Systematic Review Protocol

Efficacy and Safety of Acupoint Catgut Embedding for Knee Osteoarthritis: a Protocol for Systematic review and Meta-Analysis
1KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon, Korea
2Korean Convergence Medical Science, University of Science & Technology, School of Korea Institute of Oriental Medicine, Daejeon, Korea
3Department of Acupuncture, Beijing GuangRen Combination of Traditional Chinese and Western Medicine Hospital, Beijing, China
This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
J Acupunct Meridian Stud 2024; 17(2): 76-80
Published April 30, 2024 https://doi.org/10.51507/j.jams.2024.17.2.76
Copyright © Medical Association of Pharmacopuncture Institute.
Abstract
Methods: Eleven databases will be searched from inception to August 1, 2023, without language limitations. Additionally, two registration platforms—ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry—will be searched for ongoing trials. The primary outcomes will be assessed using the Visual Analog Scale and the Western Ontario and McMaster Universities Osteoarthritis Index. Secondary outcomes include the total effective rate, Lysholm Score, and adverse effects. Two reviewers will independently select the studies, extract data, and evaluate the risk of bias and the quality of evidence.
Discussion: This systematic review will provide evidence regarding the safety and efficacy of acupoint catgut embedding in patients with knee osteoarthritis.
Keywords
INTRODUCTION
As a degenerative disease, knee osteoarthritis (OA) causes chronic joint pain, stiffness, deformity, and a limited range of motion [1]. It involves erosion and expansion of the calcified cartilage zone and the generation of matrix degradation products and proinflammatory mediators [2]. The prevalence of knee OA is rapidly increasing globally. In Sweden, the prevalence of patients with knee OA aged 45 or older was 13.8% based on data from 1.26 million inhabitants in 2012, and it is projected to be 15.7% in 2032 [3]. According to the Korean National Health and Nutrition Examination Survey in South Korea, the prevalence of radiographic knee OA is 4.4% in males and 19.2% in females [4]. In China, the prevalence of symptomatic knee OA is 10.3% in males and 5.7% in females, based on a population-based longitudinal survey [5]. Moreover, knee OA results in substantial economic expenses, including the need for a caregiver to administer treatment and patient care [6]. The high prevalence and economic cost of knee OA necessitate suitable therapies.
Current treatments for knee OA can be divided into three categories: exercise therapy, pain medication, and joint replacement surgery [2]. Considering knee OA primarily affects older adults [7], exercise therapy for these patients leads to long-term knee performance and high self-reliance [8]; moreover, it is recommended for mild-to-moderate knee OA [9,10]. Regarding pain medication for this condition, paracetamol and NSAIDs are recommended [2]. However, paracetamol may not be as effective when used alone [11]. NSAIDs have some side effects, such as indigestion [12]. Although joint replacement surgery is clinically relevant for end-stage knee OA [13], 25% of patients continue to complain of pain and disability one year after surgery [14]. Therefore, effective low-risk therapy is recommended for this patient population.
Acupoint catgut embedding (ACE) is a complementary and alternative medicine modality that continuously stimulates acupoints by implanting threads or catguts into acupoints using acupuncture needles [15]. It has been widely used in East Asian countries [16], with gradually increasing adoption in other countries such as Mexico and Indonesia [17,18]. Based on our previous experimental systematic review, we speculate that ACE may have anti-inflammatory mechanisms by suppressing inflammatory mediators and cytokines [19]. Moreover, recipients do not require daily treatment; patients are typically treated once weekly for two weeks [16]. This approach saves practitioners time and resolves patients’ fears of acupuncture. To date, only one systematic review on knee OA has been conducted [20]. However, it was published in 2018 and represents the only final review of three randomized controlled trials (RCTs). Thus, a meta-analysis of the efficacy of ACE in knee OA has yet to be performed. Therefore, this study aims to comprehensively assess the effectiveness and safety of ACE in treating knee OA.
MATERIALS AND METHODS
1. Study registration
This systematic review protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [21]. Additionally, it has been registered in the international Prospective Review database (PROSPERO) under the registration number CRD4202345 4230. The PRISMA-P checklist is shown in Supplementary Table 1. Ethical approval was not required for this protocol.
2. Type of studies
We will include all RCTs related to knee OA associated with ACE. However, we will exclude literature reviews, animal studies, and non-RCTs (including case, observational, and cohort studies).
