Siriraj Medical Journal

SMJ

Volume 73, Number 10, October 2021

E-ISSN 2228-8082

The world-leading biomedical science of Thailand

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

E-mail: sijournal92@gmail.com

International Association of Surgeons

Gastroenterologists & Oncologists

Thailand Chapter

Thai Association for Gastrointestinal Endoscopy

Indexed by

By Taya Kitiyakara, et al.

ORIGINAL ARTICLE

REVIEW ARTICLE

MONTHLY

Siriraj Medical Journal

SMJ

Volume 73, Number 10, October 2021

ORIGINAL ARTICLE

635 Effect of Diabetes Self-Management Education (DSME) with and without Motivational

Interviewing (MI) on Glycemic Control among Children and Adolescents with Type 1

Diabetes Mellitus: A Randomized Controlled Trial

Ornsuda Lertbannaphong, et al.

644 Vaginal Tablets of Metronidazole (750 mg) plus Miconazole Nitrate (200 mg) versus

Oral Metronidazole (2 g) for Bacterial Vaginosis: A Randomized Controlled Trial

Manopchai Thamkhantho, et al.

652 Prevalence and Factors Associated with Antepartum Depression: A University

Hospital-Based

Pavarisa Choosuk, et al.

661 The Perceptions of Roles and Understanding about Forensic Evidence and Crime Scene

Preservation of Thai Paramedics

Thongpitak Huabbangyang, et al.

672 The Predictive Factors Associated with Longer Operative Time in Single-Incision

Laparoscopic Cholecystectomy

Weerayut Thowprasert, et al.

680 Clinical Outcomes of Extracranial Germ Cell Tumors: A Single Institute’s Experience

Kamala Laohverapanich, et al.

687 Renal Outcomes of Childhood IgA Nephropathy and Henoch Schönlein Purpura Nephritis

Thanaporn Chaiyapak, et al.

695 Effects of Physical Exercise Program on Physical Mobility of Patients with Cranial Surgery

Jittima Panyasarawut, et al.

702 Leak-Testing of an Endoscopic Aerosol Box for Preventing SARS-CoV-2 Infection during

Upper Gastrointestinal Endoscopy

Taya Kitiyakara, et al.

REVIEW ARTICLE

710 Operating Room and Flight Deck: What Do These Places Have in Common?

Pattarachat Maneechaeye, et al.

721 Access to Healthcare as a Fundamental Right or Privilege?

Tengiz Verulava

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

635

Original Article

SMJ

Ornsuda Lertbannaphong, M.D.*, Pimonsri Hantanasiriskul, M.D.*, Pornpimol Kiattisakthavee, M.D.*, Sunsanee

Ruangson, M.D.**, Nantawat Sitdhiraksa M.D.***, Jeerunda Santiprabhob, M.D.*,****

*Division of Endocrinology and Metabolism, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700,

ailand, **Department of Pediatrics, Nakhonpathom Hospital, Nakhonpathom 73000, ailand, ***Department of Psychiatry, ****Siriraj Diabetes

Center of Excellence, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, ailand.

Effect of Diabetes Self-Management Education

(DSME) with and without Motivational Interviewing

(MI) on Glycemic Control among Children and

Adolescents with Type 1 Diabetes Mellitus:

A Randomized Controlled Trial

ABSTRACT

Objective: Type 1 diabetes mellitus (T1DM) is a chronic disease that is dicult to control. Motivational interviewing

(MI) is a collaborative style of communication that was designed to strengthen a person’s motivation and commitment

to change and improve. We hypothesized that applying MI to diabetes care would lead to improved glycemic control

and improved diabetes self-care behavior.

Materials and Methods: Subjects were T1DM patients aged 10-18 years with HbA

≥8% that were recruited from

the Outpatient Diabetes Clinic during October 2016 - March 2017. Subjects were randomized into the diabetes

self-management education (DSME) or DSME plus MI groups. HbA

levels, diabetes knowledge test, and diabetes

self-care behavioral questionnaire were performed.

Results: irty-ve patients (17 DSME, 18 DSME + MI) completed the study. Baseline HbA

was not signicantly

dierent between groups. At the end of the study, HbA

levels were not signicantly dierent within or between

groups. From pre-intervention to post-intervention, diabetes knowledge scores were signicantly increased, and

self-care behavioral scores were signicantly increased for dietary control and medical taking. Transition to the

stages of change action stage was increased from 0 to 12 persons.

Conclusion: e eectiveness of MI on glycemic control was not found to be statistically signicant at 6 months.

However, continuation of DSME in T1DM patients is necessary for improving diabetes knowledge and care. Further

study in a larger sample size with longer duration of MI and follow-up is needed to conclusively establish the value

of MI on glycemic control in pediatric T1DM.

Keywords: T1DM; motivational interviewing diabetes; self-management education; glycemic control (Siriraj Med

J 2021; 73: 635-643)

Corresponding author: Jeerunda Santiprabhob

E-mail: jeerunda.san@mahidol.ac.th

Received 8 July 2021 Revised 30 July 2021 Accepted 2 August 2021

ORCID ID: https://orcid.org/0000-0002-4726-9360

http://dx.doi.org/10.33192/Smj.2021.82

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

636

Lertbannaphong et al.

INTRODUCTION

Type 1 diabetes mellitus (T1DM) is a complex and

chronic disease that requires lifelong insulin injections,

psychological support, and lifestyle changes. To optimize

glycemic control, regular and frequent self- monitoring

of blood glucose (SMBG) is required. Ziegler R, et al.

found one additional SMBG per day to be associated

with a decrease in HbA

of 0.20%.

Miller KM, el al. also

found a higher number of SMBGs per day to be strongly

associated with a lower HbA

level.

e numbers of

SMBGs per day in the patients at our outpatient clinic

was 2.7-3.3 times per day, which are less than the four

to six times per day recommended by ISPAD clinical

practice consensus guidelines.

A possible reason for

the inadequate number of SBMGs per day among our

patients may be due to the high cost of the glucose test

strips. For this reason, in 2015 our hospital organized

“e Universal Coverage (UC) provided free glucose

strips project for patients with T1DM”. However, een

months after initiation of this program, HbA

was

improved only in some patients in our clinic.

Another factor in addition to SMBG that contributes

to good glycemic control is motivation. Motivational

interviewing (MI), which was developed by Miller WR.

and Rollnick S., is a proven approach for working through

ambivalence and facilitating change of behavior.

has been widely used in adults to improve control of

addictive behaviors, such as reducing illicit drug use

and promoting smoking cessation.

7,8

During the last

decade, MI has been used in pediatric practice to promote

adherence to recommended treatment, including diabetes

management with variable results in reducing HbA

9-12

MI is a brief, goal-directed, patient-centered

counseling approach that was designed to help patients

increase intrinsic motivation and strengthen commitment

to change and improve via the exploration and resolution

of ambivalence. Patients are encouraged to develop

and recite their own self-motivational statement

(SMS) by facilitators. e six stages of change in MI

are described, as follows. The initial stage, which is

labeled pre-contemplation, is when the person is not

yet considering change. e next stage is the period of

contemplation, during which the person evaluates the

reasons for and against change. e third stage is when

the person reaches a state of determination where plans

for change are formulated. e person then takes action

in the fourth stage to eectuate the identied change

in behavior. If the change in behavior is successful, the

person then moves into the h stage, which is a state

of maintenance to sustain the change in behavior for the

long term. e last of the six stages occurs if and when

the patient relapse, which is dened as a return to any

of the previous behavior stages

Thus we conducted a 6-month randomized

controlled trial to evaluate the eectiveness of MI on

glycemic control, as measured by HbA

. e primary

outcome was HbA

at the 6-month follow-up. The

secondary objective was to evaluate diabetes knowledge

and self-care behavior. e secondary outcomes were

the scores of the diabetes knowledge test and the self-

care behavior questionnaire. We hypothesized that MI

would improve glycemic control, diabetes knowledge,

and self-care behavior in T1DM patients.

MATERIALS AND METHODS

Design and participants

Following randomization, participants received

either diabetes self-management education (DSME)

or DSME plus MI. Clinical sta and participants were

both aware of the group assignment. Participants were

recruited from the Outpatient Diabetes Clinic of the

Division of Endocrinology and Metabolism, Department

of Pediatrics, Siriraj Hospital during October 2016 to

March 2017. Subjects were T1DM patients aged 10-18

years with HbA

≥8% that were receiving free glucose

strips for at least 3 months. Patients who were receiving

medications that eect glycemic control, such as steroids

and switching of insulin regimen during this study, were

excluded.

Randomization was generated by random permuted

blocks with mixed block size. Group allocation results

were sealed in sequentially numbered opaque envelopes.

e person generated the allocation scheme had no

additional role in the study. The protocol for this

randomized controlled trial was approved by the Siriraj

Institutional Review Board (SIRB) of the Faculty of

Medicine Siriraj Hospital, Mahidol University, Bangkok,

ailand (COA no. Si 538/2016). Assent and written

informed consent was obtained from patients and their

parents/guardians, respectively.

The frequency of SMBG was assessed by

downloading glucometer data using accu-check 360º

soware. e information received were total numbers

of SMBG in the past 3 months and average numbers of

SMBG per day. Baseline characteristics and diabetes-

related data including age, gender, insulin regimen,

carbohydrate counting method, diabetes chronic

complication, hypertension and dyslipidemia were

collected. HbA

levels were measured prior to entering

the study and then at 3 and 6 months aer entering the

study.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

637

Original Article

SMJ

Motivational interviewing (MI)

MI sessions were conducted by 3 interventionists,

including 2 pediatric endocrinologists and a pediatric

endocrinology fellow) and a diabetes education nurse.

All interventionists were trained by experienced pediatric

and adult psychiatrists from Department of Pediatrics

and Department of Psychiatry, Faculty of Medicine

Siriraj Hospital, Mahidol University. e initial training

in MI includes hours of lecture, role play, case scenarios,

and practicing with actual patients in individual and

group sessions. Monthly discussion and supervision

among interventionists and a psychiatrist was continued

throughout the study.

MI in group session was performed at the beginning

of the study, and at 3 months aer entering the study. e

length of the two MI sessions was 45-60 minutes each.

MI by telephone call was performed individually at 1, 2,

4, and 5 months. Session dialogue included awareness

building, making choices, alternatives, goal-setting,

problem solving, and avoidance of confrontation. During

MI sessions, interventionists encouraged patients to

express self-motivational statements. e interventionists

would respond to patients according to their stage

of change. Interventionist responses included giving

information and feedback for the pre-contemplation

stage, discussion about pros and cons of undesired

behavior for the contemplation stage, giving menu and

promoting patient self-ecacy for the determination

phase, encouraging compliance and adherence for the

action stage, relapse prevention for the maintenance

stage, and recovery process for the relapse stage. e MI

manual was created by a pediatric psychologist. All MI

sessions were documented, and all documentation was

reviewed with a psychologist experienced in MI.

Diabetes self-management education (DSME)

DSME in group session was performed at the

beginning of the study, and 3 months later in both the

DSME and DSME plus MI groups. The session was

designed as an interactive lecture and workshop, with a

length of 60-90 minutes, and there were 8-10 patients in

each class session. DSME consists of a diabetes knowledge

component that was performed by physicians and a

nurse, and a nutritional component that was performed

by a nutritionist. Diabetes knowledge content included

basic knowledge about diabetes, self-monitoring blood

glucose, exercise with diabetes, hypo/hyperglycemia

management, insulin action, sick-day management, and

diabetes complications. Nutritional knowledge content

included healthy food, carbohydrate-containing food,

carbohydrate counting, food-exchange, and nutrition

facts. Food models were used for food exchange and

nutrition fact practice. Patients were encouraged to

participate in class by asking questions, giving examples,

and using case scenarios. We also focused on individual

problem-solving skills and insulin self-adjustment at

home.

Diabetes knowledge test

Diabetes knowledge test was performed at the

beginning and end of the study. We modied a multiple

choice test using 30 questions from the diabetes

knowledge test administered at the Siriraj Diabetes

Camp.

Questions covered 7 topics, including basic

diabetes knowledge, nutritional management and

carbohydrate counting, self-monitoring blood glucose,

exercise with diabetes, hypo/hyperglycemia management,

insulin treatment, and sick-day management.

Diabetes self-care behavior questionnaire

Diabetes self-care behavior questionnaire was given

at the beginning and the end of the study. A 38-question

standardized questionnaire that was developed by

Tachanivate P.

was used. e questionnaire covers 8

topics, including personal hygiene care, dietary control,

medical taking, physical activity, self-monitoring blood

glucose, problem solving, stress management, and

reducing risk of diabetes complications. e score was

reported as percentage of the mean, which was calculated

using the following equation: % of mean = (actual sore/

maximum score) x 100. A higher score indicates better

diabetes self-care behavior.

Statistical analysis

All data analyses were performed using SPSS

Statistics (SPSS, Inc., Chicago, IL, USA). Patient

characteristics were summarized using descriptive

statistics. Categorical data were compared using chi-

square test, and the results are presented as frequency

or percentage. Normally distributed continuous data

was compared using independent t-test, and the results

were presented as mean ± standard deviation (SD). Non-

normally distributed continuous data were compared

using Mann-Whitney U-test, and the results were given

as median and range (min, max). A p-value of less than

0.05 was considered statistically signicant for all tests.

RESULTS

A ow diagram of the study protocol is shown in

Fig 1. Of the 94 patients who received free glucose strips

from the UC program, 39 were eligible for this study.

ose patients were randomized into either the DSME

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

638

Lertbannaphong et al.

Figure 1: Flow diagram of the study protocol.

Eligible patients (n=94)

Excluded (n=55)

- not meeting inclusion criteria (n=54)

- received drug affected glycemic control (n=1)

Randomized (n=39)

DSME (n=20)

DSME with MI (n=19)

At 3 months (n=17)

At 6 months (n=17)

At 3 months (n=18)

At 6 months (n=18)

- lost to follow up (n=1)

- switching insulin regimen (n=2)

- drop out (n=1)

group (n=20) or the DSME plus MI group (n=19). One

patient in DSME group was lost to follow-up. One patient

in the DSME plus MI group declined to participate

aer randomization, before the rst visit. Two patients

in the DSME group were excluded due to the fact that

they switched insulin regimen during the study. e

remaining 35 patients (17 DSME, and 18 DSME plus

MI) completed the study.

Demographic characteristics

Patients in the DSME and DSME plus MI groups

were well matched for age (14.18±2.02 vs. 14.06±2.88

years, respectively), age at diagnosis (8.25±2.86 vs.

8.53±3.83 years), duration of diabetes [5.25 (0.83, 13.33)

vs. 5.08 (1, 14) years], and HbA

[10.3% (8.4, 14) vs.

9.45% (8, 14.6)]. ere were no signicant dierences

between groups for age, age at diagnosis, duration of

diabetes, or HbA

, as shown in Table 1. Counting

carbohydrate in grams was 30% and 22%; using basal

bolus regimen was 58% and 38% in the DSME and DSME

plus MI groups respectively.

Primary outcome: HbA

Baseline HbA

in the DSME and DSME plus MI

groups was 10.3 (8.4, 14) and 9.45 (8, 14.6), respectively

(p=0.204). At the end of the study, HbA

in the DSME and

DSME plus MI groups was 9.8 (7.4, 16.8) and 9.35 (7.8,

13.2), respectively (p=0.234). No signicant dierence

was observed for HbA

in each group compared between

pre-intervention and post-intervention (Table 2).

Diabetes knowledge score

Diabetes knowledge score compared between

baseline and 6 months increased signicantly in both

the DSME and DSME plus MI groups [19 (7, 24) to 21

(6, 25); p=0.012, and 18.5 (13, 24) to 21 (15, 28); p=0.001

respectively] (Table 3).

Fig 1. Flow diagram of the study protocol.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

639

Original Article

SMJ

TABLE 1. Baseline characteristics.

TABLE 2. HbA

levels compared between groups at baseline, 3 months, and 6 months.

DSME

(n=17)

DSME + MI (n=18) p-value

Age* (years) 14.18 ± 2.02 14.06 ± 2.88 0.892

Age at diagnosis* (years) 8.25 ± 2.86 8.53 ± 3.83 0.810

BMI * (kg/m

) 20.70 ± 3.70 20.66 ± 3.04 0.971

Total daily dose* (units/day) 1.26 ± 0.33 1.25 ± 0.35 0.934

Duration of DM**(years) 5.25 (0.83, 13.33) 5.08 (1, 14) 0.766

SMBG** (times/day) 2.00 (0.1, 4) 3.2 (0.07, 4.9) 0.013

HbA1C** (%) 10.3 (8.4, 14) 9.45 (8, 14.6) 0.204

Gender

male/female 10/7 9/9 0.600

Insulin regimen

basal bolus/non-basal bolus 10/7 7/11 0.472

Carbohydrate counting

grams/portion 5/12 4/14 0.627

Lipohypertrophy

yes/no 6/11 6/12 0.903

Diabetic nephropathy

yes/no 1/16 1/17 0.967

Diabetic retinopathy

yes/no 17/0 17/1 0.324

Hypertension

yes/no 0/17 0/18 -

Dyslipidemia

yes/no 8/9 13/5 0.129

* Independent t-test; mean ± SD, ** Mann-Whitney U-test; median (min, max),

Chi-square test

Abbreviations: DSME, diabetes self-management education; MI, motivational interviewing; BMI, body mass index.

DSME

(n=17)

DSME + MI (n=18) p-value*

HbA

at baseline 10.3 (8.4, 14) 9.45 (8, 14.6) 0.204

HbA

at 3 months 10.1 (7.4, 17.6) 9.35 (7.8, 14.5) 0.095

HbA

at 6 months 9.8 (7.4, 16.8) 9.35 (7.8, 13.2) 0.234

p-value** 0.813 0.459

*Compared between DSME and DSME + MI, **Compared between pre-intervention and post-intervention

Data expressed as median (min, max)

Abbreviations: DSME, diabetes self-management education; MI, motivational interviewing

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

640

Lertbannaphong et al.

Self-care behavioral score

e self-care behavioral score was signicantly

dierent at 6 months compared between the DSME and

DSME plus MI groups for the dietary control domain

[48.97 (32.65, 73.47) vs. 60.20 (30.61, 77.55); p=0.024],

and the medicine taking domain [52.38 (28.57, 78.57)

vs. 67.86 (47.62, 80.95); p=0.016] (Table 4). ere was no

signicant dierence between groups at 6 months for the

personal hygiene care, physical activity, self-monitoring,

TABLE 3. Pretest and post-test diabetic knowledge test results compared between groups.

DSME DSME + MI

(N=17) (N=18)

p-value*

Pretest score 19 (7, 24) 18.5 (13, 24) 0.816

Post-test score 21 (6, 25) 21 (15, 28) 0.326

p-value** 0.012 0.001

*Compared between DSME and DSME + MI, **Compared between pre-intervention and post-intervention

Data expressed as median (min, max)

Abbreviations: DSME, diabetes self-management education; MI, motivational interviewing

problem solving, stress management, or reducing risk

of diabetes complications domains.

Stage of MI

In DSME plus MI group, at the beginning of the

study, there was 1 patient in pre-contemplation, 8 in

contemplation, 9 in determination, and 0 in the action,

maintenance, and relapse stages. At the end of the study,

there were 12 patients in the action stage. (Table 5)

TABLE 4. Self-care behavioral score compared between groups post intervention.

Topics DSME DSME + MI

(% of mean) (% of mean)

p-value

Personal hygiene care 71.43 69.04 0.765

(28.57, 100) (33.33, 100)

Dietary control 48.97 60.20 0.024

(32.65, 73.47) (30.61, 77.55)

Medication taking 52.38 67.86 0.016

(28.57, 78.57) (47.62, 80.95)

Physical activity 57.14 64.29 0.337

(19.05, 90.48) (9.52, 85.71)

Self-monitoring 39.29 51.79 0.068

(17.86 , 78.57) (28.57 , 67.86)

Problem solving 48.21 50.89 0.895

(23.21, 78.57) (30.36, 71.43)

Stress management 47.62 40.47 0.640

(0, 71.43) (0, 71.43)

Reducing risk of diabetes complications 57.14 55.36 0.973

(35.71, 71.43) (35.71, 71.43)

Data expressed as median (min, max)

Abbreviations: DSME, diabetes self-management education; MI, motivational interviewing

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

641

Original Article

SMJ

TABLE 5. Stages of change in the motivational interviewing group (n=18).

Stage of Change Sessions (months)

0 1 2 3 4 5

Pre-contemplation 1 1 1 - - -

Contemplation 8 6 5 2 - 3

Determination 9 6 3 15 6 3

Action - 5 9 1 12 12

Maintenance & - - - - - -

relapse prevention

SMBG

Baseline SMBG frequency in the DSME and DSME

plus MI groups was 2 (0.1, 4) and 3.2 (0.07, 4.9) times/day,

respectively (p=0.013). At the end of the study, SMBG

frequency in the DSME group and the DSME plus MI

group was 2 (0, 4) and 3 (0, 4.7) times/day, respectively

(p=0.053). SMBG frequency data was downloaded from

the glucometer at baseline, 3- and 6-month time points.

DISCUSSION

We found no significant different in HbA

between the DSME and DSME plus MI groups at the

end of the study, as well as between pre- and post-

intervention. Diabetes knowledge score in both groups

was signicantly increased at the end of study. Self-care

behavioral score showed signicant improvement in 2

domains (dietary control and medicine taking) in the

DSME plus MI group. Transition to the action stage

increased from 0 to 12 patients, and the transition

occurred at approximately 4 months.

T1DM is a complex and chronic illness that requires

consistent adherence to treatment, psychological support,

and changes in lifestyle. Optimal glycemic control is not

easy to achieve, requires commitment to change, and

depends on multiple factors. Accurate carbohydrate

counting is crucial for precise insulin calculation. e

DAFNE Study Group reported signicant improvement

in HbA

at 6 months (p<0.0001) aer training patients

how to match their insulin dose to their food choice.

As demonstrated by Spiegel G, et al., T1DM patients

overestimated and underestimated carbohydrate

content, especially in mixed meals.

Moreover, less

than half of our patients were counting carbohydrates

as grams, not portions (Table 1). Calculating insulin

dose according to carbohydrate portion size may yield

a loser insulin dose than calculating according to gram

weight. is may result in a suboptimal dose of insulin

and poor glycemic control. Intensive patient education

in carbohydrate counting and encouraging patients to

count carbohydrates accurately may result in accurate

insulin calculation and improving of glycemic control.

Non-intensive insulin regimen could be a barrier to

achieving tight glycemic control. e American Diabetes

Association (ADA) recommends that individuals with

T1DM receive multiple daily insulin injections (three or

more injections per day of prandial insulin, and one to

two injections of basal insulin) or CSII.

HathoutEH,

et al. reported improvement in glycemic control with

intensive therapy as compared with conventional insulin

regimens.

Only 58% and 38% of our patients in the

DSME and DSME plus MI groups, respectively, used

intensive insulin therapy, so tight glycemic control may be

dicult to achieve. Likitmaskul S, et al. reported that ai

patients with T1DM had unsatisfactory glycemic control,

with a mean HbA

of 9.3±2.5%.

Achieving good

glycemic control in ai patients may be challenging

due to the fact that intensive diabetes treatment requires

glucose test strips, and glucose strips are not available

to all patients.

At the end of the intervention, the patients in the

DSME plus MI group did better in the dietary control

and medicine taking domains of self-care behavior than

those in the DSME group, however, the HbA

levels in

the DSME plus MI group did not improved. is may be

explained by the complexity of diabetes self-care, which

requires multiple tasks of management. eir self-care

behavior scores in other domains e.g. self-monitoring,

problem solving, stress management, etc. were relatively

low. No increase in frequency of SMBG and the fact that

majority of patients in DSME plus MI group were treated

with non-intensive insulin regimen might partly explain

the lack of improvement in glycemic control. Moreover,

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

642

Lertbannaphong et al.

psychological issue might be another factor. e burden

of having type 1 diabetes and the demands in managing

daily diabetes-related tasks can lead to negative emotions

or diabetes distress and depressive symptoms

which

can impact the glycemic control.

e duration of this study may have been too short

to observe the eect of MI. In the present study, transition

to the action stage of MI was observed at 4 months, so

measurement of HbA

at 6 months may be too early

to observe the eect of action that recently took place.

Channon S, et al. conducted a randomized controlled

trial that showed signicant reduction of HbA

in the MI

group compared to the control group at 12 months and

24 months, but not at 6 months.

In our study, HbA

was not signicantly decreased in any comparison. On

the other hand, MI may not aect glycemic control.

Walter G. suggested that verbal indices of MI to change

do not necessarily translate to actual change in response

to treatment if the patient does not also have the ability to

change, and that patient declarations should be regarded

as reecting the patient’s intent to change at that moment

as opposed to being considered a predictor of real change

in behavior.

Diabetes knowledge score was significantly

improved in both groups, which is similar to the nding

reported by Santiprabhob, et al. at 6 months post-DSME

at diabetes camp.

Despite improving of diabetes

knowledge score but the HbA

levels did not improved

may be due to the patients know the theory but did

not apply the knowledge gained to daily life problem

solving. From International Society for Pediatric and

Adolescent Diabetes (ISPAD) recommendation and

guidelines, educational interventions in children and

adolescents with diabetes have a benecial eect on both

glycemic control and psychosocial outcomes.

However,

it is important to evaluate patients’ ability to apply their

knowledge to their daily self-care.

e limitations of this study are short duration of

intervention, infrequency of motivation intervention

sessions and small sample size. Increasing the duration,

intensity, and frequency of MI sessions, as well as focusing

on individual ambivalence, may have positive impact

on MI stage progression and actual change. It should

also be considered that our small sample size may have

given our study insucient statistical power to identify

all signicant dierences in HbA

CONCLUSION

In conclusion, this study demonstrated that applying

MI to diabetes care does not lead to improvement in

glycemic control. However, diabetes knowledge was

improved in both groups, and self-care behavior score

was improved in some topics. e process and methods

for instilling and integrating diabetes knowledge, daily

diabetes management, and self-care behavior, as well

increasing the patient’s intrinsic motivation to change

and improve, requires further study. Further study

should also include a larger sample size, motivation that

is focused on individualized specic issues, and a longer

follow-up period.

ACKNOWLEDGEMENTS

e authors wish to thank the T1DM patients and

their families that participated in this study, Julaporn

Pooliam and Kanokwan Sommai for statistical analysis,

and Hathaichanok Tirapongporn and Sriwan ongpang

for nutritional teaching. is study was supported by a

Siriraj Routine to Research Fund, Faculty of Medicine

Siriraj Hospital, Mahidol University, Bangkok, ailand

(grant no. R015935055).

Conflict of interest: The authors hereby declare no

personal or professional conicts of interest relating to

any aspect of this study.

REFERENCES

1. Ziegler R, Heidtmann B, Hilgard D, Hofer S, Rosenbauer J,

Holl R. Frequency of SMBG correlates with HbA1c and acute

complications in children and adolescents with type 1 diabetes.

Pediatr Diabetes 2011;12:11-7.

2. Miller KM, Beck RW, Bergenstal RM, Goland RS, Haller MJ,

McGill JB, et al. Evidence of a strong association between

frequency of self-monitoring of blood glucose and hemoglobin

A1c levels in T1D exchange clinic registry participants. Diabetes

Care 2013;36:2009-14.

3. Patjamontri S, Khemaprasit K, Santiprabhob J, Nakavachara P,

Lertbannaphong O, Kiattisakthavee P, et al. e eect of early

diabetes self-management education on glycemic control in

children with type 1 diabetes. Southeast Asian J Trop Med Public

Health 2018;49:304-13.

4. Rewers MJ, Pillay K, de Beaufort C, Craig ME, Hanas R, Acerini

CL, et al. ISPAD Clinical Practice Consensus Guidelines 2014.

Assessment and monitoring of glycemic control in children

and adolescents with diabetes. Pediatr Diabetes 2014;15 Suppl

20:102-14.

5. Miller WR, Rollnick S. Meeting in the middle: motivational

interviewing and self-determination theory. Int J Behav Nutr

Phys Act 2012;9:25.

6. Li L, Zhu S, Tse N, Tse S, Wong P. Eectiveness of motivational

interviewing to reduce illicit drug use in adolescents: a systematic

review and meta-analysis. Addiction 2016;111:795-805.

7. Lai DT, Cahill K, Qin Y, Tang JL. Motivational interviewing for

smoking cessation. Cochrane Database Syst Rev 2010:CD006936.

8. Lindson-Hawley N, Thompson TP, Begh R. Motivational

interviewing for smoking cessation. Cochrane Database Syst

Rev 2015:CD006936.

9. Erickson SJ, Gerstle M, Feldstein SW. Brief interventions and

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

643

Original Article

SMJ

motivational interviewing with children, adolescents, and their

parents in pediatric health care settings: a review. Arch Pediatr

Adolesc Med 2005;159:1173-80.

10. Jones A, Gladstone BP, Lubeck M, Lindekilde N, Upton D, Vach

W. Motivational interventions in the management of HbA1c

levels: a systematic review and meta-analysis. Prim Care Diabetes

2014;8:91-100.

11. Sindelar HA, Abrantes AM, Hart C, Lewander W, Spirito A.

Motivational interviewing in pediatric practice. Curr Probl

Pediatr Adolesc Health Care 2004;34:322-39.

12. Suarez M, Mullins S. Motivational interviewing and pediatric

health behavior interventions. J Dev Behav Pediatr 2008;29:417-

28.

13. Santiprabhob J, Kiattisakthavee P, Likitmaskul S,

Chaichanwattanakul K, Wekawanich J, Dumrongphol H, et al.

Glycemic control, quality of life and self-care behavior among

adolescents with type 1 diabetes who attended a diabetes camp.

Southeast Asian J Trop Med Public Health 2012;43:172-84.

14. Tachanivate P. Factors inuencing quality of life in adolescents

with type 1 diabetes [Thesis]. Bangkok, Thailand: Mahidol

University; 2007.

15. DAFNE Study Group. Training in exible, intensive insulin

management to enable dietary freedom in people with type

1 diabetes: dose adjustment for normal eating (DAFNE)

randomised controlled trial. BMJ 2002;325:1-6.

16. Spiegel G, Bortsov A, Bishop FK, Owen D, Klingensmith

GJ, Mayer-Davis EJ, et al. Randomized nutrition education

intervention to improve carbohydrate counting in adolescents

with type 1 diabetes study: is more intensive education needed?

J Acad Nutr Diet 2012;112:1736-46.

17. Chiang JL, Kirkman MS, Lael LM, Peters AL. Type 1 diabetes

through the life span: a position statement of the American

Diabetes Association. Diabetes Care 2014;37:2034-54.

18. Hathout EH, Fujishige L, Geach J, Ischandar M, Maruo S, Mace

JW. Eect of therapy with insulin glargine (lantus) on glycemic

control in toddlers, children, and adolescents with diabetes.

Diabetes Technol er 2003;5:801-6.

19. Likitmaskul S, Wacharasindhu S, Rawdaree P, Ngarmukos C,

Deerochanawong C, Suwanwalaikorn S, et al. ailand diabetes

registry project: type of diabetes, glycemic control and prevalence

of microvascular complications in children and adolescents with

diabetes. J Med Assoc ai 2006;89 Suppl 1:S10-6.

20. Dejkhamron P, Santiprabhob J, Likitmaskul S, Deerochanawong

C, Rawdaree P, aravanij T, et al. Type 1 diabetes management

and outcomes: A multicenter study in Thailand. J Diabetes

Investig . 2021 Apr;12(4):516-526.

21. Channon SJ, Huws-omas MV, Rollnick S, Hood K, Cannings-

John RL, Rogers C, et al. A multicenter randomized controlled

trial of motivational interviewing in teenagers with diabetes.

Diabetes Care 2007;30:1390-5.

22. Waller G. e myths of motivation: time for a fresh look at

some received wisdom in the eating disorders? Int J Eat Disord

2012;45:1-16.

23. Santiprabhob J, Likitmaskul S, Kiattisakthavee P, Weerakulwattana

P, Chaichanwattanakul K, Nakavachara P, et al. Glycemic control

and the psychosocial benets gained by patients with type 1

diabetes mellitus attending the diabetes camp. Patient Educ

Couns 2008;73:60-6.

24. Lange K, Swi P, Pankowska E, Danne T. ISPAD Clinical Practice

Consensus Guidelines 2014. Diabetes education in children and

adolescents. Pediatr Diabetes 2014;15 Suppl 20:77-85.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

644

Manopchai amkhantho, M.D., FRCOG, M.Sc., Chenchit Chaychinda, M.D., M.Sc., Chanita Lertaroonchai, M.D.

Department of Obstetrics and Gynaecology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, ailand.

Vaginal Tablets of Metronidazole (750 mg) plus

Miconazole Nitrate (200 mg) versus Oral

Metronidazole (2 g) for Bacterial Vaginosis:

A Randomized Controlled Trial

ABSTRACT

Objective: To compare the cure rates, side eects, satisfaction, and recurrence rates of bacterial vaginosis (BV) in

women having vaginal tablets of metronidazole (750 mg) plus miconazole (200 mg) - the “NPF group” - versus

oral metronidazole (2 g) - the “MET group.”

Materials and Methods: is September 2019–March 2020 trial enrolled symptomatic women aged 18-45 years

diagnosed with BV based on Amsel’s criteria. Excluded were women who were immunocompromised; allergic to

metronidazole or miconazole; had BV episodes during the preceding 3 months; or had abnormal vaginal bleeding.

Aer randomization with a ratio 1:1, another vaginal swab was done for Nugent scoring. Two weeks later, the

evaluation using Amsel’s criteria and Nugent scores was repeated. Also, symptom resolution, side eects and

satisfaction were evaluated. Symptomatic resolution referred to 75% improvement in discharge, irritation, itching,

odor, and coital pain. At one and three months, subjective symptomatic recurrence was assessed by telephone.

Results: Data on 70 participants were analyzed (NPF, N=34; MET, N=36). eir average age was 32.3±7.9 years

(NPF, 34.1±8.1; MET, 30.6±7.3). Without statistical signicance, NPF had higher symptom resolution (67.7% vs

58.3%; P=0.420), cure rate by Amsel criteria (82.4% vs 77.8%; P=0.632), and cure rate by Nugent scoring (35.3% vs

16.9%; P=0.075). Both groups reported high satisfaction (NPF, 8.5±1.4; MET, 7.9±2.0; P=0.125). Side eects were

comparable, including appetite loss, metallic taste, nausea, and dizziness.

Conclusion: For BV treatment, both vaginal ovules containing metronidazole (750 mg) plus miconazole nitrate

(200 mg) and oral metronidazole (2 g) show comparable ecacy and side eects.

Keywords: Bacterial vaginosis; metronidazole; vaginal tablet (Siriraj Med J 2021; 73: 644-651)

Corresponding author: Chenchit Chayachinda

E-mail: chenchit.cha@mahidol.ac.th

Received 5 July 2021 Revised 18 August 2021 Accepted 19 August 2021

ORCID ID: https://orcid.org/0000-0002-0153-2231

http://dx.doi.org/10.33192/Smj.2021.83

INTRODUCTION

Bacterial Vaginosis (BV) is the most common cause

of abnormal vaginal discharge in women of childbearing

age.

It is a polymicrobial clinical syndrome characterized

by a profound change in vaginal microbiota from a

Lactobacillius- dominant state to anaerobic bacteria

of high diversity including Gardnerella vaginalis,

Atopobium vaginae, Mobiluncus spp, Prevotella spp, and

Thamkhantho et al.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

645

Original Article

SMJ

other BV-associated bacteria (BVAB).

2,3

is change

is accompanied by a rise in vaginal pH and increased

amines which produce typical odor. BV increases

the incidence of gynecologic and obstetric diseases,

including of spontaneous abortion, premature labour,

chorioamnionitis, and postpartum endometritis and

pelvic inammatory disease (PID).

4,5

Also, it associates

with a 2-3 fold increased risk of acquiring sexually

transmitted diseases (STDs) such as chlamydial infection,

gonorrhea, genital herpes and human immunodeciency

virus (HIV) infection.

6-8

The recommended treatment is metronidazole

or clindamycin.

In Thailand, oral metronidazole is

more commonly prescribed for BV. However, the

metronidazole 400 mg oral tablet taken 3 times day

commonly elicits adverse events such as a metallic taste,

nausea and vomiting resulting in poor compliance.

single oral dose of metronidazole 2gm has comparable

efficacy with a 7-day course

and previous studies

demonstrated less gastrointestinal side effects.

11-13

erefore, the 2 g metronidazole regimen is included

in the treatment guideline provided by the Australian

Sexual Health Alliance.

A novel vaginal ovule containing metronidazole

750 mg plus miconazole nitrate 200 mg (Neo-penotrans

Forte®; NPF, Exeltis, ailand) may be an alternative

treatment modality. Previous studies showed that an

oral metronidazole tablet can be used intravaginally for

treating women with BV.

10-11

e novel vaginal ovule,

which dissolves more readily, had been reported to

have high ecacy against BV, trichomoniasis and fungal

infection: 75-96%, 100%, and 82-90%, respectively.

15,16

Also, NPF can eectively cure mixed infection.

15,16

monthly 7-day course of NPF for up to 3-8 months

was found to prolong remission period among women

with recurrent BV.

Another benefit of this vaginal

suppository is that there have never been any serious

adverse events reported.

16,18

However, with dierent

backgrounds of the users, the efficacy is yet to be

validated in ai women. e present study aims to

compare the cure rate and symptomatic recurrence rate

between a 7 day-course of vaginal metronidazole 750 mg

plus miconazole nitrate 200 mg (NPF®) and a single

oral dose of 2 g oral metronidazole in treating BV. Side

eects of treatment and the women’s satisfaction were

also evaluated.

MATERIALS AND METHODS

is prospective open label randomized clinical

trial was carried out at the Department of Obstetrics

and Gynaecology, Faculty of Medicine Siriraj Hospital,

Mahidol University, during September 2019 – March

2020. The ethical approval was obtained from the

Siriraj Institutional Review Board (Si 222/2019). e

trial was registered at the ai Clinical Trials Registry

(TCTR20200902002).

Participants

All women who aged 18-45 years and were

diagnosed with BV by Amsel’s criteria were invited

to participate in the study. The diagnosis based on

Amsel’s criteria required at least 3 of the following

criteria: thin white/grey homogenous discharge,

pH>4.5, shy (amine) odor and the presence of clue

cells.

e exclusion criteria were women who: had

a history of allergy to metronidazole or miconazole,

were immunocompromised, had previous episodes

of BV within 3 months, had taken medications that

could disrupt the vaginal ecosystem e.g. anti-parasitic

drugs, oral antibiotics, any vaginal medications, anti-

coagulant, or disulram within the previous month, had

co-incidental other STIs or cervical pre-cancerous or

cancerous lesions, was currently pregnant or lactating,

or had abnormal uterine bleeding.

Intervention

All women who presented with abnormal vaginal

discharge at the Clinic were informed about the

study before entering examination rooms. en, they

underwent history-taking, pelvic examination and wet

preparation as a part of routine practice. e initial

evaluation using a microscope took around 5 minutes

for diagnosing BV based on Amsel’s criteria. e eligible

participants were explained in detail about the study by a

study nurse and signed the informed consent. Aer that,

another high vaginal swab was collected for gram stain

and consequently Nugent’s scoring system. Demographic

data, as well as pre-treatment symptom evaluation, were

then collected by the study nurse.

The randomization was computer-generated

using block-of-four with a ratio 1:1. Each participant

was allocated to receive either a 7-day course of vaginal

ovules containing metronidazole 750 mg plus miconazole

nitrate 200 mg (Neo-penotrans Forte®; NPF, Exeltis,

ailand) or a single dose of oral 2gm metronidazole

(Metrolex®, Siam Bheasach Co., Ltd., ailand).

e participants who were assigned to use vaginal

tablets were trained to perform a proper self-insertion of

vaginal tablets using a manikin. e single oral dose of

metronidazole was given 45 minutes following the oral

consumption of domperidone 10 mg at the Clinic on the

recruitment day. All participants were asked to comply

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

646

with the following prohibitions: no sexual activity, no

vaginal douching or cleansing, and avoiding alcoholic

beverages for one week following treatment.

All participants were scheduled for a 2-week

follow up visit. Clinical response, wet preparation and

gram stain for Nugent scoring system were done by

an investigator (Chayachinda C). Satisfaction and side

eects were evaluated by a study nurse. ose who had

persistent BV were treated with metronidazole 400 mg

per oral thrice a day for 7 days; or who had other

diagnosis were treated accordingly. At 1-month and

3-month post-treatment, all participants were telephoned

asking about symptomatic recurrence and/or additional

treatment.

Outcome measures

At 2-week follow-up, outcome measures were

clinical response, cure rate by Amsel’s criteria, cure rate

by Nugent’s scoring system, satisfaction and side eects.

Five key symptoms which were evaluated by a study

nurse including vaginal discharge, irritation, itching,

odor and coital pain, were graded into 0 (no/absent),

1 (mild), 2 (moderate) and 3 (severe). is results in

the ranging score from 0-15. At least 75% reduction of

the scores was dened as ‘clinical response’. Satisfaction

and side eects were also evaluated by the study nurse;

and being reported using 0-10 from ‘no’ to ‘maximum’.

The diagnosis of BV based on Amsel’s criteria

(Chayachinda C) required at least 3 of the following

criteria: thin white/grey homogenous discharge, pH

> 4.5, fishy (amine) odor and the presence of clue

cells.

e Nugent scoring was assessed by a blinded

microbiologist. e gram-stained slides, two for each

participant (rst visit and follow-up visit), were labeled

using code numbers; and were sent to the microbiologist

all at once. e scoring system was done by looking for

Lactobacillus spp., Gardnerella/ Bacteroides spp., and

curved gram variable rods. e scores ranged from 0-10

and are categorized into 3 groups: score 0-3 (normal),

score 4-6 (intermediate ora) and score 7-10 (BV).

