THERAPY OF PATIENTS WITH TYPE 2 DIABETES MELLITUS WITH GAS

GANGRENE PEDIS WHO HAVE COMPLICATIONS OF OSTEOMYELITIS,

OSTEONECROSIS, & CHARCOT-MARIE TOOTH

R. Mohamad Javier1,*, Dani Pratama Febrianto2, Bima Mahardhika Aji3, Abdillah Budi
Ksatria4, Aditya Mahendra Putra5, Andika Prasetyo Arifin6, Crysciando Jefryco Putra7, Basyar
Adnani8, Gede Ardi Saputra9, Wilbert Santoso10, Rizki Akbar Fahmi11, Ro'di Nur Fajri12,
Georaldhy Yussufy Caecarma13, Andro Pramana Witarto14, Bendix Samarta Witarto15, Asri
Pandiangan16, Kevin Christian Tjandra17, Roy Novri Ramadhan18, Derren Rampengan19, Gastin
Gabriel Jangkang20, Muhammad Hafizh21, Anggita Puspitasari22, Januar Ishak Hutasoit23,
Laksmitha Saktiono Safitri24, Fadila Risang Ayu25, Jonathan Alvin Wiryaputra26, Fadli
Ramadhan27, Aurora Rahyu Pasya28, Ni Made Adnya Suasti29, Claudia30, Hayatun Nufus31,
Anastasia Asylia32, Sukirman33, Badrul Munir34, Moch. Yunus35, Moch Aleq Sander36, Lucky
Sutanto37, Himawan Wicaksono38, Martin Yudhi Adenanta39

RSUPN dr. Cipto Mangunkusumo Jakarta1,23,32

RSUD Abdoel Wahab Sjahranie Samarinda2
RSUD dr. Soeroto Ngawi3
Rumah Sakit Islam Surabaya Ahmad Yani4
RS Universitas Muhammadiyah Malang5,21,36
RS QADR Tangerang6
Stem Cell and Cancer Research Semarang7
RS PKU Muhammadiyah Gubug8
RSUD DR. Agoesdjam9
RSUD Kriopanting Payung10, 16
RSD Kalisat Jember11
RSUD Dr. Moewardi Surakarta12
RS Universitas Airlangga13,38
RSUD Dr. M. Soewandhie14
RSUP. Dr. Kariadi Semarang17,24,25
RSUD Dr. Soetomo Surabaya15,18
RSUP Prof. dr. R.D. Kandou Manado19
RSUD Ulin Banjarmasin20
RS Marsudi Waluyo Malang22
RSPAD dr. Gatot Subroto23,28,29,30,33
Pusat Jantung Nasional Harapan Kita Jakarta26
RSUD JAYAPURA27
RSUP Persahabatan Jakarta31
RS Bhayangkara Kediri34,35
RS Tk. II Kartika Husada37
RS Mitra Keluarga Cikarang38
RS Bhayangkara Tulungagung39
Email: [email protected], [email protected] , [email protected],
[email protected], [email protected], [email protected],
[email protected], [email protected], [email protected],
[email protected], [email protected], [email protected],
[email protected], [email protected], [email protected],
[email protected], [email protected], [email protected],

1
 [email protected], [email protected], [email protected],
[email protected], [email protected], [email protected],
[email protected], [email protected], [email protected],
[email protected], [email protected], [email protected],
[email protected], [email protected], [email protected],
[email protected], [email protected], [email protected],
[email protected], [email protected], [email protected]

Correspondence
R. Mohamad Javier, Jl. Bendungan Sutami, Sumbersari, Lowokwaru, Malang City,
East Java, Indonesia
Email: [email protected]

ABSTRACT
Diabetes mellitus can be classified into three distinct types: Type 1 Diabetes Mellitus, Type 2
Diabetes Mellitus, and various other forms of the condition. One of the consequences of this
ailment is the development of gas gangrene pedis. The aim of this study is to clarify the
treatment of Type 2 Diabetes Mellitus in patients suffering from Gas Gangrene Pedis at
Bhayangkara Kediri Hospital between January 2021 and March 2022. This research employs
an observational approach (Non-Experimental Design) using a retrospective cohort design
methodology. The study's participants are individuals diagnosed with gas gangrene pedis, as
identified through patient medical records from January 2021 to March 2022 at Bhayangkara
Kediri Hospital, who also have Type 2 Diabetes Mellitus. Statistical analysis was conducted
using Pearson's Chi-square correlation. The results of the Association Test between Wagner
Grade and DM therapy produce a p-value of 0.525. Since this p-value exceeds α = 5%, we
accept the null hypothesis, indicating no significant association. Likewise, the Chi-square and
Pearson tests between Wagner Grade and gas gangrene pedis therapy yield a p-value of
0.199. Patients with Type 2 DM who have a history of irregular control visits are at an
increased risk of disease progression. Consequently, this can lead to metabolic neuropathy
and varying treatment outcomes for each patient.