1) Type of participants
This study will include patients of any age, race, or sex who have been diagnosed with knee OA using diagnostic criteria such as the American College of Rheumatology/Arthritis Foundation guidelines [22], guidelines for diagnosing and treating OA, and other valid diagnostic criteria.
2) Type of interventions
We will include studies using ACE alone or in combination with conventional treatments, which include medication, manual acupuncture, and electro-acupuncture, as well as combination treatment in both the control and experimental groups. Additionally, we will not restrict the type of ACE materials used, including, but not limited to, catgut, polydioxanone, and poly1acticcoglycolic acid.
3) Type of comparisons
This study will include various possible original therapies, such as Western medicine, articulation injection, manual acupuncture, practice, hyperbaric oxygen, and usual care. Additionally, we will incorporate placebo controls, such as sham ACE, to assess the placebo effect.
4) Outcome measures
The primary outcomes will be assessed using the Visual Analog Scale and Western Ontario and McMaster Universities OA Index. Secondary outcomes will include the total efficacy rate, Lysholm Score, and adverse effects.
3. Data sources
To identify all eligible studies, we will search the following 11 databases from inception to August 1, 2023, without language limitations: the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, Web of Science, Chinese Biomedical Literature Database, Chinese Scientific Journal Database (VIP database), Wan-Fang Database, China National Knowledge Infrastructure, Oriental Medicine Advanced Searching Integrated System, Science-On, and KoreaMed. Additionally, we will explore two databases for prospectively registered and ongoing trials: the World Health Organization International Clinical Trials Registry Platform search portal (http://apps.who.int/trialsearch/Default) and ClinicalTrials.gov (http://ClinicalTrials.gov/). The search strategy for PubMed is presented in Table 1, and the remaining relevant strategies are shown in Supplementary Table 2.
-
Table 1 . Search strategy for PubMed
#1 “osteoarthritis, knee”[MeSH Terms] #2 “Knee”[MeSH Terms] #3 “osteoarthr*”[All Fields] #4 “degenerative arthritis”[All Fields] #5 #1 OR #2 OR #3 OR #4 #6 “catgut”[All Fields] #7 “thread*”[All Fields] #8 “acupoint*”[All Fields] #9 “needle”[All Fields] #10 “acupunctural”[All Fields] #11 #6 OR #7 OR #8 OR #9 OR #10 #12 “embed*”[All Fields] #13 “implant*”[All Fields] #14 #12 OR #13 #15 #14 AND #11 #16 “Randomized Controlled Trial”[MeSH Terms] #17 “Controlled Clinical Trial”[MeSH Terms] #18 “random*”[All Fields] #19 “placebo”[All Fields] #20 “trial”[All Fields] #21 #16 OR #17 OR #18 OR #19 OR #20 #22 #21 AND #15 AND #5
4. Selection of studies
Two reviewers (HY Zhao and Y Liu) will independently select studies based on the systematic review process. First, they will screen research titles and abstracts to select relevant studies. Second, they will retrieve the full text and read the studies for double-checking. If disagreements occur, a third reviewer (CH Han) will be consulted. The flow diagram of the study selection process is shown in Supplementary Fig. 1.
5. Data extraction
We will extract the data using an Excel spreadsheet (Microsoft Office Professional Plus 2019, Microsoft, Albuquerque, NM, USA). Two reviewers will independently extract data from the selected studies. Any disagreements during the crosschecking process will be resolved through discussions. The following data will be included: first author, year of publication, country, intervention and comparison treatments, treatment duration, acupoint of intervention, outcome measurements, and adverse events.
6. Quality assessment
Two independent reviewers will evaluate the selected studies using the Cochrane Handbook for Systematic Review of Interventions [23]. Seven aspects will be assessed: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessments, incomplete outcome data, selective reporting, and other biases. Each aspect will be classified as low, high, or unclear. In case of any disagreement, a third reviewer will resolve it.
7. Data synthesis
Statistical analysis will be performed using Review Manager (RevMan) version 5.4.1 for Windows software (Copenhagen, The Nordic Cochrane Center, the Cochrane Collaboration, 2020). For continuous data, mean differences (or standardized mean differences) and standard deviations will be used in the meta-analysis with a 95% confidence interval (CI). Dichotomous results will be expressed as relative risk with a 95% CI. Furthermore, we will use I2 and χ2 to measure heterogeneity. If p > 0.1 and I2 < 50%, indicating homogeneity, a fixed-effects model will be used in the meta-analysis. Otherwise, a random-effects model will be used. If a quantitative synthesis is not appropriate for some outcomes, we will summarize the findings of the studies and conclude.
