
==== Front
Medicine (Baltimore)
Medicine (Baltimore)
MD
Medicine
0025-7974
1536-5964
Lippincott Williams & Wilkins Hagerstown, MD

39029044
MD-D-24-00555
00046
10.1097/MD.0000000000038937
3
3800
Research Article
Systematic Review and Meta-Analysis
Acupuncture for constipation in Parkinson’s disease: A systematic review and meta-analysis of randomized controlled trials
Li Zhao PhD lizhao@stu.cdutcm.edu.cn
a
Niu Qun PhD niuqun@stu.cdutcm.edu.cn
a
Yang Kai PhD 86512928@qq.com
b
Zhao Keni PhD 77669502@qq.com
c
Yin Shao PhD yinshao@stu.cdutcm.edu.cn
a
https://orcid.org/0009-0000-9617-1514
Zhu Fengya PhD 2017s350@stu.cdutcm.edu.cn
d*
a School of Clinical Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
b Department of Orthopaedics, Xi’an Hospital of Traditional Chinese Medicine, Xi’an, China
c Deriatric Department, Xi’an Hospital of Traditional Chinese Medicine, Xi’an, China
d Traditional Chinese Medicine Department, Zigong First People’s Hospital, Zigong, China.
* Correspondence: Fengya Zhu, Traditional Chinese Medicine Department, Zigong First People’s Hospital, Ziliujing District, Zigong, China (e-mail: 2017s350@stu.cdutcm.edu.cn).
19 7 2024
19 7 2024
103 29 e3893717 1 2024
20 6 2024
24 6 2024
Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.
2024
https://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal.

Background:

Parkinson’s disease (PD) is the second most common neurological disease worldwide, and there is a potential interaction between PD and constipation. PD constipation often causes significant trouble for patients and seriously affects their quality of life. Acupuncture is widely used for treating constipation and has been clinically proven. However, it is unclear whether the current evidence is sufficient to support acupuncture to improve PD constipation.

Methods:

We searched the Cochrane Central Register of Controlled Trials, Embase, PubMed, Web of Science, China National Knowledge Infrastructure, Wan Fang Data Knowledge Service Platform, and Chinese Scientific Journal Database (VIP database) for randomized controlled trials from inception through July 1, 2023. Randomized controlled trials (RCTs) included acupuncture, sham acupuncture, and medication for PD constipation. Stata 16.0 software and Cochrane RoB2.0 were used for data processing and migration risk analysis.

Results:

The 11 studies included a total of 960 patients. The results showed that acupuncture or acupuncture combined with conventional treatment seemed to have advantages in improving complete spontaneous bowel movements (WMD: 1.49, 95% CI: 0.86, 2.11; P < .00001), Patient-Assessment of Constipation Quality of Life questionnaire (WMD: −11.83, 95% CI: −15.67, −7.99; P < .00001), the chronic constipation severity scale (CCS) (SMD: −0.99, 95% CI: −1.40, −0.58; P < .01), and c(RRP) (WMD: 2.13, 95% CI: 0.44, 3.82; P < .05).

Conclusion:

The present results show that compared with conventional treatment, acupuncture combined with conventional treatment seems to increase the number of spontaneous defecations in PD patients, improve quality of life, increase rectal resting pressure, and alleviate the severity of chronic constipation. Thus, acupuncture has the potential to treat PD constipation. However, due to the study’s limitations, higher-quality RCTs are needed for verification.

acupuncture
complementary alternative therapy
constipation
meta-analysis
Parkinson’s disease
OPEN-ACCESSTRUE
SDCT
==== Body
pmc1. Introduction

Parkinson’s disease (PD) is a traditional neurodegenerative disease that occurs in approximately 1% of people aged over 60.[1,2] In the early stages of the disease, PD patients often have non-kinetic symptoms such as constipation and depression.[3] Approximately 80% of PD patients have gastrointestinal dysfunction prior to the onset of motor symptoms,[4] and it has even been suggested that PD may be caused by the gastrointestinal tract.[5] In addition, constipation may be one of the most common gastrointestinal manifestations in PD patients.[6,7] There is evidence that patients with constipation have a 2.36-fold increased risk of PD compared to patients without constipation, which can persist for decades [8,9]; the prevalence of irritable bowel syndrome in PD patients is higher than that in the general population.[10] Related studies have found that constipation is somewhat associated with the duration and severity of PD; in addition, the progression of PD accelerates the frequency and severity of constipation, and there is a strong correlation between constipation and PD risk.[11,12]