Keywords: Type 2 Diabetes Mellitus, Gas Gangrene Pedis, Neuropathy Metabolic,

Osteomyelitis, Osteonecrosis, Charcot-Marie Tooth

1 INTRODUCTION
As widely acknowledged, diabetes mellitus is a condition primarily attributed to irregularities
in insulin regulation. According to the World Health Organization (WHO), diabetes mellitus
encompasses a spectrum of structural and biochemical problems caused by various factors,
leading to either a complete or partial deficiency in insulin and impaired insulin function. It is
divided into three primary types: type 1 diabetes mellitus, type 2 diabetes mellitus, and other
forms of diabetes mellitus. It's worth noting that this research doesn't explore type 1 diabetes
mellitus and other variations. As per the 2019 statement by the International Diabetes
Federation (IDF), Indonesia ranks seventh among the top ten countries in the world with the
highest number of people affected by diabetes mellitus, with a total of 10.7 million cases.
This ailment has several repercussions, including the development of foot gangrene. In
Indonesia, the prevalence of gangrene pedis ranges from 7.3% to 24%. When diabetes
mellitus patients also suffer from infections, the likelihood of amputation due to gangrene
pedis significantly increases. It is estimated that avascular necrosis-induced amputations
related to gangrene pedis have resulted in approximately 1.5 million fatalities (Narmawan,
2019).
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Insulin therapy involves administering insulin injections to individuals diagnosed with
Diabetes Mellitus. In the case of type 1 diabetes, the pancreas is incapable of producing
insulin due to the damage inflicted on the Langerhans beta cells, resulting in a persistent need
for insulin administration (PERKENI, 2016). Conversely, in individuals with type 2 diabetes,
where insulin's effectiveness on target cells is compromised, blood glucose levels remain
elevated. This leads to an increased production of beta cells until they become exhausted
(Buboltz, 2022). The choice of the type of insulin therapy is determined by considering
several things such as the individual's body's response to insulin, the patient's lifestyle
choices, how many injections per day you want to do, how often to check blood sugar levels,
age, and blood sugar regulation targets (Cerika, 2022). One of the most up-to-date methods
that can be used as a reference is the results of the Consensus (PERKENI, 2016) and
Consensus (ADA-EASD, 2006). As a guide, if blood glucose levels are not well controlled,
Hb (A1C>7.5%) within 3 months on 2 oral drugs, then there is an indication to start
combination therapy with oral antidiabetic drugs and insulin.
Individuals who have been diagnosed with type 2 diabetes are at risk of developing
microvascular problems like retinopathy, nephropathy, and neuropathy (Erin, 2015).
Additionally, macrovascular complications may arise in people with type 2 diabetes,
including cerebrovascular disease, coronary heart disease (CHD), and conditions that affect
tissue perfusion such as diabetic gangrene. Research findings (Corina, 2018) suggest that
poorly controlled blood sugar levels significantly elevate the likelihood of chronic
complications in diabetes mellitus patients. Complications that can occur are macrovascular
and microvascular, with the most complications, namely: microvascular complications (57%)
with the most complications namely diabetic neuropathy et causa diabetic gangrene (45.6%),
and diabetic retinopathy (20.7%), while for complications The most macrovascular is a
cerebrovascular disease (38.5%) (Yuhelma, 2020).
Gas gangrene is often found in people with Type 2 DM. 2 factors play a role in gas gangrene:
causative factors and contributing factors. The causal factors of gas gangrene are: Peripheral
neuropathy (sensory, motor, autonomic), increased pressure on the soles of the patient's feet,
and trauma. Peripheral neuropathy is the leading cause and often affects >50% of the deep
sensory system. Increased pressure on the soles of the patient's feet due to limited movement
of the patient's joints, especially in the ankles and deformities in the feet was found in about
28% of the incidence of this as a factor causing gas gangrene. Contributive factors of gas
sufferers’ gangrene i.e., Atherosclerosis, diabetes. Atherosclerosis is associated with
peripheral vascular disease, and this causes the risk of ulcers to occur two times greater in
diabetic patients than in non-diabetics (Fahrun, 2017).
Avascular Necrosis, also referred to as Osteonecrosis, is a degenerative bone ailment
characterized by the death of bone cells due to an insufficient blood supply, particularly in the
subchondral region. This condition often affects the epiphyses of long bones found in weight-
bearing joints or in bones that are compromised by infections, such as those caused by the
bacterium Staphylococcus aureus (Matthew, 2022). Multiple Avascular Necrosis
(STOMACH) represents a type of osteonecrosis that results from disruptions in bone
vascularization, leading to the necrosis of bone marrow cells, osteocytes, and trabecular cells,
ultimately causing the collapse of the affected bone segments (Alalawi, 2017). In the United
States, the occurrence of Avascular Necrosis is relatively rare, with around 1000 cases
reported annually as of December 2021. However, in developing countries like India, where
access to healthcare and antibiotics is limited, the incidence is significantly higher. In 2019,
the mortality rate due to this condition exceeded 67% among the 8000 individuals affected in
India and Vietnam (Bubolz, 2022).
Based on the 2012 report from the Indonesian Ministry of Health, diabetes mellitus was listed
among the top ten non-communicable diseases in Indonesia, with the highest incidence

