperation of people with EMS

included in this paper.

ambulances are factors that affect ambulance

study

design (n=116),

were

delay. The study conducted by Lam et al (2015) stated that traffic conditions had the most significant influence on ambulance response time followed by weather and scene.

291

Figure 1. Study search and selection process

292

Table 1. Critical Appraisal for Cohort Study

Column1

Sanddal et al., 2010

Kahn et al., 2001

Ray et al., 2005

Ray et al., 2007

Custalow et al., 2004

Saunders et al., 2012

David C et al., 2012

Lam et al., 2015

Were the two groups similar and recruited from the same population?

Were the exposures measured similarly to assign people to both exposed and unexposed groups?

Was the exposure measured in a valid and reliable way?

Were confounding factors identified?

Were strategies to deal with confounding factors stated?

Was the follow up time reported and sufficient to be long enough for outcomes to occur?

Was follow up complete, and if not, were the reasons to loss to follow up described and explored?

Were strategies to address incomplete follow up utilized?

Was appropriate statistical analysis used?

Were the groups/participants free of the outcome at the start of the study (or at the moment of exposure)? Were the outcomes measured in a valid and reliable way?

Total

293

Table 2. Critical Appraisal for Qualitative Study Griffin et al., 2012

Patel et al., 2017

Noorani et al., 2014

Is there congruity between the stated philosophical perspective and the research methodology?

Is there congruity between the research methodology and the research question or objectives?

Is there congruity between the research methodology and the methods used to collect data?

Is there congruity between the research methodology and the representation and analysis of data?

Is there congruity between the research methodology and the interpretation of results?

Is there a statement locating the researcher culturally or theoretically?

Is the influence of the researcher on the research, and vice- versa, addressed?

Are participants, and their voices, adequately represented?

Is the research ethical according to current criteria or, for recent studies, and is there evidence of ethical approval by an appropriate body?

Do the conclusions drawn in the research report flow from the analysis, or interpretation, of the data?

Total

294

Table 3. Critical Appraisal for Cross sectional Study Saleh et al., 2018

Dimitriou et al., 2018

Were the criteria for inclusion in the sample clearly defined?

Were the study subjects and the setting described in detail?

Was the exposure measured in a valid and reliable way?

Were objective, standard criteria used for measurement of the condition?

Were confounding factors identified?

Were strategies to deal with confounding factors stated?

Were the outcomes measured in a valid and reliable way?

Was appropriate statistical analysis used?

Total

295

Study conducted by Griffin & McGwin (2012) also

cause ambulance crash, with all of the studies

supports that traffic conditions are the main cause

using cohort studies to look for factors that cause

of ambulance delay. In another study conducted by

ambulance crash with the longest research period

Xue & Weng (2014), the most influencing factor

10 years and the shortest research period 2 years.

for ambulance delay is holidays followed by bad

There were 5.031 total of ambulance crash that

weather and poor light conditions. In a study

were evaluated from whole article.

conducted by Saleh et al (2018) also provide different factors causing ambulance delay, namely

Outcome

knowledge of local ambulance phone number,

From the 6 studies that were reviewed, generally

referral process, and method of transferring the

there were 7 factors that mostly influence on

injured patient and type or diagnosis of injuries.

ambulance crashes: intersection, turns, other vehicle

carelessness,

ambulance

operator

carelessness, road conditions, inappropriate ambulance parking, and traffic light violations. In a study conducted by Kahn, Kuhn, & Pirallo (2001), the most influential factor in ambulance crashes is intersection, turns and other driver carelessness. Meanwhile, a study conducted by Custalow & Gravitz (2004), said that violations of traffic lights, intersections, and other driver carelessness due to alcohol are the main factors Figure 2. Graphic of Factor Ambulance Delay

of ambulance crashes. Intersection, turns, and

From that graphic we know that the most factor

collisions at traffic lights are also a major factor

that cause ambulance delay is traffic (5 from 7

in ambulance crashes in studies conducted by

studies).

Ray & Kupas (2005). Ray & Kupas (2007) also conducted a study which stated that accidents in

Factor of Ambulance Crash

urban areas were mostly caused by turns,

Study Characteristic

intersections, and carelessness from ambulance operators, while in rural areas many were caused

Six studies have been obtained that are accessed

by road conditions. While studies conducted by

in full text. Of the 6 studies that have been

Saunders & Heve (2012), mentioned that the

accessed, all studies conducted in developed

most frequent causes of ambulance crashes in

countries. All studies discuss the factors that

cities are careless ambulance drivers, traffic light violations, and unsafe parking positions.

296

Moreover, intersection, road condition, and

conditions in the form of vehicle density, poor

ambulance operator carelessness are the main

knowledge of traffic rules, and distance. two

causes of accidents in study conducted by

studies that counted the number of ambulance

Sanddal, Sanddal, Ward, & Satanley (2010).

delay cases also showed that traffic congestion was a major influence on traffic conditions. So from the literature we find that traffic conditions are the main cause of ambulance delay. Factor of Ambulance Crash Based on the journals obtained, the intersection was the most cause of the ambulance crash. Ambulance routes with multiple intersections increase the risk of ambulance accidents.

Figure 3. Graphic of Factor Ambulance Crash

Intersections are considered a dangerous site for

From that graphic, known that the most factor that

ambulances and intersections have been used

cause ambulance crashes is intersection (5 from 6

several times as interventions point by police

studies).

agencies (Kahn, Kuhn, & Pirrallo, 2001). Intersections are also the place where ambulance crashes cause the most trauma to ambulance

DISCUSSION

passengers. Ambulance drivers are required to pass the intersection with high vigilance by

Factor of Ambulance Delay

slowing down the speed of the vehicle to ensure

Two of the three studies that calculated the delay

that traffic is safe to pass and making eye contact

time interval showed the highest delay time in

with other drivers before crossing the intersection

traffic jams. In a study conducted by Griffin et al

(Custalow & Gravitz, 2004). Ambulance crashes

(2012), it showed that the average traffic jam

often occur at four-way intersections. An increase

caused an ambulance delay of 10 minutes and in

in the incidence of ambulance collisions at

a study conducted by Lam et al (2015) gave the

intersections was recorded in those with traffic

result that a dense traffic condition caused an

signals (Ray & Kupas, 2005). Ambulance

ambulance delay of 12.98 minutes longer than

crashes that occur at the intersection often occur

rare traffic conditions. Two studies using

in urban areas (Ray & Kupas, 2007). From the

qualitative methods showed that almost all

facts obtained from the literature, it supports that

respondents agreed that traffic conditions were

intersection is the main factor of ambulance

the main contributor to ambulance delay. The

crashes.

respondent also gave the main problem of traffic

297

Ambulance crashes cause a slowing of patient

not able to pass due to the congested road traffic

delivery and have the potential to worsen and

even though the ambulance sounds its emergency

endanger the condition of patients, ambulance

siren (Custalow, 2004). So that, intersections

officers, and other drivers (Pattanarattanamolee

have significant effect on ambulance delay and

et al., 2017). The existence of an ambulance crash

also ambulance crash. This still leaves an effort

will cause additional victims that need to be

to conduct more in-depth research to provide

treated and will aggravate the patient's condition

solutions in order to reduce the risk of delays and

before compared to before the ambulance crash

ambulance crash. (Kahn et al., 2001).

occurred. This will require additional medical

Comparison with Related Studies

personnel both to bring them to health facilities

There are two literature reviews about the factors

and to handle them. The

Correlation

Between

Factor

that cause ambulance crashes and one systemic

review about the factors that cause ambulance

Ambulance Delay and Ambulance Crash

have been collected. Literature review by Hsiao,

Ambulance response time and ambulance safety

Hongwei et al. has review wide field of literature

to deliver patients in order to get treatment as

related to the factors that cause emergency

soon as possible is one of the key indicators of

vehicle accidents. Reported risk factors, control

trauma

2015).

measures, and knowledge gaps relevant to

Increasing the number of vehicles has an impact

emergency vehicle accidents. Emergency vehicle

on increasing traffic density. The rapid growth in

is at risk between emergency response and return

the number of vehicles in developing countries

from a call, disruption in driving emergency

further increases the risk of ambulance delays and

vehicles, driver assistance technology in vehicles,

ambulance crashes either to pick up or deliver

and vehicle red lights running off (Hsiao, Chang

patients to the nearest health facility (Patel et al.,

& Simeonov, 2018).

management

(Lam

al.,

2017).

Literature review by Sanddal, Nels et al. state

Based on result of this study, the most important

that ambulance crashes occur with greater

factor causing ambulance delays is traffic

frequency and severity than crashes involving

congestion and the most important factor causing

vehicles

ambulance crashes is intersection. factors that

characteristics. Crashes in rural areas tend to be

cause ambulance delay and factors that cause

more severe in terms of injury or death to vehicle

ambulance crash actually are interconnected.

occupants. An annotated bibliography is followed

Traffic congestion often occurs especially on the

by a discussion and conclusion that identify

traffic signal at the intersection (Lam et al., 2015).

opportunities for prevention activities in the areas

This traffic congestion causes the ambulance do

298

similar

size

and

weight

of education, enforcement, and engineering

older than five years as a result of insufficient

(Sanddal, Albert, Hansen & Kupas, 2008).

amount of appropriate literatures available, and the data we included are suitable for our study.

Systemic review by M, Li, et al. found that many

The second limitation concerns the scope of this

researchers have investigated areas of emergency

study, as we only focused on ambulance services

department crowding and ambulance diversion;

on the mainland. Hence, the air and water

however, research focused solely on the

ambulance services are not assessed because the

ambulance offload delay problem is limited. A

use of these services is very uncommon.

common theme found throughout the reviewed articles was that this problem includes clinical, operational, and administrative perspectives, and

CONCLUSION

therefore must be addressed in a system-wide manner to be mitigated (Li, Vanberkel & Carter,

After conducting a systemic review of 13

2018).

journals, traffic conditions are the main factor causing ambulance delay, while the intersection

From our research, there is no individual study that

assessed both ambulance

delay

is the main factor causing ambulance crashes.

and

Traffic conditions and intersection have a close

ambulance crash factors. Likewise, there are also

relationship, where most traffic congestion

no literatures that connects factor of ambulance

occurs at the intersection. Intersection causes a

delay with the factor of ambulance crash.

significant impact on ambulance crashes and

Strength and Limitation

ambulance delays. Therefore, a solution is needed to reduce the adverse effects of the intersection

As far as the authors are aware, this is the first

on ambulances.

study that comprehensively describes both ambulance delay and ambulance crash factors, and analyzes the correlations between ambulance

RECOMMENDATION

delay and ambulance crash factors. Indeed, at present, general research on these topics is still in

The effect of the intersection on the response time

its infancy. Suggestions for overcoming these

and safety of the ambulance performance has a

problems is provided in this study. Compared to

significant impact. This still leaves an effort to

other systematic reviews, our study has provided

conduct more in-depth research to provide

a comprehensive bias assessment so that our

solutions in order to reduce the risk of delays and

study uses high-quality references.

ambulance accidents. Researchers have own solutions to overcome ambulance delay and

However, there may be some possible limitations

ambulance crashes that occur due to intersection.

in this study. First, we included studies that was

299

Researchers intend to make additional ambulance

After this project was carried out, the researchers

caution lamps on intersection.

suggested that the government also participate in making regulations regarding the additional

When an ambulance arrives, the additional

ambulance caution lamp. In addition, researchers

ambulance caution lamp located in the direction

also hope that the government can socialize the

of the ambulance will show a green color which

function of the additional ambulance caution

means vehicles from that direction can continue

lamp to the public.

the journey. Meanwhile, apart from the direction the ambulance is coming, the additional ambulance caution lamp will show red which

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means the vehicle from that direction must stop first. After the ambulance passes the intersection,

Cdc.gov. (2017). Ten Leading Causes of

the additional ambulance caution lamp will be

Death and Injury - PDFs|Injury Center|CDC.

deactivated.

[online]

Available

at:

https://www.cdc.gov/injury/wisqars/LeadingCau

Additional ambulance caution lamp uses a radio

ses.html [Accessed 7 Mar. 2020].

frequency receiver. Radio frequency receiver is

Custalow, & Gravitz. (2004). Emergency

installed to receive radio signals from the radio ambulance

Medical Vehicle Collisions and Potential for

automatically when ambulance in radius of 200

Preventive Intervention. Prehospital Emergency

meters from additional ambulance caution lamp.

Care , 8(2), 175-184.

frequency

transmitter

Additional ambulance caution lamp that is closest

Dimitriou, L., Efthymiou, D., & Antoniou, C.

to the ambulance, which means that along with

(2018). Saving Lives through Faster Emergency

the ambulance will receive the first radio signal.

Unit Response Times: Role of Accessibility and

After that, the additional ambulance caution lamp

Environmental Factors. Journal of Transportation

that first receives the radio signal from the

Engineering, Part A: Systems, 144(9), 04018053.

ambulance will turn on the green light, after that

https://doi.org/10.1061/JTEPBS.0000169

it transmits the radio signal to the additional Griffin,

ambulance caution lamp on a different way to

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turn on the red light. After the ambulance passes

R.,

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McGwin,

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intersection more than 200 m from the additional

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Hsiao, H., Chang, J., & Simeonov, P. (2018).

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Panyaarvudh, J. (2017). 20 per cent of

Factors: The Journal Of The Human Factors And

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delays. [online] https://www.nationthailand.com.

10.1177/0018720818786132 Kahn,

Kuhn,

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Patel, A., Vissoci, J., Hocker, M., Molina, E.,

United States : an 11-Year Retrospective

Gil, N. M., & Staton, C. (2017). Qualitative

Analysus. Prehospital Emergency Care , 5(3),

evaluation of trauma delays in road traffic injury

261-269.

patients in Maringรก, Brazil. BMC health services

Lam, S. S. W., Nguyen, F. N. H. L., Ng, Y.

research,

Y., Lee, V. P.-X., Wong, T. H., Fook-Chong, S.

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in Singapore. Accident Analysis & Prevention,

with

82, 27 35. doi:10.1016/j.aap.2015.05.007

literature. Health

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Vehicles

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Li, M., Vanberkel, P., & Carter, A. (2018). A ambulance

804.

Ray, A. F., & Kupas, D. F. (2005).

the ambulance response times of trauma incidents

17(1),

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M. C., & Ong, M. E. H. (2015). Factors affecting

review

at:

Ray, A. M., & Kupas, D. F. (2007).

delay

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crashes in Pennsylvania. Prehospital Emergency

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Care, 416-420.

018-9450-x

Saleh, H. M., Elsabagh, A. E., Elewa, M. G.,

Moher, D. et al., 2009. Preferred Reporting

Fawzy, A. A., Hassan, O. M., Comer, A. C.,

Items for Systematic Reviews and Meta-

Abdelmonem, I. M., Hirshon, J. M., & El-

Analyses: The PRISMA Statement. Ann Intern

Shinawi,

Med, 141(4), pp. 264-269.

(2018).

Admission

delays'

magnitude of traumatized patients in the

Noorani, M. M., Khaliq, M. F., Shoaib, M.,

emergency department of a hospital in Egypt: a

Sheikh, A., Moughal, U. E., Moazzum, W., &

cross-sectional study. European journal of trauma

Ali, S. A. (2014). Time intervals and associated

and emergency surgery : official publication of

factors of emergency treatment: first insight into

the European Trauma Society, 44(2), 225 230.

Pakistani system. International archives of

https://doi.org/10.1007/s00068-017-0762-1

301

Sanddal, N., Albert, S., Hansen, J., & Kupas, D. (2008). Contributing Factors andIssues Associated with Rural Ambulance Crashes: Literature

Review

andAnnotated

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Emergency

Care, 12(2),

257-267.

doi:

10.1080/10903120801907661 Sanddal, T. L., Sanddal, N. D., Ward, N., & Satanley,

(2010).

Ambulance

Crash

Characteristics in the US Defined by the Popular Press: A Retrospective Analysis. Emergency Medicine International, 1-7. Saunders, C. E., & Heye, C. J. (2012). Ambulance Collisions in an Urban Environment . Prehospital and Disaster Medicine, 118-124. Who.int. (2015). WHO | Injuries and violence: the facts 2014. [online] Available at: https://www.who.int/violence_injury_prevention /media/news/2015/Injury_violence_facts_2014/e n/ [Accessed 7 Mar. 2020]. Xue, S., & Weng, J. (2014). Analysis of Uncertainty Associated with Response Time in Work Zone Traffic Accidents. CICTP 2014. doi:10.1061/9780784413623.355

302

APPENDIX DESIGN OF FUTURE PROJECT

Figure 4. How the Additional Ambulance Caution Lamp Works

Figure 5. Additional Ambulance Caution Lamp on Intersection with Traffic Light z

Figure 6. Additional Ambulance Caution Lamp on Intersection without Traffic Light

303

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

304

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: 0.55â&#x20AC;&#x201C;1.14]). The proportion of patients with mild cognitive disabilities was also similar: 21.7% and 22.8%, respectively (RR = 0.91 [95% CI: 0.71â&#x20AC;&#x201C;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: 0.71â&#x20AC;&#x201C;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

305

HANDLING TRAUMA IN ELDERLY PATIENT

Authors:

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

Asian Medical Students Association-Indonesia (AMSA-Indonesia) 2020

306

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 50â&#x20AC;&#x201C;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 postinjury. 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,

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 10

307

event. Leong et al. studied the effect of a co-injury (injury to another part of the body) with an mTBI in young patients and found that their functional outcome was significantly worse 11 than those without a co-injury. 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

308

(RR = 0.90 [95% CI 0.58â&#x20AC;&#x201C;1.39]). We found no significant difference in cognitive outcomes at six months between these two subgroups (20.4% v. 22.9%, RR = 0.82 [95% CI 0.59â&#x20AC;&#x201C;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 11-15

cognitive status (recognized as delirium) of elderly patients.