Parkinson’s constipation has been studied for a long time and is increasingly active. Unfortunately, there is no clear guideline recommendation for evaluating drugs that can simultaneously treat constipation and control PD.[13] Conventional treatments for constipation are also often ineffective in people with PD, and measures that improve only one of the symptoms of PD may worsen others. Evidence suggests that anticholinergic drugs used to control PD symptoms can even make constipation worse.[14] Therefore, it is necessary to find an effective measure that can prevent PD progression and relieve constipation.

Acupuncture originated in China and is increasingly recognized by doctors and patients as a simple, safe, and popular complementary alternative therapy.[15] Previous studies have shown that acupuncture can improve gastrointestinal and neurological symptoms[16,17] and can effectively treat both primary and secondary constipation.[18] Studies have shown that acupuncture can improve PD-related motor symptoms, non-motor symptoms, quality of life, disease progression, reduce the occurrence of adverse events, and reduce the dose of anti-PD drugs.[19] However, some scholars have found that compared with conventional treatment, acupuncture did not have significant differences in the treatment of PD-related constipation.[20]

Clinical studies on whether acupuncture has a positive effect on PD-related constipation have not been fully confirmed. Therefore, in order to verify the efficacy of acupuncture on PD constipation, this systematic review and meta-analysis will provide statistical data on several clinical outcomes, hoping to provide a comprehensive update of clinical data for the development of evidence-based guidelines.

2. Method

The study was conducted in accordance with the Preferred Reporting Program for Systematic Review and Meta-Analysis (PRISMA)[21] and in line with the PRISMA checklist. It was approved by the International Prospective Register of Systematic Reviews (PROSPERO) on July 20, 2023, with registration number CRD42023443686.

2.1. Acceptance standard

This study included all randomized controlled trials (RCTs) of acupuncture in the treatment of PD-related constipation. PD participants met internationally recognized diagnostic criteria and had constipation or gastrointestinal dysfunction. The experimental group received acupuncture or acupuncture combined with conventional treatment, and the control group received conventional treatment, sham acupuncture, other treatment, or no intervention. The main outcome measures are complete spontaneous bowel movements (CSBMs), the Patient-Assessment of Constipation Quality of Life questionnaire (PAC-QOL), and the chronic constipation severity scale (CCS). The Unified Parkinson’s Disease Rating Scale (UPDRS), and rectal resting pressure (RRP) were secondary outcome indicators.

Reviews, conference papers, animal studies, retrospective studies, case-control studies, and self-controlled studies were excluded. RCTs that did not include constipation-related outcomes were also excluded.

2.2. Search strategy

We searched the Cochrane Central Register of Controlled Trials, Embase, PubMed, Web of Science, China National Knowledge Infrastructure, Wan Fang Data Knowledge Service Platform, and Chinese Scientific Journal Database (VIP database) for RCTs from inception through July 1, 2023. In addition, the list of references included in the study was manually searched to identify relevant trials. There were no restrictions on language, year of publication, etc. Data from gray literature was not included in the search, as we did not have access to these. A detailed search strategy can be found in Figures S1–S13, Supplemental Digital Content, http://links.lww.com/MD/N198.

2.3. Research selection

According to a strict search strategy, reviewers used Endnote X9 and manual procedures to remove duplicate documents. An initial study selection was made based on the title and abstract, followed by a full-text reading to determine the final studies for inclusion. Two reviewers (KY and KNZ) independently searched and selected the literature. Any differences between the 2 reviewers were resolved through discussion. If no agreement was reached, a third reviewer (SY) made the final decision.

2.4. Data extraction

Data extraction was carried out independently and cross-checked by 2 examiners (ZL and JF) using a standardized form developed in advance. The main contents included year of publication, first author, country, study design, participants (age, gender), sample size, intervention details (formulation, dose, duration), results, etc. Any differences between the 2 reviewers were resolved through discussion. If no agreement was reached, a third reviewer (SY) made the final decision.

