Sham Acupressure Controls Used in Randomized Controlled Trials: A Systematic Review and Critique

PLOS ONE, Jul 2015

Objectives To explore the commonly utilized sham acupressure procedures in existing acupressure trials, and to assess whether different types of sham interventions yield different therapeutic outcomes, and, as far as possible, to identify directions for the future development of an adequate sham acupressure method. Methods Randomized controlled trials comparing true acupressure with sham interventions were included. Thirteen electronic databases were adopted to locate relevant studies from inception to July 3, 2014. Meanwhile, eight Chinese journals on complementary and alternative medicine were manually searched to locate eligible articles. In addition, eligible studies listed in the reference lists of the included papers and other related systematic reviews on acupressure were also screened to further search any potentially eligible trials. Methodological quality of the included studies was evaluated using the risk of bias assessment tool developed by the Cochrane Back Review Group. Descriptive analysis was adopted to summarize the therapeutic outcomes. Results Sixty-six studies with 7265 participants were included. Methodological quality of the included trials was generally satisfactory. Six types of sham acupressure approaches were identified and “non-acupoint” stimulation was the most frequently utilized sham point while an acupressure device was the most commonly used approach for administering sham treatments. Acupressure therapy was a beneficial approach in managing a variety of health problems and the therapeutic effect was found to be more effective in the true acupressure groups than that in the sham comparative groups. No clear association could be identified between different sham acupressure modalities and the reported treatment outcomes. Conclusions A great diversity of sham acupressure controls have been used in clinical practice and research. A solid conclusion whether different sham alternatives are related to different treatment outcomes cannot be derived because of significant clinical heterogeneity among the analyzed trials. Non-acupoints are generally recommended but the definite locations should be identified with caution. For studies using single sham acupoints on hands or legs, it is suggested to apply identical acupressure devices on the same acupoint as in the active intervention without any stimulation. While for studies on pain, stimulation of sham acupoints should be avoided.

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Sham Acupressure Controls Used in Randomized Controlled Trials: A Systematic Review and Critique

July Sham Acupressure Controls Used in Randomized Controlled Trials: A Systematic Review and Critique Jing-Yu Tan 0 1 Lorna K. P. Suen 0 1 Tao Wang 0 1 Alexander Molassiotis 0 1 0 1 School of Nursing, The Hong Kong Polytechnic University , Hung Hom, Kowloon, Hong Kong SAR , China , 2 School of Nursing, Fujian University of Traditional Chinese Medicine , Fuzhou, Fujian , China , 3 The Second Affiliated People's Hospital, Fujian University of Traditional Chinese Medicine , Fuzhou, Fujian , China 1 Editor: Nguyen Tien Huy, Institute of Tropical Medicine (NEKKEN), Nagasaki University , JAPAN Randomized controlled trials comparing true acupressure with sham interventions were included. Thirteen electronic databases were adopted to locate relevant studies from inception to July 3, 2014. Meanwhile, eight Chinese journals on complementary and alternative medicine were manually searched to locate eligible articles. In addition, eligible studies listed in the reference lists of the included papers and other related systematic reviews on acupressure were also screened to further search any potentially eligible trials. Methodological quality of the included studies was evaluated using the risk of bias assessment tool developed by the Cochrane Back Review Group. Descriptive analysis was adopted to summarize the therapeutic outcomes. - Competing Interests: The authors have declared that no competing interests exist. To explore the commonly utilized sham acupressure procedures in existing