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 factors 17

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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

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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.

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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. 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.

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Table and Figures

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AMINO | AMSC 2020: LONDON

AMINO | PCC AMSC 2020: LONDON

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Knowledge, Attitude, and Practice of First Aid in Road Traffic Accidents Settings Among Online Motorcycle Drivers in Surabaya: A Cross-Sectional Study David Nugraha – Bendix Samarta Witarto – Clonia Milla – Kevin Luke AMSA-Universitas Airlangga, Surabaya, East Java, Indonesia

INTRODUCTION Over the years, road traffic accidents (RTAs) have been one of the leading cause of death worldwide, including in Indonesia. Indonesia was ranked fifth highest in number of deaths due to RTAs worldwide with 31.282 deaths. In this case, immediate pre-hospital emergency care (PHEC) performed by bystanders, including first aid, plays important roles in saving lives, preventing further injury, and reducing delays in emergency medical services.1 It is well-known that training increases b ande knowledge, willingness, and performance on doing first aid.2 Unfortunately, study related still accounted very minimal in Indonesia. Currently, advancements of information and technology affect all sectors of human life, including online transportation development. Recently, online motorcycle driver (OMDs) services in Indonesia are having substantial growth.3 These online drivers may act as RTAs bystanders since they are more likely to encounter any RTAs due to high mobility. Thus, this study aims to describe knowledge, attitude, and practice regarding first aid among OMDs in Surabaya, Indonesia.

METHODS This is a single-centered cross-sectional study conducted from March 4 15, 2020 with OMDs in Surabaya as participants. OMDs were recruited using incidental sampling and verbally consented as participants. We conducted one on one interview based on standardized online questionnaire for ease usage (http://tiny.cc/FirstAidQuestionnairehttp). The questionnaire was adapted from previous study4 and modified to suit our local condition to assess demography, knowledge, attitude, and practice of first aid in RTAs settings. Data then collected and processed using Microsoft Excel 2013.

RESULTS and DISCUSSION Figure 1. Participants were answering questionnaire

Table 2. Knowledge of study participants regarding first aid Variable

Table 4. Practice of study participants regarding first aid

Heard about first aid

40 (64.5%)

Ever received first aid training

6 (9.7%)

First aid saves life

47 (75.8%)

Emergency number known Knowledge when and where to provide first aid

23 (37.1%) 35 (56.5%)

Bystander should give first aid

53 (85.5%)

Airway problem symptom or sign known

17 (27.4%)

Correct safe position knowledge

35 (56.5%)

Apply splint for fracture

39 (62.9%)

Apply pressure for severe bleeding

45 (72.6%)

First aid priority

Table 1. Socio-demog a hic & a ici an characteristic. RTA. Road traffic accidents Variable Age (in years) 20-29 30-39 40-49 50 Marital Status Married Unmarried Experience (years) 3 4-6 7 Educational Status Illiterate Elementary Junior High Senior High Undergraduate above Hours of driving per day 5 5-10 > 10 RTA witnessed in last 6 months 0 1-5 >5

Frequency (%) 12 (19.4%) 25 (40.3%) 17 (27.4%) 8 (12.9%) 54 (87.1%) 8 (12.9%) 57 (91.9%) 4 (6.5%) 1 (1.6%) 0 (0%) 7 (11.3%) 9 (14.5%) 38 (61.3%) 8 (12.9&) 5 (8.1%) 34 (54.8%) 23 (37.1%) 31 (50%) 18 (29%) 13 (21%)

Practice

Frequency (%)

Transfer to hospital

36 (58.1%)

Bleeding control

17 (27.4%)

Breathing management

8 (12.9%)

Chest compression

6 (9.7%)

Don't know

10 (16.1%)

Splinting fracture

3 (4.8%)

Indication of hospital transfer Unconscious

47 (75.8%)

Open wound

36 (58.1%)

Fracture

35 (56.5%)

Don't know

2 (3.2%)

The assessment of a ici an Table 3. Attitude of study participants regarding first aid Attitude

Response

Willingness to provide first aid Yes No Maybe Reason not to provide Fear to worsen condition Lack of knowledge Fear to law Should lay person be trained Yes in first aid? No Don't know Willingness to attend training Yes No

Frequency (%)

First kit available Ever used first kit Ever applied first kit to victim First aid provided Attended victim of airway problem Transfer to hospital Called ambulance Did nothing Chest compression Attended victim of severe bleeding Tourniquet Called ambulance Applied pressure Limb elevation Did nothing Attended victim of head and neck injury Called ambulance Transfer to hospital Did nothing Attended victim of bone fracture Called ambulance Transfer to hospital Applied splint Did nothing

5 (8.1%) 23 (37.1%) 7 (11.3%) 28 (45.2%) 18 (29%) 16 (25.8%) 10 (16.1%) 6 (9.7%) 33 (53.2%) 15 (24.2%) 10 (16.1%) 2 (3.2%) 2 (3.2%) 33 (53.2%) 22 (35.5%) 7 (11.3%) 23 (37.1%) 17 (27.4%) 15 (24.2%) 7 (11.3%)

knowledge revealed that 64.5%

had ever heard about first aid but only 9.7% were trained, which is

Frequency (%) 46 (74.2%) 6 (9.7%) 10 (16.1%)

study.6 The correct management to severe bleeding was found to

26 (41.9%)

Ethiopia study).7 Unfortunately, splint applied to fracture is still low

23 (37.1%) 13 (21%) 51 (82.3%) 6 (9.7%) 5 (8.1%) 36 (58.1%) 26 (41.9%)

(24.2%) compare to 54.3% in previous study.8 About 85.5% of the

slightly higher percentage (11.3%) of the driver trained in previous be similar in both studies (53.2% in our study and 50.7% in the

responders agreed that bystander should give first aid, and 75.8% believed that first aid could save lives. More than half responders (58.1%) directly transfer to hospital as the top first aid priority which is similar to previous study, calling an ambulance or police

A pooled of 62 OMDs were approached for interview. All participants in our study were male with the mean age of

accorded as top priority.4 Mostly, 74.2% were willing to provide

37.9 years. Majority of the drivers (61.3%) had formal education in senior high and 91.9% of them had below 3

first aid and the rest who not mostly because fear of doing harm

years experiences in their present occupational with 54.8% drove for 5-10 hours. Half of the study participant had

than help (41.9%). On the other hand, a study from India reported

ever witnessed at least one road traffic accident in the last 6 months but only 45.2% ever provided first aid. As a

92.5% willingness to help.8 To the best of our knowledge, this is

comparison, a study in Czech Republic revealed that only 22% had experienced providing first

aid.5

the first study to assess knowledge, attitude, and practice among OMDs in Indonesia.

CONCLUSION Knowledge of first aid in RTAs settings among OMDs is considered moderate, while attitude is considered high. Unfortunately, practice is considered still low. The number of trained OMDs are very low, hence training program from stakeholders is very important to improve first aid intervention in RTAs setting by OMDs as first responder. REFERENCES 1. Riva, G., Ringh, M., Jonsson, M., Svensson, L., Herlitz, J., Claesson, A., ... & Nord, A. (2019). Survival in out-of-hospital cardiac arrest after standard cardiopulmonary resuscitation or chest compressions only before arrival of emergency medical services: nationwide study during three guideline periods. Circulation, 139(23), 2600-2609. 2. MARTONO, M., SUDIRO, S., & SATINO, S. (2018). Simulation Model Algorithm for Pre-Hospital Emergency Care (PHEC) Volunteers in Indonesia. Jurnal Sains Kesihatan Malaysia (Malaysian Journal of Health Sciences), 16(1). 3. Septiani, R., Handayani, P. W., & Azzahro, F. (2017). Factors that affecting behavioral intention in online transportation service: Case study of GO-JEK. Procedia Computer Science, 124, 504-512. 4. Awasthi, S., Pamei, G., Solanki, H. K., Kaur, A., & Bhatt, M. (2019). Knowledge, attitude, and practice of first aid among the commercial drivers in the Kumaon region of India. Journal of family medicine and primary care, 8(6), 1994. 5. Linkov, V., Trepacova, M., Kureckova, V., & Pai, C. W. . Novice Czech Drivers Ability and Willingness to Offer the First Aid after Traffic Accidents: The Positive Effect of the First-Aid Training. Communications-Scientific letters of the University of Zilina, 21(2), 114-118. 6. Olumide, A. O., Asuzu, M. C., & Kale, O. O. (2015). Effect of first aid education on first aid knowledge and skills of commercial drivers in South West Nigeria. Prehospital and disaster medicine, 30(6), 579-585. 7. Teshale, A. A., & Alemu, Z. A. (2017). Knowledge, Attitude and Practice of first aid and factors associated with practice among taxi drivers in Addis Ababa, Ethiopia. Ethiopian Journal of Health Development, 31(3), 200-207. 8. Awasthi, S., Pamei, G., Solanki, H. K., Kaur, A., & Bhatt, M. (2019). Knowledge, attitude, and practice of first aid among the commercial drivers in the Kumaon region of India. Journal of family medicine and primary care, 8(6), 1994.

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The Efficacy of Honey as a Treatment of Diabetic Foot Ulcer: A Systematic Review Hafidhatul Aisy, Faiza Chairunisa, Maimanah Zumaro Ummi Faiqoh Undergraduate Program, Faculty of Medicine, Universitas Airlangga, Surabaya Table 1. Characteristics of Studies (honey versus comparator)

1. STUDY BACKGROUND

Authors study design

The global diabetes prevalence has been increasing from year to year. In 2017, the prevalence of Diabetes Mellitus (DM) in global was 415 million people, increased to 463 million people in 2019, and was predicted rising to 10.2% (578 million) by 2030 [1,2]. Diabetes Mellitus occurred in all areas including urban, rural areas, high, and low-income countries. Until 2019, the prevalence of DM in Indonesia reached about 10.7 million people, as one of the top ten DM countries [2].

Koujalagi et al., 2020 [9] Randomized controlled trial

The use of honey for wound dressing has been extensively used to facilitate wound healing since ancient times [7]. Honey contains high sugar concentration which produces an osmotic effect and hyper-viscosity leading to bacterial dehydration as an antimicrobial effect, low pH, absorbs exudates, and keeps the wound edge together by resisting the stretching of collagen fibers [7-8]. Moreover, the topical application of honey does not lead to systemic absorption because sucrose is metabolized in the intestine. Besides the antibacterial effect, honey as a wound dressing can reduce edema and pH, promote dilation of small blood vessels and granulation tissue formation [8]. This study aimed to investigate the effectiveness of honey dressing as DFU wound healing process.

2. METHODOLOGY In this systematic review study, searching was performed on PubMed and Google Scholar. The keywords that are used are "honey", "dressing", and "diabetic foot ulcer". Limits were applied for journals that published in the last five years (20152020). Research that is not relevant to our purpose of study and outside of five years range will be excluded to avoid subjectivity and bias.

Records screened by abstract (n : 13)

Excluded full-text non availability (n : 27)

Excluded not relevant (n : 4)

3. RESULT Based on search resulted: nine clinical trials conducted on DFU patients. There were seven randomized controlled trials, one cohort, and one observational study reported which involved a total of 733 DFU patients. A total of 681 patients were included in randomized controlled clinical trials, 42 were included in a cohort study, and 10 were included in observational studies out of which almost 50% of patients were treated with topical honey as a wound dressing in DFU. Details of each study were given in Table 1.

References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20.

Cho, N., Shaw, J. E., Karuranga, S., Huang, Y., da Rocha Fernandes, J. D., Ohlrogge, A. W., & Malanda, B. (2018). IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes research and clinical practice, 138, 271-281. Saeedi, P., Petersohn, I., Salpea, P., Malanda, B., Karuranga, S., Unwin, N., Colagiuri, S., Guariguata, L., Motala, A.A., Ogurtsova, K. & Shaw, J. E. (2019). Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas. Diabetes research and clinical practice, 157, 107843. Pemayun, T. G. D., & Naibaho, R. M. (2017). Clinical profile and outcome of diabetic foot ulcer, a view from tertiary care hospital in Semarang, Indonesia. Diabetic foot & ankle, 8(1), 1312974. Bandyk, D. F. (2018, June). The diabetic foot: Pathophysiology, evaluation, and treatment. In Seminars in vascular surgery (Vol. 31, No. 2-4, pp. 43-48). WB Saunders. Armstrong, D. G., Boulton, A. J., & Bus, S. A. (2017). Diabetic foot ulcers and their recurrence. New England Journal of Medicine, 376(24), 2367-2375. Everett, E., & Mathioudakis, N. (2018). Update on management of diabetic foot ulcers. Annals of the New York Academy of Sciences, 1411(1), 153. Saikaly, S. K., & Khachemoune, A. (2017). Honey and wound healing: an update. American journal of clinical dermatology, 18(2), 237-251. Oryan, A., Alemzadeh, E., & Moshiri, A. (2019). Role of sugar-based compounds on cutaneous wound healing: what is the evidence?. Journal of wound care, 28(Sup3b), s13-s24. Koujalagi, R. S., Uppin, V. M., Shah, S., & Sharma, D. (2020). One year randomized controlled trial to compare the effectiveness of honey dressing versus povidone iodine dressing for diabetic foot ulcer at Dr. Prabhakar Kore Hospital and MRC, Belagavi. International Surgery Journal, 7(2), 506-513. Imran, M., Hussain, M. B., & Baig, M. (2015). A randomized, controlled clinical trial of honey-impregnated dressing for treating diabetic foot ulcer. J Coll Physicians Surg Pak, 25(10), 721-725. Agarwal, S., Bhardwaj, V., Singh, A., Khan, M. H., Goel, S., Bharat, M., & Krishna, J. (2015). A control clinical trial of honey-impregnated and povidone iodine dressings in the treatment of diabetic foot ulcers among northern Indian subjects. Indian Journal of Scientific Research, 6(2), 7-10. Othman, A. A., Balila, R. M., Mahdi, S. I., & Ahmed, M. E. (2016). Healing Potential of Propolis and Bee's Honey on Diabetic Foot Ulcers in Jabir Abu Eliz Diabetic Center-Khartoum. Sudan Medical Journal, 11(3687), 1-4. Tsang, K. K., Kwong, E. W. Y., To, T. S. S., Chung, J. W. Y., & Wong, T. K. S. (2017). A pilot randomized, controlled study of nanocrystalline silver, manuka honey, and conventional dressing in healing diabetic foot ulcer. Evidence-Based Complementary and Alternative Medicine, 2017. Al Saeed, M. (2019). Prospective randomized comparison of controlled release ionic silver hydrophilic dressings and medicated honey-impregnated dressings in treating neuropathic diabetic foot ulcer. Saudi Journal for Health Sciences, 8(1), 25. Haryanto, Ogai, K., Suriadi, Nakagami, G., Oe, M., Nakatani, T., Okuwa, M., Sanada, H., & Sugama, J. (2018). A prospective observational study using sea cucumber and honey as topical therapy for diabetic foot ulcers in Indonesia. Journal of Wellness and Health Care, 41(2), 41–56. Karimi, Z., Behnammoghadam, M., Rafiei, H., Abdi, N., Zoladl, M., Talebianpoor, M. S., Arya, A., & Khastavaneh, M. (2019). Impact of olive oil and honey on healing of diabetic foot: A randomized controlled trial. Clinical, Cosmetic and Investigational Dermatology, 12, 347–354. https://doi.org/10.2147/CCID.S198577 Sukarno, A., Hidayah, N., & Musdalifah, M. (2019). THE EFFECTIVENESS OF INDONESIAN HONEY ON DIABETIC FOOT ULCERS HEALING PROCESS: OBSERVATIONAL CASE STUDY. International Journal of Nursing and Health Services (IJNHS), 2(2), 20-28. Martinotti, S., & Ranzato, E. (2018). Honey, wound repair and regenerative medicine. Journal of functional biomaterials, 9(2), 34. da Silva, P. M., Gauche, C., Gonzaga, L. V., Costa, A. C. O., & Fett, R. (2016). Honey: Chemical composition, stability and authenticity. Food Chemistry, 196, 309-323. Singh, S., Young, A., & McNaught, C. E. (2017). The physiology of wound healing. Surgery (Oxford), 35(9), 473-477.