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recorded in 2017. Specifically, there were 21,159 cases of diabetes mellitus, indicating a
notable increase from the previous year (Rosa, 2019). Epidemiological studies conducted by
Ronald in 2017 revealed that more than one million amputations occur annually in Indonesia
due to diabetic gangrene. Approximately 15% of individuals in Indonesia suffer from diabetic
gangrene, and the amputation rate is around 30% (Rosa, 2019). Another research study has
shown that the likelihood of peripheral neuropathy resulting from multiple instances of
osteonecrosis in diabetic foot ulcers is more pronounced among individuals with type 2
diabetes for over five years, presenting a risk that is twice as high as those with less than five
years of type 2 diabetes (Sukmana, 2018). In the United States, osteonecrosis affects 10% of
individuals aged 30 to 65, with a higher prevalence in men compared to women. In the
population over 65, Kienbock disease, also known as Osteonecrosis Crescent, constitutes
90% of cases, and it is more prevalent among women, with a total of 3,125 cases reported in
the United States (Matthews, 2022). Indonesia, as a developing nation, continues to grapple
with substantial challenges related to type 2 diabetes and gangrene. High rates of community
infections and mortality persist, largely due to improper lifestyles (Ministry of Health, 2020).
One potential cause of Multiple Avascular Necrosis in patients with diabetic foot ulcers is
microorganisms, particularly the facultative anaerobic bacterium Staphylococcus aureus,
which can infiltrate through diabetic gangrene-affected soft tissues (Taste it, 2017). The state
of sugar levels that are not appropriately controlled can disrupt endothelial function in blood
vessels, which results in blood vessels experiencing vasoconstriction. Thromboxane A2 can
cause platelet aggregation, which can increase the risk of occurrence of hypercoagulable
plasma. The occurrence of vasoconstriction/occlusion of peripheral blood vessels can cause
decreased oxygen perfusion to the tissues so that it can occur in the lower extremities and
increases the risk of ulcers. Ulcers that are formed are also susceptible to infection and
develop into gangrene which ends in amputation is a process of pathological bacterial
infection gangrene pedis diabetic (Fahrun, 2017).
Therapy for individuals suffering from foot gangrene is imperative and should be initiated
promptly and gradually. This treatment plan involves the utilization of antibiotics, working
closely with a surgeon for wound cleaning, providing intravenous fluids for resuscitation,
closely monitoring the patient in the intensive care unit (ICU), and incorporating hyperbaric
oxygen therapy as an adjunctive treatment (Buboltz, 2022). Additionally, local astringents
like boric acid and tannic acid, as well as antibacterial agents like neobakrin ointments, may
be prescribed to address foot gangrene. These may also be combined with other irritating
medications such as iodine tincture and mercury bin-iodide, under the limited oversight of a
surgeon (Ronald, 2017). Antibiotics are the primary pharmaceutical agents employed to
combat bacterial infections associated with foot gangrene. These antibiotics are chemical
compounds capable of disrupting various microorganisms, including bacteria and fungi. In
cases of osteonecrosis, a range of preventive strategies or reconstructive surgeries can be
considered. In simpler words, this therapy aims to slow down the progression of
osteonecrosis by replacing the affected bone and soft tissue with endoprosthetics. One of the
most common preventive measures is the core decompression of the femoral head to prevent
venous congestion and support repair. A similar decompression technique can also be used
for the malleoli pedis to improve mechanical support and aid in the healing of avascular
necrosis, often associated with Staphylococcus aureus infection in foot gangrene. This has
been confirmed through arthroscopic joint examination, which revealed various levels of
chondral folds and signs of joint degeneration, ultimately leading to joint collapse in cases of
foot gangrene (Taste it, 2017). Prophylactic therapy for individuals with foot gangrene may
involve the administration of penicillin and clindamycin, owing to their broad-spectrum
coverage against streptococcal bacteria. This should be followed by post-treatment
physiotherapy (Matthew, 2022).