8. Dealing with missing data
The author will try to contact the corresponding authors to obtain specific data by using their phone number and e-mail if missing data occurs.
9. Assessment of heterogeneity
Heterogeneity will be detected using I2 and χ2 measures. High heterogeneity will be indicated if I2 is > 50. A meta-analysis will be conducted to reduce heterogeneity based on the same comparator. If high heterogeneity is observed, subgroup analyses will explore potential reasons, including the same acupoints, treatment durations, and materials.
10. Sensitivity analysis
The final included studies will exhibit a high-quality methodology, sufficient sample size, and low heterogeneity. We will conduct a sensitivity analysis to measure the robustness of the study.
11. Assessment of reporting biases
If the final number of selected studies exceeds 10, we will use funnel plots to assess reporting bias.
12 Assessment of quality of evidence
We will use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method [24] to assess the quality of evidence for primary and secondary outcomes. This method includes five major domains: inconsistency, limitations, imprecision, indirectness, and publication bias. The evidence will be categorized into four levels of evidence quality: high, moderate, low, and very low.
DISCUSSION
ACE is a method developed from manual acupuncture that has evolved over 60 years. It involves implanting threads or catguts into the skin tissue at acupoints, which can aid in managing various conditions [25]. Moreover, it is crucial to consider the patient’s economic situation when treating knee OA. A previous report indicates that the cost of ACE is lower than that of electroacupuncture for treating obesity, primarily due to the absence of daily administration requirements [26].
However, this study has some limitations that must be considered. Given the nature of systemic reviews, standardization of factors such as different acupoints and treatment durations and the inability to blind ACE practitioners will not be possible. Nonetheless, no systematic and comprehensive meta-analyses of ACE’s therapeutic effects and safety in knee OA have been conducted. Therefore, this protocol of a systematic review of ACE for knee OA will provide evidence to health policymakers and scientific researchers and offer additional treatment options for patients with knee OA.
ACKNOWLEDGEMENTS
This work was supported by the Korea Institute of Oriental Medicine grant number KSN23314113.
SUPPLEMENTARY MATERIAL
Supplementary data to this article can be found online at https://doi.org/10.51507/j.jams.2024.17.2.76.
FUNDING
This work was supported by the Korea Institute of Oriental Medicine grant number KSN23314113. The funder had no role in the review or preparation of the manuscript or the decision to publish.
AUTHORS’ CONTRIBUTIONS
Study conception, development of study criteria, and writing of the manuscript: HYZ and CHH. Conduction of preliminary searches: HYZ and YL. Examination of the relevance of the protocol in clinical practice: HYZ. Manuscript revision: CHH. All the authors have read and approved the final manuscript.
CONFLICT OF INTEREST
The authors declare no conflict of interest.
References
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- Hunter DJ, Bierma-Zeinstra S. Osteoarthritis. Lancet 2019;393:1745-59. https://doi.org/10.1016/S0140-6736(19)30417-9
- Turkiewicz A, Petersson IF, Björk J, Hawker G, Dahlberg LE, Lohmander LS, et al. Current and future impact of osteoarthritis on health care: a population-based study with projections to year 2032. Osteoarthritis Cartilage 2014;22:1826-32. https://doi.org/10.1016/j.joca.2014.07.015
- Lee S, Kim SJ. Prevalence of knee osteoarthritis, risk factors, and quality of life: the Fifth Korean National Health and Nutrition Examination Survey. Int J Rheum Dis 2017;20:809-17.
- Tang X, Wang S, Zhan S, Niu J, Tao K, Zhang Y, et al. The prevalence of symptomatic knee osteoarthritis in China: results from the China Health and Retirement Longitudinal Study. Arthritis Rheumatol 2016;68:648-53.
- Altman RD. Early management of osteoarthritis. Am J Manag Care 2010;16 Suppl Management:S41-7.
- Losina E, Weinstein AM, Reichmann WM, Burbine SA, Solomon DH, Daigle ME, et al. Lifetime risk and age at diagnosis of symptomatic knee osteoarthritis in the US. Arthritis Care Res (Hoboken) 2013;65:703-11. https://doi.org/10.1002/acr.21898
- Vincent KR, Vincent HK. Resistance exercise for knee osteoarthritis. PM R 2012;4(5 Suppl):S45-52.
- Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Arthritis Rheum 2000;43:1905-15.
- Jordan KM, Arden NK, Doherty M, Bannwarth B, Bijlsma JW, Dieppe P, et al. EULAR Recommendations 2003: an evidence based approach to the management of knee osteoarthritis: report of a Task Force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT). Ann Rheum Dis 2003;62:1145-55.
- da Costa BR, Reichenbach S, Keller N, Nartey L, Wandel S, Jüni P, et al. Effectiveness of non-steroidal anti-inflammatory drugs for the treatment of pain in knee and hip osteoarthritis: a network meta-analysis. Lancet 2017;390:e21-33.
- Laine L. Gastrointestinal effects of NSAIDs and coxibs. J Pain Symptom Manage 2003;25(2 Suppl):S32-40.
- Ruiz D Jr, Koenig L, Dall TM, Gallo P, Narzikul A, Parvizi J, et al. The direct and indirect costs to society of treatment for end-stage knee osteoarthritis. J Bone Joint Surg Am 2013;95:1473-80. https://doi.org/10.2106/JBJS.L.01488
- Singh JA, Lewallen D. Predictors of pain and use of pain medications following primary Total Hip Arthroplasty (THA): 5,707 THAs at 2-years and 3,289 THAs at 5-years. BMC Mus. culoskelet Disord 2010;11:90.
- Huo J, Zhao J, Yuan Y, Wang J. Research status of the effect mechanism on catgut-point embedding therapy. Zhongguo Zhen Jiu 2017;37:1251-4. Chinese.
- Zhao HY, Kim S, Son MJ. Comparing acupoint catgut embedding and acupuncture therapies for simple obesity: a protocol for systematic review and meta-analysis. Medicine (Baltimore) 2022;101:e31531.
- Flores M, Carlin G, Ordaz C, Oropeza L, Sánchez V, Becerril F. Effect of the acupoint catgut embedding therapy vs sham acupuncture in overweight and obese patients in México. Rev Int Acupunt 2019;13:12-6. Spanish.
- Tanudjaja CP, Simadibrata C, Srilestari A, Kresnawan T. Effects of acupoint catgut embedding therapy paired with dietary intervention on tumour necrosis factor-α levels and abdominal circumference in patients with obesity. J Phys Conf Ser 2018;1073:062032. https://doi.org/10.1088/1742-6596/1073/6/062032
- Jun P, Zhao HY, Kang SY, Han CH. Thread embedding therapy in rheumatoid arthritis: a systematic review of animal studies. Korean J Acupunct 2021;38:122-32.
- Park JM, Lee JS, Lee EY, Roh JD, Jo NY, Lee CK. A systematic review on thread embedding therapy of knee osteoarthritis. Korean J Acupunct 2018;35:159-65.
- Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ 2015;350:g7647. Erratum in: BMJ 2016;354: i4086. https://doi.org/10.1136/bmj.g7647
- Kolasinski SL, Neogi T, Hochberg MC, Oatis C, Guyatt G, Block J, et al. 2019 American College of Rheumatology/Arthritis Foundation guideline for the management of osteoarthritis of the hand, hip, and knee. Arthritis Rheumatol 2020;72:220-33. Erratum in: Arthritis Rheumatol 2021;73:799.
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- Schünemann HJ, Mustafa R, Brozek J, Santesso N, Alonso-Coello P, Guyatt G, et al. GRADE Guidelines: 16. GRADE evidence to decision frameworks for tests in clinical practice and public health. J Clin Epidemiol 2016;76:89-98.
- Sun W, Chu N, Feng Y, Wang Y, Ma Y, Jiang G. Preliminary study on depth of embedded catgut and qi arrival at cervical Jiaji (EX-B 2) under ultrasound guidance. Zhongguo Zhen Jiu 2015;35:931-4. Chinese.
- Huang LC, Pan WY. Comparation of effect and cost-benefit analysis between acupoint catgut-embedding and electroacupuncture on simple obesity. Zhongguo Zhen Jiu 2011;31:883-6. Chinese.
Related articles in JAMS

Article
Systematic Review Protocol
J Acupunct Meridian Stud 2024; 17(2): 76-80
Published online April 30, 2024 https://doi.org/10.51507/j.jams.2024.17.2.76
Copyright © Medical Association of Pharmacopuncture Institute.