acupressure trials, and to assess whether different types of sham interventions yield different therapeutic outcomes, and, as far as possible, to identify directions for the future development of an adequate sham acupressure method. Sixty-six studies with 7265 participants were included. Methodological quality of the included trials was generally satisfactory. Six types of sham acupressure approaches were identified and “non-acupoint” stimulation was the most frequently utilized sham point while an acupressure device was the most commonly used approach for administering sham treatments. Acupressure therapy was a beneficial approach in managing a variety of health problems and the therapeutic effect was found to be more effective in the true acupressure groups than that in the sham comparative groups. No clear association could be identified between different sham acupressure modalities and the reported treatment outcomes. A great diversity of sham acupressure controls have been used in clinical practice and research. A solid conclusion whether different sham alternatives are related to different treatment outcomes cannot be derived because of significant clinical heterogeneity among the analyzed trials. Non-acupoints are generally recommended but the definite locations should be identified with caution. For studies using single sham acupoints on hands or legs, it is suggested to apply identical acupressure devices on the same acupoint as in the active intervention without any stimulation. While for studies on pain, stimulation of sham acupoints should be avoided. Introduction Randomized controlled trial (RCT) is one of the commonly used experimental methods for testing the effectiveness of an intervention [1]. To distinguish the specific effect of a therapeutic approach from the non-specific effect, a placebo control is usually employed [2]. Placebo is defined as “any therapy or component of therapy used for its nonspecific, psychological, or psychophysiological effect, or that is used for its presumed specific effect, but is without specific activity for the condition being treated” [3] (p. 371). A placebo intervention is commonly used in experimental drug studies where the “placebo drug” is identical to the active agent without any specific pharmacological activity against the disease. Theoretically, placebo comparisons should be indistinguishable from the true intervention, and most importantly, should be inert, which means only create non-specific physiological and psychological changes [4]. However, an adequate placebo design becomes difficult to implement when a study is adopting complex non-pharmacological interventions such as physiotherapy, acupuncture or acupressure, etc. Multiple mechanisms involved in these types of treatments make it complicated to develop an appropriate placebo control group. Acupressure has been widely applied in dealing with a variety of health issues globally. In addition to the specific therapeutic effects, stimulation at the acupoints is also believed to generate some non-specific effects, in both physiological and psychological aspects [5]. Placebo controls adopted in acupressure trials are usually referred to as “sham interventions”, which indicate faked acupressure approaches. Various types of sham acupressure have been reported in the literature which mainly differ in three aspects, the selected acupoints, the acupressure approach, and the acupressure intensity. Acupoints adopted in sham procedures commonly include non-acupoints, true acupoints as the active acupressure group, and non-therapeutic acupoints. Non-acupoints generally refer to ineffective body points which cannot be found on established acupuncture-point charts, while non-therapeutic acupoints means irrelevant true acupoints considered to be ineffective for the targeted health problem [2,6]. Sham procedures used in acupuncture have received considerable attention in research. A number of RCTs and systematic reviews have been conducted to investigate the specific treatment effect of acupuncture in a wide range of disorders, especially in pain management, and have yielded contradictory results. Some of them supported the specific benefit of