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This study aims to describe Suffering Therapy Type 2 Diabetes Mellitus with Gas Gangrene
Pedis Complicated by Osteomyelitis, Osteonecrosis, and Charcot-Marie tooth. This study
aims to describe information on Suffering Therapy Type 2 Diabetes Mellitus with Gas
Gangrene

Pedis Complicated by Osteomyelitis, Osteonecrosis, and Charcot-Marie Tooth obtained from

the results of secondary data research at Bhayangkara Kediri Hospital for the period January
2021 - March 2022. Later it can be used as a reference for further researchers so that further
experimental research or observations can be carried out from the data studied.

2 RESEARCH METHODS
This exploration is an observational review (Non-Trial Configuration) utilizing the technique
accomplice review plan. The laboratory and admission center for medical records at
Bhayangkara Hospital in Kediri served as the setting for the study. From January 2021 to
March 2022, research will begin.
The review included people determined to have Type 2 Diabetes Mellitus, according to the
clinical records from January 2021 to Walk 2022 at Bhayangkara Medical clinic, Kediri. The
example for this exploration comprised of patients with gas gangrene pedis, distinguished
from patient clinical records inside a similar time period and clinic, every one of whom had
Type 2 Diabetes Mellitus.
The gathered information were of an illustrative sort. A measurable investigation was
directed utilizing the Pearson Chi-square connection test, which is reasonable for evaluating
the connection among free and subordinate factors with a subjective clear cut information
scale. The importance level was set at 5% (α = 0.05), and the examination was performed
involving the Factual Bundle for the Sociologies (SPSS).

3 RESULTS AND DISCUSSION

3.1 Research result
3.1.1. Descriptive statistics
Table 3.1. Descriptive statistics
n % Mean Stdev
Wagner Grade Grade I 1 8.33
Grade II 4 33.33
Grade III 1 8.33
Grade IV 3 25.00
Grade V 3 25.00
Gender Male 7 58.33
Female 5 41.67
Pseudomonas
Bacterial culture 8 66.67
aeruginosa
Staphylococcus aureus 3 25.00
Streptococcus pyogenes 1 8.33
Long period of DM II Less than 1 year 7 58.33
1 year and above 5 41.67
Osteomyelitis Negative 8 66.67
Positive 4 33.33
Avascular necrosis Negative 7 58.33
Positive 5 41.67
Charcot Negative 9 75.00

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 Positive 3 25.00
Therapy DM Glibenklamid 1 8.33
Glimepiride 1 8.33
Long & Rapid Acting 1 8.33
Metformin 4 33.33
Rapid Acting Insulin 5 41.67
Therapy Diabetic
Foot Amputation 4 33.33
Debridement 8 66.67
Age 12 42.08 17.79
Hb 12 10.50 1.93
Leukocytes 204916.6 86379.1
12 7 4
Neutrophils 5 10300.00 1717.56
ESR 5 21.40 1.67
Blood Glucose Test 12 295.42 42.61
HbA1c 12 8.33 0.49
Abbreviations: Stdev, standard deviation; DM, diabetes mellitus, Hb, haemoglobin; ESR,
Erythrocyte sedimentation rate; HbA1c, haemoglobin A1c.

