Characteristics of Traditional Chinese Medicine Use in Patients with
Rheumatoid Arthritis in Taiwan: A Nationwide Population-Based Study
Ming-Cheng Huang1,2,*, Fu-Tzu Pai3,*, Che-Chen Lin4, Ching-Mao Chang5,6,
Hen-Hong Chang2,7,8, Yu-Chen Lee2,7,9, Mao-Feng Sun2,7,8, Hung-Rong Yen 1,2,7,8
* These authors have equal contribution
1
Research Center for Traditional Chinese Medicine, Department of Medical Research,
China Medical University Hospital, Taichung 404, Taiwan
2
Department of Chinese Medicine, China Medical University Hospital, Taichung 404,
Taiwan
3
Graduate Institute of Clinical Medical Sciences, School of Medicine, Chang Gung
University, Taoyuan 333, Taiwan
4
Health Data Management Office, China Medical University Hospital, Taichung 404,
Taiwan
5
Center for Traditional Medicine, Taipei Veterans General Hospital, Taipei 112,
Taiwan
6
Graduate Institute of Clinical Medicine, and Graduate Institute of Traditional
Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 333,
Taiwan
7
Research Center for Chinese Medicine & Acupuncture, China Medical University,
Taichung 404, Taiwan
8
School of Chinese Medicine, China Medical University, Taichung 404, Taiwan
9
Graduate Institute of Acupuncture Science, China Medical University, Taichung 404,
Taiwan.
Running Title: Traditional Chinese Medicine for Rheumatoid Arthritis
Corresponding Author: Hung-Rong Yen, M.D., Ph.D.
Research Center for Traditional Chinese Medicine, Department of Medical Research,
and Department of Chinese Medicine, China Medical University Hospital
2 Yude Road, North District, Taichung 404, Taiwan.
Office: +886-4-2205-2121, ext. 7508
Fax: +886-4-2236-5141
E-mail: hungrongyen@gmail.com
1
ABSTRACT
Objective: Large-scale study of traditional Chinese medicine (TCM) usage among
patients with rheumatoid arthritis (RA) is lacking. The aim of this study is to evaluate
the TCM usage among RA patients in Taiwan.
Methods: We examined the “registry for catastrophic illness patient dataset” of the
National Health Insurance Research Database (NHIRD; n=23 million people) in
Taiwan. Patients (n=25,263) newly diagnosed as RA in 2001-2009 were included and
then followed-up until the end of 2011. Based on the medical utilization, they were
further categorized into TCM users (n=6,891; 27.3%) and non-TCM users (n=18,372;
72.7%). The demographic data, treatment modalities, disease distributions,
comorbidities and core prescription pattern of the TCM users were analyzed.
Results: Compared to non-TCM user, TCM users were younger (mean age: 49.6
versus 54.0 years), had a higher female/male ratio (82.7%/17.3% versus
74.1%/25.9%), resided in more urbanized area. Herbal remedies were the most
commonly used therapeutic approach (76.4%), followed by combining acupuncture
(21.1%). The frequency of outpatient visits in TCM users was higher across all
disease categories except circulatory system. The most commonly prescribed formula
and herb was Shang-Jong-Shiah-Tong-Yong-Tong-Feng-Wan and Rhizoma Corydalis,
respectively. RA patients who had anxiety and depression, allergic rhinitis,
osteoporosis, menstrual disorder, and menopausal syndrome were prone to have more
TCM visits compared to non-TCM users.
Conclusion: Our population-based study revealed the high prevalence and specific
usage patterns of TCM in the RA patients in Taiwan. The information could be used
for further pharmacological investigation and clinical trials.
Keywords: complementary and alternative medicine; epidemiology; national health
insurance research database; rheumatoid arthritis; traditional Chinese medicine;
2
treatment.
3
Introduction
Rheumatoid arthritis（RA）is a common disorder among autoimmune diseases
affecting approximately one percent of worldwide population [1]. Although the
annual incidence in Taiwan was only 15.8 per 100,000 people [2], lower than the data
extracted from other countries [3], it could lead to significant synovial inflammation,
bone erosion and progressive disability. Even more, it also hampers somatic systems,
resulting in cardiovascular disease, interstitial lung disease, osteoporosis [4-7] and
mortality
[8,
9].
Non-steroid
anti-inflammation
drugs
(NSAIDs)
and
Disease-modifying antirheumatic drugs (DMARDs) are conventionally used to
suppress inflammation and modulate immunity [5, 7, 10]. Biologic agents that inhibit
tumor necrosis factor (TNF-), interleukin-1 (IL-1) and interleukin-6 (IL-6) are
also available to reduce the ongoing inflammation that is refractory to conventional
therapy [7]. Despite the fact that conventional and biological therapies are effective to
inhibit the inflammation; there are still some unmet needs and concerns [11-13]. The
economic burden of using biologic products may also delay the treatment if the
patient could not afford it.