acupuncture [5,7–9], while others argued that the effects of true acupuncture were similar to that in the sham intervention [10–12], and consequently reached the conclusion that the so-called treatment effect of acupuncture may be only a non-specific physiological effect and/or a placebo effect. However, before developing such conclusions, those studies must have a precondition that the employed sham procedure is inert. Similar situations were also detected in studies of acupressure. Despite the significant amounts of research on acupressure during the past decades, it is still uncertain which type of sham acupressure is the most adequate design, and to our knowledge, no study has been conducted so far to summarize the frequently used sham acupressure modalities and to explore their strengths and drawbacks. Hence, the aims of this study are to identify the commonly utilized sham procedures in existing acupressure trials, to assess whether different types of sham intervention yield different therapeutic outcomes, and, if possible, to identify directions for the future development of an adequate sham acupressure mode. This study is a systematic review of the literature (S1 File). A review protocol was created by the first author and it was approved by two experts with experience in acupressure before the commencement of the study (S2 File). Data Sources and Search Strategies Both electronic and manual searches were used to locate relevant studies. Thirteen electronic databases were accessed including PubMed, EMBase, Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL, Allied and Complementary Medicine (AMED), PsycINFO, Thomson Reuters Web of Science, Science Direct, Foreign Medical Journal Service (FMJS), China National Knowledge Infrastructure (CNKI), WanFang Data, Chinese Scientific Journal Database (CQVIP) and Chinese Biomedical Literature Database (CBM), from inception to July 3, 2014. There was no language restriction set for electronic searches. Meanwhile, eight Chinese journals on complementary and alternative medicine (issues published within the latest three years) were manually searched to possibly identify some latest publications which were still not included in the online databases. In addition, eligible studies listed in the reference lists of the included papers and other related systematic reviews on acupressure were also screened to further search any potentially eligible trials. Literature searches were performed independently by two reviewers with Chinese medicine background (JYT and TW). Mesh terms, entry terms, key words and free words such as “acupressure”, “acupress ”, “wristband ” “shiatsu” and “chih ya” were used in the searching strategies. Four selected English and Chinese search strategies are listed in S1 Table. Inclusion and Exclusion Criteria RCTs comparing true acupressure with a sham intervention were included. Both true and sham acupressure can be manipulated through either manual intervention or acupressure devices (e.g., wristbands or attached acupressure beads, etc.). To eliminate the effect of electrical stimulation on the therapeutic outcomes of acupressure, studies on electronic acupressure devices were excluded. At the same time, studies on other modalities of acupuncture-point stimulation such as manual/electronic/laser acupuncture and moxibustion, as well as all kinds of auricular therapy were excluded. Studies published in languages other than English and Chinese were excluded. Methodological Quality Evaluation Methodological quality of the included studies was evaluated using the risk of bias assessment tool developed by the Cochrane Back Review Group [13]. The tool can be viewed as an extension of the original criteria recommended by the Cochrane Handbook. It not only includes all the necessary items described in the latest version of the Cochrane risk of bias tool, but also provides more detailed criteria for assessing “incomplete outcome data” and “other sources of potential bias”. The tool consists of 12 items including: (1) “Was the method of randomization adequate?”; (2) “Was the treatment allocation concealed?”; (3) “Was the patient blinded to the intervention?”; (4) “Was the care provider blinded