2.5. Data synthesis and statistical analysis

Data from 2 or more RCTs with the same outcome measures were statistically analyzed by 2 researchers using Stata 16.0 software for meta-analysis. Continuous variables have the same units of measure, so they are expressed using weighted mean differences (WMD) and 95% confidence intervals (CI). P < .05 was considered statistically significant; if I2 was≥50%, a random effects model was adopted, and a sensitivity analysis was performed to observe the stability of the results. As fewer than 10 RCTs were included in this study, we did not test for publication bias. For individual outcome indicators, we summarized the data and conducted a descriptive analysis.

2.6. Assessing the risk of bias and the quality of the evidence

We used Cochrane RoB2.0 to assess the risk of bias in the included literature. Each RCT was evaluated according to the following 6 items: the randomization process; interventions that deviate from expectations; lack of outcome data; measurement results; select report results; and if the methodology used was appropriate and clearly described, the study was considered low risk. If the method could not be accurately judged, it was rated as high risk, or there were problems with the method. Evaluation of the quality of evidence for recommendation grading (GRADE) included 5 main factors: risk of bias, inconsistency, imprecision, consistency, and publication bias. All evaluations were conducted independently by 2 reviewers (ZL and KY), and unresolved differences were determined by a third reviewer (SY).

3. Results

We searched a total of 151 articles from 7 databases, all published in journals; 27 duplicates were excluded. The machine automatically excluded 34 articles, 47 nonconforming studies, and 18 nonconforming PDC articles by title and abstract. A total of 14 studies were excluded after careful reading of the full text, and finally, 11 articles were included for analysis. A detailed flow chart is shown in Figure 1.

Figure 1. Flow diagram of the included and excluded studies in the systematic review.

3.1. Basic characteristics of eligible studies

The main features of the included studies are shown in Table 1: study site, sample size of the treatment and control groups, treatment method selected by the treatment group, treatment method used by the control group, duration of efficacy evaluation, efficacy evaluation indicators, and adverse events.

Table 1 The characteristics of included studies.

Study	Country	Outcome measure	Experimental treatment	Control treatment	Sample size (I/C)
Female (male)	Age (yr)
[mean (SD)]
(I/C)	Duration (wk)	Adverse events (I/C)	
Li[22]	China	CSBMs, PAC-QOL, UPDRS	Acupuncture	Sham acupuncture	22(17)/21(18)	63.9(7.34)/63.74(9.24)	8	6/0	
Li[23]	China	CSBMs, UPDRS, PAC-QOL, CCS	Electroacupuncture + Metoba	Metoba	38(45)/40(43)	67.3(8.1)/66.9(7.1)	12	11/6	
Li[24]	China	RRP, UPDRS	Electroacupuncture	Polyethylene glycol	10(37)/12(34)	69.82(8.42)/70.73(8.88)	4		
Luo[25]	China	RRP	Acupuncture + phenolphthalein tablets	phenolphthalein tablets	12(18)/13(17)	66.31(5.57)/66.07(5.48)	4		
Liu[26]	China	RRP	Acupuncture + carbidopa tablet, phenolphthalein tablets	Carbidopa tablets,
phenolphthalein tablets	20(28)/23(25)	65.28(7.32)/64.58(7.33)	1		
Xue[27]	China	PAC-QOL, RRP	Acupuncture + simo decoction	Simo decoction	20(30)/18(32)	60.17(9.25)/62.13(8.04)	1		
Li[28]	China	CSBMs, CCS	Electroacupuncture	Lactulose	27/26	–	12		
Jiang[29]	China	PAC-QOL, CCS	Acupuncture + metoba	Metoba	15(18)/16(17)	64.82(12.23)/64.41(11.89)	3		
Zhang[30]	China	CCS	Acupuncture  + edestan pill	Edestan pill	13(22)/14(21)	69.5(4.1)/70.2(3.6)	4		
Qiao[31]	China	CCS, PAC-QOL	Acupuncture + metoba	Metoba	16(13)/15(14)	76.67(4.67)/76.83(4.65)	3		
She[32]	China	PAC-QOL	Acupuncture	Lactulose	17(43)/22(38)	72.52(7.42)/72.12(8.65)	4		
C = the control group, CSBMs = complete spontaneous bowel movements, I = the treatment group, PAC-QOL = Patient-Assessment of Constipation Quality of Life questionnaire, RRP = rectal resting pressure, UPDRS = Unified Parkinson’s Disease Rating Scale.