Utilization of complementary and alternative medicine (CAM) was not
uncommon in patients with RA [14]. However, current knowledge of the usage of
CAM among RA patients is limited by research methodologies such as telephone
interview and questionnaires. Although there are some international studies on RA,
including the RAISE survey [13], as well as national studies including the Swedish
Rheumatology Quality Register (SRQ) [15], the Consortium of Rheumatology
Researchers of North America (CORRONA) registry [16, 17], the American
Rochester Epidemiology Project (REP) [3], the Italian RAPSODIA study [12] and the
Hong Kong study [9], there is a lack of large-scale surveys on the adjunctive CAM
usage specifically among RA patients.
4
Traditional Chinese medicine (TCM), including Chinese herbal remedies,
acupuncture and manipulative therapies, is commonly used as an adjunctive therapy
in different diseases in Asian countries [18]. In Chinese pollution, TCM has been used
as an adjunctive therapy for autoimmune and rheumatologic diseases. RA was viewed
as the Bi Syndrome (Impediment Syndrome) and treated according to the stages of the
disease, onset symptoms, and condition of whole body [19]. For example, Chinese
herbs might play a role in modulating cytokine networks in inflammatory response of
RA [20] or have analgesic effects [21]. In Taiwan, more than 99% of the total
population (23 million people) were enrolled in the mandatory National Health
Insurance (NHI) program since 1995 [22]. Not only Western medicine, but also TCM
treatment—including
Chinese
herbal
products,
acupuncture/moxibustion
and
manipulative therapy, were reimbursed by this program [23, 24]. We have also
identified the specific pattern of TCM usage in patients with Sjögren's syndrome [25],
asthma [26], allergic rhinitis [27] and rhinosinusitis [28].
To explore the characteristics of adjunctive TCM use in patients with RA, we
analyzed the registry for catastrophic illness patients of the National Health Insurance
Research Database (NHIRD) of Taiwan. This dataset comprehensively included all
clinical and laboratory confirmed RA patients with long-term follow-up and thus
could reduce the potential for sampling bias. The results of this study should provide
valuable information for patients, rheumatologists, and the government concerning
the healthcare of patients with RA. The Chinese herbal prescription patterns should
also serve as a candidate list for further pharmacological investigation and clinical
trial.
Methods
Data Source
5
Taiwan established the NHI program in March 1995. Nearly all of the necessary
Western medical services were reimbursed since 1995 and TCM services (Chinese
herbal remedies, acupuncture/moxibustion, and manipulative therapy) since 1996.
Any other treatment such as mediation, Qigong and tai chi were not covered. Only
licensed TCM doctors are qualified for reimbursement. In 2010, there were 23 million
people, equaled to 99.89% of the total population, enrolled in the NHI program [22].
The registry and original data comprising demographic characteristics, outpatient and
inpatient visits, diagnostic codes, assessments, procedures, prescriptions and medical
expenditure for reimbursement were included in the NHRID. The NHIRD also
established a “registry for catastrophic illnesses patient database (RCIPD)", including
about 30 disease categories such as cancer, schizophrenia, end-stage renal disease,
lupus and rheumatoid arthritis. RA patients who received complete clinical and
laboratory evaluation, followed by careful and routine review by rheumatologists
commissioned by the National Health Insurance Administration, were granted for
catastrophic illness certificates. This accuracy of the diagnosis of the RA patients
enrolled in this study is thus highly reliable [29].
Data Availability Statement: All data are deposited in an appropriate public
repository.
The
study’s
datasets
were
from
the
NHIRD
(http://w3.nhri.org.tw/nhird//date_01.html), which are maintained by National Health
Research Institutes (http://nhird.nhri.org.tw/en/index.htm), Taiwan.
Study Subjects and Variables
The flow chart for selection of RA cases was shown in Figure 1. First, all the
patients (n=47,809) with diagnosis of RA (International Classification of Diseases,
Ninth Revision, Clinical Modification (ICD-9-CM) code: 714.0) in the RCIPD of
NHIRD were included in this study. Ultimately, individuals with newly diagnosed RA
between January 2001 and December 2009 were included for this study (n=25,263)
6
and then followed-up until the end of 2011. After a confirmed diagnosis of RA, those
consulted with TCM doctors were grouped as TCM users (n=6,891), while the others
non-TCM users (n=18,372). The demographic characteristics and claims data of this
study cohort were collected and analyzed. Therapeutic actions and indication of TCM
prescription was recorded based on TCM theory [30].
