Clinical Practice Pattern of Korean Medicine Doctors in Idiopathic Short Stature Treatment: A Survey Study

Background Korean medicine (KM) interventions are attractive for children with idiopathic short stature (ISS). We investigated the real-world clinical practice patterns of KM doctors in ISS treatment. Methods The survey targeted KM doctors who have treated patients with ISS in KM clinical settings for >3 years. We included questions on the diagnosis and treatment patterns, effects, cost, and opinions of doctors on KM treatment for ISS. A frequency analysis was performed. Results There were 58 respondents, and “heights of parents” (n = 57, 98.3%), “height, weight, and growth rate of child” (n = 55, 94.8%), and “amount of meals, digestive function” (n = 52, 89.7%) were frequently used as indicators for diagnosis and treatment. The most frequently used KM interventions were “herbal medicine” (n = 58, 100%), “acupuncture” (n = 49, 84.5%), “moxibustion” (n = 38, 65.5%), “dry cupping” (n = 26, 44.8%), and “physiotherapy” (n = 22, 37.9%). Herbal medicines were generally prescribed to tonify the spleen or kidney, and the most frequently used individual herbs were Acanthopanacis cortex, Astragali Radix, and Cervi parvum cornu. The most common acupuncture points were ST36, GB34, SP6, EX-LE5, and LI4. Conclusions This study showed the use of KM for ISS in real-world clinical settings. In the future, well-designed clinical studies to verify the effect of KM treatment on ISS based on real-world clinical practice patterns should be actively performed.


Introduction
Idiopathic short stature (ISS) is defined as when the individual's height is two standard deviations or more below the corresponding average height for a given age, sex, and population group, in the absence of any systemic, endocrine, nutritional, or chromosomal abnormality [1]. Approximately 80% of children with short stature are estimated to have ISS [2] and its prevalence is estimated of 16 per 1,000 children [3]. In conventional medicine, recombinant human growth hormone (GH) has been used as the primary standard therapy for ISS since it was approved by the US Food and Drug Administration in 2003 [4]. However, this treatment is rather inconvenient and expensive because it requires daily parenteral administration. Additionally, concerns have been raised regarding the safety of long-term GH treatment, including a decreased sensitivity to insulin, an increased risk of type 2 diabetes, and an adverse effect on peak bone mineralization [5][6][7].
In South Korea, Korean medicine (KM) treatments, including acupuncture, moxibustion, and herbal medicine, also known as East Asian traditional medicine (EATM), one of the most well-known types of complementary and integrative medicine, have been widely used as an alternative treatment method to support child growth. According to a retrospective study in 2016, growth retardation was the chief complaint among children and adolescents who visited the department of Korean Pediatrics in a KM Hospital [8]. Several preclinical and clinical studies have shown that EATM therapies are effective in treating ISS [9][10][11][12].
However, clinical practice guidelines of KM for pediatric growth disorder have not been published. erefore, an indepth investigation of the diagnosis and treatment patterns of KM doctors (KMDs), as well as the treatment cost for ISS, may enhance the understanding of the actual healthcare situation and contribute to research that reflects real-world clinical settings.

Study Aim, Design, and Setting.
e aim of this study was to investigate the clinical practice patterns of KMDs in ISS treatment and their therapeutic effects and costs in realworld clinical settings.
is study used a cross-sectional survey design to assess the clinical practice patterns of KMD for ISS treatment in South Korea. e survey was conducted by Mediresearch (https://www.mediresearch.co.kr), which is a professional survey research company. e company sent a questionnaire survey via mobile phone to KMDs affiliated with KM clinics or hospitals, based on the cooperation of the Association of Pediatrics of KM. e company recruited participants with consideration of the ratio between specialists in pediatrics and general KM practitioners. e participants were enrolled voluntarily and they were informed that responses were required for all our questions in the questionnaire. e survey was conducted anonymously between November 24 and December 23, 2020.

Participants.
e purpose of this study was to observe the clinical practice patterns of KMD in real-world settings, not to verify the treatment effect; therefore, there was no special method for determining the sample size. We determined the minimum number of respondents as 40, with additional recruitment ongoing until the end of the study period. e inclusion criterion was >3 years of experience of ISS treatment in KM clinical settings.