Table 3.2 Cross tabulation results between Wagner Grade and DM therapy
Therapy DM
Wagner Tot
Glibenkla Glimepi Long & Rapid Metfor Rapid Acting p
Grade al
mid ride Acting min Insulin
Grade I 0 0 0 1 0 1
Grade II 0 0 0 2 2 4
0,52
Grade III 0 0 0 0 1 1
5
Grade IV 0 0 0 1 2 3
Grade V 1 1 1 0 0 3
1 1 1 4 5 12
Abbreviations: DM, diabetes mellitus.
According to the findings of the Association Test between Wagner Grade and DM therapy,
the p-value obtained is 0.525. Since the significance level (p) exceeds α=5%, we can
conclude that the null hypothesis H0 is upheld. This indicates that there is no significant
correlation between the Wagner Grade variable and DM Therapy.

6
Table 3.3. Cross tabulation results between Wagner Grade and Gas Therapy Gangrene
Pedis
Wagner Therapy Diabetic Foot
Total p
Grade Amputation Debridement
Grade I 0 1 1
Grade II 0 4 4
Grade III 0 1 1 0,199
Grade IV 2 1 3
Grade V 2 1 3
4 8 12
Based on the results from the Association Test connecting Wagner Grade and Diabetic Foot
Therapy, the obtained p-value is 0.199. Since the p-value exceeds the significance level (α) of
5%, we can infer that the null hypothesis H0 remains valid. This means that the Wagner
Grade variable in its association with Gas Therapy for Pedis Gangrene lacks statistical
significance.

4 DISCUSSION
A research project carried out at Bhayangkara Kediri Hospital between January 2021 and
March 2022 delved into the handling of type 2 diabetes mellitus in cases accompanied by gas
gangrene pedis. This study utilized a retrospective cohort design (Non-Experimental Design)
and encompassed the evaluation of individuals suffering from type 2 diabetes mellitus and
gas gangrene pedis at Bhayangkara Hospital Kediri. Various predetermined factors were
taken into account, and the outcomes demonstrated a lack of statistically significant results
(H0) with a p-value surpassing 0.05. This implies that the outcomes of type 2 diabetes
mellitus treatment varied among patients.
The initial treatment approach for individuals with diabetes mellitus primarily comprises non-
pharmacological interventions, such as dietary modifications and exercise. In cases where
these measures prove ineffective, pharmacological options like insulin therapy, oral
hypoglycemic drugs, or a combination of both can be considered (Khoirunnisa, 2022). Anti-
Diabetic Drugs (ADDs) are substances or combinations of components, including biological
products, used to influence or investigate physiological systems or pathological conditions for
the purposes of human diagnosis, prevention, treatment, recovery, improvement, health
maintenance, and contraception, according to Permenkes 73 of 2016. The administration of
ADDs, as per the Indonesian Ministry of Health, aims to prevent deterioration, diagnose and
treat diabetes mellitus, recognizing that medication usage can ameliorate symptoms but not
cure diabetes (Nabilah, 2019). The research findings indicate that the null hypothesis (H0) is
acceptable, signifying that the treatment of type 2 diabetes mellitus with diabetic foot
conditions varies based on the indications among patients who are prescribed ADDs.
The outcomes of each patient are different but remain on one goal, namely to improve
symptoms in patients and lower blood sugar levels in patients to make them more stable.
Metformin is ADDs used the most by patients because of the mechanism of action of
biguanide by reducing gluconeogenesis and increasing the use of glucose in tissues with KI in
AV block patients only (Khoirunnisa, 2022).
According to the information provided, this study falls under the descriptive category as it
offers an overview of the therapy for type II diabetes mellitus with diabetic foot at

7
Bhayangkara Hospital Kediri during a specified time frame. It also examines the number of
patients meeting specific criteria.
However, a notable drawback of this research is the absence of an analytical component that
would have elucidated which therapy was the most effective for patients. Due to the limited
number of participants, the study was constrained to descriptive statistics and lacked the
necessary sample size (n) for a retrospective analytical investigation.
This study is considered preliminary and has inherent weaknesses and constraints.
Consequently, further research is essential to conduct an analytical exploration of the impact
of different therapies for type 2 diabetes mellitus with diabetic foot, particularly with regards
to their effects on patients' blood sugar levels.