Urbanization of the residence areas was described previously [24, 31]. In brief,
the residence area of Taiwan township were divided into 4 levels of urbanization
which were defined by population density (people/km2), the population ratio of
different educational level, ratio of elderly people, ratio of people of agriculture
workers, and the number of physicians per 100,000 people. Level 1 had the highest
degree of urbanization and level 4 had the lowest. Urbanization levels 1 and 2 were
defined as urban areas, while levels 3 and 4 were classified as rural areas.
Statistical analysis
All statistical analyses were performed using SAS software, version 9.2 (SAS
Institute Inc., Cary, NC, U.S.A.). Univariate analysis was used to compare the TCM
users with the non-TCM users. The chi-square test was performed to examine the
relationship between the categorical variables and to examine the differences between
TCM users and non-TCM users. Prevalence rate ratio indicated how large is the
prevalence of a disease in the TCM user group relative to the non-TCM users. A P
value <0.05 was considered as statistically significant. An open-sourced freeware
NodeXL (http://nodexl.codeplex.com/) identified the core patterns of Chinese herb
medicine used in treating RA patients, and all the selected two drugs combinations
were applied in this network analysis. The thicker line width, defined as counts of
connections between formulas and herbs, indicated significant prescription patterns in
the network figure [25].
Ethics Statement
7
The NHIRD was provided by the National Health Insurance Administration and
managed by National Health Research Institutes, Taiwan. All of the released datasets
were de-identified and scrambled for research. Therefore, it was not possible to
identify individual patient by any means. This study was approved by the Research
Ethics Committee of China Medical University and Hospital (CMU-REC-101-012).
Results
There were 47,809 patients diagnosed as RA with catastrophic illness certificates
enrolled in this study (Figure 1). After excluding the prevalent cases, there were
25,263 newly diagnosed RA patients. Among them, 6,891 (27.3%) patients were TCM
users while 18,372 (72.7%) subjects were non-TCM users. Demographic
characteristics (Table 1) revealed a proportional difference among the age groups
between TCM and non-TCM users. The mean age of TCM users were younger than
non-TCM users (49.6 ± 14.3 versus 54.0 ± 16.0). Although there was a female
predominance in both groups, there was a significantly higher female to male ratio in
TCM users versus non-TCM users (82.7%/17.3% versus 74.1%/25.9%). Regarding
the urbanization level of patients’ residence area, TCM users resided in more
urbanized area. The interval between the confirmed diagnosis of RA and the first
TCM visit was 23.4 months.
To understand the frequency of visits and therapeutic approaches utilized by
these TCM users, we analyzed the distribution of clinical visits in TCM users (Table
2). A portion of the patients (n=3,024; 43.9%) visited TCM clinics less than 3 times,
while 2,808 (40.7%) patients consulted TCM doctors more than 6 times. With regard
to the therapeutic approaches, majority (n=5,268; 76.4%) of the TCM users used
Chinese herbal remedies. Only 2.5% of the patients used acupuncture or traumatology
alone and 21.1% adapted both approaches.
8
We further analyzed the frequency distribution of clinical visits of TCM and
non-TCM user by major disease categories (as the reasons for consultation) (Table 3).
Other than musculoskeletal system and connective tissue disorders, RA patients most
commonly visited TCM or non-TCM doctors due to concurrent illness in digestive
system, respiratory system, nervous system, injury, skin and subcutaneous tissue,
infectious diseases, genitourinary system, endocrine/immunity disorder, mental
disorder and neoplasms. Comparing the TCM users and non-TCM users, we noticed
that there is a statistically higher frequency of outpatient visits among TCM users
across almost all disease categories except circulatory system (Table 3). The comorbid
neoplasm drew our attention and we did an additional subtyping to further analyze the
distribution of various benign and malignant tumor types among these patients (Table
4).
Furthermore, the ten most common herbal formulas and single herbs prescribed
by licensed TCM doctors for the treatment of RA were analyzed and listed in Table 5.
The
most
commonly
used
TCM
formula
Shang-Jong-Shiah-Tong-Yong-Tong-Feng-Wan
and
and
single
Rhizoma
herb
were
Corydalis
(Yan-Hu-Suo), respectively. We utilized the network analysis to demonstrate that
Myrrha,
Olibanum,
Dang-Gui-Nian-Tong-Tang,
Shu-Jing-Huo-Xie-Tang
and
Gui-Zhi-Shao-Yao-Zhi-Mu-Tang formed the core patterns of Chinese formulas and
herbs prescribed for RA patients in Figure 2.
Comparing the disease prevalence rate ratio of TCM versus non-TCM group, we
found that RA patients with certain diseases tended to receive treatment in TCM
clinics, rather than in non-TCM clinics (Table 6). Specifically, RA patients preferred
to visit TCM doctors when they had anxiety and depression, allergic rhinitis,
menstrual disorders, menopausal syndromes and osteoporosis.