The 11 studies included 960 patients; 481 received acupuncture or acupuncture combined with conventional treatment, and 479 received sham acupuncture or the same drug as the treatment group but without acupuncture. There was a multicenter controlled trial[23]; the rest were single-center controlled experiments. For the diagnosis of PD-related constipation, 11 articles had clear diagnostic criteria. For efficacy criteria for PD-associated constipation, 3 studies evaluated SBMs.[22,23,28] Six studies investigated pre- and post-treatment differences in PAC-QOL.[22,23,27,29,31,32] Four studies documented the extent to which CCS changed.[22,29–31] Three studies reported changes in UPDRS[22–24]，and changes in anorectal dynamics were documented in 4 studies.[24–27] Adverse events were reported in 2 cases.[22,23]

3.2. Risk of bias

Of the 11 studies, 8 RCTs had a moderate or low risk of bias, 2 had a high risk due to lax randomization, 6 had a moderate risk, and 3 had a severe risk of bias (Fig. 2).

Figure 2. Risk of bias graph.

3.3. Results of individual studies

3.3.1. Complete spontaneous bowel movements

We conducted a meta-analysis of SBM outcomes in 297 patients from 3 studies, and the results showed that acupuncture combined with conventional treatment was superior to conventional treatment alone (WMD: 1.49, 95% CI: 0.86, 2.11; P < .00001). The heterogeneity was high (I2 = 86.3%, P = .001), so we adopted a random effects model (Fig. 3). Sensitivity analysis showed that the structure was stable. The Egger test suggests a possible publication bias.

Figure 3. Meta-analysis of CSBMs. CSBMs = complete spontaneous bowel movements, WMD = weighted mean differences.

3.3.2. Patient-Assessment of Constipation Quality of Life questionnaire

PAC-QOL is commonly used to assess quality of life in patients with constipation. The higher the score, and the more obvious the difference before and after treatment, the better the treatment effect. We conducted a meta-analysis of the PAC-QOL results of 588 patients in 6 studies, and the results showed that acupuncture combined with conventional treatment was superior to conventional treatment alone (WMD: −11.83, 95% CI: −15.67, −7.99; P < .00001). The heterogeneity was high (I2 = 97.8%, P = .000), so we used a random effects model (Fig. 4). Sensitivity analysis showed stability, but Egger test showed that there may be certain reasons leading to publication bias.

Figure 4. Meta-analysis of PAC-QOL. PAC-QOL = Patient-Assessment of Constipation Quality of Life questionnaire, WMD = weighted mean differences.

3.3.3. Chronic constipation severity scale

We conducted a meta-analysis of CCS outcomes in 360 patients from 4 studies, and the results showed that acupuncture-assisted conventional therapy was superior to conventional therapy in improving constipation severity scale scores (SMD: −0.99, 95% CI: −1.40, −0.58; P < .01). The heterogeneity was high (I2 = 95.3%, P = 0), so we adopted a random effects model (Fig. 5). Sensitivity analysis showed that the results were stable and the Egger test showed no publication bias.

Figure 5. Meta-analysis of CCS. CCS =. chronic constipation severity scale, WMD = weighted mean differences.

3.3.4. Unified Parkinson’s disease rating scale

We conducted a meta-analysis on 3 studies that recorded the changes in the UPDRS before and after treatment. The forest map showed that the UPDRS changes following acupuncture-assisted conventional treatment were not better than those of conventional treatment (WMD: −5.02, 95% CI: 11.02, 0.97; P = .1). The heterogeneity was high (I2 = 86.3%, P = .001), and sensitivity analysis showed that the results were stable. The Egger test showed no publication bias (Fig. 6).

Figure 6. Meta-analysis of UPDRS. UPDRS = Unified Parkinson’s Disease Rating Scale. WMD = weighted mean differences.

3.3.5. Rectal resting pressure

We conducted a meta-analysis of anorectal dynamics results in 349 patients from 4 studies, and the results showed that acupuncture combined with conventional treatment was superior to conventional treatment alone (WMD: 2.13, 95% CI: 0.44, 3.82; P < .05). The heterogeneity was high (I2 = 93.2%, P = 0), so we used a random effects model. Sensitivity analysis showed that the results were stable. The Egger test showed no publication bias (Fig. 7).