to the intervention?”; (5) “Was the outcome assessor blinded to the intervention?”; (6) “Was the drop-out rate described and acceptable?”; (7) “Were all randomized participants analyzed in the group to which they were allocated?”; (8) “Are reports of the study free of suggestion of selective outcome reporting?”; (9) “Were the groups similar at baseline regarding the most important prognostic indicators?”; (10) “Were co-interventions avoided or similar?”; (11) “Was the compliance acceptable in all groups?” and (12) “Was the timing of the outcome assessment similar in all groups?” [13]. Each item can be rated as of “yes”, “no” or “unclear” where “yes” indicates a low risk of bias [13]. Importantly, different from the original Cochrane risk of bias criteria, the tool used in this study can provide an overall methodological quality assessment for a single trial. The overall quality can be assessed as “low risk of bias” when at least six items are scored as “yes” and no serious methodological flaws are identified (e.g. 80% dropout rate found in one study arm) [13]. In this review, only RCTs with low risk of bias were eligible for final analysis. Data Extraction For each of the included studies, the following data was extracted independently by the same two reviewers: (1) study general information (first author, year of publication, full name of journal, country of origin, type of study design, and study setting); (2) participant characteristics (age, gender, sample size, dropout rate, diagnostic criteria, inclusion and exclusion criteria, and reason for acupressure); (3) true/sham acupressure protocols (practitioner, acupressure equipment, selected acupoints, treatment duration and number of sessions, and acupressure intensity and frequency, etc.); (4) main outcome(s) and results of the therapeutic effects; (5) adverse events associated with acupressure; and (6) assessment of methodological quality (12 items of the risk of bias tool plus examination of the credibility of blinding). For studies comprising more than two active treatment arms, only data from true and sham acupressure arms were extracted for analysis. Meanwhile, for studies including another control group with standard methods of care, data from the standard care arm were also extracted accordingly. Disagreement between the two reviewers was resolved by discussion or by consulting a third reviewer (AM). Classification of Sham Acupressure Methods After going through all of the sham acupressure protocols of the included studies as well as reviewing the sham control classifications for body and auricular acupuncture in previous studies [2,14,15], sham methods in this study were classified into six types which are described in Table 1. Data Analysis A quantitative synthesis of the main outcomes was originally proposed in the study protocol. However, a precise meta-analysis was deemed impossible due to the significant clinical heterogeneity identified in the health conditions, patient characteristics, intervention protocols and outcome measures among studies. A subgroup meta-analysis for the same health conditions within each sham acupressure type was also considered but finally abandoned for the reasons that clinical heterogeneity was still considerable within each sham modality, and the number of trials in some sham types was insufficient for data synthesis. To provide an exploratory analysis Types of Sham Methods Sham Acupressure at Non-acupoints by Manual Pressure Sham Acupressure at Non-acupoints by Employing Acupressure Devices Pseudo-intervention at the Same Acupoints as True Treatment Arm by Manual Light-Touch Pseudo-intervention at the Same Acupoints as True Treatment Arm by using Placebo Devices Manual Acupressure at Non-Therapeutic (Irrelevant) Acupoints Sham Acupressure at Non-Therapeutic (Irrelevant) Acupoints by Adopting Acupressure Devices of the study outcomes, responder rate and responder rate ratio (responder rate in true acupressure group/responder rate in sham group) for each study presenting dichotomous data were calculated, and a risk ratio (RR) with 95% confidence interval (CI) was used to present the responder rate ratio. Descriptive analysis was also used to summarize