The difference in the wound size between two groups at 1st day, 3rd day, at 5th day, 7th day, 10th day follow up period with baseline value were statistically not significant (p > 0.05). But at the 15th day follow up period of unprocessed honey dressing was statistically significant (p < 0.05).

Honey dressing shows more favorable results in the reduction of wound size in diabetic foot ulcers as compared with povidone iodine dressing.

Normal saline dressing. 120 days.

Sample size: 36 Inclusion criteria: Non-insulin dependent diabetes mellitus patient (NIDDM) Wagner's grade 2 Age 35—65 years Transcutaneous oxygen tension >30 mmHg Serum albumin level of >35 g/dl Exclusion criteria: Multiple medical co-morbidity Steroid therapy Neutrophil count less than 2000/mm

Povidone iodine 10% dressing. Not stated (until healing occurred).

Sample size: 86 Inclusion criteria: Wagner's grade 1—2 Exclusion criteria: Limb ischemia manifested as absent pedal pulses or Doppler Ankle/Brachial Index <0.9

Tap water dressing. Not stated (dressing continued until wounds healed or ended by amputation).

Mean wound healing time Honey: 11.55 weeks Control: 15 weeks p = 0.02 Minor toe amputation Honey: 1 Control: 6 p = 0.039 Major limb amputation Honey: 0 Control: 3 p = 0.24

Propolis and honey mixture dressing lead to early healing and reduction of the rate of minor toe amputation in DFU compared to tap water dressing.

Sample size: 31 Inclusion criteria: Type 2 DM patients, Age 40 Foot ulcer at or below malleolar region Wound size diameter 1 cm No foreseeable surgery within the 12-week study period through clinician assessment Exclusion criteria: HbA1c level 10% Ankle-brachial index 0.4 Ulcer with bone or joint exposed

NanocrystalIne silver (nAg), and conventional dressing. 12 weeks.

Cumulative Healing Incidence nAg: 81,8% MH: 50% Paraffin tulle: 40% p = 0.267 The ulcer size reduction nAg: 97.45% MH: 86.24% Paraffin tulle: 76.91% p < 0.0005 The estimated marginal mean number of microorganisms nAg: 0.86 MH: 1.17 Paraffin tulle: 1.36 p = 0.486 No significant adverse event presence.

Nanocrystalline silver alginate was potentially superior to Manuka honey (MH) and conventional dressing (paraffin tulle) in healing DFU in terms of ulcer size reduction rate.

Mohammed Al Saeed 2019 [14] Prospective, doubleblind, Randomized comparative clinical trial

Sample size: 71 Inclusion criteria: Neuropathic DFU Wagner's grade 2—4 Exclusion criteria: Age <18 Ischemic or neuroischemic ulcers Osteomyelitis Liver or kidney failure Receiving chemotherapy, radiotherapy, or immunosuppressant drugs or participating in another clinical trial

Ionic silver hydrophilic dressing. Not stated (until healing occurred).

There is no significant difference demographics, ulcer size, duration of data, mean time to eradicate infection, and mean complete ulcer healing respectively.

The study verified the effectiveness of Manuka honeyimpregnated dressings and the controlled release of silver hydrophilic dressings in controlling wound infection and promoting the complete healing of neuropathic ulcers.

Haryanto et al., 2018 [15] Prospective cohort design

Sample size: 42 Inclusion criteria: DFU patients with new ulcers

Sea cucumber. 12 weeks.

There were significant differences in the TNF-αlevel between weeks 0 vs. 8, 0 vs. 10, and 0 vs. 12 in the sea cucumber group (p = 0.005, p = 0.006, and p = 0.010, respectively; Steel post hoc test).

Agarwal et al., 2015 [11] Randomized controlled clinical trial

Tsang et al., 2017 [13] Prospective pilot randomized controlled open-label clinical trial

The mean percentage reduction of wound size in both groups of day 1,3 were almost the same and statistically not significant, while at 10th and 15th day follow up period with baseline value in honey dressing were statistically significant (p < 0.05). No adverse effect data available.

Mean wound healing time Honey: 18.00 (6—120) days Control: 29.00 (7-120) days P < 0.001 Number of completely, incompletely healed and deteriorated Honey: 136 (75.97%), 32 (17.87%), and 11 (6.16%). Control: 97 (57.39%), 53 (31.36%), and 19 (11.25). p = 0.001 No serious side effect was observed (three patients of the honey group complained of mild itching at the start of treatment and subsided after 48 hours).

Studies included (n: 9) Figure 1. Diagram Flow of Literature Search Strategy

Conclusion

Sample size: 348 Inclusion criteria: Age 18 Wagner's grade 1—2 Exclusion criteria: Wagner's grade 3—5 Ankle Brachial Pressure Index (ABPI) <0.7 Venous ulcers or malignant ulcers HbA1c >7% >1 ulcers Hb <10g/dl Local sign of infection (presence of pus, initial culture positive)

Imran et al., 2015 [10] Randomized controlled clinical trial

Total records (n : 340) Records screened by title and duplicate (n : 40)

Outcome measured

Povidone iodine dressing. 2 weeks.

Othman et. al., 2016 [12] Randomized controlled clinical trial

Pubmed (n : 12)

Google scholar (n : 328)

Comparator and follow up duration

Sample size: 64 Inclusion criteria: Diabetic patients taking insulin or oral hyperglycemic Suffering DFU which are not healed throughout >6 weeks and requiring for debridement, only clinically clean wounds without signs of inflammation, purulent discharge Wagner's grade 1—2 Exclusion criteria: Ischemic limb Osteomyelitis Cellulitis Diabetic ketoacidosis Exposed bone Hb level <10 gm% Honey or povidone iodine allergy

Diabetic foot ulcer (DFU) is one of the major DM complications. In the previous study found that the number of diabetic foot ulcer was 16.2% of Indonesian diabetes inpatient with 10.7% mortality rate [3]. The pathophysiology of the diabetic foot ulcer is a triad of neuropathy, trauma with secondary infection, and arterial occlusive disease [4]. When an invasive foot infection develops, it can cause sepsis and amputation [4]. Commonly, complications of diabetes that affect the lower extremities turn into a complicated and costly problem [5]. A therapeutic technique that improves wound healing on DFU is important for amputation prevention which reduces the need for expensive surgical procedures. The standard practices in DFU management include surgical debridement, dressings to facilitate a moist wound environment and exudate control, wound off-loading, vascular reconstruction if necessary, eradicate to infection and glycemic control [6]. Nowadays, modern dressing occurs to be applied in DFU wound care such as alginate, hydrogels, and silver hydrocolloid dressing [6]. However, there are still many people in developing countries practicing DFU methods using traditional ingredients; such as honey, olive oil, and sea cucumber [15-16].

Sample size and patient selection

Mean wound healing time Honey: 14.2 days (range 6—25 days) Control: 15.5 days (range 9—37 days) p > 0.05 All patients in the honey group experienced less pain during dressing. Edema and foul-smelling discharges resolved earlier as compared to the control dressing group. No adverse effect data available.

between two groups in diabetes, clinical laboratory hospital length of stay (LOS), time with p values >0.05

Although the meantime for complete ulcer healing was insignificant, the Manuka honey (MH) group took a shorter time than the silver hydrophilic dressing group. No deaths in either group during the follow-up period.

There was no significant difference in the change in the pattern of biofilm-like staining from positive to negative between the groups (p = 0.55, Fisher s exact test).

Honey dressing was more effectively reduced the duration of wound healing in DFU patients, in comparison with normal saline dressing.

Honeyimpregnated dressing can be a safe alternative dressing for Wagner's type 2 DFU.

These results indicated that sea cucumber and honey could be used as an alternative wound dressing for DFU.

There was no significant difference in wound healing between the sea cucumber and honey groups (p = 0.66; Kaplan-Meier analysis, logrank test). Local skin redness was seen in 2 patients of the honey group and one patient in the sea cucumber group, but those disappeared by itself. Karimi et al., 2019 [16] Randomized controlled clinical trial

Sample size: 45 Inclusion Criteria: DFU patients with new ulcers Wagner s grade 1-2 Age 20–70 years Having a wound in the feet (toes, sole, and heel) for more than 1 month No history of alcohol intake, cigarette smoking, or drug abuse

Gauzes with olive oil (4 mL) and usual dressing. 1 month.

Mean wound grade Control: 66.3 Honey: 87.3 p < 0.0001 Mean score of tissue around the wound Control: 64.5 Honey: 90.5 p = 0.02

350

Author s study design

Comparator and follow up duration

Sample size and patient selection

No history of taking medications that interfere with wound healing, such as immunosuppressants or corticosteroids No history of comorbidities that may interfere with wound healing, such as cancer, vasculitis, or failure of the kidney, liver, or heart. Exclusion criteria: Olive oil or honey allergy Having wounds or active infection needing antibiotic therapy, or gangrene needing amputation Sukarno et al., 2019 [17] Observa tional case study

Sample size: 10 Inclusion criteria: Type 2 diabetes with DFU Obtained primary honey dressing modern primary dressing Received wound care regularly Voluntarily enrolled Exclusion criteria: Honey allergy Planned for amputation

Outcome measured

Conclusion

Mean score of wound drainage Control: 74.0 Honey: 97.0 p = 0.02 Mean score of wound healing Control: 268.0 Honey: 371.5 p = 0.002

Modern primary dressing (silvercontaining dressing, cadexomer, and antimicrobial dressing). 2 weeks.

The average of wound healing (pre-test score) Kapok honey: 34 (SD= 7.90) Control: 43.8 (SD= 5.26) The average of wound healing (post-test score) Kapok honey: 28.2 (SD= 7.59) Control: 39.2 (SD= 4.65) p = 0.025

Indonesian honey (honey of pure nectar of Kapok flowers) is beneficial on DFU healing process.

Honey primary dressing showed significantly associated with decreasing wound size (p = 0.043), improving necrotic tissue type (p = 0.041), decreasing necrotic tissue amount (p = 0.042), increasing granulation tissue (p = 0.038), and increasing epithelization (p = 0.042). Although modern primary dressing was only significant in the improvement of necrotic tissue type (p = 0.046) and increasing granulation tissue (p = 0.042).

4. DISCUSSION The importance of wound dressing in DFU is to create a moist environment that promotes granulation, autolytic processes, angiogenesis and more rapid migration of epidermal cells across the wound base [6]. Out of nine clinical trials, six concluded that honey dressing was better than povidone-iodine, normal saline, tap water, and sterile gauze dressing which one of those studies using propolis and honey mixture [9-12,16,17]. Three trials concluded that honey dressing could be a safe alternative dressing as compared with nanocrystalline silver, paraffin tulle, ionic silver hydrophilic, and sea cucumber extract gel dressing [13-15]. There was no serious adverse event reported including mild itching in three patients and local skin redness in two patients [10,15]. Those symptoms will be disappeared by itself without treatment. Honey is a natural food, which primarily composed of sugar (about 76%), water (less than 20%) and other substances such as proteins, organic acids, vitamins, minerals, pigments, phenolic compounds, and a large variety of volatile compounds [18-19]. The high sugars concentration present in honey is responsible for properties such as osmotic and viscosity effect leading to absorbs exudates and bacterial dehydration as antibacterial activity [7-8]. Moreover, honey inhibits microbial growth by hydrogen peroxide which is produced by enzymatic activity [18]. Flavonoids as a phenolic compound of honey also inhibit microbial growth through non-peroxide activities [18]. Tsang et al mentioned that the Manuka honey group showed a significant decreasing number of microorganisms over the 12weeks study period [13]. Additionally, the honey group has better results in decreasing wound edema, foul-smelling, and less pain during dressing as compared with povidone-iodine dressing mentioned by Agarwal et al [11]. Wound healing comprises four distinct phases of hemostasis, inflammation, proliferation, and tissue remodeling [20]. Sukarno et al mentioned that honey impregnated dressing showed significantly improving necrotic tissue type (p = 0.041), decreasing necrotic tissue amount (p = 0.042), increasing granulation tissue (p = 0.038), and increasing epithelization (p = 0.042) as proliferation phase in wound healing [17]. There were two studies reported that the honey dressing group gave a better result in the mean duration of wound healing than normal saline and tap water dressing [10,12]. While honey also showed better results in decreasing of wound size as compared with povidone-iodine and moderns dressing (silver-containing dressing, cadexomer, and antimicrobial dressing) [9,17]. Currently, there is no standardized method for applying honey dressing. Even in this review, there were different methods of honey application. Six trials were using pure undiluted honey [9-11,15-17]. There were sterilized Beri (Ziziphus jujuba) honey, commercially available honey, kapok flower honey, and others were not explained what specific type of honey used. While the other two were using standardized honey medication (TheraHoney Sheet, Medihoney gel sheet) [13-14] and one was using propolis and honey mixture [12]. Different ingredients of honey, which help with wound healing were not discussed in any of the studies. There was no uniformity in efficacy parameters, type or grade of ulcer, type or composition of honey included or follow up period. Hence the result cannot be combined. Since none of the studies reported any serious adverse events. So we conclude that honey is quite effective, safe, and can be used as an alternative wound dressings on diabetic foot ulcer treatment.

5. CONCLUSION Honey is as effective as olive oil in the treatment of DFU.

This review concludes that honey is quite effective, safe, and can be used as an alternative wound dressing on diabetic foot ulcer (DFU) treatment. Because of honey has several benefits as dressing such as accelerate wound healing time, bacterial clearance time, reducing wound size, reducing foulsmelling, reducing wound edema, and less pain during application. Therefore, we recommend more well-designed and large-scale studies with uniformity in inclusion criteria, efficacy parameters, and follow up period to obtain better evidence.

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S T a

e a c Re e a cB a I

T e P e a e ce f B a D de Pa e a T e Lead g Ca e f P c a D de

Maria Gabrielle Vanessa , Caroline Wibo o , Jonathan J niard An rantha , Johan Wibo o Fac lt of Medicine, Uni ersit of Pelita Harapan, Tangerang, Banten, ndonesia

Bipolar disorders are described b the American Ps chiatric Association s Diagnostic and Statistical Man al of Mental Disorders (DSM-5) as a gro p of brain disorders that ca se e treme fl ct ation in a person s mood, energ , and abilit to f nction . A large cross-sectional s r e of 11 co ntries fo nd the o erall lifetime pre alence of bipolar spectr m disorders as 2.4%, ith a pre alence of 0.6% for bipolar t pe and 0.4% for bipolar t pe . St dies cond cted b Robert an Reek m et al sho s that there is a strong and gro ing bod of e idence to s pport the h pothesis that tra matic brain inj r (TB ) freq entl ca ses some, b t not all, ps chiatric disorders. n this s stematic re ie , e anted to e al ate the pre alence of bipolar disorder in the tra matic brain patient as the leading ca se of ps chiatric disorder.

B sing the P CO method itho t appl ing the inter ention, e ha e acq ired 5 cross-sectional st dies that ill be anal ed f rther. We ill be sing st dies cond cted b Kir thika, Drange, et al., Walker et al., Sla ghter et al., and Bogner et al.. We fo nd mi ed res lts bet een these st dies as 3 o t of 5 st dies stated that there as no association bet een tra matic brain inj r and bipolar disorder pre alence, hile the other 2 stated there as an association bet een these t o.

n o r s stematic re ie , e collected o r data from online jo rnals hich ere taken from P bmed, Science Direct, Google Scholar and also Ta lor and Francis Online Jo rnal. A s stematic anal sis approach as sed in this st d , for e ample, the P CO method.

n concl sion, from 5 st dies that e anal ed, e fo nd that the st dies b Kir thika, Drange et al., and Walker et al. stated that there as no association bet een bipolar disorder in TB . Other ise, in a st d b Sla ghter et al. and Bogner et al. stated that there as an association bet een bipolar disorder in TB . So, from all the st dies that e ha e anal ed, e can concl de that tra matic brain inj r does not ha e a ca sati e effect on bipolar disorder as a comprehensi e biological factor.