Efficacy and Safety of Acupoint Catgut Embedding for Knee Osteoarthritis: a Protocol for Systematic review and Meta-Analysis
HuiYan Zhao1,2,† , Yan Liu3,†
, Changsop Yang1
, Chang-Hyun Han1,2,*
1KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon, Korea
2Korean Convergence Medical Science, University of Science & Technology, School of Korea Institute of Oriental Medicine, Daejeon, Korea
3Department of Acupuncture, Beijing GuangRen Combination of Traditional Chinese and Western Medicine Hospital, Beijing, China
Correspondence to:Chang-Hyun Han
KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon, Korea
E-mail chhan@kiom.re.kr
†These authors (HuiYan Zhao, Yan Liu) share the first authorship.
This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background: Knee osteoarthritis causes physical dysfunction, and its prevalence increases with age. Although clinical studies examined acupoint catgut embedding in patients with knee osteoarthritis, no systematic reviews or meta-analyses have been conducted to date. We aim to comprehensively review the effects of acupoint catgut embedding on knee osteoarthritis.
Methods: Eleven databases will be searched from inception to August 1, 2023, without language limitations. Additionally, two registration platforms—ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry—will be searched for ongoing trials. The primary outcomes will be assessed using the Visual Analog Scale and the Western Ontario and McMaster Universities Osteoarthritis Index. Secondary outcomes include the total effective rate, Lysholm Score, and adverse effects. Two reviewers will independently select the studies, extract data, and evaluate the risk of bias and the quality of evidence.
Discussion: This systematic review will provide evidence regarding the safety and efficacy of acupoint catgut embedding in patients with knee osteoarthritis.
Keywords: Acupoint, Catgut, Knee osteoarthritis, Arthralgia
INTRODUCTION
As a degenerative disease, knee osteoarthritis (OA) causes chronic joint pain, stiffness, deformity, and a limited range of motion [1]. It involves erosion and expansion of the calcified cartilage zone and the generation of matrix degradation products and proinflammatory mediators [2]. The prevalence of knee OA is rapidly increasing globally. In Sweden, the prevalence of patients with knee OA aged 45 or older was 13.8% based on data from 1.26 million inhabitants in 2012, and it is projected to be 15.7% in 2032 [3]. According to the Korean National Health and Nutrition Examination Survey in South Korea, the prevalence of radiographic knee OA is 4.4% in males and 19.2% in females [4]. In China, the prevalence of symptomatic knee OA is 10.3% in males and 5.7% in females, based on a population-based longitudinal survey [5]. Moreover, knee OA results in substantial economic expenses, including the need for a caregiver to administer treatment and patient care [6]. The high prevalence and economic cost of knee OA necessitate suitable therapies.
Current treatments for knee OA can be divided into three categories: exercise therapy, pain medication, and joint replacement surgery [2]. Considering knee OA primarily affects older adults [7], exercise therapy for these patients leads to long-term knee performance and high self-reliance [8]; moreover, it is recommended for mild-to-moderate knee OA [9,10]. Regarding pain medication for this condition, paracetamol and NSAIDs are recommended [2]. However, paracetamol may not be as effective when used alone [11]. NSAIDs have some side effects, such as indigestion [12]. Although joint replacement surgery is clinically relevant for end-stage knee OA [13], 25% of patients continue to complain of pain and disability one year after surgery [14]. Therefore, effective low-risk therapy is recommended for this patient population.
Acupoint catgut embedding (ACE) is a complementary and alternative medicine modality that continuously stimulates acupoints by implanting threads or catguts into acupoints using acupuncture needles [15]. It has been widely used in East Asian countries [16], with gradually increasing adoption in other countries such as Mexico and Indonesia [17,18]. Based on our previous experimental systematic review, we speculate that ACE may have anti-inflammatory mechanisms by suppressing inflammatory mediators and cytokines [19]. Moreover, recipients do not require daily treatment; patients are typically treated once weekly for two weeks [16]. This approach saves practitioners time and resolves patients’ fears of acupuncture. To date, only one systematic review on knee OA has been conducted [20]. However, it was published in 2018 and represents the only final review of three randomized controlled trials (RCTs). Thus, a meta-analysis of the efficacy of ACE in knee OA has yet to be performed. Therefore, this study aims to comprehensively assess the effectiveness and safety of ACE in treating knee OA.