9
Discussion
Our study is the first large-scale population-based investigation of TCM usage in
RA patients. RA patients with a younger age, female gender, or residency in urbanized
area had a tendency to consult TCM service. The most commonly adapted TCM
therapeutic approach is Chinese herbal remedies. The frequency of outpatient visits in
TCM users was higher across all disease categories except circulatory diseases. We
also identified the prescription patterns of TCM formulas and herbs. Especially, the
prevalence rate ratio of TCM versus non-TCM users was higher in diseases such as
anxiety and depression, allergic rhinitis, osteoporosis, menstrual disorders, and
menopausal syndromes. Overall, our study provided valuable information and added
value to the existing knowledge regarding healthcare in RA patients.
The strength of this study at least included the following aspects: First, all
residents of Taiwan can access the NHI system with low-cost and convenience [22],
there was no bias regarding the accessibility of healthcare, either Western or Chinese
medicine. Until 2012, there are approximately 59,017 Western medical doctors and
5,556 board-certified TCM doctors serving 23 million people in Taiwan. 93.7% of the
hospitals/clinics are contracted with the NHI program [32]. Second, all RA patients
with catastrophic illness certificates were included in this study. They were all
diagnosed by rheumatologists with confirmed clinical and laboratory tests. This
database is highly accurate and reliable for epidemiology study in RA patients [29].
Third, a couple unmet needs of RA patients do exist [12, 33]. Our experience of
adjunctive use of TCM in RA patients may provide some thoughts in the design of
future therapeutic strategy.
Consistent with previous data [14], female patients used CAM more frequently
than did male patients, and those who used complementary therapy were younger than
those who did not. Our and other’s studies also found that female with a higher
10
socioeconomic status, higher educational level and self-perceived poor health status
used TCM more often [34, 35]. It is surprising that even though RA has been a disease
prevalent in female, there were much more female patients using TCM. Regarding the
interval between RA diagnosis and the first consultation of TCM, our result is
consistent with a previous study [36]—patients with disease duration more than two
years were more likely to use CAM than those in early period of RA. It is probably
most patients usually used western medicine as first choice initially. If unsatisfied
with conventional therapy or disturbed by recurrence of symptoms, they might further
seek adjunctive TCM consultation [14].
Unlike the tendency toward acupuncture in most of the Western countries, herbal
remedies have been widely accepted in Taiwan. Western herbal products and dietary
supplements taken orally was one of the most common forms of CAM used in Europe
and America [37, 38]. However, herein the Chinese herbal remedies referred were not
only for supplementary or complementary use. This is partly due to the long history of
TCM usage in Chinese population. Fundamental principles such as “Yin and Yang”
and “Qi and Blood” having been integrated as part of Chinese culture and lifestyle.
Furthermore, the low cost and insurance coverage for TCM treatment also contributed
to the widespread of TCM. Regarding the visiting frequency, a significant portion
(43.9%) of RA patients might only sought for second opinion because they only
visited TCM clinics for 1-3 times. On the other hand, 40.7% of the RA patients used
TCM service for more than 6 times, which might be due to the confidence in
symptoms relief or effectiveness perceived by users.
RA is not a disease merely affecting joints. There is an increased prevalence of
cardiovascular disease, incidence of infection, and the development of malignancies
result in shortened life span in patients with RA. A previous investigation revealed
that depression was the most frequently associated disease, followed by asthma,
11
cardiovascular illness, solid tumors, and chronic obstructive pulmonary disease [39].
The result was consistent with our findings that RA patients had a broad spectrum of
disease category in their clinical visits, either in TCM or non-TCM users. The finding
that RA patients had a high prevalence of various comorbidities is in accordance with
a previous international cross-sectional study (COMORA study) [39]
It is undoubted that biological agents, high-dose corticosteroid and DMARDs
all can modulate the immunity to ameliorate the disease progression. However, many
patients worried about the side effects or still had unmet needs [14, 40]. The TCM
prescriptions from this nationwide survey could be used as a candidate list for further
pharmacological investigation. The most commonly prescribed herbal formula,
Shang-Jong-Shiah-Tong-Yong-Tong-Feng-Wan was used in TCM for arthritis and
pain control. According to the TCM theory, it could dispel wind and dampness,
promote blood circulation and clear heat. It has been used in relieve and cure the
symptoms of Bi Syndrome (Impingement Syndrome) including stiffness, tenderness,
swelling and deformity of the joints and limited range of motion [19].
Xiao-Huo-Luo-Dan consisted of Radix Aconiti Preparata, which was found to be an
effective analgesic [41].
