Siriraj Medical Journal
SMJ
Volume 75, Number 1, January 2023
ORIGINAL ARTICLE
1 Evaluation of Clinical Knowledge Regarding Geriatric Skin Conditions among Thai
Physicians
Pattriya Chanyachailert, et al.
7 SARS-CoV-2 Detection on Artificially Contaminated Surfaces by Rapid Antigen Test
Nattamon Niyomdecha, et al.
13 Effects of Music on Preoperative Anxiety in Patients Undergoing Hair Transplantation:
A Preliminary Report
Supisara Wongdama, et al.
20 Functional Status of the Elderly and their Rehabilitation Needs: A Mixed-Method Study in
a Slum of Kolkata, West Bengal
Riya Halder, et al.
29 Comparative Effectiveness of Court-Type Thai Traditional Massage and Ultrasound
Therapy in Patients with Neck Pain: A Randomized Controlled Trial
Nuttapol Watcharasirikul, et al.
38 A Comparison of Serum Copper Levels in Patients with Papillary Thyroid Carcinoma,
Nodular Goiter, and Healthy Volunteers
Prachya Maneeprasopchoke, et al.
46 Telehealth Service for Patients Receiving Continuous Ambulatory Peritoneal Dialysis:
A Pilot Study
Aurawamon Sriyuktasuth, et al.
REVIEW ARTICLE
55 Recurrent Urinary Tract Infection in Women from a Urologist’s Perspective
Patkawat Ramart, et al.
SIRIRAJ MEDICAL JOURNAL
First Editor: Ouay Ketusinh Emeritus Editors: Somchai Bovornkitti, Adulya Viriyavejakul, Sommai Toongsuwan,
Nanta Maranetra, Niphon Poungvarin, Prasit Watanapa, Vithya Vathanophas, Pipop Jirapinyo, Sanya Sukpanichnant,
Somboon Kunathikom
Executive Editor: Prasit Watanapa Editorial Director: Manee Rattanachaiyanont
Managing Editor: Gulapar Srisawasdi, Chenchit Chayachinda
Editor-in-Chief: awatchai Akaraviputh
Associate Editor: Varut Lohsiriwat, Prapat Wanitpongpan Online Editor: Puttinun Patpituck
SIRIRAJ MEDICAL JOURNAL is published bimonthly, 6 issues a year (Jan-Feb, Mar-Apr, May-Jun, Jul-Aug, Sep-Oct and Nov-Dec)
and distributed by the end of the last month of that issue.
SIRIRAJ MEDICAL JOURNAL is listed as a journal following the Uniform Requirements for Manuscripts Submitted to Biomedical Journals (URM)
by the International Committee of Medical Journal Editors (ICMJE) since 9 July 2010 [http://www.icmje.org/journals.html].
Philip Board (Australian National University, Australia)
Richard J. Deckelbaum (Columbia University, USA)
Yozo Miyake (Aichi Medical University, Japan)
Yik Ying Teo (National University of Singapore, Singapore)
Harland Winter (Massachusetts General Hospital, USA)
Philip A. Brunell (State University of New York At Bualo, USA)
Noritaka Isogai (Kinki University, Japan)
Yuji Murata (Aizenbashi Hospital, Japan)
Keiichi Akita (Tokyo Medical and Dental University Hospital, Japan)
Shuji Shimizu (Kyushu University Hospital, Japan)
David S. Sheps (University of Florida, USA)
Robin CN Williamson (Royal Postgraduate Medical School, UK)
Tai-Soon Yong (Yonsei University, Korea)
Anusak Yiengpruksawan (e Valley Robotic Institute, USA)
Stanlay James Rogers (University of California, San Francisco, USA)
Kyoichi Takaori (Kyoto University Hospital, Japan)
Tomohisa Uchida (Oita University, Japan)
Yoshiki Hirooka (Nagoya University Hospital, Japan)
Hidemi Goto (Nagoya University Graduate School of Medicine, Japan)
Kazuo Hara (Aichi Cancer Center Hospital, Japan)
Shomei Ryozawa (Saitama Medical University, Japan)
Christopher Khor (Singapore General Hospital, Singapore)
Yasushi Sano (Director of Gastrointestinal Center, Japan)
Mitsuhiro Kida (Kitasato University & Hospital, Japan)
Seigo Kitano (Oita University, Japan)
Ichizo Nishino (National Institute of Neuroscience NCNP, Japan)
Masakazu Yamamoto (Tokyo Women’s Medical University, Japan)
Dong-Wan Seo (University of Ulsan College of Medicine, Korea)
George S. Baillie (University of Glasgow, UK)
G. Allen Finley (Delhousie University, Canada)
Sara Schwanke Khilji (Oregon Health & Science University, USA)
Matthew S. Dunne (Institute of Food, Nutrition, and Health, Switzerland)
Marianne Hokland (University of Aarhus, Denmark)
Marcela Hermoso Ramello (University of Chile, Chile)
Ciro Isidoro (University of Novara, Italy)
Moses Rodriguez (Mayo Clinic, USA)
Robert W. Mann (University of Hawaii, USA)
Wikrom Karnsakul (Johns Hopkins Children’s Center, USA)
Frans Laurens Moll (University Medical Center Ultrecht, Netherlands)
James P. Dolan (Oregon Health & Science University, USA)
John Hunter (Oregon Health & Science University, USA)
Nima Rezaei (Tehran University of Medical Sciences, Iran)
Dennis J. Janisse (Subsidiary of DJO Global, USA)
Folker Meyer (Argonne National Laboratory, USA)
David Wayne Ussery (University of Arkansas for Medical Sciences, USA)
Intawat Nookaew (University of Arkansas for Medical Sciences, USA)
Victor Manuel Charoenrook de la Fuente
(Centro de Oalmologia Barraquer, Spain)
Karl omas Moritz
(Swedish University of Agricultural Sciences, Sweden)
Nam H. CHO (University School of Medicine and Hospital, Korea)
www.smj.si.mahidol.ac.th
Statistician: Saowalak Hunnangkul (Mahidol University, ailand)
Medical Illustrator: Chananya Hokierti (Nopparat Rajathanee Hospital, ailand)
Online Assistant: Surang Promsorn, Wilailuck Amornmontien, Hatairat Ruangsuwan Editorial Oce Secretary: Amornrat Sangkaew
International Editorial Board
Editorial Board
Watchara Kasinrerk (Chiang Mai University, ailand)
Rungroj Krittayaphong (Siriraj Hospital, Mahidol University, ailand)
Wiroon Laupattrakasem (Khon Kaen University, ailand)
Anuwat Pongkunakorn (Lampang Hospital, ailand)
Nopporn Sittisombut (Chiang Mai University, ailand)
Vasant Sumethkul (Ramathibodi Hospital, Mahidol University, ailand)
Yuen Tanniradorm (Chulalongkorn University, ailand)
Saranatra Waikakul (Siriraj Hospital, Mahidol University, ailand)
Pa-thai Yenchitsomanus (Siriraj Hospital, Mahidol University, ailand)
Surapol Issaragrisil (Siriraj Hospital, Mahidol University,ailand)
Jaturat Kanpittaya (Khon Kaen University, ailand)
Suneerat Kongsayreepong (Siriraj Hospital, Mahidol University, ailand)
Pornchai O-Charoenrat (Siriraj Hospital, Mahidol University, ailand)
Nopphol Pausawasdi (Siriraj Hospital, Mahidol University, ailand)
Supakorn Rojananin (Siriraj Hospital, Mahidol University, ailand)
Jarupim Soongswang (Siriraj Hospital, Mahidol University, ailand)
Suttipong Wacharasindhu (Chulalongkorn University, ailand)
Prapon Wilairat (Mahidol University, ailand)
Pornprom Muangman (Siriraj Hospital, Mahidol University, ailand)
Ampaiwan Chuansumrit
(Ramathibodi Hospital, Mahidol University, ailand)
Sayomporn Sirinavin
(Ramathibodi Hospital, Mahidol University, ailand)
Vitoon Chinswangwatanakul
(Siriraj Hospital, Mahidol University, ailand)
SMJ
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
1
Original Article
SMJ
Pattriya Chanyachailert, M.D.*, Penvadee Pattanaprichakul, M.D.*, Sumanas Bunyaratavej, M.D.*, Charussri
Leeyaphan, M.D.*, Bawonpak Pongkittilar, M.D.*, Chudapa Sereeaphinan, M.D.*, David Stockman, M.D.**
*Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ailand, **Michigan Health Clinics, Saginaw,
Michigan, USA.
Evaluation of Clinical Knowledge Regarding
Geriatric Skin Conditions among Thai Physicians
ABSTRACT
Objective: Assess the knowledge of common geriatric skin conditions in ai physicians.
Materials and Methods: is retrospective study was conducted among ai physicians attending annual dermatology
courses by the Dermatological Society of ailand from 2016 to 2019. Data was assessed based on knowledge of
diagnosis and management of common geriatric skin conditions.
Results: A total of 197 participants, mainly general practitioners, were included. e highest percentage of correct
diagnoses were benign erythematous, eczematous lesions (35.5%, senile purpura; 36.0%, xerotic eczema), and malignant
diseases (35.5%, basal cell carcinoma; 27.4%, squamous cell carcinoma; 11.7%, subungual melanoma; 24.4%, acral
lentiginous melanoma). In contrasts, the lowest percentage of correct diagnosis were premalignant diseases (0.5%,
arsenical keratosis; 4.6%, actinic keratosis; 1.0% Bowen’s disease) and benign hypopigmented lesion (0.5%, stellate
pseudoscar; 7.6%, idiopathic guttate hypomelanosis). Harmful treatment with systemic antifungal therapy was used in
subungual melanoma (58.0%). Harmful management of senile comedone, subungual melanoma and acral lentiginous
melanoma was signicantly found in physicians given the incorrect diagnosis. (p = 0.027, p <0.001, p = 0.014, respectively).
Conclusion: Most physicians recognized malignant lesions, benign erythematous or eczematous diseases in elderly
skin. Surprisingly, almost all physicians couldn’t diagnose premalignant lesions and benign hypopigmented lesions.
Keywords: Geriatric skin conditions; physician (Siriraj Med J 2023; 75: 1-6)
Corresponding author: Penvadee Pattanaprichakul
E-mail: penvadee.pat@gmail.com
Received 3 August 2022 Revised 30 August 2022 Accepted 7 September 2022
ORCID ID:http://orcid.org/0000-0002-3293-7813
http://dx.doi.org/10.33192/smj.v75i1.260522
All material is licensed under terms of
the Creative Commons Attribution 4.0
International (CC-BY-NC-ND 4.0)
license unless otherwise stated.
INTRODUCTION
A major global trend in population aging is rapidly
occurring. By 2050, the proportion of the world’s population
aged 60 years will increase from 12% to 22%.
1
ailand
has also become an aging society, with 18.24% of the
population aged over 60 years in 2021.
2
e emergence
of senile dermatosis in the aging population is expected.
Elderly skin goes through changes that are both intrinsic
and extrinsic. Intrinsic changes result from chronological
aging, such as thinning of the epidermis, reduction in the
function of sweat and apocrine glands. Extrinsic changes
result from UV and other environmental pollutants.
Both changes are responsible for the susceptibility of
skin conditions in the elderly.
3,4
Diagnosis and management of skin conditions in
the elderly are challenging due to many aspects, such as
ordinary physiologic change, atypical disease presentation,
and multiple comorbidities. Yet, there was no prior
assessment report on the knowledge of geriatric skin
conditions among ai physicians. is knowledge gap
will help identify potential improvements in understanding
skin conditions in the elderly. Many studies have shown
an increase in diagnostic capabilities and proper referral in
general practitioners aer providing educated sessions.
5,6
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
2
For these reasons, this study aims to assess the knowledge
of common geriatric skin conditions in ai physicians.
MATERIALS AND METHODS
Study design
is retrospective study was conducted at the Faculty
of Medicine Siriraj Hospital, Mahidol University, ailand.
e protocol was approved by the Siriraj Institutional
Review Board (COA no. Si 456/2012). e data includes
knowledge of diagnosis and management of common
dermatological conditions in the elderly, as seen in
Table 2. We conducted a retrospective review of physicians’
demographic data and working experiences derived from
records at the annual short dermatology course for general
practitioners. Which was held by the dermatological
society of ailand from 2016 to 2019.
We compiled a reviewed list of dierential diagnoses
and management. Management was categorized as proper,
disadvantageous, and harmful. Proper management was
dened as necessary, benecial actions for patients, such
as tissue biopsy in premalignant or malignant lesions.
Disadvantageous management was dened as the actions
which provided no benefits, had no, or only minor
adverse eects on patients. Such as the use of topical
steroids in premalignant or malignant lesions, which
might cause some delay in tissue diagnosis. Dening
harmful management encompasses actions causing
severe adverse reactions or worsening skin conditions.
Statistical analysis
e PASW Statistics for Windows, version 18 (SPSS
Inc., Chicago, IL, USA), was used for data analysis.
Categorical data, such as the numbers of physicians who
answered correctly for diagnosis or dierential diagnoses
and the number of each management category, were
described using frequency and percentage. Evaluating
the relationship between physicians’ condence level, the
number of patients with skin conditions the physicians
treated per week, and harmful management used a Chi-
Squared analysis or Fisher’s exact test. e dierence in
the proportion of harmful management between those
who had correct and incorrect diagnoses were evaluated
using Chi-Squared tests or Fisher’s exact test.
RESULTS
Analysis of 197 physicians’ records with complete
data was conducted. Approximately half of the physicians
were between 26-30 years old, and most were general
practitioners (83.0%). For the working setting, 66.7% of
the physicians worked at public hospitals, while 20.3%
and 19.8% worked at private hospitals and clinics,
respectively. Regarding the experience in treating patients
with dermatologic conditions, most physicians (67.4%)
treated 0 to 10 patients per week (Table 1).
Benign erythematous, eczematous, and malignant
lesions represented the highest percentage of correct
diagnoses (Table 2). Among benign erythematous lesions,
36% of physicians gave a correct diagnosis for xerotic
eczema, followed by 35.5% for senile purpura. Malignant
lesions showed only 35.5% of physicians made accurate
diagnoses for basal cell carcinoma, 27.4% for squamous
cell carcinoma, and 24.4% for acral lentiginous melanoma.
However, less than 10% of physicians had the correct
answers in premalignant and benign hypopigmented
lesions.
Harmful treatment was commonly found in subungual
melanoma (58%). Principally, 174 physicians who had an
incorrect diagnosis of this lesion, and 93 physicians (53%)
misdiagnosed the lesions as onychomycosis. erefore,
many patients with melanoma were prescribed systemic
antifungal therapy (Table 2).
Physicians with more than 30 patients per week
recommended harmful management when diagnosing
seborrheic keratosis and actinic keratosis, as seen in
Table 3, which was signicantly higher compared to
physicians with 11-30 patients per week (11.8, 4.8, and
0.9%, respectively, with a p-value of 0.035 in seborrheic
keratosis and 16.7, 8.6, and 3.3%, respectively with a
p-value of 0.048 in actinic keratosis). In contrast, there was
no dierence in the percentage of harmful management
among physicians with dierent condence levels.
Table 4 compares the proportion of harmful
management in correct and incorrect diagnoses. In
all diseases, physicians with incorrect diagnoses tend
to prescribe damaging solutions compared to correct
diagnoses. ere was no statistical signicance between both
groups except in senile comedone, subungual melanoma,
and acral lentiginous melanoma.
DISCUSSION
is study shows that ai general practitioners
rarely recognize common skin conditions in the elderly.
Additionally, premalignant skin lesions and benign
hypopigmented lesions were the most common uncorrected
diagnosis. e largest proportion of physicians recommended
systemic antifungal therapy for subungual melanoma. For
ai general practitioners, these ndings will improve their
knowledge in recognizing skin conditions in the elderly.
In this study, physicians rarely recognized premalignant
skin lesions compared to other benign and malignant
skin lesions except for hypopigmented lesions. For
premalignant lesions, actinic keratosis and Bowen
Chanyachailert et al.
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
3
Original Article
SMJ
TABLE 1. Demographic data.
Characteristics Number/total (%)
Age group
20 – 25 years old 27/196 (13.8%)
26 – 30 years old 108/196 (55.1%)
31 – 45 years old 61/196 (31.1%)
Gender
Female 137/196 (69.9%)
Previous dermatology short course taken
No 164/168 (97.6%)
Yes 4/168 (2.4%)
Status of the doctors
General practitioner 161/194 (83.0%)
Specialist other than dermatologists 22/194 (11.3%)
Diploma or M.Sc in dermatology 3/194 (1.5%)
Medical student 3/194(1.5%)
Others 5/194 (2.6%)
Workplace*
Public hospitals 128/192 (66.7%)
Private hospitals 39/192 (20.3%)
Private clinic 38/192 (19.8%)
Number of patients treated (per week)
0 – 10 patients/week 126/187 (67.4%)
11 – 30 patients/week 42187 (22.5%)
> 30 patients/week 19/187 (10.1 %)
Condence in treating patients with dermatologic problems
Very low condence 53/194 (27.3%)
Low condence 101/194 (52.1%)
Moderate condence to High condence 40/194 (20.6%)
*One subject could have more than one work place
Abbreviation: M.Sc, Master of Science
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
4
TABLE 2. Pretest answers of participants at the beginning of dermatology short course training.
Total (n = 197) Management
Correct Correct
Diseases differential diagnosis n Proper Disadvantageous Harmful
diagnosis n (%) (%) (%) (%)
n (%)
Benign disease
Hypopigmented lesion
Stellate pseudoscar 1 (0.5) 1 (0.5) 149 37 (24.8) 84 (56.4) 28 (18.8)
Idiopathic guttate hypomelanosis 15 (7.6) 15 (7.6) 131 32 (24.4) 89 (67.9) 10 (7.6)
Erythematous/eczematous lesion
Senile purpura 81 (41.1) 70 (35.5) 143 121 (84.6) 20 (14.0) 2 (1.4)
Xerotic eczema 94 (47.7) 71 (36.0) 165 154 (93.3) 8 (4.8) 3 (1.8)
Progressive pigmentary dermatosis 4 (2.0) 2 (1.0) 130 59 (45.4) 56 (43.1) 15 (11.5)
Lump and bump lesion (Tumor and plaque)
Seborrheic keratosis 51 (25.9) 34 (17.3) 176 168 (95.5) 3 (1.7) 5 (2.8)
Solar lentigo 20 (10.2) 12 (6.1) 141 56 (39.7) 77 (54.6) 8 (5.7)
Senile comedone 46 (23.4) 41 (20.8) 121 46 (38.0) 59 (48.8) 16 (13.2)
Premalignant disease
Arsenical keratosis 3 (1.5) 1 (0.5) 163 78 (47.9) 74 (45.4) 11 (6.7)
Actinic keratosis 14 (7.1) 9 (4.6) 151 20 (13.2) 122 (80.8) 9 (6.0)
Bowen’s disease 3 (1.5) 2 (1.0) 137 36 (26.3) 86 (62.8) 15 (10.9)
Malignant disease
Basal cell carcinoma 90 (45.7) 70 (35.5) 186 179 (96.2) 5 (2.7) 2 (1.1)
Squamous cell carcinoma 71 (36.0) 54 (27.4) 173 162 (93.6) 9 (5.2) 2 (1.2)
Subungual melanoma 30 (15.2) 23 (11.7) 162 35 (21.6) 33 (20.4) 94 (58.0)
Acral lentiginous melanoma 62 (31.5) 48 (24.4) 152 126 (82.9) 13 (8.6) 13 (8.6)
disease typically present with an erythematous patch
with a dry scale that sometimes resembles other skin
conditions. As in this study, physicians mostly misdiagnosed
premalignant lesions as psoriasis or chronic eczema.
Similarly, a previous study showed general practitioners
provided correct diagnosis of benign skin tumor lesions
(seborrheic keratosis, melanocytic nervus) better than
premalignant (actinic keratosis, nervous dysplasia).
7
Most primary care physicians from selected countries
provide acceptable diagnosis of basal cell carcinoma than
actinic keratosis (90% VS 74%).
8
Yet, both studies had
signicantly higher overall correct diagnoses, including
premalignant skin lesions, compared to this study. is
study highlights the need for educational intervention for
ai general practitioners who can’t recognize common
skin lesions in the elderly. e need for intervention is
especially evident when diagnosing premalignant and
benign hypopigmented lesions. Subungual melanoma is a
severe subtype of acral lentiginous melanoma commonly
presented with longitudinal melanonychia. e presence
of Hutchinson’s sign, ulceration, and broad heterogenous
band appearance suggested the diagnosis of subungual
melanoma.
9,10
Subungual melanoma is common among
Asians and Blacks.
11
Our study demonstrated a low
correct diagnosis for these lesion types. Table 4 also
shows that harmful management was concordant with
misdiagnosis. us, ai general practitioners need to
recognize the alarming features for correct diagnosis to
avoid delayed or harmful treatment.
Limitations of this retrospective study include
collected data that may have some bias and missing data.
Management was dependent on the diagnosis. erefore,
Chanyachailert et al.
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
5
Original Article
SMJ
TABLE 3. Comparison of harmful management among physicians with dierent level of experience according to
the average numbers of dermatologic patients per week.
Number of dermatologic patients per week P-value
Diseases 0-10 patients 11-30 patients > 30 patients
n (%) n (%) n (%)
Benign disease
Hypopigmented lesion
Stellate pseudoscar 19/88 (21.6) 3/38 (7.9) 4/16 (25) 0.132
Idiopathic guttate hypomelanosis 7/79 (8.9) 2/33 (6.1) 1/14 (7.1) 1.000
Erythematous/eczematous lesion
Senile purpura 1/88 (1.1) 1/34 (2.9) 0/17 (0.0) 0.416
Xerotic eczema 2/102 (2.0) 1/37 (2.7) 0/18 (0.0)
Progressive pigmentary dermatosis 9/76 (11.8) 4/33 (12.1) 2/17 (11.8) 1.000
Lump and bump lesion
Seborrheic keratosis 1/110 (0.9) 2/42 (4.8) 2/17 (11.8) 0.035*
Solar lentigo 5/90 (5.6) 3/32 (9.4) 0/15 (0.0) 0.742
Senile comedone 12/72 (16.7) 2/30 (6.7) 2/15 (13.3)
Premalignant
Arsenical keratosis 7/101 (6.9) 1/39 (2.6) 2/17 (11.8) 0.308
Actinic keratosis 3/92 (3.3) 3/35 (8.6) 3/18 (16.7) 0.048*
Bowen’s disease 8/81 (9.9) 6/37 (16.2) 1/14 (7.1) 0.591
Malignant disease
Basal cell carcinoma 2/116 (1.7) 0/42 (0.0) 0/19 (0.0) 0.687
Squamous cell carcinoma 1/108 (0.9) 1/40 (2.5) 0/18 (0.0) 0.578
Subungual melanoma 63/100 (63.0) 19/39 (48.7) 9/16 (56.3) 0.294
Acral lentiginous melanoma 6/94 (6.4) 5/38 (13.2) 2/16 (12.5) 0.369
*A p-value less than 0.05 indicated statistical signicance, Chi-squared test.
an incorrect diagnosis leads to inappropriate treatment.
In reality, physicians should observe or refer patients to
dermatologists for proper diagnosis. In conclusion, benign
erythematous/eczematous diseases and malignant lesions,
including xerotic eczema, basal cell carcinoma, senile
purpura, squamous cell carcinoma, and acral lentiginous
melanoma, were the elderly skin conditions that the
physicians most recognized. In contrast, premalignant
lesions and benign hypopigmented lesions couldn’t be
diagnosed by almost all physicians.
Conict of interests: All authors have no conicts of
interest or nancial support to declare.
Funding: None
REFERENCES
1. World Health Organization. Aging and Health [Internet].
Switzerland: World Health Organization; 2021 Oct [cited
2022 Mar 31]. Available from: https://www.who.int/news-
room/fact-sheets/detail/ageing-and-health.
2. National Statistic Oce. Demography population and housing
branch [Internet]. ailand: National Statistic Oce; 2021 [cited
2022 Mar 31]. Available from: https://statbbi.nso.go.th/staticreport/
page/sector/en/01.aspx.
3. Jaerany M, Huynh TV, Silverman MA, Zaidi Z. Geriatric
dermatoses: a clinical review of skin diseases in an aging
population. Int J Dermatol. 2012;51(5):509-22.
4. Zalaudek I, Lallas A, Longo C, Moscarella E, Tiodorovic-Zivkovic
D, Ricci C, et al. Problematic lesions in the elderly. Dermatol
Clin. 2013;31(4):549-64, vii-viii.
5. Beecher SM, Keogh C, Healy C. Dedicated general practitioner
education sessions can improve diagnostic capabilities and may
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
6
TABLE 4. Comparison of harmful management in participants given correct and incorrect diagnosis.
Harmful management Harmful management
Diseases in correct diagnosis in incorrect diagnosis P-value
n (%) n (%)
Benign disease
Hypopigmented lesion
Stellate pseudoscar 0/1 (0.0) 28/148 (18.9) 1.000
Idiopathic guttate hypomelanosis 0/13 (0.0) 10/118 (8.5) 0.275
Erythematous/eczematous lesion
Senile purpura 0/62 (0.0) 2/81 (2.5) 0.505
Xerotic eczema 0/67 (0.0) 3/98 (3.1) 0.272
Progressive pigmentary dermatosis 0/2 (0.0) 15/128 (11.7) 1.000
Lump and bump lesion (Tumor and plaque)
Seborrheic keratosis 0/30 (0.0) 5/146 (3.4) 0.590
Solar lentigo 0/9 (0.0) 8/132 (6.1) 0.447
Senile comedone 1/36 (2.8) 15/85 (17.6) 0.027*
Premalignant disease
Arsenical keratosis 0/1 (0.0) 11/162 (6.8) 1.000
Actinic keratosis 0/8 (0.0) 9/143 (6.3) 0.464
Bowen’s disease 0/2 (0.0) 15/135 (11.1) 1.000
Malignant disease
Basal cell carcinoma 0/70 (0.0) 2/116 (1.7) 0.528
Squamous cell carcinoma 0/54 (0.0) 2/119 (1.7) 1.000
Subungual melanoma 1/23 (4.3) 93/139 (66.9) <0.001*
Acral lentiginous melanoma 0/45 (0.0) 13/107 (12.1) 0.014*
*A p-value less than 0.05 indicated statistical signicance, Chi-squared test.
have a positive eect on referral patterns for common skin
lesions. Ir J Med Sci. 2018;187(4):959-63.
6. Basarab T, Munn SE, Jones RR. Diagnostic accuracy and
appropriateness of general practitioner referrals to a dermatology
out-patient clinic. Br J Dermatol. 1996;135(1):70-3.
7. Paine SL, Cockburn J, Noy SM, Marks R. Early detection
of skin cancer. Knowledge, perceptions and practices of general
practitioners in Victoria. Med J Aust. 1994;161(3):188-9, 92-5.
8. Halpern AC, Hanson LJ. Awareness of, knowledge of and
attitudes to nonmelanoma skin cancer (NMSC) and actinic
keratosis (AK) among physicians. Int J Dermatol. 2004;43(9):
638-42.
9. Ruben BS. Pigmented lesions of the nail unit: clinical and
histopathologic features. Semin Cutan Med Surg. 2010;29(3):148-
58.
10. Cust AE. Prognostic features for acral lentiginous melanoma.
Br J Dermatol. 2018;178(2):311-2.
11. da Silva DLF, Toribio JM, Cintra ML, Magalhaes RF, Padoveze
EH. Subungual Acral Lentiginous Melanoma of the Fih Toe.
Skin Appendage Disord. 2019;5(6):401-4.
Chanyachailert et al.
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
7
Original Article
SMJ
Nattamon Niyomdecha, Ph.D., Sirinart Chomean, Ph.D., Chollanot Kaset, Ph.D.
Department of Medical Technology, Faculty of Allied Health Sciences, ammasat University, Rangsit Campus, Pathumthani, ailand.
SARS-CoV-2 Detection on Articially Contaminated
Surfaces by Rapid Antigen Test
ABSTRACT
Objective: Evaluation of an antigen-based rapid test for detection of severe acute respiratory syndrome coronavirus 2
(SARS-CoV-2) on articially contaminated objects in comparison with a real-time reverse transcription-polymerase
chain reaction (RT-qPCR) standard method.
Materials and Methods: Articial surface contamination with inactivated SARS-CoV-2 was tested on ten dierent
objects comprising fruits and common materials. ree contamination levels with virus titers of 10
3
, 10
4
, and 10
5
pfu/100 µl were studied. Each object was spiked with 200 µl of virus suspension, samples were then collected by
swabbing and evaluated by rapid antigen test and RT-qPCR. Additionally, 3- and 5-day contamination with SARS-
CoV-2 at 10
5
pfu/100 µl was tested for some materials.
Results: e detection rate obtained by the rapid antigen test with 10
3
, 10
4
, and 10
5
pfu/100 µl of SARS-CoV-2 was
10%, 90%, and 90%, respectively for the tested objects. RT-qPCR showed a detection rate of 100% at all virus titers.