Cure rate was dened as the conversion of BV to non-

BV, including reduction of Amsel’s criteria from ≥3 to

<3 criteria or that of Nugent score from ≥7 to <7.

At 1-month and 3-month post-treatment, the

telephone interview regarding current symptoms,

symptomatic recurrence and additional treatment was

done by a study nurse who was blinded to the allocation.

Sample size calculation and statistical analysis

Data analyses were carried out with STATA (version

12.0; Stata Corp., College Station, Texas, USA). To

describe the characteristics of the participants, mean

± standard deviation, n (%), and median with range

were used. For categorical variables, comparisons

were performed using the chi-squared test or Fisher’s

exact test. e distribution of each continuous variable

was tested using the Shapiro–Wilk test. Parametric

continuous variables were compared with Student’s

t-test, while nonparametric continuous variables were

analyzed with the Wilcoxon rank-sum test. Univariate

and multivariate logistic regression were used to

determine treatment ecacy. A P-value of < 0.05 was

deemed statistically signicant.

e sample size calculation was undertaken using

a formula that compares 2 proportions. A study by

Chaithongwongwatthana et al. showed that the ecacy

of a single dose of 2 g metronidazole to treat BV was

78.6%

, whereas another study by Regidor showed

that the cure rate in women using NPF was 98.1%.

e required sample size was determined to be 30 per

group (power, 70%; alpha, 0.05). As a lost-to-follow-up

rate of 30% was expected, 40 participants needed to be

recruited to each group.

RESULTS

Of 84 eligible participants, 70 came for the two-

week follow-up and were included in the analysis. (NPF

N=34, MET N=36) Sixty-nine and 60 were contacted

at one-month and three-month respectively (Fig 1).

The average age and body mass index (BMI) were

32.3±7.9 years and 21.6±3.8 kg/m

. Around half of all

participants reported regular external vaginal cleansing

aer urination and 8.6% reported ever vaginal douching.

Ten participants reported history of sexually transmitted

diseases (STD), including 5 genital warts, 3 genital herpes

and 2 PID. (Table 1)

All treatment outcomes at two weeks are shown in

Table 2. Aer adjusting for age, sexual experience and

number of lifetime sex partners, both NPF and MET

had comparable ecacy. Improvement of each symptom

is demonstrated in Table 2. Table 3 shows clinical

score, Amsel’s criteria and Nugent’s scores before the

intervention and 2-week post treatment. ere was no

dierence between NPF and MET except that the total

Nugent’s score in NPF group was signicantly lower at

2-week follow-up (5.4±1.9 vs 6.8±1.9, p=0.004). At the

two-week follow-up, four participants were diagnosed

with vaginal candidiasis (NPF 1/34, 2.9% vs MET 3/36,

8.3%, p=0.331); and none had BV.

Both groups reported high satisfaction (NPF

8.5±1.4 vs MET 7.9±2.0, p=0.125). No drug allergy was

reported but the side eects were as the followings: loss

Thamkhantho et al.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

647

Original Article

SMJ

of appetite/metallic taste (NPF 5/34, 14.7% vs MET 6/36,

16.7%, p=0.822), nausea (NPF 3/34, 8.8% vs MET 6/36,

16.7%, p=0.327), dizziness (NPF 4/34, 11.8% vs MET

5/36, 13.9%, p=0.791), vaginal irritation (NPF 3/34,

8.8% vs MET 6/36, 16.7%, p=0.327) and pelvic pain/

diarrhea (NPF 2/34, 5.9% vs MET 1/36, 2.8%, p=0.522).

No symptomatic, recurrent episode of BV was reported

at one-months and three-month telephone follow-ups.

DISCUSSION

Both vaginal tablets containing metronidazole

(750 mg) and miconazole nitrate (200 mg) and a

single dose of oral metronidazole (2 g) for treating

women with BV demonstrate comparable clinical

cure and laboratory-based cure rate. e high ecacy

demonstrated by NPF in the current investigation was

consistent with a meta-analysis done by Lugo-Miro

VI et al.

Our ndings support the potential of this

medication as a first-line treatment for BV. Given

that oral metronidazole has remarkable side eects of

gastrointestinal irritation when BV is localized dysbiosis

of the vaginal ecosystem, topical treatment modality

appears promising. Moreover, a vaginal biofilm of

G. vaginalis may limit the treatment ecacy of oral

metronidazole

whereas vaginal metronidazole may

better disrupt such protective factor.

Fig 1. Flow of the participants.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

648

TABLE 1. Characteristics of the participants (N=70).

Total (N=70) NPF (N=34) MET (N=36)

Age (years) 32.3±7.9 34.1±8.1 30.6±7.3

<25 15 (21.4) 4 (11.8) 11 (30.6)

25-35 32 (45.7) 16 (47.1) 16 (44.4)

>35 23 (32.9) 14 (41.2) 9 (25.0)

Body mass index (kg/m

) 21.6±3.8 21.5±3.7 21.7±3.8

<18 10 (14.3) 6 (17.7) 4 (11.1)

18- <25 47 (67.1) 21 (61.8) 26 (72.2)

≥25 13(18.6) 7(20.6) 6(16.7)

Being a mother 31 (44.3) 15 (44.1) 16 (44.4)

Abortion 13 (18.6) 5 (14.7) 8 (22.2)

Contraception

No 23 (32.9) 15 (44.1) 8 (22.2)

Condom 16 (22.9) 4 (11.8) 12 (33.3)

Oral contraceptive pill 21 (30.0) 9 (26.5) 12 (33.3)

Implant/ injectable contraception 4 (5.7) 3 (8.8) 1 (2.8)

No sexual experience 14 (20.0) 10 (29.4) 4 (11.1)

Number of lifetime sex partners 2 (0-4) 1 (0-4) 2 (0-4)

Vaginal hygiene

Cleansing 37 (52.9) 17 (50.0) 20 (55.6)

Douching 6 (8.6) 3 (8.8) 3 (8.3)

History of sexually transmitted diseases 10 (14.3) 3 (8.8) 7 (19.4)

*Wilcoxon Ranksum test

Abbreviations: NPF = neo-penotrans forte, MET = metronidazole

TABLE 2. Treatment outcomes (N=70).

Total NPF MET P cOR (95% CI) aOR* (95% CI)

Clinical cure rate 44/70 23/34 21/36 0.420 1.49 (0.56-3.97) 1.35 (0.46-3.99)

(62.9) (67.7) (58.3)

Amsel cure rate 56/70 28/34 28/36 0.632 1.33 (0.41-3.43) 5.79 (0.88-37.99)

(80.0) (82.4) (77.8)

Nugent cure rate 18/70 12/34 6/36 0.075 2.73 (0.89-8.39) 2.73 (0.83-8.96)

(25.7) (35.3) (16.9)

*adjusting for age, sexual experience, number of lifetime sex partners

Abbreviations: NPF = Neo-penotran forte®, MET = metronidazole, cOR = crude odd ratio, aOR = adjusted odd ratio

Thamkhantho et al.

Original Article

SMJ

Volume 73, No.9: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

649

TABLE 3. Comparison of symptoms at each visit.

Before treatment (N=70) 2 weeks (N=70) 1 month (N=69) 3 months (N=60)

NPF MET P NPF MET P NPF MET P NPF MET P

(n=34) (n=36) (n=34) (n=36) (n=33) (n=36) (n=22) (n=28)

Vaginal discharge

0 0 0 0.252 14 (41.2) 11 (30.6) 0.214 12 (36.4) 10 (27.8) 0.683 7 (31.8) 10 (35.7) 0.870

1 9 (26.5) 6 (16.7) 18 (52.9) 18 (50.0) 16 (48.5) 20 (55.6) 11 (50.0) 14 (50.0)

2 15 (44.1) 23 (63.9) 2 (5.9) 7 (19.4) 5 (15.2) 5 (13.9) 2 (9.1) 3 (10.7)

3 10 (29.4) 7 (19.4) 0 0 0 1 (2.8) 2 (9.1) 1 (3.6)

Vaginal irritation

0 1 (2.9) 0 0.397 27 (79.4) 22 (61.1) 0.114 25 (75.7) 29 (80.6) 0.964 17 (77.3) 22 (78.6) 0.248

1 7 (20.6) 8 (22.2) 7 (20.6) 11 (30.6) 5 (15.2) 4 (11.1) 4 (18.2) 3 (10.7)

2 10 (29.4) 16 (44.4) 0 3 (8.3) 2 (6.1) 2 (5.6) 0 3 (10.7)

3 16 (47.1) 12 (33.3) 0 0 1 (3.0) 1 (2.8) 1 (4.6) 0

Vaginal itching

0 8 (23.5) 8 (22.2) 0.962 26 (76.5) 24 (66.7) 0.325 28 (84.9) 29 (80.6) 0.613 17 (77.3) 22 (78.6) 0.627

1 10 (29.4) 11 (30.6) 8 (23.5) 10 (27.8) 5 (15.2) 6 (16.7) 5 (22.7) 5 (17.9)

2 12 (35.3) 14 (38.9) 0 2 (5.6) 0 0 0 1 (3.6)

3 4 (11.8) 3 (8.36) 0 0 0 1 (2.8) 0 0

Malodorous discharge

0 22 (64.7) 17 (47.2) 0.311 29 (85.3) 32 (88.9) 0.579 33 (100) 33 (91.7) 0.238 21 (95.5) 26 (92.9) 0.662

1 7 (20.6) 8 (22.2) 4 (11.8) 2 (5.6) 0 2 (5.6) 1 (4.6) 1 (3.6)

2 2 (5.9) 7 (19.4) 1 (2.9) 2 (5.6) 0 1 (2.8) 0 1 (3.6)

3 3 (8.8) 4 (11.1) 0 0 0 0 0 0

Coital pain

0 4 (11.8) 6 (16.7) 0.651 30 (88.2) 32 (88.9) 0.562 31 (93.9) 31 (86.1) 0.238 20 (90.9) 26 (92.9) 0.249

1 12 (35.3) 14 (38.9) 4 (11.8) 3 (8.3) 0 3 (8.3) 2 (9.1) 0

2 7 (20.6) 9 (25.0) 0 1 (2.8) 2 (6.1) 2 (5.6) 0 1 (3.6)

3 11 (32.4) 7 (19.4) 0 0 0 0 0 1 (3.6)

Total score 8(1-12) 8(3-11) 0.795 1(0-5) 2(0-8) 0.218 1(0-6) 1(0-9) 0.852 2(0-7) 1(0-8) 0.263

Abbreviations: NPF = Neo-penotran forte®, MET = metronidazole

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

650

CONCLUSION

Amsel’s criteria at two-week follow-up were not

dierent whereas Nugent’s scores were. Amsel’s criteria

partially belonged to clinical-based diagnostic methods

when Nugent’s scoring system was mainly a laboratory-

based method. The latter one was usually used as a

gold-standard diagnostic method in research study.

Obviously, Nugent’s scoring system had a better reection

of vaginal ecosystem as our previous study showed that,

based on this method, 20% of asymptomatic pregnant

women had BV; and tended to have worse pregnancy

outcomes.

erefore, the higher cure rate based on

Nugent’s scoring system in the present study suggested

the better resolution of vaginal dysbiosis following NPF

treatment.

Contrasting to previous studies, none of the

participants in both groups reported symptomatic

recurrence. A longer course of metronidazole results in

a lower incidence of recurrence at 1 month.

Moreover,

a long-term study in Australian women found that over

50% of BV-diagnosed women receiving or not receiving

adjuvant treatment reported recurrent BV episodes at

their 6-month follow-up.

is may be partly explained

by the fact that practice to achieve and maintain vaginal

hygiene were emphasized during participant counselling,

such as avoiding excessive cleansing, vaginal douching,

and the wearing of tight garments. Additionally,

the follow-up period was short; and BV can also be

asymptomatic.

Compatible with previous studies, the combination

of metronidazole and miconazole in a vaginal tablet

appear not to cause severe adverse events; and mitigate

the coincidence of BV and vaginal candidiasis (VC).

15,16

e coincidence of BV and VC and VC as a consequence

of BV have been evident. e coincidence was reported in

15.2% of American non-pregnant women

and 13.3% of

ai pregnant women.

Furthermore, the administration

of miconazole (200 mg) vaginal suppositories for 3 days

is a recommended regimen for treating women with

vaginal candidiasis (VC) treatment guidelines.

9,23

As a

consequence, pseudohyphae was detected around three

times higher in the MET group at 2-week.

Although none of the participants required

additional BV treatment within 3 months post-treatment,

a quarter of the participants reported a malodorous

vaginal discharge or fishy odor following sexual

intercourse. is supports the dynamic and self-heal of

vaginal microbiome. Despite the fact that seminal uid

can precipitate the incidence of BV, the resumption of

individual participant’s normal life is the goal of BV

TABLE 4. Clinical score, Amsel’s criteria and Nugent’s score before intervention and at 2-week follow-up (N=70).

Before intervention 2-week follow-up

NPF (n=34) MET (n=36) P NPF (n=34) MET (n=36) P

Sum of clinical scores 8(1-12) 8(3-11) 0.795 1(0-5) 2(0-8) 0.218

Amsel’s criteria

Homogeneous whitish discharge 17 (50.0) 22 (61.1) 0.350 11 (32.4) 11 (30.6) 0.871

pH >5 34 (100) 36 (100) 1.000 7 (20.6) 15 (41.7) 0.058

Positive whiff test 29 (85.3) 34 (94.4) 0.202 6 (17.7) 8 (22.2) 0.632

Presence of clue cells 34 (100) 35 (97.2) 0.328 7 (20.6) 11 (30.6) 0.340

Total 3 (3-4) 3 (3-4) 0.342 1 (0-3) 1 (0-3) 0.902

Nugent’s score

Normal (score <4) 0 0 0.653 8 (23.5) 4 (11.1) 0.032

 Intermediateora(4-6) 5(14.7) 4(11.1)  12(35.3) 6(16.7)

Bacterial vaginosis (>6) 29 (85.3) 32 (88.9) 14 (41.2) 26 (72.2)

Total score 7.6±1.0 7.8±0.9 0.291 5.4±1.9 6.8±1.9 0.004

Abbreviations: NPF = Neo-penotran forte®, MET = metronidazole,

Thamkhantho et al.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

651

Original Article

SMJ

treatment. As such, other risk factors of BV occurrence

should be serious taken into consideration such as

excessive vulvar cleansing and vaginal douching.

e strength of this study is its randomized design.

Although the participants could not be blinded, the

investigators who evaluated the outcome measures and

the statistician were. e limitations of the study were

its small sample size and short follow-up period. One

of the biggest concerns among women with BV is the

frequent recurrence of the condition. Only symptomatic

recurrence is approached at 1- and 3-month while BV

can be asymptomatic. Another limitation was that the

administrative route and the duration of treatment

period of the two assigned treatment were dierent.

Provide that double-dummy, placebo-controlled design

and daily self-record of symptoms had been applied, the

study would have had less bias in outcome measurement

but probably more advantage of the novel treatment.

In conclusion, for BV treatment, both vaginal tablets

containing metronidazole (750 mg) plus miconazole

nitrate (200 mg) and oral metronidazole (2 g) show

comparable ecacy and side eects.

REFERENCES

1. Chayachinda C, amkhantho M, Chalermchockcharoenkit

A, Neungton C, ipmontree W. Characteristics of Clients

at the Siriraj Female STD Clinic during 2011-2015. Siriraj

Medical Bulletin 2018;11:182-9.

2. Srinivasan S, Fredricks D. e human vaginal bacterial biota

and bacterial vaginosis. Interdiscip perspect Infect Dis 2008:

750479.

3. Hill G. e microbiology of bacterial vaginosis. Am J Obstet

Gynecol 1993;169:450-54.

4. Haggerty CL, Hillier SL, Bass DC, Ness RB, Evaluation PID,

Clinical Health study i. Bacterial vaginosis and anaerobic

bacteria are associated with endometritis. Clin Infect Dis 2004;

39:990-5.

5. Sharma H, Tal R, Clark NA, Segars JH. Microbiota and pelvic

inammatory disease. Semin Reprod Med 2014;32:43-9.

6. Atashili J, Poole C, Ndumbe PM, Adimora AA, Smith JS.

Bacterial vaginosis and HIV acquisition: a meta-analysis of

published studies. AIDS 2008;22:1493-501.

7. Cherpes TL, Meyn LA, Krohn MA, Lurie JG, Hillier SL.

Association between acquisition of herpes simplex virus type

2 in women and bacterial vaginosis. Clin Infect Dis 2003;37:

319-25.

8. Nardis C, Mosca L, Mastromarino P. Vaginal microbiota and

viral sexually transmitted diseases. Ann Ig 2013;25:443-56.

9. Workowski KA, Bolan GA, Centers for Disease C, Prevention.

Sexually transmitted diseases treatment guidelines, 2015.

MMWR Recomm Rep 2015;64:1-137.

10. Lugo-Miro VI, Green M, Mazur L. Comparison of dierent

metronidazole therapeutic regimens for bacterial vaginosis.

A meta-analysis. JAMA 1992;268:92-5.

11. Brandt M, Abels C, May T, Lohmann K, Schmidts-Winkler I,

Hoyme U. Intravaginally applied metronidazole is as eective

as orally applied in the treatment of bacterial vaginosis, but

exhibits signicantly less side eects. European Journal of

Obstetrics & Gynecology and Reproductive Biology 2008;

141:158-62.

12. Chaithongwongwatthana S, Limpongsanurak S, Sitthi-Amorn C.

Single hydrogen peroxide vaginal douching versus single-

dose oral metronidazole for the treatment of bacterial vaginosis:

a randomized controlled trial. J Med Assoc ai 2003;86:S379-

84.

13. Mitchell C, Hitti J, Agnew K, Fredricks D. Comparison of oral

and vaginal metronidazole for treatment of baterial vaginosis

in pregnancy: impact on fastidiuos bacteria. BMC Infectious

Diseases 2009;9.

14. Australian Sexual Health Alliance. Bacterial vaginosis. Australian

STI management guidelines for use in primary care2018.

15. Peixoto F, Camargos A, Duarte G, Linhares I, Bahamondes L,

Petracco A. Efficacy and tolerance of metronidazole and

miconazole nitrate in treatment of vaginitis. International

Journal of Gynecology and Obstetrics 2008;102:287-92.

16. Regidor P, Ozyurt E, Toykuliyeva M, et al. Treatment and

prevention of trichomoniasis, bacterial vaginosis and candidiasis

with a new 7-day regime containing metronidazole and

miconazole in a single vaginal pessary. International Journal

of Medical Device and Adjuvant Treatments 2018;1:e118.

17. Sobel J, Kaur N, Woznicki N, et al. Conventional oral and

secondary high dose vaginal metronidazole therapy for

recurrent bacterial vaginosis: clinical outcomes, impacts of sex

and menses. Infection and Drug Resistance 2019;12:2297-307.

18. Aguin T, Akins R, Sobel J. High-dose vaginal maintenance

metronidazole for recurrent bacterial vaginosis: a pilot study.

Sexually Transmitted Diseases 2014;41:290-1.

19. Mohammadzadeh F, Dolatian M, Jorjani M, Alavi Majd H.

Diagnostic value of Amsel’s clinical criteria for diagnosis of

bacterial vaginosis. Glob J Health Sci 2014;7:8-14.

20. Nugent RP, Krohn MA, Hillier SL. Reliability of diagnosing

bacterial vaginosis is improved by a standardized method of

gram stain interpretation. J Clin Microbiol 1991;29:297-301.

21. Verwijs M, Agaba S, Darby A, van de Wijgert J. Impact of oral

metronidazole treatment on the vaginal microbiota and

correlates of treatment failure. American Journal of Obstetrics

and Gynecology 2020;222:157.

22. Tachawatcharapunya S, Chayachinda C, Parkpinyo N. e

prevalence of bacterial vaginosis in asymptomatic pregnant

women during early third trimester and the pregnancy

complications. ai Journal of Obstetrics and Gynaecology

2017;25:96-103.

23. British Association for Sexual Health and HIV. British

Association for Sexual Health and HIV national guideline for

the management of vulvovaginal candidiasis (2019). 2019.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

652

Pavarisa Choosuk, M.D.*, Jarurin Pitanupong, M.D.*, Chitkasaem Suwanrath, M.D., M.Med.Sci.**

*Department of Psychiatry, **Department of Obstetrics and Gynaecology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, 90110,

ailand

Prevalence and Factors Associated with Antepartum

Depression: A University Hospital-Based

ABSTRACT

Objective: is study aimed to assess the prevalence of and factors associated with antepartum depression among

ai women.

Materials and Methods: All pregnant women attending the Antenatal Care Clinic at Songklanagarind Hospital

from June to August 2020 were invited to participate and evaluated through self-administered questionnaires.

Multivariate logistic regression models were used for the data analysis in order to control for potential confounders.

Results: 435 women were in their rst, second, and third trimester of pregnancy (20.2 %, 39.5 %, and 40.2 %,

respectively). e majority of them reported normal Rosenberg’s Self-esteem Scale scores (83.4 %) and a high level

of perceived social support (74.5 %). Moreover, according to the Edinburgh Postnatal Depression Scale (EPDS)

scores, the prevalence of antepartum depression was 10.6 %. A multivariate logistic regression analysis showed that

factors associated with antepartum depression were second trimester of pregnancy, survival and below-survival

levels of income, unintended pregnancy, and low level of self-esteem.

Conclusion: One-tenth of pregnant ai women suered from depression. Advanced gestational age, low income,

unintended pregnancy, and low self-esteem were signicant factors associated with antepartum depression.

Keywords: Antepartum; associated factors; depression; pregnancy; prevalence (Siriraj Med J 2021; 73: 652-660)

Corresponding author: Jarurin Pitanupong

E-mail: pjarurin@medicine.psu.ac.th

Received 18 May 2021 Revised 19 August 2021 Accepted 19 August 2021

ORCID ID: https://orcid.org/0000-0001-9312-9775

http://dx.doi.org/10.33192/Smj.2021.84

INTRODUCTION

Depression is a common psychiatric disorder.

1,2

The World Health Organization (WHO) reported

depression as the third cause of global burden of disease

in 2004 and the second cause in 2020, and it estimates

depression will be the leading cause of “lost years of

healthy life” worldwide by 2030.

Women are twice as

likely to develop depression, especially during pregnancy,

due to the physical, physiological, and hormonal changes

they undergo.

Antepartum depression is characterized by

depressive symptoms like low mood or sadness, feeling

of worthlessness, loss of interest or pleasure, sleep

disturbance, and changes in appetite

; it aects both the

maternal health and family life of women.

Moreover, it is

oen considered to be associated with adverse pregnancy

outcomes such as preterm birth and low birth weight.

6-8

Untreated antepartum depression leads to postpartum

depression

, resulting in malnourishment and a poor

relationship between mother and child.

Systematic reviews have estimated the overall

prevalence of antepartum depression at around 6.2 - 9.2 %

in high-income countries and 19.2 - 23.5 % in low-to

middle-income countries.

11-13

e onset of antepartum

depression most commonly occurs during the third

trimester.

e potential risk factors of antepartum

Choosuk et al.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

653

Original Article

SMJ

depression can be categorized into four aspects-the

personal background, obstetric, psychological or

psychiatric, and social and family aspects. e personal

background and obstetric aspects involve factors such

as parity

, advanced maternal age

16,17

, unintended

pregnancy

18,19

, and obstetric complications.

In addition,

low self-esteem

, experiencing negative life events

history of depressive symptoms

15,21

, history of illness

during the previous month

22,23

, and family history of

psychiatric disorders

, which belong to the psychological

or psychiatric aspect, are signicant factors associated

with antepartum depression.

Moreover, in regards to the social and family

aspect, factors such as low socioeconomic status

, lack of

partner support

or poor marital relationship

, history

of intimate partner violence

11,12

, dierences in religion

and/or culture between partners

, having a partner with

a smoking and drinking habit

15,18

, dicult relationship

with the mother-in-law, lack of parenting knowledge

and baby gender selection or gender preference due to

the family-related circumstances

17,23

are potential risk

factors for persistent depression during pregnancy.

The risk factors associated with antepartum

depression may dier among countries. Limited data

concerning these issues are available from Asian

countries. In ailand, only one study on this topic has

been conducted in the past ten years (2010). It reported

a 10.3 % prevalence of antepartum depression, but it

did not explore its associating risk factors.

erefore,

we conducted this study to determine the prevalence

of antepartum depression across gestational ages and

identify its associating risk factors. is research may

provide useful information for both psychiatrists and

obstetricians in their eorts to establish antepartum

depression screening programs aimed at the early

detection, prevention, and timely management of severe

depression among pregnant women.

MATERIALS AND METHODS

Aer approval by the Ethics Committee of the

Faculty of Medicine, Prince of Songkla University (REC:

63-083-3-4), this cross-sectional study was conducted

at Songklanagarind Hospital, which is an 800-bed

university hospital that serves as a tertiary referral center

in Southern ailand. All methods were carried out

following relevant guidelines and regulations. Written

informed consent was obtained from all participants

before enrollment. All pregnant women, who were at

least 18 years old and attended the hospital’s Antenatal

Care Clinic (ANC) from June to August 2020, were

invited to participate in this study. We included all the

pregnant women who were able to complete all parts of

the questionnaires. ose with a self-reported history

of psychiatric illness and who did not complete the

questionnaires in full, declined to participate in the

study, or could not read or write the ai language,

were excluded. e sample size was calculated based on

an estimated prevalence (P = 0.1, alpha = 0.05 and d =

0.03); at least 395 participants were deemed necessary

for enrollment.

All eligible pregnant women were asked to

answer the self-reported questionnaires anonymously.

en the researcher informed the participants about

the results immediately aer their completion. If they

had EPDS scores of greater than or equal to 11, which

was considered a positive screening for depression, the

psychiatrists in the research team performed in-depth

interviews by using DSM-V criteria for denite diagnosis

and proper management.

Measures

The data collection tools consisted of the

demographic data questionnaire, the Rosenberg’s Self-

esteem Scale, the Multidimensional Scale of Perceived

Social Support

1) e demographic characteristics questionnaire

consisted of questions enquiring about the woman’s age,

gestational age, educational level, occupation, religion,

healthcare coverage scheme, marital status, family

income, pregnancy intention, gravidity, parity and

abortion, obstetric complications, history of substance

abuse, underlying medical illness, and family and partner

proles.

2) Rosenberg’s Self-esteem Scale-ai version

consisted of 10 questions related to positive and negative

feelings about themselves. All items were rated via a

4-point Likert scale ranging from “0” (strongly disagree)

to “3” (strongly agree). e total score ranged from

0 - 30; a score greater than 25 indicated a high level of

self-esteem, scores in the 15 - 25 range represented a

normal level of self-esteem, and the ones less than 15

signied a low level of self-esteem.

A Cronbach’s alpha

coecient of 0.86 has been reported for this tool.

3) e Multidimensional Scale of Perceived Social

Support (MSPSS)-ai version

comprised 12 questions

grouped into 3 subcategories: family, friends, and

signicant others. All items were rated using a 7-point

Likert scale ranging from “1” (very strongly disagree)

to “7” (very strongly agree). The total score ranged

from 12 - 84, and the score of each subpart ranged from

1 to 7; a score of 1 - 2.9 was indicative of low support

level, a score in the 3 - 5 range was deemed to represent

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

654

Choosuk et al.

moderate-level support, and those from 5.1 to 7 were

considered to represent a high level of support.

e

Cronbach’s alpha coecient for this questionnaire has

been reported to be 0.91.

4) The Edinburgh Postnatal Depression Scale

(EPDS)-ai version

consisted of 10 questions. All

items were rated using a 3-point scale. e total score

ranged from 0 - 30; the cut-o score of > 11 was the

optimal cut-o points for screening both antepartum and

postpartum depression according to previous study.

30,31

e Cronbach’s alpha, sensitivity, and specicity values

for this tool have been determined to be 0.87, 100.0 %,

and 92.6 %, respectively.

Statistical methods

Descriptive statistics, the chi-square test, the

Fisher’s exact test, and multivariate logistic regression

analyses were used in the data analysis. A p-value of

< 0.05 was considered to represent statistical signicance.

RESULTS

Demographic characteristics

A total of 447 pregnant women attended the

Antenatal Care Clinic during the study period, and 435

of them (97.3 %) agreed to complete the questionnaires.

Most women were in the third and second trimesters.

Overall, the mean (SD) maternal age was 32.0 (5.2)

years, and the mean (SD) gestational age was 23.8 (10.3)

weeks. e majority of the participants were Buddhist

(69.0 %), had a high educational level (72.2 %), had a

Bachelor’s degree or higher), were employees (36.3 %),

and had a low monthly household income (66.9 %).

Besides, most women were multigravida (65.3 %) and

had planned their pregnancies (77.7 %). About one-

fourth of them had experienced pregnancy complications

such as gestational diabetes mellitus, fetal anomaly,

and threatened abortion during the current pregnancy.

However, the majority of participants had no underlying

medical illnesses (85.7 %). Moreover, only 10 participants

(2.3 %) had a family history of psychiatric illness such as

major depressive disorder, persistent depressive disorder,

generalized anxiety disorder, and schizophrenia.

Self-esteem

Using the Rosenberg’s Self-esteem Scale-Thai

version, the mean (SD) total score of self-esteem was 21.4

(3.3). e majority of participants had a normal level of

self-esteem (83.4 %); only 6 participants had low self-

esteem (1.4 %), and 15.2 % had high self-esteem (Table 1).

Perceived social support

e Multidimensional Scale of Perceived Social

Support (MSPSS)-ai version revealed a mean (SD)

total score of 69.3 (9.6) for perceived social support. e

majority of participants had a high level of perceived

social support (74.5 %), and only 2 participants (0.5 %)

reported having a low level of perceived social support

(Table 1).

TABLE 1. EPDS, self-esteem, and perceived social support scores categorized by trimester (N = 435).

Trimester; number (%)

Total First Second Third Chi

Questionnaire measures

(N = 435) trimester trimester trimester P-value

(n = 88) (n = 172) (n = 175)

EPDS

0.095

< 11 389 (89.4) 81 (92.0) 147 (85.5) 161 (92.0)

 ≥11 46(10.6) 7(8.0) 25(14.5) 14(8.0)

Self-esteem

0.293*

Low 6 (1.4) 2 (2.3) 1 (0.6) 3 (1.7)

Normal 363 (83.4) 77 (87.5) 139 (80.8) 147 (84.0)

High 66 (15.2) 9 (10.2) 32 (18.6) 25 (14.3)

MSPSS

0.530*

Low 2 (0.5) 0 (0) 0 (0) 2 (1.1)

Moderate 109 (25.1) 19 (21.6) 47 (27.3) 43 (24.6)

High 324 (74.5) 69 (78.4) 125 (72.7) 130 (74.3)

Note:

EPDS = the Edinburgh Postnatal Depression Scale;

Self-esteem = the Rosenberg’s Self-esteem Scale;

MSPSS = the Multidimensional

Scale of Perceived Social Support

* Fisher's exact test

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

655

Original Article

SMJ

Prevalence of antepartum depression

Using the Edinburgh Postnatal Depression Scale

(EPDS)-ai version, the mean (SD) total score was 5.8

(3.9). e prevalence of antepartum depression according

to EPDS was 10.6 %. e prevalence of antepartum

depression in the rst, second and third trimesters was

1.6 %, 5.7 %, and 3.2 %, respectively. However, aer

in-depth interviews by psychiatrists using the DSM-V

criteria for major depressive disorder, it was revealed

that only 3 participants (0.7 %) had major depressive

disorder, whereas the remaining 43 participants (9.9 %)

had adjustment disorder with depressed mood.

Factors associated with antepartum depression

To identify factors associated with antepartum

depression, demographic characteristics, self-esteem,

and perceived social support were included in the

univariate analysis. Variables with p-values of less

than 0.2 from the univariate analysis were included in

the nal model of the multivariate logistic regression

analysis. These factors were trimester of pregnancy,

educational level, occupation, health coverage, income,

pregnancy intention, complications during current

pregnancy, family history of psychiatric illness, partner’s

educational level, partner’s underlying diseases, self-

esteem, and perceived social support (Table 2). e

multivariate analysis showed that trimester of pregnancy,

income, pregnancy intention, and self-esteem level were

signicant factors associated with antepartum depression

(Table 3).

With regard to the factors associated with

antepartum depression, women in the second trimester

faced a 2.7 times increased risk for antepartum depression

compared to those in the first trimester. Likewise,

compared to the pregnant women with a high income

level, those who reported survival and below-survival

levels of income experienced a 3.2 and 5.4 times

increased risk for antepartum depression, respectively.

Similarly, unintended pregnancy was associated with a

2.3 times higher risk for antepartum depression than

intended pregnancy. On the other hand, a normal level

of self-esteem was found to exert a protective inuence

against antepartum depression (Table 3).

DISCUSSION

This study indicated that the prevalence of

depression during the antepartum period assessed via

EPDS was 10.6 %. Comparing the prevalence of our

study with those reported by previous researches, it

was similar to the one found by a study from ailand

(10.3 %) even if using the dierent tools.

us, we

can conclude that for the screening of antepartum

depression we can use both EPDS (our study) and

Two-question screening for depression, ai-version

(previous study) for screening antepartum depression

in ANC. However, our rate was lower than those found

in low-to middle-income countries (19.2 - 23.5 %) but

higher than those reported in high-income countries

(6.2 - 9.2 %).

11-13

ese dierences might be due to the

dierences in study instruments, population ethnicity,

family background, and gestational age at enrollment.

The factors identified to associate with antepartum

depression were advanced gestational age, low monthly

household income, unintended pregnancy, and low

self-esteem. Surprisingly, gestational age in the second

trimester has not been reported before as a signicant

factor associated with antepartum depression. is might

be due to a change in appearance and body image, along

with quickening of the baby. Moreover, obstetricians

can detect fetal abnormalities from ultrasound as well

as various pregnancy problems. All these abnormalities

can lead to anxiety or stressful in pregnant women.

Regarding family income, compared to pregnant

women with a high level of income, those with survival

or below-survival income levels had a significantly

increased risk of experiencing antepartum depression.

This result was similar to the findings reported by

previous studies.

18,22

An explanation for this could be the

possibility that economic problems can result in stress

and anxiety, especially for women who play an important

role in family care, provide food for family members,

pay for various family expenses and antenatal care, and

is expected to shoulder the cost of other medical care in

the future. Nevertheless, it was women’s point of view

which ai people normally underestimate their income.

Similarly, unintended pregnancy was associated

with twice the likelihood of antepartum depression

compared to intended pregnancy. This finding was

consistent with those of previous studies conducted

in Jordan and Kenya.

18,19

Unplanned pregnancies can

lead to concerns about oneself, the family, and the

baby’s future. Furthermore, unintended pregnancy was

high in our study because of high ratio of Islamism in

Southern ailand that they cannot do any contraception

according to the principles of their religious.

Conversely, normal self-esteem protected pregnant

women from antepartum depression. is nding was

in line with the results reported by a study conducted

in Jordan.

Women with a higher level of self-esteem

tend to feel more valuable than those with a lower level

of self-esteem. erefore, the women with a normal level

of self-esteem may feel less fearful or insecure and also

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

656

Choosuk et al.

TABLE 2. Demographic characteristics, self-esteem, and perceived social support categorized by EPDS score (N = 435).

EPDS

; number (%)

Variables

Total

< 11 ≥ 11

Chi

(N = 435)

(n = 389) (n = 46)

P-value

Age (years) 0.622

< 35 293 (67.4) 264 (67.9) 29 (63.0)

 ≥35 142(32.6) 125(32.1) 17(37.0)

Trimester 0.095

First 88 (20.2) 81 (20.8) 7 (15.2)

Second 172 (39.5) 147 (37.8) 25 (54.3)

Third 175 (40.2) 161 (41.4) 14 (30.4)

Educational level 0.197

Below Bachelor’s degree 121 (27.8) 104 (26.7) 17 (37.0)

Bachelor’s degree and higher 314 (72.2) 285 (73.3) 29 (63.0)

Occupation 0.159

Employee/self-employed 199 (45.7) 175 (45) 24 (52.2)

Government employee 158 (36.3) 147 (37.8) 11 (23.9)

Housewife/unemployed 78 (17.9) 67 (17.2) 11 (23.9)

Religion 0.414*

Buddhism 300 (69) 272 (69.9) 28 (60.9)

Islam 132 (30.3) 114 (29.3) 18 (39.1)

Christianity 3 (0.7) 3 (0.8) 0 (0.0)

Health coverage 0.093

 CivilServantMedicalBenetScheme(CSMBS) 152(34.9) 140(36) 12(26.1)

Universal Coverage Scheme (UCS) 45 (10.3) 36 (9.3) 9 (19.6)

Social Security Scheme (SSS) 101 (23.2) 88 (22.6) 13 (28.3)

Out-of-pocket 137 (31.5) 125 (32.1) 12 (26.1)

Marital status 0.637*

Single/divorced 13 (3) 11 (2.8) 2 (4.3)

Married 422 (97) 378 (97.2) 44 (95.7)

Monthly household income (Baht/month) 0.058

< 30,000; low income 291 (66.9) 254 (65.3) 37 (80.4)

 ≥30,000;highincome 144(33.1) 135(34.7) 9(19.6)

Standard of living < 0.001

High 222 (51) 211 (54.2) 11 (23.9)

Survival 183 (42.1) 156 (40.1) 27 (58.7)

Below survival 30 (6.9) 22 (5.7) 8 (17.4)

Family structure > 0.99

Nuclear 306 (70.3) 274 (70.4) 32 (69.6)

Extended 129 (29.7) 115 (29.6) 14 (30.4)

Pregnancy intention 0.002

Unintended 97 (22.3) 78 (20.1) 19 (41.3)

Intended 338 (77.7) 311 (79.9) 27 (58.7)

Parity 0.878

Nulliparity 151 (34.7) 136 (35) 15 (32.6)

Multiparity 284 (65.3) 253 (65) 31 (67.4)

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

657

Original Article

SMJ

EPDS

; number (%)

Variables

Total

< 11 ≥ 11

Chi

(N = 435)

(n = 389) (n = 46)

P-value

Complications during this pregnancy 84 (19.3) 70 (18) 14 (30.4) 0.068

Number of children 0.568

0 - 1 173 (39.8) 157 (40.4) 16 (34.8)

> 1 262 (60.2) 232 (59.6) 30 (65.2)

Complications during previous pregnancies 106 (24.4) 91 (23.4) 15 (32.6) 0.232

Previous miscarriage 89 (20.5) 76 (19.5) 13 (28.3) 0.233

Smoking 3 (0.7) 2 (0.5) 1 (2.2) 0.285*

Alcohol consumption 47 (10.8) 41 (10.5) 6 (13) 0.615*

Underlying medical illness 62 (14.3) 54 (13.9) 8 (17.4) 0.674

Family history of psychiatric illness 10 (2.3) 7 (1.8) 3 (6.5) 0.078*

Self-esteem

< 0.001

Low 6 (1.4) 2 (0.5) 4 (8.7)

Normal 363 (83.4) 321 (82.5) 42 (91.3)

High 66 (15.2) 66 (17) 0 (0)

MSPSS

0.006

Low-to-moderate 111 (25.5) 91 (23.4) 20 (43.5)

High 324 (74.5) 298 (76.6) 26 (56.5)

Partner’s demographic characteristics (n=432)**

Educational level 0.166

Below Bachelor’s degree 226 (52.3) 197 (51) 29 (63)

Bachelor’s degree and higher 206 (47.7) 189 (49) 17 (37)

Occupation 0.79

Employee/self-employed 285 (66) 253 (65.5) 32 (69.6)

Government employee 140 (32.4) 127 (32.9) 13 (28.3)

Stay-at-home dad/unemployed 7 (1.6) 6 (1.6) 1 (2.2)

Religion 0.223*

Buddhism 300 (69.4) 273 (70.7) 27 (58.7)

Islam 130 (30.1) 111 (28.8) 19 (41.3)

Christianity 2 (0.5) 2 (0.5) 0 (0.0)

Smoking 191 (44.2) 169 (43.8) 22 (47.8) 0.715

Alcohol consumption 182 (42.1) 163 (42.2) 19 (41.3) > 0.99

Other substance abuse

(E.g. Cannabis) 3 (0.7) 2 (0.5) 1 (2.2) 0.287*

Underlying medical illness 27 (6.2) 22 (5.7) 5 (10.9) 0.19*

Psychiatric illness 1 (0.2) 1 (0.3) 0 (0.0) > 0.99*

Note:

EPDS = the Edinburgh Postnatal Depression Scale;

Self-esteem = the Rosenberg’s Self-esteem Scale;

MSPSS = the Multidimensional

Scale of Perceived Social Support

* Fisher's exact test; ** ere were 3 missing values.

TABLE 2. Demographic characteristics, self-esteem, and perceived social support categorized by EPDS score (N =

435). (Continue)

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

658

Choosuk et al.

TABLE 3. Factors associated with antepartum depression by multivariate regression analysis.

Factors

Crude OR

Adjusted OR

P-value

(95 % CI

) (95 % CI

) LR

test

Trimester 0.018

First Ref

Ref

Second 1.97 (0.82, 4.75) 2.73 (1.04, 7.21)

Third 1.01 (0.39, 2.59) 1.06 (0.38, 2.95)

Standard of living 0.001

High Ref

Ref

Survival 3.32 (1.6, 6.9) 3.23 (1.5, 6.96)

Below survival 6.98 (2.54, 19.17) 5.35 (1.78, 16.03)

Pregnancy intention 0.021

Intended Ref

Ref

Unintended 2.81 (1.48, 5.31) 2.3 (1.15, 4.6)

Self-esteem level < 0.001

Low* Ref

Ref

Normal 0.07 (0.01, 0.37) 0.06 (0.01, 0.39)

High 0 (0, inf.) 0 (0, inf.)