Liu-Wei-Di-Huang-Wan was found to inhibit both Th1-
and Th2-type cytokine in human peripheral blood mononuclear cells in a previous
study [42].
Among the single herbs, Rhizoma Corydalis (Yan-Hu-Suo), has been used in
TCM for pain relief for a long time. Its extracts has been found to exert
anti-inflammatory activity in adjuvant-induced arthritis [43]. Clematichinenoside, a
kind of triterpene saponin isolated from Radix Clematidis (Wei-Ling-Xian), had been
proven its anti-inflammatory effect in collagen-induced-arthritis rats by decreasing
nitric oxide and TNF, and inhibiting the expression of NF-kappaB p65 subunits,
TNF- and cyclooxygenase-2 [44]. Radix Achyranthis Bidentatae (Niu-Xi), Cortex
12
Phellodendri (Huang-Bo) and Semen Coicis (Yi-Yi-Ren) are the three ingredients of
San-Miao-San, which could improve arthritis symptoms and lower level of
inflammatory cytokine IL-18 [20, 21]. Fructus Chaenomelis (Mu-Gua) also reduced
inflammation in adjuvant arthritis rats and inhibited of secretion of IL-1, TNF-α and
prostaglandin E2 [45].
Other than joint symptoms, depression is more common in patients with RA than
in healthy individuals. We found that the TCM prescriptions were not only for RA
itself but also covered a broad range of comorbidities. It has been reported that
vulnerable psychosocial status such as depression could be a predictor of negative
effect of RA in the follow-up period [46]. Our data showed that RA patients with
anxiety and depression were more likely to use TCM. Among the commonly
prescribed herbal remedies, Jia-Wei-Xiao-Yao-San, Tian-Wang-Bu-Xin-Dan and
Xiao-Chai-Hu-Tang, were usually used to bi-directionally adjust depressive and
anxious mood resulted from Qi stagnation and blood insufficiency according to TCM
theory [47, 48]. Women treated with Jia-Wei-Xiao-Yao-San had significantly
decreased serum IL-6 concentration, which had been reported to be increased in major
depressive disorders [49] and RA [50]. Among single herbs, Radix Salviae
Miltiorrhizae (Dan-Shen) has been widely used in the treatment of cardiovascular and
cerebrovascular diseases attributing to its capability to decrease blood clotting [51].
However, the frequency of TCM user’s clinical visit due to disease of circulatory
system was not higher than non-TCM user. It will be interesting to know whether it
could help to prevent or treat the cardiovascular complications resulting from RA.
To explore the most frequently used combinations of these formulas and single
herbs, we conduct network analysis of accumulative experiences of over five
thousands TCM practitioners and found that the core pattern consisted of “Myrrha and
Olibanum”,“Gui-Zhi-Shao-Yao-Zhi-Mu-Tang”, “Dang-Gui-Nian-Tong-Tang”, and
13
“Shu-Jing-Huo-Xie-Tang”. Two formulas, Gui-Zhi-Shao-Yao-Zhi-Mu-Tang and
Dang-Gui-Nian-Tong-Tang, were the center of connections and used to treat the
inflammation, swelling and tenderness of joints. Phellodendri Chinensis Cortex,
Atractylodis Lanceae Rhizoma and Achyranthis Bidentatae Radix composed
San-Miao-San, which could reduce inflammation. Myrrha and Olibanum made a pair
in quickening the blood and transform stasis correspond to poor periarticular
circulation or remodeling of joints. These results implied that TCM practitioners’
thoughts in treating RA were similar to the pathophysiologic mechanism proposed by
Western medicine.
Some caveats in this study merit comments. First, the laboratory data and
imaging findings were unavailable and not provided in this database. It was
impossible to judge the disease severity of the TCM users and non-TCM users.
However, most of the patients seeking CAM [14] or TCM [34] treatment perceived
themselves poor health status. It is possible these TCM users were at least not
satisfied with the current treatment. Second, Qiqong exercise or tai chi was not
covered by the NHI program. Although tai chi has been recommended in knee
osteoarthriti by the American College of Rheumatology [52], it is deemed as one of
the suggestions in the TCM consultations and thus not reimbursed by the insurance.
Except this, most of the TCM therapeutic approaches by licensed TCM doctors were
covered in the NHI system.
In conclusion, this study is the first large-scale nationwide population-based
investigation into TCM usage in RA patients. TCM use in RA patients was not
uncommon. The information could be used for further pharmacological investigation
and clinical trials. Additional basic and clinical studies on the use and mechanism of
TCM are warranted.
Key Messages:
14
1. Traditional Chinese medicine usage, especially herbal remedies, among RA patients
is not uncommon in Taiwan.