Furthermore, both rapid antigen test and RT-qPCR were able to detect the 3- and 5-day extended contamination
with SARS-CoV-2.
Conclusion: e collected data suggests that the evaluated rapid antigen test is suitable for detection of SARS-CoV-2
adhered to non-human samples as a screening method. is simple method can reduce costs and turnaround time
when compared to a standard molecular assay. It may be applied to enhance safety policies for COVID-19 prevention
in public health and international export-businesses.
Keywords: SARS-CoV-2; COVID-19; Rapid antigen test; RT-qPCR, screening method; surface contamination
(Siriraj Med J 2023; 75: 7-12)
Corresponding author: Nattamon Niyomdecha
E-mail: nattamon@tu.ac.th
Received 01 September 2022 Revised 21 September 2022 Accepted 23 September 2022
ORCID ID:http://orcid.org/0000-0002-5364-6716
http://dx.doi.org/ 10.33192/smj.v75i1.260524
All material is licensed under terms of
the Creative Commons Attribution 4.0
International (CC-BY-NC-ND 4.0)
license unless otherwise stated.
INTRODUCTION
Severe acute respiratory syndrome coronavirus 2
(SARS-CoV-2) causes the pandemic coronavirus disease
2019 (COVID-19). Transmission of infectious SARS-
CoV-2 to the human respiratory tract occurs through two
major pathways: by aerosols/droplets in direct person-
to-person contact and via exposure to contaminated
fomites in indirect contact. Viable SARS-CoV-2 has
been shown to survive on dierent surfaces for days or
weeks depending on temperature, relative humidity, and
light.
1
High safety standards are a must in the food industry,
including in food processing and distribution to maintain
consumer trust and condence in its products. However,
infected food workers, either unaware of hygiene guidelines
or not following them, might contaminate food during
processing and packaging by touching it with contaminated
hands or via infectious droplets released when talking,
coughing, or sneezing.
2
SARS-CoV-2 contamination
of food products and packaging materials can lead to
serious economic loss in food export businesses. For
example, China, known for its strict COVID-19 policy,
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
8
temporarily banned durian from ailand due to several
positive SARS-CoV-2 detection results during random
testing.
3
Although the contact with SARS-CoV-2 adhered
on food, including fruits and vegetables, or food packaging
materials is highly unlikely to cause COVID-19, such
contaminations must always be tracked, particularly in
the actual context where the virus is spreading in the
countries.
4
Real-time reverse transcription polymerase chain
reaction (RT-qPCR) is recognized as the gold standard
method for the detection of SARS-CoV-2 in clinical
and non-clinical samples. However, it is limited by a
long turnaround time due to nucleic acid extraction
and amplication and requires trained sta, expensive
instruments, and a laboratory setting with adequate
biosafety. ese resources are not always available in all
countries and in this case a rapid antigen test might be
an alternative to RT-qPCR. While it is less sensitive, it
is faster, easier to perform, more aordable and allows
for decentralized testing at eld areas.
5
At the present time, data on the use of rapid antigen
tests to detect SARS-CoV-2 in food or environmental
samples are limited. us, this study aimed to evaluate the
performance of an antigen-based rapid test for detection
of SARS-CoV-2 on articially surface-contaminated
objects in comparison with a RT-qPCR standard method.
MATERIALS AND METHODS
Inactivated SARS-CoV-2 virus preparation
An inactivated clinical isolate of SARS-CoV-2/01/
human/Jan2020/Thailand was used in this study. It
represented the original Wuhan strain isolated from
a confirmed COVID-19 patient at Bamrasnaradura
Infectious Diseases Institute, Nonthaburi, ailand.
e inactivated virus was prepared by two methods,
heating and UV-C radiation. Stock SARS-CoV-2 virus
of 10
6
pfu/ml was divided into two sets for incubation
at 65°C, 15 min, and for exposure by UV-C for 15 min.
Subsequently, the virus was inoculated onto Vero E6
cells to conrm the complete inactivation of the virus
by absence of cytopathic eects (CPE).
All processes involving inactivated SARS-CoV-2
were performed under Enhanced BSL-2 (BSL-2+) in
accordance with the biosafety guidelines. e project
was approved by the ammasat University Institutional
Biosafety Committee (101/2564).
Articial-surface contamination and sample collection
Serial dilutions of 10
3
, 10
4
, and 10
5
pfu/100 µl were
prepared from the stocks of heat- and UV-C-inactivated
SARS-CoV-2. Samples of pooled inactivated virus at
each dilution were prepared by combining 100 µl each of
heat- and UV-C-inactivated SARS-CoV-2. Ten dierent
objects comprising common fruits and packaging materials
were selected for analysis. ey were durian, rambutan,
orange, apple, leather, parcel box, fruit foam net, foam
box, foil, and plastic.
Inoculation and swab processes were performed
by dierent persons. Pooled inactivated virus of each
dilution was randomly spiked, by making tiny drops
with pipette like droplets from sneezing, onto the entire
surface of each object and the objects were then completely
dried at room temperature. e objects were collected
by randomly swabbing without knowledge of previous
inoculation site at an area of 100 to 225 cm
2
or entire
area for smaller ones at day 0, 3 and 5. Two swabs were
used for SARS-CoV-2 detection by rapid antigen test
and RT-qPCR.
SARS-CoV-2 testing
Nucleocapsid (NP) protein antigen of SARS-CoV-2
was detected by a Rapid Surface Ag 2019-nCov Kit
(Prognosis Biotech, Larissa, Greece). Briey, the collected
swab was placed in extraction buer for 30 seconds and
was then discarded. Aerwards, a test strip was immersed
into the extraction buer for 10 min. Detection of SARS-
CoV-2 resulted in visible colored bands at both Test
(T) and Control (C) lines. As shown in the test manual,
cross-reactivity with 4 dierent human coronavirus
strains is not found, and the limit of detection (LOD) is
2.5 ng/ml of NP or 5.75 x 10
3
TCID
50
/ml of inactivated
SARS-CoV-2.
6
Collected swabs for RT-qPCR assay were kept in
HiViral
TM
transport medium (HiViral
TM
Transport Kit,
HiMedia, Mumbai, India). Swabs were vortexed and
200 µl of HiViral
TM
transport medium was used to extract
RNA by using a PureLink viral RNA/DNA mini kit
(Cat no. 12280050, Invitrogen, USA) according to the
manufacturer’s instructions. e concentration of the
puried RNA was measured as ng/µl and the RNA was
kept at −80°C before RT-qPCR detection. Following
the manufacturer’s instructions and interpretations,
SARS-CoV-2 RNA targeting ORF1ab, N, and E genes
was detected by an ANDiS FAST SARS-CoV-2 RT-qPCR
Detection Kit (Cat no. 3103010069, 3DMed, Germany).
Positive (SARS-CoV-2) and negative (human
coronavirus strain OC43) controls were used to validate
results in all experiments.
Statistical analysis
Descriptive analysis as mean, standard deviation
(SD), detection rate (%) was performed and compared
between rapid antigen test and RT-qPCR at each viral
dilution.
Niyomdecha et al.
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
9
Original Article
SMJ
RESULTS
Detection of SARS-CoV-2 by rapid antigen test
and RT-qPCR on artificially contaminated objects
was compared and the results obtained on the day of
inoculation and sample collection (day 0) are shown in
Table 1 and Fig 1. RT-qPCR, the gold standard method,
had a higher sensitivity than the rapid antigen test and
detected SARS-CoV-2 contamination on all objects at
all virus dilutions. e detection rate obtained with the
rapid antigen test was 10%, 90% and 90% at 10
3
, 10
4
and 10
5
pfu/100 µl, respectively (Fig 1). e sensitivity
of the rapid test was poor at the lowest virus titer but
was much improved at 10
4
and 10
5
pfu/100 µl. Likewise,
the intensity of the detected T-band seemed to depend
on the virus titer (Fig 2). However, we observed that
the type of material aected the detection. Detection of
SARS-CoV-2 contamination was most dicult for both
methods on the parcel box made from paper. Indeed,
even contamination with virus titer at 10
4
and 10
5
pfu/
100 µl showed negative results when detected by the
rapid test. Although it could be detected by RT-qPCR,
the Ct values of all target genes were shied over ten
cycles (Table 1). Additionally, plastic was the only object
out of the ten spiked objects that could be detected by
the rapid test at 10
3
pfu/100 µl SARS-CoV-2.
Next, we investigated the detection rate aer the
articially contaminated objects were le for 3 and 5
days. All objects spiked with 10
5
pfu/100 µl SARS-CoV-2
could be detected by rapid test and RT-qPCR aer 3 and
5 days (Table 2). e results were consistent with the
same day testing (day 0).
Further comparison of RT-qPCR and rapid antigen
test showed the latter to have a limit for detection of
SARS-CoV-2 NP when the Ct values (mean±SD) of
RT-qPCR targeting the ORF1ab, N, and E genes were
in the range of 30.77±3.74, 27.02± 3.64, 26.54±9.72,
respectively (Table 1).
DISCUSSION
is study used pooled heat and UV-C inactivated
SARS-CoV-2 to contaminate ten dierent materials. Heat-
inactivation at 65°C for 15 min will denature viral proteins
but not the genomic RNA, while UV-C-inactivation for
15 min has a deleterious eect on the RNA but not on
the viral structure.
7
us, the pooled inactivated SARS-
CoV-2 used in this study allowed parallel application
of the two detection methods, i.e., antigen-based rapid
test and nucleic acid-based RT-qPCR and minimized
the risk of false negative results.
e used rapid chromatographic immunoassay
intended for qualitative detection had a lower sensitivity
in SARS-CoV-2 detection in comparison to the gold
standard method RT-qPCR. Our data showed that the
limit of detection of the rapid antigen test was at 10
4
pfu/100 µl. At this amount of virus RT-qPCR showed
average Ct values for ORF1ab, N, and E genes, across the
analyzed samples in the range of 30.77±3.74, 27.02±3.64,
26.54±9.72, respectively.
However, the results of the rapid test showed that
detection sensitivity depended on the kind of investigated
material. SARS-CoV-2 NP could be still detected at 10
3
pfu/100 µl on plastic, whereas it could not be detected
at a titer as high as 10
5
pfu/100 µl on other materials like
parcel box. Interestingly, Ct values from SARS-CoV-2
detection by RT-qPCR showed the highest value at all
virus titers on parcel box. Previous research supports
these ndings.
8-9
Most of the enveloped viruses like
SARS-CoV-1 or inuenza virus were found to survive
and persist in stable form longer on plastic and stainless
steel (1–7 days) than on paper and tissue (3–8 h).
9-11
SARS-CoV-2 was found to be inactivated much faster
on paper than on plastic. No virus could be detected
aer 3 hours of being inoculated on paper.
8,10
Corpet
hypothesized that dryness would inactivate SARS-CoV-2
like found on water absorbent porous materials.
10
Since
an enveloped virus has a lipid bilayer membrane that
needs water on both sides to maintain an intact structure
dryness might lead to oxidation of lipids and Maillard
reactions of proteins.
10
While smooth and waterproof
materials would protect the virus by keeping the moisture
from micro-droplets of water on the surface.
12
is would
explain the stability of SARS-CoV-2 on non-absorbent
materials, including durian, leather, and plastic on which
it could be detected aer many days by both, rapid test
and RT-qPCR.
Taken together, our pilot study on artificially
contaminated objects suggests that the used rapid antigen
test would be a valuable method for screening of dierent
materials. In comparison to RT-qPCR it is easier to
perform, would cost less, save time, and is suitable for
a large number of samples. Its application may enhance
safety policies in public health and international export-
businesses. However, the limitations in this study were
using only articial samples under controlled conditions
and no testing with control group of inoculation with non-
infected uid on samples that might develop interpretation
bias on an antigen-based rapid test. us, these concerns
should be considered for future study. Real-world samples
should be done with and always in comparison with a
gold standard RT-qPCR assay.
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
10
TABLE 1. Comparison of SARS-CoV-2 detection results on articially contaminated objects by rapid antigen test and
RT-qPCR on same day testing (day 0).
Cycle threshold (Ct) value (Interpret result) of RT-qPCR detection
a
Rapid
Samples
ORF1ab N gene E gene
Internal Conclusion antigen
control result
b
test result
A. Virus titer at 10
5
pfu/100 µl
SARS-CoV-2
c
11.94 (+) 12.27 (+) 9.38 (+) 34.03 (+) + +
HCOV-OC43
d
> 40 (-) > 40 (-) > 40 (-) > 40 (-) - -
Durian 27.1 (+) 23.47 (+) 25.83 (+) > 40 (-) + +
Rambutan 28.84 (+) 26.49 (+) 27 (+) > 40 (-) + Weak +
Orange 26.55 (+) 23.05 (+) 25.12 (+) > 40 (-) + +
Apple 24.14 (+) 21.52 (+) 22.6 (+) > 40 (-) + +
Leather 21.46 (+) 20.27 (+) 20.07 (+) > 40 (-) + +
Parcel box 37.56 (+) 34.2 (+) 35.62 (+) 39.71 (+) + -
Fruit foam net 25.44 (+) 22.8 (+) 24.33 (+) 38.89 (+) + +
Foam box 25.49 (+) 23.11 (+) 24.12 (+) 39.79 (+) + +
Foil 24.95 (+) 21.96 (+) 25.33 (+) > 40 (-) + +
Plastic 23.57 (+) 20.61 (+) 23.12 (+) > 40 (-) + +
Mean±SD (Positive-Ct) 26.51±4.37 23.75±4.07 25.31±4.10 11.84±19.06
B. Virus titer at 10
4
pfu/100 µl
SARS-CoV-2 16.35 (+) 16.05 (+) 15.16 (+) 37.19 (+) + +
HCOV-OC43 > 40 (-) > 40 (-) > 40 (-) > 40 (-) - -
Durian 31.57 (+) 28.57 (+) 29.93 (+) 38.15 (+) + Weak +
Rambutan 32.63 (+) 30.32 (+) 31.54 (+) > 40 (-) + Weak +
Orange 31.17 (+) 26.45 (+) 29.16 (+) 38.64 (+) + Weak +
Apple 36.06 (+) 28.69 (+) > 40 (-) > 40 (-) + Weak +
Leather 27.36 (+) 22.63 (+) 27.24 (+) 37.43 (+) + Weak +
Parcel box 36.95 (+) 34.45 (+) 35.63 (+) > 40 (-) + -
Fruit foam net 30.13 (+) 26.71 (+) 30.2 (+) 38.19 (+) + Weak +
Foam box 29.46 (+) 25.62 (+) 28.96 (+) 35.99 (+) + Weak +
Foil 26.06 (+) 23.33 (+) 26.48 (+) > 40 (-) + Weak +
Plastic 26.32 (+) 23.42 (+) 26.27 (+) > 40 (-) + +
Mean±SD (Positive-Ct) 30.77±3.74 27.02±3.64 26.54±9.72 18.84±19.87
C. Virus titer at 10
3
pfu/100 µl
SARS-CoV-2 19.89 (+) 19.30 (+) 18.44 (+) > 40 (-) + +
HCOV-OC43 > 40 (-) > 40 (-) > 40 (-) > 40 (-) - -
Durian 36.99 (+) 32.73 (+) 35.11 (+) 38.32 (+) + -
Rambutan 31.79 (+) 29.71 (+) 31.21 (+) > 40 (-) + -
Orange 34.39 (+) 30.10 (+) 33.49 (+) > 40 (-) + -
Apple 28.46 (+) 25.27 (+) 27.67 (+) > 40 (-) + -
Leather 32.39 (+) 28.17 (+) 32.75 (+) > 40 (-) + -
Parcel box 37.48 (+) 36.47 (+) 36.27 (+) > 40 (-) + -
Fruit foam net 35.49 (+) 29.06 (+) > 40 (-) > 40 (-) + -
Foam box 33.45 (+) 30.03 (+) 33.04 (+) 37.40 (+) + -
Foil 31.97 (+) 28.31 (+) 32.31 (+) 37.58 (+) + -
Plastic 32.01 (+) 28.97 (+) 32.11 (+) > 40 (-) + Weak +
Mean±SD (Positive-Ct) 33.44±2.73 29.88±2.98 29.40±10.58 11.33±18.24
a
“+” when Ct value ≤ 40, and “-” when Ct value ≥ 40.
b
Conclusion results were interpreted following the manufacturer’s instruction. In brief, positive when at least 2/3 of SARS-CoV-2 specic
RNA targets were detected without relying on internal control detection.
c
Positive control from inactivated SARS-CoV-2.
d
Negative control from inactivated human coronavirus strain OC43 (HCOV-OC43).
Niyomdecha et al.
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
11
Original Article
SMJ
Fig 1. Comparison of detection rate (%) between
rapid antigen test and RT-qPCR.
e relative number of positive results per total
samples at each tested virus titer
is shown as percentage of detection.
Fig 2. Test line intensity of rapid antigen test.
From le to right, 10
5
, 10
4
, and 10
3
pfu/100 µl
SARS-CoV-2 virus titers were
evaluated by rapid antigen tests. e observed
test line intensity depended on the virus titer.
e results were interpreted as positive, weak
positive, and negative, respectively.
TABLE 2. Comparison of SARS-CoV-2 detection results on articially contaminated objects by rapid antigen test
and RT-qPCR aer 3 and 5 days of inoculation.
Cycle threshold (Ct) value (Interpret result) of RT-qPCR detection
a
Rapid
Samples ORF1ab N gene E gene Internal Conclusion antigen test
control result
b
result
Day 3-Virus titer at 10
5
pfu/100 µl
Durian 21.91 (+) 20.88 (+) 21.14 (+) > 40 (-) + +
Leather 30.08 (+) 26.27 (+) 31.09 (+) > 40 (-) + +
Plastic 24.60 (+) 21.11 (+) 25.54 (+) 33.21 (+) + +
Day 5-Virus titer at 10
5
pfu/100 µl
Durian 24.77 (+) 23.27 (+) 23.73 (+) > 40 (-) + +
Leather 28.97 (+) 24.96 (+) 30.08 (+) > 40 (-) + +
Plastic 23.88 (+) 20.53 (+) 24.84 (+) 39.01 (+) + +
a
“+” when Ct value ≤ 40, and “-” when Ct value ≥ 40.
b
Conclusion results were interpreted following the manufacturer’s instruction. In brief, positive when at least 2/3 of SARS-CoV-2 specic
RNA targets were detected without relying on internal control detection.
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
12
CONCLUSION
is study suggests the rapid antigen test as a rst
screening assay to identify SARS-CoV-2 contamination
on various material types. It would reduce the demand
for the expensive and time-consuming RT-qPCR assay
in non-clinical samples.
ACKNOWLEDGEMENTS
e authors thank Professor Dr. Prasert Auewarakul
and Miss Chompunuch Boonarkart from the Department
of Microbiology, Faculty of Medicine Siriraj Hospital,
Mahidol University, who kindly provided the inactivated
SARS-CoV-2 virus for the experiments.
Conict of interest statement: e authors do not have
any conict of interest to declare.
REFERENCES
1. Aboubakr HA, Sharafeldin TA, Goyal SM. Stability of SARS-
CoV-2 and other coronaviruses in the environment and on
common touch surfaces and the inuence of climatic conditions:
A review. Tranbound Emerg Dis. 2021;68(2):296-312.
2. Shukla S, Cho H, Kwon OJ, Chung SH, Kim M. Prevalence and
evaluation strategies for viral contamination in food products: Risk
to human health—A review. Crit Rev Food Sci Nutr. 2018;58(3):
405-19.
3. Taylor M. China warns ailand to x durian Covid-19 problem
or face export ban [Internet]. 2022 Apr [cited 2022 Sep 25].
Available from: https://thethaiger.com/news/national/china-
warns-thailand-to-x-durian-covid-19-problem-or-face-export-
ban
4. Benkeblia N. In the landscape of SARS-CoV-2 and fresh fruits
and vegetables: e fake and hidden transmission risks. J Food
Saf. 2021;41(4):e12898.
5. Fernandez-Montero A, Argemi J, Rodríguez JA, Ariño AH,
Moreno-Galarraga L. Validation of a rapid antigen test as a
screening tool for SARS-CoV-2 infection in asymptomatic
populations. Sensitivity, specicity and predictive values.
EClinicalMedicine. 2021;37:100954.
6. ProGnosis Biotech [homepage on the Internet]. Rapid Test
Surface Ag 2019-nCoV [cited 2022 Sep 20]. Available from:https://
www.prognosis-biotech.com/product/rapid-test-surface-ag-
2019-ncov/
7. Loveday EK, Hain KS, Kochetkova I, Hedges JF, Robison A,
Snyder DT, et al. Eect of inactivation methods on SARS-
CoV-2 virion protein and structure. Viruses. 2021; 13(4):562.
8. Dehbandi R, Zazouli MA. Stability of SARS-CoV-2 in dierent
environmental conditions. Lancet Microbe. 2020;1(4):e145.
9. van Doremalen N, Bushmaker T, Morris DH, Holbrook
MG, Gamble A, Williamson BN, et al. Aerosol and surface
stability of SARS-CoV-2 as compared with SARS-CoV-1. N
Engl J Med. 2020;382(16):1564-7.
10. Corpet DE. Why does SARS-CoV-2 survive longer on plastic
than on paper? Med Hypotheses. 2021;146:110429.
11. Bean B, Moore BM, Sterner B, Peterson LR, Gerding DN,
Balfour HH Jr. Survival of inuenza viruses on environmental
surfaces. J Infect Dis. 1982;146(1):47-51.
12. Casanova LM, Jeon S, Rutala WA, Weber DJ, Sobsey MD.
Eects of air temperature and relative humidity on coronavirus
survival on surfaces. Appl Environ Microbiol. 2010;76(9):
2712-7.
Niyomdecha et al.
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
13
Original Article
SMJ
Supisara Wongdama, M.D.*, Arunotai Siriussawakul, M.D.**,***, Woraphat Ratta-apha, M.D.****, Pudit Suraprasit,
M.D.*, Kanawat Kanjanapiboon, M.D.*, Chayanan anakiattiwibun, M.Sc.***, Rattapon uangtong, M.D.*
*Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ailand., **Department of Anesthesiology, Faculty
of Medicine Siriraj Hospital, Mahidol University, Bangkok, ailand., ***Siriraj Integrated Perioperative Geriatric Excellent Research Center, Faculty
of Medicine Siriraj Hospital, Mahidol University, Bangkok, ailand., ****Department of Psychiatry, Faculty of Medicine Siriraj Hospital, Mahidol
University, Bangkok, ailand.
Effects of Music on Preoperative Anxiety in Patients
Undergoing Hair Transplantation: A Preliminary
Report
ABSTRACT
Objective: To study the eects of music on anxiety in patients undergoing hair transplantation.
Materials and Methods: is randomized controlled trial enrolled patients undergoing hair transplantation. e
patients were randomized into a music group, who listened to music for 15 minutes during the preoperative period,
and a control group, who were not exposed to music. Two scales were used to measure anxiety. One was the State-
Trait Anxiety Inventory (STAI), comprised of a state anxiety scale (STAI-S) and trait anxiety scale (STAI-T). e
other was the Visual Analog Scale for Anxiety (VASA). Demographic and physical parameters (blood pressure,
heart rate, and respiratory rate) were recorded.
Results: e 26 patients had a mean age of 40.8 ± 10.4 years. Twenty-three (88.5%) were men. e 2 groups had no
signicant dierences in their STAI-S or VASA scores, or physical parameters before and aer intervention. e
STAI-S score of the control group signicantly increased with time (P = 0.027). Additionally, a signicant decrease in
the VASA score was observed aer the intervention for the music group (P = 0.039). No adverse events were noted.
Conclusion: Listening to music is an easy, eective, and safe method of reducing preoperative anxiety in patients
undergoing hair transplantation. e method should be employed during the preoperative period for patients
undergoing hair transplantation. It may also be considered for use in similar procedures.
Keywords: Anxiety; hair transplantation; music; state-trait anxiety inventory; preoperative (Siriraj Med J 2023; 75:
13-19)
Corresponding author: Rattapon uangtong
E-mail: rattaponthuangtong@yahoo.com
Received 18 May 2022 Revised 15 November 2022 Accepted 27 November 2022
ORCID ID:http://orcid.org/0000-0001-5639-8984
http://dx.doi.org/ 10.33192/smj.v75i1.260525
All material is licensed under terms of
the Creative Commons Attribution 4.0
International (CC-BY-NC-ND 4.0)
license unless otherwise stated.
INTRODUCTION
e preoperative period is a worrying event for
patients and creates emotional, cognitive, and physiological
responses.
1
Waiting for surgery or invasive procedures
has been reported to create stress and anxiety, which
aggravate and aect physiological and psychological
parameters.
2
Preoperative anxiety is a major concern in
patients undergoing surgery. It may be attributed to a
fear of complications, unfamiliar environments, needles,
injections, pain, bleeding, or separation from friends and
family.
3
Anxiety has a considerable impact on surgical
outcomes. It is associated with an increased requirement
for postoperative pain control, a prolonged recovery
time, and an increase in postoperative complications.
4
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
14
Wongdama et al.
Pharmacological and nonpharmacological interventions
have been employed to alleviate preoperative anxiety.
Pharmacological interventions, such as sedatives and
anti-anxiety drugs, are widely used, easy to administer,
and eective.
5
However, these drugs frequently cause
adverse events like drowsiness and respiratory depression,
and they may impair decision-making. As well, patients
should not drive as the drugs can aect their judgment.
5,6
Because of the various drawbacks, a pharmacological
intervention may not be appropriate for ambulatory
surgery. In comparison, nonpharmacological interventions,
such as preoperative education and the use of relaxation
techniques and music, are being increasingly used.
7
In
particular, music is a safe, easy, and noninvasive method
of reducing anxiety. Additionally, listening to music has
proven to decrease anxiety suciently to allow the total
dose of sedatives to be reduced.
8
Hair transplantation, an outpatient procedure
performed under local anesthesia, is a treatment option
for patients who have failed to respond to standard
medical treatment.
9
Although hair transplantation is
a minimally invasive surgery, patients have reported
severe anxiety levels before the procedure.
10,11
Since
preoperative anxiety has substantial adverse inuences
on postoperative outcomes and given the ease of use, low
cost, and safety of music, this study aimed to evaluate
the eects of music in reducing preoperative anxiety in
patients undergoing hair transplantation. is study used
the State-Trait Anxiety Inventory (STAI) questionnaire
and the Visual Analog Scale for Anxiety (VASA) to
evaluate the eects of music on preoperative anxiety in
patients undergoing hair transplantation.
MATERIALS AND METHODS
is prospective, single-blind, randomized controlled
trial was conducted at the Hair Clinic, Outpatient
Dermatology Unit, in a tertiary hospital in ailand
between February 2018 and August 2021. e study
protocol was approved by the Institutional Review Board
(COA no. Si 077/2018) and was registered with the ai
Clinical Trials Registry (TCTR20210820004). All patients
gave their written informed consent.
Participants
e study enrolled patients aged 18 years or older
who underwent hair transplantation with the follicular
unit transplantation or follicular unit excision technique
and had a waiting time of at least 45 minutes before
surgery. Exclusion criteria were patients with any
psychological disease, regular use of antidepressant or
anxiolytic drugs, an inability to read and understand
ai, a visual impairment or hearing loss that impaired
their ability to communicate, and an unwillingness to
participate or listen to music. e patients were divided
into 2 groups using a simple random sampling method.
Participants in a music group received a preoperative
music intervention for 15 minutes, whereas those in a
control group did not receive the music intervention.
Data collection
Demographic and clinical data were collected using
face-to-face interviews. Anxiety levels in the patients were
assessed using an STAI questionnaire and a VASA. e
STAI is a 40-item, self-report questionnaire developed
by Spielberger et al that uses a 4-point Likert-type scale
for each item.
12
It comprises 2 parts: a state anxiety scale
(STAI-S), which measures the current state of anxiety
(“state anxiety”); and the trait anxiety scale (STAI-T),
which assesses the general state of anxiety (“trait anxiety”).
Each scale has 20 items. e score for each item ranges
from 1 (“not at all”) to 4 (“very much”), and the total score
for each part ranges from 20 to 80 points. Higher scores
indicate a greater severity of anxiety.
12,13
e STAI was
translated into ai by Nonthasak and colleagues.
14
e
reliability of ai STAI has been documented (Cronbach’s
alpha = 0.89).
15,16
With regard to the VASA, it uses a
10-cm horizontal line with a scale ranging from 0 to 10,
indicating “not anxious at all” and “extremely anxious,”
respectively. e scores are categorized to indicate mild
(≤ 3), moderate (4–6), and severe (≥ 7) degrees of anxiety.
17
Patients were instructed to indicate their level of anxiety
on the line. e distance was then measured and noted.
Intervention
All patients were requested to answer the STAI
questionnaire (both the STAI-S and STAI-T components)
and rate the VASA independently before the intervention.