5 CONCLUSION
The following conclusions can be drawn from the research and discussion that took place in
this study:
1. Suffering Therapy Type 2 Diabetes Mellitus with Gas Gangrene Pedis Complicated
by Osteomyelitis, Osteonecrosis, Charcot-Marie tooth was investigated by the method
cohort retrospective design (Non-Experimental Design).
2. Patients who have a history of not being controlled regularly as a result of their DM
treatment are more likely to see their condition worsen, one of which is metabolic
neuropathy, with varying therapeutic outcomes for each patient.
3. Glucose levels in diabetic patients above typical can diminish the awareness of the
feet of patients with type 2 diabetes mellitus.
4. Patients with type 2 diabetes mellitus who experience gangrene pedis experience the
ill effects of an issue vascular as ischemia. This is expected to the macroangiopathy
interaction and diminished tissue dissemination, described by the misfortune or
decrease of the dorsalis pedis corridor beat, tibial supply route and vein Popliteal
makes the feet become atrophic, cold and nails to thicken. Patients frequently
experience complications such as avascular necrosis, Charcot disease, or
osteomyelitis, typically beginning with the toe or leg. This hypothesis follows what
has been recently examined in regards to the reviewing of diabetic foot/gangrene
pedis in light of Wagner-Meggitt, bacterial culture, and difficulties of the sickness that
happen are hypothetically related. Notwithstanding, the result for every patient is
unique.
5. According to the provided information, this study can be classified as descriptive in
nature. It offers an overview of the treatment of patients diagnosed with type 2
diabetes mellitus and gas gangrene pedis at Bhayangkara Hospital in Kediri. It
focuses on secondary data collected within a specified time frame and examines the
number of patients meeting specific criteria.

6 COMPETING INTEREST
Author RMJ has received research funding from dr. Soepraoen Army Hospital, Malang.
Author BM is a member of committee in police that relate with army hospital in Malang.
Grant number of the funding, 1-R01-UMM-22198-23-A1.

7 ETHICAL STATEMENT
Hereby, I, R. Mohamad Javier, consciously assure that for the manuscript, “THERAPY OF
PATIENTS WITH TYPE 2 DIABETES MELLITUS WITH GAS GANGRENE PEDIS
WHO HAVE COMPLICATIONS OF OSTEOMYELITIS, OSTEONECROSIS, &
CHARCOT-MARIE TOOTH”, the conditions below have been met:
1) This material constitutes the authors' unique, unpublished work.
8
2) The paper is not under consideration for publication elsewhere at this time.
3) The paper accurately represents the authors' research and analysis in a truthful and
comprehensive manner.
4) Proper acknowledgment of co-authors and co-researchers' significant contributions is
provided in the paper.
5) The results are appropriately situated within the context of prior and current research.
6) All sources used are appropriately disclosed through accurate citations. Direct text
replication is indicated with quotation marks and proper references.
7) All authors have actively participated in substantial work that has contributed to this
paper, and they collectively accept responsibility for its content.

Failure to adhere to the Ethical Statement may lead to severe consequences.

To confirm originality, your article may undergo evaluation with the iThenticate originality
detection software.
For additional information, please visit http://www.elsevier.com/editors/plagdetect.
I concur with the aforementioned conditions and affirm that this submission aligns with the
guidelines established by Solid State Ionics, as specified in the Guide for Authors and the
Ethical Statement.

Date: 10 September, 2023

Signature of Corresponding Author:

8 CONFLICTS OF INTEREST
The authors declare that they have no conflicts of interest

9 FUNDING
This research received financial support from Soepraoen Army Hospital, which made this
research possible.

10 ACKNOWLEDGEMENTS
We sincerely appreciate everyone who contributed to this research paper. We are especially
grateful to Dr. Badrul Munir, Sp.PD, for his invaluable mentorship and support. His guidance
profoundly shaped our research.We are grateful to the Medical Profession at the University of
Muhammadiyah Malang for providing essential resources for completing this project
successfully.Furthermore, we want to thank our colleagues at Krida Wacana University for
their valuable feedback during our study. Special appreciation goes to Dr. Moch. Yunus,
Sp.OT, and Dr. Moch. Aleq Sander, Sp.B, for their insightful contributions. We also extend
our thanks to Soepraoen Army Hospital for their financial support, which made this research
possible.

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