the therapeutic outcomes of acupressure, for both the overall effect and the subgroup effect by each sham alternative. The overall assessment was to investigate whether true acupressure is superior to sham comparisons while the subgroup analysis was used to assess whether different types of sham methods could induce different therapeutic effects. Results of the treatment effect for each main outcome in each individual study were extracted by two reviewers according to the following vote counts [2]: “++”: true acupressure is significantly better than sham control for the main outcome; “+”: trend of the main outcome in favor of true acupressure but without statistical significance; “0”: no difference between true and sham acupressure; “−”:trend of the main outcome in favor of sham acupressure but without statistical significance; and “− −”: sham intervention is significantly better than true acupressure for the main outcome. For studies reporting multiple main outcomes, all such outcomes were included for analysis. For studies not indicating the main outcomes, all variables with between-group comparison were extracted accordingly. In addition, subgroup descriptive analyses for different types of health problems, intervention duration and frequency as well as acupressure intensity were also considered when data were available. Based on the analyzed trials, length of treatment was categorized into “extremely short-term” (less than one hour), “short-term” (more than one hour but less than one day), “mid-term” (more than one day but less than one week), and “long-term” (more than one week). For studies on postoperative issue (e.g. nausea, vomiting and pain, etc.) which employed multiple assessment time points, postoperative data within the first 24 hours were abstracted for analysis. The chi-square test was used to assess the difference in dropout rates between the true and sham acupressure arms. Results Characteristics of the Included Studies A total of 5225 items were located. Among those 2283 duplicated articles were excluded after screening by the reference management software NoteExpress. A total of 2694 records were subsequently removed by checking titles and abstracts. For the remaining 248 items, full-texts were accessed for evaluating eligibility, among which, 160 were further removed because they failed to include a sham control group (n = 92), were conference proceedings (n = 32), were auricular acupressure studies (n = 11), and were articles published in Arabic/Farsi (n = 21), Korean (n = 3) and French (n = 1). The remaining 88 articles were further adopted for methodological quality evaluation, of which, 22 with high risk of bias were removed (S2 Table) and 66 studies [16–81] were finally included for analysis. Fig 1 shows the flow chart of the study selection. The included studies comprised 7265 subjects, with an average sample size of 110 patients per study. These studies were published between 1991 and 2015 and were conducted in 18 different countries or regions. Of which, 13 studies originated from Iran, 12 from the United States, ten from Taiwan, five from Sweden, four from the United Kingdom, three from Austria, three from South Korea, three from Canada, two from Italy, two from Ireland, two from India, and one each from Hong Kong, Denmark, Australia, Turkey, Pakistan, Poland and Norway. More than half were carried out in hospitals or medical centers. Acupressure was used to deal with a variety of health problems including nausea and vomiting, labor pain, primary dysmenorrhea, sleep disturbance, postoperative gastrointestinal dysfunction, and anxiety, etc. Characteristics of the included studies can be seen in Table 2. Tang et al. 2014 [16], Pulmonary Wards of A Medical Center, Taiwan Atrian et al. 2013 [17], Dormitories of Kashan University of Medical Sciences, Iran Sehhatie-Shafaie et al. 2013 [18], The Public Hospitals of Ardebil, Iran Chao et al. 2013 [19], An Urban Medical Center in Taipei, Taiwan Valiee et al. 2012 [21], Surgery Wards, Hospital of Tehran University of Medical Science, Iran Rad et al. 2012 [22], Rouhani Hospital of Babol University of Medical Science, Iran Chang et al. 2011 [23], A Urogynecology Clinic