Note:

OR = odds ratio;

CI = condence interval;

LR = likelihood-ratio;

Ref = reference category

*We could not use a normal self-esteem value as a reference due to the imprecision of the estimation (the 95 % CI was too wide).

experience less stress or anxiety than those with a low

level of self-esteem. us, this may serve as an indication

for targeting the enhancement of the self-esteem of

pregnant women in our country. In addition, screening

pregnant women with low self-esteem using Rosenberg’s

Self-esteem Scale-ai version during antenatal care

might be useful.

Finally, the information provided by our

ndings might prove useful in establishing a screening

program that utilizes EPDS for pregnant women in the

future, which can be applied from the rst trimester

of the antepartum period. e rationale of using the

first trimester as a reference point was is based on

evidence from a previous study, which demonstrated

an increasing risk for antepartum depression with

advancing gestational age.

Such programs may be

especially benecial for women at risk for antepartum

depression, e.g., those with unintended pregnancy, low

family income, low self-esteem, and a gestational age

of the second trimester onwards. is screening would

be very helpful for the early detection, prevention, and

timely management of severe depressive episodes among

pregnant women. Furthermore, health agencies that

play a role in pregnancy care should design and conduct

activities aimed at enhancing the self-esteem of pregnant

women, their ability to manage stress properly, as well

as their problem-coping skills during antenatal visits. In

addition, educating family members and other inuential

persons about the detection, care, and prevention of

antenatal depression would be a worthwhile goal. We

recommend that the antenatal care book, which is made

available as a handout for the general public, should

contain essential information regarding the warning

signs of depression as well as appropriate self-care to

prevent depression during pregnancy. Moreover, for

pregnant women with unintended pregnancy, critical

socioeconomic problems, and severe psychiatric

disorders that are at risk for major depression with

suicidal ideation, termination of pregnancy at an

early gestational age should be oered as an option.

Such strategy may prevent suicide during pregnancy.

Additionally, effective contraception, sex education

also risks and benet of multiparity should be provided

to women who wish to prevent future unintended

pregnancies.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

659

Original Article

SMJ

Strengths and limitations

To our knowledge, this is the only study on this

topic conducted in ailand during the past decade,

which employed an adequate sample size and covered

pregnant women in all trimesters of pregnancy. Another

strength of this study is that we identified factors

associated with antepartum depression, which can be

very useful in detecting pregnant women at risk for this

signicant health problem. However, our study suered

from some limitations. It utilized self-administered

questionnaires; therefore, some misunderstandings

regarding the intended meaning of the questions

might have occurred. Nevertheless, to minimize this,

the questionnaires were validated and showed good

reliability (good Cronbach’s alpha coecient values).

Another drawback was that our data were collected

from pregnant women without any previous history of

depression or other psychiatric illnesses in the lower

part of Southern ailand. Hence, this dataset may not

represent fairly the situation of pregnant women in the

whole country.

Future recommendations and implications

For further study, screening from the rst ANC

visit until the postpartum period and conducting multi-

centric research on this topic are necessary before making

a denite guideline for screening depression during

pregnancy.

CONCLUSION

One-tenth of Thai women responders were

found to suer from antepartum depression via EPDS

screening. Advanced gestation, low income, unintended

pregnancy, and low self-esteem were determined to

relate to antepartum depression. Future longitudinal

studies encompassing the time interval from the rst

antenatal visit to the postpartum period should be

conducted in order to assess the exact onset of depression.

Furthermore, multi-centric studies are recommended.

ACKNOWLEDGEMENTS

e authors would like to acknowledge all the

participants for their willingness to provide information

and the nursing staff of the antenatal clinic for

facilitating this study by providing space at the clinic

and support to carry out the study. We would like to

also acknowledge Associate Professor Hutcha Sriplung,

and the research assistants; Nisan Werachattawan and

Kruewan Jongborwanwiwat, for their assistance with

the data analysis. Moreover, we genuinely appreciate the

International Aairs Unit of the Faculty of Medicine for

proof-reading the English.

is study was fully supported by the Faculty of

Medicine, Prince of Songkla University, ailand. e

funders played no role in the study design, data collection

and analysis, decision to publish, or preparation of the

manuscript.

Disclosure statement: e authors declare no conict

of interest.

REFERENCES

1. World Health Organization. let’s talk [Internet]. 2019 [cited

2019 Aug 5] Available from: https://www.who.int/mental_health/

management/ depression/en/.

2. Kittirattanapaiboon P, Tantirangsee N, Chutha W, Tanaree A,

Kwansanit P, Assanangkornchai S, et al. ai mental health

survey working group 1bureau of mental health service

administration, department of mental health. prevalence of

mental disorders and mental health problems: results from

ai national mental health survey 2013. Bangkok: Bureau

of Mental Health Service Administration, Department of

Mental Health; 2016.

3. Sadock B, Sadock V, Ruiz P. Synopsis of psychiatry: behavioral

sciences/clinical psychiatry. 11th ed. Philadelphia: Lippincott

Williams & Wilkins, 2014.

4. Howard LM, Molyneaux E, Dennis CL, Rochat T, Stein A,

Milgrom J. Non-psychotic mental disorders in the perinatal

period. Lancet 2014;384:1775-88.

5. Burt V, Hendrick V. Clinical manual of women’s mental health.

Arlington (VA): American Psychiatric Publishing, 2005.

6. Grigoriadis S, VonderPorten E, Mamisashvili L, Tomlinson G,

Dennis C, Koren G, et al. e impact of maternal depression

during pregnancy on perinatal outcomes. J Clin Psychiatry

2013;74:e321-41.

7. Straub H, Adams M, Kim J, Silver R. Antenatal depressive

symptoms increase the likelihood of preterm birth. Am J Obstet

Gynecol 2012;207(4):329:e1-4.

8. Yonkers K, Wisner K, Stewart D, Oberlander T, Dell D, Stotland

N, et al. e management of depression during pregnancy: a

report from the American psychiatric association and the

American college of obstetricians and gynecologists. Gen Hosp

Psychiatry 2009;31(5):403-13.

9. Carter D, Kostaras X. Psychiatric disorders in pregnancy. BC

Med J 2005;47:96-9.

10. Kids C. Depression in pregnant women and mothers: how

it aects you and your child - caring for kids [Internet]. Ottawa:

Canadian Paediatric Society. 2019 [cited 2019 Sept 8]. Available

from: https://www.caringforkids.cps.ca/handouts/depression_in_

pregnant_women_ and_mothers.

11. Kaiyo-Utete M, Dambi JM, Chingono A, Mazhandu FSM,

Madziro-Ruwizhu TB, Henderson C, et al. Antenatal depression:

an examination of prevalence and its associated factors among

pregnant women attending Harare polyclinics. BMC Pregnancy

and Childbirth 2020;20:197.

12. Ogbo F, Eastwood J, Hendry A, Jalaludin B, Agho K, Barnett B,

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

660

et al. Determinants of antenatal depression and postnatal

depression in Australia. BMC Psychiatry 2018;18:49.

13. Woody CA, Ferrari AJ, Siskind DJ, Whiteford HA, Harris

MG. A systemic review and meta-regression of the prevalence

and incidence of perinatal depression. J Aect Discord 2017;219:

86-92.

14. Okagbue H, Adamu P, Bishop S, Oguntunde P, Opanuga A,

Akhmetshin E. Systematic review of prevalence of antepartum

depression during the trimesters of pregnancy. Maced J Med

Sci 2019;7:1555-60.

15. Gebremichael G, Yihune M, Ajema D, Hau D, Gedamu G.

Perinatal depression and associated factors among mothers

in southern Ethiopia: evidence from Arba Minch Zuria health

and demographic surveillance site. Psychiatry J 2018;2018:

7930684.

16. Bitew T, Hanlon C, Kebede E, Honikman S, Fekadu A. Antenatal

depressive symptoms and perinatal complications: a prospective

study in rural Ethiopia. BMC Psychiatry 2017;17:301.

17. Hu Y, Wang Y, Wen S, Guo X, Xu L, Chen B, et al. Association

between social and family support and antenatal depression:

a hospital-based study in Chengdu, China. BMC pregnancy

and childbirth 2019;19:420.

18. Mohammad K, Gamble J, Creedy D. Prevalence and factors

associated with the development of antenatal and postnatal

depression among Jordanian women. Midwifery 2011;27:e238-

45.

19. Ongeri L, Otieno P, Mbui J, Juma E, Mathai M. Antepartum risk

factors for postpartum depression: a follow up study among

urban women living in Nairobi, Kenya. J Preg Child Health 2016;

3:288.

20. Fransson E, Ortenstrand A, Hjelmstedt A. Antenatal depressive

symptoms and preterm birth: a prospective study of a Swedish

National sample. Birth 2010;38:10-6.

21. Milgrom J, Gemmill AW, Bilszta JL, Hayes B, Barnett B,

Brooks J, et al. Antenatal risk factors for postnatal depression:

a large prospective study. J Aect Disord 2008;108:147-57.

22. Babu GR, Murthy GVS, Singh N, Nath A, Rathnaiah M, Saldanha

N, et al. Sociodemographic and medical risk factors associated

with antepartum depression. Front Public Health 2018;6:127.

23. Joshi D, Shrestha S, Shrestha N. Understanding the antepartum

depressive symptoms and its risk factors among the pregnant women

visiting public health facilities of Nepal. PLoS One 2019;14:e0214992.

24. Rwakarema M, Premji SS, Nyanza EC, Riziki P, Palacios-

Deringher L. Antenatal depression is associated with pregnancy-

related anxiety, partner relation, and wealth in women in

northern Tanzania: a cross-sectional study. BMC Women

Health 2015;15:68.

25. Sitdhiraksa N, Nandidarbha R, Limsrichareon K, itadilok W.

e prevalence of major depressive disorder during pregnancy

at the antenatal care clinic Siriraj hospital. J Psychiatr Assoc

ailand 2010;55:15-26.

26. Wongpakaran T, Wongpakaran N. Conrmatory factor analysis

of Rosenberg self-esteem scale: a study of ai student sample.

J Psychiatr Assoc ailand 2011;56:59-70.

27. Rosenberg M. Society and the Adolescent Self-Image. New

Jersey: Princeton University Press, 1965.

28. Wongpakaran T, Wongpakaran N, Ruktrakul R. Reliability

and Validity of the Multidimensional Scale of Perceived Social

Support (MSPSS): ai Version. Clin Pract Epidemiol Ment

Health 2011;7:161-6.

29. Zimet GD, Dahlem N, Zimet SG, Farley G. e multidimensional

scale of perceived social support. J Pers Assess 1988;52:30-41.

30. Vacharaporn K, Pitanupong J, Samangsri N. Development

of the Edinburgh Postnatal Depression Scale ai version. J

Ment Health ai 2003;11:164-9.

31. Health M. What is e Best Screening Tool for Antenatal Depression.

Boston: e MGH Center for Women’s Mental Health [Internet].

2015 [cited 2016 Sept 9]. Available from: https://womensmentalhealth.

org/posts/what-is-the-best-screening-tool-for-antenatal-

depression/.

Choosuk et al.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

661

Original Article

SMJ

ongpitak Huabbangyang, PMD., M.Sc.*, Narong Kulnides, Ph.D.**

*Master of Science Program in Forensic Science, Graduate School, Suan Sunandha Rajabhat University, Bangkok 10300, ailand and Department

of Disaster and Emergency Medical Operation, Faculty of Science and Health Technology, Navamindradhiraj University, Bangkok 10300, ailand,

**Doctor of Philosophy Program in Forensic Science, Graduate School, Suan Sunandha Rajabhat University, Bangkok 10300, ailand.

The Perceptions of Roles and Understanding about

Forensic Evidence and Crime Scene Preservation of

Thai Paramedics

ABSTRACT

Objective: 1. To study the perceptions of roles and understanding of FECSP of ai paramedics. 2. To study the

problems, obstacles, and solutions for development of ai paramedics FECSP practices.3. To study the factors

aecting the perceptions of roles and understanding of FECSP in ai paramedics.

Materials and Methods: ai paramedics data over the country registered with National Institute for Emergency

Medicine (NIEMS) during 1

March – 31

March 2021 was collected in this cross-sectional survey. e questionnaires

were sent as Google forms to them by e-mail.

Results: 382 questionnaires were sent, and 281 responses (74%) were obtained. Most were female (61.9%). e

average age was 26.09±4.44 years. e most common crime scene experienced was trac accidents. Most had

never had additional training related to forensic science. e perceptions of roles and understanding about FECSP

were at the highest level. e most common problem and hindrance about FECSP was no FECSP law and the most

common solution for improvement of the FECSP was the standard FECSP guideline development.Hospital level

was found to be a factor related to the perceptions of roles of FECSP in ai paramedics. Average score of a cohort

who worked at university hospital was higher than those working at tertiary hospitals 0.220 (B = -0.220, p-value =

0.018). Additionally, hospital level was also a factor concerning the understanding about FECSP of ai paramedics.

e average score of cohorts who worked at university hospitals was greater than those working in primary or

secondary hospitals 0.197 (B = -0.197, p-value = 0.022).

Conclusion: e paramedics had the perception of the roles and understanding about FECSP at the highest level.

Hospital level was a signicant factor related to the perception of the roles and understanding about FECSP. Relevant

health institutes should develop standard guidelines and promote FECSP training.

Keywords: Crime scene; forensic evidence; paramedic; role; understanding (Siriraj Med J 2021; 73: 661-671)

Corresponding author: Narong Kulnides

E-mail: Narong.ku@ssru.ac.th

Received 21 June 2021 Revised 16 August 2021 Accepted 31 August 2021

ORCID ID: https://orcid.org/0000-0001-5151-4325

http://dx.doi.org/10.33192/Smj.2021.85

INTRODUCTION

Paramedicine is a new profession in ailand. e

most important role of paramedics is to provide pre-

hospital advanced life support for emergency patients.

Paramedics oen need to assist the injured at crime

scenes. However, paramedics have not received any

ocial educational sessions or trainings to deal with crime

scene management.

Currently, the role of paramedics in

forensic evidence and crime scene preservation (FECSP)

is unclear in ailand. In the past, the management of

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

662

the evidence and the crime scene depended on individual

knowledge and experience. Consequently, paramedics

might damage the evidence and crime scene due to a

lack of a recognized role and understanding of FECSP

and may damage evidence at the crime scene while

performing their duties due to not following appropriate

handling processes, potentially causing a more complicated

inquest, an inconclusive judgement or even a miscarriage

of justice.

The aim is to study the perceptions of roles

and understanding about FECSP of ai paramedics

as well as factors aecting the perceptions of roles and

understanding of FECSP in ai paramedics.

MATERIALS AND METHODS

e study design was a cross-sectional survey. e

sample was composed of ai paramedics registered with

National Institute for Emergency Medicine (NIEMS).

e questionnaire data was collected during 1

March –

March 2021. Inclusion criteria were being registered

with NIEMS and having the intention to renew their

5-year license. Exclusion criteria were incomplete data

in NIEMS database, such missing as e-mail addresses,

as well as declining participation. e questionnaire

was examined using a validity index by three forensic

experts. e validity index was 1 for all questionnaires.

e questionnaire was comprised of 4 parts. Part

one was comprised of of 9 questions about participants’

personal information and included questions about

participant sex, age, education level, income, position,

employment period, hospital level, crime scene experience

and additional forensic training experience. e second

and third parts contained 30 questions in total: 15

questions referred to the perception of roles in FECSP

of Thai paramedics and another 15 regarding their

understanding of FECSP. e questionnaire employed

closed questions, with responses structured using 5-point

Likert rating scales - 5 being the highest, 4 being high,

3 being neutral, and 2 and 1 being low and lowest respectively.

Parts two and three were validated via a tryout, tested

by 30 fourth-year paramedic students who had similar

characteristics to the sample. Reliability indices were

calculated using Cronbach’s alpha and were 0.868 and

0.875 for parts two and three respectively, indicating high

reliability. e scoring criteria of the questionnaire parts

two and three was divided into 5 levels, in accordance with

the mean score (Best, 1986). Mean scores of 4.21-5.00,

3.41-4.20, 2.61-3.40, 1.81-2.60 and 1.00-1.80 mean highest,

high, neutral, low, and lowest, respectively.

Part four

contained two questions relating to problems, obstacles,

and solutions to improve FECSP. e questionnaires

were sent out as Google forms to the paramedics by

e-mail. Participants were given 30 days to complete

the survey. e denitions of factors were determined,

rstly, hospital level regarding geographic information

system (GIS), including tertiary, secondary and primary

hospitals, as well as university hospital, separated from

tertiary hospital. e university hospital was dened as a

super tertiary hospital with the highest service capability

and treatment readiness as well as provided medical

personnel training and medical research. e tertiary

hospital was an excellence center dedicated to sub-

specialty care. Low, middle and high levels of secondary

services were assembled in secondary hospital. e low

secondary service level consisted of general practice to

in-patient department (cared by general practitioner/

family medicine physician). While the middle level

was composed of major sub-specialty care. Both major

and minor sub-specialty cares were oered in the high

level of secondary service. e primary hospital was a

combination of initial and main levels of primary service.

e initial primary service level included elementary health

promotion, prevention, rehabilitation and treatment

(serviced by non-physician personnel). Whereas the

main level of primary service comprised preliminary

promotion, prevention, rehabilitation and treatment to

out-patient department (cared by general practitioner/

family medicine physician, etc.), besides paramedics

under local administration were involved. Secondly,

the perceptions of roles about FECSP were dened as

paramedics’ behavior or duty regarding knowledge and

profession in FESCP according to emergency medicine.

irdly, the understanding about FECSP was dened

as paramedics’ psychological process and evaluation

in FECSP.

Statistical analyses

382 paramedics both registered with NIEMS in 2021

and determined to renew their 5-year license responded

(NIEMS, 2021). e Taro Yamane formula was used

for sample size calculation (Taro Yamane, 1973). e

calculated sample size was 196, with an error margin of

0.05. Aer 20% of sample size was added to compensate

for non-responses using the formula n

new

= 196 / (1-0.2)

nal sample size was 245. However, the questionnaire

was sent to every paramedic.

Descriptive statistics were used to analyze the personal

data including sex, age, education level, income, position,

employment period, hospital level, crime scene experience

and additional forensic training experience. For the

qualitative data, frequency distribution and percentage

were reported. Mean with standard deviation (SD) or

Huabbangyang et al.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

663

Original Article

SMJ

median with interquartile range (IQR) were used for

the quantitative data, as appropriate. For the data of

perceptions of roles and understanding about FECSP

of ai paramedic, mean with SD were reported, while

frequency distribution and percentage were reported for

problems, obstacles, and solutions for improvement of

FECSP in ai paramedics. Inferential statistics, multiple

linear regression, were utilized for analysis of factors

aecting perceptions of roles and understanding about

FECSP of ai paramedics.

IBM SPSS Statistics for Windows, Version 26.0 (IBM

SPSS Statistics for Windows, Version 26.0. Armonk,

NY, USA: IBM Corp.) was used. All statistical tests were

considered statistically signicant at P-value ≤.05.

Ethical approval

is study was approved by the institutional review

board of Suan Sunandha Rajabhat University, No. COA.

1-006/2021.

RESULTS

Of 382 questionnaires sent, 281 responded (74%).

Most respondents were female (61.9%). e average age

was 26.09 ± 4.44 years. e average employment period

was 1 year (IQR 1-3 years) for most paramedics. e

most common crime scenes experienced were trac

accidents (91.1%), physical assaults (56.6%), and suicide

attempts (55.5%). Most ai paramedics (73%) had never

received additional training related to forensic science

(Table 1).

Mean of overall perceptions of roles about FECSP

of this cohort was at the highest level (𝑥= 4.27, SD =

0.51). (Table 2)

Mean of overall understanding about FECSP of

the sample was at the highest level (𝑥= 4.28, SD = 0.63).

(Table 3)

Most paramedics (99.6%) faced problems and

obstacles in FECSP. e most reported problems were:

no FECSP law (68.7%), no standard FECSP guideline

(64.8%), and lack of forensic evidence preservation

equipment and collection systems (61.2%). e most

commonly reported solutions to improve the practice

of FECSP were: standard FECSP guideline development

(83.3%), FECSP training program development (82.9%)

and the passing of FECSP related laws (Table 4).

Multiple linear regression analysis revealed hospital

level was the key factor related to the perceptions of roles

about FECSP of ai paramedics. e average score of

a cohort who worked at tertiary hospitals was less than

the cohort working at university hospitals (B = -0.220,

p-value = 0.018), aer controlling for current position

and crime scene experience (physical assault, falls from

height, poisoning, occupational accident and suspicious

death or suspected homicide) (Tables 5 and 6).

Hospital level was also the factor most related with

the understanding about FECSP of ai paramedics, as

shown by multiple linear regression analysis. e average

score of cohorts who worked at primary or secondary

hospitals was less than that of university hospitals

(B = -0.197, p-value = 0.022), aer controlling for crime

scene experience (falls from height and sexual assault)

(Tables 7 and 8).

DISCUSSION

Overall, the perception of roles and understanding

of FECSP reported in this study were at the highest level,

reecting a good quality of educational institutions

providing training in paramedicine. Presently there are only

four institutions, namely Navamindradhiraj University,

Mahidol University, Mahasarakham University and

University of Phayao that provide education and training

about roles and understanding of FECSP, even though,

most paramedics in this study did not have additional

forensic training. Most paramedics in university hospitals

were teachers and teacher assistants which had a higher

level of perception of roles and understanding of FECSP

than ones in tertiary, secondary and primary hospitals,

respectively. Although they mainly didn’t have experience

in the eld, due to their skill and knowledge in forensic

science and crime scene, their level of perception of

roles and understanding of FECSP was higher. Further,

consistent with Khamya’s study, emergency medical

responders(EMRs) at the Poh Teck Tung Foundation

in Bangkok mostly did not have additional forensic

training, while overall knowledge and understanding,

regard to emergency calls management aspect and crime

scene preservation aspect were at the highest level, and

forensic evidence understanding was at a high level.

addition, the most common problems and hindrances

of FECSP the paramedics faced was a lack of an FECSP

law and a lack of standard FECSP guidelines for EMRs,

emergency medical technicians (EMTs), advanced

emergency medical technicians (AEMTs), paramedics,

emergency nurse practitioners (ENPs) and emergency

physicians (EPs).

7-8

At this moment, no FECSP guideline

has been developed in ailand, comparable to the study

by Asci et al. in which there was no proper guideline

relating to forensic patients for emergency medical

sta and emergency stations in Turkey.

EMRs did not

clearly recognize the role as well as confronted problems

and obstacles in handling the subject, while overall

role perception was at a middle level for personnel, as

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

664

TABLE 1. Personal and Employment Information (n = 281).

Variables No. %

Sex

Male 107 (38.1)

Female 174 (61.9)

Age (years), mean ± SD 26.09 ± 4.44

Education level

Bachelor degree 275 (97.9)

Master degree 5 (1.8)

Doctoral degree 1 (0.4)

Income (per month)

Less than 15,000 baht 57 (20.3)

15,001 - 20,000 baht 79 (28.1)

20,001 - 25,000 baht 56 (19.9)

25,001 - 30,000 baht 52 (18.5)

30,001 - 35,000 baht 13 (4.6)

35,001 - 40,000 baht 12 (4.3)

More than 40,001 baht 12 (4.3)

Current position

Teacher/Teacher assistant 18 (6.4)

University employee/State Enterprise 39 (13.9)

 Civilservant/MinistryofPublicHealthofcer 106 (37.7)

Employee/Freelance 114 (40.6)

Other 4 (1.4)

Employment period (year), median (IQR) 1 (1 - 3)

Hospital level

University hospital 104 (37.0)

Tertiary hospital 65 (23.1)

Secondary hospital 70 (24.9)

Primary hospital 20 (7.1)

Private hospital 10 (3.6)

Local Administration 12 (4.3)

Crime scene experience

 Trafcaccident 256 (91.1)

Suicide attempt 156 (55.5)

Physical assault 159 (56.6)

Fall from height 150 (53.4)

Shooting 98 (34.9)

Poisoning 98 (34.9)

Occupational accident 114 (40.6)

Electrical accident 111 (39.5)

Burn 86 (30.6)

Drowning 130 (46.3)

Suspicious death/homicide 94 (33.5)

Sexual assault 37 (13.2)

Incised wound 115 (40.9)

Additional forensic training

No 205 (73.0)

Yes 76 (27.0)

Huabbangyang et al.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

665

Original Article

SMJ

TABLE 2. e perceptions of ai paramedics regarding their roles in FECSP.

Questions mean SD Level of

Understanding/

Awareness

1. Paramedics always remember that lifesaving is more important 4.26 0.79 Highest

than forensic considerations.

2. Paramedics should damage the crime scene as little as possible 4.72 0.58 Highest

for forensic evidence preservation.

3. Paramedics and team member should not enter the crime scene 4.84 0.47 Highest

until the crime scene is safe and controlled by police.

4. Paramedics have a role in recording details of the crime scene 3.93 1.09 High

and forensic evidence in the patient record.

5. Paramedics have a role in giving information and advice regarding 4.27 0.84 Highest

critical emergency state to prehospital forensic patient.

6. Paramedics have a duty to examine forensic evidence, especially 3.68 1.17 High

when recording the medical details of the case.

7. Paramedics have a role in history taking and recording information 4.60 0.66 Highest

of forensic patient at the scene, during delivery, history taking,

physical examination, treatment at the scene and vital signs, clearly.

8. Paramedics have a role to contact dispatch center for coordination 4.54 0.75 Highest

 withpoliceofcerorauthoritiesinvolvedincaseofforensicpatient. 

9. Paramedics have a role in explanation of required information regarding 4.17 0.92 High

 crimesceneexaminationtoforensicdoctorandinquiryofcial. 

10. Paramedics have a role as an advanced life support team leader and 4.66 0.72 Highest

has a duty in security check of the team before entering the crime scene.

11. Paramedics often have a role in assisting forensic patient. 3.89 0.99 High

12. Paramedics have an important role in forensic evidence and crime scene 4.17 0.91 High

preservation as well as often been related to this activity in daily operation.

13. Paramedics have a role in Chain of Custody. 3.89 1.08 High

14. Paramedics have a role in assisting forensic patient by applying holistic 4.25 0.91 Highest

approach, included physical, mental, social and spiritual aspects,

according to emergency medicine theory.

15. Overall, what level of a role in forensic evidence and crime scene 4.15 0.88 High

preservation does paramedic has?

Overall perception of roles in forensic evidence and crime scene preservation. 4.27 0.51 Highest

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

666

TABLE 3. e understanding of FECSP of ai paramedics.

Questions mean SD Level of

Understanding/

Awareness

1. You must control ambulance parking at the scene to be far from 4.32 0.93 Highest

skid marks, tire prints or other evidence.

2. From the ambulance, you must use the same walking route to and 4.16 0.93 High

from the scene to avoid evidence damage.

3. Youarenotiedaboutabodyfoundhangingathome.Youaretherst 3.95 1.34 High

team arriving the scene, the body found hanging, slightly faced down

with the knot at the posterior. You will cut the rope far from the knot

and the hanging loop.

4. You will avoid touching the weapon or moving the object possible to be 4.70 0.59 Highest

a clue for forensic patient except only as needed for patient assistance.

5. You must record patient’s state and injured person’s character when 4.48 0.82 Highest

arriving the scene as well as surrounding.

6. You will cut or tear victim’s clothes regarding seam to avoid mark 4.38 1.02 Highest

penetrated from object and avoid cutting and tearing at the mark.

7. You will not shake the clothes but collect all the clothes in the paper bag, 4.40 0.94 Highest

instead of plastic bag due to evidence change and you will not give

the clothes to unknown people, even victim’s family.

8. Youwillpreservetissueorotherpartsforthebenetofforensicexamination. 4.08 1.17 High

9. Ifyoundbulletatthescene,youwillputitinthecontainerpaddedwith 3.63 1.45 High

cotton or protection sheet to prevent any mark on the bullet and you will

keep the evidence until giving to the police.

10. You will record victim’s dying declaration and report to EMS director and 3.96 1.20 High

 policeofcer. 

11. You will make a report recording all the change EMS team make to the 4.12 1.11 High

 sceneandphysicalevidence,tocrimesceneinvestigatorandpoliceofcer. 

12. You will keep all the irrelevant ones away from the patient and the scene. 4.57 0.79 Highest

13. You will not smoke or eat at the scene. 4.77 0.66 Highest

14. You will not make any comment relating the case. 4.63 0.82 Highest

15. What level do you have for overall understanding of forensic evidence 4.12 0.89 High

and crime scene preservation?

Overall understanding of forensic evidence and crime scene preservation. 4.28 0.63 Highest

Huabbangyang et al.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

667

Original Article

SMJ

TABLE 4. e problems, obstacles and solutions for improvement of FECSP.

Problems and Obstacles/Solutions No. %

Problems and obstacles of forensic evidence and crime scene preservation 280 (99.6)

Not knowing the detail of the role. 103 (36.7)

No standard guidelines for forensic evidence and crime scene preservation. 182 (64.8)

Lack of knowledge, education and training of forensic evidence and crime scene preservation. 143 (50.9)

No law of forensic evidence and crime scene preservation. 193 (68.7)

 Insufcientinformationofforensicevidenceandcrimescenepreservation. 137 (48.8)

Lack of device in forensic evidence and crime scene preservation, systematically. 172 (61.2)

Other solutions. 6 (2.1)

TABLE 5. Univariable analysis regarding the perceptions of roles about FECSP of ai paramedic.

Factors B SE(B) β p-value

Sex

Male Reference

Female -0.059 0.063 -0.056 0.348

Age (years) 0.003 0.007 0.027 0.650

Education level

Graduate and above Reference

Undergraduate -0.009 0.212 -0.003 0.965

Income (per month)

Less than 15,000 baths Reference

15,001 - 20,000 baths 0.044 0.089 0.039 0.619

20,001 - 25,000 baths -0.066 0.097 -0.052 0.493

More than 25,000 baths -0.062 0.087 -0.056 0.478

Current position

Teacher/Teacher assistant/ University employee/State Enterprise Reference

 Civilservant/MinistryofPublicHealthofcer -0.168 0.084 -0.159 0.046

Employee/Freelance/Other -0.170 0.082 -0.164 0.040

Employment period (year) -0.017 0.013 -0.082 0.169

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

668

TABLE 5. Univariable analysis regarding the perceptions of roles about FECSP of ai paramedic. (Continue)

TABLE 6. Multivariable analysis regarding the perceptions of roles about FECSP of ai paramedic.

Factors B SE(B) β p-value

Hospital level

University hospital Reference

Tertiary hospital -0.172 0.081 -0.142 0.034

Primary/Secondary hospital -0.113 0.074 -0.103 0.127

Private hospital/ Local Administration -0.094 0.120 -0.049 0.432

Crime scene experience

 Trafcaccident 0.026 0.108 0.014 0.813

Suicidal attempt 0.082 0.061 0.080 0.182

Physical assault 0.136 0.061 0.131 0.028

Falls from height 0.192 0.060 0.187 0.002

Shooting incident 0.038 0.064 0.035 0.557

Poisoning 0.169 0.064 0.158 0.008

Occupational accident 0.169 0.062 0.162 0.006

Electrical accident 0.112 0.062 0.107 0.074

Burn 0.087 0.066 0.078 0.193

Drowning 0.066 0.061 0.064 0.282

Suspicious death/Suspected homicide 0.137 0.064 0.126 0.035

Sexual assault 0.145 0.090 0.096 0.109

Incised wound 0.083 0.062 0.080 0.182

Additional forensic training 0.012 0.069 0.010 0.864

B = Regression coecient, SE(B) = Standard error of B, β = Standardized regression coecient

Factors B SE(B) β p-value

Current position

Teacher/Teacher assistant/ University employee/State Enterprise Reference

 Civilservant/MinistryofPublicHealthofcer -0.039 0.098 -0.037 0.692

Employee/Freelance/Other -0.109 0.086 -0.106 0.204

Hospital level

University hospital Reference

Tertiary hospital -0.220 0.093 -0.181 0.018

Primary/Secondary hospital -0.119 0.080 -0.108 0.140

Private hospital/ Local Administration -0.016 0.121 -0.008 0.897

Crime scene experience

Physical assault 0.042 0.071 0.041 0.553

Fall from height 0.107 0.071 0.105 0.133

Poisoning 0.073 0.073 0.068 0.318

Occupational accident 0.060 0.075 0.058 0.422

Suspicious death/Suspected homicide 0.097 0.068 0.090 0.154

B = Regression coecient, SE(B) = Standard error of B, β = Standardized regression coecient, Constant = 4.255, R

= 0.086

Huabbangyang et al.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

669

Original Article

SMJ

TABLE 7. Univariable analysis regarding the understanding about FECSP of ai paramedic.

Factors B SE(B) β p-value

Sex

Male Reference

Female 0.111 0.074 0.090 0.134

Age (years) 0.003 0.008 0.020 0.739

Education level

Graduate and above Reference

Undergraduate -0.004 0.248 -0.001 0.988

Income (per month)

Less than 15,000 baht Reference

15,001 - 20,000 baht -0.064 0.105 -0.048 0.543

20,001 - 25,000 baht -0.125 0.113 -0.083 0.272

More than 25,000 baht -0.059 0.102 -0.046 0.563

Current position

Teacher/Teacher assistant/ University employee/State Enterprise Reference

 CivilServant/MinistryofPublicHealthofcer -0.036 0.099 -0.029 0.720

Employee/Freelance/Other -0.003 0.097 -0.003 0.974

Employment period (year) -0.011 0.015 -0.045 0.456

Hospital level

University hospital Reference

Tertiary hospital -0.108 0.094 -0.076 0.254

Primary/Secondary hospital -0.195 0.086 -0.152 0.024

Private hospital/ Local Administration -0.031 0.140 -0.014 0.823

Crime scene experience

 Trafcaccident 0.036 0.126 0.017 0.777

Suicide attempt 0.072 0.072 0.060 0.320

Physical assault 0.134 0.072 0.111 0.063

Fall from height 0.144 0.071 0.120 0.045

Shooting 0.045 0.075 0.036 0.548

Poisoning -0.004 0.075 -0.003 0.958

Occupational accident 0.104 0.073 0.085 0.155

Electrical accident 0.110 0.073 0.090 0.134

Burn -0.018 0.078 -0.014 0.814

Drowning -0.040 0.072 -0.034 0.576

Suspicious death/homicide 0.051 0.076 0.040 0.500

Sexual assault 0.209 0.105 0.118 0.048

Incised wound 0.015 0.073 0.013 0.833

Additional forensic training 0.015 0.081 0.011 0.851

B = Regression coecient, SE(B) = Standard error of B, β = Standardized regression coecient

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

670

TABLE 8. Multivariable analysis regarding the understanding about FECSP of ai paramedic.

Factors B SE(B) β p-value

Hospital level

University hospital Reference

Tertiary hospital -0.135 0.094 -0.095 0.152

Primary/Secondary hospital -0.197 0.085 -0.153 0.022

Private hospital/ Local Administration 0.021 0.140 0.009 0.881

Crime scene experience

Fall from height 0.126 0.072 0.105 0.082

Sexual assault 0.208 0.106 0.118 0.051

B = Regression coecient, SE(B) = Standard error of B, β = Standardized regression coecient, Constant = 4.294, R

= 0.047

Sadudee reported.

Regarding solutions for improving

FECSP, the paramedics most wanted development of

standard guidelines for FECSP and FECSP training

programs, agreeing with the study by Saenkaew showing

the best crime scene investigation improvement was

annual training and guideline development.

To improve

emergency nurses’ practice, hospitals should focus on

and support forensic tasks by providing training in

forensic medicine and forensic science, as suggested in

Suwanchasri’s study.

is paper would encourage the

National Institute for Emergency Medicine to develop

Forensic Evidence and Crime Scene Preservation training

course together with launching national standard FECSP

law and guidelines. In ailand, the multidisciplinary

team involved with crime scene, including crime scene

investigators, forensic medicine doctors, pathologists

and forensic anthropologists.

Paramedics were required

only if there is injury necessary for emergency treatment

and hospital admission. Sexual assault was common in

ailand and counted as a criminal case. Sperm detection

in specimen collection aer male sexual assault was

essential in court.

13-14

erefore, knowledge of forensic

evidence preservation in sexual assault case was crucial

for paramedics to prevent forensic evidence damage and

investigation compromise.

e most important limitation of this study was that

of potential insucient experience on the part of survey

respondents, as their average employment period was

only 1 year. Hence, information regarding problems,

hindrances and solutions for FECSP improvement might

not be representative, because they had less experience

about problems and hindrances of FECSP. Secondly, no

e-mail addresses of the older generation of paramedics

was in the database, hence they could not be included

in this study. irdly, the second and third parts of the

questionnaire regarding the perceptions of roles and

understanding about FECSP of ai paramedics were

positive questions only because most paramedics might

choose without consideration, possibly leading to bias.

Hence, the highest levels of the perceptions of roles and

understanding about FECSP of ai paramedics were

presented. In the future study, both positive and negative

questions should be set to get rid of this limitation.

CONCLUSION

ai paramedics had overall perceptions of the roles

and understanding of FECSP at the highest level. Hospital

level was the factor related to the perceptions of the roles

of ai paramedics, with the group working in tertiary

hospitals scoring less than those at university hospitals.

e factor related to the understanding of FECSP of

ai paramedics was hospital level, as the scores of those

working in primary or secondary hospitals were lower

than those at university hospitals. e professional council,

NIEMS and educational or training institutes should

focus on roles of paramedics in FECSP, by developing

standard guidelines and FECSP training for paramedics.

ACKNOWLEDGEMENTS

The present study was supported by Assistant

Professor Police Lieutenant General Narong Kulnides

Ph.D, my thesis adviser, who suggested publication of the

Huabbangyang et al.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

671

Original Article

SMJ

study. e authors thank the experts of the Department

of Forensic Medicine, Faculty of Medicine Vajira

Hospital, Navamindradhiraj University for validating

and improving our research tools; e National Institute

for Emergency Medicine for their eort in obtaining the

contact information of the certied paramedics used in

the study; e Research Facilitation Division, Faculty of

Medicine Vajira Hospital, Navamindradhiraj University

for statistical analysis guidance as well as providing third

and fourth-year paramedicine students who assisted

in collecting the data and monitoring questionnaire

responses. e authors were grateful to Institute for

Research and Development and Suan Sunandha Rajabhat

University for proofreading the manuscript regarding

universally standard research methodology and ethics

and also thanked Aniwat Berpan MD for correcting

English for the present study.

Conicts of interest: ere are no conicts of interest.

REFERENCES

1. epmanee D, Huabbangyang T, Samanprom T, Tavilsup P,

Muangchaing S, Suraphakdee N. e Survey of ai Paramedics’

Recognition in Performing Advanced Procedures. Vajira Med

J 2019;63:S43-54.

2. Sawyer S, Coles J, Williams A, Lucas P, Williams B. Paramedic

students’ knowledge, attitudes, and preparedness to manage

intimate partner violence patients. Prehosp Emerg Care 2017;

21:750-60.

3. Asci O, Hazar G, Sercan I. e approach of prehospital health

care personnel working at emergency stations towards forensic

cases. Turk J Emerg Med 2015;15:131-5.

4. Best JW, Kahn JV. Research in Education (9th ad.). New Delhi:

Prentice Hall of India Private Limited; 2007.

5. Textbook of clinical research fourth edition. revised and expanded.

Bangkok: Faculty of Tropical Medicine, Mahidol University,

2011.

6. Khamya A. Study and compare the understanding of forensic

evidence preservation at the scene [dissertation]. Bangkok:

Suan Sunandha Rajabhat University; 2017.

7. Apiratwarakul K, Jumroenketpratheep K, Ienghong K, Ruttanaseeha

W, Buranasakda M, Bhudhisawasdi V. Hand hygiene of

emergency medical service healthcare providers. J Med Assoc

ai 2020;103:8-10.

8. Sittichanbuncha Y, Prachanukool T, Sarathep P, Sawanyawisuth

K. An emergency medical service system in ailand: providers’

perspectives. J Med Assoc ai 2014;97:1016-21.

9. Sadudee S, Niyomdecha M. Understanding of Forensic Medical

Evidence by Sawangprateep Sriracha Rescue Volunteer in

Chonburi Province. JCFS 2018;4:169-79.

10. Saenkaew K. e Study on Knowledge and Understanding

of Crime Scene Investigation of Police Enquiry Ocers in

Nakhon Pathom Province. RDIBRU 2019;14:121-36.

11. Suwanchasri P, Choosakoonkriang S, Supaluknari S, Imsin A.

Understanding Of Forensic And Medical Evidence By Profesional

Nurses In Emergency Department Of Phramongkutklao Hospital.

Veridian E Journal 2016;3:1-12.

12. Suntirukpong A, Mann RW, DeFreytas JR. Postmortem scavenging

of human remains by domestic cats. Siriraj Med J 2017;69:

384-7.

13. Suttipasit P. Comparison of two seminal detection methods,

the acid phosphatase test and the zinc test for sensitivities in

sexually assaulted females positive of sperm. Siriraj Med J

2015;67.

14. Fongsiripaibul V. Determination of posterior fourchette coital

wounds in rape victims by using toluidine blue. Siriraj Med J

1999;5:27-35.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

672

Weerayut owprasert, M.D. FRCST, Saritphat Orrapin, M.D. FRCST

Department of Surgery, Faculty of Medicine, ammasat University, ammasat University Hospital, Pathum ani 12120, ailand.

The Predictive Factors Associated with Longer

Operative Time in Single-Incision Laparoscopic

Cholecystectomy

ABSTRACT

Objective: e dicult laparoscopic cholecystectomy (LC) is dened as the presence of one of the following

conditions including prolonged operative time, conversion to open cholecystectomy or signicant blood loss. At

present, there is no evidence of predictive factors related to longer operative time in single-incision laparoscopic

cholecystectomy (SILC). e aim of this study is to determine predictive factors associated with longer operative

time in SILC procedure.

Materials and Methods: A retrospective study was conducted of patients with benign gallbladder disease who

underwent SILC in ammasat University Hospital between October 2014 and December 2020. Patients’ records

were reviewed. Primary outcomes were preoperative predictive factors associated with DSLC. Secondary outcomes

were perioperative and 3-month postoperative adverse outcomes.