MATERIALS AND METHODS
1. Study registration
This systematic review protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [21]. Additionally, it has been registered in the international Prospective Review database (PROSPERO) under the registration number CRD4202345 4230. The PRISMA-P checklist is shown in Supplementary Table 1. Ethical approval was not required for this protocol.
2. Type of studies
We will include all RCTs related to knee OA associated with ACE. However, we will exclude literature reviews, animal studies, and non-RCTs (including case, observational, and cohort studies).
1) Type of participants
This study will include patients of any age, race, or sex who have been diagnosed with knee OA using diagnostic criteria such as the American College of Rheumatology/Arthritis Foundation guidelines [22], guidelines for diagnosing and treating OA, and other valid diagnostic criteria.
2) Type of interventions
We will include studies using ACE alone or in combination with conventional treatments, which include medication, manual acupuncture, and electro-acupuncture, as well as combination treatment in both the control and experimental groups. Additionally, we will not restrict the type of ACE materials used, including, but not limited to, catgut, polydioxanone, and poly1acticcoglycolic acid.
3) Type of comparisons
This study will include various possible original therapies, such as Western medicine, articulation injection, manual acupuncture, practice, hyperbaric oxygen, and usual care. Additionally, we will incorporate placebo controls, such as sham ACE, to assess the placebo effect.
4) Outcome measures
The primary outcomes will be assessed using the Visual Analog Scale and Western Ontario and McMaster Universities OA Index. Secondary outcomes will include the total efficacy rate, Lysholm Score, and adverse effects.
3. Data sources
To identify all eligible studies, we will search the following 11 databases from inception to August 1, 2023, without language limitations: the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, Web of Science, Chinese Biomedical Literature Database, Chinese Scientific Journal Database (VIP database), Wan-Fang Database, China National Knowledge Infrastructure, Oriental Medicine Advanced Searching Integrated System, Science-On, and KoreaMed. Additionally, we will explore two databases for prospectively registered and ongoing trials: the World Health Organization International Clinical Trials Registry Platform search portal (http://apps.who.int/trialsearch/Default) and ClinicalTrials.gov (http://ClinicalTrials.gov/). The search strategy for PubMed is presented in Table 1, and the remaining relevant strategies are shown in Supplementary Table 2.
-
Table 1
Search strategy for PubMed.
#1 “osteoarthritis, knee”[MeSH Terms] #2 “Knee”[MeSH Terms] #3 “osteoarthr*”[All Fields] #4 “degenerative arthritis”[All Fields] #5 #1 OR #2 OR #3 OR #4 #6 “catgut”[All Fields] #7 “thread*”[All Fields] #8 “acupoint*”[All Fields] #9 “needle”[All Fields] #10 “acupunctural”[All Fields] #11 #6 OR #7 OR #8 OR #9 OR #10 #12 “embed*”[All Fields] #13 “implant*”[All Fields] #14 #12 OR #13 #15 #14 AND #11 #16 “Randomized Controlled Trial”[MeSH Terms] #17 “Controlled Clinical Trial”[MeSH Terms] #18 “random*”[All Fields] #19 “placebo”[All Fields] #20 “trial”[All Fields] #21 #16 OR #17 OR #18 OR #19 OR #20 #22 #21 AND #15 AND #5
4. Selection of studies
Two reviewers (HY Zhao and Y Liu) will independently select studies based on the systematic review process. First, they will screen research titles and abstracts to select relevant studies. Second, they will retrieve the full text and read the studies for double-checking. If disagreements occur, a third reviewer (CH Han) will be consulted. The flow diagram of the study selection process is shown in Supplementary Fig. 1.
5. Data extraction
We will extract the data using an Excel spreadsheet (Microsoft Office Professional Plus 2019, Microsoft, Albuquerque, NM, USA). Two reviewers will independently extract data from the selected studies. Any disagreements during the crosschecking process will be resolved through discussions. The following data will be included: first author, year of publication, country, intervention and comparison treatments, treatment duration, acupoint of intervention, outcome measurements, and adverse events.
6. Quality assessment
Two independent reviewers will evaluate the selected studies using the Cochrane Handbook for Systematic Review of Interventions [23]. Seven aspects will be assessed: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessments, incomplete outcome data, selective reporting, and other biases. Each aspect will be classified as low, high, or unclear. In case of any disagreement, a third reviewer will resolve it.