of Queen Elizabeth Hospital, Hong Kong Cancer-related Fatigue Primary Dysmenorrhea Labor Pain in Nulliparous Women Postoperative Gastrointestinal Function Stress Reduction Preoperative Anxiety Nausea and Vomiting in Pregnancy TAG 1: Manual Acupressure at True Acupoints, TAG 2: Manual Acupressure at True Acupoints + Essential Oils, SAG: Manual Acupressure at Non-Acupoints Total: 67/ TAG: Manual 8, TAG: Acupressure at True 33/6, SAG: Acupoints, SAG: 34/2 Manual Acupressure at Non-Acupoints Total: 84/ TAG: Manual 0, TAG: Acupressure at True 42/0, SAG: Acupoints, SAG: 42/0 Manual Acupressure at Non-Acupoints TAG: Manual Acupressure at True Acupoints + Routine Care, SAG: Manual Acupressure at NonAcupoints + Routine Care TAG: Manual Acupressure at True Acupoints, SAG: Manual Acupressure at Non-Acupoints, CG: An Audio Relaxation CD Total: 70/ TAG: Manual 0, TAG: Acupressure at True 35/0, SAG: Acupoints, SAG: 35/0 Manual Acupressure at Non-Acupoints Total: 85/ TAG: Manual 5, TAG: Acupressure at True 43/3, SAG: Acupoints, SAG: 42/2 Manual Acupressure at Non-Acupoints Study & Setting(s) Type 1—Sham Acupressure at Non-Acupoints: Manual Acupressure Main Outcome(s) Therapeutic Effects of Acupressure* Fatigue (Tang Fatigue Rating Scale) Pain Intensity (VAS) Pain Intensity (Visual Pain Scale) Frequency of Bowel Sounds, Time to the First Flatus Passage and Defecation, and Time to Oral Liquid and Solid Intake Stress Responses (Heart Rate, Heart Rate Variability, Skin Conductance Response, State Anxiety Inventory, and Psychological Stress Measure) Preoperative Anxiety (VAS), and Vital Signs (Blood Pressure, Heart Rate, and Respiratory Rate) Intensity of Nausea (VAS) and Vomiting (Frequency of Vomiting) ++(For Bowel Sounds, Flatus Passage, and Liquid Intake), + (For Solid Intake and Defecation) ++ (For Anxiety, Respiratory Rate, and Systolic Blood Pressure), + (For Heart Rate and Diastolic Blood Pressure) ++, TAG was Significantly Better than SAG and CG; No Difference was Found between SAG and CG Acupressurerelated AEs Not Reported2 No AEs Found in the Study Not Reported2 Not Reported2 Not Reported2 Not Reported2 No AEs Found in the Study Not Reported2 Study & Setting(s) McFadden et al. 2011 [24], A Community in Colorado, United States Kashefi et al. 2011 [25], Bojnoord University of Medical Science, Iran Reza et al. 2010 [26], Kahrizak Charity Nursing Home, Iran Bertalanffy et al. 2004 [30], Sites of Accident, Austria Chen et al. 2003 [31], A Mid-Taiwan Teaching Hospital, Taiwan Cardiovascular Function in Stroke Survivors Symptoms and Health-Related Quality of Life in Bronchiectasis Patients Nausea, Vomiting, and Ketonuria Levels in Women with Hyperemesis Gravidarum Gastrointestinal Motility after Surgery Main Outcome(s) TAG: Manual Acupressure at True Acupoints, SAG: Manual Acupressure at Non-Acupoints TAG: Manual Acupressure at True Acupoints, SAG: Manual Acupressure at Non-Acupoints TAG: Manual Acupressure at True Acupoints + Usual Care, SAG: Manual Acupressure at NonAcupoints + Usual Care, CG: Usual Care TAG: Manual Acupressure at True Acupoints, SAG: Manual Acupressure at Non-Acupoints TAG: Manual Acupressure at True Acupoints + Standard Care, SAG: Manual Acupressure at NonAcupoints + Standard Care, CG: Standard Care TAG: Manual Acupressure at True Acupoints + Routine Intravenous Therapy, SAG: Manual Acupressure at NonAcupoints + Routine Intravenous Therapy, CG: Routine Intravenous Treatment TAG: Manual Acupressure at True Acupoints, SAG: Manual Acupressure at Non-Acupoints TAG: Manual Acupressure at True Acupoints, SAG: Manual Acupressure at Non-Acupoints Cognitive Impairment and State of Being following Traumatic Brain Injury Women’s General Health (General Health Questionnaire) Self-Reported Sleep Habits (Pittsburgh Sleep Quality Index) Daily Sputum Amounts, Efforts to clean Secretions (Sputum SelfAssessment), SixMinute Walking Distance, Breathing Difficulty, and Quality of Life (SGRQ) Degree of Nausea and Vomiting (The Rhodes Index of Nausea, Vomiting, and Retching), and Degree of Ketonuria Gastrointestinal Motility (Multifunctional Stethoscope) Therapeutic Effects of Acupressure* ++, TAG was Significantly Better than SAG and CG; The Sleep Quality in SAG