1. American Ps chiatric Association. (2013). Diagnostic and Statistical Man al of Mental Disorders (5th ed.). Arlington, VA. Bipolar Disorder. (2020). Retrie ed 7 March 2020, from https:// .nimh.nih.go /health/topics/bipolar-disorder/inde .shtml 2. N MH .ncbi.nlm.nih.go /pmc/articles/PMC6116765/ 3. Ro land, T., & Mar aha, S. (2018). Epidemiolog and risk factors for bipolar disorder. Retrie ed 7 March 2020, from https:// 4.Tra matic Brain nj r Ca ses, S mptoms and Treatments. (2020). Retrie ed 7 March 2020, from https:// .aans.org/en/Patients/Ne ros rgical-Conditions-and-Treatments/Tra matic-Brain- nj r 5. Van Reek m, R., Cohen, T., & Wong, J. (2015). Can Tra matic Brain nj r Ca se Ps chiatric Disorders? The Jo rnal of Ne rops chiatr and Clinical Ne rosciences. Retrie ed 7 March 2020, from https://ne ro.ps chiatr online.org/doi/f ll/10.1176/jnp.12.3.316 6.Kir thika, A. (2019). Ps chiatric Morbidit in Patients ith Tra matic Brain nj r - EPrints@Tamil Nad Dr MGR Medical Uni ersit . Retrie ed 8 March 2020, from http://repositor tnmgrm .ac.in/10970/ 7. Drange, O., Vaaler, A., Morken, G., Andreassen, O., Malt, U., & Finseth, P. (2018). Clinical characteristics of patients ith bipolar disorder and premorbid tra matic brain inj r : a cross-sectional st d . Retrie ed 8 March 2020, from https:// .ncbi.nlm.nih.go /p bmed/30198055 8. Walker, W., Franke, L., McDonald, S., Sima, A., & Ke ser-Marc s, L. (2015). Pre alence of mental health conditions after militar blast e pos re, their co-occ rrence, and their relation to mild tra matic brain inj r . Retrie ed 8 March 2020, from https:// .tandfonline.com/doi/abs/10.3109/02699052.2015.1075151 9.Sla ghter, B., Fann, J., & Ehde, D. (2003). Tra matic brain inj r in a co nt jail pop lation: pre alence, ne rops chological f nctioning and ps chiatric disorders. Retrie ed 8 March 2020, from https:// .tandfonline.com/doi/abs/10.1080/0269905031000088649 1 0 .B o g n e r , J . , C o r r i g a n , J . , Y i , H . , S i n g i c h e t t i , B . , M a n c h e s t e r , K . , H a n g , L . , & Y a n g , J . ( 2 0 1 9 ) . L i f e t i m e H i s t o r o f T r a m a t i c B r a i n n j r a n d B e h a i o r a l H e a l t h P r o b l e m s i n a P o p l a t i o n - B a s e d S a m p l e . P bMed - NCB . Retrie ed 9 March 2020, from https:// .ncbi.nlm.nih.go /p bmed/31033748

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Diagnos ic Performance of Glial Fibrillar Acidic Pro ein as A Biomarker for Mild Tra ma ic Brain Inj r Among Children: A S s ema ic Re ie and Me a-Anal sis of Cohor S dies Muhammad Kevin Ardian, Gideon Hot Partogi Sinaga, Rania Rifah Taufiq, Ugiadam Farhan Firmansyah Undergraduate Program, Faculty of Medicine, Universitas Indonesia

Introduction

Results

Almost one billion people around the world have been injured. Among those, 69 million people are affected by traumatic brain injury TBI World Health Organization, 2006 . TBI is also one of the most common head injuries in children, occurring in more than 837,000 children in the US alone. In children, TBI is the leading cause of cognitive impairment of death, especially in children, which can lead to difficulties in memory and coordination. Children with TBI, especially mild TBI, who may not seek medical attention after injury, may be lethal and problematic in the future Frieden et al., 2015 .

Table 1. Cha ac e i ic of S

die

It is generally thought that 75 – 90 of TBI is classified as mild TBI mTBI or concussion. A TBI is caused by a bump, blow, or head jolt that disrupts the normal function of the brain. The severity of the TBI is usually indicated by the Glasgow Coma Scale GCS World Health Organization, 2006 . However, the initial GCS scores may be incorrect and the classification of TBI as mild or moderate may change based on the CT scan and the presence of factors that change mental status, such as intoxication, medication and other injuries Papa et al., 2016 . Cranial computed tomography CT scan is used as a standard gold diagnostic tool for detecting mTBI. However, most patients may have negative or undetected CT scans until multiple scans in children increase the expensive cost and exposure of CT radiation, which may lead to cancer in the future Papa et al., 2015 . In addition, the blood proteome of children differs dramatically from that of adults, and limited research suggests that children may recover from concussion at a slower rate James et al., 2019 . As a result, Glial Fibrillary Acid Protein GFAP as an astrocyte protein that can only be raised in the blood in the event of mechanical head injury e.g. TBI could replace the CT scan of the head Brunkhorst et al., 2010 . Additionally, GFAP outperforms other brain biomarkers, such as S100B, and has the potential to become a better alternative in the diagnosis of mTBI in children Papa et al., 2016 .

Methods

Fig

e 3. F nnel Plo

Fig

e 4. Fo e Plo Compa ing Mean Diffe ence of GFAP Le el in Pedia ic Pa ien con ol g o p

i h mTB and

Discussion Se

e e

g f ca ce

From the meta analysis above, we could see that our studies consist of considerable heterogenous studies but showed significant difference of GFAP serum level between case and control group. Studies included in our meta analysis demonstrated tau square test was 0.01, chi square test was 309.23, degrees of freedom was 3, and I2 value was 99 implying considerable heterogeneity studies p 0.00001 . Beside it, test for overall effect, the Z value of 4.89 revealed significant difference between intervention and control group p 0.00001 . Hence, the serum GFAP level in children with mTBI was significantly higher compared with control.

Mea

e e

f GFAP Se

Le e

Two of four studies collected venous blood samples within 24 hours of injury, except for Papa, 2016 Papa et al., 2015 within 6 hours of injury. Blood samples from each study were collected for 2.5 5 mL and centrifuged at 3000 RPM for 30 minutes at room temperature. Serum samples were then pipetted and stored within 70 to 80 degrees until analyzed with Enzyme linked Immunosorbent ELISA GFAP detection kits, except except Mondello et al., 2016 which used Electrochemiluminscent Immunoassay ECL IA . Papa et al., 2015, 2016 reported that the serum concentration of GFAP was detectable within 1 hour of injury, peaked at 20 hours after injury and steadily decreased over 72 hours after injury.

Fig

e 1. Con ep

al F ame o k

GFAP a A Sc ee

A total of 4 cohort studies were reviewed and analyzed, with a total sample size of 542 patients, 381 patients were grouped with positive mild traumatic brain injury patients and 161 patients were included as control patients. In all studies, areas under the Receiver Operating Characteristics ROC Curve AUC were developed to explore the ability of GFAP to detect the presence of mild TBI and to detect intracranial lesions on CT scans Papa et al., 2015, 2016 . The AUC estimate of 1.0 indicates a perfect diagnostic test, the AUC of 0.8–0.9 is considered to be very good, the AUC of 0.7–0.8 is considered to be adequate and the AUC 0.6 is considered to be poor or non discriminatory Papa et al., 2016 . Based on the studies, all AUC values range from 0.8 0.89 which is considered to be good. Overall, GFAP had a higher AUC for detecting mTBI on CT scan than other blood biomarkers and was best suited to discriminating CT negative and CT positive patients Mondello et al., 2016 Papa et al., 2016 . We found that the GFAP sensitivity is relatively high range 89 100 which is excellent for screening tools. However, the specificity is rather moderate range 36 65 which is poor as a diagnostic tool. Based on the AUC and GFAP sensitivity, the GFAP cut off level ranges from 0.43 to 0.68 which can be used as a threshold for the detection of positive mTBI.

S d S e g ha dL

This study is the first systematic review and meta analysis that sees the possibility of GFAP becoming a diagnostic tool for detecting mTBI in children. Early measurement of GFAP can contribute to more accurate screening and triage of mTBI patients and to a reduction in the number of unnecessary child CT scans, which reduces the costly cost and risk ofcancer. Our findings, which were heterogeneous, could be due to the lack of a specific standardized control group, the different diagnostic methods used i.e. ELISA and ECL IA and the different timing of blood withdrawals.

Conclusion

Fig

e 2. Sea ch Me hod

In conclusion, the serum level of GFAP was significantly higher in children with mTBI and exceeded other blood biomarkers. Based on high sensitivity, GFAP can be an excellent and promising screening tool to reduce unnecessary CT scans. However, further research is needed to discover the potential for a combination of GFAP and other biomarkers to achieve better results.

References: Brunkhorst, R., et al. 2010 . Astroglial proteins as diagnostic markers of acute intracerebral hemorrhage pathophysiological background and clinical findings. Translational Stroke Research, 1 4 , 246–251. Frieden TR, et al. 2015 . Traumatic brain injury in the United States: epidemiology and rehabilitation. In CDC Vol. 116, Issue 1 . James, S. L., et al. 2019 . Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. The Lancet Neurology, 18 1 , 56–87.

Mondello, S., et al. 2016 . Serum Concentrations of Ubiquitin C Terminal Hydrolase L1 and Glial Fibrillary Acidic Protein after Pediatric Traumatic Brain Injury. Scientific Reports, 6 June , 1–8. Papa, L., et al. 2016 . In children and youth with mild and moderate traumatic brain injury, glial fibrillary acidic protein out performs s100β in detecting traumatic intracranial lesions on computed tomography. In Journal of Neurotrauma Vol. 33, Issue 1 .

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Papa, L., et al. 2015 . Performance of Glial Fibrillary Acidic Protein in Detecting Traumatic Intracranial Lesions on Computed Tomography in Children and Youth with Mild Head Trauma. Academic Emergency Medicine, 22 11 , 1274–1282. World Health Organization. 2006 . Neurological disorders public health challenges. In World Health Organization Press Vol. 54, Issue 7 .

356

Bioresorbable Polymer-based and Allograft Scaffold Augmentation in Massive Rotator Cuff Tears: A Systematic Review of Clinical Trials Ni i a Labi Na ha ae Ta e S e e Mi e i AMSA U i e i a Sa a a gi

Je e

R i g

BACKGROUND

RESULTS AND DISCUSSION

Sickness or injury can prompt harm and degeneration of tissues in the human body, which

Table 1. Characteristics of studies

Study

requires treatment to encourage their fix or recovery. Rotator cuff is one of the tendons that is often torn, tear rates increases with age in adults. Treatment that replacing or strengthening the

Synthetic

tendons and ligaments is a challenge in surgery across the world. Tissue engineering

Nada et al., 2010

immune reactions (Smith et al., 2017). Many grafts has provided effective therapeutic support,

Technique

LARS Ligament

Sample size/follow-up

Open bridging and augmentation

17/36 months

Mini-open bridging

52/3 years

(Polyethylene Terephthalate)

combines few characteristics. Scaffold should provides bioactive cues for cellular proliferation, adequate mechanical properties and great biocompatibility to prevent toxic degradation or

Scaffold (materials)

Ciampi et al., 2014

Polypropylene patch

Ranebo et al., 2018 Teflon (Polytetrafluoroethylene) Mini-open bridging

12/ 18 years

but still maintains few limitations. Recently, biological scaffold from human or animal tissue

Allograft

and synthetic scaffolds has been produced. Synthetic scaffolds and allografts have shown

Gupta et al, 2012

Mini-open bridging

24/29-40 months

lower retear rates and better functional outcome than xenografts (Ramakhrisna et al., 2019).

Agrawal et al, 2012 Allopatch HD (Human dermis)

Arthroscopic augmentation

14/12-24 months

However, substantial clinical works is needed to allow definitive conclusion on the use of

Pandey et al., 2017 GraftJacket (Human dermis)

Mini-open bridging

13/ 2 years

scaffolds in tendon augmentation.

Sharma et al., 2018 GraftJacket (Human dermis)

Mini-open bridging

22/ 18-24 months

GraftJacket (Human dermis)

Table 2. Outcome of studies

Study

OBJECTIVES To investigate the utility of allograft and synthetic scaffolds in biomaterials field for massive rotator cuff tear augmentation.

CRITERIA

Keywords: rotator cuff injury, massive rotator cuff tear, tendon

Systematic Review Collecting studies from PubMed,

Inclusion and exclusion criteria screening

- Xenograft scaffolds

USG: 17% retear rate, mean OSS increased (from 17,5 to 44,8)

<0,01

No complication

<0,01

Nine cuff tear arthropathy

MRI: 5 partially intact, the rest is fully intact, mean ASES

<0,0005 No comp;ications

improved (66,6 to 88,7) Agrawal et al, 2012 MRI: 2 partial tears, 12 structurally intact, mean

<0,01

No comp;ications

<0,01

No comp;ications

Constant-Murley score increased (from 49,7 to 81) Pandey et al., 2017 MRI: Retear four patients, mean Constant-Murley score increased (from 41,2 to 83,9), mean OSS increased (from 14,9 to 43,9) Sharma et al., 2018 MRI:-, mean OSS improved (from 22 to 45,5)

<0,005 One persistent pain ended up with a total

Total of seven studies included

shoulder replacement

Figure 1. Conceptual Framework

IDENTIFICATION

Gupta et al, 2012

ScienceDirect, Scopus and Springer

on animal

- Synthetic, biosynthetic or - Tendinopathy/other disorder with rotator cuff tendon biological allograft

Note: ASES, American Shoulder and Elbow Surgeon; OSS, Ocford Shoulder Score

Records identified through database searching (n= 536) Pubmed (n=74)

A total of seven clinical studies were reviewed, with total sample size are 154 subjects. A study by Nada

ScienceDirect (n=167)

et al (2010) showed promising outcomes at a follow-up of three years RC repair using polyethylene

Scopus (n=248)

terephthalate graft, Every patients had improvement (p<0,001), although MRI showed 2 uncomplete

Springer (n=47) Document excluded on the basis of duplication (n=11)

healings. Ciampi et al (2014) study had 17% retear rate at three-years follow-up with polypropylene patch, mean OSS increased from 17,5 to 44,8 in 52 subjects. Ranebo et al (2018) examined 12 patients (18 years follow-up) following RC repair with polytetrafluoroethylene, there is increasing of mean

Records screened based on title and abstract (n=525)

INCLUDED ELIGIBILITY

SCREENING

<0,001 No complication

(from 25,5 to 44,5)

tissue engineering, scaffold and synthetic scaffold

and experimental studies

scaffolds

Complications

Allograft

CRITERIA

- Massive rotator cuff tear

p-value

mean Constant-Murley score increased (from 46 to 74,8)

- Expert opinion, review paper

beings

MRI: Intact tendon in 15/17 patients, mean OSS improved

Ranebo et al., 2018 MRI: 9/12 arthropathy patients, three needed arthroplasty,

EXCLUSION

- Clinical studies in human

Nada et al., 2010

Ciampi et al., 2014

METHODS INCLUSION

Outcome

Synthetic

Document excluded on the basis of inclusion and exclusion (n=513)

Constant-Murley score at minimum follow up, nine out of 12 developed tear arthropathy and three needed arthroplasty. In a study by Gupta et al (2012) showed no major complications at an average three years follow-up with human dermis allograft (p<0,0005), besides that, MRI revealed 5 partially intact tendons. Meanwhile, at a minimum follow up of 18 months, Constant-Murley score increased in

Full text articles assessed for eligibility (n=12) Document excluded on the

Agrawal et al (2012) study, MRI showed 2 partial tears from 14 subjects. Similar results with no

basis of lack essential data

complications were replicated in a study by Pandey et al (2017), Constant-Murley score and OSS

(n=5)

improved from preoperative score after bridged repair with human dermis allograft. Sharma et al (2018)

Studies included in qualitative synthesis (n=7) Figure 2. Search Method

References Agrawal, V. (2012). Healing rates for challenging rotator cuff tears utilizing an acellular human dermal reinforcement graft. International Journal of Shoulder Surgery, 6(2), 36. doi: 10.4103/0973-6042.96992 Ciampi, P., Scotti, C., Nonis, A., Vitali, M., Serio, C. D., Peretti, G. M., & Fraschini, G. (2014). The Benefit of Synthetic Versus Biological Patch Augmentation in the Repair of Posterosuperior Massive Rotator Cuff Tears. The American Journal of Sports

Medicine, 42(5), 1169–1175. doi: 10.1177/0363546514525592

assessed human dermis allograft to bridge a massive cuff tear in 20 patients, at a 18 to 24 months follow up, OSS improved (p<0,005), there is no radiological evaluation of the repair integrity.