2. TCM users were younger, had a higher female/male ratio and resided in more
urbanized area.
3. RA patients who had anxiety and depression, allergic rhinitis, osteoporosis,
menstrual disorder, and menopausal syndrome were prone to have more TCM visits.
Acknowledgments
This study was based in part on data from the National Health Insurance Research
Database, provided by the National Health Insurance Administration, Ministry of
Health and Welfare, and managed by National Health Research Institutes. The
interpretation and conclusions contained herein do not represent those of National
Health Insurance Administration, Ministry of Health and Welfare, or National Health
Research Institutes.
Funding: This study was supported by China Medical University under the Aim for
Top University Plan of the Ministry of Education, Taiwan (Ａ-1-2-a (10343TU5)).
This study was also supported in part by China Medical University Hospital
(DMR-104-003) and the Taiwan Ministry of Health and Welfare Clinical Trial and
Research Center of Excellence (MOHW104-TDU-B-212-113002). Yen H-R. was
supported
by
a
career-developing
grant
(NHRI-EX101-10124SC,
NHRI-EX102-10124SC, NHRI-EX103-10124SC and NHRI-EX104-10124SC) from
the National Health Research Institutes, Taiwan.
Disclosure statement: The authors have declared no conflict of interest.
15
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19
Table 1. Demographic characteristics of the patients newly diagnosed with rheumatic
arthritis in Taiwan in 2001-2009
Variable
Non-TCM user
TCM user
N= 18372
N = 6891
(72.7%)
(27.3%)
Sex
p value*
<0.0001
Female
13606 (74.1)
5697 (82.7)
Male
4766 (25.9)
1194 (17.3)
54.0 ± 16.0
49.6 ± 14.3
604 (3.3)
228 (3.3)
20-39
2592 (14.1)
1322 (19.2)
40-59
8515 (46.3)
3752 (54.4)
≧60
6661 (36.3)
1589 (23.1)
Age at baseline
<0.0001
mean age (years ± SD)
<20
Urbanization
<0.0001
1 (most urbanized)
5008 (27.3)
1983 (28.8)
2
5429 (29.6)
2190 (31.8)
3
3003 (16.3)
1119 (16.2)
4 (least urbanized)
4932 (26.8)
1599 (23.2)
Interval between the diagnosis and
23.4
initial TCM use, median (months)
* P value between TCM and non TCM-user
TCM: traditional Chinese medicine
20
Table 2. The frequency distribution of therapeutic approaches in TCM users
Number of
Only Chinese
Only Acupuncture Combination of
Total
TCM visits
herbal remedies
or traumatology
both treatment
N = 5268 (%)
N = 170 (%)
N = 1453 (%)
1-3
2575 (48.9)
151 (88.8)
298 (20.5)
3024 (43.9)
4-6
803 (15.2)
13 (7.6)
243 (16.7)
1059 (15.4)
>6
1890 (35.9)
6 (3.5)
912 (62.8)
2808 (40.7)
N = 6891 (%)
TCM: traditional Chinese medicine
21
Table 3. The frequency distribution of TCM and non-TCM user by major disease categories
Disease (ICD-9-CM)
Non-TCM user TCM user
Total
N= 18372 (%)
N = 6891 (%)
N=25263
(%)
11421 (62.2)
4995 (72.5)
16416
(65.0)
<0.0001
1098 (6.0)
529 (7.7)
1627
(6.4)
<0.0001
10022 (54.6)
4117 (59.7)
14139
(56.0)
<0.0001
4009 (21.8)
1922 (27.9)
5931
(23.4)
<0.0001
Anemia (280.9,285.9)
3025 (16.5)
1483 (21.5)
3208
(12.7)
<0.0001
Mental disorder (290-319)
7141 (38.9)
3306 (48.0)
10447
(41.4)
<0.0001
Nervous system (320-389)
15076 (82.1)
6182 (89.7)
21258
(84.1)
<0.0001
Circulatory system
11640 (63.4)
4444 (64.5)
16084
(63.7)
0.0955
17083 (93)
6660 (96.6)
23743
(94.0)
<0.0001
17502 (95.3)
6792 (98.6)
24294
(96.1)
<0.0001