Nursing sta also recorded the physical parameters of
each patient: heart rate, systolic blood pressure, diastolic
blood pressure, and respiratory rate. Aer that, members
of the music group were invited to listen to music on
YouTube via headphones through mobile telephones
that were made available to them. ey were allowed
to choose 1 set of classical music from a list using the
keyword “relaxing instrumental music” and listen for
15 minutes during the preoperative period. e volume
of the music was modied by each patient according
to their personal preference. In contrast, the members
of the control group were instructed to wait in a silent
room and were not allowed to listen to any music for
15 minutes. Subsequently, all patients independently
redetermined their STAI-S and VASA scores, and the
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
15
Original Article
SMJ
RESULTS
A total of 30 patients were evaluated for eligibility.
Four were excluded: 2 had a waiting time less than
45 minutes, 1 regularly used anxiolytic drugs, and
1 declined to participate (Fig 1) erefore, 26 patients
were included in the study (control group, n =14; music
group, n = 12). e mean age of the patients was 40.8
years, and 23 of the 26 (88.5%) were men. Most of the
patients (96.2%) were diagnosed with androgenetic
alopecia, and 1 (3.8%) had scarring alopecia from burns. All
patients had educational levels higher than primary school
grade 9. e mean trait anxiety scores of the control and
music groups were 46.2±4.5 and 47.5±2.7, respectively.
ere were no statistically signicant dierences in any
of the demographic parameters of the groups, except
age and marital status. e demographic data of the 26
patients are detailed in Table 1.
nursing sta remeasured their physical parameters. e
patients then had a 5- to 15-minute wait before the hair
transplantation procedure commenced. All processes
were performed before the surgery and were completed
in a single visit.
Statistical analyses
Demographic data were calculated using descriptive
statistics. Categorical data are presented as numbers
(percentages). Continuous data with normal distributions
are shown as the mean±SD and were compared by
an independent t-test. e Wilcoxon signed-rank test
was used to determine the dierences between each
group before and aer the intervention. Spearman’s
rank correlation coecient was used to calculate the
association between pairs of variables. Data were analyzed
using PASW Statistics for Windows (version 18; SPSS
Inc., Chicago, IL., USA).
Fig 1. Flowchart outlining patient enrollment, randomization, follow-up, and analysis.
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
16
TABLE 1. Demographic data of patients undergoing hair transplantation.
Characteristic
Total Control group Music group
(N, 26) (n, 14) (n, 12)
P value
Sex
Male 23 (88.5) 12 (85.7) 11 (91.7) 1.000
Female 3 (11.5) 2 (14.3) 1 (8.3)
Age (years) 40.8 ± 10.4 45.0 ± 9.8 35.9 ± 9.1 0.022*
Age onset (years) 24.2 ± 10.0 25.1 ± 12.5 23.1 ± 6.0 0.609
Body mass index (kg/m
2
) 23.5 ± 2.2 23.3 ± 2.4 23.7 ± 2.0 0.653
Marital status
Single 14 (53.8) 5 (35.7) 9 (75.0) 0.045*
Married 12 (46.2) 9 (64.3) 3 (25.0)
Living
With family 20 (76.9) 12 (85.7) 8 (66.7) 0.365
Alone 6 (23.1) 2 (14.3) 4 (33.3)
Previous hair transplantation
No 12 (46.2) 4 (28.6) 8 (66.7) 0.052
Yes 14 (53.8) 10 (71.4) 4 (33.3)
Hair transplantation in this visit
FUE 19 (73.1) 10 (71.4) 9 (75.0) 1.000
FUT 7 (26.9) 4 (28.6) 3 (25.0)
Trait anxiety score 46.8 ± 3.8 46.2 ± 4.5 47.5 ± 2.7 0.395
e data are presented as mean ± SD or number (%)
*, statistically signicant (P <0.05)
Abbreviations: FUE: follicular unit excision; FUT: follicular unit transplantation
Wongdama et al.
Although patients in the music group were 10 years
younger than those in the control group, age was not
associated with the baseline STAI-S scores of the music
and control groups (r = 0.049; P =0.812). Similarly, while
most of the patients were single, there was no dierence in
the baseline STAI-S scores of single and married patients
(P = 0.413). At baseline, the mean state anxiety scores,
mean VASA scores, and physical parameters of the 2
groups were similar. Aer the intervention, there were
no statistical dierences in any of the data items of the
2 groups (P > 0.050; Table 2). However, a comparison
of the changes in the pre- and postintervention values
within each group revealed signicant dierences for 2
items. On the one hand, the mean state anxiety score
of the control group signicantly increased aer the
patients waited in the silent room for 15 minutes (before,
45.6±3.5; aer, 48.4±4.3; P = 0.027). On the other hand,
the VASA score of the music group signicantly decreased
as a result of listening to music (before, 2.7±2.3; aer,
1.9±2.0; P = 0.039). No other signicant dierences
within the groups were revealed. Moreover, no side
eects were reported during the study period.
DISCUSSION
Regarding the cognitive behavioral model of social
anxiety, exposure to a feared social situation activates
assumptions that have been formed by past experiences.
ese assumptions activate socially anxious individuals
to regard certain social situations as dangerous, leading
to low self-esteem.
18
According to this theory, the loss of
hair can create anxiety and aect self-esteem and self-
image. Consequently, eective treatments are sought for
patients with hair loss.
19
Several studies have reported
hair transplantation to be an eective way to potentially
reverse psychosocial problems by reducing anxiety and
improving self-condence.
19,20
However, eective strategies
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
17
Original Article
SMJ
TABLE 2. Comparison of rst- and second-measured state anxiety scores, VASA scores, and physical parameters
of control and music groups.
Mean ± SD
Variable Control group Music group P value
(n, 14) (n, 12)
State anxiety score
1
st
measurement 45.6 ± 3.5 45.7 ± 3.6 0.946
2
nd
measurement 48.4 ± 4.3 46.3 ± 3.5 0.173
VASA (n = 19)
1
st
measurement 2.2 ± 2.4 2.7 ± 2.3 0.652
2
nd
measurement 1.6 ± 1.7 1.9 ± 2.0 0.730
Heart rate
1
st
measurement 82.6 ± 12.8 82.1 ± 12.9 0.924
2
nd
measurement 76.8 ± 15.9 80.4 ± 10.9 0.518
Respiration rate
1
st
measurement 15.9 ± 0.9 15.5 ± 1.2 0.339
2
nd
measurement 15.8 ± 1.0 16.2 ± 0.6 0.415
SBP
1
st
measurement 126.1 ± 11.2 129.4 ± 13.4 0.495
2
nd
measurement 126.5 ± 12.3 129.4 ± 10.2 0.535
DBP
1
st
measurement 79.3 ± 11.9 78.3 ± 6.2 0.788
2
nd
measurement 81.2 ± 15.5 77.4 ± 11.7 0.510
e data are presented as mean ± SD
Abbreviations: DBP, diastolic blood pressure; SBP, systolic blood pressure; SD, standard deviation; VASA, visual analog scale for anxiety
to decrease preoperative anxiety in hair transplant patients
have not been explored.
Previous studies demonstrated that listening to
music signicantly reduced anxiety in patients undergoing
dermatological procedures.
21-23
Vachiramon and associates
found signicant reductions in the anxiety of patients who
listened to self-selected music while waiting for physicians
and during the rst stage of Mohs micrographic surgery.
is was especially the case for patients undergoing
the surgery for the rst time.
21
Sorensen and others
concluded that listening to classical music during an
injection of local anesthesia signicantly decreased pain
and anxiety in non-Mohs dermatologic procedures.
22
Similarly, Deivasigamani and colleagues found that music
intervention reduced anxiety in patients undergoing
dermatosurgery under local anesthesia.
23
In contrast,
Alam and coauthors reported that relaxing music was
not associated with any signicant dierences in pain,
anxiety, blood pressure, or heart rate in patients undergoing
excisional surgery for basal and squamous cell carcinoma.
24
In the present study, listening to music was not
associated with reducing the anxiety of the patients
undergoing hair transplantation, and it did not aect their
physical parameters. ere are several possible reasons
for this. First, the state anxiety score of the patients in
this study was only slightly higher than 40, which is the
cuto score used to detect anxiety symptoms.
25
Similarly,
anxiety levels measured by VASA showed mild anxiety.
is is contrary to the work by Ahmad and Mohmand,
who reported moderate to severe anxiety in patients
undergoing hair transplantation.
10
is dierence from
our study may be because individuals are increasingly
using the Internet to access a wide range of health
information. eir internet research may cause them
to perceive that hair transplantation is a safe and minor
surgical procedure with very few complications, leading
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
18
Wongdama et al.
them to worry less.
26
Listening to music may therefore
be unable to measurably decrease their low level of
state anxiety. On the other hand, the patients in our
study had a high mean trait anxiety score.
27
is may be
because the patients had previous personality or mental
health problems. Patients who suer severely from hair
loss experience multiple feelings and emotions due to
personal and social pressures. e hair loss may lead to
psychological stress out of proportion to the problem.
28
Accordingly, such patients are more likely to have high
expectations for their hair transplant results. erefore,
these expectations might also impact the eects of music
on their pre-intervention anxiety.
Second, the patients were instructed to listen to
classical music and were unable to select the music of
their choice. Although classical music was shown to oer
greater benets than other musical genres, some authors
reported that the greatest anxiolytic eect may be achieved
when patients select familiar music that they enjoy.
6,21
ird, the duration of music intervention in the current
investigation may have been a contributing factor. is
study administered a 15-minute music intervention.
is is shorter than the intervention period of previous
studies, in which patients listened to 30 minutes of music
in the preoperative setting.
29,30
Further studies with larger
sample sizes and longer music interventions may be
required to elucidate the eects of music on anxiety in
hair transplant patients.
Although this study did not detect significant
differences between the music and control groups,
signicant dierences within the groups were reported.
ere was a signicant increase in anxiety measured by
STAI-S in the control group. is could be attributed to
an increasing trend of preoperative anxiety over time.
31
Additionally, a reduction in anxiety using VASA was
demonstrated by the music group after listening to
music. e theoretical basis of music in terms of anxiety
reduction lies in the impact of music on the autonomic
nervous system, which enhances relaxation. e auditory
stimulation of music is believed to aect a number of
neurotransmitters and alter the experience of anxiety,
fear, and pain. Consequently, more positive perceptual
experiences, including stimulation of stress and anxiety
reduction, are achieved. Additionally, music promotes
feelings of physical and mental relaxation by refocusing
attention on pleasurable emotional states.
32
While listening
to music, patients’ awareness of time passing was distracted
because their attention was on the music, resulting in
greater relaxation.
33
is study demonstrated a trend
of reduction in anxiety through music listening. Since
music listening is a noninvasive, easy-to-administer,
eective, and safe method, its introduction should be
considered as a means of reducing the anxiety of patients
undergoing hair transplantation or similar procedures.
is study has some limitations. As it was a preliminary
study, only 26 patients were included. In addition, the
prevalence and severity of androgenetic alopecia have
been reported to be higher in males than in females.
34
Consequently, most of the hair transplant patients in this
study were men. Validation through a larger sample size
and a sex-balanced distribution is needed to conclusively
demonstrate the eects of music on preoperative anxiety
in patients undergoing hair transplantation. Moreover,
the patients in our study could not be blinded to the group
assignments. is may have aected their evaluations,
resulting in bias. In addition, the unequal waiting times
before the commencement of the procedures may have
aected the patients’ pre- and post-surgery anxiety scores.
In conclusion, music is an easy-to-administer,
eective, and safe method to reduce preoperative anxiety
in patients undergoing hair transplantation surgery.
During the preoperative period, listening to music should
be recommended to the patients. e method may also
be considered for use in similar procedures.
Conicts of Interest: All authors declare that there are no
conicts of interest related to any aspect of this research.
Funding sources: is research project was nancially aided
through a grant provided by the Faculty of Medicine Siriraj
Hospital, Mahidol University, ailand (R016231035),
and it was facilitated by the Siriraj Integrated Perioperative
Geriatric Excellence Research Center.
REFERENCES
1. Sigdel S. Perioperative anxiety: a short review. Glob Anaesth
Perioper Med 2015;1:107-8.
2. Roomruangwong C, Tangwongchai S, Chokchainon A. Preoperative
anxiety among patients who were about to receive uterine
dilatation and curettage. J Med Assoc ai 2012;95:1344-51.
3. Jiwanmall M, Jiwanmall SA, Williams A, Kamakshi S, Sugirtharaj
L, Poornima K, et al. Preoperative Anxiety in Adult Patients
Undergoing Day Care Surgery: Prevalence and Associated
Factors. Indian J Psychol Med 2020;42:87-92.
4. Gan TJ. Poorly controlled postoperative pain: prevalence,
consequences, and prevention. J Pain Res 2017;10:2287-98.
5. Donaldson M, Gizzarelli G, Chanpong B. Oral sedation: a primer
on anxiolysis for the adult patient. Anesth Prog 2007;54:118-
29.
6. Bradt J, Dileo C, Shim M. Music interventions for preoperative
anxiety. Cochrane Database Syst Rev 2013;(6):CD006908.
7. Ju W, Ren L, Chen J, Du Y. Ecacy of relaxation therapy as
an eective nursing intervention for post-operative pain relief
in patients undergoing abdominal surgery: A systematic review
and meta-analysis. Exp er Med 2019;18:2909-16.
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
19
Original Article
SMJ
8. López-Cepero Andrada JM, Amaya Vidal A, Castro Aguilar-
Tablada T, García Reina I, Silva L, Ruiz Guinaldo A, et al.
Anxiety during the performance of colonoscopies: modication
using music therapy. Eur J Gastroenterol Hepatol 2004;16:
1381-6.
9. Varothai S, Bergfeld WF. Androgenetic alopecia: an evidence-
based treatment update. Am J Clin Dermatol 2014;15:217-30.
10. Ahmad M, Mohmand M. Anxiety and Hair Restoration Surgery.
e American Journal of Cosmetic Surgery 2021;38:71-4.
11. Matza LS, Morlock R, Sexton C, Malley K, Feltner D. Identifying
HAM-A cutos for mild, moderate, and severe generalized
anxiety disorder. Int J Methods Psychiatr Res 2010;19:223-32.
12. Julian LJ. Measures of anxiety: State-Trait Anxiety Inventory
(STAI), Beck Anxiety Inventory (BAI), and Hospital Anxiety and
Depression Scale-Anxiety (HADS-A). Arthritis Care Res
(Hoboken) 2011;63:S467-72.
13. Zsido AN, Teleki SA, Csokasi K, Rozsa S, Bandi SA. Development
of the short version of the spielberger state-trait anxiety inventory.
Psychiatry Res 2020;291:113223.
14. Techakomol W. Selected factors aecting self regulated learning
of secondary school students in Bangkok Metropolis [Master’
thesis]. Bangkok. (ailand): Chulalongkorn University; 1998.
15. Wongpakaran T, Wongpakaran N, Wannarit K. Validity and
reliability of the ai version of the Experiences of Close
Relationships-Revised questionnaire. Singapore Med J 2011;52:
100-6.
16. Vitasari P, Wahab MNA, Herawan T, Othman A, Sinnadurai SK.
Re-test of State Trait Anxiety Inventory (STAI) among Engineering
Students in Malaysia: Reliability and Validity tests. Procedia
Soc Behav Sci. 2011;15:3843-8.
17. Mimouni M, Abualhasan H, Mtanes K, Mazzawi F, Barak Y.
Patients’ Experience of Anxiety and Pain during Retrobulbar
Injections prior to Vitrectomy. J Ophthalmol 2019;2019:8098765.
18. Clark DM, Wells A. A cognitive model of social phobia. In:
Heimberg RG, Liebowitz MR, Hope DA, Schneier FR, editors.
Social Phobia: Diagnosis, assessment and treatment. New
York: Guilford Press; 1995. p. 69-93.
19. Liu F, Miao Y, Li X, Qu Q, Liu Y, Li K, et al. e relationship
between self-esteem and hair transplantation satisfaction in
male androgenetic alopecia patients. J Cosmet Dermatol 2018.
doi: 10.1111/jocd.12839.
20. Mohebi P, Rassman WR. Psychology of hair transplants.
International Society of Hair Restoration Surgery 2008;18:41-7.
21. Vachiramon V, Sobanko JF, Rattanaumpawan P, Miller CJ.
Music reduces patient anxiety during Mohs surgery: an open-
label randomized controlled trial. Dermatol Surg 2013;39:
298-305.
22. Sorensen EP, Gu H, Tabacchi M, Council ML. Music reduces
pain and anxiety associated with local anesthesia for dermatologic
procedures: A randomized controlled trial. J Am Acad Dermatol
2021;85:989-91.
23. Deivasigamani D, Sreedevi A, Sundar S, Balasundaram S,
Pragasam S. Evaluation of music interventions for anxiety
during dermatosurgery under local anesthesia. Int J Res Dermatol
2020;6:376-82.
24. Alam M, Roongpisuthipong W, Kim NA, Goyal A, Swary JH,
Brindise RT, et al. Utility of recorded guided imagery and
relaxing music in reducing patient pain and anxiety, and surgeon
anxiety, during cutaneous surgical procedures: A single-blinded
randomized controlled trial. J Am Acad Dermatol 2016;75:
585-9.
25. Emons WH, Habibović M, Pedersen SS. Prevalence of anxiety in
patients with an implantable cardioverter defibrillator:
measurement equivalence of the HADS-A and the STAI-S.
Qual Life Res 2019;28:3107-16.
26. Kerure AS, Patwardhan N. Complications in Hair Transplantation.
J Cutan Aesthet Surg 2018;11:182-9.
27. Kayikcioglu O, Bilgin S, Seymenoglu G, Deveci A. State and
Trait Anxiety Scores of Patients Receiving Intravitreal Injections.
Biomed Hub 2017;2:1-5.
28. Dhami L. Psychology of Hair Loss Patients and Importance
of Counseling. Indian J Plast Surg 2021;54:411-5.
29. Uğraş GA, Yıldırım G, Yüksel S, Öztürkçü Y, Kuzdere M, Öztekin
SD. e eect of dierent types of music on patients’ preoperative
anxiety: A randomized controlled trial. Complement er
Clin Pract 2018;31:158-63.
30. Cooke M, Chaboyer W, Schluter P, Hiratos M. e eect of
music on preoperative anxiety in day surgery. J Adv Nurs 2005;
52:47-55.
31. Kumar A, Dubey PK, Ranjan A. Assessment of Anxiety in Surgical
Patients: An Observational Study. Anesth Essays Res 2019;13:
503-8.
32. aut M. Neuropsychological processes in music perception and
their relevance in music therapy. In: R U, editor. Music erapy in
the Treatment of Adults with Mental Disorders New York:
Macmillan; 1990. p. 3-32.
33. Guzzetta C. Music therapy: nursing the music of the soul.
In: D C, editor. Music Physician for Times to Come. Illinois:
Quest Books; 1991. p. 146-66.
34. Ghafoor R, Ali SM, Patil A, Goldust M. Association of androgenetic
alopecia and severity of coronavirus disease 2019. J Cosmet
Dermatol 2022;21:874-9.
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
20
Riya Halder, MBBS*, Bobby Paul, MD (PSM), DCH**, Ankush Banerjee, MBBS, M.D.***, Ranjan Das, MD
(PSM)**,
Trina Sengupta, MBBS*
*MD Community Medicine, All India Institute of Hygiene and Public Health, Kolkata, West Bengal, India, **Department of Preventive and Social Medicine,
All India Institute of Hygiene and Public Health, Kolkata, West Bengal, India, ***All India Institute of Hygiene and Public Health, Kolkata, West Bengal, India.
Functional Status of the Elderly and their
Rehabilitation Needs: A Mixed-Method Study in
a Slum of Kolkata, West Bengal
ABSTRACT
Objective: A comprehensive understanding of the requirements of elderly is necessary to preserve their “functional
capacity”, an important indicator of their health status. is study aimed to assess the functional status of the elderly
and their rehabilitation needs.
Materials and Methods: A mixed-method study was conducted from November 2021 to June 2022 at a health centre
in Chetla, West Bengal, India. Quantitative data, collected from 172 elderly persons using a pretested questionnaire,
were analyzed by logistic regression analysis. Qualitative data, collected via focus group discussions, were analyzed
thematically.
Results: Overall, 11.62% and 66.86% participants were functionally dependent in one or more activities of daily
living (ADL) and instrumental activities of daily living (IADL), respectively. Signicant association of age ≥70 years
(AOR = 4.06, 95% CI= 1.13-14.63), male gender (AOR= 5.21, 95% CI= 1.57-17.28) and assistive device use (AOR=
6.92, 95% CI= 1.85-25.83) was found with ADL limitations. Increasing age (AOR= 1.29, 95% CI= 1.13-1.50), female
gender (AOR= 13.97, 95%CI= 3.61-54.00), residence in joint family (AOR= 3.95, 95%CI=1.47-10.61), without
spouse (AOR= 3.59, 95% CI= 1.12-11.44) and daily intake of multiple medications (AOR= 4.99, 95%CI= 1.45-
17.13) were factors signicantly associated with IADL limitations. Major identied needs of the elderly were related
to development of peer support groups, transportation systems and delivery of services from the health system.
Conclusion: Rehabilitative services like providing assistive devices to the needy, developing elderly support groups,
undertaking household visits for bedridden and those with restricted mobility, and building supportive environments
within families and communities should be ensured.
Keywords: Activities of daily living; elderly; functional status; instrumental activities of daily living; rehabilitation
(Siriraj Med J 2023; 75: 20-28)
Corresponding author: Trina Sengupta
E-mail: ghoto1995@gmail.com
Received 22 September 2022 Revised 27 October 2022 Accepted 4 December 2022
ORCID ID:http://orcid.org/0000-0003-4864-8159
http://dx.doi.org/ 10.33192/smj.v75i1.260526
All material is licensed under terms of
the Creative Commons Attribution 4.0
International (CC-BY-NC-ND 4.0)
license unless otherwise stated.
INTRODUCTION
e unprecedented increase in human longevity
in the 20
th
century has led to a global rise in the elderly
population. India is soon destined to become home to the
second-largest number of elderly persons in the world.
e Census data has demonstrated a steady increase in
the proportion of older people from 7.7% of the total
population in 2001 to 10.1% in 2021, which is estimated
to reach 300.96 million by 2051.
1
Over the past decade, ‘Healthy aging’ has emerged
as an important concept concerning health issues of the
elderly. It has been dened as “not only the mere absence
Halder et al.
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
21
Original Article
SMJ
of a disease but the process which enables older people to
continue to do the things that are important to them”.
2
Data provided by the United Nations has shown that
more than 46% of the global elderly population (≥60
years of age) live with disabilities.
3
Disabilities are the
negative aspects of the interaction between the individual
and the environment, i.e., decits, limitations in the
activity and restrictions in his/her social participation.
4
us, maintenance of functional capacity becomes an
important indicator of health status in the elderly.
5
Activities of daily living (ADL) are considered as those
activities that are essential for an independent life while
instrumental activities of daily living (IADL) are more
complex tasks that involve decision making and greater
interaction with the environment.
6
Studies conducted
previously across dierent countries have assessed the
functional capacity of the elderly and have demonstrated
varying prevalence of limitations in activities of daily living
(ADL) ranging from 17.3% to 34.6% while limitations
in instrumental activities of daily living (IADL) ranged
from 35.75% to 59.3%.
7-10
Although laudable eorts have
been made by the researchers for assessing the functional
status, the issue of social and healthcare needs of the
elderly required for healthy ageing has been largely
overlooked. erefore, a comprehensive understanding
of the requirements of our elderly population is needed
to preserve their functional capacity and promote healthy
aging so that they can continue to make their positive
contributions towards the society. With this backdrop,
this mixed method study was undertaken to assess the
functional status of the elderly residing in an urban slum
in West Bengal and to explore their unmet needs from
the health system for rehabilitation
MATERIALS AND METHODS
is cross-sectional study with convergent parallel
mixed method design (QUAN+QUAL) was conducted
from November 2021 to June 2022 among the elderly
persons (age≥60 years) attending the non-communicable
disease (NCD) clinic at Urban Health Unit and Training
Centre, Chetla, Kolkata, West Bengal. Participants who
did not give written informed consent were excluded
from the study.
Sampling
For the quantitative strand of the study, considering
the prevalence of ADL disability and IADL disability
among the study population to be 53.6%
11
and 48%
9
respectively and relative error of 20% with a condence
level of 95%, the sample size was calculated separately
using the standard Cochran’s formula.
12
It came to be
84 and 105 respectively. Taking into account the larger
value, that is 105, the nal sample size was estimated by
adding a design eect of 1.5 and 10% non-response rate
allowance which came to be 172.
Data collection was performed on 1 day per week.
So, for estimated sample size of 172, it took approximately
12 weeks for data collection. Study participants were
selected by systematic random sampling technique
for the quantitative strand. Approximately 30 elderly
persons attended the NCD clinic per day. Study piloting
revealed that only 15 patients could be interviewed per
day. erefore, taking sampling interval of 30/15= 2, every
2
nd
patient attending the NCD clinic was interviewed.
Separate days were taken to conduct Focus group
discussions (FGDs) for collecting data for the qualitative
strand of our study. Data was collected till the point of
data saturation which was reached aer conduction of
2 FGDs. Each FGD constituted 6 members who were
recruited purposively from the patients visiting the NCD
clinic.
Study Tools and Parameters Used
Medical records were checked and face-to-face
interview technique was performed using pre-tested,
pre-designed structured questionnaire to collect data
for the quantitative strand of our study. Pretesting was
done on 15 elderly patients diagnosed with NCDs in a
dierent setting who were not included in the study.
Reliability of the scales used within the questionnaire
was checked with Cronbach’s alpha along with inter-item
correlation. Face & construct validity of the scales used
was checked by public health experts. e questionnaire
consisted of the following domains:
(a) Independent variables
i. Socio-demographic variables: age, religion, caste, gender,
marital status, living arrangement, education, employment
status, nancial status, socioeconomic status, availability
of medical insurance
ii. Physical health status: body mass index (BMI), pain
on visual analog scale (VAS), number of chronic diseases
(from medical records), number of daily medicine intake
(from medical records)
iii. Environmental characteristics: presence of assistive
technology (handrails, grab bars, hearing aid, glasses, walker
wheelchair etc.), home modications (widened doors,
lowered cabinets) and material adjustments (removing
throw rugs, rearranging furniture etc.)
iv. Multidimensional scale of perceived social support
(MSPSS): It was assessed via a 12-item tool for measuring
perceptions of support from 3 sources: family, friends,
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
22
and signicant others. [Cronbach’s alpha= 0.87].
13
A
mean score of 1-2.9 meant low support, 3-5 indicated
moderate support and 5.1-7 indicated high support.
v. Geriatric depression scale 15 (GDS 15) consisted of
a 15-item preliminary screening tool for depression in
elderly [Cronbach’s alpha= 0.71].
14
Scores of 0-4 were
considered normal, 5-8 indicated mild depression; 9-11
as moderate depression; and 12-15 indicated severe
depression.
(b) Dependent variable
i. Katz Index of Independence in Activities of Daily Living
(ADL): It assessed the client’s ability to independently
perform six activities of daily living i.e bathing, dressing,
toileting, transferring, continence, and feeding.
15
Participants
were given 1 point if they required no assistance in
performing their daily activities and 0 point if they
required help, personal assistance or total care for the
same. (Cronbach’s alpha=0.79). Study participants were
categorized into two groups according to their summary
scores:
1. Independent (score of 6, needed no assistance
in any of the activities)
2. Dependent (score 0-5, assistance needed in some
or the other activity)
ii. Lawton- Brody Instrumental Activities of Daily Living
Scale (IADL): It measured the client’s ability to perform
independent living skills, measured across 8 domains.
16
Women were scored on all 8 areas of function; whereas,
for men, the areas of food preparation, housekeeping,
laundering were excluded [Cronbach’s alpha= 0.82].
Participants were given 1 point if they required no
assistance in performing the activities and 0 point if
they required help, personal assistance or total care for
the same. Study participants were categorized into two
groups according to their summary scores:
For females: 1. Independent (score of 8, needed no
assistance in any of the activities)
2. Dependent (score of 0-7, assistance
needed in some or the other activity)
For males: 1. Independent (score of 5, needs no
assistance in any of the activities)
2. Dependent (score 0-4, assistance needed in some
or the other activity)
For the qualitative part of the study, two FGDs were
conducted among the study participants to nd out their
expectations from the health system with respect to their
healthcare needs, using a predesigned FGD guide, audio
recorder and eld notes.
Data analysis
Quantitative data was analysed using Microso
Excel 2016 and Statistical Package for Social Sciences
soware (version 16). Descriptive statistics were shown
by frequency table, mean, median and interquartile range.
Aer excluding multicollinearity (variance ination
factor>10), factors were analyzed by test of signicance
(p-value< 0.05) at 95% condence interval via univariate
regression model. All the biologically plausible signicant
factors in the respective univariate analysis where then
included in the nal multivariable model.
For qualitative data, thematic analysis approach
was undertaken. e recorded statements from the FGD
were rst transcribed in verbatim format and translated
back to English language. Simultaneously, eld notes
were reviewed. Appropriate codes were then generated
from the transcripts. Similar codes were put together
to generate subthemes followed by the generation of
appropriate themes.