CONCLUSION

Gupta, A. K., Hug, K., Berkoff, D. J., Boggess, B. R., Gavigan, M., Malley, P. C., & Toth, A. P. (2012). Dermal Tissue Allograft for the Repair of Massive Irreparable Rotator Cuff Tears. The American Journal of Sports Medicine, 40(1), 141–147. doi: 10.1177/0363546511422795 Nada, A. N., Debnath, U. K., Robinson, D. A., & Jordan, C. (2010). Treatment of massive rotator-cuff tears with a polyester ligament (Dacron) augmentation. The Journal of Bone and Joint Surgery. British Volume, 92-B(10), 1397–1402. doi:

Massive rotator cuff repair with polymer-based synthetic scaffolds and human dermal allograft related

10.1302/0301-620x.92b10.24299 Pandey, R., Tafazal, S., Shyamsundar, S., Modi, A., & Singh, H. P. (2016). Outcome of partial repair of massive rotator cuff tears with and without human tissue allograft bridging repair. Shoulder & Elbow, 9(1), 23–30. Ramakrishna, H., Li, T., He, T., Temple, J., King, M. W., & Spagnoli, A. (2019). Tissue engineering a tendon-bone junction with biodegradable braided scaffolds. Biomaterials research, 23(1), 11. Ranebo, M. C., Hallgren, H. C. B., Norlin, R., & Adolfsson, L. E. (2018). Long-term clinical and radiographic outcome of rotator cuff repair with a synthetic interposition graft: a consecutive case series with 17 to 20 years of follow-up. Journal of Shoulder

and Elbow Surgery, 27(9), 1622–1628. doi: 10.1016/j.jse.2018.03.011 Sharma, N., Refaiy, A. E., & Sibly, T. (2018). Short-term results of rotator cuff repair using GraftJacket as an interpositional tissue-matched thickness graft. Journal of Orthopaedics, 15(2), 732–735. Smith, R. D., Zargar, N., Brown, C. P., Nagra, N. S., Dakin, S. G., Snelling, S. J., ... & Carr, A. (2017). Characterizing the macro and micro mechanical properties of scaffolds for rotator cuff repair. Journal of shoulder and elbow surgery, 26(11), 2038-2046.

with acceptable practical and basic results, low retear rates and generally did not exhibit much inflammatory reactions. Prospectively, the fuse of strategies in tissue engineering and nanotechnology

could improve the mechanical properties and biocompatibility of the scaffolds.

357

358

Clover Flower Honey and Binahong (Anredera codifolia) Positive Effects to Wound Healing Parameters Jerrick Lo Abednego (A-Team), Risha Diranti Ananda Putri, Tjong Michella Florencia, Kasandra Indriani Veronica Methodology

Introduction Our skin is the key to our survival, sensing the environment, maintaining physicochemical and thermal homeostasis, acting as a reservoir of essential nutrients, providing passive and active defense, and responding to trauma and injury. People commonly use herbal medication to heal various diseases because the cost is relatively low and it is easily accessible.

For a study with the keyword "topical clover flower" obtained 100 journals from researchgate.net, then sorted based on years of published, from 2015-2020, received 49 journals and re-sorted with the test subject rats received 1 journals.

Clover flower honey is a herbal therapy used as an alternative wound treatment. Clover flower honey also contains flavonoid and phenolic acid (especially P-hydroxybenzoic) which is higher than other honey. Flavonoid and phenolic acid are some chemical materials which have such benefits as anti-inflammation and antioxidant. Binahong or Madeira vine (Anredera cordifolia (Ten.) Steenis) is a herbal plant that is most frequently used to cure various kinds of diseases in a number of Asian countries, such as Vietnam, Taiwan, China, and Korea. Its leaves have such benefits as anti-inflammation, antioxidant, antibacterial, and analgesics.(4,5)

For Study with the keyword “Anredera cordifolia obtained 10 journals from PubMed.gov, then sorted based on year published, from 2015-2020, received 5 journals and re-sorted with the test subject rats received 1 journals

Results and Discussion

Clover Flower Honey Result

Anredera Cordifolia

We can see from table 1, 2, and 3 that the cure rate for the wound (it depends on the degree of reepithelialization, fibroblast density, and collagen density) will significantly increase if we also increase the amount of extract honey from the clover flower. From the three concentrations of honey, only 100% honey concentration was significantly different compared with 1% feracrylum at the degree of reepithelialization, fibroblast density, and collagen density (p = 0.017, p = 0.014, p = 0.014). This shows that 100% honey was better than 1% feracrylum.

Anredera cordifolia Result · G0: Rats with skin burns, treated with · G1: Rats with skin burns, treated with · G2: Rats with skin burns, treated with · G3: Rats with skin burns, treated with Table 1

silver sulfadiazine extract ointment 2.5% extract ointment 5% extract ointment 10%.

Improvement in the wound healing process due to 5% Madeira vine or Binahong, has an antioxidant, anti-inflammation, and antibacterial activities. This is shown by the acceleration in the wound healing process, marked with the low number of PMN, high quality of collagen, and mild angiogenesis, and medium fibrosis. This condition is even better compared to the treatment group which received silver sulfadiazine as the standard therapy for burn patients. From the result, It was found that the process of wound healing in G2 (5% extract) is better than the other groups. This result showed that the leaf extract of Madeira vine with a 5% concentration is an optimum dose that can increase the wound healing process. This is connected to the secondary metabolites of Madeira vine that function as medicine. These metabolites are flavonoid, saponin, tannin, and ascorbic acid [11]. Flavonoid has the ability to be an antioxidant that can reduce free radicals.[12], Flavonoid can also function as a destroyer of microbes, especially Gram-negative bacteria. Saponin can increase the proliferation of monocytes which eventually will increase the number of macrophages that secrete the growth factor which is crucial for the wound healing process.[13]. Tannin in the Madeira vine leaves functions as an astringent that can cause skin pores to shrink and stop exudates and mild bleeding, causing wound to close and preventing bleeding on the wound [14]

Conclusion An increase in the degree of reepithelialization, density of fibroblasts, and density of collagen can occur because honey (including Clover Flower Honey) increases transforming growth factor (TGF- ), IL-1 which induces proliferation of keratinocytes and fibroblasts. Honey also enhances the regulation of matrix metallopeptidase 9 (MMP-9), a protease that plays a role in keratinocyte migration so that the reepithelialization process takes place more quickly.

The burn treatment using 5% leaf extracts ointment of Madeira vine (A. cordifolia (Ten.) Steenis) was proven to accelerate the healing process of burn wound in the skins of white rats (R. norvegicus).

References 1. Kristian, Hans & Budiman, Iwan & Hasianna, Stella. (2018). Topical Clover Flower Honey Administration Accelerated Wound Healing in Swiss Webster Mice. Journal of Medicine & Health. 2. 10.28932/jmh.v2i2.1018. 2. Molan P. Honey a Biologic Wound Dressing. Wounds. 2015 Jun;27(6):141-51. 3. Yuniarti WM, Lukiswanto BS. Effects of herbal ointment containing the leaf extracts of Madeira vine (Anredera cordifolia (Ten.) Steenis) for burn wound healing process on albino rats. VetWorld. 2017;10(7):808–813. doi:10.14202/vetworld.2017.808-813 4. Astuti S.M, Mimi S.A.M, Retno A.B.M, Awalludin R. Determination of saponin compound from Anredera cordifolia (Ten) steenis plant (Binahong) to potential treatment for several diseases. J. Agric. Sci. 2011;3(4):224–232. 5. Lestari D, Sukandar Y, Fidrianny I. Anredera cordifolia leaves extract as anti-hyperlipidemia and endothelial fat content reducer in male Wistar rat. Int. J. Pharm. Clin. Res. 2015;7(6):435–439. 6. Martins S.S, Torres O.J.M, dos Santos O.J, Limeira J.F.A, Filho E.N.S, da Costa-Melo S.P, Santos R.H.P, Silva V.B. Analysis of the healing process of the wounds occurring in rats using laser therapy in association with hydrocolloid. Acta Cir. Bras. 2015;30(10):681–685. - PubMed 7. Sen C.K, Khanna K, Gordillo G, Bagchi D, Bagchi M, Roy S. Oxygen, oxidants, and antioxidants in wound healing an emerging paradigm. Ann. N. Y. Acad. Sci. 2002;957:239– 249. -PubMed 8. Kurahashi T, Fujii J. Review: Roles of antioxidative enzymes in wound healing. J. Dev. Biol. 2015;3:57–70. 9. Koh T.J, DiPietro L.A. Inflammation and wound healing: The role of the macrophage. Exp. Rev. Mol. Med. 2013;13(3):1–14. 10.Nijveldt R.J, Van N.E, Van H.E, Boelens P.G, Van N.K, Van L. Flavonoids: A review of probable mechanisms of action and potential application. Am. J. Clin. Nutr. 2001;77(4):418–425. –PubMed 11.Nayak B.S, Vinutha B, Geetha B, Sudha B. Experimental evaluation of Pentas lanceolata flowers for wound healing activity in rats. Fitoterapia. 2005;76(7-8):671–675. -PubMed 12.Barku V.Y.A, Boye A, Ayaba S. Phytochemical screening and assessment of wound healing activity of the leaves of Anogeissus leiocarpus. Eur. J. Exp. Bio. 2013;3(4):18–25. 13.Kimura Y, Sumiyoshi M, Kawahira K, Sakanaka M. Effects of ginseng saponins isolated from red ginseng roots on burn wound healing in mice. Br. J. Pharmacol. 2006;148:860–870. - PMC - PubMed 14.Ashok P.K, Upadhyaya K. Tannins are astringent. J. Pharmacogn. Phytochem. 2012;1(3):45–50

359

360

Mortality Rate in Trauma Patients Following Massive Transfusion with Savannah Quila Thirza¹, Putu Ijiya Danta Awatara¹, Audrey Patricia Tandayu¹, William Wiradinata¹ ¹AMSA Medical Faculty of Brawijaya University

Introduction

Methodology

Results

Search Term :

Country

Keywords : “massive transfusion”, “trauma”, “hemmorhage”,

Study design

year USA cohort Germany

NCBI n = 401

n = 571

ScienceDirect n = 150

USA

Google Scholar n = 400

Germany

cohort

cohort cohort

size 2474 1250

703 1362 organ failure

n = 326

n = 282

Analysis of 6 hours mortality incidence following high tration in massively transfused

n = 34 full text review n = 25

Analysis of 24 hours mortality incidence following high

Studies collected for detailed evaluation and data extraction n=9

tration in massively transfused

Analysis of 30 days mortality incidence following high

n=4

tration in massively transfused

Inclusion Criteria Analysis of overall mortality incidence following high randomized controlled trial

tration in massively transfused

Discussion Authors found 4 eligible studies according to the inclusion criteria. Acute traumatic coaguloapthy (ATC) contributed around one-third of deaths related to traumatic hemorrhage. ATC has been linked to up to four-fold increase in mortality at previous studies. Majority of patients with traumatic injury undergo massive transfusion with up to 90% of total blood products adminisaspect.

Key :

Blinding

Allocation concealment

Authors analyzed 3 studies on the 6-hour mortality incidence in massively transfused patients which showed improvement in

dences from 4 studies demonstrated that there is an improvement for 30-days mortality incidences in patients who had been

Conclusion References 361

362

AMINO | AMSC 2020: LONDON

AMINO | PCC AMSC 2020: LONDON

INNOVATION TOWARDS EMERGENCY MEDICAL SYSTEM WITH M-BULANCE APPLICATION INVOLVING EMERGENCY BUTTON TO MINIMIZE ROAD TRAUMA DEATH IN INDONESIA Rc a dP a

e Na a a Ze g, Da

K a ,A

Medical Faculty, Hasanuddin University Abstract. Road traffic injuries are the eighth leading cause of death globally, and the leading cause of death for young people aged 5â&#x20AC;&#x201C;29. The injury characteristics for road traffic accident in developing countries differ from developed countries. Indonesia in 2017 reached 39.827 or 2.37% total death cause of road injury in the world and become the number 95 ranks in the world (WHO, 2017). According to Kemenkes RI 2019 said that 70% of death rates in Indonesia occur before they arrive to the hospital an 30% other die at hospital. There are several problems regarding emergency medical services in Indonesia. First, there is no tangible movement from the government itself for emergency regulation. Most of the patients use any kind of public transportation to hospital due to inadequate ambulances provision and less information about how to reach the ambulance service The other problem is the core component of prehospital care is not only taking an injured patient to hospital, but the first responder care is also important. Due to these problems we come up with a solution to invent a mobile application named M-Bulance. The application that we design has one multifunctional emergency button, which will be connected to volunteers as the first respondent care. Once the volunteer have arrived, they make the situation safe, provide a proper first-aid and do a patient health monitoring. This mobile application is equipped with GPS. This can be a new solution to make emergency medical services more reachable and usable by the society. Still, to ensure this solution work well, it is a necessity for government to promote and create new policy as well. We hope all stakeholders that involved can socialize this application to be well known in the society Keywords : Ambulance, Emergency medical system, Road injury, Road trauma, Mobile Application, Emergency Button

365

INNOVATION TOWARDS EMERGENCY MEDICAL SYSTEM WITH M-BULANCE APPLICATION INVOLVING EMERGENCY BUTTON TO MINIMIZE ROAD TRAUMA DEATH IN INDONESIA

By : Richard Pinarto Trixie Nathania Zelig Da

a l Khai

Alma Sutyono

AMSA UNIVERSITAS HASANUDDIN

366

INTRODUCTION Road traffic injuries is used to describe both the physical and mental injuries resulting from an event involving a transport crash, to those involved both directly and indirectly (WHO, 2019). Approximately 1.35

illi

le a e killed

ad each ea . Road traffic injuries are the eighth leading

cause of death globally, and the leading cause of death for young people aged 5 29. Between 20 and 50 million more people suffer non-fatal injuries, with many incurring a disability as a result of their injury (WHO, 2020). Globally, the burden of road traffic injuries, measured in terms of number of disabilityadjusted life years (DALYs) ranked ninth in 2015 but are projected to be the fourth leading cause of disease burden by 2030. According to WHO, 2018 said that the risk of dying in a road traffic crash is more than 3 times higher in low-income countries than in high-income countries. The injury characteristics for road traffic accident in developing countries differ from developed countries. The victim have an injury due to a number of factors, including poor knowledge and practice of road safety measures by the general population, recklessness behavior of motorists, and high speed driving. Indonesia as one of development country in the world in 2017 reached 39.827 or 2.37% total death cause of road injury in the world and become the number 95 ranks in the world (WHO, 2017). Indonesia crash data reports are a statistical data based on information obtained from the Regional Police of Republic of Indonesia from 34 provinces in Indonesia as part of the National Traffic Police Corps Republic of Indonesia. The data indicate that there have been a total of 250.000 road deaths in Indonesia from 2004 to 2014. Every person who has an injury needs first aid before they are taken to the hospital as fast as we can (Jusuf, A., 2017) As we know in Indonesia there are so many civilian hospitals with emergency departments of varying standards and size. The hospitals usually have their own ambulances, which are generally tied to that hospital and are predominantly used for inter-hospital transfers. According to the ambulance service guidelines by the Health Insurance Administering Agency (BPJS) 2018 saying that ambulance services are only provided for referral between health facilities: a. Between first-level health facilities. b. From the first level health facilities to the referral health facilities. c. Between secondary referral health facilities. d. From secondary health facilities to tertiary health facilities. e. Between tertiary health facilities. f. And referral back to health facilities with type in underneath.

367

118 Emergency Ambulance Service is the only public ambulance service in Indonesia. It is based in the seven cities which are Jakarta, Palembang, Yogyakarta, Surabaya, Makassar, Denpasar, and Malang. It is not government funded but charges those who can afford to pay. Access is achieved by dialing the toll free number 118. In the case of an emergency, the patient or by stander would call the hospital emergency department or public heath center where they want to be admitted. Then, depending on the availability of an ambulance, the patient may be picked-up by an ambulance, but in most cases the patient tends to use a private vehicle instead of using an ambulance (Suryanto,2017). Emergency service system nowadays has not fully had a good system yet. From several many case report about the system of ambulance said that there are still some ambulance operators who have not operate it optimally. According to Perhimpunan Rumah Sakit Seluruh Indonesia (PERSI) meeting in 2018 said that an ambulance driver is not only a driver who has a skill at driving a car but also good at understanding the situation. The driver should understanding the patient condition, road condition. Speeding an ambulance at high speed is not always the right decision in an emergency. Because in a several conditions, patients actually feel a worse conditions if they are in a vehicle that have an unstable condition According to Kementrian Kesehatan Republik Indonesia (Kemenkes RI) 2019 said that 70% of death rates in Indonesia occur before they arrive to the hospital an 30% other die at hospital. The next problem is

e a b la ce i I d h a ig ed i I d

e ia

e ia d a b la ce

ha e a g

d e ice a d e i

e . The e

a a edic

aid that the ambulance waiting time can usually be up to 1-1.5

hours and is not possible for an emergency situation and it is caused by many situation like the operators d

he add e

f de i a i , affic ja

e e al

ad , a d he e

le h call f

a b la ce

shows the incorrect address, other than that the death happens cause inadequate first aid given to the patients. According to WHO review about The Republic Indonesia Health System in 2017 said that In the mid1970s, pre-h

i al ca e adicall i

he I d

e ia S ge

Association established the

118 Emergency Ambulance Service in Jakarta with the support of the local government. Every ambulance is equipped with emergency equipment and emergency medical technicians. But nowadays the ambulance d

ha e a

edical technicians involved in it to help the victim. So even though the ambulance

came to pick up the victim, the victim was not given an adequte first aid as he had to get before take to the hospital, to reduce the risk of severe injury or the worst can happen, death.