Results: 592 SILC procedures were categorized as 80 DSLC and 512 non-dicult SILC (NDSLC). e median

(interquartile range) of operative time in all SILC procedure is 48 (38, 62) minutes. e threshold of operative time

of dicult SILC was 72 minutes. e multivariate analysis indicated 5 signicant predictive factors. Obesity (body

mass index > 25 kg/m

)) and abdominal pain reected the diculty of SILC procedures (p = 0.041 and p = 0.009).

Calcied gallbladder showed the highest RR of 14.08 (p = 0.011). Contracted gallbladder and chronic cholecystitis

were also predictive factors with RR of 13.79 and 3.64, respectively (p < 0.001 and p = 0.007).

Conclusion: Obesity, abdominal pain, chronic cholecystitis, contracted gallbladder and calcied gallbladder were

preoperative predictive factors. Surgeons should perform the SILC procedure carefully when predictive factors are

identied.

Keywords: Laparoscopic cholecystectomy; single-incision laparoscopic cholecystectomy; predictive factors; dicult

laparoscopic cholecystectomy (Siriraj Med J 2021; 73: 672-679)

Corresponding author: Saritphat Orrapin

E-mail: sam3_orra@hotmail.com

Received 28 May 2021 Revised 8 August 2021 Accepted 14 August 2021

ORCID ID: https://orcid.org/0000-0002-1330-6215

http://dx.doi.org/10.33192/Smj.2021.86

INTRODUCTION

Laparoscopic cholecystectomy (LC) can reduce

pain and surgical scar aer surgery.

Single incision

laparoscopic cholecystectomy (SILC) is the LC procedure

that has the least number of incisions. It was reported

for the rst time by Navara et al.

without dierence

in the overall rate of complications, including biliary

tract injury, bile leakage and wound infection, when

compared with conventional LC. e cosmetic result of

SILC was superior to that of conventional LC.

However,

some reports revealed that SILC had a higher incidence

of incisional hernia than conventional LC.

4,5

e SILC

Thowprasert et al.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

673

Original Article

SMJ

procedure may not be familiar to the surgeon which

may take longer operative time and higher perioperative

complication rates than conventional LC.

ere were a lot of predictive factors of dicult LC

in conventional LC procedure.

6-12

However, there was no

report about predictive factors of dicult SILC, which

may be dierent from conventional LC due to a dierent

step of the procedure, surgeon’s skill and familiarity.

The definition of difficult LC is varied by operative

time, bile duct injury, vascular injury, open conversion.

The operative time is the important determinant to

categorized the diculty of LC procedure.

6,8,11

e aim of our study was to investigate predictive

factors aecting the diculty of SILC. e predictive

factors included baseline characteristic and demographic

data, clinical presentation, and preoperative ultrasound

nding.

6-20

e predictive factors are benecial to caution

surgeons, especially those in residency training, and to

determine the patient’s prognosis before SILC surgery.

MATERIALS AND METHODS

Study design and participants

Retrospective data of patients who underwent SILC

in ammasat University Hospital between October 2014

and December 2020 were reviewed. e inclusion criteria

were patients who had indications for cholecystectomy,

including: (1) symptomatic gallstone, (2) acute

cholecystitis, (3) chronic cholecystitis, (4) gallbladder

polyp size more than 1 centimeters or increasing size

during imaging surveillance,

(5) calcied gallbladder,

and (6) biliary dyskinesia.

The exclusion criteria

included: (1) the patients with malignant gallbladder

or suspected gallbladder malignancy by preoperative

presentation and imaging, (2) an LC procedure

which required additional intraoperative procedures,

including choledocholithotomy, choledochoscope or

cholangiography and, (3) patients who failed to follow up

in the 3 months aer the SILC procedure. e patient’s

characteristics, clinical presentation, pre-operative

ultrasound nding, and operative time were collected.

e criteria to categorize as dicult SILC procedure

and outcomes

e dicult SILC is dened as the presence of one

of the following conditions including prolonged operative

duration, conversion from LC to open cholecystectomy

or significant blood loss, biliovascular injury. The

incidence of signicant blood loss and biliovascular

injury of our study is very low. So, the operative time

which is the important determinant to categorize the

diculty of LC procedure were used in this study. SILC

procedure was performed as a standard technique by a

single surgeon who was highly experienced in the LC

procedure (more than 1,000 cases of LC in 10 years).

The operative time is the determinant to categorize

the diculty of LC procedure.

6,8,11,13

Dicult LC was

identied for each surgeon when the operative time for

a procedure exceeded 1.5 times the surgeon’s individual

base time. Patients were classified into two groups:

non-dicult SILC (NDSLC) (operative time <1.5 times

the surgeon’s individual operative time) and dicult

SILC (DSLC) (operative time ≥1.5 times the surgeon’s

individual operative time).

The primary outcomes objectives were pre-

operative predictive factors which included (1) baseline

characteristic and demographic data, including old

age, male gender, obesity by body mass index ((BMI

(kilograms (kgs) per square meters (m

) ≥ 25 kg/m

diabetes mellitus (DM), dyslipidemia (DLP) (2) the

clinical presentation, including symptomatic gallstones,

suspected acute cholecystitis (acute cholecystitis by

clinical diagnosis at the same admission of SILC

operation), history of acute cholecystitis (subside

cholecystitis), common bile duct (CBD) stone, history

of endoscopic retrograde cholangiopancreatography

(ERCP), gallstone (GS) pancreatitis, GS cholangitis,

acute cholecystitis and (3) preoperative ultrasound

findings including thickening of gallbladder wall,

definited acute cholecystitis, chronic cholecystitis,

gangrenous cholecystitis, adenomyosis, gallbladder

polyps, contracted gallbladder, calcied gallbladder,

CBD dilatation. Symptomatic gallstones were included

dyspepsia and abdominal pain at any time during follow-

up before the SILC operation. e dyspepsia was a non-

specic pain in the epigastrium area. e abdominal pain

refers to dull aching in the upper part abdomen which

specic to biliary colic without evidence of pancreatitis,

cholangitis, or cholecystitis. e chronic cholecystitis

from the ultrasound imaging was used the clinical

correlation to establish the diagnosis of U/S. e SILC

was performed via transumbilical incision. e Calot’s

triangle has been identied for the exposed cystic duct

and artery to obtain a critical view of safety. Aer ligating

of cystic duct and cystic artery by clip, the gallbladder

was dissected from the liver bed and removed through

Alexis® retractor. e pathologic studies were conrmed

all of the ultrasonographic results reports. Intra-op

complications including bile leakage and cystic artery

injury were collected as secondary outcomes objectives

Post-operative care and follow-up

In postoperative care, patients were monitored for

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

674

postoperative complications. Most of the patients were

discharged within 24 hours aer surgery and followed

up 2 weeks, 6 weeks, and 3 months postoperatively.

e post-operative surgical complications, including

infected wound surgical site infection (SSI) and incisional

hernia were collected and analyzed to identify adverse

outcomes associated with dicult SILC which depend

on the operative time.

Sample size calculation

e strong predictive factors for dicult SILC

including BMI, history of acute cholecystitis and

gallbladder wall thickening were used to calculated

sample size. Retrospective data of predictors that aected

the diculty of SILC (measured by operative time) were

used to calculate the power of the sample size under

0.05 alpha error and 0.02 beta error.

6,7,11,13,15-20

e power

calculations were more than 80% at the total number of

592 procedure.

Statistical analysis

e associations between baseline characteristic

and demographic data, clinical presentation, and

preoperative predictive factors were assessed and

presented in percentage or mean with standard deviation

(SD). Student’s t-test was used for analysis of independent

continuous variables and the χ

test for dependent

categorized variables. e predictors of dicult SILC

were tested using multivariate logistic regression.

Relative risk (RR) and 95% condence interval (CI)

were reported. P <0.05 was considered signicant. All

the statistical analyses were performed with STATA/

SE 15.1 for Mac (Stata Corp LP, TX, USA). e study

process and report follow the strengthening the reporting

of observational studies in epidemiology (STROBE)

statement on reports of cohort studies.

RESULTS

A total of 592 SILC procedures were included in

this study. e mean operative time with SD was 53.44

± 22.86 minutes. e distribution of operative time data

was an asymmetric pattern. e median (interquartile

range) of operative time in all SILC procedure is 48 (38,

62) minutes. So, the threshold of DSLC by operative

time was 48 x 1.5 = 72 minutes.

512 (86.5%) patients

were classified as NDSLC and 80 (13.5%) patients

were classied as DSLC.

None of the SILC procedures

required conversion to open cholecystectomy.

Baseline characteristic and demographic data

between NDSLC and DSLC are shown in Table 1. DSLC

was more oen associated with male gender. (p = 0.015).

e DSLC group had higher BMI than the NDSLC group

(27.74 ± 5.70 vs 25.31 ± 4.42, p < 0.001). e weight and

height parameters were higher in the DSLC group when

compared with the NDSLC group. e distribution of

clinical presentation is given in Table 2.

Multivariate logistic regression analysis showed

5 significant predictive factors (Table 3). BMI and

clinical presentation of abdominal pain were statistically

signicant predictive factors that inuenced the diculty

of SILC procedures (95%CI 0.002 – 0.084, p = 0.041 and

RR 2.35, 95%CI 1.236 – 4.466, p = 0.009, respectively).

The preoperative ultrasound findings, which were

signicant predictive factors are presented in Table 3.

Calcied gallbladder showed the highest RR of 14.08 (RR

14.08, 95%CI 1.822 – 108.771, p = 0.011). Contracted

gallbladder and chronic cholecystitis were also predictive

factors with RR of 13.79 and 3.64, respectively (RR =

13.79, 95%CI 14.512 – 42.193, p < 0.001 and RR = 3.64,

95%CI 1.413 – 9.403, p = 0.007, respectively).

e adverse outcomes of SILC procedures were

reported in Table 4. e adverse outcomes which were

more frequent in DSLC procedure included bile leakage,

cystic artery injury and wound infection. At the end of

the three-month follow-up period, the complication

was a single case (0.2%) of incisional hernia. The

intraoperative bile leakage was not associated with

wound infection. In addition, the wound infection was

not related to incisional hernia.

DISCUSSION

Our study demonstrated high BMI as the one of

predictive factor for dicult SILC procedure. Recent

studies have reported that high BMI is associated with

dicult LC.

7,11,15,17,18

Obesity increases abdominal wall

thickness and mesenteric fat volume.

Hassan technique

for single-port insertion may be dicult when a thick

abdominal wall and pendulous abdomen cause the

downward displacement of umbilicus to the level of the

pubic symphysis. So, longer operating time is required

to encounter the thick abdominal wall and the diculty

of abdominal wall closure when compared with thin

abdominal wall. e incidence of incisional hernia in

SILC at our study was found to be 1 out of all 592 patients

(0.17%). Previous studies report incisional hernia

following SILC surgery as well as wound infection related

to obesity due to a thick layer of fat on the abdominal

wall.

However, there are only 8 wound infections and

1 incisional hernia reported in our study. ere is no

correlation between wound infection, incisional hernia,

and BMI in our study.

Abdominal pain was found to be associated with

Thowprasert et al.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

675

Original Article

SMJ

TABLE 1. Comparison of patients’ demographic and clinical data between NDSLC and DSLC groups.

NDSLC DSLC P-value

(n1 = 512) (n2 = 80)

Age (years ± SD) 58.68 ± 14.16 61.06 ± 15.31 0.167

Male gender 149 (29.1%) 34 (42.5%) 0.015

Weight (kg ± SD) 64.74 ± 13.50 72.46 ± 13.74 <0.001

Height (cm ± SD) 159.57 ± 8.56 161.95 ± 7.09 0.019

BMI (kg/m

± SD) 25.31 ± 4.42 27.74 ± 5.70 <0.001

Underlying disease

DM 102 (19.92%) 17 (21.25%) 0.782

HTN 203 (39.65%) 36 (45.00%) 0.364

DLP 212 (41.41%) 32 (40%) 0.812

CAD 14 (2.73%) 3 (3.75%) 0.613

Thalassemia 12 (2.34%) 3 (3.75%) 0.456

CKD 10 (1.95%) 2 (2.50%) 0.746

Asthma 9 (1.76%) 1 (1.25%) 0.743

Other 48 (9.38%) 12 (15.00%) 0.121

Blood thinner used

Antiplatelet 57 (11.13%) 9 (11.25%) 0.975

Anticoagulant 4 (0.75%) 0 (0%) 0.427

Median operative time (minutes) 46 94.5 <0.001

Abbreviations: kg, kilograms; m, meters; cm, centimeters; NDSLC, non-dicult single-port laparoscopic cholecystectomy; DSLC, dicult

single-port laparoscopic cholecystectomy; SD, standard deviation; BMI, body mass index; DM; diabetes mellitus; HTN, hypertension; DLP,

dyslipidemia; CAD, coronary artery disease; CKD, chronic kidney disease.

the dicult SILC. Abdominal pain is more present in

patients who categorized as DSLC (55%). Abdominal

pain is known to be symptomatic of gallstones and

multiple episodes of cholecystitis.

6,17,18

Recurrent

episodes of inammation can create adhesion around

peritoneal cavity which increase the diculty of the

SILC procedure.

6,9,16

Chronic cholecystitis, contracted and calcied

gallbladder were associated with DSLC procedure due to

long operative time. ese predictive factors which can

be identied preoperatively by ultrasound were caused

by chronic, repeated episodes of inammation.

studies have reported association between chronic

cholecystitis and the diculty of LC.

29,30

at contracted

gallbladder is related to dicult LC procedure has also

been reported in previous studies.

31,32

e calcication of

the gallbladder wall is a variant of chronic cholecystitis

and inammatory scarring of the wall. Likewise with

abdominal pain symptom, the chronic inammation

parameters lead to surrounding adhesion of Calot’s

triangle and gallbladder wall.

7,11,13,17,18,20

us, chronic

cholecystitis, contracted gallbladder and calcified

gallbladder on preoperative ultrasound finding can

predict the diculty of SILC procedure.

A lot of previous studies have reported relationships

between gallbladder wall thickening ≥ 4 mm and the

diculty of SILC.

7,11,13,17,18,20

In our study, we collected

data of gallbladder wall thickening and cholecystitis

factors. So, we did not compare DSLC procedure with

the factor of isolated gallbladder wall thickening without

any evidence of inammation on clinical and imaging

results. Previous studies have revealed that cholecystitis is

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

676

TABLE 2. Clinical presentation and preoperative ultrasound nding between NDSLC and DSLC groups.

Variables NDSLC DSLC P-value

(n1 = 512) (n2 = 80)

Clinical presentation

Dyspepsia 495 (96.68%) 79 (98.75%) 0.316

Abdominal pain 199 (38.87%) 44 (55.00%) 0.006

History of acute cholecystitis 25 (4.88%) 13 (16.25%) <0.001

CBD stone 15 (2.93%) 12 (15.00%) <0.001

History of ERCP 13 (2.54%) 10 (12.5%) <0.001

GS pancreatitis 6 (1.17%) 4 (5.00%) 0.013

GS cholangitis* 3 (0.59%) 3 (3.75%) 0.009

Suspected acute cholecystitis** 0 (0%) 3 (3.75%) <0.001

Pre-operative ultrasound nding

GS 492 (96.09%) 80 (100%) 0.072

 Gallbladderwallthickening≥4mm 51(9.96%) 21(26.25%) <0.001

 Deniteacutecholecystitis*** 2(0.39%) 2(2.50%) 0.032

Gangrenous cholecystitis 0 (0%) 1 (1.25%) 0.011

Chronic cholecystitis**** 21 (4.10%) 12 (15.00%) <0.001

Adenomyosis 30 (5.86%) 6 (7.50%) 0.568

Gallbladder polyp 45 (8.79%) 5 (6.25%) 0.447

Contracted gallbladder 7 (1.37%) 15 (18.75%) <0.001

 Calciedgallbladder 2(0.39%) 5(6.25%) <0.001

CBD dilatation 8 (1.56%) 8 (10.00%) <0.001

*Systemic inammation (fever and/or chills or laboratory data) + cholestasis (Jaundice or Laboratory data) + imaging (biliary dilatation or

evidence of the etiology on imaging), **Clinical diagnosis (local signs of inammation (murphy’s sign or right upper quadrant mass/pain/

tenderness) + systemic signs of inammation (fever or elevated C-reactive protein or elevated white blood cell count), *** Ultrasound nding

characteristic diagnosis, ****Gallbladder wall thickening ≥ 4 mm with non-distended gallbladder with clinical diagnosis.

Abbreviations: NDSLC, non-dicult single-port laparoscopic cholecystectomy; DSLC, dicult single-port laparoscopic cholecystectomy;

CBD, common bile duct, ERCP, Endoscopic retrograde cholangiopancreatography; GS, gallstones; mm, millimeters.

related to the diculty of LC procedure.

6,14,16-19

However,

the incidence of acute cholecystitis and gangrenous

cholecystitis in this study was very low.

The adverse outcomes of the study, which

signicantly related to DSLC included intraoperative

bile leakage and cystic artery injury. e DSLC from

adhesion and inammation of Calot’s triangle had a

high risk of major biliovascular injury during SILC.

6,7,17

In addition, biliovascular injury may have increased

operative time for controlling bile leakage or stopping

bleeding. Wound infections were reported more in

DSLC procedure but there was no correlation between

wound infection and intraoperative biliary leakage.

Cystic artery injury and bile leakage can be managed

via laparoscopic technique without open conversion.

ree-month follow-up demonstrated one patient with

incisional hernia without incarceration. Nevertheless,

the DSLC procedure was not associated with incisional

hernia. e limitations of the study included the bias

inherent in the retrospective nature of the design. In

addition, the operative time, intraoperative complication

and open conversion surgery was related to the surgeon’s

Thowprasert et al.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

677

Original Article

SMJ

TABLE 3. Multivariate analysis of inuencing predictive factors on diculty of SILC procedures.

Variables Relative risk 95% Condence P-value

(RR) interval (CI)

Male gender 0.79 0.419 – 1.502 0.477

Weight (kg) N/A 0.029 - 0.004 0.136

Height (cm) N/A 0.003 – 0.023 0.131

Obesity(BMI≥25kg/m

) 1.72 1.125 – 2.639 0.041

Clinical presentation

Abdominal pain 2.35 1.236 – 4.466 0.009

History of acute cholecystitis 1.82 0.616 – 5.406 0.277

CBD stone 2.76 0.431 – 17.660 0.283

History of ERCP 0.62 0.063 – 6.029 0.679

GS pancreatitis 2.59 0.286 – 23.399 0.397

GS cholangitis* 2.35 0.235 – 23.524 0.467

Suspected acute cholecystitis** N/A N/A N/A

Pre-operative ultrasound nding

 Gallbladderwallthickening≥4mm 1.44 0.657–3.154  0.362

 Deniteacutecholecystitis*** N/A N/A  N/A

Gangrenous cholecystitis N/A N/A N/A

Chronic cholecystitis**** 3.64 1.413 – 9.403 0.007

Contracted gallbladder 13.79 4.512 – 42.193 < 0.001

 Calciedgallbladder 14.08 1.822–108.771  0.011

CBD dilatation 3.92 0.637 – 24.133 0.140

*Systemic inammation (fever and/or chills or laboratory data) + cholestasis (Jaundice or Laboratory data) + imaging (biliary dilatation or

evidence of the etiology on imaging), **Clinical diagnosis (local signs of inammation (murphy’s sign or right upper quadrant mass/pain/

tenderness) + systemic signs of inammation (fever or elevated C-reactive protein or elevated white blood cell count), *** Ultrasound nding

characteristic diagnosis, ****Gallbladder wall thickening ≥ 4mm with non-distended gallbladder.

Abbreviations: N/A, not applicable; kg, kilograms; m, meters; cm, centimeters; BMI, body mass index; a P < 0.05, statistically signicant

TABLE 4. Adverse outcomes between NDSLC and DSLC groups.

Variables NDSLC DSLC SUM P-value

(n1 = 512) (n2 = 80) (n=592)

Intraoperative complication

Intraoperative bile leakage 0 (0%) 1 (1.25%) 1 (0.17%) 0.011

Cystic artery injury 0 (0%) 1 (1.25%) 1 (0.17%) 0.011

Other critical adverse events* 0 (0%) 0 (0%) 0 (0%)

Post-operative complication

Wound infection 4 (0.78%) 4 (5.00%) 8 (1.35%) 0.002

Incisional hernia 1 (0.20%) 0 (0%) 1 (0.17%) 0.692

*common hepatic duct, common bile duct, hepatic artery proper injury.

Abbreviations: NDSLC, non-dicult single-port laparoscopic cholecystectomy; DSLC, dicult single-port laparoscopic cholecystectomy.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

678

experience (operator dependent). SILC may not be

recommended if performed by a relatively inexperienced

laparoscopic surgeon or trainee. ree-month follow-up

period cannot represent the long-term complications

such as incisional hernia.

e signicant preoperative predictive factors for

DSLC included BMI (obese), abdominal pain symptom,

chronic cholecystitis, contracted gallbladder, and

calcied gallbladder.

CONCLUSION

DSLC depends on individual operative time

and experience of surgeons. The predictive factors

which determine the difficulty of SILC procedure

were concordant with conventional LC. Obesity,

abdominal pain, chronic cholecystitis, contracted and

calcified gallbladder were significant preoperative

predictive factors for DSLC. Surgeons should perform

the SILC procedure carefully by surgeon who was highly

experienced in the LC procedure when predictive factors

are identied. Wound infection and biliovascular injury

were the major adverse outcomes of the DSLC procedure.

ACKNOWLEDGEMENT

e research group in surgery, Faculty of Medicine,

ammasat University.

REFERENCES

1. Van den Boezem PB, Velthuis S, Lourens HJ, Cuesta MA,

Sietses C. Single-incision and NOTES cholecystectomy, are

there clinical or cosmetic advantages when compared

to conventional laparoscopic cholecystectomy? A case-control

study comparing single-incision, transvaginal, and

conventional laparoscopic technique for cholecystectomy.

World J Surg 2014;38:25-32.

2. Navarra G, Pozza E, Occhionorelli S, Carcoforo P, Donini I.

One-wound laparoscopic cholecystectomy. Br J Surg 1997;

84:695.

3. Qu J-W, Xin C, Wang G-Y, Yuan Z-Q, Li K-W. Feasibility

and safety of single-incision laparoscopic cholecystectomy

versus conventional laparoscopic cholecystectomy in an

ambulatory setting. Hepatobiliary & Pancreat Dis Int 2019;18:

273-7.

4. Arezzo A, Passera R, Forcignanò E, Rapetti L, Cirocchi R,

Morino M. Single-incision laparoscopic cholecystectomy is

responsible for increased adverse events: results of a meta-

analysis of randomized controlled trials. Surg Endosc 2018;

32:3739-53.

5. Hoyuela C, Juvany M, Guillaumes S, Ardid J, Trias M, Bachero

I, et al. Long-term incisional hernia rate aer single-incision

laparoscopic cholecystectomy is signicantly higher than that

aer standard three-port laparoscopy: a cohort study. Hernia

2019;23:1205-13.

6. Bourgouin S, Mancini J, Monchal T, Calvary R, Bordes J,

Balandraud P. How to predict difficult laparoscopic

cholecystectomy? Proposal for a simple preoperative scoring

system. Am J Surg 2016;212:873-81.

7. Wakabayashi G, Iwashita Y, Hibi T, Takada T, Strasberg

SM, Asbun HJ, et al. Tokyo Guidelines 2018: surgical

management of acute cholecystitis: safe steps in laparoscopic

cholecystectomy for acute cholecystitis (with videos). J

Hepatobiliary Pancreat Sci 2018;25:73-86.

8. Wu T, Luo M, Guo Y, Bi J, Guo Y, Bao S. Role of procalcitonin

as a predictor in dicult laparoscopic cholecystectomy for

acute cholecystitis case: A retrospective study based on the

TG18 criteria. Sci Rep 2019;9:10976.

9. Nidoni R, Udachan TV, Sasnur P, Baloorkar R, Sindgikar V,

Narasangi B. Predicting dicult laparoscopic cholecystectomy

based on clinicoradiological assessment. J Clin Diagn Res

2015;9:PC09-PC12.

10. Chong JU, Lee JH, Yoon YC, Kwon KH, Cho JY, Kim SJ, et al.

Influencing factors on postoperative hospital stay after

laparoscopic cholecystectomy. Korean J Hepatobiliary Pancreat

Surg 2016;20:12-6.

11. Randhawa JS, Pujahari AK. Preoperative prediction of dicult

lap chole: a scoring method. Indian J Surg 2009;71:198-201.

12. Hayama S, Ohtaka K, Shoji Y, Ichimura T, Fujita M, Senmaru

N, et al. Risk factors for dicult laparoscopic cholecystectomy

in acute cholecystitis. JSLS 2016;20:e2016.00065.

13. Stanisic V, Milicevic M, Kocev N, Stanisic B. A prospective cohort

study for prediction of dicult laparoscopic cholecystectomy.

Ann Med Surg (Lond) 2020;60:728-33.

14. Seehawong U, Sumritpradit P, Krutsri C, Singhatat P, ampongsa

T, P T. Risk factors of dicult laparoscopic cholecystectomy

for acute cholecystitis in acute care surgery patients. J Med

Assoc ai 2019;102:56.

15. Poonkeaw T. Predicting Factors of the dicult laparoscopic

cholecystectomy in Phatthalung Hospital. Region 11 Medical

Journal 2019;30:251-60.

16. Inoue K, Ueno T, Douchi D, Shima K, Goto S, Takahashi M,

et al. Risk factors for diculty of laparoscopic cholecystectomy

in grade II acute cholecystitis according to the Tokyo guidelines

2013. BMC Surgery 2017;17:114.

17. Elgammal AS, Elmeligi MH, Koura MMA. Evaluation of

preoperative predictive factors for difficult laparoscopic

cholecystectomy. Int Surg J 2019;6:3052-6.13

18. Yassein T, Iyoab I, Sallam A, Gomaa M, Sadek A, Osman M,

et al. Predicting the risk factors of difficult laparoscopic

cholecystectomy step by step. Egypt J Surg 2020;39:515-22.

19. Di Buono G, Romano G, Galia M, Amato G, Maienza E, Vernuccio

F, et al. Dicult laparoscopic cholecystectomy and preoperative

predictive factors. Sci Rep 2021;11:2559.

20. Saleem A-E-A, Abdallah H. Evaluation of preoperative

predictive factors for dicult laparoscopic cholecystectomy

in comparison with intraoperative parameters. Egypt J Surg

2018;37:504-11.

21. Ferrarese A, Gentile V, Bindi M, Rivelli M, Cumbo J, Solej M,

et al. e learning curve of laparoscopic cholecystectomy in

general surgery resident training: old age of the patient may be

a risk factor? Open Med (Wars) 2016;11:489-96.

22. Joong Choi C, Roh YH, Kim MC, Choi HJ, Kim YH, Jung GJ.

Single-Port Laparoscopic Cholecystectomy for Gall Bladder

Polyps. JSLS 2015;19:e2014.00183.

23. Tomioka T, Inoue K, Onizuka S, Ikematsu Y, Kanematsu T.

Laparoscopic cholecystectomy is a safe procedure for the

Thowprasert et al.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

679

Original Article

SMJ

treatment of porcelain gallbladder. Endoscopy 1997;29:225.

24. Toouli J. Biliary Dyskinesia. Curr Treat Options Gastroenterol

2002;5:285-91.

25. Chow SC, Shao J, Wang H. Sample size calculations in clinical

research, 2 ed. New York: John Wiley & Sons, 2008.

26. Von Elm E, Dg. A, Egger M, Pocock S, Gøtzsche P, Vandenbroucke

JP. e strengthening the reporting of observational studies

in epidemiology (STROBE) statement: guidelines for reporting

observational studies. J Clin Epidemiol 2008;61:344-9.

27. Tiong L, Oh J. Safety and ecacy of a laparoscopic cholecystectomy

in the morbid and super obese patients. HPB (Oxford) 2015;

17:600-4.

28. Lyu Y, Cheng Y, Wang B, Zhao S, Chen L. Single-incision versus

conventional multiport laparoscopic cholecystectomy: a

current meta-analysis of randomized controlled trials. Surg

Endosc 2020;34:4315-29.

29. Bat O. e analysis of 146 patients with dicult laparoscopic

cholecystectomy. Int J Clin Exp Med 2015;8:16127-31.

30. Gupta N, Ranjan G, Arora MP, Goswami B, Chaudhary P, Kapur

A, et al. Validation of a scoring system to predict dicult

laparoscopic cholecystectomy. International Journal of Surgery

2013;11:1002-6.

31. Lal P, Agarwal PN, Malik VK, Chakravarti AL. A dicult

laparoscopic cholecystectomy that requires conversion to open

procedure can be predicted by preoperative ultrasonography.

JSLS 2002;6:59-63.

32. Vivek MAKM, Augustine AJ, Rao R. A comprehensive predictive

scoring method for dicult laparoscopic cholecystectomy. J

Minim Access Surg 2014;10:62-7.1

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

680

Kamala Laohverapanich, M.D.*, Jassada Buaboonnam, M.D.*, Nassawee Vathana, M.D.*, Kleebsabai Sanpakit,

M.D.*, Chayamon Takpradit, M.D.*, Nattee Narkbunnum, M.D.*, Bunchoo Pongtanakul, M.D.*, Panjarat

Sowithayasakul, M.D.**, Kamon Phuakpet, M.D.*

*Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, ailand, **Department of Pediatrics, Faculty

of Medicine, Srinakharinwirot University, Nakhon Nayok 26120, ailand.

Clinical Outcomes of Extracranial Germ Cell

Tumors: A Single Institute’s Experience

ABSTRACT

Objective: To determine the clinical features and treatment outcomes of pediatric extracranial germ cell tumor

(EGCT) in ailand.

Materials and Methods: A retrospective chart review of children under 15 years old with newly diagnosed EGCT

who were treated at Faculty of Medicine Siriraj Hospital from January, 2004 to December, 2013 was conducted.

Results: Forty-four patients were included in the study. e median age at diagnosis was 1.74 years (1 day-14.7 years)

with the median follow up time of 6.9 years (14 days-15.2 years). Twenty-eight patients (64%) had extragonadal

tumor. e most common primary tumor location was the sacrococcygeal area. Majority of the patients (61%) had

malignant EGCT; yolk sac tumor was the most common diagnosis. Six patients (14%) had stage IV disease. Forty

patients (91%) underwent surgery; 27 patients (61%) received chemotherapy. irty-eight patients (86%) achieved

remission; 3 patients (7%) subsequently relapsed at a median time of 1 year. Eight patients (18%) died, mostly

from tumor progression. e 5-year event-free survival (EFS) and overall survival (OS) rate were 78.3% and 81.1%,

respectively. Patients achieving total tumor removal had signicantly better 5-year EFS and OS. Cox regression

analysis revealed that the adequacy of surgery was the only prognostic factor for survival.

Conclusion: e survival rate of pediatric EGCT in our study was relatively favorable, but still inferior to that of

developed countries. Novel therapy may be warranted for those patients who are unresponsive to the current treatment.

Keywords: Extracranial germ cell tumor, EGCT, survival rate, treatment outcome, ailand (Siriraj Med J 2021;

73: 680-686)

Corresponding author: Kamon Phuakpet

E-mail: kphuakpet@gmail.com

Received 28 May 2021 Revised 13 August 2021 Accepted 16 August 2021

ORCID ID: https://orcid.org/0000-0003-2101-2206

http://dx.doi.org/10.33192/Smj.2021.87

INTRODUCTION

Germ cell tumor (GCT) is a rare tumor, accounting

for 3% of childhood cancers.

Extracranial germ cell

tumor (EGCT) is more common than intracranial germ

cell tumor (IGCT), and more than half of EGCT was

extragonadal in origin

. EGCT can be classied based

on histological features into 2 categories: teratoma and

malignant GCT. e clinical manifestations are varied,

depending on the location of the tumor. EGCT is found

to be associated with several genetic syndromes causing

gonadal dysgenesis such as Klinefelter syndrome, Turner

syndrome, and Swyer syndrome.

2-4

ose with EGCT

appear to respond well to the treatment and can attain

long term remission. e mainstay of treatment of EGCT

is surgery, although chemotherapy may be benecial in

some cases which harbor a malignant component. e

Laohverapanich et al.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

681

Original Article

SMJ

outcome of EGCT in developed countries was relatively

favorable.

Previous study in ailand demonstrated the

5-year overall survival (OS) rate of pediatric germ cell

tumor (GCT) of 70.6%; however, this study included both

IGCT and EGCT.

e clinical information regarding

ai patients with EGCT has been scarce. Our study

aimed to determine the clinical features and outcomes of

pediatric EGCT in one of the tertiary centers in ailand.

MATERIALS AND METHODS

is retrospective study was conducted in patients

diagnosed with EGCT at the Department of Pediatrics,

Faculty of Medicine Siriraj Hospital, from January 2004

to December 2013. All patients with newly diagnosed

EGCT during the study period were recruited; those

who refuse the treatment were further excluded. e

diagnosis of EGCT was established based on clinical

features, tumor markers, and radiographic ndings.

Patients who had normal serum tumor markers must

have a histopathology result to conrm a diagnosis of

EGCT. e clinical staging of testicular, ovarian, and

extragonadal GCT was determined by the Children’s

Oncology Group staging system.

7,8

Surgery was a primary

treatment for resectable tumors. Those who had an

unresectable tumor received neoadjuvant chemotherapy

consisting of cisplatin, etoposide, and bleomycin (PEB)

before surgery.

Patients with teratoma were treated

with surgery solely. However, those children with

immature teratoma (IT) either greater than stage II or

grade III tumor may have received PEB upon physician

discretions. Among patients with nonteratomatous

EGCT, those with stage I testicular GCT did not receive

adjuvant chemotherapy aer surgery, while other patients

were subsequently treated with adjuvant PEB. The

responses to the treatment were classied using RECIST

guidelines.

is retrospective study was approved by

the Siriraj Institutional Review Board (SIRB), Faculty of

Medicine Siriraj Hospital, Mahidol University, Bangkok,

ailand (Si 380/2020).

Statistical analysis

The collected data were analyzed using SPSS

Statistic version 22.0 for Windows (SPSS Inc., Chicago,

IL). Demographic data were described using mean,

medians, and percentage. e Kaplan-Meier survival

curve was used to demonstrate the OS and event-

free survival (EFS) rate of EGCT patients; event was

dened as tumor relapse or death. e patients’ age

at diagnosis, stage, histopathology subtype, site of

tumor, and adequacy of surgery were analyzed using

the Cox regression analysis to determine the predictors

of survival. e adjusted hazard ratio (HR) and 95%

condence intervals (CIs) were calculated. A p-value of

<0.05 was regarded as being statistically signicant.

RESULTS

Forty-seven patients were diagnosed with EGCT;

3 patients were excluded due to treatment refusal.

ere were 44 patients included in this study, with the

median age at diagnosis of 1.74 years (range 1 day-14.7

year). Twenty-eight patients (64%) had extragonadal

tumor; sacrococcygeal area was the most common

primary tumor location. Majority of the patients (61%)

had malignant EGCT. Yolk sac tumor (YST) was the

most common histopathological diagnosis, followed

by mature teratoma (MT) and mixed GCT. Of all 10

patients with mixed GCT, MT with a component of YST

was the most common diagnosis. e demographic data,

clinical features, histopathology and staging of EGCT

are presented in Table 1. ree patients had underlying

genetic diseases, including 1 Down syndrome (DS)

with stage I retroperitoneal IT grade II, 1 DS with stage

I ovarian dysgerminoma, and 1 Cornelia de Lange

syndrome (CdLS) with stage III sacrococygeal mixed

GCT comprising of MT and YST.

One patient presented with hemophagocytic

lymphohistiocytosis (HLH) and subsequently diagnosed

with mediastinal germinoma. He ultimately died of

infectious complication before receiving treatment for

EGCT. irty patients (68%) were treated with upfront

surgery while 13 patients (29%) received chemotherapy

as an initial treatment. Of all 30 patients undergoing

upfront surgery, 16 patients did not receive adjuvant

chemotherapy since their tumors were completely

resected and contained no malignant component.

Twenty-four patients (55%) received combination

treatment of surgery and chemotherapy, while 16 patients

(36%) were solely treated with surgery and 3 patients

(7%) received chemotherapy without surgical treatment

(Fig 1). Chemotherapy (PEB) was prescribed for 27

patients, including 26 patients with malignant EGCT

and 1 patient who had sacrococcygeal IT grade III with

lymph node metastasis.

ree patients with a pathological diagnosis of

sacrococcygeal IT grade II (1 patient) and III (2 patients)

had elevated serum tumor markers, but did not receive

chemotherapy. All of them were alive and free of disease

at the end of the study.

One patient died before the treatment of EGCT

was initiated. irty-eight patients (86%) had a complete

response; 5 patients who were unresponsive to treatment

subsequently died of disease. Relapse occurred in 3

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

682

TABLE 1. Demographic data, histopathology and staging of all patients (n=44).

Characteristics Number (%)

Gender Male 18 (41)

Female 26 (59)

Primary site of tumor Sacrococcygeal area 12 (27)

Ovary 11 (25)

Retroperitoneum 6 (14)

Mediastinum 6 (14)

Testis 5 (11)

Mandible 1 (2)

Bladder 1 (2)

Vaginal wall 1 (2)

Stomach 1 (2)

Histopathology results Teratoma

-IT 12 (27)

-MT 5 (11)

Malignant germ cell tumor

-YST 13 (29)

-Germinoma 4 (9)

-Mixed germ cell tumor

-MT with YST 5 (11)

-IT with YST with choriocarcinoma 3 (7)

-IT with YST 1 (2)

-Germinoma with choriocarcinoma 1 (2)

Staging I 17 (39)

II 3 (7)

III 18 (41)

IV 6 (14)

Abbreviations: IT, immature teratoma; MT, mature teratoma; YST, yolk sac tumor

Fig 1. Treatment of patients with extracranial germ cell tumor.

Laohverapanich et al.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

683

Original Article

SMJ

patients, with a median time to relapse of 1 year (range

3.3 months-1.1 years). Of all 3 patients with relapse,

2 patients (1 patient with YST at vaginal wall and the

other with IT at mandible) achieved remission aer a

combination of surgery and chemotherapy, and 1 patient

died of disease progression. e mortality of EGCT in

this study is detailed in Table 2. Among 27 patients who

received chemotherapy, 19 patients (70%) experienced

treatment-related toxicity. e most common adverse

reaction from chemotherapy were infection (55%)

and hematotoxicity (55%), followed by renal toxicity

(37%). Two patients with mediastinal mixed GCT had

concomitant hematologic malignancies. One of them

developed prolonged cytopenias during treatment; his

bone marrow aspiration result was compatible with acute

megakaryoblastic leukemia. e other patient had tumor

progression and subsequently died of disease; the autopsy

result revealed a component of myeloid sarcoma within

the remaining mediastinal mass with the presence of

isochromosome 12p abnormality.

e 5-year EFS and OS were 78.3% (95%CI 10.3-

13.9) and 81.1% (95%CI 10.8-14.2), respectively (Fig 2).

e median follow-up time was 6.9 years (range 14 days-

15.2 years). e comparison of EFS and OS according to

clinical factors is demonstrated in Table 3. Cox regression

analysis was performed to determine the predictors of

mortality; the only factor associated with survival was

the adequacy of surgery (HR 8.69, 95% CI 1.44-52.26,

p-value 0.018).

DISCUSSION

In our study, EGCT was common among patients

under 2 years of age, with a female preponderance; this

was concordant with other studies.

1,11

Sacrococcygeal

area appeared to be the most common primary site,

which corresponds with a previous study.

Klinefelter syndrome, Turner syndrome, and Swyer

syndrome were found to be associated with EGCT

2-4

but none of the patients in our study harbor those

conditions. However, 3 of our patients had underlying

genetic diseases including DS and CdLS. Individuals with

DS have been reported to have EGCT, but the incidence

of EGCT in DS was relatively low compared to that of

hematologic malignancies.

CdLS is a rare syndrome

resulting from mutation in cohesin protein

, and

typically aected craniofacial, gastrointestinal and central

nervous systems. Although mutation of cohesin might

be associated with the development of cancer, there was

no clear evidence that CdLS increased the risk of cancer.

Few case reports of CdLS with Wilms tumor and liver

hemangioendothelioma have been documented

, but

there was still no report of EGCT in CdLS. Hence, we

believe that the nding of EGCT in CdLS in our study

might be an incidental nding.

TABLE 2. Mortality of extracranial germ cell tumor patients (n=8).

Patient Diagnosis Stage Treatment Response of Cause of death

treatment

1 DS with retroperitoneal I TTR CR Infection (not related to

IT grade II cancer treatment)

2 Mediastinal IT grade III I TTR CR, then relapse Disease progression due

to treatment refusal

3 Sacrococcygeal IT grade III III TTR with CMT PD Disease progression

4 Mediastinal germinoma III None Not evaluable HLH

5 Mediastinal mixed GCT III CMT with TTR PR Disease progression

6 Mediastinal mixed GCT III CMT PR, concomitant Disease progression

myeloid sarcoma

7 Mediastinal mixed GCT III CMT PD, concomitant AML Disease progression

8 Sacrococcygeal YST IV CMT PD Disease progression

Abbreviations: AML, acute myeloid leukemia; CR, complete response; DS, Down syndrome; GCT, germ cell tumor; HLH, hemophagocytic

lymphohistiocytosis; IT, immature teratoma; PD, progressive disease; PR, partial response, TTR, total tumor removal; YST, yolk sac tumor

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

684

Fig 2. e 5-year event-free survival and overall survival

rate of patients with extracranial germ cell tumor.

TABLE 3. Comparison of survival rates according to various clinical factors.