Ethical approval
Permission was taken from Institutional Ethics
Committee of All India institute of Hygiene and Public
Health, Kolkata. All the ethical principles as per Declaration
of Helsinki were strictly adhered to. Informed written
consent was taken from each participant before data
collection. Condentiality was maintained throughout
the process.
RESULTS
Among the 172 study participants, 118 were females
and 54 were males with a median age of 62.50 years
(IQR =61.00- 67.75). Majority of the male participants
were married (81.5%) whereas only 36.4% females were
married. Around 30.8% of the participants had two
children. 47.1% of elderly were living with ‘spouse and
other members’. Almost 55.2% of the participants had
no formal education and considered themselves to be
nancially dependent on their family members. Around
one-fourth (25.6%) of the study participants were formally
retired. More than half (60.5%) of the study participants
belonged to class V of B.G Prasad’s socioeconomic scale.
e median per capita income was Rs 1,000/-. More than
half of the participants (52.3%) were covered under
state government nanced medical insurance schemes
like ‘Swasthya Sathi’.
With regard to their health status, as many as 56.9%
of individuals suered from multiple chronic diseases
and 55.8% were taking multiple medicines daily. Around
44.8% individuals reported to be suering from moderate
pain on Visual Analogue Scale (VAS).
On the part of environmental modications, only 0.6%
and 5.8% of participants had special equipment attached
to their home structure and did material adjustments
Halder et al.
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
23
Original Article
SMJ
respectively, for unhindered movement. Assistive devices
were used by 24.4% of the elderly. None of the participants
had the interior of their homes modied as per their
necessity of old age.
Almost 65.7% of the elderly received moderate
social support (friends, family and signicant other
combined) with median score of 4(IQR= 3.44-5.04).
Majority (82.6%) of study participants were suering
from some or other form of depression with a median
score of 6(IQR= 5-9) as measured by GDS 15.
Functional Status of the elderly:
e respondents reported at least one problem with
IADL (66.86 %) more frequently than with ADL (11.62
%). Among the female participants 7.6% and among
males 20.4% were dependent in one or more ADL while
80.5% of females and 37% of males were found to be one
or more IADL (Fig 1 & 2).
e most frequent problem in ADL was related to
transferring (6.4%) followed by continence (4.7%) and
toileting (4.7%). e most frequent problem associated
with IADL was food preparation (61.9%) among the
females and shopping in males (52.3%).
Factors associated with functional limitations among
the study participants
Signicant factors associated with functional limitations
in ADL were age of ≥70 years {Adjusted odds ratio (AOR)
= 4.06, 95% CI= 1.13-14.63}, male gender (AOR= 5.21,
95% CI= 1.57-17.28) and use of assistive devices (AOR=
6.92, 95% CI= 1.85-25.83) (Table 1).
With respect to IADL limitations, increasing age
(AOR= 1.29, 95% CI= 1.13-1.50), female gender (AOR=
13.97, 95% CI= 3.61-54.00), participants residing in
joint family (AOR= 3.95, 95% CI= 1.47-10.61) without
spouse (AOR= 3.59, 95% CI= 1.12-11.44) and taking
multiple medicines daily (AOR= 4.99, 95% CI= 1.45-17.13)
were the factors that came to be statistically signicant
(Table 2).
e models examining the inuences of factors on
ADL and IADL explained 16.6%-32.3% and 39.7%-55.1%
of the variance respectively.
4( 4.1%)
5 (25.0%)
75 (76.5%)
20 (100.0%)
0
10
20
30
40
50
60
70
80
<70 yrs ≥70 yrs
Number of females
Age groups
Dependent in ≥1 ADL Dependent in ≥1 IADL
5 (11.9%)
6 (50.0%)
10 (23.8%) 10 (83.3%)
0
2
4
6
8
10
12
<70 yrs ≥70 yrs
Number of males
Age groups
Dependent in ≥1 ADL Dependent in ≥1 IADL
Fig 1. Multiple bar diagram showing
functional status of female participants
across age groups (n=118).
Fig 2. Multiple bar diagram showing
functional status of male participants across
age groups (n=54).
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
24
TABLE 1. Factors associated with functional limitation in ADL among study participants: Univariate and
Multivariable logistic regression analysis (n=172).
Parameters Total number Dependent in Unadjusted OR Adjusted OR
(n) ≥1 ADL (%) (95% CI) (95% CI)
Age
<70 yrs 140 9(6.4) 1(Ref) 1(Ref)
≥70 yrs 32 11(34.4) 7.62(2.82-20.60) 4.06(1.13-14.63)
Gender
Female 118 9(7.6) 1(Ref) 1(Ref)
Male 54 11(20.4) 3.09(1.19-8.00) 5.21(1.57-17.28)
Number of chronic diseases
<2 74 4(5.4) 1(Ref) 1(Ref)
≥2 98 16(16.3) 3.41(1.09-10.68) 0.57(0.09-3.61)
Number of medicines taking daily
<2 76 4(5.3) 1(Ref) 1(Ref)
≥2 96 16(16.7) 3.60(1.15-11.26) 3.04(0.52-17.83)
Use of assistive devices (hearing aid, wheelchair, walker etc)
Absent 130 8(6.2) 1(Ref) 1(Ref)
Present 42 12(28.6) 6.10(2.29-16.24) 6.92(1.85-25.83)
Material adjustments at residence (removing through rugs, rearranging furniture, adjusted lighting etc.)
Absent 162 16(9.9) 1(Ref) 1(Ref)
Present 10 4(40.0) 6.08(1.55-23.85) 0.81(0.12-5.35)
Hosmer-Lemeshow test statistic=0.669, Cox and Snell’s R
2
=0.166, and Nagelkerke’s R
2
=0.323.
Qualitative exploration of the unmet needs of the
elderly from the health system for rehabilitation
e FGDs revealed three major themes: (I) need to
cater to service issues (II) need to cater to transportation
issues (III) need for development of peer support group.
Under the rst theme the major sub themes identied
were ‘Homebased services’, ‘Supplies and logistics’, ‘Social
protection schemes’ and ‘Other health services’.
Under the ‘Homebased services’ subtheme, the
need for domiciliary visits at least once every month
by trained healthcare workers for routine health check-
ups was identied. In this context P4 (60 years, female)
reiterated:
“If it was possible that once or twice in a month
the health workers come and visit us in our house and
do a checkup of our sugar, pressure it would have been
very very helpful.”
e major ‘Supplies and logistics’ need identied
was ensuring the availability of medicines and assistive
devices such as glasses, hearing aids etc. from the health
centre, better if free of cost. P3 (61 years, female) said
in this regard:
“Sometimes they ask us to buy medicines from
outside but we cannot buy them due to our economic
constraint. So, we miss the dose for that month.”
Under the ‘Social protection schemes’, the need
for old age pension, increase in pension amount, and
health insurance schemes were identied. P2 (62 years,
female) said in this respect:
“I get old age pension of ₹1,000 per month. But
you tell me, in these days does ₹1,000 have any value?”
e study participants also highlighted the need
for provision of ‘Other health services’ such as dental
facility, ophthalmology, psychiatry, otorhinolaryngology
and investigations such as thyroid prole from the PHC.
P1 (64 years, male) & P2 said in this regard:
“I hear less in one ear. If facility for ear check-up
was present over here I would go for the same.”
Halder et al.
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
25
Original Article
SMJ
TABLE 2. Factors associated with functional limitation in IADL among study participants: Univariate and
Multivariable logistic regression analysis (n=172).
Parameters Total number Dependent in Unadjusted OR Adjusted OR
(n) ≥1 IADL (%) (95% CI) (95% CI)
Age(↑)* 1.14(1.05-1.24) 1.29(1.13-1.50)
Gender
Female 118 95(80.5) 7.20(3.43-14.36) 13.97(3.61-54.00)
Male 54 20(37.0) 1(Ref) 1(Ref)
Type of family
Joint 99 78(78.8) 3.61(1.85-7.03) 3.95(1.47-10.61)
Nuclear 73 37(50.7) 1(Ref) 1(Ref)
Marital Status
No spouse 83 70(84.3) 5.26(2.55-10.85) 3.59(1.12-11.44)
Married 89 45(50.6) 1(Ref) 1(Ref)
Education
No formal education 95 70(73.7) 2.06(1.07-3.96) 0.79(0.28-2.17)
Educated (any form) 73 42(57.5) 1(Ref) 1(Ref)
Socioeconomic status †
Class V 104 83(79.8) 4.44(2.26-8.73) 0.87(0.31-2.41)
Class IV & below 68 32(47.1) 1(Ref) 1(Ref)
Pain
Severe pain 27 24(88.9) 4.74(1.36-16.51) 5.56(0.93-33.18)
Less than severe pain 145 91(62.8) 1(Ref) 1(Ref)
Number of chronic diseases
≥2 98 73(74.5) 2.22(1.16-4.24) 0.60(0.16-2.23)
<2 74 42(56.8) 1(Ref) 1(Ref)
Number of medicines taking daily
≥2 96 75(78.1) 3.21(1.66-6.22) 4.99(1.45-17.13)
<2 76 40(52.6) 1(Ref) 1(Ref)
Multidimensional scale of perceived social support
Lower support 131 96(73.3) 3.17(1.53-6.56) 0.71(0.23-2.11)
High support 41 19(46.3) 1(Ref) 1(Ref)
Hosmer-Lemeshow test statistic=0.095, Cox and Snell’s R
2
=0.397, and Nagelkerke’s R
2
=0.551.
*Continuous variables, OR=odds ratio, CI=condence interval
† According to Revised B.G Prasad Scale for January 2021 based on labour bureau statistics of November 2020
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
26
“I have pain in my gums and teeth but no dental
facility is available here”.
Under the second theme, the distant location of
tertiary care hospitals, poor access to accessible, comfortable
and reliable transport services were reported to cause
hindrance to patients’ journey to hospitals for specialized
care. Notable verbatim by P7 (61 years, female) in this
aspect is:
“Sometimes we are said to go to specialized hospitals
since all the treatment is not available here. But our old
age and restricted mobility prevent us from going there
and getting better treatment”
e third theme highlighted the ‘need for development
of peer support groups’. e elderly valued peer support
as an important source of happiness, information and
companionship as stated by P8 (65 years, male):
“It feels good to talk among your friends and relieve
your mental burden. You can hear their side of their
stories as well as you can express your concerns.”
DISCUSSION
e study ndings revealed the overall prevalence
of ADL and IADL limitations among the elderly to be
11.62% and 66.86% respectively, which is comparable to
the ndings from other studies. A study done in Nepal
by Chalise et al.
18
showed around 30% & 52% elderly
aged 65 yrs and older were having functional limitation
on at least one ADL and IADL respectively. In a study
done in India by Patel et al. 22% & 48% of the older
adults reported some form of ADL and IADL disability
respectively.
9
Increasing age showed signicant association with
functional limitations, both ADL and IADL in elderly
proving that it can be the most important risk factor for
the deterioration of the functional state in the elderly.
e current study showed that males were more
dependent in ADL than females which is in contrast
to other studies that showed female gender to be more
predisposed to functional limitations in ADL.
7,19,20
is
may be attributed to the fact that there were more older
male participants (22.2%) compared to females (6.9%)
in this study.
With respect to IADL limitations and gender dierences,
this study is in line with ndings from other studies that
showed that female elderly are signicantly more dependent
in one or more IADL.
7,19,20
is can be explained by the
fact that in an Indian society, which is predominantly
male dominated, women are traditionally bound to do
household work whereas their male counterparts do work
outside and are mainly responsible to handle nances.
Participants residing in joint family reported to have
more dependency in IADL in our study. is nding
substantiates the fact that those who live with others
have the opportunity to depend on them for shopping,
food preparation, housekeeping etc., than those who
live alone.
Signicant association between functional limitation
of IADL and absence of spouse can be explained by the
fact that loss of signicant other in the extreme of age
has a huge emotional impact on the surviving elderly to
the extent that it can lead to depression. Many previous
studies have also found a positive correlation between
depression and worsened mobility in elderly.
21,22
As disability and mobility problems increase with
age, use of assistive devices such as canes, crutches, and
walkers, increase a patient’s base of support, improves
balance, increased activity and independence, proving that
signicant association between functional dependency
in ADL and assistive device use among the elderly may
exist, as found in our study.
Signicant association between dependency in IADL
and intake of multiple medicines has been found in our
study which can be ascribed to the fact that advancing age
brings increased number of comorbidities and thereby
increasing number of daily medicines intake.
e ndings from the qualitative part of our study
also substantiates our quantitative ndings (Table 3).
Subjective needs assessment is required for addressing
the complexity of needs of dependent older people. Due
to limitations in mobility and economic constraints, older
people cannot access health facilities located far away
from home or buy medicines from outside. ere is a
paramount need for provision of various rehabilitative
and healthcare services like home visits, ensuring all-
time supply of medicines and logistics, service delivery
nearer to homes, easy availability and accessibility of
social protection schemes and development of peer
support groups.
CONCLUSION
is study revealed that emotional health is as
important as physical health of the elderly. With advancing
age there is not only an increasing limitation in the
functional capacity of the elderly but also an increasing
requirement of meaningful relationships and experiences.
Declining agility and unsteadiness may result in falls
and devastating injuries among the aged population.
Similarly feeling of loneliness, isolation and lack of self-
worth may result in depression among elderly. Health
care administrators and policy makers should take into
note the physical and emotional needs of the elderly
while implementing strategies for their rehabilitation.
Halder et al.
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
27
Original Article
SMJ
TABLE 3. Joint Display of health care needs of elderly with respect to their functional status.
Themes Sub themes Qualitative results (Codes) Quantitative results
Service issues Need for home domiciliary visits by health 11.62% & 66.86% elderly are
based services workers for health check up dependent in ADL & IADL
respectively, hindering their regular
visit to health centre.
15.7% participants reported severe
body pain
Need for supplies ensure availability of 56.9% and 55.8% participants
and logistics medicines, insulin supply, respectively, were having ≥2
supply of hearing aids, chronic diseases and taking ≥2
glasses, cane medications daily.
24.4% elderly required assistive
devices in their daily activities.
Need for Social provision of government More than half of the study
Protection health insurance scheme, participants (55.2%) were nancially
Schemes (SPS) increment in amount of old age dependent and belonged
pension schemes, nancial to lower socio-economic group
dependence on children (60.5%).
47.7% were not covered by any
medical insurance.
Other services dental facility, psychiatry, 17.4% elderly had visual
Eye and ENT doctors, impairment, 6.4% had impaired
thyroid prole test hearing, 1.2% had dental problems,
1.2% had thyroid disorder.
Transportation inconvenient and distant 11.6% were found to be dependent
issues location of tertiary care hospitals on ‘mode of transportation’ item of
providing specialized care and Lawton Brody IADL Scale.
treatment
Peer support isolation & neglect of family, 82.6% suffered from some form of
groups loss of spouse, feeling of burden depression in GDS 15 scale
on children, no one to share 8.7% participants reported to have
emotional feelings low social support in MSPSS scale.
Tailor-made interventions are the need of the hour for
holistically addressing the rehabilitative needs- both
physical and emotional, of our elderly. Availability of
various services such as mental health clinics, dental
clinics, ophthalmology and otorhinolaryngology services
etc, provision of assistive devices to the needy, developing
elderly support groups, undertaking household visits for
bedridden elderly, counseling about improved care-seeking,
and increasing supportive environment in families and
community should be ensured at the primary care level.
Limitations
is study was done in an outpatient clinic and
hence elderly who are bedridden, too sick to attend OPD
could not be interviewed. While most of the responses
were recall-based, bias might be possible.
Conict of interest : Nil
Funding: Nil
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
28
REFERENCES
1. Training Manual on Elderly Care for Medical Ocer at Ayushman
Bharat – Health and Wellness Centres. Ministry of Health
& Family Welfare. Government of India. Available from:
https://nhsrcindia.org/
2. Ageing and health [Internet]. [cited 2022 Jan 15]. Available
from: https://www.who.int/news-room/fact-sheets/detail/
ageing-and-health
3. Ageing and disability | United Nations Enable [Internet]. [cited
2022 Jan 15]. Available from: https://www.un.org/development/
desa/disabilities/disability-and-ageing.html
4. International Classication of Functioning, Disability and
Health (ICF) [Internet]. [cited 2022 Jan 15]. Available from: https://
www.who.int/standards/classications/international-classication-
of-functioning-disability-and-health
5. Stuck AE, Walthert JM, Nikolaus T, Büla CJ, Hohmann C,
Beck JC. Risk factors for functional status decline in community-
living elderly people: a systematic literature review. Soc Sci
Med [Internet]. 1999 [cited 2022 Jan 15];48(4):445-69. Available
from: https://pubmed.ncbi.nlm.nih.gov/10075171/
6. Judge JO, Schechtman K, Cress E. e relationship between
physical performance measures and independence in instrumental
activities of daily living. e FICSIT Group. Frailty and Injury:
Cooperative Studies of Intervention Trials. J Am Geriatr Soc
[Internet]. 1996 [cited 2022 Jan 15];44(11):1332-41. Available
from: https://pubmed.ncbi.nlm.nih.gov/8909349/
7. Millán-Calenti JC, Tubío J, Pita-Fernández S, González-Abraldes I,
Lorenzo T, Fernández-Arruty T, et al. Prevalence of functional
disability in activities of daily living (ADL), instrumental
activities of daily living (IADL) and associated factors, as
predictors of morbidity and mortality. Arch Gerontol Geriatr.
2010;50(3):306-10.
8. Ćwirlej-Sozańska A, Wiśniowska-Szurlej A, Wilmowska-
Pietruszyńska A, Sozański B. Determinants of ADL and IADL
disability in older adults in southeastern Poland. Available
from: https://doi.org/10.1186/s12877-019-1319-4
9. Patel R. Prevalence and Determinants of Activity of Daily Living
and Instrumental Activity of Daily Living Among Elderly
in India. 2021 [cited 2021 Nov 24]; Available from: https://
doi.org/10.21203/rs.3.rs-523499/v1
10. Burman J, Sembiah S, Dasgupta A, Paul B, Pawar N, Roy A.
Assessment of Poor Functional Status and its Predictors among
the Elderly in a Rural Area of West Bengal. J Midlife Health
[Internet]. 2019 Jul 1 [cited 2021 Jun 6];10(3):123-30. Available
from: http://www.ncbi.nlm.nih.gov/pubmed/31579173
11. Keshari P, Shankar H.Prevalence and spectrum of functional
disability of urban elderly subjects: A community-based study
from Central India. J Fam Community Med 2017;24:86-
90. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/
PMC5426108/pdf/JFCM-24-86.pdf
12. Saha I, Paul B. Essentials of Biostatistics & Research Methodology.
3
rd
ed. Kolkata: Academic Publishers, 2020.p.86-114.
13. Zimet G. Multidimensional scale of perceived social support
(MSPSS)-scale items and scoring information. Johns Hopkins
Univ Press [Internet]. 2016;(December):50-52. Available from:
https://openscholarship.wustl.edu/bsltests/2977
14. Courses O. Geriatric Depression Scale (GDS) Short Form.
Clin Gerontol. 1986;5(1):5-6.
15. Wallace M. Katz Index of Independence in Activities of Daily
Living (ADL) [Internet]. [cited 2021 Jun 3]. Available from:
www.ConsultGeriRN.org.
16. Lawton MP, Brody EM. Assessment of older people: Self-
maintaining and instrumental activities of daily living. Gerontologist
[Internet]. 1969 [cited 2022 Jan 16];9(3):179-86. Available
from: /record/2011-21299-001
17. Majhi MM, Bhatnagar N. Updated B. G Prasad’s classication
for the year 2021: consideration for new base year 2016. J Family
Med Prim Care. 2021[cited 2022 Apr 17];10(11):4318-9. Available
from: https://pubmed.ncbi.nlm.nih.gov/35136812/
18. Chalise HN, Khanal B. Functional Disability on Instrumental/
Activities of Daily Livings Among Rural Older People in Nepal.
J Karnali Acad Heal Sci [Internet]. 2020;3(3):1-6. Available
from: http://jkahs.org.np/jkahs/index.php/jkahs/article/view/338
19. Nagarkar A, Kashikar Y. Predictors of functional disability
with focus on activities of daily living: A community based
follow-up study in older adults in India. Arch Gerontol Geriatr
[Internet]. 2017 Mar 1 [cited 2022 Jan 22];69:151-5. Available
from: https://pubmed.ncbi.nlm.nih.gov/27936458/
20. Veerapu N, A. PB, P. S, G. A. Functional dependence among
elderly people in a rural community of Andhra Pradesh, South
India. Int J Community Med Public Heal [Internet]. 2016 Dec
28 [cited 2022 Jan 22];3(7):1835-40. Available from: https://
www.ijcmph.com/index.php/ijcmph/article/view/319
21. Hung Y-C, Chen Y-H, Lee M-C, Yeh C-J. Eect of Spousal
Loss on Depression in Older Adults: Impacts of Time Passing,
Living Arrangement, and Spouse’s Health Status before Death.
Int J Environ Res Public Health [Internet]. 2021 Dec 10 [cited
2022 Jan 22];18(24):13032. Available from: https://pubmed.
ncbi.nlm.nih.gov/34948641/
22. Das A. Spousal loss and health in late life: moving beyond
emotional trauma. J Aging Health [Internet]. 2013 Mar [cited
2022 Jan 22];25(2):221-42. Available from: https://pubmed.
ncbi.nlm.nih.gov/23271727/
Halder et al.
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
29
Original Article
SMJ
Nuttapol Watcharasirikul, B.ATM.*, Manmas Vannabhum, B.ATM., Ph.D.*, Rungsima Yamthed M.Sc.**,
Tanida Srikhlo B.Sc.**,
Pravit Akarasereenont, M.D., Ph.D.*, Kamontip Harnphadungkit, M.D.**
*Center of Applied ai Traditional Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, ailand, **Department of
Rehabilitation Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, ailand.
Comparative Effectiveness of Court-Type Thai
Traditional Massage and Ultrasound Therapy in
Patients with Neck Pain: A Randomized Controlled
Trial
ABSTRACT
Objective: Neck pain is a common problem. Lomplaipattakad Sanyan-4-Lang (LPP-S4L) disease is a frequent cause
of neck pain in ai traditional medicine. ai traditional medicine recommends treating neck pain with court-type
ai traditional massage (CTTM). Meanwhile, in conventional medicine, ultrasound modality (US) is used to treat
neck discomfort. However, there is no scientic evidence if CTTM has potential analgesic advantages on LPP-S4L
compared to ultrasound therapy. e study aims to evaluate the ecacy of CTTM compared to US and nd body
elements of participants based on aspects of ai traditional medicine.
Materials and Methods: Sixty-six participants were diagnosed with LPP-S4L, with a numerical rating scale (NRS)
≥ 4. Patients were randomly assigned to one of two groups (33 per group). Participants underwent CTTM or US
therapy eight times in total (twice a week). Pain intensity, pressure pain threshold, Range of motion (ROM), quality
of life, and a body element questionnaire were used to assess patients.
Results: Both treatments showed a signicant reduction in pain intensity, increase in pain threshold, increase in
ROM, and improvement in quality of life in patients with LPP-S4L. e current study found that CTTM is more
eective than US in most parameters, except Quality of life (QoL). Moreover, a decrease in pain intensity is related
body elements, which indicates the inuence of CTTM, or mostly the re element.
Conclusion: We recommend employing CTTM, an alternative therapy, to treat patients with neck pain caused by
LPP-S4L disease.
e trial was registered at thaiclinicaltrials.org (number: TCTR20211004008).
Keywords: Musculoskeletal pain; myofascial pain syndrome; ai traditional medicine; massage; ultrasound therapy;
body elements (Siriraj Med J 2023; 75: 29-37)
Corresponding author: Kamontip Harnphadungkit
E-mail: kamontip.har@gmail.com
Received 22 September 2022 Revised 27 October 2022 Accepted 4 December 2022
ORCID ID:http://orcid.org/0000-0003-3101-8804
http://dx.doi.org/ 10.33192/smj.v75i1.260527
All material is licensed under terms of
the Creative Commons Attribution 4.0
International (CC-BY-NC-ND 4.0)
license unless otherwise stated.
INTRODUCTION
Neck pain is a problem that aects both individuals
and families, the healthcare system, and organizations.
1
e prevalence of neck pain in adults is signicant, with
the problem aecting up to 75% of the global population.
1,2
Neck pain is a type of discomfort that originates at the
posterior of the neck and extends to the head, scapula,
shoulder, trunk, and upper limbs.
3
Pain usually lasts more
than three months and is commonly characterized by
hyperalgesia in the skin, ligaments, and muscle palpations,
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
30
as well as a limitation of the range of motion (ROM) of
the neck and shoulder joints.
4
A variety of risk factors
are thought to play a role in the development of neck
pain. ese risk factors can be divided into three main
categories: physical, psychosocial, and individual-related
risk factors. Although physical risk factors for neck pain
are generally emphasized, psychosocial risk factors appear
to play a more important role in the development of
neck pain. In fact, neck pain is associated with multiple
psychological risk factors such as having a demanding
job, poor social support, and low job security.
4
is
can also aect the quality of life.
5
In ailand, a study
reported a signicant prevalence of neck pain in both
adults and teenagers, with the main causes being poor
body posture and stress.
6
Neck pain is also a prevalent condition in individuals
with musculoskeletal pain, according to traditional medicine,
especially ai traditional medicine where the condition
is known as Lomplaipattakad Sanyan 4 Lang (LPP-
S4L) disease. Lomplaipattakad are diseases caused by a
defect in the wind element in the body while Sanyan 4
Lang denes the location of disease. When combined,
LPP-S4L is a muscular discomfort of the posterior neck
region, with a painful spot and muscle tightness above
the 7
th
cervical vertebra (C7). e discomfort might
be perceived in the scapula region, the anterior chest
wall, and the upper limbs. erefore, the practitioner
must carry out a physical examination to assess range
of motion (ROM) of the neck and palpation.
LPP-S4L is also frequently associated with neck
myofascial pain syndrome (MPS). e ai traditional
medicine practice guidelines for neck pain recommend
massage, hot herbal compression
7
, or combination
treatment.
8
ai massage, also known as Nuad ai
in ailand, has various styles. It is classied based on
characteristics and the goal of the massage. e court-
type ai traditional massage (CTTM) is typically used
for therapeutic purposes, while the general type is used
for relaxation.
9,10
CTTM focuses on rehabilitation and
treatment of musculoskeletal complaints and disorders.
Its technique relies on the application of pressure on
muscles with thumbs or palms, with a goal to reduce
muscular tension, joint stiness, and pain.
9
e principal
focus of CTTM is major signal points (MaSPs) since
anatomical examinations of each MaSP have shown that
the majority of points are linked to muscles connected
to branches of arteries and nerves. e eectiveness
of CTTM therapy is the result of eective massage of
MaSPs.
11,12
Massage has proven to have an impact on the
musculoskeletal system, nervous system, cardiovascular
system, and the mind. Several previous CTTM studies
have revealed that a massage results in a rise of skin
temperature and blood ow rate, indicating that it targets
both local and systemic circulation.
13
Meanwhile, other
studies show that each CTTM massage session should
last between 30 and 60 minutes to relieve neck pain.
14-20
CTTM reduces pain intensity in the upper trapezius MPS
more than topical diclofenac.
14, 15
Furthermore, CTTM
also reduces the pain score and improves pain threshold
in patients with chronic myofascial pain syndrome. It
has also been suggested that CTTM be used with Ruesi
dad ton (hermit doing body contortion) exercise to
increase neck and shoulder joint ROM.
16
Last but not
least, CTTM alleviates discomfort and reduces the need
for medication in chronic headaches.
17-20
In conventional medicine, most MPS patients receive
various therapies
21
, including medicine, ultrasound
22
,
acupuncture
23
, stretching exercises
24
, and massage.
15,16,25
One of the most common therapies is ultrasound (US),
which uses high frequency acoustic vibrations convert to
heat at the tissue level.
26
e thermal and non-thermal
eects of US increase muscle ber, tendons, ligaments,
and joint capsule exibility, and in the process reduce pain
intensity and joint stiness.
27
In a previous clinical study,
US was able to rapidly reduce trigger point stiness in the
upper trapezius muscle in the US treatment group.
22
One
study found that combining US, massage, and exercise
for treatment of myofascial pain was not dier from a
sham-US group combining massage and exercise.
28
However,
there is no scientic clinical trial data to demonstrate
that CTTM has potential analgesic eects on LPP-S4L
compared to US.
e aim of this study was to compare the ecacy of
CTTM and US on pain reduction in patients with LPP-S4L
by measuring pain intensity, neck ROM, pressure pain
threshold, and quality of life aer 4-weeks of treatment.
e secondary objective was to discover a relationship
between body elements, based on ai traditional medicine,
and pain severity. We hypothesized that CTTM would
provide more pain relief than US in LPP-S4L disease.