368

Based on the problem above that the emergency medical system in Indonesia should be more have a better service and can reach all of part in Indonesia, we purpose an innovation about the new application for emergency medical system. This application will make it easier for people to contact and reach the ambulance around Indonesia. Beside that the person who have an accident can also receive an adequate first aid than what ordinary people usually do when there are an accident happen. OUTLINE PROBLEMS Road trauma is an immense global issue which is frequently neglected, though heavily contribute on injury deaths. Approximately 1.35 million people died each year as a result of road traffic crashes, and 93% occurs in low and middle income countries. Comparing to other health problems, the public policy responses towards road trauma has been slow on national and international levels. Acc di g

I d

e ia

Na i al Heal h W k Mee i g i 2020, he e a e fi e hi g

ha bec

e he

main focuses of Health Ministry, which are maternal and child mortality, stunting, disease prevention and control, GERMAS, and health system governance. Referring to health system governance as one of the main focuses, emergency medical services require more attention since there are many cases where road injury lead to death in Indonesia and one of the main contributing factor is an inadequate pre hospital care. There are several problems regarding emergency medical services in Indonesia. First, there is none substantial movement from the government itself for emergency regulation. The closest thing to an actual emergency medical services system that Indonesia have is Ambulans Gawat Darurat (AGD) 118 in Jakarta. Even then, AGD is initiated by Indonesian Surgeon Association and not by government funded, therefore the service might be too costly for most people. The limitedness from AGD as a result of lack of government support, induce more problems. AGD is only available in 27 big cities with most of which are in Java Islands. When people call 118, it will be c a b la ce

ec ed

AGD

a i al i 37

ce e and continue to the related cities. The average time from first call to i

e , i i 27

e l

ge ha a b la ce

e ice i US. I fac , he

World Report on Road Traffic Injury Prevention said that intervention have to take place as fast as possible to prevent severe injuries. With all the ineffectiveness, emergency services in Indonesia is getting e eglec ed ha e e . I h

cie

a ce on what number to call for emergency,

they choose to use private transportation to transport the injured patient. Using private transportation without a specialized knowledge can cause more damage. The ambulance service in Indonesia is either public health center based or hospital-based not all emergency departments of a public health center or hospital can provide emergency care, which includes

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an ambulance service. Most of the patients use any kind of public transportation to hospital due to inadequate ambulances provision and less information about how to reach the ambulance service. From the problem mentioned, we can say that the country has not allocated enough state budget for emergency edical

a d he h

i al d e

ciali e

ch ab

he ambulance service in their hospital.

The other problem is the paucity of knowledge on how to take care an injury patient, specifically right after a road trauma. The core component of prehospital care is not only taking an injured patient to hospital, but the first responder care is also important. It is shown that when there is an accident occurs, e

le a

di d

he ha l

ki g f

eciali ed hel . I

a be

ible

well-placed workers, such as public servants, taxi drivers, or society in general to provide a more comprehensive level first aid skill. Although, it is quite difficult to found heath worker in the near incident location, instead we could arrange more trained people in the health fields to be more exposed on the accident happen. As the conclusion, emergency medical system in Indonesia is disorganized and far from perfect which each country should have. We have to recognize the importance of emergency medical system so we could develop and run the system. Certainly, it requires cooperation from government, hospital and we as citizens. SOLUTION The emergency medical service should be widely publicized, accessible and the time taken to answer emergency calls should be minimized. Efficient and well-organized emergency medical dispatch is necessary. Thus, we would like to offer a solution of the problems listed earlier through mobile technology that has brought an exceptional step-up in health zone. We come up with a solution to invent a mobile application named M-Bulance. The application that we design has one multifunctional emergency button, which will be connected to volunteers as the first respondent care. Here, volunteers must be a medical worker including clinical students, general practitioner, specialist, and nurses. One simple click of the emergency button from anyone who needs help will immediately send a trained volunteer to the road traffic accident site. Considering that the volunteer who came is the closest to the site, so this will avoid delayed care. Once the volunteer have arrived, they make the situation safe, provide a proper first-aid and do a patient health monitoring. All details about the patient will be inserted by volunteers in the mobile application and will be sent to the nearest hospital. After receiving patient condition details, hospital can do the necessary preparation for a suitable treatment of coming patient.

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M-Bulance is equipped with Global Positioning System (GPS), which is a system that can show the exact position of the mobile app user. As the time when the emergency button is clicked, ambulance will soon headed to the site. So the time taken will be minimized and the operator of ambulance will arrive to their destination accurately.

Figure 1. Mechanism of M-bulance for user

Figure 2. Mechanism of M-bulance for volunteers Be ide

ha ,

e al

e a idea

add

fea

be a

ee .

Clicking the sign up feature will lead the volunteer to fill some personal information, including Full Name, Gender, Date/Place of Birth, Address, Nationality, Occupation, Last Education, Email Address, Phone,

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Institution and Photo. All of this personal information, especially Occupation, Last Education and Institution needs to be confirmed to ensure that all volunteers are truly trained and certified.

Figure 3. Mechanism of sign up feature on M-bulance for volunteers To make sure that this idea can be executed successfully, we need a massive publication, promotion and socialization to the society so that they know how to use it correctly. That is why we also need the help of every medical worker and government to socialize this new application. CONCLUSION Road trauma has been one of the biggest cause of death but we can see that public policy and g e

ad a

a ha bee

. In fact, emergency medical system in every

country play a massive role where ironically Indonesia, and other low-middle income countries is far from perfect and slowly lost trust from society as it is not reliable. By providing a new mechanism on an application that can contact directly near-by hospital, trusted first responder care, and send location through GPS with one button. This can be a new solution to make emergency medical services more reachable and usable by the society. Still, to ensure this solution work well, it is a necessity for government to promote and create new policy as well. RECOMMENDATION We desire that the government could be allocating more on emergency medical system by support the funding of the advance research of this application and create new policy, which requires fresh graduated doctors to sign up as volunteers and giving socialization to internship doctors. Other than that, we also hope health workers, in this case clinical phase medical students, nurses, doctors, and specialist to contribute as a volunteer in developing and carry out this application. We concern that all hospital in

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Indonesia to participate and cooperate on preparing the needing of emergency. Not forgetting the society as the user to actively use this application in a proper way and maximize the feature available to help others. At last, we hope all stakeholders that involved can socialize this application to be well known in the society. REFERENCES BPJS Kesehatan RI. (2018). Panduan Praktis Pelayanan Ambulans. Jakarta: BPJS Ksehatan RI. E. Pitt, A. P. (2005). Prehospital care in Indonesia. Emergency Medicine Journal, 144-147. Europan Commision(2020, January). Time Between Road Crash and Road Death? Retrieved March 13, 2020, from European Commision: https://ec.europa.eu/transport/road_safety/specialist/knowledge/postimpact/the_problem_road_tra ffic_injury_consequences/time_between_road_crash_and_road_death_en Jusuf, A., Nurprasetio, I. P. (2017). Macro Data Analysis of Traffic Accidents in Indonesia. Journal of Engineering and Technological Science, 49(1), 132-143 Kementrian Kesehatan Repulik Indonesia. (2019). Emergency System Indonesia. Kementrian Kesehatan Republik Indonesia. Lumanauw, D. D. (2018, May 18). Emergency Medical System Unprepared for Attacks. Retrieved March 15, 2020, from The Jakarta Post: https://www.thejakartapost.com/academia/2018/05/18/emergency-medical-system-unpreparedfor-attacks.html Paniker, J., Graham, S. M., & Harrison, J. W. (2015, July 21). Global Trauma: The Great Divide. SICOT Journal, I, 19. Perhimpunan Rumah Sakit Indonesia. (2018). Permasalahan Ambulans Indonesia. Yogyakarta. Suryanto, Boyle, M., & Plummer, V. (2017). The Pre-Hospital and Healthcare System in Malang, Indonesia. Australian Jurnal of Paramedicine, 14(2), 1-8. World Health Organization (2006). Roadsafety Training Manual Unit 5. New Delhi, India: World Health Organization, Regional Office for South-East Asia. World Health Organization (2017). The Republic of Indonesia Health System Review. New Delhi, India: World Health Organization. World Health Organization (2018). New WHO Report Highlights Insufficient Progress to Tackle Lack of Safety on The World's Roads. World Health Organization. World Health Organization (2019). Road Safety : Basic Facts. World Health Organization.

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World Health Organization. (2020, February 7). Road Traffic Injuries. Retrieved March 13, 2020, from World Health Organization: https://www.who.int/news-room/fact-sheets/detail/road-trafficinjuries

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BE A ARE, DON

PLA

I H FIRE: FIR

AID REA MEN OF B RN

MITIGATE ADVERSE EFFECTS DUE TO THE WRONG HANDLING IN COMMUNITY Dwi Ari Santi Putri, M. Aqib Husni Fadhli, Natasya Febrilia Yulianti, Putri Daffa Salsabila Jember University

Abstract Burn injuries are one of the most common and devastating forms of trauma, making it a major global public health crisis. Burn injuries often cause morbidity and even mortality that can affect everyone's life physically, psychologically, and economically. Each person has their own way to treat burns such as by applying toothpaste, oil, butter, and other unscientific remedies. Not all of those treatments are right and may even make it worse. In solving this problem, we make a tagline called Be "AWARE" don't play with "FIRE" and take advantage of social media and streaming platforms so it can reach people of all ages. The words "AWARE" and "FIRE" are actually the abbreviations of how to handle burns properly. "AWARE" shows what to do while "FIRE" shows the don'ts. Some of the strategies implemented in the socialization are: make abbreviations related to burns that are easy to remember, show real interviews with a person affected by the adverse effects of improper treatment, direct socialization to the public, and encourage the community to participate in the campaign including word-of-mouth strategy. Collaboration on every element in the health sector, especially medical students to educate directly and indirectly regarding this subject is needed to increase public knowledge. Government actions are also very important through policymaking in workplace safety in the industry, standards use of electrical equipment and safety in the use of gas for cooking in reducing the incidence of fires around us. Key Findings: burns, first-aid treatment, trauma, strategy.

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BE A ARE, DON

PLA

I H FIRE: FIR

AID REA MEN OF B RN

MITIGATE ADVERSE EFFECTS DUE TO THE WRONG HANDLING IN COMMUNITY

By : Dwi Ari Santi Putri M. Aqib Husni Fadhli Natasya Febrilia Yulianti Putri Daffa Salsabila

AMSA-JEMBER INDONESIA 2020

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Introduction A burn is one of the most common and devastating forms of trauma, produces significant morbidity and mortality, making it a major global public health crisis. Based on the World Health Organization (WHO), the incidence of severe burns was nearly 11 million people worldwide and approximately 180.000 deaths every year. According to the Pediatric Annual Report of the National Trauma Data Bank (NTBD), more than 5.000 children are treated in emergency departments because of burns. The incidence requires attention because the prevalence is the fourth most common type of trauma worldwide, higher than the combined incidence of tuberculosis and HIV infections. In Cipto Mangunkusumo National Central General Hospital Indonesia, 54,9% of burns are caused by flame, 29,2% by heat temperature water, 12,8% by electricity, and 3% by chemical substance. The most frequent degree of burns is the second degree. Most of these burns are not fatal but become a leading cause of morbidity and disability. The first aid awareness has been shown to reduce morbidity and mortality. Each person have their own way to treat burns such as by applying toothpaste, oil, butter, and other unscientific remedies. Not all of those treatments are the right way to do it and some may even make it worse. This video and white paper aim to raise awareness of the first aid treatment in the community so that it will reduce morbidity caused by burns. Outlined Problems Burn injuries often cause morbidity and even mortality that can affect e e

life physically,

psychologically, and economically. Burns are estimated to cause approximately 180,000 deaths annually worldwide, mostly in low- to middle-income countries. Burns accounted for the primary diagnosis in 424,000 visits to emergency departments (EDs) in the United States in 2014, while in 2016, there were approximately 40,000 burn-related hospitalizations in the United States, 30,000 of which were at specialized burn centers. In Indonesia, burns caused approximately 195,000 deaths annually. The Cipto Mangunkusumo General Hospital Burn Center - the national referral center for burns in Indonesia - received more than 130 patients annually from all over the country. People of all ages ranging from children to elderly often experience burn injuries from minor to severe cases. It is caused mainly due to contact with hot surfaces or hot liquids. Generally, there are differences between the causes of burns in women and men. In women burn injuries are often caused by open cooking fires, unsafe cookstoves, or splashing oil when cooking. For men often related to the work environment for example work in the field of industry.

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Low economic status, poor living conditions, and population density are high-risk factors for fires. Many conditions around us can cause burns. Unfortunately, there are still many people who don't know how to properly treat burns. Actions against burn injury can affect the severity of the burn. More effective first aid and time in handling can minimize the impact of burn injuries. Unfortunately, there is still a lot of wrong knowledge about first aid treatment for burns that are still trusted and carried out obediently by Indonesian people. For example the non recommended use of toothpaste, soy sauce, oil on burns that cause skin irritation or applies neither ice nor cold water to cool down the wound. Toothpaste contains harmful chemicals like calcium and peppermint. It increases the risk of infections and also affects the tissue of the skin. Apply ice frequently led to cases of serious and potentially fatal hypothermia, particularly with larger surface area burns. A common misconception in many areas is the use of eggs, mud, oil, butter and other traditional remedies that are harmful, certainly irritate the injury and creating a more favorable environment for infection and these remedies are no benefit. Solution In solving this problem, it must be realized that human trust that has been done for a long time might not easy to change. This also applies to mismanagement of burns and the unscientific remedies. As part of society that has a higher degree of education than the general public, especially medical students are supposed to do something regarding this subject. Social media and streaming platforms are currently loved by people of all ages and provide features for showing videos, including educational videos. By starting to make an educational video about how to properly treat burns can help reduce the adverse effects of burn injuries. Some of the strategies implemented in the socialization through educational video are as follows. 1. Make abbreviations related to burns that are easy to remember Based on WHO guideline (2007) about Management of Burns, a tagline called Be "AWARE" don't play with "FIRE" was created. The words "AWARE" and "FIRE" are actually the abbreviations of how to handle burns properly. "AWARE" shows what to do while "FIRE" shows the don'ts. Those are made related to burns so they are easy to remember. A for avoid sources of fire, W for water the burns with normal temperature water, A for anticipation of bacteria by wrapping burns using safe material, R for rush to the nearest medical services, E for Early treatment from professional medical personnel while F for fluffy dressing, I for iced or cold water, R for ruin the blister, E for Endanger the burns by applying alcohol, toothpaste, ketchup, oil, and butter. In addition to presenting what needs to be done, things that are forbidden are also listed because of the false myths that develop in the community. Since a long time ago, people applied

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toothpaste, butter, oil, and even tomato sauce to burns. There are still many people who think that if the burns are drenched in water, it will form blisters. In fact, the blister was not caused by water but because the burn was already in the second degree. 2. Include real interviews with a person affected by the adverse effects of improper treatment. People tend to believe more when facts are presented. The audience was presented with the experience of wrong handling burns and the adverse effects were shown too so that people will not make the same mistake. 3. Direct socialization to the public Socialization refers to the process of social influence through which the community acquires the information of a group, and in the course of acquiring these elements the self and habits of individuals as part of the community are shaped. Because of its broad scope and importance, direct socialization about the treatment of burns is carried out both to children and adults. This action is expected to be a memorable impression. 4. Encourage the community to participate in the campaign Participation in this campaign is not only in the form of direct outreach. However, this can be executed in the form of a word-of-mouth strategy. This is how false health myths continue to be believed and therefore can be used to spread facts as they were. This will definitely create a significant impact if done earnestly. Conclusion In the first aid treatment of burn trauma, the community needs to be involved to reduce morbidity and m

ali . T

ai e c mm i

a ae e ,

e a cam aig

l ga a d agli e Be AWARE,

i h FIRE . AWARE i a abbreviation of avoiding flammable sources of fire, water the

burns with clean normal-temperature water, anticipation of bacteria, rush to the nearest medical services, and early treatment. Meanwhile, forbidden things to do, summarizing reminder for people, FIRE: fluffy clothes, iced or cold water, ruin the blisters, and endanger the burns by applying alcohol, toothpaste, ketchup, oil, and butter. Furthermore, we also do direct socialization to the public and encourage the community to participate in the campaign. By solution we are proposing, we hope that people can do the first aid treatment of burn trauma properly. Recommendation Collaboration on every element in the health sector, especially medical students to educate directly and indirectly through social media, television, and others regarding the correct treatment of burn injury is needed to increase community knowledge, especially for people at high risk of burns.