Factors 5-year EFS p-value 5-year OS p-value

Age group at diagnosis

<11 yr (n=33) 83.8 0.088 87.4 0.056

 ≥11yr(n=11) 61.4  61.4

Site of tumor

Gonadal (n=16) 100 0.170 100 0.203

Extragonadal (n=28) 65.9 70.5

Diagnosis

Teratoma (n=17) 73.7 0.614 80.7 0.961

Malignant germ cell tumor (n=27) 81.1 81.3

Stage

I (n=17) 80 0.861 86.7 0.723

II (n=3) 100 100

III (n=18) 72.2 72.2

IV (n=6) 80 80

Adequacy of surgery

Partial tumor removal (n=3) 33.3 0.023 33.3 0.018

Total tumor removal (n=37) 88.6 91.6

Abbreviations: EFS, event-free survival; OS, overall survival

Laohverapanich et al.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

685

Original Article

SMJ

Several type of hematologic malignancies, especially

acute megakaryoblastic leumemia, were reported in

patients with mediastinal GCT.

9,15

Isochromosome 12p

might be responsible for the concomitant hematologic

malignancies in these patients.

Although only one of

our patients harbor this abnormal chromosome, we

believed that the hematologic malignancies in both of

them were related to the mediastinal GCT rather than a

secondary malignancy related to cancer treatment since

theirs myeloid neoplasms developed very early aer the

initiation of chemotherapy.

Chemotherapy treatment in IT is controversial,

especially in ovarian IT.

However, several reports

have revealed that chemotherapy might not benefit

for other IT patients, even if they have malignant foci

or elevated tumor markers.

18,19

In accordance with the

aforementioned studies, all 3 IT patients with elevated

serum tumor markers in our study survived aer having

a solely surgical intervention.

Previous reports revealed that teratoma usually had

a better outcome than malignant EGCT.

In contrast,

patients with teratomatous EGCT in our study had an

inferior survival rate compared to malignant EGCT, but

without statistical signicance. However, other factors,

such as treatment abandonment or a patient’s preexisting

conditions, might have aected the treatment outcome.

Among the 3 teratomatous EGCT patients who died in

this study, only 1 patient died of a refractory disease,

while another patient died of disease progression due to

treatment refusal and the other patient with DS died of

infection not related to cancer treatment several months

aer completing therapy.

e 5-year OS rate of 81.1% in this cohort was

comparatively favorable to 70.6% of the previous ai

study.

However, the aforementioned study included

both IGCT and EGCT; the interpretation should

be cautious. Improvements in supportive care may

account for the better outcome in our study, given the

fact that the chemotherapy protocol has not drastically

changed. e outcome of present study was inferior

to that of developed countries

; this may be due to the

higher proportion of teratomatous EGCT in that study

compared to our study, 78.7% versus 38.6%.

e survival rate of advanced-stage disease was

still inferior to early-stage disease

, including the results

of our study. Although several treatment approaches,

such as an intensive dose of PEB

and high dose

chemotherapy with autologous stem cell rescue

were

initiated in patients with advanced disease, they failed

to demonstrate any survival benet. In addition, disease

progression was the major cause of death in our study

especially in patients with advanced stage. More eective

treatment approaches may be required for such patients.

Younger age at diagnosis i.e. less than 11 years old and

gonadal tumor in origin were also reported to be a

good predictor for survival.

Both groups also provided

the better survival in our study but without statistical

signicance, a larger sample size might be needed to

better determine the prognostic factors.

A few patients with relapse can be salvaged by

surgery. e Cox regression analysis in our study also

demonstrated that surgery significantly improved

the survival rate. erefore, for patients whose tumor

cannot be completely removed, repeated surgery may

be warranted.

ere were limitations in this study that need to

be mentioned. First, as is common with retrospective

studies, some data might be missing or incomplete.

Secondly, the sample size in this cohort appears to be

small; some signicant prognostic factors might be not

salient. irdly, our center oen receives complicated

cases, possibly limiting the generalizability of our data

and ndings.

CONCLUSION

e outcome of EGCT in this study seemed to be

favorable but still inferior to that of developed countries,

possibly due to the higher proportion of nonteratomatous

EGCT in our study. e adequacy of surgery appeared

to be factor-associated with better clinical outcomes,

whereas novel therapy may be warranted for those

patients who are unresponsive to the current treatment.

Conict of interest: e authors have no conicts of

interest to declare.

REFERENCES

1. Kaatsch P, Hafner C, Calaminus G, Blettner M, Tulla M.

Pediatric germ cell tumors from 1987 to 2011: Incidence rates,

time trends, and survival. Pediatrics 2015;135:e136-43.

2. Matsumoto F, Shimada K, Ida S. Tumors of bilateral streak

gonads in patients with disorders of sex development containing

y chromosome material. Clin Pediatr Endocrinol 2014;23:93-7.

3. Piazza MJ, Urbanetz AA. Germ cell tumors in dysgenetic

gonads. Clinics (Sao Paulo) 2019;74:e408.

4. Williams LA, Pankratz N, Lane J, Krailo M, Roesler M,

Richardson M, et al. Klinefelter syndrome in males with germ

cell tumors: A report from the children’s oncology group.

Cancer 2018;124:3900-8.

5. De Backer A, Madern GC, Pieters R, Haentjens P, Hakvoort-

Cammel FG, Oosterhuis JW, et al. Inuence of tumor site and

histology on long-term survival in 193 children with extra-

cranial germ cell tumors. Eur J Pediatr Surg 2008;18:1-6.

6. Wiangnon S, Veerakul G, Nuchprayoon I, Seksarn P, Hongeng

S, Krutvecho T, et al. Childhood cancer incidence and

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

686

survival 2003-2005, thailand: Study from the thai pediatric

oncology group. Asian Pac J Cancer Prev 2011;12:2215-20.

7. Olson TA, Murray MJ, Rodriguez-Galindo C, Nicholson JC,

Billmire DF, Krailo MD, et al. Pediatric and adolescent

extracranial germ cell tumors: e road to collaboration. J

Clin Oncol 2015;33:3018-28.

8. Rogers PC, Olson TA, Cullen JW, Billmire DF, Marina N,

Rescorla F, et al. Treatment of children and adolescents with

stage ii testicular and stages i and ii ovarian malignant germ

cell tumors: A pediatric intergroup study--pediatric oncology

group 9048 and children’s cancer group 8891. J Clin Oncol

2004;22:3563-9.

9. Sowithayasakul P, Sinlapamongkolkul P, Treetipsatit J,

Vathana N, Narkbunnam N, Sanpakit K, et al. Hematologic

malignancies associated with mediastinal germ cell tumors:

10 years’ experience at thailand’s national pediatric tertiary

referral center. J Pediatr Hematol Oncol 2018;40:450-5.

10. Eisenhauer EA, erasse P, Bogaerts J, Schwartz LH, Sargent

D, Ford R, et al. New response evaluation criteria in solid

tumours: Revised recist guideline (version 1.1). Eur J Cancer

2009;45:228-47.

11. Schneider DT, Calaminus G, Koch S, Teske C, Schmidt P,

Haas RJ, et al. Epidemiologic analysis of 1,442 children and

adolescents registered in the german germ cell tumor protocols.

Pediatr Blood Cancer 2004;42:169-75.

12. Hasle H. Pattern of malignant disorders in individuals with

down’s syndrome. Lancet Oncol 2001;2:429-36.

13. Liu J, Krantz ID. Cornelia de lange syndrome, cohesin, and

beyond. Clin Genet 2009;76:303-14.

14. Maruiwa M, Nakamura Y, Motomura K, Murakami T, Kojiro

M, Kato M, et al. Cornelia de lange syndrome associated with

wilms’ tumour and infantile haemangioendothelioma of the

liver: Report of two autopsy cases. Virchows Arch A Pathol

Anat Histopathol 1988;413:463-8.

15. Nichols CR, Roth BJ, Heerema N, Griep J, Tricot G. Hema-

tologic neoplasia associated with primary mediastinal germ-

cell tumors. N Engl J Med 1990;322:1425-9.

16.

Bosl GJ, Ilson DH, Rodriguez E, Motzer RJ, Reuter VE, Chaganti

RS. Clinical relevance of the i(12p) marker chromosome in

germ cell tumors. J Natl Cancer Inst 1994;86:349-55.

17. Faure-Conter C, Pashankar F. Immature ovarian teratoma:

When to give adjuvant therapy? J Pediatr Hematol Oncol

2017;39:487-9.

18. Mann JR, Gray ES, ornton C, Raafat F, Robinson K, Collins

GS, et al. Mature and immature extracranial teratomas in

children: e uk children’s cancer study group experience. J

Clin Oncol 2008;26:3590-7.

19. Marina NM, Cushing B, Giller R, Cohen L, Lauer SJ, Ablin A,

et al. Complete surgical excision is eective treatment for

children with immature teratomas with or without malignant

elements: A pediatric oncology group/children’s cancer group

intergroup study. J Clin Oncol 1999;17:2137-43.

20. Rescorla FJ, Sawin RS, Coran AG, Dillon PW, Azizkhan RG.

Long-term outcome for infants and children with sacrococ-

cygeal teratoma: A report from the childrens cancer group. J

Pediatr Surg 1998;33:171-6.

21. Cushing B, Giller R, Cullen JW, Marina NM, Lauer SJ, Olson

TA, et al. Randomized comparison of combination chemo-

therapy with etoposide, bleomycin, and either high-dose or

standard-dose cisplatin in children and adolescents with

high-risk malignant germ cell tumors: A pediatric intergroup

study--pediatric oncology group 9049 and children’s cancer

group 8882. J Clin Oncol 2004;22:2691-700.

22. Necchi A, Mariani L, Di Nicola M, Lo Vullo S, Nicolai N,

Giannatempo P, et al. High-dose sequential chemotherapy

(hds) versus peb chemotherapy as rst-line treatment of

patients with poor prognosis germ-cell tumors: Mature results

of an italian randomized phase ii study. Ann Oncol 2015;

26:167-72.

23. Frazier AL, Hale JP, Rodriguez-Galindo C, Dang H, Olson T,

Murray MJ, et al. Revised risk classication for pediatric

extracranial germ cell tumors based on 25 years of clinical

trial data from the United Kingdom and United States. J Clin

Oncol 2015;33:195-201.

Laohverapanich et al.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

687

Original Article

SMJ

anaporn Chaiyapak, M.D.*, Anirut Pattaragarn, M.D.*, Suroj Supavekin, M.D.*, Nuntawan Piyaphanee,

M.D.*, Kraisoon Lomjansook, M.D.*, Julaporn Pooliam, M.Sc.**, Achra Sumboonnanonda, M.D.*

*Department of Pediatrics, **Oce for Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, ailand.

Renal Outcomes of Childhood IgA Nephropathy

and Henoch Schönlein Purpura Nephritis

ABSTRACT

Objective: Henoch-Schönlein purpura nephritis (HSPN) is considered the systemic form of IgA nephropathy

(IgAN). However, diering clinicopathological features and renal outcomes of children with IgAN and HSPN have

been reported in some studies.

Materials and Methods: is study retrospectively reviewed children with IgAN and HSPN younger than 18

years, between January 2004 and December 2015. e clinicopathological characteristics at diagnosis and the renal

outcomes aer at least 1 year of follow-up were compared between the two groups.

Results: A total of 54 children, comprising 21 with IgAN and 33 with HSPN, were recruited. e children with HSPN

were younger than the children with IgAN. Gross hematuria and nephritic syndrome at the initial presentation

were more common in children with IgAN. Regarding the pathological ndings, IgAN had greater chronicity than

HSPN. Aer a median follow-up period from rst presentation to renal outcomes measurement of 4.0 years (1.3-

12.2) in children with IgAN and 4.2 years (1.1-11.4) in children with HSPN, the renal outcomes were better in the

latter group. e incidence of chronic kidney disease (CKD) was 28.6% in children with IgAN and 6.1% in children

with HSPN (p = 0.02). Complete recovery was observed more frequently in children with HSPN than in children

with IgAN (57.1% in IgAN vs. 87.9% in HSPN, p = 0.01).

Conclusion: Childhood IgAN has greater chronicity and worse renal outcomes than childhood HSPN, with a

lower rate of complete recovery and a higher frequency of CKD. We recommend long-term follow-up for CKD in

children with IgAN.

Keywords: Chronic kidney disease; Chronic renal disease; End-stage renal disease; Henoch-Schönlein purpura

nephritis; IgA nephropathy (Siriraj Med J 2021; 73: 687-694)

Corresponding author: Achra Sumboonnanonda

E-mail: achrasu@gmail.com, thanaporn.cha@mahidol.ac.th

Received 31 March 2021 Revised 11 August 2021 Accepted 26 August 2021

ORCID ID: https://orcid.org/0000-0001-5855-5314

http://dx.doi.org/10.33192/Smj.2021.88

INTRODUCTION

IgA nephropathy (IgAN) and Henoch-Schönlein

purpura (HSP) are common causes of glomerulonephritis in

children.

IgAN is a type of primary glomerulonephritis.

2,3

HSP is a clinical syndrome that aects many organs,

including the kidneys (HSP nephritis, HSPN), and is

classied as a type of systemic vasculitis.

1,4

HSP was

redesignated IgA vasculitis in the second International

Chapel Hill Consensus Conference (CHCC 2012),

but this term has not yet come into widespread use. A

multivariate analysis showed that age of onset > 4 years,

severe abdominal pain, and persistent purpura were

signicantly associated with the development of HSPN.

HSP is thought to be a systemic form of IgAN

because these two conditions share several clinical,

histological, and immunological features.

7,8

e renal

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

688

pathological features of HSPN are identical to those in

IgAN, which is associated with the deposition of IgA in

the mesangium. HSP mainly aects children,

whereas

IgAN occurs more frequently in adults.

Recently, Kamei

et al

posited that the two disorders were variants of a

single disease because 6 children with IgAN developed

HSPN 5 months to 14 years later. Few clinical studies

have compared IgAN and HSPN in adults.

11,12

A study of

adults by Calvo-Rio et al.

observed more severe renal

outcomes in patients with IgAN than in patients with

HSPN (not limited to biopsy-proven HSPN). Another

matched cohort in Korea demonstrated that there were

no signicant dierences in renal outcomes between

these two conditions.

To date, the only one clinical

study comparing IgAN and HSPN in children has been

published; that study was conducted in 1987

and showed

that children with HSPN had a higher incidence of chronic

kidney disease (CKD) than children with IgAN (16% in

HSPN vs. 5% in IgAN), in contrast to comparative studies

conducted in adults. However, limited data were available

on children receiving immunosuppressive drugs in that

study. Additionally, that report included the time period

before the routine use of angiotensin-converting enzyme

inhibitors (ACEIs) and/or angiotensin receptor blockers

(ARBs). e results of previous studies

14,15

revealed an

association between treatment with ACEIs and/or ARBs

and reduced proteinuria in children with IgAN and

HSPN. e reduction of proteinuria over time can slow

progression to end-stage renal disease (ESRD) in patients

with IgAN and HSPN.

14,16

erefore, the dierences in

clinicopathological characteristics and renal outcomes

between childhood IgAN and HSPN have not yet been

determined.

e aim of this study was to compare the clinical

characteristics, renal pathology, and renal outcomes of

children with IgAN and HSPN during the period when

ACEIs and/or ARBs were routinely used at a single

tertiary care hospital.

MATERIALS AND METHODS

Study population

e study population included all children aged

less than 18 years who were diagnosed with IgAN or

HSPN at Siriraj Hospital between January 2004 and

December 2015. e exclusion criteria were (i) a renal

biopsy performed at another institution, (ii) less than

1 year of follow-up, and (iii) missing data. All children

with IgAN underwent renal biopsy and were diagnosed

according to the Oxford classication

which is based on

the presence of dominant or codominant IgA staining

in glomeruli without systemic disease.

HSP was diagnosed according to the European League

Against Rheumatism (EULAR)/Paediatric Rheumatology

European Society (PreS)-endorsed consensus criteria for

the classication of childhood vasculitides.

e diagnostic

criteria included palpable purpura in the presence of

at least one of the following four features: (i) diuse

abdominal pain, (ii) any biopsy showing predominant

IgA deposition, (iii) arthritis or arthralgia, and (iv) renal

involvement. HSPN was dened as HSP accompanied by

renal involvement including at least one of the following:

(i) proteinuria, (ii) hematuria, (iii) acute kidney injury

or rapidly progressive glomerulonephritis (RPGN), or

(iv) renal biopsy showing predominant IgA deposition.

Renal biopsy was performed in patients with nephrotic

syndrome, decreased renal function, or substantial

proteinuria that persisted for more than 1 month.

Clinical denitions

Proteinuria was dened as a urine protein-to-creatinine

ratio (UPCR) greater than 0.2 mg/mg and categorized

as absent, mild or severe proteinuria. Mild and severe

proteinuria were dened as UPCR 0.2-1 and > 1 mg/

mg, respectively. e estimated glomerular ltration

rate (eGFR) was calculated using the Schwartz formula

with an enzymatic method.

Nephritic syndrome was

dened as hematuria with either hypertension or eGFR

< 90 ml/min/1.73 m

at presentation. Nephrotic syndrome

was diagnosed if nephrotic-range proteinuria (UPCR

> 2 mg/mg) and hypoalbuminemia (serum albumin

< 2.5 g/dL) were present. Hypertension was diagnosed

if blood pressure was greater than the 95

percentile for

age, gender, and height or greater than 130/90 mmHg in

adolescent participants. RPGN was a clinical syndrome

diagnosed if children manifested features of nephritis

syndrome and had progressive loss of renal function

over a short period of time.

Renal outcomes were classied into 3 categories

according to renal manifestations observed at the last

follow-up visit: (i) remission, (ii) isolated microscopic

hematuria, or (iii) CKD. Remission was dened as normal

renal function with no proteinuria or microscopic hematuria.

Hematuria was dened as > 5 red blood cells per high-

power eld in a centrifuged urine specimen. Isolated

microscopic hematuria was diagnosed if children had

microscopic hematuria with normal renal function and

no proteinuria. We dened CKD as a persistent eGFR

< 60 ml/min/1.73 m

for at least 3 months or persistent

proteinuria > 3 months. ESRD was dened as eGFR

< 15 ml/min/1.73 m

Chaiyapak et al.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

689

Original Article

SMJ

Treatment

All patients received supportive treatment according

to their individual needs, including uid and electrolyte

control, blood pressure control, correction of acidosis,

and renal replacement therapy. Furthermore, the children

received immunosuppressive drugs, such as pulse

methylprednisolone, glucocorticoids, cyclophosphamide,

or azathioprine, depending on the disease severity. Some

children with HSPN received glucocorticoids due to

extrarenal symptoms such as severe abdominal pain.

e children received ACEIs and/or ARBs to reduce

proteinuria and treat hypertension.

Statistical analysis

Descriptive statistics were calculated for the baseline

demographic and clinical characteristics. Continuous data

were presented as the mean (± standard deviation) for

variables with a normal distribution or as the median and

range for variables that were not normally distributed.

Categorical data were expressed as absolute numbers

and percentages. Statistical signicance was determined

using Pearson’s chi-square test or Fisher’s exact test for

categorical variables and Student’s t-test or the Mann-

Whitney U test for continuous variables, as appropriate.

A P value < 0.05 was considered statistically signicant.

All statistical calculations were performed using PASW

Statistics (SPSS) 18.0 (SPSS Inc., Chicago, IL, USA).

Data were obtained from electronic patient records.

is study was approved by the Siriraj Hospital Ethics

Board.

RESULTS

Clinical and pathological features

Seventy children were diagnosed with either IgAN

or HSPN from January 2004 to December 2015 at Siriraj

Hospital. Of these children, 16 were followed up for less

than 1 year, thus meeting the exclusion criteria. Fiy-four

children were included in the nal study population,

with 21 (38.9%) in the IgAN group and 33 (61.1%) in

the HSPN group. e median follow-up durations in

the IgAN and HSPN groups were 4.0 years (1.3-12.2)

and 4.2 years (1.1-11.4), respectively, and there was no

statistically signicant dierence between them (p =

0.97). Baseline demographic and clinical characteristics

are summarized in Table 1. Children with IgAN were

signicantly older. e mean age of onset was 11.2±3.0

years and 9.0±3.3 years (p = 0.02) for children with IgAN

and HSPN, respectively. e two groups were similar

in sex distribution and severity of renal involvement

(proteinuria, initial eGFR, and nephrotic syndrome)

at presentation. However, children with IgAN were

more likely than those with HSPN to present with gross

hematuria (61.9% in IgAN vs. 30.3% in HSPN, p = 0.03)

and nephritic syndrome (81.0% in IgAN vs. 39.4% in

HSPN, p = 0.01). Baseline eGFR was comparable between

the two groups (87.5 (9.2-253.2) ml/min/1.73 m

in IgAN

vs. 104.5 (9.5-261.4) ml/min/1.73 m

in HSPN, p= 0.13).

Renal biopsy was performed in all children with

IgAN and 20 (60.6%) children with HSPN. e median

(min-max) time from rst presentation to renal biopsy

were similar between groups: 10 days (0-359) in the

IgAN group and 7 days (0-271) in HSPN group (p =

0.71). Table 2 shows the frequency of renal pathological

features at the time of diagnosis. e most common

pathological nding was mesangial proliferation in both

groups (76.2% in IgAN vs. 70.0% in HSPN, p = 0.73).

Crescents (57.1% in IgAN vs. 55.0% in HSPN, p = 1.00)

and endocapillary proliferation (23.8% in IgAN vs. 40.0%

in HSPN, p = 0.33) were similar in both groups. Children

with IgAN were more likely than those with HSPN

to show chronicity on renal biopsy, including tubular

atrophy and interstitial brosis (76.2% in IgAN vs. 25.0%

in HSPN, p = 0.002). Additionally, children with IgAN

had a higher percentage of global sclerosis than those with

HSPN, but the dierence was not statistically signicant

(42.9% in IgAN vs. 15.0% in HSPN, p = 0.09).

Treatment

e immunosuppressive medications used within the

year aer diagnosis are summarized in Table 3. Due to

the retrospective nature of the study, treatment showed

some variation among physicians. Pulse methylprednisolone

30 mg/kg (maximum 1 g) for 3-5 consecutive days was

initially prescribed to 19.0% of children with IgAN and

12.1% of children with HSPN due to RPGN (p=0.70).

Most children with HSPN received prednisolone (90.9%),

whereas only 57.1% of children with IgAN received

prednisolone (p = 0.006). One possible reason is that

prednisolone was generally prescribed in many children

with HSP because of extrarenal symptoms such as severe

abdominal pain. In contrast, all children with IgAN

received prednisolone due to renal indications. However,

the prescription frequency of other immunosuppressive

drugs, such as cyclophosphamide and azathioprine, did

not dier between the groups. ese drugs were used

in a small number of children who did not respond

to corticosteroids. None of the children in this study

received mycophenolate mofetil. ACEIs were prescribed

to 42.9% (9/21) and 36.4% (12/33) of children with IgAN

and HSPN (p = 0.64), respectively.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

690

TABLE 1. Baseline demographic and clinical characteristics of children with HSPN and IgAN.

TABLE 2. Frequency of renal pathologic features at time of diagnosis.

TABLE 3. Immunosuppressive medications within the 1st year aer diagnosis.

Characteristics HSPN IgAN P

(n=33) (n=21)

Sex, n (%)

Male 18 (54.5) 16 (76.2) 0.15

Age, years (mean±SD) 9.0±3.3 11.2±3.0 0.02

Gross hematuria, n (%) 10 (30.3) 13 (61.9) 0.03

Proteinuria

, n (%)

No proteinuria 5 (15.2) 8 (38.1) 0.15

Mild proteinuria 14 (42.4) 5 (23.8)

Heavy proteinuria 14 (42.4) 8 (38.1)

eGFR, ml/min/ 1.73m

(median, max-min) 104.5 (9.5-261.4) 87.5 (9.2-253.2) 0.13

Nephritic syndrome

, n (%) 13 (39.4) 17 (81.0) 0.01

Nephrotic syndrome

, n (%) 2 (14.3) 3 (23.1) 0.65

HSPN, Henoch Schönlein Purpura Nephritis; IgAN, IgA nephropathy; UPCR, urine protein to creatinine ratio; eGFR, estimated glomerular

ltration rate

No, UPCR < 0.2; mild, UPCR 0.2-1; heavy proteinuria, UPCR > 1 mg/mg

Nephritic syndrome includes hematuria with either hypertension or eGFR < 90 ml/min/ 1.73m

Nephrotic syndrome includes hypoalbuminemia (serum albumin < 2.5 g/dL) and nephrotic range proteinuria (UPCR > 2 mg/mg)

Renal pathology HSPN IgAN P

(n=20) (n=21)

Mesangial proloferation, n (%) 14 (70.0) 16 (76.2) 0.73

Endocapillary proliferation, n (%) 8 (40.0) 5 (23.8) 0.33

Crescents

, n (%) 11 (55.0) 12 (57.1) 1.00

Global sclerosis, n (%) 3 (15.0) 9 (42.9) 0.09

Tubular atrophy and interstitial brosis, n (%) 5 (25.0) 16 (76.2) 0.002

Any crescents

Medication HSPN IgAN P

(n=33) (n=21)

Pulse methylprednisolone, n (%) 4 (12.1) 4 (19.0) 0.70

Prednisolone, n (%) 30 (90.9) 12 (57.1) 0.006

Cyclophosphamide, n (%) 9 (27.3) 4 (19.0) 0.54

Azathioprine, n (%) 2 (6.1) 2 (9.5) 0.64

Chaiyapak et al.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

691

Original Article

SMJ

Renal outcomes

e renal outcomes at the last follow-up visit in

21 children with IgAN and 33 children with HSPN are

summarized in Table 4. e median (min-max) length

of follow-up from rst presentation to renal outcomes

measurement was similar between groups: 4.0 years

(1.3-12.2) in the IgAN group and 4.2 years (1.1-11.4) in

the HSPN group (p = 0.97). e renal outcomes were

better in children with HSPN than with IgAN. Complete

recovery was more frequent in children with HSPN than

with IgAN (87.9% in HSPN vs. 57.1% in IgAN, p = 0.01).

Persistent isolated microscopic hematuria was observed

more frequently in children with IgAN than with HSPN

(14.3% in IgAN vs. 6.1% in HSPN, p = 0.32).

e incidence of CKD was 28.6% in children with

IgAN and 6.1% in those with HSPN (p = 0.02). ere

was no signicant dierence in ESRD in either group

(14.3% in IgAN vs 6.1% in HSPN, p = 0.37). Three

children with IgAN (14.3%) required renal replacement

therapy. Two children with HSPN (6.1%) progressed

to ESRD and required renal replacement therapy. All

children with ESRD exhibited signicant crescentic

involvement greater than 50% and tubular atrophy

and interstitial brosis greater than 25% on their rst

renal biopsy. ey received immunosuppressive drugs,

including pulse methylprednisolone, prednisolone, and

pulse cyclophosphamide, but did not respond.

None of the children in this study died.

DISCUSSION

IgAN and HSPN are common glomerular disorders

in pediatric patients with the potential to progress to

CKD.

1,2,7

e pathogenesis of these two conditions is

similar, being associated with galactose-decient IgA1

and increased formation of IgA1 immune complexes in

circulation; these complexes are ultimately deposited in

glomeruli.

20,21

is study demonstrated that childhood

IgAN has greater chronicity and worse renal outcomes

than childhood HSPN. e incidence of CKD was 28.6% in

children with IgAN and 6.1% in children with HSPN (p=

0.02). Complete recovery was observed more frequently

in children with HSPN than in children with IgAN.

Demographic data demonstrated a predominance

of males in both diseases (76.2% in IgAN vs. 54.5% in

HSPN), and children with HSPN were signicantly

younger than children with IgAN (11.2±3.0 years in

IgAN vs. 9.0±3.3 years in HSPN, p = 0.02), as in previous

pediatric studies.

8,9,13,22-25

Both groups included in this

study exhibited similar characteristics of initial renal

involvement, including proteinuria, nephrotic syndrome

and initial eGFR, except that children with IgAN were

more likely to present with gross hematuria (61.9% in

IgAN vs. 30.3% in HSPN, p =0.03) and nephritic syndrome

(81.0% in IgAN vs. 39.4% in HSPN, p = 0.01). In this

regard, no major dierences were observed when our

results were compared with those from other pediatric

series.

9,14,23,24,26

Although IgAN is the most common glomerular

disease during the second and third decades of life, the

mean age of children with IgAN in previous studies

was approximately 10-15 years old.

8,15,23,25

In support of

this notion, the mean age of children with IgAN in this

study was 11.2±3.0 years. Gross hematuria is commonly

present in children with IgAN (71.0%).

As expected,

our results showed that 13 of 21 (61.9%) children with

IgAN had gross hematuria at initial presentation. e

presence of nephrotic syndrome in previous pediatric

series was 1.1-14%,

8,26

which was lower than the rate

observed in this study (23.1%).

e mean age of HSP in children is approximately

6-8 years old.

1,8,14

However, the mean age of children with

HSPN in pediatric series is higher, at approximately 8-14

years old.

8,9,14,24,27,2

Likewise, the mean age at presentation

in children with HSPN in this study was 9.0 ± 3.3 years.

Gross hematuria is uncommon in children with HSPN,

occurring in approximately 10-14% of cases.

24,27

In this

TABLE 4. Renal outcome at last follow up.

Renal outcome HSPN IgAN P

(n=33) (n=21)

Complete recovery, n (%) 29 (87.9) 12 (57.1) 0.01

Isolated microscopic hematuria, n (%) 2 (6.1) 3 (14.3) 0.32

Chronic kidney disease, n (%) 2 (6.1) 6 (28.6) 0.02

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

692

study, however, a larger proportion of children with

HSPN (30.3%) had gross hematuria at presentation.

Previous series demonstrated that the rate of nephrotic

syndrome in childhood HSPN was 5-45%.

8,9,14,24,27,28

is

range was supported by this study, in which 14.3% of

children with HSPN had nephrotic syndrome at the

initial presentation.

Pathological ndings in children with IgAN and

HSPN have been shown to depend on the timing of renal

biopsy.

9,29

Children in the early stages of both disorders

generally have mesangial and endocapillary proliferation,

while those with late-stage disease generally have segmental

or global sclerosis and tubular atrophy interstitial brosis.

9,22

Consistent with a previous study,

considerable mesangial

proliferation was the most common renal pathological

feature observed in patients with both disorders in this

study (76.2% in patients with IgAN vs 70.0% in patients

with HSPN). Tubular atrophy and interstitial brosis are

pathological features that are independently associated

with unfavorable renal outcomes.

9,23,30

Our results would

appear to conrm a higher rate of tubular atrophy and

interstitial brosis in children with IgAN than in children

with HSPN (76.2% in IgAN vs 25% in HSPN, p=0.002),

which led us to hypothesize that renal biopsy in children

with HSPN was performed earlier.

Corticosteroids decrease the intensity and duration

of abdominal pain and the severity of arthritis in children

with HSP.

4,31

However, the use of corticosteroids in children

with HSP does not eectively prevent the development of

nephritis.

31,32

e use of corticosteroids was more common

in children with HSPN than with IgAN in this study

(57.1% in IgAN vs 90.9% in HSPN, p=0.006), probably

due to the frequent extrarenal manifestations presented

in children with HSPN. In contrast, corticosteroids were

generally given to children with IgAN only if there were

renal indications. To date, there is little evidence to

support the additional use of adjunctive therapy with

immunosuppression, such as mycophenolate mofetil or

azathioprine, as a standard regimen in either children

with IgAN or children with HSPN.

33,34

Data on renal outcomes in children with IgAN and

HSPN varied from complete recovery to ESRD. In a series

of pediatric patients, 5-43% of children with IgAN

13,23

and 4-13% of children with HSPN

13,14,24,35

developed

CKD, including ESRD. However, these results should be

interpreted with caution because discrepancies could be

related to several factors, such as dierences in patient

selection, treatment strategies, duration of follow-up, and

outcome measurement. Patient selection bias existed,

particularly for HSPN, can make renal outcomes highly

variable. In this regard, some centers included only

biopsy-proven HSPN,

9,14,27,28

while others analyzed data

regardless of whether a biopsy was performed.

13,24,36

Additionally, some countries have active urine screening

programs, which increase the likelihood that children with

IgAN will be diagnosed and treated in the early stages

of disease; this may aect renal outcomes. Moreover,

immunosuppressive medications diered depending

on the preferences of individual centers, and dierent

treatment strategies may also aect renal outcomes.

Furthermore, the discrepancy between renal outcome

measurements among centers made these variables

dicult to compare.

A study comparing childhood IgAN and HSPN

in a single center

found that HSPN could be more

aggressive than IgAN, since higher incidence of CKD

was observed in children with HSPN (5.0% in IgAN vs.

16.0% in HSPN). In contrast, this study reported better

renal outcomes in children with HSPN than with IgAN,

since children with HSPN achieved a higher rate of

complete recovery (57.1% in IgAN vs 87.9% in HSPN,

p=0.01) and a lower incidence of CKD than children with

IgAN (28.6% in IgAN vs. 6.1% in HSPN, p=0.02). e

median time from rst presentation to renal outcomes

measurement was similar between groups in this study.

One possible explanation is that children with IgAN had

a longer course of disease before being diagnosed and

this was supported by the ndings that IFTA was more

common in children with IgAN than in children with

HSPN in this study. Although the median time from

rst presentation to renal biopsy were similar between

groups in this study, the diagnosis of IgAN depended

on a renal biopsy, and thus children with early-stage

IgAN and subtle clinical symptoms might be missed

initially and present later with full-blown disease and

had chronicity on the renal pathology. In addition, our

country has no routine screening urinalysis in children;

therefore, mild cases of IgAN are probably missed. In

contrast, the diagnosis of HSP was based on clinical

symptoms; almost all children with HSP presented with

obvious, palpable purpura that led them to seek medical

attention. Routine urinalysis was required in all children

with HSP; therefore, renal involvement may be identied

and treated in the early stages of disease. is nding

might explain why children with IgAN had worse renal

outcomes than children with HSPN in this study.

Long-term follow-up studies revealed that the

urinalysis of 29-43% of pediatric patients with IgAN

returned to normal.

13,23,34

is was supported by this

study, in which more than half of children with IgAN

(57.1%) completely recovered. e incidence of CKD

in this study was 28.6% which was close to the overall

Chaiyapak et al.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

693

Original Article

SMJ

incidence of childhood IgAN in previous pediatric studies

(5-43%).

13,23

ree (14.3%) of the 21 children with IgAN

in our study developed ESRD, similar to the long-term

ESRD rate (11%) reported by a Finnish study.

All

patients with ESRD in this study experienced signicant

tubular atrophy and interstitial brosis.

e course of HSPN is usually favorable. Most

children with HSPN (87.9%) achieved complete recovery

aer a median follow-up period of 3.5 years (1.1-11.4) in

this study. ese results are consistent with previously

reported rates (66-85%).

24,28,35

However, approximately

4-13% of children with HSPN develop CKD.

14,24,35

Similar

to the previous study, the incidence of CKD in this study

was 6.1%. Two (6.1%) of the 33 children with HSPN in

this study developed ESRD, which was similar to the

rates reported in other pediatric studies (0-7%).

24,27,34,36

is study has several strengths. First, this report

is the rst to compare renal outcomes between children

with HSPN and IgAN in the era of ACEIs and/or ARBs,

revealing superior renal outcomes in childhood IgAN.

Second, this study is homogenous in terms of the analysis

of renal outcomes because the same diagnostic criteria

were used for both IgAN and HSPN. ird, the children

received similar immunosuppressive treatment according

to disease severity, despite the absence of standardized

management for both diseases. Our study also has several

limitations. First, this study employed a retrospective

design. Second, the renal outcome data for childhood

IgAN and HSPN in this study were obtained from a

tertiary center in ailand; therefore, these data may

be dicult to generalize to the whole population. For

example, many children with HSPN were referred when

they had severe renal involvement at onset. Patients with

mild cases of HSPN, might not be referred and might

instead be followed at primary and secondary hospitals.

ird, our country does not perform school urinalysis

screening programs; therefore, children with early-stage

IgAN are not detected and were not included. Overall,

children with IgAN in this study are not representative

of the whole childhood IgA population, especially mild

cases. Fourth, relatively fewer patients were analyzed in

this study. Further prospective cohort multicenter studies

and studies comparing the renal outcomes between 2

groups with similar renal pathologies are required to

clarify these limitations.

CONCLUSION

In conclusion, dierences were observed between

childhood IgAN and HSPN. Children with HSPN were

younger than children with IgAN. Gross hematuria and

nephritis syndrome occurred more frequently in children

with IgAN than in those with HSPN, and the chronicity

of renal pathology was also higher in children with IgAN.

Additionally, the renal outcomes of children with IgAN

were worse than children with HSPN. We recommend

long-term follow-up for CKD in children with IgAN.

ACKNOWLEDGEMENTS

e authors are grateful to all of the participants

and attending physicians for their contributions.

Funding Sources: This study was supported by the

Research Department, Faculty of Medicine Siriraj Hospital,

Mahidol University, Bangkok, ailand.

Conicts of interest: e authors declare that there are

no conicts of interest in this study.

Statement of Ethics: is study was approved by the

Siriraj Hospital Ethics Board (Si 380/2016).

REFERENCES

1. Delos Santos NM, Wyatt RJ. Pediatric IgA nephropathies: clinical

aspects and therapeutic approaches. Semin Nephrol. 2004;24(3):

269-86.

2. Wyatt RJ, Julian BA. IgA nephropathy. N Engl J Med. 2013;

368(25):2402-14.

3. Calviño MC, Llorca J, García-Porrúa C, Fernández-Iglesias JL,

Rodriguez-Ledo P, González-Gay MA. Henoch-Schönlein

purpura in children from northwestern Spain: a 20-year

epidemiologic and clinical study. Medicine (Baltimore). 2001;

80(5):279-90.

4. Saulsbury FT. Clinical update: Henoch-Schönlein purpura.

Lancet. 2007;369(9566):976-8.

5. Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F,

et al. 2012 revised International Chapel Hill Consensus Conference

Nomenclature of Vasculitides. Arthritis Rheum. 2013;65(1):1-11.

6. Sano H, Izumida M, Shimizu H, Ogawa Y. Risk factors of renal

involvement and signicant proteinuria in Henoch-Schönlein

purpura. Eur J Pediatr. 2002;161(4):196-201.

7. Sanders JT, Wyatt RJ. IgA nephropathy and Henoch-Schönlein

purpura nephritis. Curr Opin Pediatr. 2008;20(2):163-70.

8. Komatsu H, Fujimoto S, Yoshikawa N, Kitamura H, Sugiyama H,

Yokoyama H. Clinical manifestations of Henoch-Schönlein

purpura nephritis and IgA nephropathy: comparative analysis

of data from the Japan Renal Biopsy Registry (J-RBR). Clin

Exp Nephrol. 2016;20(4):552-60.

9. Lu S, Liu D, Xiao J, Yuan W, Wang X, Zhang X, et al. Comparison

between adults and children with Henoch-Schönlein purpura

nephritis. Pediatr Nephrol. 2015;30(5):791-6.

10. Kamei K, Ogura M, Sato M, Ito S, Ishikura K. Evolution of IgA

nephropathy into anaphylactoid purpura in six cases--further

evidence that IgA nephropathy and Henoch-Schonlein purpura

nephritis share common pathogenesis. Pediatr Nephrol. 2016;

31(5):779-85.

11. Calvo-Río V, Loricera J, Martín L, Ortiz-Sanjuán F, Alvarez L,

González-Vela MC, et al. Henoch-Schönlein purpura nephritis

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

694

and IgA nephropathy: a comparative clinical study. Clin Exp

Rheumatol. 2013;31(1 Suppl 75):S45-51.

12. Oh HJ, Ahn SV, Yoo DE, Kim SJ, Shin DH, Lee MJ, et al.

Clinical outcomes, when matched at presentation, do not vary

between adult-onset Henöch-Schönlein purpura nephritis and

IgA nephropathy. Kidney Int. 2012;82(12):1304-12.

13. Yoshikawa N, Ito H, Yoshiya K, Nakahara C, Yoshiara S, Hasegawa

O, et al. Henoch-Schoenlein nephritis and IgA nephropathy in

children: a comparison of clinical course. Clin Nephrol. 1987;

27(5):233-7.

14. Tudorache E, Azema C, Hogan J, Wannous H, Aoun B, Decramer S,

et al. Even mild cases of paediatric Henoch-Schönlein purpura

nephritis show signicant long-term proteinuria. Acta Paediatr.

2015;104(8):843-8.

15. Yata N, Nakanishi K, Shima Y, Togawa H, Obana M, Sako M,

et al. Improved renal survival in Japanese children with IgA

nephropathy. Pediatr Nephrol. 2008;23(6):905-12.

16. Coppo R, Peruzzi L, Amore A, Piccoli A, Cochat P, Stone R,

et al. IgACE: a placebo-controlled, randomized trial of angiotensin-

converting enzyme inhibitors in children and young people

with IgA nephropathy and moderate proteinuria. J Am Soc

Nephrol. 2007;18(6):1880-8.

17. Roberts IS, Cook HT, Troyanov S, Alpers CE, Amore A, Barratt J,

et al. e Oxford classication of IgA nephropathy: pathology

denitions, correlations, and reproducibility. Kidney Int.

2009;76(5):546-56.

18. Ozen S, Ruperto N, Dillon MJ, Bagga A, Barron K, Davin JC,

et al. EULAR/PReS endorsed consensus criteria for the classication

of childhood vasculitides. Ann Rheum Dis. 2006;65(7):936-

41.

19. Schwartz GJ, Muñoz A, Schneider MF, Mak RH, Kaskel F,

Warady BA, et al. New equations to estimate GFR in children

with CKD. J Am Soc Nephrol. 2009;20(3):629-37.

20. Moldoveanu Z, Wyatt RJ, Lee JY, Tomana M, Julian BA,

Mestecky J, et al. Patients with IgA nephropathy have increased

serum galactose-decient IgA1 levels. Kidney Int. 2007;71(11):1148-

54.