MATERIALS AND METHODS
Subjects were recruited between May 2019 and
November 2020 at the Ayurved Clinic and Rehabilitation
Center, Faculty of Medicine Siriraj Hospital. All study
participants were randomized by computerized block
randomization. ere were 33 per group. e research
was approved by the ethical committee of the Faculty
of Medicine Siriraj Hospital (COA no. Si 648/2018).
e inclusion criteria was participants aged between
18-60 with chronic neck pain, and moderate to severe
pain intensity (NRS ≥ 4). All subjects were screened and
Watcharasirikul et al.
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
31
Original Article
SMJ
diagnosed for LPP-S4L by a licensed ai Traditional
medicine practitioner with over 10 years clinical experience.
Participants were excluded if they met the following
criteria: open wound on the neck and related areas,
fever with temperature over 38.5°C, history of trauma
or surgery involving bones of the neck, shoulder and/or
back, inammatory arthritis, neuropathic pain, pregnant,
uncontrolled hypertension (BP>140/90mmHg), use of
medication such as analgesics or muscle relaxants within
one week of the experiment. Researcher enrolled and
assigned participants aer signed inform consent.
Court-type ai traditional massage (CTTM)
Five licensed ai traditional medicine massage
therapists with at least 10 years of clinical experience
massaged patients in this study. ey were trained using
the same massage protocol.
17,48
e massage therapists
were in a standing position while patients were in the
sitting position during massage. CTTM therapy was
carried out for 30 minutes per session, twice a week for
a total of four weeks as per standard protocol in clinical
practice guideline. CTTM starts as a basic massage of the
shoulder, neck and pressure on major signal points on
both sides. e treatment targets the trapezius muscle,
levator scapulae muscle, splenius muscle and suboccipital
muscle. e therapists were randomized for each round
of treatment (Fig 1).
weeks following the standard protocol as per clinical
practice guidelines. The treatment area covered the
common source of neck pain such as trapezius, levator
scapulae, splenius and suboccipital muscles (Fig 1).
Outcome measurement
Pain intensity
Pain intensity was measured by the numerical rating
scale (NRS). Participants self-assessed pain intensity
using a numerical rating scale (0-10). During the study,
an assistant researcher inquired about the pain before
and aer treatment (eight visits). A score of 0 meant no
discomfort while 10 indicated maximum pain.
Pressure pain threshold (PPT)
Algometry is a method to measure pain sensitivity.
is study used pressure algometry (Algomed algometry,
Compass medical technologies, Inc. Medoc advance
medical system, U.S.). e PPT was evaluated on the
trigger point or the most hard tendon in the upper
trapezius muscle which was the major diagnosis area of
LPP-S4L. An assistant researcher put algometry force
(kg/cm
2
) slowly on the point until the participant pressed
a button on the algometer response unit to stop the
pressure. Data from the same area was collected an
average of two times or before and aer of treatment.
Range of Motion (ROM)
Two assistant researchers underwent a training
session for measuring the ROM of the neck, including
exion, extension, lateral exion and rotation of both
sides using a goniometer. e ROM was collected before
and aer treatment during the study (eight visits).
Quality of life (SF-36)
SF-36 (short form 36) is a health survey questionnaire
that assesses quality of life. SF-36 has thirty-six questions
covering eight important points of quality of life, including
physical function, role-physical, bodily pain, general
health, vitality, social function, role-emotional and
mental health. SF-36 is administered before and aer
the last treatment. is study used SF-36 version 2 (ai
version).
29
Percentage usage of rescue drug
Each participant received 20 tablets of 500mg
acetaminophen (paracetamol). They were asked to
state the remaining in each visit.
Dominant body element questionnaire
Participants were evaluated using the dominant
Fig 1. Treatment area.
Ultrasound treatment (US)
Two licensed physical therapists with 10 years of
clinical experience underwent training sessions for this
study. Ultrasound treatment was set at an intensity of 0.8
W/cm
2
and the frequency was 1 Mhz. Physical therapists
were also in the standing position while patients were in
the sitting position. Ultrasound treatment was carried
out for 10 minutes in each session, twice a week for four
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
32
body element questionnaire
30
in their rst visit. e
body element questionnaire determines innate body
elements and present body elements of participants.
e innate body elements, including re, wind, water
and earth were obtained by birth month. Meanwhile,
present body elements, including Pitta, Vata, Semha, and
mixed elements were obtained from 33 questionnaire
items. e present body element can be indicated by a
higher percentage score.
30
Statistical analysis
Data was analyzed by using SPSS version 18. Data is
presented as the mean, mean dierence, SD, changes in
value, and percent dierence. is study was parallel or
independent-group study. Comparison between groups
was performed by an unpaired T-test, while a paired
Student’s t-test was used to compare within group. A
comparison of NRS and PTT over the time points was
performed by repeated measures ANOVA with the
Bonferroni method for the dierences within group,
and eect of times. e dierence between group used
unpaired T-test. A p-value of less than 0.05 was considered
statistically signicant.
RESULTS
A total of 69 patients with LPP-S4L were recruited.
ree participants were excluded due to low pain score
and hypertension. A total of 66 patients with LPP-S4L
were enrolled and received treatment twice a week for
four weeks, or a total of eight times, with 33 patients
per group (Fig 2). e demographic characteristics are
presented in Table 1. ere was no signicant dierence
in demographic ndings between CTTM and US.
TABLE 1. Demographic data of participants.
Characteristics Total CTTM group US group
(n=66) (n=33) (n=33)
P-value
Gender; n (%)
Female 46 (69.70) 23 (69.70) 23 (69.70) 1.000
a
Age (years);
Mean ± SD 32.92 ± 6.46 33.8 ± 6.5 32.0 ± 6.3
Min, Max 24, 48 25, 44 24, 48
0.265
b
Weight (kg); Mean ± SD 61.86±11.29 59.6±10.2 64.1±12.0 0.102
b
Height (kg); Mean ± SD 162.62±8.37 161.9±8.6 163.3±8.2 0.494
b
BMI (kg/m
2
); Mean ± SD 23.33±3.59 22.7±3.2 24.0±3.7 0.141
b
a
Fisher’s exact test,
b
Independent T test.
Fig 2. Study owchart.
Watcharasirikul et al.
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
33
Original Article
SMJ
TABLE 2. Clinical parameters of patients in both groups before and aer the fourth week.
Outcomes CTTM group (n=33) US group (n=33) P-value
b
P-value
b
Before After P-value
a
Before After P-value
a
CTTM CTTM
(4
th
week) before vs (4
th
week) before vs vs US vs US
after after Before After
VAS 5.58±1.23 0.94±0.93 <0.001* 5.33±0.98 2.42±1.44 <0.001* 0.380 <0.001*
PPT 3.73±1.90 5.91±2.42 <0.001* 2.97±1.46 3.83±1.94 0.003* 0.074 <0.001*
ROM
Flexion 36.97±10.13 42.09±10.85 <0.001* 44.82±13.60 51.85±8.60 <0.001* 0.010* 0.010*
Extension 36.36±11.02 38.27±9.80 <0.001* 39.42±8.62 37.06±8.74 0.031* 0.214 0.120
Lateral exion 23.21±5.79 23.83±5.34 <0.001* 20.97±5.06 23.47±4.31 <0.001* 0.099 0.105
Rotation 58.55±9.51 66.61±7.94 <0.001* 68.27±8.55 75.29±9.28 <0.001* <0.001* 0.025*
SF-36
Physical function 69.55±20.13 70.91±17.48 0.702 73.48±20.90 74.55±21.04 0.745 0.438 0.448
Role physical 72.73±17.32 78.98±14.97 0.024* 74.05±19.46 78.22±17.48 0.155 0.711 0.851
Bodily pain 32.29±18.07 55.68±17.70 <0.001* 29.92±13.60 50.38±19.13 <0.001* 0.550 0.247
General health 50.21±17.3 59.67±18.19 0.002* 54.79±16.54 57.00±17.49 0.380 0.276 0.546
Vitality 49.06±15.85 60.41±12.85 <0.001* 50.95±15.32 56.25±17.54 0.072 0.625 0.275
Social function 61.36±15.74 75.38±15.14 <0.001* 68.94±17.43 72.35±22.48 0.348 0.069 0.523
Role emotional 75.76±19.80 79.29±18.99 0.364 76.77±20.70 74.49±24.47 0.514 0.840 0.377
Mental health 61.06±14.62 68.33±11.30 0.001* 63.48±12.96 64.67±16.63 0.538 0.479 0.303
a
Paired t-test.
b
Unpaired t-test. Signicant (p-value<0.05).
Pain intensity
Baseline NRS in both groups was not signicantly
dierent (Table 2). NRS signicantly decreased aer
treatment at the four-week point in both groups (p<0.05).
In the CTTM group, the level of pain relief was lower
than the US group and significantly different at all
time points of treatment over the course of four weeks
(Fig 3A).
Pressure pain threshold
Baseline PPT in both groups was not signicantly
dierent (Table 2). PPT signicantly increased aer
treatment at the four-week point in both groups (p<0.05).
In the CTTM group, the level of pain increased more
than the US group and was signicantly dierent all
time points of treatment over four weeks (Fig 3B).
Neck range of motion
The baseline of neck flexion and neck rotation
was signicantly dierent between both groups (Table
2). Both groups showed improved ROM of the neck,
including exion, extension, lateral exion, and rotation
at four weeks. At the four-week point, lateral exion and
rotation improved by 7.56±3.84 and 10.29±5.78 degrees,
indicating a signicant dierence between CTTM and
US group (p=0.038 and 0.005, respectively).
Quality of life
e baseline of quality of life was acquired from SF-
36 in both groups, but it was not signicantly dierent
in all parameters (Table 2). There were significant
improvements in physical, bodily pain, general health,
vitality, social function, and mental health aer four
weeks of treatment in the CTTM group. In the US group,
bodily pain improved signicantly aer four weeks of
treatment. However, aer four weeks, there were no
signicant dierences in any other parameters.
Percentage of rescue drug use
No signicant dierences between the two groups
were noted regarding the percentage of use of rescue drug
over four weeks. During the eight visits for treatment,
only one (3.03%) patient in the CTTM group used two
tablets of rescue drug during the third visit because of
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
34
menstrual pain. One (3.03%) patient in the US group also
used four tablets of rescue drug on the fourth visit due
to headache. No side eects were linked to intervention
during the study.
Relationship between body elements based on
ai traditional medicine
Both groups showed a similar proportion of innate
body elements (Fig 4A). Using the innate body elements
to stratify the pain dierence (Fig 4B). NRS dierent for
re, wind, water, and earth elements of CTTM group were
4.75±0.89, 5.20±1.10, 4.55±2.20, 4.33±1.73, respectively.
NRS dierent for re, wind, water, and earth elements of
US group were 2.30±1.42, 2.40±1.34, 4.00±1.41, 3.00±1.61,
respectively. Patients with the re element in the CTTM
group showed a greater decrease compared to US group
(p<0.001). ere were no signicant dierent between
group for wind, water, and earth (p-value 0.07, 0.53,
0.09). Both groups also showed a high proportion of
the Pita-Vata-Semha element for present body elements
(Fig 4C).
DISCUSSION
is study examined the impact of CTTM and US
on neck pain relief in patients with LPP-S4L disease.
Although the outcomes of massage have been investigated
in patients with neck pain, the majority of whom had
MPS
16
, it was a broader diagnosis than ai traditional
medicine. MPS in the neck can be identied with LPSS-
4L disease, LPSS-5L disease, Lompakang disease, and
Koh-tok-mhon disease, among others. Each condition
has its own set of treatment regions and protocols. Our
study found that LPP-S4L patients in the CTTM as well
as US group experienced signicant improvements in
pain intensity, pressure pain threshold, neck ROM, and
quality of life. According to clinical practice guidelines
of ai Traditional Medicine
8
, treatment should last at
least four weeks. is helps maintain pain relief, muscle
tightness, and improves daily life.
31
Over the course of the study, patients with LPP-
S4L who experienced moderate levels of chronic pain
were examined for pain intensity. When comparing the
before and aer treatment across all time points, both
treatments exhibited statistically signicant reductions
in pain intensity. When comparing CTTM to US, the
study found a statistically signicant dierence in impact
in terms of lower pain intensity in CTTM across all
time points. CTTM can reduce pain by around 50%
aer the rst session and by 80% of baseline aer four
weeks, indicating clinical therapeutic eects. CTTM
treatment claims to be a muscle relaxant.
32
Pain alleviation
is achieved by lowering muscular pain and tension in the
Watcharasirikul et al.
Fig 3. Pain parameters over four weeks of treatment
(twice a week). (A) pain score measured by numeric
rating scale (0-10). (B) pressure pain threshold
(0-10 kg/cm
2
). Data compared with mean dierences
± SD between CTTM and US groups (n=33 each
group). Signicant dierences between groups are
* p-value<0.05, ** p-value<0.01, *** p-value<0.001,
unpaired T-test. ere were signicant dierences
compared before with over time of NRS and PPT,
repeated measured ANOVA with Bonferroni
(
#
p-value <0.001).
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
35
Original Article
SMJ
Fig 4. Body elements in ai traditional medicine (A) Number
of participants characterized by innate body elements. (B) Innate
body elements with comparison of pain score Data compared
with mean dierences ± SD between CTTM and US groups
(n=33 each group). Signicant dierences between groups are
*** p-value<0.001, unpaired T-test. (C) Number of participants
characterized by present body elements.
back of the neck and upper back. ese ndings were
consistent with reports that aer four weeks of CTTM
and US, the pain response increased.
16,33
In this study,
the CTTM group had a higher pain threshold than the
US group. e decrease in pain intensity and increase in
pain threshold suggests ecacy and pain relief. CTTM
is more ecient than the US. is could be because
CTTM treatments primarily target tender points and
press deeply into the muscle. Its therapeutic eect is
derived from various pathways such as stress reduction,
increased relaxation, muscle soreness reduction, and
improved circulation. While ultrasound therapy works
primarily by increasing temperature and improving
circulation. Perhaps CTTM is more eective because it
has more pain-reduction mechanisms. It may result in
less muscle tension than in the US.
e current study found that an increase in ROM in
all directions at all time-points was statistically signicant
when comparing the before and aer treatment in the
CTTM group. Our ndings were similar to those of
previous studies. A single course of CTTM treatment
for LPP-S4L reduced pain intensity, raised the pain
threshold, and increased cervical ROM.
33
However, when
compared to US, a dierent result was reported in a
previous study.
34
ere was no dierence in cervical ROM
or VAS between the two treatments. In individuals with
cervical MPS, both ai massage and ultrasonography
can dramatically raise cervical ROM while decreasing the
pain rating and suering during activities of daily life.
When compared to ultrasound, ai massage improved
patients’ capacity to complete daily activities and improve
clinical satisfaction.
34
According to the current study, both therapies
can improve quality of life. In the CTTM group, there
were signicant dierences in six out of eight categories,
including role physical, bodily pain, general health,
vitality, social function, and mental health. However, no
statistically signicant variations in physical function or
emotion were found. ere were dierences only in the
physical pain category in the US group. When comparing
the before and aer results in the US group, there was
no statistically signicant dierence in other categories.
ere were also no statistically signicant dierences
between the CTTM and US groups in any category. e
ndings were comparable to those of a previous report.
15
Participants with neck pain in the CTTM group have
higher quality of life in all domains, although there are
no statistically signicant dierences when compared
to the control group. e results suggest that CTTM
improves quality of life more than US. In this study, no
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
36
signicant change of quality of life in both groups might
be from a ceiling eect of the SF-36 in detecting change
before and aer treatment.
As per ai traditional medicine, this investigation
evaluated innate and present body elements and found
that patients’innate body elements were not dominant,
but that both groups had a similar proportion. When the
pain intensity was assessed before and aer the study,
participants with the re element in the CTTM group
had the greatest reduction in pain intensity compared to
the US group. Meanwhile, the water and earth elements
provided comparable pain alleviation. e present body
elements were mostly of the mixed-type (Pitta-Vata-
Semha). According to ai traditional theory, the wind
element is the primary cause of pain. It may impact the
re, water, and earth components, resulting in muscle
spasms. us, people who have the wind element may
be more aected than others.
32
CTTM can help reduce
muscle spasms and restore normal wind element ow.
A large population must be investigated in order to
collect all elements for analysis to understand the body
elements.
Participant bias may have occurred due to a lack
of blind treatment intervention in each group. Since
the majority of participants were young, the ndings
cannot be generalized to all age groups. e proportion
of patients with dierent body elements may not fully
represent the relationship between the type of element
and the severity of pain. In contrast, this study indicated
the overall makeup of patients’ body elements. With
body elements and age-classied inclusion, a larger
sample size should be observed. e eect of CTTM
on patients’ suering from various diseases should be
investigated further. Also, CTTM’s eectiveness beyond
a period of three to six months should be established for
future clinical trials.
is study determined that a four-week course of
CTTM is an appropriate amount of time to treat LPP-
S4L and reduce pain intensity. CTTM, a recognized
alternative and integrative medicine, can be used as a
primary treatment for people suering from neck pain.
However, cost of treatment for CTTM and US diers.
While CTTM costs around 300 baht/session (30 minutes),
US costs 200 baht/session (20 minutes). Both treatments
have minimal side eects. A patient can select his or her
treatment based on preference, condence, risk factors,
precaution, and practitioner experience.
CONCLUSION
is study suggests that CTTM and US treatment on
the neck muscle twice a week for four weeks is eective
in decreasing pain intensity, increasing pain threshold,
increasing cervical ROM, and improving quality of life
of patients with LPP-S4L. Both treatments are non-drug
interventions with no side eects. In addition, the ndings
in the present study found that CTTM is more eective
than US across all domains in patients with LPP-S4L.
Moreover, we found that a change in pain intensity
relates to dierences in the body element in the patient,
especially the wind and re element. Consequently,
we recommend using CTTM, an alternative therapy,
to treat neck pain caused by LPP-S4L disease. Future
research should be conducted to determine the ecacy
of CTTM and US for diseases that last longer than three
to six months.
ACKNOWLEDGMENTS
e authors are grateful to CTTM experts from the
center of Applied ai Traditional medicine, Faculty
of Medicine Siriraj Hospital, Mahidol University. Dr.
Onusa amsermsang for investigating the result.
Funding sources: e grant from the Siriraj routine
to research unit, Faculty of Medicine Siriraj Hospital,
Mahidol University, Bangkok, ailand (granted no.
R016235007) for funding this research.
REFERENCES
1. Hoy DG, Protani M, De R, Buchbinder R. e epidemiology
of neck pain. Best Pract Res Clin Rheumatol. 2010;24:783-92.
2. Fejer R, Kyvik KO, Hartvigsen J. e prevalence of neck pain
in the world population: a systematic critical review of the
literature. Eur Spine J. 2006;15:834-48.
3. Misailidou V, Malliou P, Beneka A, Karagiannidis A, Godolias
G. Assessment of patients with neck pain: a review of denitions,
selection criteria, and measurement tools. J Chiropr Med.
2010;9:49-59.
4. Ylinen J. Physical exercises and functional rehabilitation for the
management of chronic neck pain. Eura Medicophys. 2007;43:
119-32.
5. Nolet PS, Cote P, Kristman VL, Rezai M, Carroll LJ, Cassidy
JD. Is neck pain associated with worse health-related quality
of life 6 months later? A population-based cohort study. Spine
J. 2015;15:675-84.
6. Kanchanomai S, Janwantanakul P, Pensri P, Jiamjarasrangsi W.
Risk factors for the onset and persistence of neck pain in
undergraduate students: 1-year prospective cohort study. BMC
Public Health. 2011;11:566.
7. Tangchitchareon S, Chuachang P, Jaiveerawattana C, Onsa-
ard A, Suwannatrai U, Vannabhum M, et al. e Comparison
Study Between the Ecacy of Fresh Herbal Compression and
Dried Herbal Compression in Patients with Neck and Back
Pain: A Randomized Trial. Siriraj Med Bull. 2022;15:22-30.
8. Department of ai traditional and alternative medicine Moph.
ai Traditional Medicine Clinical Practice Guideline. Bangkok;
2007.
Watcharasirikul et al.
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
37
Original Article
SMJ
9. Laohapand T, Jaturatamrong U, Jantabut C, Tonglue T, Kamkaew
P, Punpeng P, et al. ai Traditional Medicine in the Faculty
of Medicine Siriraj Hospital. 1st ed., editor. Bangkok: Supavanich
Press; 2009.
10. World Health O. Benchmarks for training in traditional /
complementary and alternative medicine: benchmarks for
training in Nuad ai. Geneva: World Health Organization;
2010.
11. Plakornkul V, Vannabhum M, Viravud Y, Roongruangchai J,
Mutirangura P, Akarasereenont P, et al. e eects of the
court-type ai traditional massage on anatomical relations,
blood ow, and skin temperature of the neck, shoulder, and
arm. BMC Complement Altern Med. 2016;16:363.
12. Viravud Y, Apichartvorakit A, Mutirangura P, Plakornkul V,
Roongruangchai J, Vannabhum M, et al. e anatomical study
of the major signal points of the court-type ai traditional
massage on legs and their effects on blood flow and skin
temperature. J Integr Med. 2017;15:142-50.
13. Miake-Lye I, Lee J, Lugar T, Taylor S, Shanman R, Beroes J, et al.
Massage for Pain: An Evidence Map. VA ESP Project. 2016:
05-226.
14. Boonruab J, Niempoog S, Pattaraarchachai J, Palanuvej C,
Ruangrungsi N. Eectiveness of the court-type traditional ai
massage versus topical diclofenac in treating patients with
myofascial pain syndrome in the upper trapezius. IJTK. 2016;
15:30-4.
15. Boonruab J, Niempoog S, Pattaraarchachai J, Palanuvej C,
Ruangrungsi N. A Comparison of the Quality of Life in Myofascial
Pain Syndrome Patients Treated with the Court-Type Traditional
ai Massage and Topical Diclofenac. J Health Res. 2015;29:
371-5.
16. Butdapan P, Narajeenarone K, Apichartvorakit A, Kade S,
Jansomsarit S, Jamjuntra P, et al. e Eect of the Posture of the
“Hermit Doing Body Contortion” on Relief of Shoulder
and Scapular Pain Caused by Chronic Myofascial Pain Syndrome:
A Randomized, Parallel Group, Controlled Trial. Siriraj Med
J. 2016;68:350-7.
17. Damapong P, Kanchanakhan N, Eungpinichpong W, Putthapitak
P, Damapong P. Eectiveness of Court-Type Traditional ai
Massage in Patients with Chronic Tension-Type Headache: a
Pilot Study. J Health Res. 2015;29:351-6.
18. Damapong P, Kanchanakhan N, Eungpinichpong W, Putthapitak
P, Damapong P. Short-term eects of court-type traditional
ai massage on pressure pain threshold and pain intensity in
patients with chronic tension-type headache. International
Journal of Geomate. 2016;11:2824-9.
19. Damapong P, Kanchanakhan N, Eungpinichpong W, Putthapitak
P, Damapong P. A Randomized Controlled Trial on the
Eectiveness of Court-Type Traditional ai Massage versus
Amitriptyline in Patients with Chronic Tension-Type Headache.
Evid Based Complement Alternat Med. 2015;2015:930175.
20. Prompituck W, Henggrathock S, Sangsumart P, Trakulbanmahing
P, Jamnian A, Changlek N, et al. e Eectiveness of Court-
type ai Traditional Massage for Relieving Tension-type
Headache. Journal of ai Traditional & Alternative Medicine.
2016;14(1):14-20.
21. De las Peñas CF, Sohrbeck Campo M, Fernández Carnero J,
Miangolarra Page JC. Manual therapies in myofascial trigger
point treatment: a systematic review. J Bodyw Mov er. 2005;
9:27-34.
22. Draper DO, Mahaey C, Kaiser D, Eggett D, Jarmin J. ermal
ultrasound decreases tissue stiness of trigger points in upper
trapezius muscles. Physiother eory Pract. 2010;26:167-72.
23. Melzack R SD, Fox EJ. Trigger points and acupuncture points
for pain: correlations and implications. J Pain. 1977;3:3-23.
24. Ahmed S, Khattab S, Haddad C, Babineau J, Furlan A, Kumbhare
D. Eect of aerobic exercise in the treatment of myofascial
pain: a systematic review. J Exerc Rehabil. 2018;14:902-10.
25. Buttagat V, Narktro T, Onsrira K, Pobsamai C. Short-term
eects of traditional ai massage on electromyogram, muscle
tension and pain among patients with upper back pain associated
with myofascial trigger points. Complement er Med. 2016;28:
8-12.
26. O’Brien WD. Ultrasound—biophysics mechanisms. Prog
Biophys Mol Biol. 2007;93:212-55.
27. Noori SA, Rasheed A, Aiyer R, Jung B, Bansal N, Chang KV,
et al. erapeutic Ultrasound for Pain Management in Chronic
Low Back Pain and Chronic Neck Pain: A Systematic Review.
Pain Med. 2020;21:1482-93.
28. Gam AN, Warming S, Larsen LH, Jensen B, Høydalsmo O,
Allon I, et al. Treatment of myofascial trigger-points with
ultrasound combined with massage and exercise--a randomised
controlled trial. Pain. 1998;77:73-9.
29. Jirarattanaphochai K, Jung S, Sumananont C, Saengnipanthkul
S. Reliability of the Medical Outcomes Study Short-Form
Survey Version 2.0 (ai version) for the Evaluation of Low
Back Pain Patients. J Med Assoc ai. 2005;88:1355-61.
30. Mahajaroensiri S, Vannabhum M, amsermsang O, Iampornchai
S, Akarasereenont P, Laohapand T. The development of
evaluation form for present body elements (Present Dhat
Chao Ruean) diagnosis in ai Traditional Medicine. Siriraj
Med Bull. 2017;10:65-73.
31. Keeratitanont K, Jensen MP, Chatchawan U, Auvichayapat P.
e ecacy of traditional ai massage for the treatment of
chronic pain: A systematic review. Complement er Clin
Pract. 2015;21:26-32.
32. Laohapand T, Jaturatamrong U. ai traditional massage
(e court-type ai traditional massage): Basic massage line.
2
nd
ed. Bangkok: Supavanich Press; 2011.
33. Sooktho S, Singtong P, Chaiyachit P, Hlongchin W. Short Term
Effect of Court – Type Thai Massage on Patients with Lomplaipattakat
Sanyan 4 of the Back. Journal of Traditional ai Medical
Research. 2020;6(1):1-20.
34. Kowithayanon K, aechasubamorn P. A Comparison of
Outcomes of Treatment with ai Traditional Massage and
Ultrasound in Patients with Cervical Myofascial Pain Syndrome.
Journal of ai Traditional & Alternative Medicine. 2010;8
(2-3):179-90.
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
38
Prachya Maneeprasopchoke, M.D.*, Phoupong Phousamran, M.D.*, Warut Pongsapich, MD*, Paveena Pithuksurachai,
M.D.*, Jakrit Worrakulpanit, M.D.**, Tippanate Keawvijit***, Naravat Poungvarin, M.D., Ph.D.****, Kanchana
Amornpichetkul, M.D.*****, Cheerasook Chongkolwatana, M.D.*
*Department of Otorhinolaryngology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ailand, **Department of Otorhinolaryngology,
Bhumibol Adulyadej Hospital, Bangkok, ailand, ***Clinical Toxicology Laboratory, Siriraj Poison Control Center, Faculty of Medicine Siriraj Hospital,
Mahidol University, Bangkok, ailand, ****Department of Clinical Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok,
ailand, *****Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ailand.
A Comparison of Serum Copper Levels in Patients
with Papillary Thyroid Carcinoma, Nodular Goiter,
and Healthy Volunteers
ABSTRACT
Objective: Serum copper (Cu) is an essential trace element that plays a key role in thyroid hormone production. An
inappropriate level of serum Cu might be related to development of both benign and malignant thyroid neoplasm.
Nodular goiter and papillary thyroid carcinoma (PTC) are common benign and malignant tumors of the thyroid,
respectively. is study aims to compare the serum Cu levels of healthy women with women with PTC or nodular
goiter.
Materials and Methods: A total of 205 ai women were recruited for this cross-sectional study. e reference
group was comprised of 100 healthy volunteers. ere were 61 nodular goiter and 41 PTC patients that had been
treated with surgery. Serum Cu was measured using an atomic absorption spectrophotometer and the three groups
were compared.
Results: e serum Cu levels of the PTC, nodular goiter and the reference group were 0.93 (0.85, 1.11) μg/ml, 1.03
(0.90, 1.14) μg/ml and 0.97 (0.80, 1.11) μg/ml, respectively. e results were not statistically dierent (P = 0.10). A
post hoc subgroup analysis in the PTC group showed only serum Cu levels were signicantly higher in the blood
vessel invasion group (P = 0.02).
Conclusion: e serum Cu levels of patients with PTC and nodular goiter were not dierent and did not dier
signicantly from the reference group. Despite related to withonly one pattern of histopathologically aggressive PTC-
Blood vessel invasion, serum Cu levels cannot be used as an assistive tool for diagnosis and the prognosis of PTC.