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Through the tag line "Be Aware, Don't Play with Fire" the message to be delivered will be easy to understand and remember. Government actions are also very important through policymaking in workplace safety in the industry, standards use of electrical equipment and safety in the use of gas for cooking in reducing the incidence of fires around us.

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References Health, N. (2019). Burn Patient Management CLINICAL GUIDELINES. Retrieved from https://www.aci.health.nsw.gov.au/__data/assets/pdf_file/0009/250020/Burn-patientmanagement-guidelines.pdf Joshua

Vorstenbosch.

(2016).

Thermal

Burns.

Accessed

23th March

2020

https://emedicine.medscape.com/article/1278244-overview Kattan, A. E., AlShomer, F., Alhujayri, A. K., Addar, A., & Aljerian, A. (2016). Current knowledge of burn injury first aid practices and applied traditional remedies: a nationwide survey. Burns & Trauma, 4(1), 1 7. https://doi.org/10.1186/s41038-016-0063-7 Kementerian Kesehatan Republik Indonesia. 2019. Pedoman Nasional Pelayanan Kedokteran Tata Laksana Luka Bakar. Jakarta: Menteri Kesehatan Republik Indonesia. Peck, M. D. (2011). Epidemiology of burns throughout the world. Part I: Distribution and risk factors. Burns, 37(7), 1087 1100. https://doi.org/10.1016/j.burns.2011.06.005 Shrestha, S., & Gurung, P. (2018). Awareness on Prevention and First Aid Management of Burn Injury among Adolescents. Journal of College of Medical Sciences-Nepal, 14(4), 200 205. https://doi.org/10.3126/jcmsn.v14i4.21330 Stewart, R. M., Rotondo, M. F., Nathens, A. B., Neal, M., Caden-P ice, C., L Weinand,

(2016).

NTDB

Pediatric

Report

2016,

128.

ch, J.,

Retrieved

from

https://www.facs.org/~/media/files/quality programs/trauma/ntdb/ntdb pediatric annual report 2016.ashx Wardhana, A., Basuki, A., Prameswara, A. D. H., Rizkita, D. N., Andarie, A. A., & Canintika, A. F. (2017). The e idemi l g

i I d

e ia

a i nal referral burn center from

2013 to 2015. Burns Open, 1(2), 67 73. https://doi.org/10.1016/j.burnso.2017.08.002 World Health Organization. (2018). Burns. Retrieved from https://www.who.int/newsroom/fact-sheets/detail/burns

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Lifesaving Lesson Since the Beginning: Inclusion of CPR in Indonesian Education System Satria Angga Widitama Kiran Shadentyra Akbari Nadira Nibras Taqiyya Fildza Intan Rizkia Universitas Padjadjaran

ABSTRACT Out-of-hospital cardiac arrests (OHCA) is a leading cause of death in settings outside of the hospital. The minutes between the onset of arrest and the arrival of medical assistance is crucial. Chances of survival can be increased two to threefold when quali

ca di

ci a i

(CPR) i

e f med. I d

e ia

public health officials seem to have a low level of interest and investment in educating the community about CPR. There is no national program in place to increase the public level of knowledge towards cardiopulmonary resuscitation (CPR) and basic life support (BLS). This adds up to a low rate of bystander CPR and not enough people do not feel encouraged and confident enough to perform bystander CPR. The authors feel that it is important to educate and encourage the community to perform bystander CPR in cases of emergency. Capability and acknowledgement of cardiopulmonary resuscitation (CPR) of student-aged may prevent the number of mortality rate of those who get out-of-hospital cardiac arrests (OHCA). By making the CPR to be a mandatory curriculum, it is expected that students as bystanders may be able to witness the arrest, recognize arrests, and ability to perform CPR in situations needed.

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Improving Pre-hospital Trauma Care System in Asia Salsabilla, HC1, Ghassani AN1, Nurhalizah D1, Taufiq RR1 1

Undergraduate Program, Faculty of Medicine Universitas Indonesia

Emergency services remain one of the most important yet challenging components of the medical system. In Asia especially, these problems are multi-layered, affected by geographical and cultural differences. However, it is important to be addressed in order to reduce the high mortality rate due to unforeseen events in which death is preventable if treated faster. Thus, this essay will emphasize on the three problems of EMS; The quality of EMS including healthcare professional skill and infrastructure, accessibility of EMS including vehicle availability, along with public awareness and trust regarding EMS in order to educate the policymakers, government officials, and the general public regarding the current situation of EMS in some countries in Asia and the possible solution to produce a better outcome in the future. Three issues were found to be correlated to EMS, this includes the lack of certified staff in the EMS system and dispatcher that render them of less quality, the barrier to gain access to care such as inadequacy of both transportation and roads and lack of financial s pport, and people s a areness regarding ambulances service. To address the aforementioned issues, several actions can be taken. Maximizing the awareness of the general public and gaining trust from them are important and this can be achieved by doing campaigns with the aim to gain the public's interest and trust. Assessment, monitoring, and collaboration are required to be done by the government in order to improve the quality of service of EMS. Emergency Medical Services must be readily available and easily accessible for the public and if possible require little to no cost at all.

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Improving Pre-hospital Trauma Care System in Asia Salsabilla, HC1, Ghassani AN1, Nurhalizah D1, Taufiq RR1 1

Undergraduate Program, Faculty of Medicine Universitas Indonesia

INTRODUCTION AND PURPOSE OF THE PROBLEM Time-sensitive illnesses such as stroke, cardiac arrest, obstetric emergencies, sepsis and injuries contribute significantly to premature disability and mortality in countries with low to middle income. Emergency medical service comprises of three components which include care during transportation which is related to the access, care in the community, and care at the receiving health care facility. Emergency medical services have a critical role to improve the outcomes of both acute worsening of chronic illnesses and acute diseases as EMS itself includes a regional, local, or international systems for the delivery of pre-hospital care and coordinates all aspects of medical care which is provided to patients in the setting of pre-hospital. The EMS itself is aimed to overcome the factors which are most commonly involved in preventable mortality, such as the provision of adequate care at the health care facility, delays in seeking care, and access to health facilities. Hence, the inadequacy of pre-hospital care has a negative effect on the outcomes of pediatric, obstetric, and medical emergencies. Meanwhile, when pre-hospital care is available, trauma-related mortality decreases 25% and when combined with prompt facility-based emergency care, result in a larger cumulative effect (Choudry et al., 2017; Hooper et al., 2019). Despite this urgency to have adequate pre-hospital care, there are three main problems lie in the improvement of EMS. The quality of the system, the access from and to the system, and the awareness of the public regarding the system itself. In several Asian countries, the public awareness towards ambulance or emergency hotline service is low, in addition to surfacing doubt regarding the quality of the service. This is partly due to the lack of emergency infrastructure and adequate staff, and the un-proportional distribution of dispatch systems. The barrier in improving emergency services also created by the lack of transportation and financial support, and inadequacy of roads. The purpose of this white paper is to educate government officials, policymakers, and the public regarding the current situation on a pre-hospital trauma care all across Asia by taking notes of the setbacks and successes of some countries in the continent. Readers are expected to gain a new perspective regarding the problems in EMS in Asia and the possible solutions regarding those conditions, in hopes to encourage the improvement of the medical services for a better outcome.

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AWARENESS TOWARDS AMBULANCE Problem Statement There are so little knowledge and few pieces of research about public awareness and perception regarding EMS,

. T

range of cultural differences even though the effectiveness and outcomes of emergency medical service rely on trust and awareness of the people to both the medical health care professional and the services. For instance, a study was done in India to prove the effectiveness of traffic safety showed that the general population is not 108 vehicle or others in conditions of transporting victims of traffic accidents compared to ambulances. Thus, in t

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ability to do so (Vasudevan et al., 2016). Another questionnaire collected from the state of Mahasrashtra, India showed that only 17.5% of people are willing to try and check for responsiveness if ever they found a stranger out of consciousness at the side of the . 96,2%

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20.2%

had ever used the ambulance service. Interestingly, 78.9% of health care professionals that participated in filling the questionnaire stated that they will not check for responsiveness. This shows that even with the knowledge they should have obtained, a guaranteed rightful act regarding an emergency situation still cannot be obtained (Modi et al., 2018). Only 43.8% of responders have the opinion of inadequate EMS coverage based on previous experience of using EMS. Approximately 25% rated it as good, while 53.5% rated EMS as average and another 6.9% rated it poor (Modi et al., 2018). In this case, some people's unwillingness to call out for EMS might be due to distrust of the quality of the service and instead utilize other available services. Additionally, people who rated it as average might still have a fear of the EMS not arriving fast enough to the accident site, thus choosing to bring the victims by their own vehicle. In Singapore, where the emergency service was first recognized in Asia, the awareness of the people regarding EMS was better than in most Southeast Asian countries. Even from a research conducted in the year of 2002, most showed the knowledge about emergency ambulance numbers and good indications of calling an ambulance if ever needed. The respondents' expectations of the ambulance response time were greatly shorter than paramedics (Ong et al., 2004). If we compared with a study in Saudi Arabia, 18.8% expected to wait 1 hour before help showed up and 94.5% thought that there were not enough ambulance services distributed across the city (Hamam et al., 2015). Beside suggesting room for improvements, this also implies that the public in Singapore has higher trust towards the EMS, thus more likely to use their service.

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An effort should be made to ensure that all general public are aware of the emergency medical system, and build the trust for them to be able to rely on medical professionals in handling situations like this. Due to the number of casualties involving accidents, especially death on the road, it is also important for all the public to have knowledge about the emergency number. Many surveys showed that there are still a significant amount of people that do not know about emergency hotlines. In addition, many respondents in various studies stated that they preferred various emergency services numbers (medical, fire, police, etc.) to be under one dispatched number in countries that do not provide it. Solutions As of now, most countries in Asia included emergency medicine in the medical school curriculum (Pek et al., 2015). However, health care practitioners are only a small portion of the society and the general public also need to have knowledge regarding this field. The faster the public acts in case of emergency, the faster the medical professional can act to save the person. Thus, more training regarding basic life support should be conducted. If all people know how to act accordingly in accidents, they are able to buy some time for the medical professionals to go to the site and proceed with a more advanced medical act. Campaigns should also be eagerly spread. One of the objectives of the campaign should be diminishing the I

ill

me that happens to be a frequent misconception. In fact, many die due to

unforeseen events such as a heart attack and run out of time to be saved. It is important that the public realize that it can happen to their families, close friends, and relatives so they have more willpower to dig more about first aid. Other points include promoting the confidence to act in an emergency, the need to act fast, and obtaining a basic first aid kit at home. Because most of the problems arise due to not enough knowledge and distrust of EMS and its effectiveness, campaigns should also emphasize on the importance of utilizing the EMS in case of emergency, the available emergency hotline, promoting the better quality of the current system, and gain the public trust to be comfortable in using the system.

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QUALITY OF EMERGENCY MEDICAL SERVICES Problem Statement Among Asian nations, the trauma care system varies depending on the needs and available resources. This includes the pre-hospital system, such as dispatch and ambulance protocols. These systems are the backbone of trauma care because, time frame-wise, their presence and efforts are within the golden hour. Speediness and tenacity in these few minutes make a substantial difference. The dispatch service in these countries, including Korea, Singapore, and Thailand, is often segregated into two different phone numbers for police and ambulance. Computer-aided dispatch is preferred. Many of the dispatch systems are only available to certain urban areas instead of nationwide (Ong et al., 2012, Suryanto et al., 2017). Some countries, such as Indonesia, prefer a centralized dispatch system in which a national control center will receive a call then relay it to a regional controller-

system manages ambulance services and maintains a stable influx of patients to hospital emergency units. Unfortunately, some on-field obstacles such as the lack of infrastructure and staff led to delay in transferring instructions and thus hampering effectiveness (Suryanto et al., 2017). Another issue to look into is the Emergency Medical Service personnel. Even within countries, personnel composition may differ. Providers of Western origins, such as the Red Cross, equipped each vehicle with two paramedics. Thai government manned the ambulance with a physician, a nurse and two paramedics. Malaysia had an ambulance driver with no medical training and a medical worker (i.e. physician or nurse) who performs care alone. This variety of compositions showed there is a diverse investment and priorities among countries when it comes to their trauma care scene (Hisamuddin et al., 2007). Despite the difficulties in coordination and human resources, there are visions to improve the capability of healthcare workers in handling trauma first-response situations. Countries have programs to train providers in field triage and prehospital care. EMS providers have primary certifications. Even in low-resource settings, there is a need to maintain trauma educational programs. Despite that, we are still having a shortage of qualified staff manning the dispatchers and ambulances (Sun et al., 2016). Solutions With all the problems and silver-linings laid out, the question now would be: how to streamline the current EMS system? The answer to that lies in an assiduous agenda of assessment, collaboration, and monitoring. A thorough assessment will help specify the unique needs of a country (Callese et al., 2015). As the saying goes, , S A

.C .P

sider the Philippines

-density slums, which is a usual sight to many Southeast

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landscape. The Philippines

German EMS model because compact housings and unpaved roads are impenetrable by ambulance or helicopters. Transporting trauma patients may not be a wise option too, since the uneven roads may lead to more damage to the patient. Singapore, on the other hand, may use a motorcycle ambulance to cut through the traffic and transport a patient at a faster rate than a normal car ambulance (Ho et al., 2014). Needs-based assessment may be carried out by: -

Scouring the literature

Studying the epidemiology of trauma and other emergencies to fully grasp the competencies that the professional first-responders should have. I.e. in an area with a large elderly population, such as Japan, fall may be the prevalent trauma case instead of road accidents that commonly occur in downtowns.

Analyzing the urban planning and locations of trauma facilities to decide the best hotspots for ambulance and fire trucks

Surveys involving the community and emergency units may encourage the participation and allow the voices of civilians to be heard

Through planning and implementation, collaboration is heavily crucial. Stakeholders, including private businesses, local governments, non-profit organizations, communities, legislators, on-field experts and researchers, must be involved in the agenda. Active participation will ensure political commitment, community awareness, and holistic implementation. From the Pakistanis experience, one of the keys to a successful EMS system is providing a legislative framework in favor of the growth of the system (Suryanto et al., 2017). Working with private businesses and NGOs may help places with limited resources to kickstart their own EMS system. This is th

-15, where trained local police officers and doctors work

together with the resources provided by a local construction company, the Red Crescent, an NGO called Integrated Health Services, and the Chambers of Commerce of Islamabad (Ali et al., 2006). Another way to rein in collaboration to improve pre-hospital care may be working with nationwide telecommunication companies to set up a system of dispatch that reaches all the nooks and crannies of the country. By partnering with paramedics from developed countries, the government can build a platform for knowledge transfer to their .T

launch of the first EMS system in the country. The assistance came in the form of classes, designing and acquiring ambulances, equipment, and a management system (Suryanto et al., 2017). Last but not least, to maintain EMS effectiveness and identify rooms for improvement, a monitoring system should be made. Monitoring can be done through trauma registries which may help monitor the epidemiology, processes, and outcomes from trauma care. Trauma registry may inform the future treatment for injured patients. They can also be a platform for surveillance for trauma care. However, to run trauma registries, a significant amount of resources are needed. This prevents countries from utilizing this method. With the

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advancement of technology, however, a trauma registry needs no grand infrastructure. A simple daily log system, like the ones in Karachi, Pakistan, and subsequent input to the trauma registry software provided by the CDC help observe data on trauma deaths and outcome (Sun et al., 2016).

ACCESS TO EMERGENCY MEDICAL SERVICES Problem Statement Emergency medical services have evolved in many ways over the past decade. However, many parts of the world, including South-East Asia still lack the essential basic emergency services up to this day. WHO itself emphasizes the importance of emergency medical services for acute conditions as the first point to come in contact with the healthcare system. However, many factors make the delivery of care to be very difficult to be provided to patients, this includes inadequacy of a proper ambulance service (Choudry, Mahwish, & Areeba, 2017). The unavailability of emergency medical transport is a form of common barrier to emergency medical care which happens due to several factors, including the inadequacy or absence of roads, the incapability to pay for transport fees, and the lack of appropriate vehicles (Razzak & Kellermann, 2002). Emergency itself is a very sensitive time where every action and moments count. Hence, timing of care must be properly monitored along with best treatment to be given to the patients in cases of emergency. Therefore, there should be a proper communication system to be implemented between the hospital and the ambulance. However, in South Asia, provision of timely care has an obstacle, which is the unavailability of trauma centers and pre-hospital management. Patients are usually brought by bystanders or relatives in taxis, private cars, or other modes of transportations which are readily available to the emergency department. Hence, there is no emergency equipment and no trained EMTs or emergency medical technicians, and no system to communicate with the hospitals (Choudry et al., 2017). Ambulance case time is influenced by issues such as response and dispatch time. An extension of time between the occurrence of an incident and the identification of the need for an ambulance and getting hold of an organization to send an ambulance impacts the ambulance case time. That time intervals might be prolonged in cases where there are barriers to access, including clinical service quality, cost, and feelings of exclusion. P

availability, acceptability, accommodation, and affordability as reasons to delay access to care (Hooper, Ranse, & Hutton, 2019).