21. Kaumann RH, Herrmann WA, Meÿer CJ, Daha MR, Van Es

LA. Circulating IgA-immune complexes in Henoch-Schönlein

purpura. A longitudinal study of their relationship to disease

activity and vascular deposition of IgA. Am J Med. 1980;69(6):859-

66.

22. Mao S, Xuan X, Sha Y, Zhao S, Zhu C, Zhang A, et al. Clinico-

pathological association of Henoch-Schoenlein purpura nephritis

and IgA nephropathy in children. Int J Clin Exp Pathol. 2015;

8(3):2334-42.

23. Ronkainen J, Ala-Houhala M, Autio-Harmainen H, Jahnukainen

T, Koskimies O, Merenmies J, et al. Long-term outcome 19

years aer childhood IgA nephritis: a retrospective cohort

study. Pediatr Nephrol. 2006;21(9):1266-73.

24. Soylemezoglu O, Ozkaya O, Ozen S, Bakkaloglu A, Dusunsel

R, Peru H, et al. Henoch-Schönlein nephritis: a nationwide

study. Nephron Clin Pract. 2009;112(3):c199-204.

25. Shibano T, Takagi N, Maekawa K, Mae H, Hattori M, Takeshima

Y, et al. Epidemiological survey and clinical investigation of

pediatric IgA nephropathy. Clin Exp Nephrol. 2016;20(1):111-7.

26. Villatoro-Villar M, Crowson CS, Warrington KJ, Makol A,

Ytterberg SR, Koster MJ. Clinical Characteristics of Biopsy-

Proven IgA Vasculitis in Children and Adults: ARetrospective

Cohort Study. Mayo Clin Proc. 2019;94(9):1769-80.

27. Edström Halling S, Söderberg MP, Berg UB. Predictors of outcome

in Henoch-Schönlein nephritis. Pediatr Nephrol. 2010;25(6):

1101-8.

28. Delbet JD, Hogan J, Aoun B, Stoica I, Salomon R, Decramer S,

et al. Clinical outcomes in children with Henoch-Schönlein

purpura nephritis without crescents. Pediatr Nephrol. 2017;

32(7):1193-9.

29. Shima Y, Nakanishi K, Hama T, Sato M, Mukaiyama H, Togawa

H, et al. Biopsy timing and Oxford classication variables in

childhood/adolescent IgA nephropathy. Pediatr Nephrol. 2015;

30(2):293-9.

30. Coppo R. Clinical and histological risk factors for progression

of IgA nephropathy: an update in children, young and adult

patients. J Nephrol. 2017;30(3):339-46.

31. Ronkainen J, Koskimies O, Ala-Houhala M, Antikainen M,

Merenmies J, Rajantie J, et al. Early prednisone therapy in

Henoch-Schönlein purpura: a randomized, double-blind,

placebo-controlled trial. J Pediatr. 2006;149(2):241-7.

32. Floege J, Feehally J. Treatment of IgA nephropathy and Henoch-

Schönlein nephritis. Nat Rev Nephrol. 2013;9(6):320-7.

33. Barratt J, Feehally J. Treatment of IgA nephropathy. Kidney

Int. 2006;69(11):1934-8.

34. Shima Y, Nakanishi K, Hama T, Mukaiyama H, Togawa H, Sako

M, et al. Spontaneous remission in children with IgA nephropathy.

Pediatr Nephrol. 2013;28(1):71-6.

35. Narchi H. Risk of long term renal impairment and duration

of follow up recommended for Henoch-Schonlein purpura

with normal or minimal urinary ndings: a systematic review.

Arch Dis Child. 2005;90(9):916-20.

36. Ronkainen J, Nuutinen M, Koskimies O. e adult kidney 24

years aer childhood Henoch-Schönlein purpura: a retrospective

cohort study. Lancet. 2002;360(9334):666-70.

Chaiyapak et al.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

695

Original Article

SMJ

Jittima Panyasarawut, M.N.S.*, Wallada Chanruangvanich, D.N.S.**, Prangtip Chayaput, Ph.D.**, eerapol

Witthiwej, M.D.***

*Master of Nursing Science Program in Adult and Gerontological Nursing, Faculty of Nursing, Mahidol University, **Department of Surgical Nursing,

Faculty of Nursing, Mahidol University, ***Division of Neurosurgery, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University,

Bangkok 10700, ailand.

Effects of Physical Exercise Program on Physical

Mobility of Patients with Cranial Surgery

ABSTRACT

Objective: is research aimed to study the eects of a physical exercise program on physical mobility in cranial

surgery patients.

Materials and Methods: e researcher used a quasi-experimental method of surveying 58 patients who had cranial

surgery at Siriraj Hospital. e research group was divided into two groups: an experimental group (28 patients)

participating in a physical exercise program of patients aer cranial surgery, and a control group (30 patients)

receiving routine nursing care only. e evaluation of the patients’ physical mobility was performed three days

aer the surgery.

Results: Most patients in the research group had an intracranial tumor (86.2%). One day aer the surgery, the

experimental group had minor pain at the wound site while the control group had moderate pain. Both groups felt

discomfort (64.2%) or had muscle stiness in the neck and shoulder areas (63.3%). ree days aer the surgery, at

the end of the program, the body movement function of both groups was reduced compared with the preoperative

data. However, the experimental group showed better body movement function scores than the control one as the

scores of the former were reduced less than those of the latter at p < 0.05.

Conclusion: Nurses who provide health care services to patients aer cranial surgery should apply the physical

exercise program to promote the recovery of the patients’ physical mobility.

Keywords: Physical exercise; physical mobility; cranial surgery (Siriraj Med J 2021; 73: 695-701)

Corresponding author: Wallada Chanruangvanich

E-mail: wallada.cha@mahidol.ac.th

Received 21 February 2021 Revised 19 July 2021 Accepted 20 July 2021

ORCID ID: https://orcid.org/0000-0002-2593-389X

http://dx.doi.org/10.33192/Smj.2021.89

INTRODUCTION

Cranial surgery can be applied to treat dierent

intracranial diseases

such as tumors, blood clots, brain

abscesses, repair broken cranial bones or clip blood

vessels in patients with cerebrovascular aneurysms.

However, the surgery aects the brain and blood vessels.

e brain tissues are damaged, leading to limited activity,

decreased mobility

and dierent neurological decits:

gait (76.3%) and balance (48.3%).

Hence, the patients

face the inability to self-care.

Moreover, the patients

need to be positioned correctly to facilitate the surgery.

is includes forcing the head to be raised up and stay in

an appropriate angle while being pressed by a Mayeld

for 4-6 hours.

e patients’ neck and shoulder muscles

take the weight, creating taut bands

7,8

and aches in the

muscles. ey have diculties lowering, raising and

turning their heads. e pressure on the blood vessels

reduces blood and oxygen circulation to the muscles

7,9

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

696

so the patients feel dizzy when changing the position.

Moreover, the postoperative pain complicates early

ambulation and delays early recovery.

10-12

Most patients who have had cranial surgery face

limitations in performing daily activities, and only 18%

of these patients can resume working normally following

surgery.

Fostering early recovery is very important. In

general, 59% of patients who have normal preoperative

body movement and receive postoperative recovery

promotion show a better body movement function at an

81.5% rate.

e recovery promotion should start from

the patients’ admission.

Physicians or nurses should

provide them with general preoperative knowledge

and teach physical exercise, step by step, to prepare

the muscles while the patients stay in bed until they

can walk.

16,17

is is considered nursing therapeutics

capable of fostering cranial surgery patients, who are in

health and illness transition of Meleis’ transition theory,

achieve complete this transition

18,19

, which contributes

in turn to postoperative recovery, improves physical

mobility, reduces complications from bed bounding

and

admission days.

Before starting exercise, the patients

will be evaluated in terms of dizziness and wound pain

and will be eased of muscle pain in the neck and shoulder

areas. Many studies have shown that massaging can

reduce pain

and stress to blood vessels in the muscles,

while increasing blood and oxygen circulation to the

brain and eliminating dizziness.

us, massage is an

appropriate and eective treatment for relieving neck and

shoulder muscle stress and promoting early ambulation

in patients who have had surgery.

Most of the previous studies were rehabilitation

programs for patients who had chronic neurological

symptoms and long-term impaired body functions.

23-25

the area of patients who had cranial surgery, a previous

study concerning early recovery aer surgery (ERAS)

programs was found to have encouraged patients to

have early mobility from the rst 24 hours aer surgery.

Furthermore, patients who received the ERAS program

had early recovery with reduced LOS in hospital.

12,17,20,26

However, rehabilitation and ERAS programs in the past

did not study massage for relief of muscle pain, massaging

to ease muscle pain was done with patients who had a

thyroidectomy

, and nurses did not begin exercise from

the rst 24 hours aer surgery when patients were in

the ICU. erefore, to prepare muscles for ambulation

with exercise and to prepare patients for transfer from

the ICU to the ward on the second day aer surgery,

patients received massage to relax the neck and shoulder

muscles. is role was performed by nurses for comfort,

relieve muscle pain and increase blood circulation to the

brain tissues of patients, as a consequence, patients were

more likely to have improved physical mobility. us,

the researcher developed a physical exercise program

for patients who had a cranial surgery. e rst phase of

the exercise started 24 hours aer the surgery. Once the

patients’ conditions were stable

16,26

, they were massaged

to relieve muscle stress in the neck and shoulder areas

before starting active ROM exercise, strengthen the

thigh muscles and quadriceps extension until they could

get up from the bed and walk. e goal was to promote

physical mobility to recover quickly.

MATERIALS AND METHODS

This quasi-experimental research was certified

by the Human Research Ethics Committee, Faculty

of Medicine, Siriraj Hospital, Mahidol University (Si

065/2020). e research groups were calculated using

inuence size determination from mean dierence of

body functions in similar research studies.

e results

were 26 patients for a group. Additional patients were

included at a 15% rate in case some dropped out.

e

power of test was 0.80, and condence in the test (α) was

0.05. e nal research groups had 30 patients each.

Population and samples

e population was patients who had cranial surgery

at a super tertiary hospital. e samples had the same

characteristics as the population. e selection criteria

were 1) undergoing cranial surgery; 2) age ≥ 18 years

old; 3) Glasgow Coma Scale = 15; 4) ai Mental State

Examination scores > 23; 5) ability to move the body

or no limitations in terms of body movement; and

6) understanding and being able to communicate in

ai. e exclusion criteria were 1) having a mental

disease history; 2) wearing ventriculostomy drain when

starting active exercise; and 3) having a congenital disease

which prevents exercising and massaging. e criteria to

consider termination from the research were 1) severe

postoperative complications; 2) consciousness level

decreasing by 2 points in 24 hours; and 3) failing the

readiness assessment before starting physical exercise.

Data collection method

e research group received a physical exercise

program of patients after cranial surgery (CVI 0.9)

from the researcher, who is a nurse. e duration of the

exercise was approximately 30 - 45 minutes each time. e

program included sharing of knowledge from manuals

of physical exercise for patients with cranial surgery

(CVI 0.8) one day before the operation. Next, one day

aer the operation in the ICU, the researcher stimulated

Panyasarawut et al.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

697

Original Article

SMJ

the patients via a breathing exercise and passive ROM

exercises for both upper and lower extremities (totality 11

positions, 10 times per position, for two sessions) while

staying in bed. Two to three days aer, the patients could

partially move their bodies. e researcher massaged

the patients’ upper trapezius and splenius capitis areas

to relax muscles by using vibration, stroking, petrissage

and friction along with encouraging patients to perform

active ROM exercises for both the upper and lower

extremities (totality 11 positions, 10 times per position,

for 2 sessions). Next, the patients performed an exercise

to strengthen the thigh muscles for ve times and did

quadriceps extensions for ve minutes. e researcher

then helped the patients step down from the bed to sit

by the bedside and stimulated them to stand beside the

bed before leading the patients to tread for ve minutes,

take a break for 2-3 minutes, continue treading for ve

minutes, then walk around the bed. e exercises depended

on the ability of each patient. e researcher assessed

the physical readiness and treated wound pain for the

patients before starting the program every time. During

the exercises, the researcher monitored any changes and

pain levels for safety. For the control group, the patients

received routine nursing care.

Data collection

Data collection was conducted by a research assistant,

starting from the control group and then the experimental

group. First data collection: one day before the operation.

is data was used as baseline data. Physical mobility

data were collected by the Clinical Outcome Variables

Scale (COVS). ree points were related: 1) gross motor

and gait; 2) mobility; and 3) arm function. e higher

the COVS, the better the physical mobility. e COVS

assessment revealed inter-rater reliability at 0.97

and

internal consistency at 0.93.

ROM of the neck and

shoulders was measured by a goniometer. e condence

value of goniometer use between the expert and research

assistant was 0.97. Second data collection: three days aer

the operation. Physical mobility was assessed by COVS,

and ROM of the neck and shoulder was measured by a

goniometer. ird data collection: one day before leaving

the hospital physical mobility was assessed by COVS.

Statistical analysis

All of the data were analyzed using SPSS (version

25). Continuous variables were expressed as mean ±

standard deviation or median (interquartile range),

and were compared using independent t-test or Mann-

Whitney U test. Categorical data were expressed as

number (percentage), and were compared using the

Pearson chi-square test or Fisher’s exact test. A p-value

< 0.05 was considered statistically signicant.

RESULTS

e experimental group consisted of 22 female

and 6 male patients for a total of 28. e average age

was 53.86. e control group consisted of 20 female

and 10 male patients for a total of 30. e average age

was 50.67. Personal data of the patients are shown in

Table 1. ere were no dierences between both groups.

Two patients in the experimental group dropped out as

arrhythmia and high blood pressure were identied at

the beginning.

One day aer the surgery, before starting the program,

both the experimental and control groups felt discomfort

and muscle stiness (p = 1.0). ere were no dierences

in the wound pain of both groups (p = 0.074) (Table 1).

ree days aer the surgery, the discomfort and muscle

stiness of the experimental group was better at a 63.3%

rate. Also, easing the wound pain every time before

starting the program dierentiated the pain of both

groups signicantly (p = 0.003) (Table 2).

e results of the physical exercise program of

patients aer cranial surgery and muscle relief massage

dierentiated COVS scores of both groups. ree days

aer the operation, the reduction of COVS scores of the

experimental group was signicantly less than those of

the control group (p = 0.03). is meant the physical

mobility of the former was better. e patients resumed

walking faster, both three days aer and one day before

discharge, with statistical signicance (p = 0.01, 0.004,

respectively) (Fig 1). Furthermore, ROM of the neck

and shoulder was signicantly better than that of the

control group (p = 0.001, 0.001, respectively) (Table 2).

DISCUSSION

Due to cranial surgery, both groups’ physical mobility

scores of three days aer the operation decreased more than

preoperative scores. ese ndings were in line with many

other studies that found issues of reduced postoperative

body movement

3,4

, resulting from the operation, wound

pain and muscle overuse at the upper trapezius and

splenius capitis areas. e latter led to leakage to Ca

from sarcoplasmic reticulum to sarcolemma, combination

of Ca

and adenosine triphosphate, and attachment of

actin to myosin, which created a taut band.

Pressure to

blood vessels and circulation under the muscles produced

local hypoxia and anaerobic metabolism. Lactic acid was

built up in the muscles and stimulated the nerve endings

to feel pain, so the patients felt acute muscle aches and

pains. e symptoms could last days or weeks, but no

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

698

TABLE 1. Personal data and treatment.

Experimental group Control group

(n = 28) (n = 30)

p-value

Age: year 53.86 ± 12.55 50.67 ± 14.84 0.382

Female 22 (78.6) 20 (66.7) 0.385

BMI 25.33 ± 4.42 25.31 ± 5.31 0.988

Hypertension 9 (32.1) 13 (43.3) 0.427

Diabetes 5 (17.9) 3 (10.0) 0.464

Hyperlipidemia 9 (32.1) 9 (30.0) 1.00

Diagnosis

Intracranial tumor 24 (85.7) 26 (86.7) 0.626

Cerebrovascular 2 (7.1) 1 (3.3)

Cranial trauma 0 2 (6.7)

Functional 2 (7.1) 1 (3.3)

Lesion location: lobe

Frontal lobe 4 (14.3) 5 (16.7) 0.547

Temporal lobe 2 (7.1) 5 (16.7)

Parietal lobe 7 (25) 3 (10)

Occipital lobe 7 (25) 9 (30)

Multiple lobes 8 (28.6) 8 (26.7)

Operation: craniotomy with

Tumor removal 24 (85.7) 26 (86.7) 0.922

Clipping aneurysm 2 (7.1) 1 (3.3)

Temporal lobectomy 1 (3.6) 1 (3.3)

Other 1 (3.6) 2 (6.7)

Duration of surgery: hours

≤ 4 13 (46.4) 13 (43.3) 1.00

> 4 15 (53.6) 17 (56.7)

Discomfort or stiffness of muscle

Yes 18 (64.2) 19 (63.3) 1.00

Area of muscle

Upper trapezius 6 (21.4) 7 (23.3) 0.565

Neck (splenius capitis) 4 (14.3) 4 (13.3)

Shoulder 1 (3.6) 2 (6.7)

Neck and upper trapezius 1 (3.6) 2 (6.7)

Upper trapezius and shoulder 2 (7.1) 0 (0)

Neck, upper trapezius and shoulder 0 (0) 2 (6.7)

Arms and legs 2

(7.1) 11 (3.3)

Back 2

(7.1) 1 (3.3)

Surgery position in patients with discomfort or stiffness of muscle

Supine 10 (55.6) 9 (47.4) 1.00

Lateral 1 (5.6) 2 (10.5)

Park – bench 5 (27.8) 5 (26.3)

Prone 2 (11.1) 3 (15.8)

Pain on POD1 (NRS)

Mild 14 (50.0) 6 (20.0) 0.074

Moderate 9 (32.1) 14 (46.7)

Severe 4 (14.3) 9 (30.0)

In conjunction with neck or upper trapezius,

combined with upper trapezius or shoulder

Values are expressed as number (percentage), mean ± standard deviation

Panyasarawut et al.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

699

Original Article

SMJ

TABLE 2. COVS and ROM scores before and aer surgery.

Experimental group Control group p-value

(n = 28) (n = 30)

COVS (pre-operation)

80 (7) 80 (8) 0.453

COVS (POD3)

68 (9) 62 (27)

Difference COVS scores (posttest – pretest)

-10.5 (8.5) -16.5 (18.25) 0.03*

POD3

ROM of neck

190 (59) 127.50 (84) 0.001*

ROM of shoulder

1244.50 (203) 1085 (298) 0.001*

Pain (NRS)

†

0.25 ± 0.64 1.60 ± 1.97 0.003*

LOS

7 (3) 10 (4) 0.001*

Fig 1. Comparison of speed between experimental and control groups.

*p-value < 0.05

†

Value is expressed as mean ± standard deviation,

Values are expressed median (interquartile range)

more than two months.

8,27

e motion range of the neck

and shoulders was reduced, which slowed the patients’

movement and aected postoperative recovery.

is study showed that the physical exercise program of

patients aer cranial surgery including preoperative exercise

knowledge sharing, early body movement stimulation

and muscle preparation within the rst 24 hours aer

the operation such as passive and active ROM exercises

of both the upper and lower extremities, strengthen the

thigh muscles and quadriceps extension, caused striated

a skeletal muscle to contract harder. Consequently, the

muscles used more energy, converting chemical energy

into kinetic energy and increasing the cross-sectional

area of Type 2 muscle bers and resulting in muscle

hypertrophy. With full growth of muscle bers, the

muscles became stronger, enabling patients to exercise

more and move better, respectively.

is also prepared

the patients’ muscles before they could step down from

the bed until walk around. Overall recovery was faster.

More than three-quarters of the patients were able to

walk by the bedside three days aer surgery at a rate

of 86.7%. e physical mobility of the experimental

group decreased less than the physical mobility of those

without the support program. erefore, the patients in

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

700

the experimental group had complete health and illness

transition.

e study of Wang et al. (2018) found that

the elective craniotomy patients who received the ERAS

program could do early o-bed activities and ambulation

by the third day aer the surgery. e success rate was

95%, which was signicantly more than another group

that did not have the program (p < 0.0001).

In terms of the assessment of body readiness and

management of localized wound pain from injuries at

brain tissues, cortex nerves and blood vessels, which could

be relieved pain by medication

, both study groups had

similar levels of wound pain before they were forced to step

down from the bed, and they received similar amounts of

painkiller. However, the experimental group had lower

wound pain scores in POD3 than the control group

(Table 2). e results were similar to those of the study of

Qu et al. (2020) who found that pain management aer

cranial surgery in the patients receiving ERAS programs

generated signicantly lower wound pain scores in POD3

than the other group (p < 0.001).

Moreover, massaging

was an alternative medicine that had a mechanism to

send nerve currents along a beta or alpha nerve ber to

signal and stimulate S.G. cells to inhibit the function

of transmission cells. e mechanism controlling the

gate at the spinal cord level was thus closed. No nerval

signal was sent to the brain, so the patients felt no pain.

Also, there was endorphins and enkephalins secretion

to defy Substance P. is caused the gate to close and

inhibited the transmission of nerve pain from the brain.

e perception of pain was reduced. e patients felt

relaxed, which enhanced pain relief.

e patients’ ameliorated body movement was

partially from discomfort management and massaging

to relax the muscles. Aer receiving massages, two-

thirds of the patients felt more comfort and less muscle

stress. Furthermore, ROM of the neck and shoulders

was better than the control group, and the experimental

group could recover close to the normal state. us,

they could exercise and move their bodies actively. e

results were similar to those of Gemmell et al. (2008)

who used post-isometric relaxation, which is similar

to massage. e study found that the pain decreased

immediately, and ROM was increased significantly

(p < 0.05).

Increased ROM is related to decreased pain

the results aer massaging by Doppler ultrasound showed

increased blood and lymph circulation.

is circulation

led to nutrient and oxygen supplies to the muscles, waste

removal from the tissue cells and signal stimulation of

focal adhesion kinase enzyme and extracellular signal-

regulated kinase enzyme to reduce the contracture of

sarcomere. e trigger points were relaxed with less

cytokine and more mitochondria synthesis.

e muscles

were stimulated to recover from fatigue more quickly.

Moreover, massaging relaxed the upper trapezius muscle,

loosened the pressure of the vertebral artery under the

muscle and increased blood circulation to the cerebral

and basilar arteries. e brain tissues gained more oxygen

so the patients’ headache and dizziness were eased.

35,22

e experimental group could move their bodies more

comfortably than the other group.

e physical exercise program of patients aer

cranial surgery was important in terms of promoting

body movements such as sitting and standing, stepping

down to sit beside the bed, performing various activities

to help the patients resume walking faster (Fig 1) and

leaving the hospital earlier than the other group (Table 2).

e nursing method helped enhance recovery aer surgery.

CONCLUSION

e physical exercise program of patients aer

cranial surgery including body exercise, muscle relaxing

massage, knowledge sharing and management of symptoms

aecting postoperative recovery improved the patients’

physical mobility. As a result, nurses who take care of

cranial surgery patients should use this program as a

guideline to promote early movement of patients aer

surgery.

ACKNOWLEDGEMENTS

I would like to thank the Division of Neurosurgery,

Department of Surgery, Faculty of Medicine Siriraj Hospital,

Mahidol University, for supporting the neurosurgery

research funding from the Siriraj Foundation, and Associate

Professor Doctor Wattana Jalayondeja, specialist from

the Faculty of Physical erapy, Mahidol University,

who taught muscle relaxing massage techniques and

how to use a goniometer. I also would like to thank the

head of the patient ward, stas and research participants

who cooperated and helped with data collection.

Abbreviations: ERAS = enhance recovery aer surgery,

LOS = length of stay, ICU = Intensive Care Unit, CVI =

content validity index, ROM = range of motion, COVS

= Clinical Outcome Variable Scale, BMI = body mass

index, NRS = numeric rating scale, POD = postoperative

day, S.G. cell = Substantia gelatinosa cell,

REFERENCES

1. Foust. (2018). e experience of post-craniotomy pain among

person with brain tumors (dissertation). Bloomington: Indiana

University; 2018.

2. Hemmings G. Neurosurgery aer cranial surgery information

for patients. (internet). Oxford: Oxford University Hospital

Panyasarawut et al.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

701

Original Article

SMJ

NHS Trust; 2018 (cited 2019 Aug 18). Available from https://

www.ouh.nhs.uk/patient-guide/leaets/les/11585Pcranial.

pdf

3. Khan F, Amatya B, Drummond K, Galea MP. Eectiveness of

integrated multidisciplinary rehabilitation in primary brain

cancer survivors in an Australian community cohort: a controlled

clinical trial. J Rehabil Med 2014;46(8):754-60.

4. Pace A, Villani V, Parisi C, Di Felice S, Lamaro M, Falcicchio C,

et al. Rehabilitation pathways in adult brain tumor patients

in the rst 12 months of disease. A retrospective analysis of services

utilization in 719 patients. Support Care Cancer 2016;24(11):

4801-6.

5. Nader R, Gragnaniello C, Berta SC, Sabbagh AJ, Levy ML.

Neurosurgery tricks of the trade. New York: ieme Medical

Publishers; 2014.

6. Meng L, Berger MS, Gelb AW. e potential benets of awake

craniotomy for brain tumor resection: an anesthesiologist's

perspective. J Neurosurg Anesthesiol 2015;27(4):310-7.

7. Boonprakob Y, Phadungkit S, Nongharnpitak S, Srijessadarak

T, Supasatean W, Nakhengrit C. Trigger point: curable or

palliative symptoms. J Assoc Med Sci 2016;49(1):155-66.

8. Sriwicha W. Myofascial pain syndrome. Hua Hin Sook Jai

Klai Kangwon Journal 2016;1(1):10-28.

9. Minerbi A, Vulfsons S. Challenging the Cinderella Hypothesis:

a new model for the role of the motor unit recruitment pattern

in the pathogenesis of myofascial pain syndrome in postural

muscles. Rambam Maimonides Med J 2018;9(3):e0021.

10. Flexman AM, Ng JL, Gelb AW. Acute and chronic pain following

craniotomy. Curr Opin Anaesthesiol 2010;23(5):551-7.

11. Pavlin DJ, Chen C, Penaloza DA, Polissar NL, Buckley FP. Pain

as a factor complicating recovery and discharge aer ambulatory

surgery. Anesth Analg 2002;95(3).

12. Wang Y, Liu B, Zhao T, Zhao B, Yu D, Jiang X, et al. Safety

and ecacy of a novel neurosurgical enhanced recovery aer

surgery protocol for elective craniotomy:a prospective randomized

controlled trial. J Neurosurg 2018:1-12.

13. Janda M, Steginga S, Dunn J, Langbecker D, Walker D, Eakin E.

Unmet supportive care needs and interest in services among

patients with a brain tumour and their carers. Patient Educ

Couns. 2008;71(2):251-8.

14. Giordana MT, Clara E. Functional rehabilitation and brain

tumour patients. A review of outcome. Neurol Sci 2006;27(4):

240-4.

15. Wattradul D. Cardiac rehabilitation: transition care from hospital

to home. ai Journal of Cardio-oracic Nursing 2015;26(1):

89-103.

16. Hickey JV. e Clinical practice of neurological and neurosurgical

nursing. 8

ed. Philadelphia: Lippincott, Williams & Wilkins;

2019.

17. Liu B, Liu S, Wang Y, Lu D, Chen L, Zheng T, et al. Impact of

neurosurgical enhanced recovery aer surgery (ERAS) program

on health-related quality of life in glioma patients: a secondary

analysis of a randomized controlled trial. J Neurooncol 2020;

148(3):555-67.

18. Meleis A.I. Transitions theory: e use of a middle-range

and situation-specific theory in the research and care of

individuals, families and communities. New York: Springer;

2010.

19. Eun-Ok Im. Situation-specic theories from the middle-range

transitions theory. ANS Adv Nurs Sci 2014;37(1):19-31.

20. Lu D, Wang Y, Zhao T, Liu B, Ye L, Zhao L, et al. Successful

implementation of an Enhanced Recovery Aer Surgery (ERAS)

protocol reduces nausea and vomiting aer infratentorial

craniotomy for tumour resection: a randomized controlled

trial. BMC Neurol 2020;20(1):1-11.

21. Gemmell H, Miller P, Nordstrom H. Immediate eect of

ischaemic compression and trigger point pressure release on

neck pain and upper trapezius trigger points:a randomised

controlled trial. Clin Chiropr 2008;11(1):30-6.

22. Taspinar F, Aslan UB, Sabir N, Cavlak U. Implementation of

matrix rhythm therapy and conventional massage in young

females and comparison of their acute eects on circulation.

J Altern Complement Med 2013;19(10):826-32.

23. Andersson P, Franzén E. Eects of weight-shi training on

walking ability, ambulation, and weight distribution in individuals

with chronic stroke: a pilot study. Top Stroke Rehabil 2015;22(6):

437-43.

24. Liljehult MM, Buus L, Liljehult J, Rasmussen BK. Walking ability

in patients with glioblastoma: prognostic value of the Berg Balance

Scale and the 10 meter walk test. J Neurooncol 2017;135(2):335-

42.

25. Noinawakul U, Pinyopasakul W, Kimpee S, Puwarawuttipanit

W. e eects of a walking exercise program on perceived self-

ecacy and functional capacity in stroke patients with hemiparesis.

J Nurs Sci 2010;28(4):45-53.

26. Qu L, Liu B, Zhang H, Sankey EW, Chai W, Wang B, et al.

Management of postoperative pain aer elective craniotomy: a

prospective randomized controlled trial of a neurosurgical

Enhanced Recovery Aer Surgery (ERAS) program. Int J Med

Sci. 2020;17(11):1541-9.

27. Teerateadtakul B. e eect of massage and exercise of neck

on the level of the headache in surgical patients with head

elevated position. ai J Nurs Res 1996;46(1):23-32.

28. Choy NL, Kuys S, Richards M, Isles R. Measurement of functional

ability following traumatic brain injury using the Clinical

Outcomes Variable Scale: a reliability study. Aust J Physiother

2002;48(1):35-9.

29. Leelayuwat N. Physiology of exercise. Khon Kaen: Khon Kaen

University; 2553.

30. Fox SW, Lyon D, Farace E. Symptom clusters in patients with

high-grade glioma. J Nurs Scholarsh 2007;39(1):61-7.

31. Treede, Rolf-Detlef. Gain control mechanisms in the nociceptive

system. PAIN 2016;157(6):99-1204.

32. Field T, Diego M, Gonzalez G, Funk CG. Neck arthritis pain

is reduced and range of motion is increased by massage therapy.

Complement er Clin Pract 2014;20(4):219-23.

33. Flinder LI, Timofeeva OA, Rosseland CM, Wierød L, Huitfeldt

HS, Skarpen E. EGF – induced ERK-activation downstream of

FAK requires Rac1-NADPH oxidase. J Cell Physiol 2011;226:

2267–78.

34. Braun, Beth M. Introduction to massage therapy. 2

ed.

Philadelphia: Lippincott Williams & Wilkins; 2008.

35. Pianbanyat K, Choowattanapakorn T. e eect of nursing

process combined with Swedish massage on pain in older persons

with lung cancer. Kuakarun Journal of Nursing 2015;22(1):98-

112.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

702

Taya Kitiyakara, MBBS.*, Patarapong Kamalaporn, M.D.*, Akharawit Poolsombat, M.D.*, Patthama Anumas,

BNS.**, anyaluck T. Tawarate, BNS.**, Kesrada Akkanit, BBA.**

*Division of Gastroenterology and Hepatology, Department of Medicine, **Endoscopy Unit, Debharatana Building, Ramathibodi Hospital, Mahidol

University, Bangkok 10400, ailand.

Leak-Testing of an Endoscopic Aerosol Box for

Preventing SARS-CoV-2 Infection during Upper

Gastrointestinal Endoscopy

ABSTRACT

Objective: e SARS-CoV-2 virus has infected many healthcare professionals. Endoscopy is an aerosol-generating

procedure and the endoscopy team is at risk of exposure and infection. We describe the leak-testing of an aerosol

box that uses a glove-covering for the endoscope.

Materials and Methods: An endoscopic aerosol box with a glove-covering over the endoscope was made for

gastroscopy, EUS and ERCP procedures and was tested for leakage of aerosol/airborne particles. Fine particulate

matter (PM) from burnt incense sticks was used as a model for viral aerosol. e leakage from the box was measured

by comparing readings from 2 PM light-scattering sensors, one placed inside the box and the other just outside

the glove opening in a sealed container. Negative pressure conditions were also used to see if this had any eect

on the leakage.

Results: e concentration levels of the particulate matter diered with dierent negative pressure conditions and

movement of the endoscope through the glove. Very little leakage was seen with the endoscope stationary even with

no negative pressure, at 2.4%, 0.17% and 0.07% for PM1, PM2.5 and PM10, respectively. e maximum leakage was

14% for PM1, 8.7% for PM2.5 and 2.6% for PM10 in the moving-endoscope condition and no negative pressure.

is reduced to 6.2%, 1.3% and 0.37% respectively when suction was applied at full strength (negative pressure of

-0.05 bar).

Conclusion: e glove covering signicantly reduced the passage of particles. e particulate leak was seen most

with the smallest particles and reached 14% for PM1 without negative pressure. is reduced to 6.2% with maximum

negative pressure using the wall suction.

Keywords: SARS-CoV-2, Endoscopy; aerosol; barrier; aerosol generating procedure (Siriraj Med J 2021; 73: 702-709)

Corresponding author: Taya Kitiyakara

E-mail: tayakiti@gmail.com

Received 30 April 2021 Revised 12 August 2021 Accepted 13 August 2021

ORCID ID: https://orcid.org/0000-0002-7938-1752

http://dx.doi.org/10.33192/Smj.2021.90

INTRODUCTION

e current SARS-CoV-2 pandemic has caused

worldwide social and economic disruption and death.

e SARS-CoV-2 virus causes gastrointestinal symptoms

and has been found in the gastrointestinal tract

2-4

and

oral mucosa.

ere is a risk that the virus may aerosolize

during upper GI endoscopy

, putting the endoscopy

sta at risk of infection. International guidelines have

recommended, amongst other things, postponing routine

procedure, screening patients and wearing appropriate

Kitiyakara et al.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

703

Original Article

SMJ

personal protective equipment (PPE) during the endoscopic

procedure.

7,8

However, guidelines have not recommended

the use of any additional barrier methods other than

PPE in preventing aerosolized droplet spreading to the

endoscopist.

A similar concern for the infection risk from aerosolized

droplets has arisen during intubation and extubation of

endotracheal tubes for COVID-19 positive patients and

a report has suggested that an “aerosol box” can limit the

aerosol exposure of the anesthetist during endotracheal

tube manipulation.

A similar aerosol box has recently

been proposed for use in upper GI endoscopy to prevent

aerosol exposure of the endoscopist.

More recently

another report has described an adaptation of the aerosol

box by using a glove covering for the endoscope as it

enters the box.

Our upper GI endoscopy aerosol box is an adaptation

of the aerosol box described above, made specically for

upper GI endoscopy. Although the core concept of our

aerosol box is similar in the use of a glove-covering for

the endoscope, we had designed it prior to seeing the

report above and have some dierences to the design.

In this report we describe our design of the endoscopic

aerosol box and the results of leak testing from the box

using ne particulate matter (PM1, PM2.5, PM10) as

a model for viral aerosol particles.

METHODS AND MATERIALS

e aerosol endoscopic box used in this study was

designed, tested and produced using transparent acrylic

plastic material (Fig 1) prior to seeing the reports from

Japan.

10,11

e essential component of the adapted aerosol

box in this study is the opening through which the scope

is passed. e opening uses a rubber glove to cover the

endoscope to prevent viral aerosol and droplets from

reaching the endoscopist. e adapted aerosol box has a

round opening with raised rounded edges with a diameter

of 9 cm specically made so that the rubber glove may

be stretched over and attached to it (Fig 1). is opening

is on a separate acrylic plate that can be slid into a slot

on the main aerosol box (Figs 1 & 2). ree plates, each

with the opening at a dierent position on the plate, are

available for use with each endoscopic aerosol box, so

that the position of the opening can be adjusted to be

opposite the mouth of each patient.

To use the rubber glove as a covering for the endoscope,

a small cut is made in one of the nger-ends of the glove,

through which the endoscope could be passed (Figs 3

& 4). e size of the glove can be varied depending the

diameter of the scope. During the procedure, the scope

has room to maneuver as the opening of the box where

the glove is attached to is 9 cm in diameter. As the scope

is removed at the end of the procedure, the glove nger

can be pinched to prevent leakage and another glove can

be placed over the opening to seal o any possible aerosol

leak once the endoscope is completely removed. e

glove(s) can then be removed and disposed appropriately

at the end of the procedure. e other sides of the box

have openings which can be opened and closed, to be

used for reaching into the box as necessary, while the

pedal side of the box (where the patient’s body extends)

can be covered with a waterproof material that is attached

to the box and sealed around the patient (see example

in Fig 2 below).

Fig 1. Acrylic plates with the opening for the glove cover at dierent

positions.

Fig 2. e transparent endoscopic aerosol box, showing the opening

for the scope (An endoscopy unit sta is modeling as the patient).

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

704

Fig 4. e insertion of the endoscope through the glove when attached

to the opening of the endoscopic aerosol box. (An endoscopy unit

sta is modeling as a patient).

Fig 3. e endoscope passing through the cut end of the nger of

the glove.

e adapted aerosol box also has other smaller

openings to allow various tubes to pass through (but

can be closed if not used). It has a separate smaller hole

through which a rubber tube can be inserted and negative

pressure applied using an additional wall suction. In our

experiment, two modes were used, regular and high suction

modes, producing pressures of -190 mmHg and -280

mmHg respectively. is tube, which could be attached

to a ventilator HEPA lter, is used to suck out the air

inside the box and remove both the carbon dioxide and

viral aerosol from the box. ere is also another opening

through which the ventilator’s corrugated tube can pass

in cases where the patient is intubated.

e design of the box is shown in the supplemental

materials.

e endoscopic aerosol box was tested for leakage of

ne particulate matters (PM1, PM2.5, PM10) produced

from burning a commercially available incense stick

inside the endoscopy aerosol box. is was used as a

model for viral particles. In order to monitor the leakage

characteristics of the box, the testing method similar

to that done by Ng et al.

was adapted. e leaked ne

particulate matter was measured with an optical sensor

(PMS7003 G7 sensor Module Air Particle dust laser sensor)

capable of scattering and absorbance measurements of

light to target in situ sensing of ﬁne particulate matter.

e sensing system had the capability to measure the

averaged concentration of particulate matter sized 1.0 mm,

2.5 mm and 10 mm. One sensor was placed in the

endoscopic aerosol box with the burning incensing stick

and another was placed in a sealed container attached

to the endoscope-glove-opening of the box to measure

the percentage leakage of the particulate matter through

the opening. e sealed container prevented entry of

ne particulate matter from the ambient environment

which would distort the readings of the leaked PM from

the box. e concentration of the particulate matter was

measured simultaneously and at the steady state, dened

as no progressive increase or decrease in concentration

over 2 mins of observation.

e light scattering sensor was also able to measure

the ambient pressure and this was used to measure the

level of negative pressure achieved in the box at dierent

levels of wall suction (no suction, regular suction, high

suction). An Arduino UNO was used as an interface

between a computer and the sensing system. e data

acquisition was performed through a serial communication

application that was developed within the Arduino

platform. Due to the sealed container holding the PM

sensor, an actual endoscope could not be passed through

the glove and a large pen with a similar diameter to a

gastroscope was used in its stead. e attached glove was

cut at the ngertip and the pen was passed through the

cut opening connecting the inside of the aerosol box to

the sealed container holding the sensor. e PM leakage

was measured when the pen in a stationary position,

and also when the pen was moved vigorously (to mimic

movement of the endoscope), and at dierent levels of

suction/negative pressure within the box. e ambient

leakage of the particulate matter was also measured near

the other openings on the side of the box closest to the

patient’s vertex, through which the corrugated tubes

leading to the ventilator would pass. e PM sensors

would measure the three PM levels every second and

record these in the computer.

Kitiyakara et al.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

705

Original Article

SMJ

e set up for the PM leakage test is shown in

Fig 5.

e study was approved by the local ethics committee

of the hospital (COA. MURA2020/799) on the 14

May

2020

Fig 5. e set up for testing PM leakage from the opening with glove

attached. e burning incense stick can be seen in the endoscopic

aerosol box and the two PM sensors are placed inside the aerosol

box and the sealed compartment attached to the endoscope-glove

opening respectively.

Statistical analysis

Statistical analysis was performed using SPSS Statistics

by IBM version 25. Continuous variables with normal

distribution were expressed as mean (standard deviation)

and analyzed with student T-test. Paired t-tests and

Pearson correlation were performed to compare the

leakage rates using dierent suction pressures within

the endoscopic aerosol box.

RESULTS

e overall averaged concentrations of PM 1.0, 2.5

and 10 inside the chamber (n=14, p<0.05) were found to

be 140 µg/m

, 2,134 µg/m

and 6,089 µg/m

respectively.

Tests were conducted at dierent pressure conditions

to identify the role of pressure/suction on the concentration

of particulate matter in the chamber and the eects in

controlling the leakage. e results are shown in Table 1.

As can be seen from the table, negative pressures produced

by wall suction reduced the PM concentration in the

chamber, particularly PM1 and PM10.

To determine the rate of leakage from the chamber,

paired t-test was conducted on the set of raw data measured

from the chamber and the target location corresponding

to the dierent testing scenario. e results are tabulated

below in Table 2. us the leakage was calculated as a

percentage of the averaged concentration in the endoscopic

aerosol box.