12421 (67.6)
5473 (79.4)
17894
(71.0)
<0.0001
2815 (20.7)
1765 (31.0)
4580
(18.1)
<0.0001
Infectious and parasitic
p value*
disease (001-139)
HBV (070.2, 070.3, and
V02.61)
Endocrine, nutritional and
metabolic disease and
immunity disorder
(240-279)
Blood and blood-forming
organs (280-289)
(390-459)
Respiratory system
(460-519)
Digestive system
(520-579)
Genitourinary system
(580-629)
Menstruation disorder
22
and other abnormal
bleeding from female
genital tract (626)
Menopausal and
3062 (22.5)
1984 (34.8)
5046
(20.0)
<0.0001
118 (0.9)
98 (1.7)
216
(0.9)
<0.0001
512 (2.8)
376 (5.5)
888
(3.5)
<0.0001
14009 (76.3)
5872 (85.2)
19881
(78.7)
<0.0001
18284 (99.5)
6891 (100.0)
25175
(99.7)
<0.0001
16005 (87.1)
6481 (94.1)
22486
(89.0)
<0.0001
14127 (76.9)
5880 (85.3)
20007
(79.2)
<0.0001
1216 (6.6)
786 (11.4)
2002
(7.9)
<0.0001
postmenopausal
disorders (627)
Female infertility (628)
Complications of
pregnancy, childbirth and
the puerperium (630-676)
Skin and subcutaneous
tissue (680-709)
Musculoskeletal system
and connective tissue
(710-739)
Symptoms, signs and
ill-defined conditions
(780-799)
Injury and poisoning
(800-999)
Others**
* p value between TCM and non TCM-user
**Others included ICD-9-CM code range 630–677, 740–759, 760–779, and missing/error data
TCM: traditional Chinese medicine; HBV: Viral hepatitis B
23
Table 4. The frequency distribution of TCM and non-TCM user by various tumor types
Disease (ICD-9-CM)
Non-TCM user TCM user
Total
N= 18372 (%)
N = 6891 (%) N=25263 (%)
6442 (35.1)
3160 (45.9)
9602
(38.0)
1624 (8.8)
514 (7.4)
2138
(8.5)
Female genital organs (**)
213 (1.2)
87 (1.2)
300
(1.2)
Thyroid gland (193)
62 (0.3)
22 (0.3)
84
(0.3)
4818 (26.2)
2646 (38.4)
7464
(29.5)
212 (1.2)
116 (1.7)
328
(1.3)
Other digestive system (211)
781 (4.3)
400 (5.8)
1181
(4.7)
Respiratory organs (212)
99 (0.5)
52 (0.8)
151
(0.6)
Bone and articular cartilage
73 (0.4)
40 (0.6)
113
(0.4)
Lipoma (214)
154 (0.8)
82 (1.2)
236
(0.9)
Other connective/soft tissue
579 (3.2)
314 (4.6)
893
(3.5)
Skin (216)
1285 (7.0)
743 (10.8)
2028
(8.0)
Breast (217)
836 (4.6)
531 (7.7)
1367
(5.4)
Uterine leiomyoma (218)
996 (5.4)
721 (10.5)
1717
(6.8)
Uterus, excluding leiomyoma
318 (1.7)
222 (3.2)
540
(2.1)
Ovary (220)
511 (2.8)
356 (5.2)
867
(3.4)
Other female genital organs
34 (0.2)
27 (0.4)
61
(0.2)
Neoplasms (140-239)*
Malignant
Benign
Lip, oral cavity and pharynx
(210)
(213)
(215)
(219)
(221 )
24
Male genital organs (222)
27 (0.1)
6 (0.1)
33
(0.1)
Kidney/other urinary organs
43 (0.2)
29 (0.4)
72
(0.3)
Eye (224)
16 (0.1)
10 (0.1)
26
(0.1)
Brain/other nervous system
125 (0.7)
70 (1.0)
195
(0.8)
Thyroid glands (226)
75 (0.4)
46 (0.7)
121
(0.5)
Other endocrine glands (227)
29 (0.2)
24 (0.3)
53
(0.2)
Hemangioma/lymphangioma
90 (0.5)
40 (0.6)
130
(0.5)
208 (1.1)
106 (1.5)
314
(1.2)
(223)
(225)
(228)
Others (229)
* p value between TCM and non-TCM users: <0.0001
** Female genital organs (ICD-9-CM) included uterus-unspecified part (179), cervix uteri
(180), placenta (181), body of uterus (182), ovary and other uterine adnexa (183) and
unspecified female genital organs (184)
TCM: traditional Chinese medicine
25
Table 5. Ten most common herbal formulas and single herbs prescribed for patients with
rheumatoid arthritis
TCM prescription
Therapeutic actions/