Figure 7. Meta-analysis of RRP. RRP = rectal resting pressure, WMD = weighted mean differences.

4. Discussion

The objective of this study was to evaluate the efficacy of acupuncture and moxibustion combined with conventional treatment in improving PD-related constipation. According to the meta-analysis, acupuncture-assisted conventional treatment has advantages over conventional treatment in improving SBMs, PAC-QOL, CCS, and anorectal dynamics in PD patients. However, acupuncture combined with conventional treatment has no apparent advantages compared to conventional treatment in improving UPDRS in PD patients.

PD is the second most common neurodegenerative disease after Alzheimer’s disease, but its exact etiology is not fully understood. Studies have shown that intestinal exposure to neurotoxins and intestinal ecological disorders are related to the pathogenesis and progression of PD.[33] Relevant studies have found that PD and intestinal flora establish an important relationship through brain–gut axis interaction. Changes in intestinal flora composition may lead to changes in intestinal barrier function and intestinal permeability, which not only affect intestinal epithelial cells and the immune system but also affect the occurrence and progression of neurodegenerative diseases and mental disorders.[34–36] In addition, the pathophysiology of gastrointestinal dysfunction in PD patients is unclear, and it may be related to endogenous and extrinsic nervous system damage, neuro-gastrointestinal hormone and signaling disorders, and adverse reactions to anti-PD drugs.[37,38]

Gastrointestinal dysfunction in PD patients includes dysphagia, nausea, bloating, constipation, etc. Constipation is the most significant manifestation of gastrointestinal dysfunction in PD and can develop many years before the motor symptoms of PD.[39] Constipation is often severe with the progression of PD.[40] In addition to seriously impacting the quality of life, the presence and severity of long-term chronic constipation are related to the poor prognosis of PD.[41,42] Currently, the main clinical strategy for PD constipation is symptomatic treatment, and the commonly used drugs have many side effects and limitations.[43,44] Increasing fiber intake is known to help improve constipation symptoms, but studies have found that excessive fiber intake may cause or worsen bloating in some patients.[45] In clinical practice, there is currently insufficient evidence to support the use of probiotics, polyethylene glycol, and beta-blockers for PD constipation.

Acupuncture, a complementary alternative therapy, has been widely used for various causes of constipation, including PD.[23,46] It has been reported that the effect of acupuncture on gastrointestinal dysfunction is related to the activation of the solitary tract nucleus, dorsal vagus motor nucleus, and periureter gray matter by regulating the imbalance of sympathetic and parasympathetic nerve activity.[47] Many scholars have conducted research and demonstrations on the mechanisms of acupuncture in treating PD constipation. Evidence shows that electroacupuncture can improve constipation symptoms in PD mice by reducing alpha-SYN aggregation in colon tissue.[48] Electroacupuncture can promote the clearance of alpha-SYN and damaged mitochondria by regulating colonic autophagy, thereby restoring the Enteric Nervous System function and acting as an ameliorator of PD constipation.[49] Acupuncture can prevent intestinal microbiota from affecting the nervous system of PD mice by regulating and improving the diversity of intestinal microbiota, thus protecting substantia nigra neurons.[50] In addition, studies have shown that electroacupuncture improves stool excretion, accelerates intestinal propulsion, and improves intestinal motility in Thy1-αSYN mice. By upregulating 5-HT and 5-HT4R in colon tissue, electroacupuncture can activate the downstream cAMP/PKA pathway, regulate the expression of related neurotransmitters SP and CGRP, and then regulate the intestinal nervous system and improve intestinal movement disorders, thereby relieving constipation in PD.[51] Evidence has found that acupuncture can treat functional constipation by promoting gastrointestinal peristalsis, regulating hormones in the peripheral gastrointestinal tract, and maintaining a balance between excitatory and inhibitory neurons in the Enteric Nervous System.[52–54]