Very little leakage occurred when the pen was

stationary, with PM1 leak of 2.4%, PM2.5 0.17% and

PM10 leak of 0.07%. ere was no detectable leakage

when the pen was stationary and the suction was on. e

highest leakage of 14% was recorded the pen was moved

vigorously in the glove without any suction pressure. But

the averaged concentration of leaked PM1 decreased

subsequently to 8.9% and 6.2% when negative suction

pressure was increased from zero to -0.01 and -0.05 bar

respectively. A similar trend was observed in the ambient

leakage test. Another trend was evident regarding the

size of the particles; the leakage was higher for smaller

particle size.

The effect of pressure on leakage can also be

comprehended from a Pearson-correlation test which

correlated between the pressure and PM concentration

levels as shown in Table 3 below.

TABLE 1. Concentration of particulate matter for each pressure condition at stable state.

Concentration of Particulate Matter inside Chamber at Stable condition(µg/m

)

Pressure (bar)

PM1.0 PM2.5 PM10

210.53 2531.7 10792.8

(SD=12.46 CV=0.059) (SD=85.5 CV=0.03) (SD=408.5 CV=0.03)

-0.01

148.5 2312.01 6662.2

(SD=12.44 CV=0.08) (SD=213.1 CV=0.09) (SD=562.6 CV=0.08)

-0.05

96.3 2298.4 3831.817

(SD=8.67 CV=0.09) (SD=155.99 CV=0.067) (SD=491.9 CV=0.12)

Abbreviations: SD= standard deviation, CV= Coecient of Variation.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

706

TABLE 2. e percentage of particulate matter leak from the averaged PM level in the endoscopic aerosol box for

each pressure level

TABLE 3. e eect of pressure on PM leakage

Leakage %

Chamber Gauge Pressure(bar) PM1 PM2.5 PM10

Without Moving pen 0 2.4 0.17 0.07

-0.01 0 0 0

-0.05 0 0 0

Moving pen 0 14 8.7 2.6

-0.01 8.9 1.5 0.75

-0.05 6.2 1.3 0.37

Ambient Leakage 0 9.6 7.6 3.7

-0.01 3.2 0.6 0.4

-0.05 2.4 0.4 0.2

Pressure Pm1.0 PM2.5 PM10

Pressure Pearson Correlation 1 .434 .481 .501

Sig. (2-tailed) .243 .190 .170

N 9 9 9 9

When the incense stick was removed from the

box, the rate of reduction of the ne particulate matter

inside the box, with the wall suction at -0.05 bar, is

Fig 7. e rate of reduction of PM10 within the

box with aspiration of the air inside using full

strength wall suction.

shown in Fig 7. As can be seen from the graph, it took

approximately 2 mins, using the high suction mode, for

the PM10 concentration to decrease by 50%.

Kitiyakara et al.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

707

Original Article

SMJ

DISCUSSION

e SARS-CoV-2 virus has infected many healthcare

workers

13,14

and is transmitted by aerosols and droplets.

It has also been found in the buccal mucosa and the

gastrointestinal tract.

2,4,5

Gastroscopy and EUS/ERCP

are thought to be at-risk procedures because of aerosol

generation from the patient.

For protection various

endoscopic societies have recommended endoscopists

wear PPE for protection.

7,8

Here we report the evaluation

of an endoscopic aerosol box using a glove-cover opening,

which was designed to decrease aerosol exposure to the

endoscopist.

Previously an aerosol box for endoscopy has been

reported, similar in design to that suggested for intubation

by anaesthetists, with just a hole for the endoscope to

pass through. However, there is a concern that the virus

may be airborne and much smaller particles are produced

by the patient

and therefore the risk of exposure may

not be solely from the spray of large particles. Another

recent report in fact raised the concern that these ‘open’

aerosol boxes may actually increase the exposure for

medical personnel to the virus.

An endoscopic aerosol

box barrier with a glove-covering for the endoscope may

thus be a solution to reduce the exposure of viruses to

the endoscopist, both from direct spray of large particles

and leakage of smaller particles from the box.

Although there has been an earlier publication

describing an aerosol endoscopy box using a glove-

covering for the endoscope

, our aerosol box was designed

independently and our study was performed before

seeing the publication. Our aerosol box design also

varied in some ways from the prior published design.

Our aerosol box used a dierent method to attach the

glove, had sliding doors/ openings which could be used

to pass tubes or for assistants to insert their hands to

help the patient if necessary, and our aerosol box was

also smaller in design so that it would be easier to close

o the open side where the patient’s body protruded, to

prevent small particulate matter/aerosol leak, rather than

just preventing direct spray from the patient’s mouth.

We tested the passage of ne particulate matter of

dierent sizes leaking through the glove-covering of our

aerosol box. Although previous articles have demonstrated

visually that such a design may decrease the amount of

sprayed droplets from patients

10,11

, we quantied the

amount of leakage of small particles of dierent sizes.

e dierent sizes of the particulate matter used in our

experiment was used to demonstrate the dierent levels

of leakage of SARS-CoV-2 virus particles depending on

their size, as there is a concern that viral particles are

produced from infected patients in a variety of sizes.

is leakage is likely to be more pronounced in ‘open’

aerosol boxes.

Our results demonstrated that there was very little

leakage of PM of all sizes when the glove covering was

used and pen/endoscope model was stationary (2.4%,

0.7% and 0.17% for PM1, PM2, PM10 in the no suction

group respectively, and no leakage when suction was

switched on), but this increased when the pen was moved

vigorously. e results also demonstrated that smaller

particles leaked more than larger particles. e percent

leakage was 14%, 8.7% and 2.6% for PM1, PM2.5 and

PM10 respectively, when measured in the worst condition,

namely vigorous movement of the pen with no suction

applied. e leakage was reduced when the suction was

turned on and negative pressure was applied through a

rubber tube inserted into the box. e leakage dropped

to 6.2%, 1.3% and 0.37% for PM1, PM2.5 and PM10,

respectively. We suspect that this situation would be

closest to clinical practice, and this would therefore mean

than the glove-covering, along with wall suction, would

help reduce the exposure of approximately 93.8%, 98.7%

and 99.6% of exhaled aerosol with approximate sizes

of PM1, PM2, PM10, respectively, for the endoscopist

during the procedure. We also demonstrated that the

wall suction, commonly used for aspirating saliva during

an endoscopic procedure, when used to suck out the

air in the endoscopic aerosol box, was able to reduce

the PM level by 50% over an interval of approximately

2 minutes. e use of the pen as a model for the endoscopy

was necessary to keep the particulate matter inside the

container for analysis. However, during the testing of

our model, we wiggled the pen very vigorously, much

more than an endoscope would normally be moved

in a procedure done by an expert. Consequently, we

think that our results cover the range of leakage that

would be seen in a normal gastroscopy. In a separate

on-going study, the use of the box (in non-COVID-19

patients) was not dicult for expert endoscopists, and

the movement of scope was not thought to be limited nor

need to be specically adapted for the glove covering. e

normal endoscopic movements in and out of the glove

in a straight path would minimize the aerosol leakage

from the covering.

e glove covering set-up for our aerosol box could

be used repeatedly with cheap and commonly available

materials. It also allowed exibility of movement of the

scope during the procedure whilst also preventing viral

aerosol directly reaching the endoscopist. A report has

suggested that uncovered openings of the aerosol/intubation

boxes actually increase the risk of airborne exposure from

the patient.

Although we did not directly compare with

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

708

other aerosol box models, our glove-covering model for

the endoscopy should decrease exposure from both the

direct spray of large particle aerosols, and the leakage of

smaller airborne particles from the patient in comparison

to uncovered intubation boxes. Although in our model

we used the rubber gloves available in our endoscopic

unit as it was cheap and easily available, other gloves,

such as latex-allergy gloves could be used. eoretically

other elastic materials could also be used as the endoscope

cover, but we thought that general availability and cost

of the material would be important in the situation of

the pandemic, so we did not try to test other materials

in our model.

We also note that another group has suggested using

an anesthetic mask to prevent aerosol droplet spread

during the endoscopic procedure.

We think that our

endoscopic aerosol box allows more exibility for the

endoscopist in two ways. Firstly, larger endoscopes, such

as those used for endoscopic ultrasound or ERCP with

stent removal, may be more easily manipulated using our

endoscopic aerosol box, as the opening size can be varied

as needed. Secondly, the box can easily be used for the

intubated patient, in comparison to the anesthetic mask

which would impede the endotracheal tube. is may

be particularly pertinent for the patient with COVID-19

who may have problems with oxygenation or in cases

with variceal bleeding who require intubation.

In comparison to a box with a single uncovered hole

for the scope, as suggested by Sagami et al

, we think

that our design is also more exible. e positioning of

the opening hole and scope can be adjusted to dierent

patient size and anatomy, as well as the opening can be

adapted for endoscopes of diering sizes. As mentioned

previously, Kagami et al. reported the use of the glove-

covering for an endoscopic aerosol box.

eir design

appears to be slightly dierent to ours, and as their design

has only been reported briey, so we are unable to see

if there is any practical dierence compared with our

design.

We have used the endoscopic aerosol box in our

unit on patients for EGD, ERCP and EUS without any

complications. However, because ailand had managed

to control the initial spread in the country well, and testing

was limited to symptomatic or high-risk patients, we did

not have any conrmed COVID-19 infected patients to

use the aerosol endoscopic box on. Nevertheless, we feel

that the box is a useful equipment to improve the safety

of the endoscopy team, and we wanted to report and

share the design of the endoscopic aerosol box for other

endoscopists to use in view of the ongoing infection from

SARS-CoV-2 virus in many countries. e design can

be seen in the supplementary data, and can be copied

and used without asking for further permission. Some

adaptation and change in size of the box may be required

for the larger Caucasian and African population. In the

future the glove-covered aerosol box may be useful for

endoscopy of patients with risk of other infections such

as patients with active tuberculosis.

e main limitation of this study was that the use of

ne particulate matter from burning an incense stick, as

a model for viral aerosol, may not have been identical to

real-life conditions as the concentration from the incense

stick did not uctuate with respiration or coughing.

Further testing with models that are closer to human

respiration/coughing would be useful to conrm the

benet of the box and the level of particle leakage from

the box. Also, we could not measure the leakage of

particles at the time of removal of the box for cleaning.

We do not know if endoscopy assistants would be at

increased risk during the removal of the box and during

cleaning or not. However, the endoscopic aerosol box is

easily cleaned by wiping with 75-90% alcohol solution

and washing with liquid soap.

CONCLUSION

An endoscopic aerosol box using a glove-cover for

the endoscope decreased the leakage of ne particles of

various sizes substantially. e addition of negative pressure

to remove the air inside the box using standard wall

suction decreases this leak even further. e combination

of the endoscopic aerosol box with a glove cover and in-

box suction would decrease the risk of infection from

COVID-19 infected patients for the endoscopist and

other team members. e box may be replicated and

used in areas with high COVID-19 prevalence to reduce

the transmission to healthcare sta during endoscopy.

ACKNOWLEDGMENTS

We are grateful for Mr. Bibhu Sharma from the

BART lab, Faculty of Engineering, Mahidol University

for helping with the PM measurement and analysis. We

also thank Mr. Noppon Chuklin and Retail Business

Solutions Co Ltd for the production and design art of

the aerosol endoscopy box.

Supplemental material: Design specications of the

endoscopic aerosol box.

REFERENCES

1. Wasuwanich P, awillarp S, Ingviya T, Karnsakul W. Coronavirus

Disease 2019 (COVID-19) and Its Gastrointestinal and Hepatic

Manifestations. Siriraj Med J 2020;72:272-82

Kitiyakara et al.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

709

Original Article

SMJ

2. Zhang W, Du RH, Li B, Zheng XS, Yang XL, Hu B, et al.

Molecular and serological investigation of 2019-nCoV infected

patients: implication of multiple shedding routes. Emerg

Microbes Infect 2020;9:386-9.

3. Holshue ML, DeBolt C, Lindquist S, Lofy KH, Wiesman J,

Bruce H, et al. First Case of 2019 Novel Coronavirus in the

United States. N Engl J Med 2020;382:929-36.

4. Xiao F, Tang M, Zheng X, Liu Y, Li X, Shan H. Evidence for

Gastrointestinal Infection of SARS-CoV-2. Gastroenterology.

2020;158:1831-33.

5. Xu H, Zhong L, Deng J, Peng J, Dan H, Zeng X, et al. High

expression of ACE2 receptor of 2019-nCoV on the epithelial

cells of oral mucosa. Int J Oral Sci 2020;12:8.

6. Soetikno R, Teoh AY, Kaltenbach T, Lau JY, Asokkumar R,

Cabral-Prodigalidad P, et al. Considerations in performing

endoscopy during the COVID-19 pandemic. Gastrointest

Endosc 2020;92:176-83.

7. Ong J, Cross GB, Dan YY. Prevention of nosocomial SARS-

CoV-2 transmission in endoscopy: international recommendations

and the need for a gold standard. Gut 2020;69:1145-8.

8. Kongkam P, Tiankanon, K., Ratanalert, S., Janthakun, V., Kitiyakara,

T., Angsuwatcharakon, P., Chantarojanasiri, T., Mekaroonkamol,

P., Ridtitid, W., Aniwan, S., Pittayanon, R., Attasaranya, S.,

Linlawan, S., Pausawasdi, N., Akaraviputh, P. T., Ratanachu-ek, T.,

& Rerknimitr, P. R. e Practice of Endoscopy during the

COVID-19 Pandemic:Recommendations from the ai Association

for Gastrointestinal Endoscopy (TAGE) In collaboration with

the Endoscopy Nurse Society (ailand) Siriraj Med J 2020;72:

283-6.

9. Canelli R, Connor CW, Gonzalez M, Nozari A, Ortega R.

Barrier Enclosure during Endotracheal Intubation. N Engl J

Med 2020;14:1957-8..

10. Sagami R, Nishikiori H, Sato T, Murakami K. Endoscopic

shield: barrier enclosure during the endoscopy to prevent

aerosol droplets during the COVID-19 pandemic. VideoGIE

2020;5:445-8.

11. Kagawa Y, Fukuzawa M, Itoi T. Novel dedicated plastic cube

for infection prevention during gastrointestinal endoscopy

and endoscopic retrograde cholangiopancreatography. Dig

Endosc 2020;32:991.

12. Ng C-L, Kai F-M, Tee M-H, Tan N, Hemond HF. A Prototype

Sensor for In Situ Sensing of Fine Particulate Matter and

Volatile Organic Compounds. Sensors. 017;18:1-9.

13. Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, et al. Early

Transmission Dynamics in Wuhan, China, of Novel Coronavirus-

Infected Pneumonia. N Engl J Med 2020;382:1199-207.

14. Jin YH, Huang Q, Wang YY, Zeng XT, Luo LS, Pan ZY, et al.

Perceived infection transmission routes, infection control

practices, psychosocial changes, and management of COVID-19

infected healthcare workers in a tertiary acute care hospital in

Wuhan: a cross-sectional survey. Mil Med Res 2020;7:24.

15. Patel KP, Vunnam SR, Patel PA, Krill KL, Korbitz PM, Gallagher

JP, et al. Transmission of SARS-CoV-2: an update of current

literature. Eur J Clin Microbiol Infect Dis 2020;39:2005-11.

16. Prather KA, Wang CC, Schooley RT. Reducing transmission

of SARS-CoV-2. Science 2020;368:1422-4.

17. Simpson JP, Wong DN, Verco L, Carter R, Dzidowski M, Chan

PY. Measurement of airborne particle exposure during simulated

tracheal intubation using various proposed aerosol containment

devices during the COVID-19 pandemic. Anaesthesia 2020;75:

1587-95.

18. Marchese M, Capannolo A, Lombardi L, Di Carlo M, Marinangeli

F, Fusco P. Use of a Modied Ventilation Mask to Avoid

Aerosolizing Spread of Droplets for Short Endoscopic Procedures

during Coronavirus Covid-19 Outbreak. Gastrointest Endosc

2020;92:439-440.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

710

Pattarachat Maneechaeye, B.Acc, MBA, Ph.D.*, Watcharaphat Maneechaeye, M.D., M.Sc.**, Wisanupong

Potipiroon, B.A., M.S., Ph.D.***

*Ph.D. Candidate, Faculty of Management Sciences, Prince of Songkhla University, Songkla 90112, ailand, **Occupational Medical Doctor and Fort

Hospital Vice Director, Fort Khunchueangthammikkarat Hospital, Payao 56000, ailand, ***Faculty of Management Sciences, Prince of Songkhla

University, Songkla 90112, ailand.

Operating Room and Flight Deck: What Do These

Places Have in Common?

ABSTRACT

is review article grounds itself into the advent of aviation safety concepts that share some aspects into

healthcare industry, practically and theoretically. ese concepts are originally invented for aviation-related

operation to ensure safety in ight but there are some aspects that can be related to healthcare context especially

in surgery. Because aviation and healthcare are high reliability industries and neither patients nor passenger safety

are compromised, safety concepts from aviation may prove useful for healthcare. e objective of this review was

to scrutinize the concepts of aviation safety that may be applicable to healthcare. Data collection was based upon

a review of literatures. is review article contributes to a broader knowledge from both elds of work regarding

operational safety. e review shows that there are several practical concepts including Crew Resource Management,

checklists and readbacks, sterile cockpit, and human factors of fatigue and stress that healthcare professionals can

adopt and adapt them into their daily operation. Moreover, theoretical concepts such as Swiss cheese model and

reat and Error Management can be applied into healthcare context. is review invokes scenarios of each concept

from both industries. e results show that communication is the key to promote safer operation and those concepts

can be adopted to promote better safety at work. Future studies should extend the concepts of this review into an

experimental research to analyze the eect of concepts on actual healthcare settings or utilize qualitative study to

investigate the application of concepts in healthcare environment.

Keywords: Aviation; patient safety; pilot; safety; surgeon; surgery (Siriraj Med J 2021; 73: 710-720)

Corresponding author: Pattarachat Maneechaeye

E-mail: pattarachat@gmail.com

Received 22 June 2021 Revised 315 August 2021 Accepted 31 August 2021

ORCID ID: https://orcid.org/0000-0001-5020-1140

http://dx.doi.org/10.33192/Smj.2021.91

INTRODUCTION

Safety is essential and considered an utmost goal in

aviation. e problem is that aviation accidents always

result in enormous loss of life and assets, attracting

worldwide attention as well as huge financial costs

for all stakeholders. erefore, the aviation industry

is rigorously determined to learn from past lessons

from incidents and accidents to prompt better safety

procedures and practices. In terms of the rules in pilots’

standard operating procedures, there is always someone

who has paid for it with their life. In an honest, sincere

and truthful way, pilots’ standard operating procedures

are written in blood. ereby, pilots have an interest in

conforming to the rigorous safety policies and procedures

they must follow as the probability exists that they would

pay for any shortcomings of the safety procedures

with their own lives as well. These are the reasons

why the aviation industry has instigated a dominant

Maneechaeye et al.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

711

Review Article

SMJ

safety culture. However, pilot error seems to remain

the primary cause of aviation accidents.

On the other

hand, medical errors in the healthcare industry provide

a serious threat to patient safety as they are estimated

to be accountable for 3% of all hospital admissions.

Toward the goal of reducing the risk of patient harm,

the notion of aviation safety policies and practices may

be adopted for the medical eld, especially for surgeons.

Both the operating room in a hospital and the cockpit

in an aircra, surgeons and ight crews, share a lot of

things in common in terms of rigorous training, in-depth

technical knowledge, keen eye-hand coordination, and

responsibility for operational safety. Moreover, these

intangible components of professionalism in both

professions are commodied and considered valuable

capital for an organization.

3,4

e objective of this review article is to scrutinize the

advent concepts of aviation safety that may be applicable

to the healthcare industry. Data collection was based

upon a systematic review of related literature including

texts, research papers, practitioner papers, academic

manuscripts, and other relevant online resources from

both academic and practitioner perspectives. is review

article contributes to a broader knowledge from both

elds of work regarding operational safety.

Described below are reviews of several aviation

safety concepts, practically and theoretically, that have

been introduced and could possibly be adapted into

medical practices. This review article also aims to

incorporate existing safety-related literature, pointing

towards reported aviation safety philosophy and

providing examples related to daily surgical practices.

Practical Concepts

Crew Resource Management (CRM)

Hazard industries, namely healthcare and aviation,

rely mostly on eective teamwork exercise owing to the

complicate, dynamic and critical safety nature context

of their industries. It is inadequate that these teams are

built upon individual experts, but the team itself must

be high expertise team in order to practice high level of

technical performance and team attitudes and behaviors

to function safely and adaptively to achieve goals.

An expert team is dened as a set of interdependent

team members, each of whom possesses unique and

expert-level knowledge, skills and experience related

to task performance, and who adapt, coordinate and

cooperate as a team, thereby producing sustainable and

repeatable team functioning at superior or at least near

optimal level of performance.

Team working on surgical

operation share similar characteristic to those in aviation

in that they operate in high-risk environments where

situation between life and death of patient involves.

Moreover, team members always change and surgical

operation team are built upon skillful individuals such

as surgeons, anesthesiologists, anesthetists, nurses and

medical technicians who might or might not know each

other and might not have been working together before.

Members need assurance that their teammates know

and understand their duties and can use their abilities

and knowledge collaboratively to intervene or recover

operation. is can be built over time as members feel

familiar with each other and improve personal working

relationships. When there is the possibility for things

to go wrong or rapidly deteriorate at work such as

midight engine failure in aviation or a patient blood

pressure rapidly drop during operation, there is even

more reliance on the teamwork capability to respond

quickly to manage the unforeseen situations.

Apart from those CRM factors aforementioned,

there are several crucial elements regarding CRM

practices that describe safer operation among aviation

and medical practitioners alike. These are situation

awareness, decision making and SHELL Model.

Situation awareness comprises three stages which

are, the perception of the elements in the environment

in a matter of current time and space orientation, the

comprehension of their meaning and the projection of

their status in the near future and thus, proper decision

making is made to mitigate risks.

With these three

components combined, situation awareness may support

better choice of action as this involves cognition and

short-term memory or working memory. Moreover,

situation awareness is relevant to dynamic working

environment such as ight deck and operating room and

hence is not the same as the still knowledge of long-term

memory under static working 1condition.

Flight crew

and surgeons, who are always situationally aware, have an

ability to access to a precise mental representation of the

dynamic environment that is broader than that which can

be upheld in the restricted capacity of working memory.

For instance, in aviation 1context, during nal approach

stage, there is a sudden conict of aircra trac during

nal approach path, but if the good situation-aware

pilot can call on suddenly to respond accordingly to this

situation, the pilot will decide accordingly to maneuver

aircra so rapidly and accurately that the ight path is

safe from air trac collision during nal approach due to

the ability to rapidly access the information from working

memory.

In healthcare context, during perfusion and

cardioplegia management, aer an administration of a

bolus of cardioplegia solution, the surge11on noties

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

712

that the heart is lling up with blood or full heart. e

good situation-aware surgeo1n can recall to root cause

suddenly to respond to this situation that there might

be an improper operation of heart-lung bypass circuits.

e surgeon suddenly makes a decision to fully isolate

the heart’s profusion circuit by adjusting the aortic

cross-clamp and bolus of cardioplegia will later on be

re-administrated.

Situation awareness helps support the

response to the unexpected events that may arise anytime

during their ight mission or operating procedure.

According to SHELL model in Fig 1, this model can

help understand human factor element in CRM concept.

The SHELL model is a conceptual model of human

factors that helps clarify the human factor relationships

between resource, system, environment and human.

e model represents several wavy squares to illustrate

dierent elements of imperfect interacting components

which are Soware (policies, procedures, practices),

Hardware (machines, aircra), Environment (working

context) and Liveware (man). e core component of

this model is the man (Liveware), ight crew or operating

room crew in this case, and this is considered as the

most sensitive system component as human is subject

to great variation in performance and limitation and all

other components ought to be adapted to t with this

centered Liveware such as Liveware-Hardware (man

and machine), Liveware-Soware (man and procedure),

Liveware-Environment (man and working environment).

According to CRM concept, Liveware-Liveware (man

and man) is the most essential interaction term as this

interface is about interpersonal interaction; moreover,

the human is the weakest point in safety operation

and considered as the major cause of an accident.

13,14

Liveware-Liveware (L-L) interaction encompasses the

interrelationships among the individuals within operator

groups. In aviation context, pilots are the centered

liveware that interacts with engineers, ground crew, cabin

crew, air trac controller and passengers. In healthcare

context, surgeons are the centered liveware that interacts

with anesthesiologists, anesthetists, perfusionist,

medical interns and patients. Human interaction can

inuence work behavior and performance. ereby, the

L-L interface is mostly concerned with interpersonal

relationship, crew cooperation, communication and

leadership. Poor L-L interface can be result in a risky

working situation. For example, bad interpersonal

relationship between captain and rst ocer can lead

to an undesirable cockpit environment and this can

also lead to an accident as seen in Korean Air Flight

801. First ocer and ight engineer failed to challenge

captain for the wrong ground base radio navigation aid

approach and captain did not listen to his subordinates

then the aircra crashed into the hill about 3 nautical

miles short of the runway.

To mitigate L-L interface risk,

appropriate CRM training can be applied to those ight

crew and operating room crew that always assigned to

work together as a team.

Fig 1. SHELL Model Adapted from ICAO

Both healthcare and aviation are high reliable

industries and specific training is necessary. Crew

Resource Management (CRM) concept is introduced

to support and enhance teamwork exercise and team

performance. CRM is the eective use of all available

resources for ight crew personnel to assure a safe and

ecient operation, reducing error, avoiding stress and

increasing eciency.

is type of training incorporates

simulator-based scenarios and on the job training (OJT)

to allow team members to practice both technical skill

and so skill and attain feedback on their performance

from instructors. CRM ensures that team members

responsibilities are clearly dened and properly delegated

when a sudden change in workload occurs. In summary,

it helps team members to solve unforeseen problem.

In aviation, problem solving is more efficient when

the immediate corrective actions of designated crew

members are clearly dened. In operating room, the

need for close cooperation and intensive communication

between members may be slightly deviant from aviation

as many surgeons, anesthesiologists, technicians and

nurses tend to focus on their own work and only consult

with each other whenever they need.

19,20

However, cardiac

surgeons represents a close CRM practice to pilots seeing

that they are accustomed to frequently communicate with

perfusion technicians, anesthetist and anesthesiologist at

their mission.

Less cooperation between medical sta in

operating room tends to rise due to distinct and delimit

competencies and responsibilities of surgeons and

anesthesiologist compared to ight crews. Disagreement

Maneechaeye et al.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

713

Review Article

SMJ

between surgeons and anesthesiologist needs to be

resolved by absolute consensus as these two professions

share the same level of responsibility. While in aviation,

captain or Pilot-in-Command (PIC) always has ultimate

decision.

In practice, active communication between

operating team members is the key and can help improve

a smoother operating process and yield a better result.

For example, if anesthetists were briefed in advance

regarding patient condition, they would cope with

hemodynamic and metabolic changes condently and

then they can mitigate the risk of detrimental impact

from aorta-cross clamping.

Checklists and readbacks

In aviation context, checklists have been developed

for each phase of the ight mission including taxi, takeo,

climb, level ight, descend, approach and landing as

well as for emergency situations that may arise during

mission. Pilots are strongly encouraged and committed

to abide by these checklists and any deviation from

checklists is considered a ight regulation violation.

Moreover, checklists are specically designed to the

specic type of aircra to assure that all safety-related

elements are included. In healthcare, back in 2008, the

World Health Organization (WHO) released surgical

safety checklists to embrace patient safety. WHO surgical

safety checklist tries to imitate each phase of the ight

mission by dividing each phase of surgical operation

including anesthesia, incision and wound closure.

Even though WHO did not force medical practitioners

to adhere to this checklist but WHO strongly encourages

them to edit the proposed checklist to their own

operation. In fact, by customizing checklist for their

own interests of interventions like aviation checklist

that is tailored made for specic type of aircra, may

seem logical.

For instance, vascular surgery operation

might need dierent safety checks for endovascular

procedures than for orthopaedical surgery. For the most

complicated or infrequent performed procedures, even

more intervention-specic checklist may be necessary.

Eective, yet ecient communication is determined

as a very basic human necessity which is particularly

essential to assure safety in high-reliability industries,

healthcare and aviation alike. In spite of minor error

in communication during operation, damage and loss

can be anticipated.

A readback, in aviation, is dened

as a procedure whereby the receiving station repeats a

received transmitted message or an appropriate part

thereof back to the transmitting station in order to obtain

conrmation of correct reception.

In short, the process

of readback involves the person receiving information

repeating it back verbally to the sender and this will let

the sender know the message has been received and

provides a chance to correct any discrepancies. Some past

air accidents involving poor communication between

pilots and air traffic controller and this emphasizes

that human errors in communication still occur even

in advances technology in aviation. On the contrary,

it is essential to develop communication phraseology

or standard protocols in high-reliability industries like,

marine, aviation and surgery.

Past study revealed that a

signicant source of surgical errors can be contributed to

a poor communication before, during and aer surgery.

Poor verbal communication accounted for approximately

85% of undesired event related to verbal communication

but poor written communication only accounted

for approximately 4%.

According to this result, the

patient safety needs formal readback. Readback, in this

medical-related case, can be ranging from readbacking

orders among team members operating on patient so

as to reduce incidence of perioperative complications

to readbacking medication orders over the phone

when verbal transmission of critical information is

inevitable.

31,32

Past study quantified the impact of

readback as a communication technique for improving

transmission of clinically relevant information during a

critical phrase of work. It found that when anesthetists

mentioned items of information to anesthesiologists in

a simulated emergency situation, the anesthesiologists

were much more likely to correctly answer a question

about the information aer the scenario if they had

repeated it back at the time it was mentioned to them

and this could promote a better level of patient safety

during operation.

Moreover, psychology study also

suggested that repeating back important information

is likely to help improve memory. is is determined

as ‘production eect’, the phenomenon where speaking

words improve memory of those spoken words.

While

aviation checklists is mandatory to mitigate human error

risk that might lead to an unsafe situation, in operating

room setting, surgeons and team members should

consider which scenarios are critical and design their

own specic checklist as per scenarios, especially in the

critical phrase of the procedure that requires immediate

action.

Sterile cockpit

Even though an operating room is literally sterile

for sanitary purpose, sterile cockpit, in aviation context,

does not mean that the ight deck is sanitized by any

disinfection agents. It means that the ight crews in the

cockpit keep the environment of a cockpit safe from all

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

714

non-pertinent conversation and non-essential activities

are disregarded during critical phases of ight especially

takeo and landing. is concept of sterile cockpit has

stemmed from the notion that distracting activities

cause pilot errors and reduce pilot ight performance.

Nonetheless, the working environment of an operating

theater is less structured than a cockpit with much more

distractions including noisy sound from outside operating

room, ringing phone, non-relevant conversation about

next patients among members, inquiries from medical

students and nurses, and many more.

ese are sources

of distraction and might contribute to a lower levels of

dexterity and concentration of surgeon at procedure.

For instance, a cardiovascular surgeon is going to start

a complex endovascular procedure that two catheter

introducers have to be placed. While attempting to

bilateral femoral access, surgeon is distracted by an

incoming phone call consulting about previously

operated patient and the assisting medical student

needing to discuss his report log. In the same time,

anesthetist has le the operating room to fetch a stent

gra and the anesthesiologist also le the room for a

coee break. Later on, surgeon nds out that heparin

was administrated twice from new coming anesthetist

and anesthesiologist. Countermeasures to mitigate

the distraction risk could be simple such as reducing

background noise by using sound proof material wall

or prohibition of phone call might help create more

peaceful environment. Lead surgeon can encourage

team members to regain a focus by telling them that a

critical phase of procedure is about to commence and

all team members need to focus on the work at present

before everything else. As the concept of sterile cockpit

is to remain focus and concentrate on the current critical

situation, surgeons ought to perform leadership and

professional demeanor at work and they must take the

current job at hand seriously.

Human factors: fatigue and stress

Fatigue is one of the most common physiological

problems for flight crews and will adversely affect

individuals who are otherwise in good health condition.

It has frequently been considered as the causal factor

in aviation incidents and accidents as fatigue degrades

performance and tired ight crews cannot carry out

ying tasks as reliably and accurately as they should

normally perform. Moreover, ey are irritable and less

alert, willing to accept lower standards of accuracy and

performance.

Fatigue begins when the pilot commences

a ight continuously and increases with each hour in

the air. As a result, at the time of landing when reexes

and judgement should be at high, the pilot is most

aected by the cumulative eects of fatigue. In addition,

the major danger of fatigue is that it is cumulative and

the pilot might not recognize its eect. Fatigue can be

caused by many factors such as lack of sleep, poor food,

long-haul ight, heavy workloads, frustration from work

and uncomfortable working condition.

In this matter,

pilots share the same occupational fatigue with surgeons.

Many surgeons also face long working hours, night

shi duties and several pressures at work. e eect of

fatigue from various factor such as long working hour

and work challenges on the quality of work of surgeons

has been studied and it eect the same way as found in

pilots.

Acute fatigue is easily treated by good nutrition

and sucient rest. A sound physical condition and a

healthy psychological attitude combining with good diet

and adequate sleep are pilots and surgeons best super

weapons in fighting fatigue.

For the long working

hours in surgeons’ duty, hospital managements and

surgeons need to work together and discuss the proper

working hours. If surgeon and anesthesiologist decide

to adjourn a procedure in case of fatigue and weariness,

it may turn out to be better o for patient safety and

hospital management should consider this as a proper

decision.

43,44

Stress indeed is generated by the task itself and it is

not always negative as the sympathetic nervous system

responds to stress and supplies the resources to deal

with the upcoming demands. Factors contributing to

stress are generally classied into three categories which

are physical, physiological and psychological stressors.

Physical stressors include extreme temperature, noise,

vibration, lack of oxygen, etc. Physiological stressors

include fatigue, hunger, disease, etc. Psychological

stressors relate to emotional factors such as worries,

poor personal relationship, nancial problem, etc.

is quintessential that both pilot and surgeon are able to

recognize when stress levels are getting too high. If they

are suering from domestic stress, divorce, bereavement

or even moody sensation, the cockpit or operating

room might not be suitable places for them. Besides,

the stress of ying or operating also consume energy.

is energy is derived from oxygen and blood sugar.

Pilots who y for too long without eating or surgeons

who operate procedures for too long and skip meal will

face low blood sugar or hypo glycaemia; that is to say,

their energy reserve will be low and cause reactions

to be sluggish and effect their work performance

drastically.

Due to high-reliability work context in

aviation, every pilot needs to pass physical and mental

tness checkup annually to be qualied for ight duty

Maneechaeye et al.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

715

Review Article

SMJ

and medical tness. is ensures adequate operational

safety in every ight. Sign of chronic stress are varied

such as forgetfulness, repeated mistakes, tense stomach

and it may erode individuals’ self-image. Challenges

at work can also lead to burnout.

However, stress

is manageable. ere are several ways that pilots and

surgeons can deal with stress. e physiological stressors

can be controlled by maintaining sound physical tness

or getting adequate sleep. e physical stressors can

be reduced by making the cockpit or operating room

environment as relax as possible. A conscious eort to

avoid stressful situation and support from family, friends

and colleagues can minimize psychological stressors.

If needed, professional mental counseling help restore

psychological equanimity.

48-50

eoretical concepts

Swiss cheese model

Swiss cheese model, portrayed in Fig 2, was

hypothesized that most accidents or incidents could be

traced to one or more of four level of failure that had

been placed in order consecutively.

ese four levels of

failure include organizational inuences (organization-

level), unsafe supervision (supervision controls),

preconditions for unsafe acts (work-related processes)

and the unsafe acts themselves (people). e cheese layers

can be portrayed as layers of defenses and the holes are

considered as lapses in defensive layers. Whether or not

latent or manifested failures, it can be seen that over time,

the holes in the cheese will line up straights and threats

will nd a way to get through all cheese layers and cause

an incidents or accidents. is event is considered as a

trajectory of accident opportunities. e underpinned

concepts proposed by Swiss cheese model is a proper

view on human factors in term of error, that is to say,

human error is a general symptom of system failures

that demands explanation.

In aviation context, for instance, even when many

things can go wrong such as an aircra trac separation

infringement in case that the traffic conflict is not

regarded or resolved by air trac controller, pilots or

trac collision avoidance system (TCAS) in the aircra

will still get the job done and cause a very small chance

that aircra may collide each other midair. Air trac

controller inability to resolve conict trac is considers

and a threat that pass through a hole of one cheese but

pilot and TCAS ability to detect conict trac is another

cheese that block this threat to pass through. However, if

threat can pass through all the layers of cheese, accident

or incident can be anticipated. In aviation scenarios,

ight crew working for an airline that has poor safety

procedure (organization influence) with poor pilot

training record and supervision (unsafe supervision) are

operating a commercial ight, when there is an air trac

conict during critical nal approach (precondition of

unsafe acts), pilots ignore cautions from both TCAS and

air trac controller (unsafe acts). In this case all holes

in the cheese will line up straights and threats will get

through all cheese layers and cause a serious accident.

In operating room context, a vascular surgeon working

for a hospital that has marginal standard operating

procedure (organization inuence) with poorly-trained

operating room crew (unsafe supervision) is operating

an axillofemoral by pass, the procedure is uneventful

until the anesthesiologist notices a sharp drop in

blood pressure causing a demand in blood transfusion

(precondition of unsafe acts). Anesthesiologist suggests

that excessive blood loss is the cause but it is disregarded

by surgeon (unsafe acts). Later on, it is found that the

cause is stemmed from a disagreement between the

Fig 2. Swiss Cheese Model Adapted

from James Reason

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

716

forceful femoral pulses and the perceived hypotension.

It is also recognized that cross-clamping of the axillary

artery has also intervened blood ow towards the radial

artery where invasive pressure measurement occurs. In

this case, the threat can pass through all defensive line

and causing incident.

53,54

reat and error management

Originally, threat and error management model

may be developed for ight deck operation; nevertheless,

this can be used at healthcare or other industries as well.

reat and Error Management (TEM) is a conceptualized

framework that helps in understanding, from an

operational perspective, the intra-relationship between

operational safety and human performance in dynamic

and challenging operational context.

is model is

descriptive and diagnostic of both human and system

performance and the main objective of this model is to

understand error management namely error detection

and error response rather than only focusing on error

causality. ere are three main components in TEM,

from aviation perspective: threats, errors and undesired

aircra states (UAS).

reats are dened as events or errors that occur

beyond the influence of the flight crew, increase

operational complexity and which must be managed to

maintain the margins of safety.

During operation, ight

crews need to manage various external complexities.

such as adverse meteorological condition, air trac

congestion and aircra technical malfunction. Some

threats can be anticipated as they are expected to ight

crews such as adverse meteorological condition and air

trac. ese can be found in notice to airman (NOTAM)

and weather forecast information. However, some

threats cannot be anticipated such as in-ight technical

malfunction occurring without any warning. In this

case aircrews need to apply skills and knowledge to

cope with this threat. To simplify, threats are something

bad that arise from outside the cockpit. However, there

are some internal threats relating to human factor and

limitations such as inappropriate crew scheduling event.

When current ight crew are unexpectedly assigned

to y an extra ight due to an absence of other crew

calling in sick, this can possibly deteriorate their ight

performance and aect human factor limitation, which is

fatigue.

Another example for internal threat ascribed to

human factors is an instant diarrhea attack in ight crew

during ight due to unclean food intake or norovirus

transmission on an airplane. In this case, good situation

awareness needs to be exercised to correct and properly

manage the situation. Pilot needs to detect the symptom

early and instantly pass aircra ight control to co-pilot

to avoid unusual aircra ight attitudes.

Error are dened as actions or inactions by the

ight crews that lead to deviations from ight crews

intentions or expectations.

Unmanaged or mismanaged

errors mostly lead to undesired aircra stated and error

in the operational context hence leads to reduce the

margins of safety and increase the possibility of adverse

events to occur. Despite the modern aircra computer

technology, erroneous pilot can input incorrect ight

parameter into ight computer and this will lead to

future adverse event. Regardless of the error types, errors

eect on safety depends upon whether the ight crews

detect and responds to the error before it may lead to

an adverse event or potential unsafe outcome. From the

safety aspects, operational errors that are timely detected

and promptly responded to will not reduce margins of

safety; besides, proper error management represents

an example of successful human performance.

59,60

simplify, errors are something bad that arise from the

pilots.

Undesired Aircra States (UAS) are dened as

ight crew-induced aircra position or speed deviations,

misapplication of ight controls, or incorrect automation

system conguration, associated with a reduction in

margins of safety.

UAS resulting from ineective threat

and error management may lead to adverse situation and

reduce margins of safety in ight mission as UAS is the

last chance for pilots to act accordingly so as to prevent

upcoming incident or accident. Examples of UAS include

exceeding speed restriction during an approach, landing

short of runway or lining up for the incorrect runway

for takeo. To simplify, Undesired Aircra States (UAS)

are the result from threats and errors.

In healthcare context, disturbing sound made by

an overly excited orthopedic surgeon in the operating

room nearby or inexperience crewmates performing

incorrect procedure may contribute to reduced levels of

concentration of a surgeon and these can be considered

as threats. Moreover, overwork that causing fatigue

and stress and surgeon’s poor health condition can be

considered as internal threats that aect human factor

and limitations. Mismanaged operating treatment or

failure to following standard operating procedure due

to various factors that are stemmed from surgeon can

be regarded as error. A sign of sudden drop in blood

pressure and patient arrest are, in this case, considered

as undesired aircra states.

According to Fig 3, at the top of the inverted

triangle is considered as safe operations. at is where

the operation always strives to be; nonetheless, pilots and

Maneechaeye et al.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

717

Review Article

SMJ

surgeons experience several threats during their mission.

erefore, they should constantly be prepared for those

threats to maintain a safe operation. In addition, apart

from threat, several errors stemmed from pilots and

surgeons can be anticipated. ey need to instantly act

accordingly to prevent further adverse event that will

lead to undesired aircra states and eventually accident.

Proper communication also plays an important role in

TEM. It was regarded as Concerned, Uncomfortable and

Safety (CUS) words. If surgeons hear another teammate

says “I am concerned.”, “I feel uncomfortable about this.”,

or “Patient safety is currently being compromised.”, they

should stop what they are doing and listen to address

those concerns accordingly.