Keywords: Serum copper (Cu); nodular goiter; papillary thyroid carcinoma; thyroid cancer; BRAF mutation (Siriraj
Med J 2023; 75: 38-45)
Corresponding author: Cheerasook Chongkolwatana
E-mail: cheerasook.cho@mahidol.ac.th
Received 8 September 2022 Revised 6 December 2022 Accepted 8 December 2022
ORCID ID:http://orcid.org/0000-0002-8423-6357
http://dx.doi.org/ 10.33192/smj.v75i1.260528
All material is licensed under terms of
the Creative Commons Attribution 4.0
International (CC-BY-NC-ND 4.0)
license unless otherwise stated.
INTRODUCTION
Serum Cu is an arbitrary marker for many types of
malignancies and is more available and less expensive
than genetic testing. Serum Cu levels rise signicantly in
many types of malignancies, such as esophageal cancer,
gynecologic cancer, pancreatic cancer, and melanoma.
1-4
Why serum Cu is elevated in the presence of malignancy
is not yet clear. Copper may be a key factor in tumor
angiogenesis.
5,6
Ceruloplasmin, the Cu-binding protein,
can increase in malignancies due to decreased metabolism
Maneeprasopchoke et al.
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
39
Original Article
SMJ
or an inammatory response state.
7,8
Zhu et al. found that
Cu transportation in tumor cells increased as a result of
elevated expressions of transporter genes.
9
Coates and
coauthors reported that the sensitivity and specicity of
high serum copper for the risk of developing a cancer
were 40% and 80.4%, respectively, but a cuto value was
not determined.
10
Serum copper plays a key role in thyroid hormone
production.
11
is trace element controls T4 levels by
regulating calcium homeostasis.
12
An inappropriate
serum Cu level also stimulates the growth of transformed
cell by providing energy (ATP) in cell cycle process.
13
Furthermore, Cu is an essential nutrient that be integrated
in the antioxidant process as a cofactor of the enzyme
superoxide dismutase, eliminating free radicals caused by
various tissue damage in the body.
14
However, excessively
high Cu levels can cause abnormal cell growth by creating
free radicals and damaging DNA.
15,16
Several studies have reported that the serum Cu
levels of patients with thyroid carcinoma were higher
than those of normal subjects.
17-20
Additionally, Baltaci
et al. also found that serum Cu decreased aer removal
of thyroid tumors.
21
In contrast, Al-Sayer et al. did not
identify a dierence between the serum Cu levels of patients
with thyroid cancer and healthy controls, and serum Cu
increased aer thyroidectomy.
22
Due to insucient data
and inconclusive evidence, the association between serum
copper and thyroid cancer needs further investigation.
erefore, we aimed to compare the serum copper levels
of patients with PTC, nodular goiter and healthy ai
women.
MATERIALS AND METHODS
Study design
is cross-sectional study was conducted at the
Department of Otorhinolaryngology, Faculty of Medicine
Siriraj Hospital, from July 2018 to June 2021. Serum Cu
was measured by the Clinical Toxicology Laboratory of
the Faculty of Medicine Siriraj Hospital. e laboratory
has been certied to the ISO 15189 accreditation standard
since 2013. is study was approved by the Institutional
Review Board, Faculty of Medicine Siriraj Hospital,
Mahidol University (COA no. Si 367/2017) and was
conducted in accordance with the Declaration of Helsinki.
Study population
Diseases of the thyroid gland are generally more
common in females than males. In the ai population,
the female to male ratio of incidence of thyroid cancer
is approximately 4.3:1, and the gender ratio of thyroid
surgery was 5.2:1 during 2018-2020.
23
Because serum Cu
levels can vary by gender,
24
we investigated only female
patients. e sample size calculationwas based on the
primary assumption of dierences betweenserum Cu
in thyroid disease and the normal population.Totally,
we aimed to collect data from 100 patientswiththyroid
disease (PTC and nodular goiter) and 100 normal controls.
e thyroid disease group was consisted of ai women
aged 18 years and older who had thyroid nodules. Fine
needle aspiration was performed prior to surgery. All
patients with pathological reports of PTC or nodular goiter
who needed surgical treatment for thyroid diseases were
eligible. Patients with incidental papillary microcarcinoma,
thyroid carcinoma other than PTC, or other thyroid
or systemic diseases that could alter serum Cu levels
(i.e., thyroiditis, Wilson’s disease, pulmonary disease,
cardiovascular disease, infectious disease, and other
types of cancer) were excluded. Patients with current
medications or supplements that would alter serum Cu
levels, a history of previous thyroid surgery, or abnormal
levels of FT4 or TSH were also excluded. e reference
group consisted of healthy female volunteers with normal
thyroid glands conrmed by ultrasonography and blood
tests showing FT4, TSH, Cr, and eGFR within normal
limits. All study subjects were fully informed about the
treatment options and study protocol before signing
informed-consent forms.
Data collection
Demographic data and ultrasonographic ndings
of the thyroid gland were recorded. Blood samples were
tested for FT4, TSH, Cr, eGFR, and serum Cu levels. For
the cancer group, a pathology-conrmed specimen was
sent for detection of the BRAF
V600E
mutation using the
PCR-based Sanger sequencing technique combined with
allele-specic, real-time PCR. Adverse features such as
multifocality, blood vessel invasion, capsular invasion,
extrathyroidal extension and evidence of transformation
from coexisting nodular goiter were noted. e maximum
diameter of the tumors was recorded in centimeters. e
risk of recurrence was classied according to the 2015
guidelines of the American yroid Association.
25
Stage
was classied using the 8
th
edition of the AJCC/TNM
staging system of thyroid cancer.
26
If indicated, post-
treatment I-131 total body scans and serum thyroglobulin
(Tg) levels were used to detect residual diseases and
distant metastases.
Serum Cu level analysis
Blood samples 5 ml were collected with the standard
method in accordance with the Clinical and Laboratory
Standards Institute guidelines for trace element analysis.
27
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
40
Collection and access procedures were performed in the
patient ward one day before surgery with talc-free gloves,
a 21-gauge needle, and a BD Vacutainer plastic blood
collection tube for trace element testing (K2EDTA). e
tubes were kept upright and either immediately sent to the
Clinical Toxicology Laboratory or stored in a refrigerator
at 2º to 8º C for no longer than 24 hours. e samples
were prepared by centrifugation process (3500 round
per minute) for 10 minutes then the extracted plasma
0.5 ml was collected and diluted with deionized water
1 ml (1:2). Before analysis, internal quality assurance
for trace elements was routinely performed using Clin
Check Controls. Next, the sample was analyzed with a
ame atomic absorption spectrophotometer to produce
free atoms of Cu in the gaseous state. e absorbance of
light with the specic wavelength of Cu was measured.
e intensity of the absorbed light wave was proportional
to the amount of copper in the sample. Subsequently,
a standard calibration curve was plotted with linear
regression. Serum Cu levels were reported as mg/dl and
converted to μg/ml as a standard unit.
Statistical analysis
Demographic data are presented using descriptive
statistics. One-way analysis of variance was used to
compare the three groups (Reference, PTC, and nodular
goiter). If the P values were less than 0.05, post hoc analysis
was applied. Serum Cu levels (μg/ml) are reported as
median and interquartile range. Subgroup analyses of the
serum Cu levels of the PTC group were performed for
histopathological aggressiveness and BRAF
V600E
mutation
using the Mann-Whitney U test. Variant of PTC, risk
of recurrence and the TNM staging were compared by
one-way analysis of variance. Pearson’s correlation was
used to test the association between the size of the PTC
or nodular goiter and the serum Cu level. A P value of
< 0.05 was considered statistically signicant. Statistical
analyses were carried out using PASW Statistics for
Windows (version 18; SPSS Inc., Chicago, IL, USA).
RESULTS
Two hundred and twenty-two subjects were enrolled
and 17 were later excluded. e excluded subjects comprised
10 cases with papillary thyroid microcarcinoma, ve
cases with follicular thyroid carcinoma, and two cases
with thyroiditis. erefore, the study population was
205 subjects, consisting of 105 patients with thyroid
disease (44 with PTC and 61 with nodular goiter),
and 100 healthy controls. The unequal distribution
between PTC (n=44) and nodular goiter (n=61) was
due tothe enrollment nature of our cross-sectional
studydesignthataimed to recruit consecutive cases and
could notpreoperativelypredictthepathological results
of patients.
Serum Cu levels
e serum Cu levels of the PTC group, the nodular
goiter group and the reference group, were 0.93 (0.85,
1.11) μg/ml, 1.03 (0.90, 1.14) μg/ml and 0.97 (0.80, 1.11)
μg/ml, respectively (Fig 1). e results were not statistically
dierent (P = 0.10). Age, serum creatinine and eGFR
were signicantly dierent among the PTC, nodular
goiter and reference groups (Table 1). Aer adjustment
for age, serum creatinine and eGFR, there was still no
statistical dierence.
Fig 1. e serum Cu levels of the PTC
group, nodular goiter group and the
reference group were 0.93 (0.85, 1.11)
μg/ml, 1.03 (0.90, 1.14) μg/ml and 0.97
(0.80, 1.11) μg/ml, respectively
Maneeprasopchoke et al.
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
41
Original Article
SMJ
TABLE 1. Demographic data and characteristics of PTC, nodular goiter, and the reference group.
Patient characteristics PTC Nodular goiter Reference P value
Median (IQR25,75) (n = 44) (n = 61) (n = 100)
Age (years) 45.00 (36.25, 56.25) 48.00 (36.00, 58.00) 37.00 (29.00, 51.00) 0.001*
,a,b
Weight (kg) 57.55 (53.20, 68.80) 58.00 (50.00, 66.00) 54.00 (50.00, 65.00) 0.47
Height (cm) 157.00 (152.00, 161.50) 155.00 (153.00, 160.00) 156.00 (153.00, 160.00) 0.83
FT4 (ng/dL) 1.21 (1.08, 1.35) 1.20 (1.10, 1.29) 1.20 (1.08, 1.29) 0.42
TSH (uIU/mL) 1.44 (0.91, 2.76) 1.28 (0.80, 1.92) 1.79 (1.28, 2.49) 0.14
Cr (mg/dL) 0.71 (0.67, 0.83) 0.68 (0.60, 0.77) 0.67 (0.60, 0.74) < 0.001*
,a,c
eGFR(L/min/1.73m
2
) 96.54 (86.08, 108.51) 101.18 (89.74, 110.12) 109.07 (99.94, 120.34) < 0.001*
,a,b
* P values less than .05 considered statistically signicant.
a
P value between reference and PTC was < 0.05
b
P value between reference and nodular goiter was < 0.05
c
P value between PTC and nodular goiter was < 0.05
Abbreviations: PTC, papillary thyroid carcinoma; FT4, free thyroxine; TSH, thyroid stimulating hormone; Cr, creatinine; eGFR, estimated
glomerular ltration rate.
PTC group
Histopathological aggressiveness
Of the 44 PTC cases, the classical variant was found
in 88.6% (n = 39) and the follicular variant in 6.8% (n =
3). Two patients (4.5%) had non-invasive encapsulated
follicular variant of papillary thyroid carcinoma (NIFTP).
Multifocal cancers were identied in 70.5% (n = 31) of
cases with no statistical dierence (P = 0.24). e serum
Cu in the blood vessel invasion group was signicantly
higher than those without invasion (Table 2). ere
were no signicant dierences in serum Cu levels for
coexisting nodular goiter, capsular invasion, extrathyroidal
extension, high- risk of recurrence and TNM staging.
ere was no correlation between tumor size and serum
Cu levels (r =-0.04; P = 0.81). Four patients (9.1%) had
distant metastases detected by I-131 total body scan.
eir serum Culevels were higher than those in the no
metastasis group, but no signicant dierence of 1.05
(0.91, 1.38) μg/ml, and 0.93 (0.84, 1.08) μg/ml, respectively
(P=0.26).Meanwhile,there was also no signicant
dierence of serum Cu levels among the subgroup of
PTC histopathological aggressiveness, nodular goiter
and healthy groups.
Molecular testing
e BRAF
V600E
mutation was positive in 20 patients
(45.5%) and negative in 24 (54.5%). e serum Cu levels
of BRAF-positive cases were not signicantly higher than
in the negative groups. 1.02 (0.86, 1.17) μg/ml, and 0.92
(0.83, 0.97) μg/ml, respectively; P = 0.06). Nevertheless, the
results from both groups remained within the reference
range.
Nodular goiter group
e correlation coecient between the diameters
of the nodular goiter and serum Cu levels was (r=
0.02; P = 0.89). e median serum Cu level in cases
of PTC with nodular goiter was 0.92 (0.87, 1.10) μg/ml
(n = 17), while the median serum Cu level for cases with
pure nodular goiter was 1.03 (0.90, 1.14) μg/ml (n = 61)
(P = 0.76).
DISCUSSION
We compared serum Cu levels of patients with PTC,
nodular goiter and normal healthy subjects. Zhang
24
and
Shen
12
reported that gender and ethnicity inuence serum
Cu levels and so we investigated only ai women, the
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
42
TABLE 2. Comparison of the histopathological, molecular status, risk of recurrence and staging of 44 PTC cases
and their serum copper levels.
Histopathological
n (%) Serum copper level (μg/ml) P value
aggressiveness
Coexisting nodular goiter Yes 17 (38.6) 0.92 (0.87, 1.10) 0.77
No 27 (61.4) 0.93 (0.84, 1.12)
Multifocal (Foci > 1) Yes 31 (70.5) 0.93 (0.85, 1.07) 0.24
No 13 (29.5) 0.93 (0.83, 1.17)
Blood vessel invasion Yes 26 (59.1) 1.01 (0.87, 1.16) 0.02*
No 18 (40.9) 0.89 (0.82, 0.96)
Capsular invasion Yes 25 (56.8) 0.93 (0.85, 1.16) 0.484
No 19 (43.2) 0.92 (0.85, 1.04)
Extrathyroidal extension Yes 20 (45.5) 0.92 (0.84, 1.04) 0.289
No 24 (54.5) 0.95 (0.86, 1.17)
Variant Classic 39 (88.6) 0.93 (0.85, 1.12) 0.50
Follicular 3 (6.8) 0.92 (0.87, 1.17)
a
NIFTP 2 (4.5) 0.84 (0.75, 0.92)
a
BRAF
V600E
mutation Yes 20 (45.5) 1.02 (0.86, 1.17) 0.06
No 24 (54.5) 0.92 (0.83, 0.97)
Risk of recurrence Low 11 (25) 0.92 (0.85, 1.04) 0.89
Intermediate 23 (52.3) 0.93 (0.82, 1.15)
High 10 (22.7) 0.92 (0.86, 1.24)
Tumor (T) T1 15 (34.1) 0.92 (0.84, 1.04) 0.59
T2 14 (31.8) 0.95 (0.86, 1.15)
T3 12 (27.3) 0.99 (0.83, 1.17)
T4 3 (6.8) 0.87 (0.86, 0.88)
a
Node (N) N0 21 (47.7) 0.93 (0.86, 1.06) 0.99
N1 23 (52.3) 0.93 (0.83, 1.14)
Metastasis M0 40 (90.9) 0.93 (0.84, 1.08) 0.26
M1 4 (9.1) 1.05 (0.91, 1.38)
Stage 1 34 (77.3) 0.92 (0.84, 1.03) 0.76
2 7 (15.9) 1.08 (0.91, 1.15)
3 1 (2.3) 1.00†
4 2 (4.5) 1.19 (0.92, 1.45)
a
* P values less than .05 considered statistically signicant.
†
No min, max as there was only one data item for that category.
a
Use min, max instead of interquartile range.
Abbreviations: NIFTP, Noninvasive follicular thyroid neoplasm with papillary-like nuclear features
Maneeprasopchoke et al.
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
43
Original Article
SMJ
gender most oen aected by this disease. e median
serum Cu levels of our reference group were comparable
to those in diverse populations (Table 3). e most
common method to measured serum Cu was the atomic
absorption spectrometry, so the median serum Cu levels
in healthy subjects of our study were very close to the
mean value of the studies that used this technique as well
as the biggest dataset in a Chinese population.
20,24,28
e
results in the reference group showed reliable; However,
we did not identify any statistically signicant dierences
in the serum Cu levels among the PTC, nodular goiter,
and reference groups.
e use of Cu to support the diagnosis of thyroid
cancer remains inconclusive. Baltaci et al.
21
showed
that serum Cu levels of women with thyroid cancer
were signicantly higher than those of healthy controls.
Additionally, the serum Cu levels of female patients with
thyroid cancer signicantly decreased to levels close
to those of the control group within two weeks aer
surgery. Vesna and colleagues
17
compared 35 cases of
PTC and 13 cases of papillary thyroid microcarcinoma
with 82 cases of benign thyroid tumor. e serum Cu
levels of patients with PTC and microcarcinoma were
signicantly higher than patients with benign thyroid
tumor. However, because incidental microcarcinoma was
included in the PTC group, their ndings are challenging
to interpret and to compare with our study.
In 2015, Shen and colleagues published a meta-
analysis of ve case-control studies investigating serum
Cu levels.
12
One study was carried out in China, three
in Poland, and one in Turkey. Overall, patients with
thyroid cancer had higher serum Cu levels than healthy
controls. However, consistent with our results, the Polish
studies did not nd higher serum Cu levels in patients
with thyroid cancer relative to their controls. A 2004
study from Kuwait also reported that serum Cu levels in
thyroid cancer patients were not dierent from healthy
controls and rose signicantly aer thyroidectomy.
22
Hence, ethnicity can inuence serum Cu levels. Normally,
Cu is actively recycled in the digestive tract, body uids
and tissues, and is mainly excreted from the body via
bile. Copper levels are primarily controlled by recycling
and resorption, and dietary Cu represents only a small
proportion of total Cu resorption.
15
erefore, dietary
intake of Cu has an insignicant eect on serum Cu
levels and does not need to be controlled.
In the post hoc subgroup analysis of PTC, we found
signicantly higher serum Cu levels in patients with blood
vessel invasion. Cu is postulated to be a potent stimulator
of tumor growth through its activation of angiogenic
factors.
29
Nevertheless, the median serum Cu levels were
not statistically signicant in the presence of adverse
features such as positive capsular invasion, extrathyroidal
extension, lymph node involvement, distant metastases
and high stage. Although, this incidental nding is less
likely to demonstrate a relationship between serum Cu
levels and the aggressiveness of PTC, the association
between serum Cu levels and angiogenesis in thyroid
cancer requires further exploration. Furthermore, the
additional comparison of serum Cu in each subgroup of
TABLE 3. Serum copper levels in healthy subjects.
Studies Year Country Measurement N Sex Serum copper levels
technique (mean ± SD; μg/ml)
Maneeprasopchoke et al. 2022 Thailand AAS 100 Female 0.97 (0.80, 1.11)
†
Zhang et al.
24
2009 China AAS 890 Female 1.01 ± 0.24
Baltaci et al.
21
2017 Turkey AES 15 Female 0.74 ± 0.24
Przybylik-Mazurek et al.
28
2011 Poland AAS 20 All 1.11 ± 0.19
Kosova et al.
20
2012 Turkey AAS 37 All 1.06 ± 0.11
Leung et al.
19
1996 China AES 50 All 0.74 ± 0.19
Kucharzewski et al.
18
2003 Poland TRXRF 50 All 0.69 ± 0.06
†
Median and interquartile range
Abbreviations: AAS, atomic absorption spectrometry; AES, atomic emission spectrometry; TRXRF,
total reection uorescence
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
44
PTC with nodular goiter to that of the healthy population
showed no signicant dierences. us, we cannot infer
that high serum Cu can be used to prognosticate the
invasiveness of PTC.
e potential relationship between serum Cu levels
and gene mutation in humans has not been studied.
Since copper regulates the function of follicular cells,
aberrant levels of serum Cu may be associated with
molecular alterations. Currently, there are several genetic
mutations reported in thyroid cancer and the BRAF
V600E
mutation is the most common biomarker for PTC.
Brady et al. demonstrated that Cu is required for BRAF
signaling and tumorigenesis. A reduction in serum Cu
levels caused the size of BRAF
V600E
-driven melanomas to
decrease in laboratory animals.
30
A recent investigation by
Baldari et al. also found that Cu-chelating agents reduced
the proliferation, survival, and migration of human
colon cancer cells carrying the BRAF
V600E
mutation.
31
We hypothesized that in thyroid cancer, the BRAF
V600E
mutation would be associated with increased serum
Cu levels, as is seen in melanoma and colon cancer.
Besides,no signicantelevation ofserum Culevels was
observedin PTC with BRAF
V600E
mutation, suggesting
that serum copperdoes not indicatethe severity of PTC.
To our knowledge, this is the rst study to report
serum Cu levels in terms of histopathological aggressiveness,
risk of recurrence, staging, and molecular status in
PTC. In addition, we screened all healthy subjects with
ultrasonography of the thyroid gland to avoid unexpected
thyroid nodules in the control group. is ensured that
the reference serum Cu values of the healthy ai women
were reliable and could be used as a standard for further
studies. On the other hand, our analyses suggest that
serum Cu levels are not appropriate for diagnostic and
the prognosis of PTC.
Our study has some limitations. Our subjects were
ai women with PTC and nodular goiter. We did not
address the role of serum Cu levels in men, other types
of thyroid cancer, and in advanced-stage thyroid cancers
such as tracheal or recurrent laryngeal nerve invasion.
In addition to Cu, other essential trace elements such
as selenium, cadmium, zinc were likely involved in
the carcinogenesis of thyroid.
32
e expand study of
multiple trace element levels and their ratios would give
more informative data about the relation between trace
elements and thyroid cancer.
CONCLUSION
The role of serum Cu in the pathogenesis and
prognosis of thyroid tumors remains unclear. Serum Cu
levels in patients with PTC and nodular goiter were not
dierent, and also were not dierent from the reference
group. However, serum Cu was associated withonly one
pattern of histopathologically aggressive PTC- Blood
vessel invasion.erefore, serum Cu levels cannot be
used as an assistive tool for diagnosis and the prognosis
of PTC.
ACKNOWLEDGMENTS
e authors appreciate the assistance provided by
Dr. Saowalak Hunnangkul, Ph.D., Division of Clinical
Epidemiology, Department of Health Research and
Development, Faculty of Medicine Siriraj Hospital,
Mahidol University, for her assistance with the sample
size calculation and statistical analyses. We also thank
Miss Jeerapa Kerdnoppakhun of the Department of
Otorhinolaryngology, Faculty of Medicine Siriraj Hospital,
for secretarial support. The authors also gratefully
acknowledge the professional English editing of this
paper by Mr. Mark Simmerman.
Conicts of interest: e authors declare that they do
not have any conict of interest regarding this research.
Funding statement: is work was supported by Faculty
of Medicine Siriraj Hospital, Mahidol University [grant
number R016133003]
REFERENCES
1. Goyal MM, Kalwar AK, Vyas RK, Bhati A. A study of serum
zinc, selenium and copper levels in carcinoma of esophagus
patients. Indian J Clin Biochem. 2006;21(1):208-10.
2. Margalioth EJ, Udassin R, Cohen C, Maor J, Anteby SO,
Schenker JG. Serum copper level in gynecologic malignancies.
Am J Obstet Gynecol. 1987;157(1):93-6.
3. Lener MR, Scott RJ, Wiechowska-Kozlowska A, Serrano-Fernandez
P, Baszuk P, Jaworska-Bieniek K, et al. Serum Concentrations
of Selenium and Copper in Patients Diagnosed with Pancreatic
Cancer. Cancer Res Treat. 2016;48(3):1056-64.
4. Fisher GL, Spitler LE, McNeill KL, Rosenblatt LS. Serum copper
and zinc levels in melanoma patients. Cancer. 1981;47(7):1838-
44.
5. Mulware SJ. Trace elements and carcinogenicity: a subject in
review. 3 Biotech. 2013;3(2):85-96.
6. Gullino PM, Ziche M, Alessandri G. Gangliosides, copper
ions and angiogenic capacity of adult tissues. Cancer Metastasis
Rev. 1990;9(3):239-51.
7. Fisher GL, Shifrine M. Hypothesis for the mechanism of elevated
serum copper in cancer patients. Oncology. 1978;35(1):22-5.
8. Tapiero H, Townsend DM, Tew KD. Trace elements in
human physiology and pathology. Copper. Biomed Pharmacother.
2003;57(9):386-98.
9. Zhu S, Shanbhag V, Wang Y, Lee J, Petris M. A Role for
e ATP7A Copper Transporter in Tumorigenesis and Cisplatin
Resistance. J Cancer. 2017;8(11):1952-8.
10. Coates RJ, Weiss NS, Daling JR, Rettmer RL, Warnick GR. Cancer
Maneeprasopchoke et al.
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
45
Original Article
SMJ
risk in relation to serum copper levels. Cancer Res. 1989;49(15):
4353-6.
11. Harris ED. Copper homeostasis: the role of cellular transporters.
Nutr Rev. 2001;59(9):281-5.
12. Shen F, Cai WS, Li JL, Feng Z, Cao J, Xu B. e Association
Between Serum Levels of Selenium, Copper, and Magnesium with
yroid Cancer: a Meta-analysis. Biol Trace Elem Res. 2015;
167(2):225-35.
13. Ishida S, Andreux P, Poitry-Yamate C, Auwerx J, Hanahan D.
Bioavailable copper modulates oxidative phosphorylation and
growth of tumors. Proc Natl Acad Sci U S A. 2013;110(48):19507-
12.
14. Fukai T, Ushio-Fukai M. Superoxide dismutases: role in redox
signaling, vascular function, and diseases. Antioxid Redox
Signal. 2011;15(6):1583-606.
15. Araya M, Pizarro F, Olivares M, Arredondo M, Gonzalez M,
Mendez M. Understanding copper homeostasis in humans
and copper eects on health. Biol Res. 2006;39(1):183-7.
16. Bonham M, O’Connor JM, Hannigan BM, Strain JJ. e immune
system as a physiological indicator of marginal copper status?
Br J Nutr. 2002;87(5):393-403.
17. Dragutinovic VV, Tatic SB, Nikolic-Mandic SD, Tripkovic TM,
Dunderovic DM, Paunovic IR. Copper as ancillary diagnostic
tool in preoperative evaluation of possible papillary thyroid
carcinoma in patients with benign thyroid disease. Biol Trace
Elem Res. 2014;160(3):311-5.
18. Kucharzewski M, Braziewicz J, Majewska U, Gozdz S. Copper,
zinc, and selenium in whole blood and thyroid tissue of people
with various thyroid diseases. Biol Trace Elem Res. 2003;93
(1-3):9-18.
19. Leung PL, Li XL. Multielement analysis in serum of thyroid
cancer patients before and aer a surgical operation. Biol Trace
Elem Res. 1996;51(3):259-66.
20. Kosova F, Cetin B, Akinci M, Aslan S, Seki A, Pirhan Y, et al.
Serum copper levels in benign and malignant thyroid diseases.
Bratisl Lek Listy. 2012;113(12):718-20.
21. Baltaci AK, Dundar TK, Aksoy F, Mogulkoc R. Changes in the
Serum Levels of Trace Elements Before and Aer the Operation
in yroid Cancer Patients. Biol Trace Elem Res. 2017;175(1):57-
64.
22. Al-Sayer H, Mathew TC, Asfar S, Khourshed M, Al-Bader A,
Behbehani A, et al. Serum changes in trace elements during
thyroid cancers. Mol Cell Biochem. 2004;260(1-2):1-5.
23. Rojanamatin J, Ukranun W, Supaattagorn P, Chiawiriyabunya I,
Wongsena M, Chaiwerawattana A. Cancer in ailand. Vol.X,
2016-2018. Bangkok, ailand: National Cancer Institute;
2021.
24. Zhang HQ, Li N, Zhang Z, Gao S, Yin HY, Guo DM, et al.
Serum zinc, copper, and zinc/copper in healthy residents of
Jinan. Biol Trace Elem Res. 2009;131(1):25-32.
25. Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ,
Nikiforov YE, et al. 2015 American Thyroid Association
Management Guidelines for Adult Patients with yroid Nodules
and Dierentiated yroid Cancer: e American yroid
Association Guidelines Task Force on yroid Nodules and
Dierentiated yroid Cancer. yroid. 2016;26(1):1-133.
26. Amin MB, Greene FL, Edge SB, Compton CC, Gershenwald
JE, Brookland RK, et al. e Eighth Edition AJCC Cancer Staging
Manual: Continuing to build a bridge from a population-based
to a more “personalized” approach to cancer staging. CA
Cancer J Clin. 2017;67(2):93-9.
27. Lockitch G, Fassett J, Gerson B, Nixon D, Parsons P, Savory J.
Control of Pre-Analytical Variation in Trace Element
Determinations; Approved Guideline. NCCLS document
C38-A. J National Committee for Clinical Laboratory Standards
Wayne, PA. 1997:30.
28. Przybylik-Mazurek E, Zagrodzki P, Kuzniarz-Rymarz S,
Hubalewska-Dydejczyk A. yroid disorders-assessments of
trace elements, clinical, and laboratory parameters. Biol Trace
Elem Res. 2011;141(1-3):65-75.