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Asides from the issues with ambulatory transportation, a large number of people are still unaware of the role of ambulances or even think that ambulances are useless. Ambulance services running in developing countries are mostly work based on charity and donations or privately owned and ambulances are considered to be prehospital transportation instead of pre-hospital care (Choudry et al., 2017). Within the eight PAROS AsiaPacific regions/countries studied, the number of ambulances available per 40,000 populations varies from 0.27 per 40,000 in Singapore to 1.66 per 40,000 in Dubai. Based on the study on PAROS regions/countries, the majority of ambulances there are public services with EMTs on board. A unique feature was shown to be reported in the UAE, Taiwan, and Singapore, where motorcycles were used as the first responders (Ong et al., 2012). In one of the South East Asia Countries, which is Cambodia, one of its province, in Sim Reap, there is .T those attached to private clinics and hospitals. These offer basic transport to the clinic or hospital represented and are rudimentary. Cambodians who require medical treatment or assessment can bear up to seven-hour rides by any transport they have followed by further waiting time for medical assessment up to six hours. Some popular modes of private transport are scooters and motorcycles due to the high cost of fuel. Poor road quality and non-compulsory helmet use contribute to a significant proportion of road trauma being the emergency health cases in Siem Reap. Hence, it can be concluded that Siem Reap has a great absence of a proper preC to develop a proper pre-hospital care system (Smith, 2008). Solutions The long-term aim regarding this issue is to increase public understanding regarding the importance of prehospital emergency service. Proper funding should also be provided by the government to fund the emergency medical service so that all of the ambulances can be maintained in a good condition and all of the equipment should be monitored regularly so that they are in good function (Choudry et al., 2017). The access to EMS itself must be easy to reach, easily accessible to all communities. If the main concern regarding the cost required in order to gain an access to ambulance is true, then a database regarding the nearest ambulance must be made so that a concern regarding the cost does not become a barrier to gain medical access in an emergency situation. T

EMS

knowledge regarding EMS is required for them to actually know how to get an access to EMS. Without the basic knowledge regarding EMS, one will not be able to act in appropriate ways in situations which require an emergency medical care.

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CONCLUSION To conclude, despite the cruciality of having an excellent EMS, there remain three issues regarding EMS, including the awareness of people regarding ambulance services, the lack of infrastructure and certified staff in the dispatcher and EMS system render them of less quality, and the barrier to access care such as inadequacy of roads, lack of financial support, and transportation. To overcome said problems, campaigns and training to educate the general public should be done. Conducting needs-based assessments, establishing collaboration, and monitoring trauma outcomes should also be done to improve the quality of EMS. Efforts to make it freely accessible to all communities should always be advocated.

RECOMMENDATION Both the public and government should pay more attention to the importance of Emergency Medical Service, hence, proper education regarding EMS must be given to the public to increase their knowledge and also awareness about the important role of EMS in dealing with emergency situations, one of which is by knowing how to contact an ambulance. One of the ways to raise public awareness can be achieved by giving more training about basic emergency life skills and campaigns regarding the importance of using EMS in emergency situations. Through these campaigns, the public can have knowledge about the quality of EMS and therefore build trust in EMS and use the system comfortably. Asides from that, other objectives of those campaigns are to make the public know how to maximally utilize the emergency medical service, hence, maximizing campaigns regarding the importance of EMS is really important to achieve a better public awareness. In terms of quality of service, the government should do assessment, collaboration, and monitoring. Assessment is necessary if we are starting from ground zero. It will help define the needs of the country and its local regions. Needs-based assessment can be conducted by literature review, epidemiology study, urban planning, and community surveys. It is also necessary for the government to work with a diverse range of stakeholders including private businesses, local governments, non-profit organizations, communities, legislators, on-field experts and researchers. This ensures an enabling environment for the growth of the trauma care system. Legislative and material backups are much needed for the system to work. Monitoring by establishing trauma care registry should also be done in order to see rooms for improvement.

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The access is correlated to the awareness of EMS, hence, in order to ensure that the public knows how to get proper access to EMS, they first must have knowledge regarding EMS. The EMS itself must be easily accessible, requires less or if possible, no cost at all for those who need the service. If cost becomes a reason for a person to hesitate to gain medical access, then a database regarding the nearest ambulance from the site of the incident must be made in order to decrease the cost for those in need of the medical care. This is important to ensure that the public will not hesitate to gain medical access from medical professionalism in critical and emergency situations.

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REFERENCES Ali, M., Miyoshi, C., & Ushijima, H. (2006). Emergency medical services in Islamabad, Pakistan: a public private partnership. Public Health, 120(1), 50 57. doi: 10.1016/j.puhe.2005.03.009 Callese, T. E., Richards, C. T., Shaw, P., Schuetz, S. J., Paladino, L., Issa, N., & Swaroop, M. (2015). Trauma system development in low- and middle-income countries: a review. Journal of Surgical Research, 193(1), 300 307. doi: 10.1016/j.jss.2014.09.040 Choudry, U., Mahwish, A., & Areeba, A. (2017). Emergency patient transportation in South Asia-call for a proper pre-hospital care system. Journal of Surgery and Emergency Medicine, 1, 1 3. Hisamuddin, N. N., Hamzah, M. S., & Holliman, C. J. (2007). Prehospital Emergency Medical Services in Malaysia. The Journal of Emergency Medicine, 32(4), 415 421. doi:10.1016/j.jemermed.2006.08.021 H , A. F. W., C

, D., W

, T. H., N , . ., P , P. P., L

, S. H.,

O , M. E. H. (2014). P

Trauma Care in Singapore. Prehospital Emergency Care, 19(3), 409 415. doi: 10.3109/10903127.2014.980477 Hamam A, Bagis M, AlJohani K, Tashkandi A. (2015). Public awareness of the EMS system in Western Saudi Arabia: identifying the weakest link. International Journal of Emergency Med, 8(1). doi: https://doi.org/10.1186/s12245-015-0070-7 Hooper, C., Ranse, J., & Hutton, A. (2019). How is ambulance patient care and response time data collected and reported in Malaysia and Indonesia? Australian Journal of Paramedicine, 16, 2 4. Mehmood, A., Rowther, A. A., Kobusingye, O., & Hyder, A. A. (2018). Assessment of pre-hospital emergency medical services in low-income settings using a health systems approach. International Journal of Emergency Medicine, 11(1), 1 5. doi: https://doi.org/10.1186/s12245-018-0207-6 Modi, P., Solanki, R., Nagdev, T., Yadav, P., Bharucha, N., & Desai, A. et al. (2018). Public awareness of the emergency medical services in Maharashtra, India: A questionnaire-based survey. Cureus, 10(9), e3309. doi: 10.7759/cureus.3309 Ong ME, Ang PH, Chan YH, Yap S. (2004). Public attitudes to emergency medical sevices in Singapore: EMS day 2002. Singapore Medicine Journal, 45(9), 419-22. Ong, M., Cho, J., Ma, M., Tanaka, H., Nishiuchi, T., & Sakaf, O. (2012). Comparison of emergency medical service system in the pan-Asian resuscitation outcomes study countries: Report from a literature review and survey. Emergency Medicine Australasia, 1 7. Pek J, Lim S, Ho H, Ramakrishnan T, Jamaluddin S, Mesa-Gaerlan F et al. (2015). Emergency medicine as a specialty in Asia. Acute Medicine and Surgery, 3(2), 65-73. doi: 10.1002/ams2.154 Razzak, J., & Kellermann, A. (2002). Emergency medical care in developing countries: is it worthwhile?. Bulletin of the World Health Organization, 80(11), 900 903.

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Smith, G. (2008). Policy and service delivery pre-hospital emergency care in South East Asia: Three cities. Journal of Emergency Primary Health Care, 6(2), 3 4. Sun, K. M., Song, K. J., Shin, S. D., Tanaka, H., Shaun, G. E., Chiang, W.-C.,

, J. F. (2016).

Comparison of Emergency Medical Services and Trauma Care Systems Among Pan-Asian Countries: An International, Multicenter, Population-Based Survey. Prehospital Emergency Care, 21(2), 242 251. doi: 10.1080/10903127.2016.1241325 Suryanto, S., Boyle, M., & Plummer, V. (2017). The pre-hospital and healthcare system in Malang, Indonesia. Australasian Journal of Paramedicine, 14(2). doi: 10.33151/ajp.14.2.554 Vasudevan, V., Singh, P., & Basu, S. (2016). Importance of awareness in improving performance of emergency medical services (EMS) systems in enhancing traffic safety: A lesson from India. Traffic Injury Prevention, 17(7), 699-704. doi: 10.1080/15389588.2016.1163689 References are managed using Mendeley Citation Manager.

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Everlasting Anguish Dyta Ghezhanny William, Jessica Anastasia Setiawan, Peter Sylvanus

Abstract A meta-analysis of 48 studies about PTSD in adult critical care survivor shows that overall prevalence of PTSD varied widely across studies with the range of 3.70% to 43.73% in 95% of settings. One study about PTSD in patient following war in former Yugoslavia found that 264 subjects had suffered PTSD after the war but never received psychiatric or psychological treatment. A decade after the war, all the subjects were assessed and 83.7% was diagnosed to experience PTSD. Indonesia is one of many countries with a lot of risk factors for PTSD to occur. Indonesia is known as a country that has a high risk of many types of natural disaster such as flood, earthquake, volcano, etc. Indonesian crime rate that was measured by Badan Pusat Statistik (BPS) stated that crimes in Indonesia are increasing overtime, although thereâ&#x20AC;&#x2122;s a small decline in 2017 with crime rate as high as 129. Another study conducted in Bali stated that many stigmas are used for mentally ill patient such as: called crazy, caused by genetics, unable to be cured, seen as a dangerous being and are socially exiled, etc One study conducted a research about determining the risk of developing PTSD after a traumatic event, of 338 individuals that were screened positive, only 9 was receiving treatment. This paper proposed a solution of doing a screening test using TSQ or IES towards patient that went to the emergency unit and has just experienced traumatizing events such as natural disasters, suicide, etc. We suggest the medical team to note personal contact pf the patient to be further assessed for PTSD, approximately 2 weeks â&#x20AC;&#x201C; a month post-trauma. Key findings : Post Traumatic Stress Disorder, Screening, TSQ, IES,

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Asian Medical Students’ Competition London 2020 “Everlasting Anguish”

Authors: Dyta Ghezhanny William Jessica Anastasia Setiawan Peter Sylvanus

Asian Medical Students’ Association 2020

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Introduction World Health Organization (WHO) defined health as a state of complete physical, mental, and social well-being. There are 3 definitions of health that are used. First, health is the absence of any disease or impairment, second is health is a state that allows individual to adequately cope with all demands of daily life, and third is health is a state of balance, an equilibrium that an individual has established within himself and between himself and his social and physical environment. WHO also defined mental health as a state of well-being in which the individual realizes his or her own abilities, can cope with the normal stresses of life, can work productively and fruitfully, and is able to make a contribution to his or her community. Post-traumatic stress disorder (PTSD) is a disorder that develops in some people who have experienced a shocking, scary, or dangerous event. PTSD may occur among people that experienced traumatic events such as military combat, natural disaster, sexual assault, or unexpected loss of loved ones. To diagnose a PTSD, there are 4 criteria that need to be fulfilled: at least one re-experiencing symptoms (flashbacks reliving the trauma over and over, including physical symptoms like a racing heart or sweating, bad dreams, or frightening thoughts), at least one avoidance symptoms (Staying away from places, events, or objects that are reminders of the experience, avoiding thoughts or feelings related to the traumatic event), at least two arousal and reactivity symptoms (Being easily startled, Feeling tense or â&#x20AC;&#x153;on edgeâ&#x20AC;?, Having difficulty sleeping, and/or having angry outbursts), and at least two cognition and mood symptoms (Trouble remembering key features of the traumatic event, Negative thoughts about oneself or the world, Distorted feelings like guilt or blame, Loss of interest in enjoyable activities) for a minimal of 1 month.

II.

Outlined Problem A meta-analysis of 48 studies about PTSD in adult critical care survivor shows that overall prevalence of PTSD varied widely across studies with the range of 3.70% to 43.73% in 95% of settings. Another study found that psychiatric disorder, anxiety disorder, major depression, and PTSD is higher in groups that witness a suicide than the control group. Post-Traumatic Stress Disorder had a prevalence of 19.9% among people that were victims of natural disaster in Indonesia. Another study conducted in RSUP Sanglah Denpasar Bali 2013 showed that 4 out of 10 people that experience

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traffic accident, acquire PTSD which are measured using PTSD Symptom Scale (PSS). Other studies found that among 416 students in Aceh 2018, the prevalence of PTSD is 21% with difficulty concentrating as the most prominent symptoms (47.8%). All studies above stated that thereâ&#x20AC;&#x2122;s still a high prevalence of PTSD. Which means PTSD is quite common, but inadequate treatment and lack of attention towards people with PTSD are still high. One study about PTSD in patient following war in former Yugoslavia found that 264 subjects had suffered PTSD after the war but never received psychiatric or psychological treatment. A decade after the war, all the subjects were assessed and 83.7% was diagnosed to experience PTSD. Indonesia is one of many countries with a lot of risk factors for PTSD to occur. Indonesia is known as a country that has a high risk of many types of natural disaster such as flood, earthquake, volcano, etc. According to Global Facility for Disaster Reduction and Recovery (GDFRR), over the last 30 years, Indonesia has an average of 289 natural disaster per year and an annual death of approximately 8.000 life. Other than that, Indonesian crime rate that was measured by Badan Pusat Statistik (BPS) stated that crimes in Indonesia are increasing overtime, although thereâ&#x20AC;&#x2122;s a small decline in 2017 with crime rate as high as 129.

Picture 1. Risk and crime rate in Indonesia by BPS

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Stigma is a negative reputation or a negative label towards some people that are formed and are affected by the community. One study that was conducted on 155 respondent using Community attitudes toward the mentally ill in RW 09 Cileles Village, Sumedang found that the highest median score falls to authoritarianism domain stigma, which means thereâ&#x20AC;&#x2122;s still a lot of people that believed treating the mentally ill rudely is the right thing. Another study conducted in Bali stated that many stigmas are used for mentally ill patient such as: called crazy, caused by genetics, unable to be cured, seen as a dangerous being and are socially exiled, etc. One study conducted a research about determining the risk of developing PTSD after a traumatic event. It was found that of 3.349 Individuals who presented to the emergency unit and contacted after 2 weeks, 572 individuals responded, 338 individuals were screened positive using TSQ, 26 individuals attended the assessment program, and only 9 individuals received treatment for their PTSD. This shows how much people are developing PTSD yet are neglecting treatment from medical professionals. Based on the problems that are stated above, there are 4 main concerns regarding PTSD. First, PTSD is one of the mental illness that happens often especially post-trauma. Second, Indonesia is one of many countries that is at high-risk of developing PTSD sufferers due to natural disasters, crime rates, etc. Third, stigmatization towards mentally ill people still roots deeply in Indonesia Society. Fourth, people that had been screened and are diagnosed with PTSD are rejecting treatments. In this paper, we propose a solution to reduce the number of people that are at risk of experiencing PTSD symptoms after certain traumas. As medical professionals, it is part of our duty to educate masses about PTSD so that society understand about PTSD itself and its impact to quality of life, and also to reduce the infamous stigma about mental illness, and to encourage people to treat their PTSD.

III.

Solution The solution we propose which are often neglected are screening, especially trauma patient. After the patient went through traumatizing event such as natural disasters, witness of a suicide, post-traffic accident, ICU patient, etc are assessed by a psychiatry to determine and screened for risk of developing PTSD. A study reviewed

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13 instruments to be used as a screening method towards adult with risk of PTSD, found that the mean diagnostic efficiency of screening instruments were as high as 86.5%, although only two instruments performed well consistently within one year, which are Trauma Screening Questionnaire (TSQ) and Impact of Event Scale (IES). It is also found that screening immediately post trauma isnâ&#x20AC;&#x2122;t a good predictor of later disorder, it is advised that screening takes place after a minimal of a month post-trauma. Therefore, emergency unit should take notes on personal contact of the patient, and later contact the patient for further assessment towards risks of developing PTSD. Mental health is often overlooked by Indonesian people, causing people to think that having someone with PTSD was an exaggeration of what they experienced and are only their way of looking for attention, which are then followed by all the negative stigmas. Some people that has been diagnosed with PTSD also deals with negative stigmas, therefore they reject medical assesments so they are not excommunicated from the community around them. We suggest that both as medical students and medical professionals, we need to start educating people and society about PTSD and towards all the stigmas, that it could be treated, and it is not shameful.

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IV.

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