Fig 3. reat and Error Management Model Adapted from United

Airlines

All in all, both practical and theoretical concepts

regarding safety can be summarized as shown in

Table 1.

DISCUSSION

According to the four operational concepts and

two theoretical concepts of aviation safety mentioned

previously, it can be seen that there is one element that

the concepts have in common, which is “communication”.

is nding shares the same insight corresponding with

past research concerning the impact of communication

in healthcare.

63-66

erefore, even these aviation-related

safety concepts might not be entirely applied to healthcare

industry. Rest assured; eective communication is still

be the key to promote better patient safety in healthcare

environment. In regard to effective communication

within team members, lead surgeons should lower

their ego at work and listen to their team members even

more. Even seasoned or highly-experienced surgeons

can still be questioned regarding the operating problem

at present and their resolution or problem-solving

procedure should be explained to their teammates to

ensure that the team is on the same page. Surgeons

should not take team communication as the challenge

to their authority but they should consider the eective

communication as a better way to promote teamwork

to ensure better patient safety. Another aspect relating

to eective communication is briengs, pre-operative

brieng is also important to promote patient safety.

In aviation, pre-ight brieng is mandatory and this

process is written in every company standard operating

procedures (SOPs) as pre-ight brieng allows a clear

understanding and awareness among ight crew about

weather condition, planned ight route, passenger and

cargo status and aircra condition. Healthcare alike, pre-

operative brieng regarding patient’s status and planned

operation procedures could allow a better understanding

and awareness among team members at their mission.

Aer nishing ight mission or operating procedure,

post-ight debrief or post-operative debrief can be done

to summarize overall mission scenarios. By debrieng,

team members can be readily prepared for the next

mission and apply experience from the past job to the

next assignments.

As mentioned earlier, both aviation and health

care are high-reliability elds; passenger safety must

never be compromised, just as patient safety must never

be compromised. at is to say, the margin of safety

must never be diminished. Both pilots and surgeons

must adopt these safety concepts together with eective

communication skills and bring these important assets

with them to the cockpit or operating room to ensure

more reliability in their day-to-day operations to promote

the utmost goal, which is safety at work.

CONCLUSION

is review article aims to portray aviation-related

concepts that apply to surgical safety strategies. However,

these concepts remain only partially applicable to

healthcare. Even though a few of these operationalized

concepts have been applied to surgical practice, none

have been properly veried or validated. Past studies

have claimed that these concepts could improve patient

safety and operating outcomes, but there have also been

various arguments that these concepts may not be totally

compatible with healthcare.

67,68

At the very least, eective

communication plays an important role to promote

safety at work for both professions. Indeed, despite

Volume 73, No.9: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

718

TABLE 1. Summary of Practical Concepts and eoretical Concepts in Safety.

Safety Concepts Aviation Context Healthcare Context Similarities Differences

Crew Resource

Management

(CRM)

Checklists

Readbacks

Sterile Cockpit

Human Factor:

Fatigue

Human Factor:

Stress

Swiss Cheese

Model

Threat and Error

Management

(TEM)

- Two pilots, which are Captain and

First Ofcer, work with Cabin Crew,

Engineer and Air Trafc Controller

within the ight mission.

- Checklists are mandatory and any

deviation from checklists is

considered as a violation.

- Checklists have been developed for

each phase of the ight.

- A procedure whereby the receiving

station repeats a received transmitted

message or an appropriate part

thereof back to the transmitting

station to attain conrmation of

correct reception.

- Flight crews keep the environment

of a cockpit free from all non-relevant

conversation during critical phases

of ight.

- Fatigue begins after a long ight

hour.

- Stress is generated by continuous

challenges at ight mission.

- Four levels of failure can be poor

SOPs, inadequate training, instrument

failure and poor piloting technique

- Threat: Bad weather, congested air

trafc, technical failure.

- Error: Poor piloting technique,

cockpit mismanagement.

- UAS: Improper airspeed, Failure to

maintain glide path during approach.

- Surgeon works with

Anesthesiologist, Anesthetist,

Medical Technician within the

operating room.

- Checklists are optional.

- Surgical Checklists proposed by

WHO can be edited to suite different

interests of interventions.

- The person receiving information

repeats it back verbally to the sender

and the sender will know whether

the message has been received

correctly.

- Operating crews encourage each

other to regain a focus in a critical

phase of procedure.

- Fatigue begins after a long hour

of clinical work.

- Stress is generated by the

operating task itself.

- Four levels of failure can be poor

SOPs, insufcient training, poor

operating tools technique, and

improper operating skill

- Threat: Improper procedure

performed

by inexperience teammate.

- Error: Mismanaged operating

treatment by surgeon.

- UAS: A sign of sudden drop in

blood pressure, patient arrest.

- Team working operates in high-risk

environments.

- Team members are skillful and professional

and always change in difference tasks.

- Checklists have been designed to suite

different phrase or different progress of

work.

- The concept of “reading-it-back” to

conrm the correctness and

completeness of communication.

- The notion of “staying focus” on the critical

phase of work.

- Fatigue degrades work performance.

- Mind stress is acceptable but intensive

stress will deteriorate work performance.

- Four levels of failure include organizational

inuence, unsafe supervision, preconditions

for unsafe acts and unsafe acts.

- Threat is considered as an external factor.

- Error is regarded as an internal factor.

- Undesired Aircraft States (UAS) is a result

from threat and error and this considered

as a last chance to correct to prevent future

adverse event.

- Pilot-in-Command or Captain is

responsible for absolute decision.

- Disagreement needs to be solved by

consensus from both surgeon and

anesthesiologist.

- In aviation, checklists are mandatory.

- In healthcare checklists are optional.

- In ight, readbacks are required as a

transmission over radio frequency might not

be clear due to radio noise and frequency

interruption.

- In healthcare, readbacks are encouraged in

the critical phase of clinical communication to

promote more patient safety.

- Flight deck is isolated and well-structured.

- Operating room is less-structured than

a cockpit with more distractions from both

inside and outside

- Flight duty time is regulated by law.

- Management and surgeons need to set a

middle ground on working hour.

- Annually, every pilot needs to pass both

physical and mental tness examination

before ight.

- Physical and mental tness examination is

not required to perform duty in healthcare.

- Aviation accident result in enormous loss

of lives and assets and pilots pay it with their

own life.

- Failure in operating room cause a single

loss of life.

- In aviation, in spite of advance technology of

aircraft computer, aircraft automation can be

overridden by erroneous pilot.

- In operating theater, error can be prevented

by suitable communication between crews.

Maneechaeye et al.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

719

Review Article

SMJ

obvious similarities between these two professions,

there are a number of dierences as well. Besides, the

implementation of aviation safety practices and concepts

in the surgical context may be less than optimal. For

example, pilots are required to conform to ight duty

time strictly as this is regulated by law. Nonconformity

to this rule and overworking as a pilot can be considered

a serious safety violation; both the pilots and their

airlines will be penalized accordingly. However, long

working hours contributing to fatigue among healthcare

professionals are not formally regulated by law. In this

matter, hospital management and surgeons need to have a

mutual agreement regarding the limits of working hours.

Notwithstanding, the sound and solid safety record of

aviation has been indisputable and proven itself for

decades. ese aviation safety concepts will continue

to be a useful source of inspiration for any healthcare

professional striving to achieve superior patient safety

standards.

Limitations

Even though this review article shed light on novel

aspects of aviation safety concepts into patient safety

in healthcare context, there were some limitations.

Because this article is a review article, future study

should probably extend the concepts of this review into

an experimental research to analyze the eect of those

concepts on actual healthcare settings. Additionally,

qualitative research may prove useful to investigate the

real application of these concepts in actual healthcare

context as qualitative study can delve deep down into

richer results that quantitative research cannot nd.

ACKNOWLEDGEMENTS

e lead author would like to thank my co-authors

for great support on this work. is review was funded

by Graduate School Scholarship, Prince of Songkla

University. Scholarship Contract Number PSU_

PHD2562-001

Conict of interest: ere is no conict of interest.

REFERENCES

1. DaRBy R. Commercial jet hull losses, fatalities rose sharply

in 2005. Aviat Saf World 2006;1:51-53.

Sox Jr HC, Woloshin S. How many deaths are due to medical error?

getting the number right. E Clin Pract ECP 2000;3:277-83.

3. Kao LS, omas EJ. Navigating towards improved surgical

safety using aviation-based strategies. J Surg Res 2008;145:327-

35.

4. Maneechaeye P. e Commodication of Idol Culture with

a Loot-Boxes-Style Marketing Strategy Practice in ai Idol

Culture and Aspects of Consumer Psychology toward

Uncertainties. Humanit Arts Soc Sci Stud [Internet]. 2021;

21:179-87. Available from: https://so02.tci-thaijo.org/index.

php/hasss/article/view/239553/168245

5. Day D V, Gronn P, Salas E. Leadership in team-based

organizations: On the threshold of a new era. Leadersh Q

2006;17:211-6.

6. Entin EE, Serfaty D. Adaptive team coordination. Hum Factors

1999;41:312-25.

7. Endsley MR, Robertson MM. Situation awareness in aircra

maintenance teams. Int J Ind Ergon 2000;26:301-25.

8. Adams MJ, Tenney YJ, Pew RW. Situation awareness and

the cognitive management of complex systems. Hum Factors

1995;37:85-104.

9. Ericsson KA, Kintsch W. Long-term working memory.

Psychol Rev 1995;102:211.

10. Hazlehurst B, McMullen CK, Gorman PN. Distributed

cognition in the heart room: how situation awareness arises

from coordinated communications during cardiac surgery.

J Biomed Inform 2007;40:539-51.

11. Wickens CD. Situation awareness and workload in aviation.

Curr Dir Psychol Sci 2002;11:128-33.

12. Hawkins FH, Orlady HW. Human factors in ight. Routledge;

2017.

13. Hosseinian SS, Torghabeh ZJ. Major theories of construction

accident causation models: A literature review. Int J Adv Eng

Technol 2012;4:53.

14. McKenna FP. e human factor in driving accidents An

overview of approaches and problems. Ergonomics 1982;

25:867-77.

15. Briggs CL. Rethinking the Public: Folklorists and the

Contestation of Public Cultures. J Folk Res 1999:283-6.

16. Salas E, Burke CS, Bowers CA, Wilson KA. Team training in

the skies: does crew resource management (CRM) training

work? Hum Factors 2001;43:641-74.

17. Powell SM, Hill RK. My copilot is a nurse—using crew

resource management in the OR. AORN J 2006;83:178-202.

18. Helmreich RL. Does CRM training work? Air Line Pilot 1991;

60:17-20.

19. Flin R, Yule S, McKenzie L, Paterson-Brown S, Maran N.

Attitudes to teamwork and safety in the operating theatre.

Surg 2006;4:145-51.

20. Makary MA, Sexton JB, Freischlag JA, Holzmueller CG,

Millman EA, Rowen L, et al. Operating room teamwork

among physicians and nurses: teamwork in the eye of the

beholder. J Am Coll Surg 2006;202:746-52.

21. de Leval MR, Carthey J, Wright DJ, Farewell VT, Reason JT.

Human factors and cardiac surgery: a multicenter study. J

orac Cardiovasc Surg 2000;119:661-72.

22. Ricci MA, Brumsted JR. Crew resource management: using

aviation techniques to improve operating room safety. Aviat

Space Environ Med 2012;83:441-4.

23. Pizzi L, Goldfarb NI, Nash DB. Crew resource management

and its applications in medicine. Mak Heal care safer A Crit

Anal patient Saf Pract 2001;44:511-9.

24. Allard J, Bleakley A, Hobbs A, Coombes L. Pre-surgery

briengs and safety climate in the operating theatre. BMJ

Qual Saf 2011;20:711-7.

25. Hales BM, Pronovost PJ. The checklist—a tool for error

management and performance improvement. J Crit Care

2006;21:231-5.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

720

26. Weiser TG, Haynes AB, Lashoher A, Dziekan G, Boorman DJ,

Berry WR, et al. Perspectives in quality: designing the WHO

Surgical Safety Checklist. Int J Qual Heal Care 2010;22:365-70.

27. Catchpole KR, Dale TJ, Hirst DG, Smith JP, Giddings TAEB.

A multicenter trial of aviation-style training for surgical teams.

J Patient Saf 2010;6(3):180–6.

28. Prinzo OV, Morrow DG. Improving pilot/air trac control

voice communication in general aviation. Int J Aviat Psychol

2002;12(4):341-57.

29. Prabhakar H, Cooper JB, Sabel A, Weckbach S, Mehler PS,

Stahel PF. Introducing standardized readbacks to improve

patient safety in surgery: A prospective survey in 92 providers

at a public safety-net hospital. BMC Surg 2012:12.

30. Greenberg CC, Regenbogen SE, Studdert DM, Lipsitz SR,

Rogers SO, Zinner MJ, et al. Patterns of communication

breakdowns resulting in injury to surgical patients. J Am Coll

Surg 2007;204(4):533-40.

31. Stahel PF. Learning from aviation safety: a call for formal

“readbacks” in surgery. Patient Saf Surg 2008;2(1):1-2.

32. Stahel PF, Maurey C. Patient safety in surgery. Patient Saf

Surg 2014:1-513.

33. Boyd M, Cumin D, Lombard B, Torrie J, Civil N, Weller J.

Read-back improves information transfer in simulated clinical

crises. BMJ Qual Saf 2014;23:989-93.

34. MacLeod CM, Gopie N, Hourihan KL, Neary KR, Ozubko JD.

e production eect: Delineation of a phenomenon. J Exp

Psychol Learn Mem Cogn 2010;36:671.

35. Wiener EL. Beyond the sterile cockpit. Hum Factors

1985;27:75-90.

36. Broom MA, Capek AL, Carachi P, Akeroyd MA, Hilditch G.

Critical phase distractions in anaesthesia and the sterile cockpit

concept. Anaesthesia 2011;66:175-9.

37. Hohenhaus SM, Powell SM. Distractions and interruptions:

development of a healthcare sterile cockpit. Newborn Infant

Nurs Rev 2008;8:108-10.

38. Federwisch M, Ramos H, Shonte’C A. e sterile cockpit: an

eective approach to reducing medication errors? AJN Am J

Nurs 2014;114:47-55.

39. Bennett SA. Flight crew stress and fatigue in low-cost

commercial air operations-an appraisal. Int J Risk Assess

Manag 2003;4:207-31.

40. Powell D, Spencer MB, Holland D, Broadbent E, Petrie KJ.

Pilot fatigue in short-haul operations: Eects of number of

sectors, duty length, and time of day. Aviat Space Environ

Med 2007;78:698-701.

41. Lockley SW, Landrigan CP, Barger LK, Czeisler CA. When

policy meets physiology: the challenge of reducing resident

work hours. Clin Orthop Relat Res 2006;449:116-27.

42. Caldwell JA. Fatigue in aviation. Travel Med Infect Dis 2005;

3:85-96.

43. Staender SE. Patient safety in anesthesia. Minerva Anestesiol

2010;76:45-50.

44. Sinha A, Singh A, Tewari A. e fatigued anesthesiologist: A

threat to patient safety? J Anaesthesiol Clin Pharmacol 2013;

29:151.

45. Friend TH. Behavioral aspects of stress. J Dairy Sci 1991;74:292-

303.

46. Taylor LA, Rachman SJ. The effects of blood sugar level

changes on cognitive function, aective state, and somatic

symptoms. J Behav Med 1988;11:279-91.

47. Maneechaeye P. Factors Aecting Burnout in Out-of-Oce

Workers in Thailand: a Moderated Multiple Regression

Approach. ASEAN J Manag Innov [Internet]. 2020;7:108-18.

Available from: https://ajmi.stamford.edu/index.php/ajmi/

article/view/139/139

48. Dahlqvist V, Söderberg A, Norberg A. Dealing with stress:

Patterns of self-comfort among healthcare students. Nurse

Educ Today 2008;28:476-84.

49. Lyckholm L. Dealing with stress, burnout, and grief in the

practice of oncology. Lancet Oncol 2001;2:750-5.

50. Otto K, Schmidt S. Dealing with stress in the workplace:

Compensatory eects of belief in a just world. Eur Psychol

2007;12:272-82.

51. Peltomaa K. James Reason: Patient safety, human error, and

Swiss cheese. Qual Manag Healthc 2012;21:59-63.

52. Reason J, Hollnagel E, Paries J. Revisiting the Swiss cheese

model of accidents. J Clin Eng 2006;27:110-5.

53. Perneger T V. e Swiss cheese model of safety incidents: are

there holes in the metaphor? BMC Health Serv Res 2005;5:1-7.

54. Collins SJ, Newhouse R, Porter J, Talsma A. Eectiveness of

the surgical safety checklist in correcting errors: a literature

review applying Reason’s Swiss cheese model. AORN J 2014;

100:65-79.

55. Helmreich RL, Musson DM. reat and error management

model: Components and examples. Br Med J 2000;9:1-23.

56. Brennan PA, De Martino M, Ponnusamy M, White S, De Martino

R, Oeppen RS. Avoid, trap, and mitigate–an overview of threat

and error management. Br J Oral Maxillofac Surg 2020;58:

146-50.

57. Jackson CA, Earl L. Prevalence of fatigue among commercial

pilots. Occup Med (Chic Ill) 2006;56:263-8.

58. Ruskin KJ, Stiegler MP, Park K, Guey P, Kurup V, Chidester T.

Threat and error management for anesthesiologists: a

predictive risk taxonomy. Curr Opin Anaesthesiol 2013;26:707.

59. omas MJW. Predictors of threat and error management:

Identication of core nontechnical skills and implications for

training systems design. Int J Aviat Psychol 2004;14:207–31.

60. Dekker SWA, Lundstrom J. From threat and error management

(TEM) to resilience. Hum Factors Aerosp Saf 2006;6:261.

61. Marušić Ž, Alrević I, Radišić T. Analysis of the aviation safety

issues using TEM framework. Teh Vjesn 2009;16:79-84.

62. Kalra J, Kalra N, Baniak N. Medical error, disclosure and

patient safety: A global view of quality care. Clin Biochem

2013;46:1161-9.

63. Eisenberg EM, Murphy AG, Sutclie K, Wears R, Schenkel S,

Perry S, et al. Communication in emergency medicine: implications

for patient safety. Commun Monogr 2005;72:390-413.

64. Nadzam DM. Nurses’ role in communication and patient

safety. J Nurs Care Qual 2009;24:184-8.

65. Lingard L, Espin S, Whyte S, Regehr G, Baker GR, Reznick R,

et al. Communication failures in the operating room: an

observational classication of recurrent types and eects. BMJ

Qual Saf 2004;13:330-4.

66. Christian CK, Gustafson ML, Roth EM, Sheridan TB, Gandhi

TK, Dwyer K, et al. A prospective study of patient safety in

the operating room. Surgery 2006;139:159-73.

67. Rissmiller R. Patients are not airplanes and doctors are not

pilots. Crit Care Med 2006;34:2869.

68. omas EJ, Helmreich RL. Will airline safety models work

in medicine. Med error what do we know. 2002:325.

Maneechaeye et al.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

721

Review Article

SMJ

Tengiz Verulava, M.D., Ph.D. *,**

*School of Medicine and Healthcare Management, Caucasus University, Tbilisi, Georgia, **School of Psychology and Public Health, La Trobe University,

Melbourne, Australia.

Access to Healthcare as a Fundamental Right or

Privilege?

ABSTRACT

Right to health is a government obligation to provide its citizens with necessary medical services regardless of

their ability to pay. e right to health requires the state to develop policies and action plans to achieve accessible

health care. Ensuring access to healthcare services is an important social responsibility; because of its socio-economic

nature, demand for it oen carries not only individual but also social aspects that need to be considered and requires

the consolidation of consumer funds. Peculiarities of the medical market such as health risk and uncertainty,

incomplete information, limited competition, external eects, production of public goods, lead to special forms of

economic relations in the medical market, which requires the development of appropriate regulatory mechanisms.

In countries, where an individual’s nancial contribution to health care does not depend on his or her health risk,

there is a principle of universal health care, which covers the entire population. Human is a higher social capital

for whom health care is considered a right and not a privilege not only for humanistic and moral reasons, but also

for rational, utilitarian approaches, as universal access benets both the individual and society as it increases labor

productivity.

Keywords: Healthcare; human rights; healthcare rights; universal healthcare (Siriraj Med J 2021; 73: 721-726)

Corresponding author: Tengiz Verulava

E-mail: tverulava@cu.edu.ge

Received 15 June 2021 Revised 30 July 2021 Accepted 16 August 2021

ORCID ID: https://orcid.org/0000-0001-8110-5485

http://dx.doi.org/10.33192/Smj.2021.92

e scope of the right to healthcare

Human rights are universal legal guarantees protecting

individuals and groups against actions and omissions

that interfere with fundamental freedoms, entitlements

and human dignity. e international community must

treat human rights on a global, equitable and equal basis.

e state is responsible for protecting human rights,

regardless of national identity.

Aer World War II, the international community

adopted the Universal Declaration of Human Rights

(1948). e International Covenant on Economic, Social

and Cultural Rights and the International Covenant on

Civil and Political Rights were adopted by the United

Nations General Assembly in 1966. Rights fall into two

categories: individual freedoms and population-based

entitlements. Population-based entitlements require that

the government allocate adequate funds for services, or

mandate organizations to pay for services, for example,

the right to education or to healthcare.

We must distinguish between the right to health and

the right to health care. e right to health includes many

determinants of health, such as income and social status,

social support networks, education, working conditions,

social and physical environments, individual health

practices and coping skills, healthy child development,

biology and genetic endowment, gender and culture. us,

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

722

the right to health requires a much broader guarantee

than the right to health care.

According to the Constitution of the World Health

Organization, health is a state of complete physical,

mental and social well-being and not merely the absence

of disease or inrmity; enjoyment of the highest attainable

standard of health is one of the fundamental rights of every

human being without distinction of race, religion, political

belief, economic or social condition.

In many countries

of the world, according to the national constitution, the

population has the right to guaranteed health care.

Pope

John XXIII in his encyclical, Pacem in Terris (Peace on

Earth), explicitly stated that healthcare is a right rather

than a privilege.

e right to health does not mean the right to be

healthy, and that the governments of poor countries are

obliged to create high-tech expensive medical services for

which they do not have adequate resources. However, the

right to health care requires the state to develop policies

and action plans to achieve accessible health care.

Health

care, as a right, does not mean the provision of services

by medical organizations in the form of charity, or the

provision of absolutely all services by the state. e

right to health care means that the state is obliged to do

everything possible to provide the population with the

necessary medical services, regardless of their solvency.

e right to health is assessed according to four criteria:

1) Existence. Public health and medical organizations,

goods and services should be in sufficient quantity;

2) Accessibility: Medical organizations and health services

should be accessible to all without any discrimination.

Accessibility is assessed by 4 criteria: non-discrimination,

physical accessibility, economic accessibility, access to

information; 3) Acceptability: All medical organizations,

goods and services must comply with the principles of

medical ethics, take into account cultural characteristics,

gender and age requirements, condentiality. 4) Quality:

Medical organizations, goods and services must be of

adequate quality.

ere are two approaches to the right to health

care. One part advocates health care as a human right

because healthcare is a human necessity. e second part

opposes and believes that healthcare is one of the types

of commodity and it can be supplied by the market.

A market can only be eective when the distribution

of resources is based on solvency and not on the principle

of equity. Health is not a marketable product. e law of

supply and demand do not work in the medical market

as health commodities has specic characteristics that

make it dierent from marketable goods. ese specic

peculiarities are asymmetric information, uncertainty,

limited competition, production of public good and the

externalities.

Such a dierence between the medical market

and the normal market is due to the socio-economic

nature of medical services. Such situations where the

market is unable to allocate resources eciently are called

market failures. is specicity of the health sector leads

to special forms of economic relations in the medical

market, which requires the development of appropriate

regulatory mechanisms. To achieve equal access to medical

services, the government will develop a health policy

based on the principle of equitable funding.

In European countries and Canada, health care is

considered as a public service, the provision of which

is the responsibility of the public sector and does not

depend on individual income. e principle of universal

healthcare operates in these countries. Universal coverage

means not only protecting the population from nancial

risks, but also guaranteeing the provision of high quality

medical services and ensuring a fair and equal right

to health for all people. e right of access to health

services for all promotes solidarity among them and

is considered an important cornerstone of statehood.

Healthcare funding is not based on actuarial principles,

accordingly, person’s nancial contributions to health

care do not depend on his or her health status or risk.

Health care is considered a fundamental human

right not only for humanistic and moral reasons, but also

because of rational, utilitarian approaches.

Universal

access benets both the individual and the community

as it provides an increase in workforce productivity.

Unlike many developed countries, health care in

the USA is not considered a right or a constitutional

principle. ere is no legislative framework in the U.S.

that provides for the right to health. ere is a selective

social protection system in the United States. It is based

on population needs assessment procedures and involves

the state covering only that part of the population who

are socially vulnerable or need services more because of

high risk.

e U.S. healthcare system reects the peculiarities

of the American socio-economic model, ideology, and

traditions. In the rst half of the nineteenth century,

the French political scientist and historian Alexis de

Tocqueville was the rst to emphasize American exclusivity

and uniqueness. “e condition of Americans is quite

special, and it can be said that no other democratic people

can ever achieve something like this”. e principles of

individualism and anti-statism have been rmly entrenched

in American public consciousness. Recognition of individual

rights hindered the development of social rights, as state

interventions were oen perceived as an obstacle to

Verulava.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

723

Review Article

SMJ

the right to liberty. If the principles of equality, social

protection and public solidarity have always prevailed in

the development of social policy in European countries,

in the US such a thing proved unacceptable for a certain

part of the citizens. From their point of view, a person is

responsible for his/her own destiny and actions, while

the idea of transferring responsibility to the state does

not enjoy much support. In the US, healthcare is not

considered as the most important social function of the

state, but as a service that, like other services, is sold in

the medical market.

However, according to polls, 65–86%

of respondents in the US support access to health care

should be a right.

Despite the annual increase in health care spending,

there is still a problem with access to healthcare in the

United States.

Even the state program such as Medicare,

which covers high risk people of retirement age and with

disabilities, requires patients to share signicant costs,

so-called Co-payments. Because of this, about half of

healthcare costs are borne by the insured themselves,

which places a heavy burden on them. As of 2018, the

number of uninsured in the US is 11% (30 million people).

In addition, there are so-called insuciently insured

people who have health insurance but spend 10% or more

of their income out of pocket out of medical expenses.

e number of people with insucient insurance is 29

million. In contrast to the US, other developed countries

have universal medical coverage which covers medical

services for the population at much lower costs. Child

mortality and life expectancy in the US lag signicantly

behind those of other developed countries.

Nevertheless, the right to health care in the USA

is not a radical concept. is is evidenced by the state

programs “medicare” and “medicaid”, as well as the

program of medical care for war veterans, which treats

health care as a right. However, in the US, the state is

not obliged to provide healthcare to all its citizens.

Ensuring the right to health care requires large

investment resources. Various funding mechanisms are

used to achieve universal health care goals, namely the social

security model (Bismarck model) and the tax-based model

(Beveridge model). Social insurance was rst introduced in

Germany in 1883. Employees and employers are required

to pay social security contributions at hospital box oces.

Bismarck’s model of social insurance is based on the

principles of federalism and decentralization of powers.

Federal governing bodies dene the institutional model

and guidelines, the parties have residual legislative powers,

and the regional institutions exercise legal oversight over

local health structures. Despite universal health care, there

is no state monopoly on funding, in particular, hospital

cash registers (Kranken Kassen) and regional disease

funds are public rather than governmental institutions.

e state establishes a basic package of medical services.

Social insurance funds have dierent insurance premiums,

which are calculated on the basis of income and are

co-nanced by employers and employees. Despite this,

the role of the private sector in the delivery of medical

services is important. Social security systems have been

introduced in many Western European countries. In

addition to social security contributions,

Philosophical aspects of access to health care

It is interesting to discuss the issue - access to healthcare

is a human right or a privilege - from a philosophical point

of view. According to the Greek philosopher Aristotle

(384-322 BC), everything that is alive has a soul. e

soul is the life-giving force and is responsible for the

development of all living things. e soul cannot grow

by itself, by its own forces. Its development requires the

eorts of both the individual and society as a whole.

Aristotle believed that humanity could not be better if

man existed only by himself, on his own, and was not

cared for by social mechanisms. e same can be said

of human health, which cannot be achieved by itself, on

its own. Public eorts are essential for human health.

omas Hobbes (1588-1679) in his work - “Leviathan”

presents “right by nature” (jus naturales) and “law by

nature” (lex naturalis). “e natural right is the freedom

of man to use his power as he wishes, to sustain his life,

and therefore to do whatever he thinks is the best way

to achieve this goal”. Unlike “right by nature”, the “law

of nature,” or the mind, allows a person to gure out

what must be done to sustain life. When people have

the freedom to “do what they want, everyone is at war

with each other”. e law of nature requires each of us

to relinquish our right to renounce freedom and thus

give more freedom to other people. With this concession

people think that others will have the same kindness

towards them and they will also give up their freedom.

When a person relinquishes freedom or transfers any

right to another, “he does so because he himself receives

equal rights. e motive and purpose of the waiver or

transfer of the right is nothing but the personal security

of the person in terms of being able to protect his life”.

“Obligation” is created by “denial of a natural right”.

“Natural right” does not require obligations from a

person. In the natural state, everyone is self-reliant and

a person can do everything that suits his interests. By

denying the “natural right”, all members of society pledge

to each other to coexist peacefully and thus ensure each

other’s security. When people renounce a “natural right”

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

724

or transfer it to another, a contract or agreement arises.

e transition from “natural right” to “natural law” takes

the form of a public contract: people agree to obey the

law, because the alternative is a state of total war. If we

consider the Hobbes concept in relation to health, for a

safe life, people transfer the “right” to access medical care

to a society in which all members pledge to cooperate.

at is, society agrees that healthcare is a right and it

should be accessible to all.

e American publicist omas Paine (1737-1809)

distinguishes natural rights and civil rights. Natural rights

belong to man by the force of his existence (freedom

of belief, right to expression, striving for happiness ...),

while civil rights belong to man as long as he is a member

of society. Civil rights are guaranteed by society. ey

cannot be fully implemented without the help of the

community.

Civil rights arose from natural rights. Man alone

cannot ensure security. Ensuring collective security is

handed over to the state. Civil power should not be used

to suppress the natural rights of individuals. Human

rights include the rights of other human beings, the

protection of which is incumbent on this person.

us, access to health is considered a matter of

both personal and national security. In modern society,

all people transfer their natural rights to the state, thus

creating a capital of collective security. Every person has

a safety and benet from common well-being, as well as

the right to access health.

According to Hannah Arendt (1906-1975), and her

work “e Human Condition” (1958), people reached an

agreement on common welfare and handed over their

natural rights to the state for their collective security.

People, in addition to being equal, are dierent from

each other. People dier from each other in word (what

they say) and action (what initiative they take). Some

people become better known for their words, while

others become richer by their actions. Such diversity

between people creates “dierence”, but it does not

change equality. People dier in height, weight, ethnicity,

income, gender, age, or religion. ey have distinctive

features and individual places in the world, but they are

all equal. People make their own contribution to the

development of society. In this public space where the

rule of law prevails, people coexist, they interact with

each other through words and actions, thus wanting to

population have dierent needs for medical care. e

poor and the elderly tend to need medical care more.

e united eorts of the people, solidarity, are needed

to eliminate the problem of access to medical services

arising from this dierence. “For man, the reality of the

world is guaranteed by the existence of others.”

John Rawls (1921-2002) paid special attention to

access to health for all in his book “eory of Justice”

(1971). According to Rawls’s social justice argument,

health care is a right because, (1) it promotes equality

of opportunity and benets the least well-o members

of society; And (2) from a utilitarian point of view,

guaranteed medical care increases the well-being of

more people.

Norman Daniels, based on the principle of John

Rawls, gave us the rationale for universal health care.

John Rawls believes that every person has the right to

inviolability (protection of physical and mental condition,

right to life, right to privacy ...), which is based on justice.

erefore, the rights secured by the judiciary in a just

society are not subject to political bargaining.

CONCLUSION

People are socially valuable entities that, through

the power of morality, have made implicit agreements

with each other as well as with the state. rough natural

rights, we protect our own individuality, and also those

to whom we collectively transmit common good. Under

natural laws and natural rights, access to health for

human beings is a right and not a privilege. e health

status of the population depends on the social structure

of a particular country, state policy and national culture.

In rich countries, the average life expectancy of people

is high. However, the health of the population depends

not only on the country’s economy, but also on the

distribution of wealth. e more the state invests in

healthcare, the higher the health rates. e problem of

health inequality in dierent groups of the population must

be addressed by correcting economic inequality. Health

care reform should focus not only on the provision of

medical services, but also on access to health care for the

entire population. us, state policy plays a major role in

improving the health of the population. e health care

system should be arranged in such a way that the welfare

of the patient is paramount for him. Every health care

system must guarantee accessibility to healthcare for the

entire population and must protect it from catastrophic

health care costs. Every citizen should have access to

high quality medical services. Good health benets all:

the individual and the community, and the well-being of

the country in general. Health is a determinant of human

productivity. e healthier a person is, the more able-

bodied he is. Improving health promotes the acquisition

of knowledge, the development of learning skills and

creativity. Healthy and educated workers respond more

Verulava.

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

725

Review Article

SMJ

easily to technological and innovative processes, which is

the determining factor for the successful implementation

of reforms. us, human health contributes to the growth

of the economy as it increases the able-bodied population.

REFERENCES

1. Human Rights. A Basic Handbook for UN Sta. Oce of the

High Commissioner for Human Rights, United Nations Sta

College Project; 1999.

2. Vienna Declaration and Programme of Action. Adopted by

the World Conference on Human Rights in Vienna on 25 June

1993. e World Conference on Human Rights. Oce of the

High Commissioner for Human Rights, United Nations.

3. Winstone H. Human rights in the new millennium. Med Leg

J 1999;67:35-39.

4. Bodenheimer T. e Political Divide in Health Care: A Liberal

Perspective. Health A 2005; 24:1426-35.

5. Braveman P, Gottlieb L. e social determinants of health:

it's time to consider the causes of the causes. Public Health

Rep 2014;129:19-31.

6. Constitution of the World Health Organization. Geneva:

World Health Organization. 1948.

7. World Health Organization. Primary Health Care. International

Conference on Primary Health Care. Alma-Ata, USSR, 6-12

September, 1978.

8. Kinney D. e International Human Right to Health: What

does is Mean for Our Nation And World? Indiana Law Rev

2001;34:1465.

9. Curran WJ. e Constitutional Right to Health Care: Denial

in the Court. N Engl J Med 1989;320:788-9.

10. Pacem in Terris. Encyclical of Pope John XXIII on Establishing

Universal Peace in Truth, Justice, Charity, and Liberty. April

11, 1963. Libreria Editrice Vaticana.

11. UN General Assembly, International Covenant on Economic,

Social and Cultural Rights (December 16, 1966, entered into

force on January 3, 1976.

12. Verulava T, Jorbenadze R, Dagadze B, Eliava E. Access to

Ambulatory Medicines for the Elderly in Georgia. Home

Health Care Management & Practice 2019;39:107-12.

13. Verulava T, Gabuldani M. Accessibility of Urgent Neurosurgery

Diseases by the State Universal Healthcare Program in Georgia

(country). Gazi Medical J 2015;26:2-45.

14. Laur A. Patients' responsibilities for their health. Med Leg J

2013;81:119-23.

15. World Health Organization. Gender, equity and human rights:

Availability, accessibility, acceptability, quality—Infographic.

2016. https://www.who.int/gender-equity-rights/knowledge/

aaaq-infographic/en/

16. Mwacho A, Al-Assaf AF. Health care market deviations from

the ideal market. Sultan Qaboos Univ Med J 2011;11:328-37.

17. Vladeck BC. Paradigm lost: provider concentration and the

failure of market theory. Health A 2014;33:1083-7.

18. Reinhardt U. Hard choices in health care: a matter of ethics.

In: Health Care: How to Improve It and Pay for It. Washington,

DC: Center for National Policy 1985.p.19-31.

19. Daniels N. Just Health Cambridge: Cambridge University

Press; 1985

20. Havers P. e impact of the European Convention on Human

Rights on Medical Law. Med Leg J 2002;70:57-70.

21. Kunakornvong W, Ngoasri K. Public awareness and attitude

toward palliative care in ailand. Siriraj Med J 2020;72:424-

30.

22. Burnton S. Doctors, patients and the human rights act. Med

Leg J 2011;79:115-25.

23. Verulava T, Dangadze B. Health capital and economic growth:

evidence from Georgia. e Open Public Health J 2018;11:

401-6.

24. Verulava T. Health Capital, Primary Health Care and Economic

Growth. East J Med 2019;24:57- 62.

25. O’Rourke TW. Lost in the Health Care Reform Discussion:

Health Care as a Right or Privilege, Am J Health Educ 2017;48:

138-41.

26. Swendiman KS. Health Care: Constitutional Rights and Legislative

Powers. Congressional Research Service. July 9, 2012. Available

from: https://fas.org/sgp/crs/misc/R40846.pdf

27. Fuchs VR. ree “Inconvenient Truths” About Health Care.

N Engl J Med 2008;359:1749-51.

28. Tocqueville A. Democracy in America. Chicago: University

of Chicago Press; 2000.

29. Shafer BE. Is America Dierent? A New Look at American

Exceptionalism. Oxford University Press, 1991.

30. Tanner M. A Fork in the Road Obama, McCain, and Health

Care. Cato Institute; 2008.

31. Blendon RJ, Brodie M, Benson JM, Altman DE, Buhr T.

Americans' Views of Health Care Costs, Access, and Quality.

e Milbank Q 2006;84:623-57.

32. Squires D, Anderson C. U.S. health care from a global perspective:

spending, use of services, prices, and health in 13 countries.

e commonwealth fund; 2015.

33. Anderson GF, Reinhardt UE, Hussey PS. It’s the prices, stupid:

why the United States is so dierent from other countries.

Health A 2003;22:89-105

34. Collins SR, Rasmussen PW, Beutel S, Doty MM. e problem

of underinsurance and how rising deductibles will make it

worse. Findings from the Commonwealth Fund Biennial

Health Insurance Survey 2014, 2015.

35. U.S. Health Care Coverage and Spending. Available from:

https://fas.org/sgp/crs/misc/IF10830.pdf

36. Cohen RA and Terlizzi EP. Health insurance coverage: Early

release of quarterly estimates from the National Health Interview

Survey, April 2019–June 2020. National Center for Health

Statistics. February 2021. Available from: https://www.cdc.

gov/nchs/nhis/releases.htm

37. Collins SR, Gunja, MZ, Aboulaa GZ. U.S. Health Insurance

Coverage in 2020: A Looming Crisis in Affordability. Commonwealth

Fund Biennial Health Insurance Survey, 2020. Available from:

https://www.commonwealthfund.org/publications/issue-

briefs/2020/aug/looming-crisis-health-coverage-2020-biennial

38. Barnett JC, Vornovitsky MS. Health insurance coverage in

the United States 2015. Available from: https://www.census.

gov/content/dam/Census/library/publications/2016/demo/

p60-257.pdf

39. Davis K, Stremikis K, Squires D, Schoen C. Mirror, mirror on

the wall: how the performance of the U.S. health care system

compares internationally, 2014. Available from: https://www.

commonwealthfund.org/sites/default/les/documents/___

media_les_publications_fund_report_2014_jun_1755_davis_

mirror_mirror_2014.pdf

40. Ashish P. akrar, Alexandra D. Forrest, Mitchell G. Maltenfort,

Volume 73, No.10: 2021 Siriraj Medical Journal

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

726

Christopher B. Forrest. Child Mortality In e US And 19

OECD Comparator Nations: A 50-Year Time-Trend Analysis.

Health Aairs 2018;37:140.

41. Avendano M, Kawachi I. Why do Americans have shorter life

expectancy and worse health than do people in other high-

income countries? Ann Rev Public Health 2014;35:307-25.

42. Avendano M, Kok R, Glymour M, Berkman L, Kawachi I. Do

Americans Have Higher Mortality an Europeans Because

ey Have Higher Excess Mortality at Lower Socioeconomic

Levels? A Comparison of Mortality by Education in the United

States and 14 European countries. In: Crimmins E, Preston S,

Cohen B, editors. International Dierences in Mortality at

Older Ages: Dimensions and Sources. Washington, D.C.: e

National Academies Press; 2010.p.313-32.

43. Isaacs SL, Schroeder SA. Class - the Ignored Determinant of

the Nation’s Health. N Engl J Med 2004;351:1137-42.

44. Aristotle. e Soul. Edited by: Smith JA. Whitesh: Kessinger

Publishing; 2005.

45. Talyor AE. Aristotle Toronto: Dover Publications; 1955.

46. Hobbes . Leviathan; 2014.

47. Paine T. Rights of Man. In Rights of Man Mineola: Dover

Publications 1999.p.7-64.

48. Arendt H. e Human Condition Chicago: University of

Chicago Press; 1958.

49. Reinhardt U. Hard choices in health care: a matter of ethics.

In: Health Care: How to Improve It and Pay for It. Washington,

DC: Center for National Policy 1985.p.19-31.

50. Rawls J. A eory of Justice Cambridge: Harvard University

Press; 1999.

51. Kawachi I, Daniels N, Robinson DE. Health Disparities by

Race and Class: Why Both Matter. Health A 2005;24:343-52.

52. Daniels N. Justice, Health, and Healthcare. Am J Bioeth 2001;1:

2-16.

53. Papadimos TJ. Healthcare access as a right, not a privilege:

a construct of Western thought. Philos Ethics Humanit Med

2007;2(2). Available from: https://peh-med.biomedcentral.

com/articles/10.1186/1747-5341-2-2

Verulava.