29. Li Y. Copper homeostasis: Emerging target for cancer treatment.
J IUBMB life. 2020;72(9):1900-8.
30. Brady DC, Crowe MS, Turski ML, Hobbs GA, Yao X, Chaikuad
A, et al. Copper is required for oncogenic BRAF signaling and
tumorigenesis. Nature. 2014;509(7501):492-6.
31. Baldari S, Di Rocco G, Heern MC, Su TA, Chang CJ, Toietta G.
Eects of Copper Chelation on BRAF(V600E) Positive Colon
Carcinoma Cells. Cancers (Basel). 2019;11(5):659.
32. Stojsavljević A, Rovčanin B. Impact of Essential and Toxic
Trace Metals on yroid Health and Cancer: A Review. Exposure
and Health 2021;13:613-27.
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
46
Aurawamon Sriyuktasuth, D.S.N.*, Piyatida Chuengsaman, M.D.**, Worapan Kusakunniran, Ph.D.***,
Assadarat Khurat,
Ph.D.***, Nattaya Rattana-umpa, Ph.D.*
*Faculty of Nursing, Mahidol University, Bangkok 10700, ailand, **Banphaeo Dialysis Group, Bangkok, ailand, ***Faculty of Information and
Communication Technology, Mahidol University, Nakhon Pathom 73170, ailand.
Telehealth Service for Patients Receiving Continuous
Ambulatory Peritoneal Dialysis: A Pilot Study
ABSTRACT
Objective: is study aimed to assess the feasibility and acceptability of delivering a telehealth intervention, called
PD Telehealth, for improving health outcomes among ai patients receiving continuous ambulatory peritoneal
dialysis (CAPD).
Materials and Methods: is pilot study enrolled 104 patients receiving CAPD, who were randomly classied into
two groups: PD Telehealth group (PD Telehealth service plus usual care; n = 52) and usual care group (usual care
only; n = 52). e 6-month telehealth service was provided to participants to deliver self-management support
and telemonitoring while they received home-based treatment. Further, the repeated measures mixed analysis of
variance test was used to assess health outcomes at baseline, 3months, and 6months. Additionally, feasibility and
acceptability were assessed.
Results: Notably, the measured baseline characteristics of the two groups were not dierent. Regarding quality of life, a
signicant interaction eect was observedon two domains of the 36-Item Short Form Survey-general health (p = 0.002) and
reported health transition (p = 0.018). However, self-management and clinical outcomes did not dier signicantly between
the two groups over 6 months. e PD Telehealth group demonstrated high acceptability and feasibility of the application.
Conclusion: e PD Telehealth service has been demonstrated to be feasible and acceptable for providing care to
patients receiving CAPD. However, there were no signicant dierences in the main outcomes of the study. Further
research studies involving a larger and more diverse sample population and conducted over a longer period are
needed.
Keywords: PD Telehealth; peritoneal dialysis; telehealth (Siriraj Med J 2023; 75: 46-54)
Corresponding author: Aurawamon Sriyuktasuth
E-mail: aurawamon.sri@mahidol.ac.th
Received 22 September 2022 Revised 9 December 2022 Accepted 11 December 2022
ORCID ID:http://orcid.org/0000-0002-6899-5927
http://dx.doi.org/ 10.33192/smj.v75i1.260529
All material is licensed under terms of
the Creative Commons Attribution 4.0
International (CC-BY-NC-ND 4.0)
license unless otherwise stated.
INTRODUCTION
In 2008, the ai government implemented the PD
First policy to increase the access to dialysis treatment
among ai citizens. Under universal health coverage,
people can access dialysis treatment for free in the form of
continuous ambulatory peritoneal dialysis (CAPD) as the
rst dialysis modality unless contraindicated.
1
Notably,
CAPD has fewer technical requirements and lesser need
for medical sta,
2
and it is more cost-eective.
3
erefore,
the number of patients receiving CAPD in ailand has
increased. According to the ai Renal Replacement
erapy registry, the number of patients receiving PD
has increased from 5,133 in 2009 to 34,467 in 2020.
4
Of
all patients receiving PD in ailand, 97% were receiving
CAPD, and only 3% were receiving automated PD.
1
e challenges associated with CAPD care include
complication management and prevention, technique
failure intervention, long-term CAPD sustenance, and
Sriyuktasuth et al.
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
47
Original Article
SMJ
quality of life (QOL) improvement. However, currently
available healthcare services for CAPD do not support
patients and their families to eectively and safely perform
dialysis at home. us, a well-designed healthcare service
is required to support home-based treatment and provide
eective care to this population.
Telehealth was developed to promote PD regimen
adherence and ensure continuous safety and eectiveness.
5,6
Although evidence suggests improved patient outcomes
by telehealth programs among those receiving PD,
7-9
in
ailand, there is a lack of tailored telehealth to support
patients receiving CAPD. erefore, PD Telehealth was
developed for ai patients receiving CAPD as well
as caregivers and healthcare professionals to provide
self-management support, monitor home dialysis, and
enhance patient health and professional communication
as required by all key stakeholders.
10
PD Telehealth
aimed to transform its current care delivery model,
support home-based treatment, and improve health
outcomes in patients receiving CAPD. is study reports
the results of a pilot study designed to assess the eects
of PD Telehealth on self-management behaviors, QOL,
and clinical outcomes and to evaluate the feasibility and
acceptability of PD Telehealth in ai contexts.
MATERIALS AND METHODS
Study design and participants
is two parallel-group randomized controlled pilot
study was conducted at Banphaeo Dialysis Center, Bangkok,
ailand (ai Clinical Trials Registry identication
number: TCTR20221121004). Eligibility criteria were as
follows: patients aged >18 years, those who had received
CAPD for at least 3 months and were actively undergoing
dialysis procedures, those who had no prior peritonitis
in the last 3 months, and those using a smartphone or
tablet with an android operating system of ≥version 6
and internet access. Patients who were bedridden or
had cognitive impairment, psychiatric illness, or serious
illness/condition were excluded from the study. Notably,
participants who discontinued CAPD treatment or were
referred to other PD clinics were withdrawn from the
study sample. The sample size was calculated using
power analysis. e required sample size calculation for
repeated measures mixed analysis of variance (ANOVA)
test indicated a sample of 104 participants (52 per group),
with a power (p) of 0.80, signicance level (α) of 0.05,
medium eect size (f) of 0.25,
11
and attrition rate of 20%.
e study objectives, protocol, benets, risks, privacy,
and condentiality were explained to all eligible participants.
e participants were then randomly assigned to group
receiving PD Telehealth plus usual care or that receiving
usual care alone over 6months aer obtaining their
informed consent and preforming the baseline assessment
(Fig 1). ey were evaluated using a questionnaire at 3
and 6months, and their health information was obtained
from medical records.
Fig 1. Flow diagram of participant eligibility and randomization process
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
48
Intervention
PD Telehealth is a service operated through a
mobile application (patient side) and a web application
(dialysis center side) called PD Easy. It was developed
by a multidisciplinary team based on a user-centered
approach. Both applications comprise multiple features
to serve the needs of patients, caregivers, and healthcare
professionals.
10
ese features were linked using the
central database and processing unit at the server.
e patient-side mobile application included eight
core functions: (a) daily health and dialysis records,
(b) information, (c) health advice, (d) reminders, (e)
health alerts, (f) social forum, (g) news and knowledge
management, and (h) contacts (Fig 2.1). e participants
in the intervention group installed the application on
their smartphone or tablet and were trained about its use.
ey were instructed to send the daily dialysis records and
health-related information to the dialysis center. ey were
notied when the recorded data exceeded the set value.
ey could review PD-related resources using video clips
and text-based materials. In addition, they were informed
about follow-up and treatment appointments at the clinic
through personal health alerts and reminders. e social
forum allowed participants to share and learn from each
other. Participants’ contacts were used to remotely connect
with healthcare providers, which potentially reduced
patient visits to the clinic; moreover, participants could
upload photos of, for example, exit site and dialysis uid
and contact healthcare providers for advice via the chat
box. However, participants were informed that the data
they sent would be checked regularly but not in real time.
ey had to call the healthcare providers for urgent or
immediate medical assistance because PD Telehealth
was not designed to support emergency services.
A web application was used to manage the PD Telehealth
service at the dialysis center (Fig 2.2). Healthcare providers
monitored patients by reviewing their health records
through a secure password-protected web application.
e clinic’s health team, including a PD nurse, a dietician,
and two public health technical ocers, regularly reviewed
alerts based on their assigned responsibilities. e team
was notied via the web application when participants
entered the alert zone, and the team coordinated with
other healthcare providers as needed to provide care.
Appropriate contacts and follow-up were established
through the application, telephone call, and home or
clinic visit as required.
Outcome measurement
e study outcomes included self-management (using
the PD Self-Management Scale [PDSMS]),
12
QOL (using
the Choice Health Experience Questionnaire [CHEQ]
ai version),
13
and clinical outcomes (obtained from
patient’s medical records). Furthermore, the feasibility
and acceptability of PD Telehealth services among ai
patients receiving CAPD were evaluated. Notably, the
feasibility was determined by application usage (obtained
from Google Analytics) and retention rates, and the
acceptability was assessed using the Perceived Benets
of the PD Telehealth Questionnaire developed by the
research team.
Log in page Main menu Main board Individual health and dialysis
Fig 2. Sample screenshots of PD Telehealth
2.1 e mobile application 2.2 e web application
Sriyuktasuth et al.
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
49
Original Article
SMJ
Statistical analysis
All statistical analyses were performed using the
Statistical Package for the Social Sciences (SPSS Inc.,
Chicago, IL). Descriptive statistical analysis was used
to summarize patient characteristics, feasibility, and
acceptability. e chi-square, Fisher’s exact, or independent
t test was used to compare baseline characteristics between
the two groups. Repeated measures mixed ANOVA test
was used to compare self-management, QOL, and clinical
outcomes between the two groups at baseline, 3months,
and 6months. Furthermore, intention-to-treat analysis
was used for study analysis.
RESULTS
Patient characteristics
Overall, 104 participants completed the pretest. Of
these, 3 and 9 from the intervention and control groups
withdrew from the study, respectively. In contrast, 92
participants completed the post-test at the end of the study
(49 and 43 from the experimental and control groups,
respectively). Furthermore, there was no difference
between the two groups at baseline (Table 1).
Self-management
Self-management was assessed using PDSMS, and
there was no dierence in self-management in the overall
scores or each of the ve domains between the two groups
at any time point (Table 2).
QOL
In this study, the QOL was determined using the
CHEQ ai version, which included the general health
36-Item Short Form Survey (SF-36) and end-stage kidney
disease (ESKD)-specic domains. Notably, there was a
signicant interaction eect between groups and time on
two domains of the 36-Item Short Form Survey—general
health (p = 0.002) and reported health transition (p =
0.018). ere was no signicant dierence between the
two groups in the ESKD domains throughout the study
period (Table 3).
Clinical outcomes
Clinical outcomes (i.e., hematocrit, albumin, and
phosphate levels) were measured at baseline, 3months,
and 6months. ere was no signicant dierence at
any time point in this study (Table 4). Additionally,
no signicant dierence in other clinical outcomes,
including overhydration (OH) value and peritonitis, exit
site infection, and mortality rates, was found between
the two groups.
Feasibility of PD Telehealth
Overall, 52 participants received the intervention
(PD Telehealth); of these, 49 (94.2%) completed the study,
and 3 (5.8%) did not complete the planned follow-up
because of death. Notably, PD Telehealth adherence was
high. In the intervention group, 70.2% participants used
TABLE 1. Participant characteristics at baseline (n = 104).
Characteristics Experimental group Control group P value
(n = 52) (n = 52)
n (%) or mean ± SD n (%) or mean ± SD
Age (years) 52.8 ± 13.9 51.7 ± 11.5 0.524
c
Gender (male) 31 (59.6) 29 (55.8) 0.691
a
Marital status (married) 30 (57.7) 29 (55.8) 0.749
a
Income (<15,000/month) 36 (69.2) 28 (53.8) 0.362
b
Education (primary school) 24 (46.2) 19 (36.5) 0.714
a
Employment status (unemployed) 30 (57.7) 26 (50.0) 0.241
a
Healthcare scheme (universal coverage) 44 (84.6) 43 (82.7) 0.798
b
Duration of dialysis (months) 32.5 ± 23.7 35.4 ± 25.6 0.362
c
a
Chi-square test.
b
Fisher’s exact test.
c
Independent t test.
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
50
TABLE 2. Self-management at baseline, 3 months, and 6 months between the two groups.
Self-management Intervention Control Repeated measures*
n Mean ± SD n Mean ± SD Within Between Interaction
times, p groups, p effect, p
Overall score
b
Baseline 52 80.9 ± 10.3 52 83.0 ± 8.3 0.765 0.795 0.772
3 months 50 81.5 ± 9.0 51 82.8 ± 9.5
6 months 49 80.8 ± 8.9 43 81.2 ± 10.2
Dialysis
a
Baseline 52 36.0 ± 4.1 52 36.8 ± 3.6 0.616 0.621 0.455
3 months 50 36.5 ± 3.7 51 36.6 ± 4.1
6 months 49 36.3 ± 3.7 43 36.1 ± 4.5
Diet and uid Baseline 52 12.4 ± 2.4 52 12.1 ± 2.6 0.800 0.961 0.122
intake
a
3 months 50 12.1 ± 2.3 51 12.5 ± 2.5
6 months 49 12.3 ± 2.0 43 11.9 ± 2.4
Medication
b
Baseline 52 10.1 ± 2.4 52 10.8 ± 1.5 0.837 0.794 0.820
3 months 50 10.5 ± 1.4 51 10.6 ± 1.5
6 months 49 10.1 ± 2.1 43 10.7 ± 1.5
Self-assessment
a
Baseline 52 13.0 ± 2.1 52 12.8 ± 2.1 0.357 0.866 0.102
3 months 50 12.5 ± 2.4 51 13.1 ± 2.0
6 months 49 12.7 ± 2.4 43 12.5 ± 1.9
Complication Baseline 52 9.3 ± 2.2 52 9.6 ± 2.2 0.463 0.709 0.903
management
a
3 months 50 9.9 ± 2.0 51 9.8 ± 2.0
6 months 49 9.6 ± 2.1 43 9.7 ± 1.7
a
Sphericity assumed.
b
Within-group eects by Greenhouse–Geisser test.
the application more than thrice a week, 55.3% used it
daily to report dialysis and health-related information,
and 4.3% used it once a month. Over a 6-month period,
the top three most frequently used features were personal
health and dialysis records (5,788 times), social forums
(1,092 times), and personal health alerts (814 times).
PD Telehealth acceptability
At the end of the study, the PD Telehealth group
rated the mobile application as useful (8.73±1.70). e
top three advantages were health problem management
(8.71±1.59), health information provision (8.67±1.77),
and home healthcare support (8.59±1.80; Table 5).
DISCUSSION
To the best of our knowledge, this is the rst pilot
study in ailand to develop a telehealth service for
CAPD. e ecacy of PD Telehealth demonstrated fewer
opportunities to improve the measured outcomes. In this
study, participants’ self-management scores were good
at baseline and throughout all follow-up periods. Based
on the inclusion criteria, all participants were required
to actively perform CAPD themselves, indicating that
they were able to manage their own care. erefore, the
mobile application in CAPD care in this study did not
contribute to changes in self-management.
In terms of QOL, the results showed that the SF-
36 general health and reported health transition scores
improved in the PD Telehealth group aer 3 and 6months,
respectively, whereas these scores declined in the control
group. Notably, our study results are consistent with
previous systematic reviews by Cartwright et al.,
8
Yang
et al.,
6
and Lunney et al.,
5
which reported that some domains
of QOL were signicantly improved in patients receiving
PD and chronic dialysis aer telehealth interventions. Our
telehealth service provided remote monitoring, supported
home-based treatment, and fullled the healthcare needs
of such patients. However, the eects were small; therefore,
its eects on QOL should be investigated further in ai
patients receiving CAPD.
Sriyuktasuth et al.
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
51
Original Article
SMJ
TABLE 3. Quality of life at baseline, 3 months, and 6 months between the two groups.
Treatment time Repeated measures
QOL Group Baseline 3 months 6 months Within Between Interaction
times, p groups, p effect, p
SF-36
PF
a
Intervention 51.9 ± 24.6 56.4 ± 24.1 59.1 ± 23.9 0.479 0.847 0.234
Control 57.9 ± 28.1 52.2 ± 28.9 57.9 ± 23.8
RP
a
Intervention 48.1 ± 41.1 57.0 ± 41.7 47.4 ± 44.0 0.694 0.353 0.168
Control 46.1 ± 43.0 41.7 ± 41.7 45.3 ± 43.7
BP
a
Intervention 67.3 ± 23.9 69.6 ± 23.3 68.3 ± 22.7 0.637 0.322 0.842
Control 65.5 ± 25.2 65.6 ± 28.3 63.3 ± 25.6
MH
a
Intervention 63.8 ± 10.7 63.6 ± 11.1 62.9 ± 9.4 0.254 0.612 0.857
Control 69.0 ± 17.3 66.0 ± 15.7 67.0 ± 16.8
RE
a
Intervention 61.1 ± 42.4 66.5 ± 43.6 57.1 ± 46.5 0.326 0.383 0.057
Control 63.5 ± 41.5 48.5 ± 44.5 53.5 ± 44.5
SF
a
Intervention 80.0 ± 18.1 77.5 ± 19.8 79.3 ± 23.0 0.890 0.704 0.768
Control 78.4 ± 22.6 79.0 ± 20.3 77.6 ± 19.6
VT
a
Intervention 59.7 ± 14.8 59.7 ± 10.7 60.8 ± 11.2 0.764 0.235 0.865
Control 58.2 ± 18.8 58.2 ± 18.8 58.2 ± 16.9
GH
a
Intervention 54.1 ± 18.8 46.6 ± 18.4 50.8 ± 14.1 0.336 0.149 0.002
Control 49.1 ± 25.1 47.1 ± 21.4 45.3 ± 20.7
HT
a
Intervention 69.7 ± 25.4 65.3 ± 25.9 74.0 ± 22.8 0.882 0.764 0.018
Control 67.8 ± 22.9 70.0 ± 26.2 65.7 ± 25.6
ESKD
CRP
a
Intervention 78.8 ± 25.9 74.5 ± 26.5 75.5 ± 24.2 0.463 0.240 0.791
Control 84.6 ± 19.9 82.8 ± 26.4 80.2 ± 22.2
CMH
a
Intervention 74.8 ± 19.3 74.0 ± 15.3 72.6 ± 17.8 0.509 0.421 0.396
Control 71.6 ± 20.6 74.6 ± 20.1 72.6 ± 17.2
CGH
a
Intervention 59.2 ± 31.7 59.6 ± 28.1 63.3 ± 24.3 0.900 0.861 0.579
Control 66.9 ± 34.0 63.5 ± 33.8 60.9 ± 33.5
FRE
b
Intervention 55.6 ± 26.5 54.6 ± 29.9 58.8 ± 23.9 0.497 0.391 0.755
Control 62.3 ± 24.0 64.6 ± 29.8 62.3 ± 25.4
TRV
a
Intervention 73.6 ± 25.9 71.8 ± 30.2 70.4 ± 26.4 0.453 0.747 0.280
Control 74.5 ± 29.5 79.7 ± 23.4 73.2 ± 26.1
CF
a
Intervention 64.5 ± 19.7 65.8 ± 24.0 66.3 ± 21.5 0.481 0.785 0.692
Control 67.9 ± 20.1 68.3 ± 21.8 65.7 ± 18.5
FIN
a
Intervention 75.0 ± 27.6 72.9 ± 28.6 71.9 ± 27.3 0.654 0.774 0.961
Control 75.0 ± 27.6 76.0 ± 26.8 74.4 ± 31.6
DR
a
Intervention 61.1 ± 24.5 60.4 ± 26.7 61.7 ± 25.6 0.332 0.439 0.254
Control 64.4 ± 31.4 62.5 ± 30.5 69.8 ± 24.1
REC
a
Intervention 65.4 ± 23.8 67.7 ± 25.8 64.6 ± 25.2 0.534 0.989 0.634
Control 71.6 ± 32.5 66.1 ± 28.9 66.3 ± 25.5
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
52
TABLE 3. Quality of life at baseline, 3 months, and 6 months between the two groups. (Continued)
Treatment time Repeated measures
QOL Group Baseline 3 months 6 months Within Between Interaction
times, p groups, p effect, p
ESKD
WRK
a
Intervention 58.6 ± 38.9 55.2 ± 38.9 58.2 ± 37.6 0.264 0.018 0.627
Control 78.8 ± 29.4 68.7 ± 37.0 66.3 ± 35.3
BI
b
Intervention 81.7 ± 21.6 84.0 ± 21.9 80.7 ± 23.8 0.518 0.028 0.980
Control 88.5 ± 20.7 90.5 ± 16.7 88.4 ± 17.5
SYM
a
Intervention 20.3 ± 12.1 20.1 ± 13.2 18.9 ± 11.3 0.631 0.100 0.951
Control 23.0 ± 14.3 21.5 ± 14.5 23.2 ± 13.3
SEX
b
Intervention 79.6 ± 29.8 80.2 ± 27.1 74.0 ± 28.3 <0.001 0.613 0.125
Control 85.1 ± 25.0 76.8 ± 31.9 77.2 ± 26.1
SLP
a
Intervention 46.7 ± 16.3 46.9 ± 16.5 48.3 ± 16.4 0.482 0.366 0.307
Control 44.1 ± 18.1 48.4 ± 21.5 49.5 ± 20.8
DAC
a
Intervention 80.2 ± 16.5 83.6 ± 16.0 78.7 ± 22.7 0.002 0.204 0.594
Control 85.9 ± 19.1 88.0 ± 16.7 80.6 ± 20.6
QOL
a
Intervention 66.9 ± 19.9 64.6 ± 19.5 66.1 ± 18.9 0.101 0.588 0.733
Control 64.6 ± 21.4 60.8 ± 16.4 62.9 ± 18.9
Abbreviations: BI, body image; BP, bodily pain; CF, cognitive function; CGH, CHEQ general health; CMH, CHEQ mental health; CRP,
CHEQ role physical; DAC, dialysis access-related problems; DR, dietary restrictions; FIN, nances; FRE, freedom; GH, general health; HT,
reported health transition; MH, mental health; PF, physical functioning; QOL, quality of life; RE, role emotional; REC, recreation; RP, role
physical; SEX, sexual functioning; SF, social functioning; SLP, sleep; SYM, symptoms; TRV, travel restrictions; VT, vitality; WRK, work.
a
Sphericity assumed.
b
Within-group eects by Greenhouse–Geisser test.
TABLE 4. Clinical outcomes at baseline, 3 months, and 6 months between the two groups
Items Group Treatment time Repeated measures
Baseline 3 months 6 months Within Between Interaction
times, p groups, p effect, p
Hematocrit
b
Intervention 30.2 ± 6.2 30.1 ± 6.0 29.7 ± 6.3 0.320 0.681 0.386
Control 31.3 ± 6.3 29.5 ± 6.6 30.6 ± 6.7
Albumin
a
Intervention 3.3 ± 0.5 3.4 ± 0.6 3.3 ± 0.5 0.791 0.809 0.051
Control 3.3 ± 0.6 3.2 ± 0.6 3.3 ± 0.6
Phosphate
b
Intervention 4.3 ± 1.6 4.6 ± 1.6 4.5 ± 1.5 0.915 0.963 0.080
Control 4.8 ± 2.0 4.5 ± 1.6 4.7 ± 1.7
a
Sphericity assumed.
b
Within-group eects by Greenhouse–Geisser test.
Sriyuktasuth et al.
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
53
Original Article
SMJ
TABLE 5. Perceived benets of the PD Telehealth service (n = 49).
PD Telehealth usefulness n Possible range Actual range Mean SD
Overall 49 0–10 2–10 8.73 1.70
Managing health problems more appropriately 49 0–10 2–10 8.71 1.59
Receiving useful health information 49 0–10 2–10 8.67 1.77
Taking care own health more appropriately 49 0–10 2–10 8.59 1.80
Motivating to take care of oneself 49 0–10 2–10 8.53 1.73
More access to health information 49 0–10 2–10 8.49 1.82
Enhancing learning 48 0–10 2–10 8.42 1.92
Reducing anxiety related to health 49 0–10 2–10 8.39 1.80
More access to healthcare services 49 0–10 2–10 8.35 1.95
Being assessed and monitored 49 0–10 2–10 8.31 1.88
Receiving more healthcare 49 0–10 2–10 8.20 1.87
Clinical results revealed no statistically signicant
changes in laboratory measures. Moreover, no statistically
signicant dierences were found between the two groups,
although the control group had a higher number of
participants who had peritonitis and died during the
study. ese results were consistent with the ndings of a
systematic review on the impact of telehealth interventions
in patients with ESKD, including PD and HD.
5
More
eective strategies and a longer period may be required
to determine clinical outcome changes caused by the PD
Telehealth service.
The intervention group’s application use and
retention rates were accepted in terms of feasibility and
acceptability. Only two participants, who rarely used
the mobile application, rated its benets as minor. PD
Telehealth development was focused on those with low
computer skill levels and vision problems because most
patients receiving CAPD under universal coverage in
ailand are in their middle and late adulthood. Hence,
most participants, particularly the older adults, reported
no diculties in using the application. e results of this
study demonstrated that this platform is acceptable for
patients receiving CAPD. All available functions were
used, with high-level benets reported. e main features
of PD Telehealth were designed to meet the needs of key
stakeholders to solve their problems related to health
service.
10
erefore, PD Telehealth can be used in ai
contexts. Some ndings of this study are consistent
with those reported in pilot studies, which revealed that
telehealth programs are a viable solution for monitoring
and optimizing the care of patients receiving PD.
14,15
Our results underscore the potential of telehealth
services for the delivery of CAPD care in ailand. is
platform is intended for use by healthcare providers in PD
centers and eventually as part of their routine practice.
e service can be used to engage patients with CAPD
in their own care, as proposed by the World Kidney
Day Steering Committee.
16
However, more research is
needed to demonstrate the ability of PD Telehealth to
improve patient outcomes and the quality of healthcare. A
larger longer-term controlled study is needed to conrm
the eectiveness of PD Telehealth in patients receiving
CAPD.
is study has some limitations. e sample size
was small and the study duration was short; thus, the
dierences in health outcomes could not be observed.
Furthermore, this study was limited by its single-center
nature and sample population size as the participants
were recruited from only one dialysis center in Bangkok,
ailand.
ACKNOWLEDGMENTS
is work was funded by the Health Systems Research
Institute, ailand. We would like to thank all the patients
and healthcare providers who were involved in this
study.
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
54
Ethics Statement: e present study was approved by the
Institution Review Broad, Faculty of Nursing Mahidol
University (COA: No. IRB-NS2018/455.1307).
Conict of interest: All authors declare that they have
no personal or professional conict of interest.
REFERENCES
1. Kanjanabuch T, Takkavatakarn K. Global dialysis perspective:
ailand. Kidney360. 2020;1:671-75.
2. Mehrotra R, Devuyst O, Davies SJ, Johnson DW. e current
state of peritoneal dialysis. J Am Soc Nephrol. 2016;27:3238-52.
3. Karopadi AN, Mason G, Rettore E, Ronco C. e role of economies
of scale in the cost of dialysis across the world: a macroeconomic
perspective. Nephrol Dial Transplant. 2014;29:885-92.
4. Chuasuwan A, Lumpaopong A. ailand renal replacement
therapy year 2020 [Internet]. Bangkok: e Nephrology Society
of ailand, 2020 [cited 2022 Jun 16]. Available from:https://
www.nephrothai.org/wp-content/uploads/2021/10/Final-
TRT-report-2020.pdf.
5. Lunney M, Lee R, Tang K, Wiebe N, Bello AK, omas C, et al.
Impact of telehealth interventions on processes and quality of
care for patients with ESRD. Am J Kidney Dis. 2018;72:592-
600.
6. Yang Y, Chen H, Qazi H, Morita PP. Intervention and evaluation
of mobile health technologies in management of patients
undergoing chronic dialysis: scoping review. JMIR MHealth
UHealth. 2020;8:e15549.
7. Lew SQ, Sikka N, ompson C, Magnus M. Impact of remote
biometric monitoring on cost and hospitalization outcomes
in peritoneal dialysis. J Telemed Telecare. 2019;25:581-6.
8. Cartwright EJ, Goh Zs Z, Foo M, Chan CM, Htay H, Griva K.
eHealth interventions to support patients in delivering and
managing peritoneal dialysis at home: a systematic review.
Perit Dial Int. 2021;41:32-41.
9. Milan Manani S, Baretta M, Giuliani A, Virzì GM, Martino F,
Crepaldi C, et al. Remote monitoring in peritoneal dialysis:
benets on clinical outcomes and on quality of life. J Nephrol.
2020;33:1301-8.
10. Rattana-umpa N, Sriyuktasuth A, Jeungsmarn P. Problems
with health services and assessment of telehealth needs for
peritoneal dialysis: patient, caregiver, and health professional’s
perspectives. Nurs Sci J ail. 2022;40:140-56.