Number Average
indications in TCM
daily
dose
(g)
Herbal formula
169525
6.5
4310
7.3
blood
3514
5.5
Liu-Wei-Di-Huang-Wan
Enrich Yin
2716
6.3
Xiao-Huo-Luo-Dan
Dispel wind-damp
2309
6.5
Ban-Xia-Xie-Xin-Tang
Relieve GI upset
2218
3.5
Ping-Wei-San
Dry dampness
1519
3.8
Xiao-Chai-Hu-Tang
Harmonize Qi
1266
7.9
Tian-Wang-Bu-Xin-Dan
Enrich Yin
1247
4
Zuo-Gui-Wan
Enrich Yin
1024
4.9
Xiao-Qing-Long-Tang
Suppress cough and clam
704
3.3
264577
2.2
Shang-Jong-Shiah-Tong-Yong-Tong-Feng- Dispel wind-damp
Wan
Jia-Wei-Xiao-Yao-San
Rectify Qi and nourish
panting
Single herbs
Rhizoma Corydalis (Yan-Hu-Suo)
Relieve pain
7087
1.6
Radix Clematidis (Wei-Ling-Xian)
Dispel wind-damp
5623
1.6
Caulis Spatholobi (Ji-Xue-Teng)
Move the blood
5525
1.9
Semen Coicis (Yi-Yi-Ren)
Clear dampness
5199
1.9
26
Radix Achyranthis Bidentatae (Niu-Xi)
Strengthen sinew and bone
5187
2.7
Radix Salviae Miltiorrhizae (Dan-Shen)
Transform stasis
5068
1.4
Cortex Phellodendri (Huang-Bo)
Clear heat and dampness
4809
2.9
Ramulus Mori (Sang-Zhi)
Free the channels
4643
2
Ramulus Cinnamomi (Gui-Zhi)
Free the channels
4275
2.9
Fructus Chaenomelis (Mu-Gua)
Soothe the sinews
3885
1.7
TCM: traditional Chinese medicine
27
Table 6. Prevalence rate ratio of diseases between non-TCM and TCM user
Disease (ICD-9-CM) Non-TCM user
TCM user
PRR (95% CI)
Age group (year)
N (%)
N (%)
Anxiety (300) and depression (311)
All
4233 (23.0)
2267 (32.9)
1.18(1.12-1.24)
<20
37 (6.1)
19 (8.3)
1.16(0.67-2.02)
20-39
430 (16.6)
330 (25.0)
1.32(1.15-1.53)
40-59
2072 (24.3)
1334 (35.6)
1.24(1.16-1.33)
≧60
1694 (25.4)
584 (36.8)
1.13(1.03-1.24)
All
4135 (22.5)
2198 (31.9)
1.17(1.11-1.23)
<20
248 (41.1)
111 (48.7)
1.02(0.81-1.27)
20-39
646 (24.9)
455 (34.4)
1.21(1.08-1.37)
40-59
1987 (23.3)
1174 (31.3)
1.14(1.06-1.23)
≧60
1254 (18.8)
458 (28.8)
1.20(1.08-1.33)
All
3612 (19.7)
1749 (25.4)
1.07(1.01-1.13)
<20
10 (1.7)
10 (4.4)
2.27(0.94-5.45)
20-39
143 (5.5)
97 (7.3)
1.17(0.90-1.51)
40-59
1356 (15.9)
936 (25.0)
1.33(1.23-1.45)
≧60
2103 (31.6)
706 (44.4)
1.10(1.01-1.20)
All
2815 (20.7)
1765 (31.0)
1.25(1.18-1.33)
<20
103 (33.9)
61 (50.8)
1.33(0.97-1.82)
20-39
1214 (58.5)
789 (67.9)
1.02(0.93-1.11)
Allergic rhinitis (477.9)
Osteoporosis (733)
Menstrual disorder (626)
28
40-59
1410 (21.6)
880 (27.7)
1.10(1.01-1.19)
≧60
88 (1.9)
35 (2.8)
1.20(0.81-1.78)
3062 (22.5)
1984 (34.8)
1.29(1.22-1.37)
20-39
111 (5.4)
90 (7.8)
1.27(0.96-1.68)
40-59
2188 (33.5)
1548 (48.7)
1.24(1.16-1.33)
≧60
761 (16.2)
346 (28.0)
1.38(1.21-1.56)
Menopausal syndrome (627)
All
*PRR: prevalence rate ratio: the prevalence of a disease in the TCM user group
relative to the non-TCM user
CI: confidential interval
TCM: traditional Chinese medicine
29
Figure Legend
Figure 1. Flow recruitment chart of subjects from the registry for catastrophic illness
patient database (RCIPD) obtained from the National Health Insurance Research
Database (NHIRD) in Taiwan. TCM: traditional Chinese medicine.
Figure 2: The top 50 herbal formulas and single herbs for rheumatoid arthritis patients
were analyzed through open-sourced freeware NodeXL, and the core pattern of these
Chinese herbal medicine showed that Myrrha, Olibanum, Dang-Gui-Nian-Tong-Tang
Shu-Jing-Huo-Xie-Tang, and Gui-Zhi-Shao-Yao-Zhi-Mu-Tang were among the most
frequently used combinations.
30