Questionnaire.
e questionnaire was developed by three traditional KM experts who discussed and selected investigation items. e experts sought to create a concise and easily readable questionnaire to raise the response rate.
ey conducted a pilot test with a draft questionnaire and feedback was collected. e final version of the questionnaire was developed for respondent convenience using smartphones. e questionnaire consisted of five categories. Variable descriptions are as follows: (

Ethical Considerations.
e study was explained to all participants prior to the initiation of the survey. Only those who voluntarily agreed to participate and for their collected data to be published were enrolled in the study. is study was approved by the Institutional Review Board of Korea Institution of Oriental Medicine (IRB No. I-2010-008-002-01).

Effectiveness and Cost of Korean Medicine Treatment for ISS.
According to the response of KMDs, the mean (standard deviation) of growth height after KM treatment was 6.03 (0.98) cm before puberty and 9.03 (1.56) cm during puberty in boys; and 5.83 (1.05) cm before puberty and 8.36 (1.71) cm during puberty in girls (Table 5). e distribution of the cost of each intervention is described in Table 6. e cost of moxibustion, dry cupping, and physiotherapy was typically <9 dollars per visit, and acupuncture was <11 dollars per visit. e cost of herbal medicine for the majority of respondents (n � 45, 77.6%) ranged from 156 to 268 dollars per 15 days. e daily cost of herbal medicine was between 10.4 and 17.9 dollars.