11. Cohen J. Statistical Power Analysis for the Behavioral Science:
2
nd
ed. Hillsdale, NJ: Erlbaum, 1988.
12. Varitsakul R, Sindhu S, Sriyuktasuth A, Viwatwongkasem C,
Himmelfarb CRD. e relationships between clinical, socio-
demographic and self-management: factors and complications
in ai peritoneal dialysis patients. Ren Soc Australas J. 2013;9:85.
13. Aiyasanon N, Premasathian N, Nimmannit A, Jetanavanich P,
Sritippayawan S. Validity and reliability of CHOICE Health
Experience Questionnaire: ai version. J Med Assoc ai.
2009;92:1159-66.
14. Dey V, Jones A, Spalding EM. Telehealth: acceptability, clinical
interventions and quality of life in peritoneal dialysis. SAGE
Open Med. 2016;4:2050312116670188.
15. Harrington DM, Myers L, Eisenman K, Bhise V, Nayak KS,
Rosner MH. e use of a tablet computer platform to optimize
the care of patients receiving peritoneal dialysis: a pilot study.
Blood Purif. 2014;37:311-5.
16. Kalantar-Zadeh K, Li PK, Tantisattamo E, Kumaraswami L,
Liakopoulos V, Lui SF, et al. Living well with kidney disease by
patient and care-partner empowerment: kidney health for
everyone everywhere. Siriraj Med J. 2021;73:209-15.
Sriyuktasuth et al.
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
55
Review Article
SMJ
Patkawat Ramart, M.D.*, Anne Lenore Ackerman, M.D.**
*Division of Urology, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ailand, **Division of Female Pelvic
Medicine and Reconstructive Surgery, Department of Urology
David Geen School of Medicine, University of California, Los Angeles, United States of America.
Recurrent Urinary Tract Infection in Women from
a Urologist’s Perspective
ABSTRACT
Urinary tract infection (UTI) referred to microbial invasion of the urinary tract system, typically due to bacteria.
UTI is more common in women than men, which is thought to be due to dierences in lower urinary tract anatomy.
Making a diagnosis of UTI begins with the presence of clinical symptoms consistent with either pyelonephritis
and cystitis. When pyelonephritis symptoms are present, it is usually associated with bacterial infection, while the
symptoms of clinical cystitis may or may not be caused by infection. As both urologic and non-urologic conditions
can produce the clinical symptoms of cystitis, diagnosis of UTI requires both pyuria and bacteriuria on urine
examination. Complicated UTI is when the infection is associated with either host or bacterial factors that increase
the chance of reinfection and decrease treatment ecacy, such as altered organism virulence, immunocompromise,
or urinary tract abnormalities. e urologist’s primary role in UTI management is to evaluate for such urinary tract
abnormalities and, if needed, resolve those conditions to prevent recurrent infection. is review will describe the
urologists’ evaluation and management of complicated and recurrent UTI and inform physician about the urinary
tract abnormalities that can predispose to recurrent UTI.
Keywords: Cystitis; urinary tract infection; urologic condition; investigation (Siriraj Med J 2023; 75: 55-61)
Corresponding author: Patkawat Ramart
E-mail: patkawat.ram@mahidol.ac.th
Received 11 November 2022 Revised 15 December 2022 Accepted 15 December 2022
ORCID ID:http://orcid.org/0000-0002-3394-9349
https://doi.org/10.33192/smj.v75i1.260531
All material is licensed under terms of
the Creative Commons Attribution 4.0
International (CC-BY-NC-ND 4.0)
license unless otherwise stated.
INTRODUCTION
Urinary tract infection (UTI) is microbial invasion,
typically bacterial, of the urinary tract. e global number
of individuals with UTIs in 2019 is more than 404.6
million, with an incidence that is higher in women
than in men.
1
In the United States, 10.8% of women
self-reported that they had at least one presumed UTI
during the past 12 months.
2
Several non-infectious
genitourinary tract conditions can present with the
same symptoms as UTI, so the diagnosis of UTI relies
upon the combination of clinical symptoms consistent
with pyelonephritis or cystitis accompanied by pyuria
on urine analysis (UA) and signicant bacteriuria on
urine culture (UC). Importantly, in a small number
of cases, recurrent episodes may suggest the presence
of factors that increase the chance of reinfection or
decrease treatment ecacy, factors which distinguish
uncomplicated from complicated UTI. ree main factors,
including organism virulence, host immune system,
and urinary tract abnormality, must be considered. To
prevent reinfection, these factors need to be identied
and properly treated. Collaboration among health care
providers, especially infectious disease specialists and
urologists are needed to cure patients with complicated
UTI. From the urologist’s prespective, a wide range of
genitourinary tract conditions can present with the
clinical syndromes of UTI; as these symptoms may or
may not be associated with true bacterial infection, lack
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
56
of complete evaluation can frequently result in delayed
or missed diagnoses of underlying conditions. erefore,
this review would like to guide urologists in how to
evaluate and diagnose complicated UTI, particularly
in the context of genitourinary tract abnormalities, as
well as inform physicians about preventive strategy for
patients with uncorrectable conditions.
How to diagnose UTI?
Basically, there are two clinical syndromes of UTI:
pyelonephritis when the infection occurs in the upper
urinary tract and cystitis for infection of the lower urinary
tract. e symptoms of pyelonephritis are fever, ank
pain, and/or chills, while the symptoms of cystitis are
dysuria, frequency, urgency, urgency urinary incontinence,
hematuria, and/or suprapubic pain. A meta-analysis
examining the accuracy and precision of factors derived
from the history and physical examination for UTI
diagnosis in women showed that four symptoms: dysuria,
frequency, hematuria, and back pain with costovertebral
angle tenderness on exam signicantly increased the
probability of UTI. When dysuria and frequency were
combined without vaginal discharge or irritation, the
probability of UTI was greater than 90%.
3
However,
while these clinical syndromes are most commonly
linked to infections, non-infectious conditions, such
as malignancy, may sometimes present with similar
symptoms. To diagnose UTI correctly, urine examination
including urine analysis (UA) and urine culture (UC) are
essential. To be consistent with a diagnosis of UTI, UA
should demonstrate pyuria, dened as the presence of ≥ 3
white blood cells per high power eld of unspun urine or
≥ 10 white blood cell per cubic millimeter
4
and signicant
bacteriuria. Pyuria without bacteriuria, termed sterile
pyuria, may indicate urologic malignancy, urolithiasis,
or genitourinary tract tuberculosis. It is also important
to note that the presence of bacteriuria on UA is not
always indicative of an infection. Both colonization and
contamination can present with signicant bacteriuria, so
symptoms are an important component of the diagnosis
of UTI.
Urine culture (UC) is still considered the gold
standard investigation for diagnosis of bacterial UTI;
but there is substantial debate about the appropriate
threshold of colony forming units (CFU) count. Previously,
a cut-o value of 10
5
CFU/ml was widely accepted as
signicant bacteriuria consistent with infection. However,
in patients with convince ing signs and symptoms of
infection, a lower threshold of 10
2
CFU/ml is reasonable.
5
In addition, standard clinical urine culture does not
detect all bacteria equally, preferentially detecting aerobic
bacteria. If anaerobic bacterial or mycobacterial infections
are suspected, special staining, culture techniques, or
molecular diagnostic approaches, such as polymerase
chain reaction (PCR), may be required.
In summary, a diagnosis of UTI requires the
combination of the constellation of symptoms seen
in UTI clinical syndromes and abnormal urine testing
demonstrating pyuria and signicant bacteriuria.
What is complicated UTI?
To determine appropriate management, UTI should
be divided into uncomplicated and complicated subtypes.
Complicated UTI is dened as infections associated
with factors that increase the chance of reinfection and/
or decrease treatment ecacy, such as atypical, highly
virulent or drug-resistant organisms, host immune
dysregulation, and urinary tract abnormalities.
5
e
management of complicated UTI requires thorough
evaluation and management of any correctable factors
to break the cycle of recurrence.
Recurrent UTI is dened as ≥ 2 episodes within 6 months
or ≥ 3 episodes of within 12 months of microbiologically
diagnosed UTI. With these infections, symptoms should
resolve between episodes prior to diagnosis of another
UTI.
5,6
Risk factors for recurrent UTIs dier between
age groups. In women age less than 40 years of age, risk
factors typically relate to sexual behavior and spermicide
use.
7-9
In postmenopausal women, a history of previous
UTIs, prior urogenital surgery, symptomatic urinary
incontinence, presence of cystocele on vaginal examination,
maximal urine ow ≤ 15 ml/sec dened by uroowmetry,
and elevated post-void residuals were associated with
a higher risk of recurrent UTI.
10
erefore, there is a
higher likelihood of functional and anatomic urinary tract
abnormalities in this older population, which necessitates
thorough investigation.
Conditions associated with clinical cystitis
Most episodes of clinical pyelonephritis are bacterial
infections, which typically requires hospital admission for
evaluation and treatment. In contrast, the clinical syndrome
of cystitis is typically managed in the outpatient setting,
and thus is not always thoroughly evaluated. Multiple
urologic and non-urologic conditions with or without
simultaneous bacterial infection can cause recurrent
clinical cystitis symptoms. In addition to uncomplicated
cystitis, other urologic conditions, such as malignancy,
urolithiasis, neurogenic lower urinary tract dysfunction,
tuberculosis of urinary tract, ketamine-induced cystitis,
radiation-induced cystitis, interstitial cystitis, bladder
diverticulum, urethral diverticulum, urethral stricture,
Ramart et al.
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
57
Review Article
SMJ
periurethral fibrosis, and functional bladder outlet
obstruction, can cause cystitis-like symptoms. Non-
urologic conditions can be of a gynecologic (e.g., pelvic
organ prolapse, endometriosis, and uterine/cervical/vaginal
tumor) or colorectal (colovesical stula, diverticulitis, and
rectal tumor) origin. (Fig 1 & 2) Other rare conditions
Fig 1. (A) Ultrasonography demonstrates a bladder diverticulum, an outpouching lesion arising from the posterior bladder wall. (B)
Computed tomography demonstrates a rectovesical stula, occurring aer low anterior resection for rectal cancer. (Yellow arrows) (C)
Magnetic resonance imaging shows a urethral diverticulum, an outpouching lesion arising from and wrapping around the urethra. (Yellow
circle) (D) Cystoscopy demonstrated endometriosis, involved posterior bladder wall, seen as tortuous dark-blue lesions. (White arrows)
(E) Vaginal examination demonstrated mesh extrusion (white circle) aer pelvic organ prolapse repair, causing of vaginal infection and
clinical cystitis-like symptoms. (F) Intraoperative ndings from abdominal cystotomy demonstrated a severely contracted and inamed
bladder wall (white circle) from ketamine abuse.
causing clinical symptoms of cystitis are pelvic congestion
syndrome and non-relaxing pelvic oor dysfunction.
All conditions can initially be evaluated with careful
history and physical examination. If needed, additional
investigations can be considered to conrm the suspected
diagnosis.
Fig 2. Voiding cystourethrography with concomitant intravesical pressure measurement on videourodynamics demonstrated urethral
distortion (Red circle) and high detrusor contraction with low urine ow (Graph) consistent with bladder outlet obstruction aer anterior
vaginal wall repair.
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
58
Investigation for recurrent UTIs
Generally, anatomical evaluation for urinary tract
abnormalities can include ultrasonography (US), intravenous
urography (IVU), computed tomography (CT), and
magnetic resonance imaging (MRI). Multiple studies,
however, have shown little benet for routine anatomical
investigation in women with recurrent UTI.
11,12
IVU is
rarely helpful; more than 80% of IVU in women with
recurrent UTIs are completely normal.
13-15
As an initial
investigation in women in whom there is suspicion
of anatomic abnormalities, US is recommended as an
initial investigation to replace IVU; US is inexpensive,
non-invasive, confers no radiation exposure, and can
provide guidance for further investigations.
16
CT and
MRI are not routinely performed and only recommended
in cases in which specic conditions, such as colovesical
stula, are suspected or abnormalities were previously
detected on physical examination or US. Cystoscopy rarely
provides any information that would alter management;
the most common nding is mucosal inammation.
12,14,17
If no abnormal ndings are seen on US or CT, 94%
of subsequent cystoscopies are normal.
17
Therefore,
cystoscopy is only considered in specic conditions,
such as hematuria, suspected malignancy, or suspicion
for other specic clinical condition.
If anatomic investigation fails to demonstrate an
abnormality, it is reasonable to consider functional
investigation of the lower urinary tract.
12,18
Investigation
can include non-invasive uroowmetry (UFM), assessment
of post-void residual urine (PVR), and urodynamic
(UDS) assessment with or without video assessment
(VUDS). In principle, functional abnormalities should
be focused on incomplete bladder emptying and voiding
dysfunction. VUDS showed evidence of lower urinary
tract dysfunction in 67 – 90% in women with recurrent
UTIs.
18,19
e most common nding was bladder outlet
dysfunctions in 63% of women, with a hypocontractile
detrusor seen in 16%.
19
Together, this evidence suggests
an algorithmic investigation of women with recurrent
UTI. (Fig 3)
(*) Cystourethroscopy when US, CT or MRI demonstrates lower urinary tract abnormality or history of lower urinary tract surgery.
(
#
) UDS or VUDS is indicated when uroowmetry shows abnormality or PVR measurement is more than 20% of bladder capacity.
Fig 3. Proposed investigation ow for women with recurrent UTI
Ramart et al.
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
59
Review Article
SMJ
Reasons of treatment failure in urinary tract abnormality
UTIs can continue to recur due to antimicrobial
resistance, biolm formation, and immunocompromise
in the host, as well as the anatomical and functional
abnormalities discussed above. When the underlying
cause is clearly diagnosed and appropriately treated
either with surgery or medication, UTI can oen be
cured without recurrences. Unfortunately, majority of
cases are combined between both abnormalities. Even
aer correcting an anatomical abnormality, UTI can
still recur, frequently because of a previously co-existing
or new-onset functional abnormality. Such new-onset
(“de novo”) abnormalities may or may not be associated
with the surgical repair. It is important to consider re-
evauation if UTIs continue to recur aer anatomical
correction, although this should only proceed aer an
appropriate interval for healing to avoid confounding
factors occurring aer surgery. Occasionally, it is not
possible to correct the urinary tract abnormalities and
continuous preventive strategies are necessary.
Prevention for recurrent UTIs
Prevention strategies aim to decrease UTI episodes
in patients waiting for denitive treatment, those with
uncorrectable conditions who have little chance of complete
bacterial eradication, or those who are unable or unt
for surgical correction of their underlying condition.
Strategies include antibiotic and non-antibiotic prophylaxis
regimens.
Antibiotic prophylaxis regimens including continuous
low-dose and post-coital antibiotics. One systematic
review indicated that continuous antibiotic prophylaxis
for 6 – 12 months could signicantly reduce the rates of
UTI in comparison to placebo.
20
Post-coital antibiotics
are a reasonable option for prevention in patients whose
cases of UTI are associated with sexual intercourse.
20
While continuous antibiotic prophylaxis can prevent
recurrent episodes, however, this regimen potentially
increases urinary and fecal antibiotic resistance. In addition,
infections tend to recur once the antibiotics are stopped.
21
Given these limitations, there are many agents to use
for non-antibiotic prophylaxis, including probiotics,
estrogen, urine acidication agents, cranberries, and
D-mannose.
Probiotics
Food and Agriculture Organization of the United
Nations (FAO) and the World Health Organization
(WHO) defines probiotics as live microorganisms
which, when administered in adequate amounts, confer
a health benet to the host.
22
e most common probiotic
used for preventing UTI in women is Lactobacillus. A
randomized, double-blinded, non-inferiority trial comparing
antibiotic prophylaxis with 480 mg of trimethoprim-
sulfamethoxazole once daily to oral capsules containing
Lactobacilli twice daily for 12 months demonstrated that
Lactobacilli were not inferior to antibiotic prophylaxis
in the prevention of UTI. Moreover, Lactobacilli did not
increase antibiotic resistance.
23
However, given only a
small number of equivocal studies, a lack of consistent
probiotic formulations, and a high risk of bias, a recent
systematic review and meta-analysis study concluded
there was insucient evidence to determine the benet
of probiotics for UTI.
24
Estrogen
Lack of estrogen in postmenopausal women may
contribute to a risk of recurrent UTI because the changing
vaginal environment. Loss of the normal ora may allow
pathogens to colonize and infect the lower urinary tract.
A systematic review and meta-analysis showed that while
oral estrogen did not signicantly reduce the number
of women with UTI in comparison to placebo, vaginal
estrogen use signicantly reduced the number of UTI when
compared to both placebo and no treatment.
25
Reported
adverse events were rare, but include breast tenderness,
vaginal bleeding or spotting, vaginal discharge, and vaginal
irritation or burning.
25
While typical vaginal estrogen
doses are associated with little systemic absorption,
treatment with estrogen must be used with caution
in endometrial cancer, breast cancer, cardiovascular
disease, deep venous thrombosis, pulmonary embolism
and chronic liver disease.
Urine acidication agents
Bacterial growth is inhibited by acidied urine,
so agents which can reduce urine pH may be eective
treatments. Commonly used agents are Methenamine
Hippurate and ascorbic acid. While the concept of
urinary acidication has promoted the use of ascorbic
acid, known as vitamin C, for UTI prevention, there is
no strong evidence to support its use in prevention of
recurrent UTI. Methenamine hippurate will also acidify
the urine and has an additional bacteriostatic eect
due to its peripheral metabolism into formaldehyde
in the urinary tract. Dosage ranges between 1 and 4 g
daily. Common adverse events are gastrointestinal
irritation, abdominal cramps, anorexia, rash, stomatitis,
and dysuria. While previous data had suggested a small
benet in patients without urinary tract abnormalities, a
systematic review and meta-analysis demonstrated that
the overall quality of the previous studies was poor, oen
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
60
examining heterogenous populations.
26
As a result, this
agent had not been recommended in any guidelines. A
recent, randomized clinical trial, however, demonstrated
non-inferiority of methenamine to continuous antibiotic
prophylaxis in the prevention of recurrent UTI, suggesting
this agent may have utility in UTI prophylaxis.
27
Cranberries
A-type proanthocyanidins (PACs), found in high
levels in cranberries, can prevent bacterial adhesion.
28
As a result, cranberries have been suggested as non-
antibiotic prophylaxis for UTI because many studies
had demonstrated that it can prevent bacterial adhesion
to the urothelium in vitro.
29,30
Focusing on the outcome
of women with recurrent UTI in systematic review and
meta-analysis study, a meta-analysis of four studies
comparing between cranberry and placebo or no treatment
showed a small, non-signicant reduction in risk of repeat
symptomatic UTI but the analysis of two studies comparing
cranberry product and antibiotic prophylaxis showed
equally eective.
31
Importantly, cranberry tablets may
alter urinary oxalate and uric acid excretion, so patients
with a history of urolithiasis should be counselled about
this risk before choosing cranberry as a preventative
approach.
32
Until now, the evidence to support a role of
cranberries for UTI prevention is inconclusive. Recent
evidence, however, suggests that some of the conicting
evidence regarding cranberry ecacy in UTI prevention
may come from dierences in cranberry formulations
and products; varying amounts of bioactive PACs within
each product may underlie diering ecacies in UTI
prevention.
33,34
As no serious adverse events have been
reported, cranberries may be used in patients who desire
a non-antibiotic approach.
D-mannose
D-mannose, a type of sugar, prevents bacterial adhesion
to the urothelium both in vitro and in animal studies
by binding to bacterial pili.
35,36
For clinical use, a recent
meta-analysis of two randomized controlled trials and
one prospective study showed that D-mannose treatment
had similar eectiveness in preventing subsequent UTIs
as antibiotic prophylaxis with minimal adverse events,
but the studies were again of poor to fair quality due to
allocation concealment and lack of blinding. Dosage was
various from 420 to 6,000 mg daily, varying signicantly
between studies and formulations used. Adverse events,
such as diarrhea and gastrointestinal irritation, were
typically mild.
37
CONCLUSION
Urinary tract infection (UTI) is a common problem
in women. Many urologic and non-urologic conditions
may present with the same clinical syndrome as UTI,
including pyelonephritis and cystitis. erefore, urine
examination including urine analysis and culture is
critical to conrm infection. In addition, some of these
non-infectious conditions can confer an increased risk of
recurrent UTI; therefore, in cases in which an anatomic
abnormality is suspected from history and physical
examination or recurrent episodes are refractory to
treatment, further investigation should be considered.
In cases of complicated UTI that are unable to be cured
by denitive treatment, preventive strategies should be
employed to decrease UTI episodes and prevent further
consequences.
REFERENCES
1. Zeng Z, Zhan J, Zhang K, Chen H, Cheng S. Global, regional,
and national burden of urinary tract infections from 1990 to
2019: an analysis of the global burden of disease study 2019.
World J Urol. 2022;40(3):755-63.
2. Foxman B, Barlow R, D’Arcy H, Gillespie B, Sobel JD. Urinary
tract infection: self-reported incidence and associated costs.
Ann Epidemiol. 2000;10(8):509-15.
3. Bent S, Nallamothu BK, Simel DL, Fihn SD, Saint S. Does this
woman have an acute uncomplicated urinary tract infection?
JAMA. 2002;287(20):2701-10.
4. Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance
denition of health care-associated infection and criteria for
specic types of infections in the acute care setting. Am J Infect
Control. 2008;36(5):309-32.
5. Anger J, Lee U, Ackerman AL, Chou R, Chughtai B, Clemens
JQ, et al. Recurrent Uncomplicated Urinary Tract Infections
in Women: AUA/CUA/SUFU Guideline. J Urol. 2019;202(2):
282-9.
6. Haylen BT, de Ridder D, Freeman RM, Swi SE, Berghmans B,
Lee J, et al. An International Urogynecological Association
(IUGA)/International Continence Society (ICS) joint report
on the terminology for female pelvic oor dysfunction. Neurourol
Urodyn. 2010;29(1):4-20.
7. Hooton TM, Scholes D, Hughes JP, Winter C, Roberts PL, Stapleton
AE, et al. A prospective study of risk factors for symptomatic
urinary tract infection in young women. N Engl J Med. 1996;
335(7):468-74.
8. Foxman B, Gillespie B, Koopman J, Zhang L, Palin K, Tallman
P, et al. Risk factors for second urinary tract infection among
college women. Am J Epidemiol. 2000;151(12):1194-205.
9. Scholes D, Hooton TM, Roberts PL, Stapleton AE, Gupta K,
Stamm WE. Risk factors for recurrent urinary tract infection
in young women. J Infect Dis. 2000;182(4):1177-82.
10. Raz R, Gennesin Y, Wasser J, Stoler Z, Rosenfeld S, Rottensterich
E, et al. Recurrent urinary tract infections in postmenopausal
women. Clin Infect Dis. 2000;30(1):152-6.
11. van Haarst EP, van Andel G, Heldeweg EA, Schlatmann TJ,
Ramart et al.
Volume 75, No.1: 2023 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index
61
Review Article
SMJ
van der Horst HJ. Evaluation of the diagnostic workup in
young women referred for recurrent lower urinary tract infections.
Urology. 2001;57(6):1068-72.
12. Santoni N, Ng A, Skews R, Aboumarzouk OM. Recurrent
Urinary Tract Infections in Women: What Is the Evidence for
Investigating with Flexible Cystoscopy, Imaging and Urodynamics?
Urol Int. 2018;101(4):373-81.
13. Engel G, Schaeer AJ, Grayhack JT, Wendel EF. e role of
excretory urography and cystoscopy in the evaluation and
management of women with recurrent urinary tract infection.
J Urol. 1980;123(2):190-1.
14. Fowler JE, Jr., Pulaski ET. Excretory urography, cystography, and
cystoscopy in the evaluation of women with urinary-tract
infection: a prospective study. N Engl J Med. 1981;304(8):462-5.
15. Lieberman E, Macchia RJ. Excretory urography in women
with urinary tract infection. J Urol. 1982;127(2):263-4.
16. Aslaksen A, Baerheim A, Hunskaar S, Gothlin JH. Intravenous
urography versus ultrasonography in evaluation of women
with recurrent urinary tract infection. Scand J Prim Health
Care. 1990;8(2):85-9.
17. Pagano MJ, Barbalat Y, eofanides MC, Edokpolo L, James
MB, Cooper KL. Diagnostic yield of cystoscopy in the evaluation
of recurrent urinary tract infection in women. Neurourol
Urodyn. 2017;36(3):692-6.
18. Hijazi S, Leitsmann C. Clinical signicance of video-urodynamic
in female recurrent urinary tract infections. Int J Womens
Health. 2016;8:31-4.
19. Lee PJ, Kuo HC. High incidence of lower urinary tract dysfunction
in women with recurrent urinary tract infections. Low Urin
Tract Symptoms. 2020;12(1):33-40.
20. Albert X, Huertas I, Pereiro, II, Sanfelix J, Gosalbes V, Perrota
C. Antibiotics for preventing recurrent urinary tract infection in
non-pregnant women. Cochrane Database Syst Rev. 2004(3):
CD001209.
21. Ahmed H, Davies F, Francis N, Farewell D, Butler C, Paranjothy
S. Long-term antibiotics for prevention of recurrent urinary
tract infection in older adults: systematic review and meta-
analysis of randomised trials. BMJ Open. 2017;7(5):e015233.
22. Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B,
et al. Expert consensus document. e International Scientic
Association for Probiotics and Prebiotics consensus statement
on the scope and appropriate use of the term probiotic. Nat
Rev Gastroenterol Hepatol. 2014;11(8):506-14.
23. Beerepoot MA, ter Riet G, Nys S, van der Wal WM, de Borgie
CA, de Reijke TM, et al. Lactobacilli vs antibiotics to prevent
urinary tract infections: a randomized, double-blind, noninferiority
trial in postmenopausal women. Arch Intern Med. 2012;172(9):
704-12.
24. Schwenger EM, Tejani AM, Loewen PS. Probiotics for preventing
urinary tract infections in adults and children. Cochrane
Database Syst Rev. 2015(12):CD008772.
25. Perrotta C, Aznar M, Mejia R, Albert X, Ng CW. Oestrogens
for preventing recurrent urinary tract infection in postmenopausal
women. Cochrane Database Syst Rev. 2008(2):CD005131.
26. Lee BS, Bhuta T, Simpson JM, Craig JC. Methenamine hippurate
for preventing urinary tract infections. Cochrane Database
Syst Rev. 2012;10:CD003265.
27. Harding C, Mossop H, Homer T, Chadwick T, King W, Carnell S,
et al. Alternative to prophylactic antibiotics for the treatment
of recurrent urinary tract infections in women: multicentre,
open label, randomised, non-inferiority trial. BMJ. 2022;376:e068229.
28. Howell AB, Reed JD, Krueger CG, Winterbottom R, Cunningham
DG, Leahy M. A-type cranberry proanthocyanidins and
uropathogenic bacterial anti-adhesion activity. Phytochemistry.
2005;66(18):2281-91.
29. Schmidt DR, Sobota AE. An examination of the anti-adherence
activity of cranberry juice on urinary and nonurinary bacterial
isolates. Microbios. 1988;55(224-225):173-81.
30. Sobota AE. Inhibition of bacterial adherence by cranberry
juice: potential use for the treatment of urinary tract infections.
J Urol. 1984;131(5):1013-6.
31. Jepson RG, Williams G, Craig JC. Cranberries for preventing
urinary tract infections. Cochrane Database Syst Rev. 2012;
10:CD001321.
32. Redmond EJ, Murphy CF, Leonard J, Faulds K, Abdelfadil S,
Crowley VE, et al. e inuence of dietary supplementation
with cranberry tablets on the urinary risk factors for nephrolithiasis.
World J Urol. 2019;37(3):561-6.
33. Chughtai B, omas D, Howell A. Variability of commercial
cranberry dietary supplements for the prevention of uropathogenic
bacterial adhesion. Am J Obstet Gynecol. 2016;215(1):122-3.
34. Howell AB, Dreyfus JF, Chughtai B. Dierences in Urinary
Bacterial Anti-Adhesion Activity aer Intake of Cranberry
Dietary Supplements with Soluble versus Insoluble
Proanthocyanidins. J Diet Suppl. 2022;19(5):621-39.
35. Schaeer AJ, Amundsen SK, Jones JM. Eect of carbohydrates
on adherence of Escherichica coli to human urinary tract
epithelial cells. Infect Immun. 1980;30(2):531-7.
36. Aronson M, Medalia O, Schori L, Mirelman D, Sharon N,
Ofek I. Prevention of colonization of the urinary tract of mice
with Escherichia coli by blocking of bacterial adherence with
methyl alpha-D-mannopyranoside. J Infect Dis. 1979;139(3):
329-32.
37. Lenger SM, Bradley MS, omas DA, Bertolet MH, Lowder
JL, Sutclie S. D-mannose vs other agents for recurrent urinary
tract infection prevention in adult women: a systematic review
and meta-analysis. Am J Obstet Gynecol. 2020;223(2):265.
e1-265.e13.