The results of the meta-analysis of 11 RCTs showed that acupuncture combined with conventional treatment could assist in alleviating the constipation of PD patients, effectively increase the number of spontaneous defecations, improve quality of life, increase rectal resting pressure, and lessen the severity of chronic constipation. For the results with high heterogeneity, we attempted to find the heterogeneity source. We performed subgroup analyses of PAC-QOL, CCS, and RRP data based on duration of treatment, but found no reliable sources of heterogeneity (see Figures S1–S13, Supplemental Digital Content, http://links.lww.com/MD/N198). Differences in point selection, treatment time, follow-up time, sample size, and the risk of bias in the included RCTs all affected heterogeneity. Studies have shown that differences in the effectiveness of various acupuncture trials are mainly driven by differences in the treatment received by the control group rather than differences in the characteristics of acupuncture treatment.[55]

4.1. Advantages and limitations

This study conducted a systematic evaluation in strict accordance with the PRISMA report list. It analyzed the existing evidence of acupuncture treatment for PD constipation, which provided a theoretical basis for evidence-based medicine and clinical treatment. However, there are certain shortcomings. We tried to identify all relevant studies, including Western and Eastern studies; however, all included RCTs were conducted in China, which may limit the generality of the survey, may lead to publication bias, and the corresponding conclusions may not apply to other fields. Therefore, the lack of high-quality RCTs has inevitably hindered the robust evaluation of the efficacy of acupuncture. Although acupuncture has been used in many countries, acupuncture combined with conventional treatment for PD constipation is currently not widely available abroad. It is extremely difficult to achieve completely double-blind trials. The blindness caused by acupuncture and sham acupuncture will be suspected by patients because of the differences in intervention; whether compared with drugs or sham acupuncture, patients can easily feel the difference in acupuncture experiments. We believe that the main reason is related to patients’ self-assessments. Therefore, conducting further rigorous RCTs on acupuncture treatment of PD constipation is necessary.

The suggestions are as follows: The design quality of the study should be improved, including randomization, assignment hiding, and the blind method; International cooperation should be developed to obtain more research and ensure the universality of research results; as far as possible, standardized acupuncture and drug use are used, and more reasonable intervention measures are designed to improve the feasibility and credibility of the experiment, and provide more strict and clear theoretical support for clinical drug use.

However, the limitations of this study are described in detail, which provide specific recommendations for subsequent experimental design to provide more reliable results.

5. Conclusion

The present results show that compared with conventional treatment, acupuncture combined with conventional treatment seems to increase the number of spontaneous defecations in PD patients, improve quality of life, increase rectal resting pressure, and alleviate the severity of chronic constipation, indicating that acupuncture certainly has potential for treating PD constipation. However, due to the study’s limitations, higher-quality RCTs are needed for verification.

Author contributions

Conceptualization: Zhao Li, Qun Niu, Shao Yin, Fengya Zhu.

Data curation: Zhao Li, Kai Yang, Keni Zhao.

Formal analysis: Qun Niu, Kai Yang, Keni Zhao.

Investigation: Kai Yang, Keni Zhao.

Methodology: Kai Yang, Keni Zhao.

Software: Qun Niu, Shao Yin.

Supervision: Qun Niu, Shao Yin.

Validation: Qun Niu, Shao Yin.

Visualization: Qun Niu, Shao Yin.

Writing – original draft: Zhao Li, Qun Niu, Shao Yin, Fengya Zhu.

Writing – review & editing: Zhao Li, Qun Niu, Shao Yin, Fengya Zhu.

Supplementary Material

Abbreviations:

CCS chronic constipation severity scale

CI confidence intervals

CSBMs complete spontaneous bowel movements

PAC-QOL Patient-Assessment of Constipation Quality of Life questionnaire

PD Parkinson’s disease

PRISMA Program for Systematic Review and Meta-Analysis

RRP rectal resting pressure

RCTs Randomized Controlled Trials

UPDRS Unified Parkinson’s Disease Rating Scale

VIP Chinese Scientific Journal Database

WMD weighted mean differences.

The authors have no funding and conflicts of interest to disclose.

All data generated or analyzed during this study are included in this published article [and its supplementary information files].

Supplemental Digital Content is available for this article.

How to cite this article: Li Z, Niu Q, Yang K, Zhao K, Yin S, Zhu F. Acupuncture for constipation in Parkinson’s disease: A systematic review and meta-analysis of randomized controlled trials. Medicine 2024;103:29(e38937).
==== Refs
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