Discussion
is survey investigated the clinical practice patterns of KM treatment for ISS, including a detailed evaluation of diagnosis, treatment, effectiveness, and costs. Furthermore, we sought the opinions of KMDs regarding their use of these Evidence-Based Complementary and Alternative Medicine 3 treatments. We have also previously reported a network meta-analysis [13] and an observational case series [14] of integrative KM treatment for ISS. e findings suggested that EATM plus GH might have a synergistic effect in comparison with EATM or GH alone [13]. In addition, the changes in growth indicators in children with ISS before and after KM treatment showed the potential of KM for the management of ISS [14]. However, detailed information regarding interventions and costs could not be obtained by both studies because they were secondary research studies using existing data. erefore, we designed this survey to obtain specific information regarding ISS treatment. Pattern identification based on KM theory could be a significant method for treating ISS because it is a primary growth disorder with an unknown cause. ISS is typically regarded as a problem with digestive disorders or lack of nourishment in KM [15].
is is consistent with the majority of respondents focusing on "tonifying the spleen (補脾) or the kidney (補腎)" as the purpose of ISS treatment in our study. In EATM, "tonifying the spleen" is    Evidence-Based Complementary and Alternative Medicine defined as a therapeutic method to treat diminished functional activities of the spleen by using tonifying medicines. "Tonifying the kidney" is a general term for treating deficiency patterns/syndromes of the kidney with tonifying medicines [16]. Taken together, these data show that herbal medicine is regarded as an essential ISS treatment intervention. Furthermore, acupuncture and moxibustion are also necessary for ISS treatment. e administration period for herbal medicines was between 2 and 6 months, and the frequency of other interventions was once a week. Yukmijihwang-tang (六味地黃湯) [17], the most common herbal prescription requiring coverage by health insurance, is a representative herbal medicine for tonifying the kidney. Sogeonjung-tang (小建中湯) [18] and Yukgunja-tang (六君子湯) [19], which were the second and third most commonly recorded, are herbal medicines used to tonify the spleen. In particular, Sogeonjung-tang is a first-line KM treatment for children with a lack of appetite or poor digestion [18]. e most frequently used individual herbs for ISS treatment in clinical settings were Acanthopanacis cortex (五 加皮), followed by Astragali Radix (黃芪) and Cervi parvum cornu (鹿茸). e effects of a complex herbal mixture containing Acanthopanacis cortex, Astragali Radix, and Dipsaci Radix (續斷) on height growth have been studied previously and the study showed that height gain was significantly higher in the herbal mixture group than in the placebo group after 24 weeks [12]. Additionally, Cervi parvum cornu is the most popular supplement for growth promotion and continues to grow in popularity [20]. In addition, ST36 (Zusanli), the acupuncture point that KMDs reported using most frequently, is actively used in traditional Chinese medicine clinical research, and its positive effect on growth has been studied [21].  Evidence-Based Complementary and Alternative Medicine  Evidence-Based Complementary and Alternative Medicine All the acupoints frequently used for the treatment of ISS, except GV20 (Baihui) and CV12 (Zhongwan), were located below the knee to the toes (Table 4).
is could stimulate height growth by stimulating the bones of the knee, tibia, and ankle. ST36 (Zusanli) is the most frequently selected acupoint and has been also used for the treatment of short stature in other studies [22,23]. SP6 (Sanyinjiao)is an acupoint where the three yin meridians of the liver, spleen, and kidney meet, and is used to tonify the liver, spleen, and kidney. GV20 (Baihui) is placed at the top of the head where all yang-qi gathers, and CV12 (Zhongwan), which strengthens digestive functions, is placed at the middle of the umbilicus and the xiphisternal joint.
Several studies have conducted the economic evaluation of GH treatment on ISS [24,25]. Furthermore, clinical trials have examined the growth effects of herbal medicines in China [26,27]; however, studies conducting economic evaluation of complementary therapies, such as herbal medicines and acupuncture, for ISS treatment have not been published. We sought to calculate the incremental cost-effectiveness ratio of KM intervention for ISS by extracting the data from systematic reviews, randomized controlled trials, or national secondary data; however, no proper data provided the costs and growth effects of KM interventions.
Accordingly, we collected costs and height growth data in this survey, although it was not sufficient to make any conclusions. Nonetheless, we estimated that three months (the most responsive treatment period) of treatment with herbal medicine, acupuncture, and moxibustion would cost in the range of USD 1,554-1,824. e frequency and cost of acupuncture and moxibustion were assumed to be as once a week and USD 9 per session, respectively. e difference in height growth before and after KM treatment was 1.93 cm (before puberty) and 2.53 cm (puberty) in boys; and 1.69 cm (before puberty) and 2.22 cm (puberty) in girls (Table 5). erefore, considering the relatively low cost and the effect of height growth of the KM treatment, KM treatment may be cost-effective for ISS treatment. Additionally, almost half of the KMDs who participated in this survey answered that KM treatment was more cost-effective than GH (Table 7). However, the estimated effectiveness and cost of KM treatment were based on the response of a small number of KMDs and not the actual patient data; thus, it was difficult to compare it with GH treatment (currently used treatment). In is is reported as the primary limitation of KM treatment for growth disorders. Several health promotion programs have reported using KM interventions for child growth in public health centers [28]. Health promotion, in contrast to clinical treatment, consists of exercise, education, herbal medicine, and acupuncture. In addition, we are developing a KM health promotion program for children's growth based on the results of this survey. Many KMDs responded that herbal medicine with a type of decoction should be included in a health promotion program; however, it is difficult to provide decoctions because of costs and quality control. Health promotion programs are generally provided free of charge to residents in need; therefore, this could help children with ISS safely and effectively.
ere are several limitations in this study. First, the number of participants was small and not representative of the entire KMD population. is survey aimed to recruit KMDs who focused on pediatric care with >3 years of clinical experience with ISS rather than more respondents to investigate clinical patterns in detail. e total number of KMDs is approximately 22,000, and there are only about 130 pediatric specialists focusing on KM in South Korea [29]. In addition, the sample size was small for realistic reasons, such as the study period and funding size. Second, recall bias is likely because the survey depended on the memory of respondents. A future chart analysis study is recommended to extract more accurate data. Additionally, the cost of herbal medicines varies significantly depending on the herb; therefore, the cost effectiveness can only be assessed as reference. Nevertheless, to the best of our knowledge, this study is the first to assess the clinical treatment pattern of ISS in a real-world KM setting.

Conclusions
is study analyzed the current KM clinical practice for the treatment of ISS, focusing on diagnosis indices and treatment patterns. e effects and costs of height growth and opinions of KMDs were also investigated. In the future, studies evaluating the efficacy and cost-effectiveness of KM treatment for ISS should be performed based on real-world clinical practice.