7. Data synthesis
Statistical analysis will be performed using Review Manager (RevMan) version 5.4.1 for Windows software (Copenhagen, The Nordic Cochrane Center, the Cochrane Collaboration, 2020). For continuous data, mean differences (or standardized mean differences) and standard deviations will be used in the meta-analysis with a 95% confidence interval (CI). Dichotomous results will be expressed as relative risk with a 95% CI. Furthermore, we will use I2 and χ2 to measure heterogeneity. If p > 0.1 and I2 < 50%, indicating homogeneity, a fixed-effects model will be used in the meta-analysis. Otherwise, a random-effects model will be used. If a quantitative synthesis is not appropriate for some outcomes, we will summarize the findings of the studies and conclude.
8. Dealing with missing data
The author will try to contact the corresponding authors to obtain specific data by using their phone number and e-mail if missing data occurs.
9. Assessment of heterogeneity
Heterogeneity will be detected using I2 and χ2 measures. High heterogeneity will be indicated if I2 is > 50. A meta-analysis will be conducted to reduce heterogeneity based on the same comparator. If high heterogeneity is observed, subgroup analyses will explore potential reasons, including the same acupoints, treatment durations, and materials.
10. Sensitivity analysis
The final included studies will exhibit a high-quality methodology, sufficient sample size, and low heterogeneity. We will conduct a sensitivity analysis to measure the robustness of the study.
11. Assessment of reporting biases
If the final number of selected studies exceeds 10, we will use funnel plots to assess reporting bias.
12 Assessment of quality of evidence
We will use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method [24] to assess the quality of evidence for primary and secondary outcomes. This method includes five major domains: inconsistency, limitations, imprecision, indirectness, and publication bias. The evidence will be categorized into four levels of evidence quality: high, moderate, low, and very low.
DISCUSSION
ACE is a method developed from manual acupuncture that has evolved over 60 years. It involves implanting threads or catguts into the skin tissue at acupoints, which can aid in managing various conditions [25]. Moreover, it is crucial to consider the patient’s economic situation when treating knee OA. A previous report indicates that the cost of ACE is lower than that of electroacupuncture for treating obesity, primarily due to the absence of daily administration requirements [26].
However, this study has some limitations that must be considered. Given the nature of systemic reviews, standardization of factors such as different acupoints and treatment durations and the inability to blind ACE practitioners will not be possible. Nonetheless, no systematic and comprehensive meta-analyses of ACE’s therapeutic effects and safety in knee OA have been conducted. Therefore, this protocol of a systematic review of ACE for knee OA will provide evidence to health policymakers and scientific researchers and offer additional treatment options for patients with knee OA.
ACKNOWLEDGEMENTS
This work was supported by the Korea Institute of Oriental Medicine grant number KSN23314113.
SUPPLEMENTARY MATERIAL
Supplementary data to this article can be found online at https://doi.org/10.51507/j.jams.2024.17.2.76.
FUNDING
This work was supported by the Korea Institute of Oriental Medicine grant number KSN23314113. The funder had no role in the review or preparation of the manuscript or the decision to publish.
AUTHORS’ CONTRIBUTIONS
Study conception, development of study criteria, and writing of the manuscript: HYZ and CHH. Conduction of preliminary searches: HYZ and YL. Examination of the relevance of the protocol in clinical practice: HYZ. Manuscript revision: CHH. All the authors have read and approved the final manuscript.
CONFLICT OF INTEREST
The authors declare no conflict of interest.
There is no Figure.
-
Table 1 . Search strategy for PubMed.
#1 “osteoarthritis, knee”[MeSH Terms] #2 “Knee”[MeSH Terms] #3 “osteoarthr*”[All Fields] #4 “degenerative arthritis”[All Fields] #5 #1 OR #2 OR #3 OR #4 #6 “catgut”[All Fields] #7 “thread*”[All Fields] #8 “acupoint*”[All Fields] #9 “needle”[All Fields] #10 “acupunctural”[All Fields] #11 #6 OR #7 OR #8 OR #9 OR #10 #12 “embed*”[All Fields] #13 “implant*”[All Fields] #14 #12 OR #13 #15 #14 AND #11 #16 “Randomized Controlled Trial”[MeSH Terms] #17 “Controlled Clinical Trial”[MeSH Terms] #18 “random*”[All Fields] #19 “placebo”[All Fields] #20 “trial”[All Fields] #21 #16 OR #17 OR #18 OR #19 OR #20 #22 #21 AND #15 AND #5
References
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