was Better than That in CG but There was no Statistical Significance 0, TAG was Better than CG Regarding to the SGRQ Activity Domain, and SAG was better than CG in the Improvement of Sputum SelfAssessment ++, The Degree of Nausea and Vomiting in TAG was Statistically Lower than SAG and CG, and No Difference was Found between SAG and CG Acupressurerelated AEs Not Reported2 No AEs Found in the Study Not Reported2 Not Reported2 Not Reported2 Not Reported2 Not Reported2 Not Reported2 Study & Setting(s) Tsay & Chen 2003 [32], Four Dialysis Centers in Major Hospitals in Taipei, Taiwan Kober et al. 2002 [33], Sites of Accident, Austria Belluomini et al. 1994 [34], Department of Obstetrics and Gynecology, California Pacific Medical Center, United States Adib-Hajbaghery & Etri, 2013 [35], A General Surgical Ward of A University Hospital, Iran Alessandrini et al. 2012 [36], Otolaryngology Department, University of Rome “Tor Vergata”, Italy Pre-Hospital Analgesia Nausea and Vomiting in Pregnancy Postoperative Pain, Nausea, and Vomiting Postoperative Nausea and Vomiting Type 2—Sham Acupressure at Non-Acupoints: Acupressure Bands or Other Devices Total: 105/ TAG: Manual 7, TAG: Acupressure at True NR, SAG: Acupoints + Usual NR, CG: Care, SAG: Manual NR Acupressure at Non Acupoints + Usual Care, CG: Usual Care Total: 60/ TAG: Manual 0, TAG: Acupressure at True 19/0, SAG: Acupoints, SAG: 20/0, CG: Manual Acupressure at 21/0 Non-Acupoints, CG: No Acupressure TAG: Manual Acupressure at True Acupoints, SAG: Manual Acupressure at Non-Acupoints Total: 70/ TAG: Acupressure at 0, TAG: True Acupoints using 35/0, SAG: Acupressure Band, 35/0 SAG: Acupressure at Non-Acupoints using Acupressure Band Total: 204/ TAG: Acupressure at 0, TAG: True Acupoints using 102/0, Acupressure Band, SAG: 102/ SAG: Acupressure at 0 Non-Acupoints using Acupressure Band Total: 200/ TAG: Using 0, TAG: Acupressure Wrist Band 50/0, SAG at True Acupoints, SAG 1: 50/0, 1: Using Acupressure SAG 2: 50/ Wrist Band at Non0, SAG 3: Acupoints, SAG 2: 50/0 Using Acupressure Wrist Band at NonAcupoints + Metoclopramide, SAG 3: Using Acupressure Wrist Band at NonAcupoints + Ondansetron Main Outcome(s) Sleep Quality (Pittsburgh Sleep Quality Index) Nausea and Vomiting (The Index of Nausea, Vomiting, and Retching) Severity of Nausea and Pain (VAS), and Severity of Vomiting (Frequency of Vomiting) Severity of Vertigo and Neurovegetative Symptoms (VAS) Postoperative Nausea and Vomiting during the First Two Hours (0–2 Hours) and the Following 22 Hours (2–24 Hours) after Surgery Therapeutic Effects of Acupressure* 0, TAG was Significantly Better than CG; No Difference was Found between SAG and CG Comparisons between Groups were not Performed (or Not Clearly Reported) ++ (For Nausea), + (For Vomiting) ++ (For Pain), 0 (For Nausea), NA (For Vomiting)3 Comparisons between Groups were not Performed (or Not Clearly Reported) Acupressurerelated AEs Not Reported2 Not Reported2 Not Reported2 Not Reported2 Not Reported2 Not Reported2 Study & Setting(s) Bao et al. 2011 [38], The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, United States Sinha et al. 2011 [40], A Single Tertiary Maternity Unit, Australia Turgut et al. 2007 [42], Department of Anesthesiology, Ankara Oncology Hospital, Turkey Postoperative Nausea and Vomiting Postoperative Nausea and Vomiting Nausea and Vomiting in Early Pregnancy Preoperative Parental Anxiety Total: 78/ TAG: Acupressure at 1, TAG: True Acupoints using 38/1, SAG: Magnetic Acupressure 40/0 Suction Cups + Standard Local Analgesics, SAG: Acupressure at NonAcupoints using Magnetic Acupressure Suction Cups + Standard Local Analgesics Total: 134/ TAG: Acupressure at 22, TAG: True Acupoints using 67/8, SAG: Acupressure Band, 67/14 SAG: Acupressure at Non-Acupoints using Acupressure Band Total: 340/ TAG: Acupressure at 11, TAG: True Acupoints using 170/6, Acupressure Band, SAG: 170/ SAG: Acupressure at 5 Non-Acupoints using Placebo Acupressure Band Total: 52/ TAG: Acupressure at 0, TAG: True Acupoints using 26/0, SAG: Acupressure Beads, 26/0 SAG: Acupressure at Non-Acupoints using Acupressure Beads Total: 102/ TAG: Acupressure at 2, TAG: True Acupoints using 51/1, SAG: Acupressure Band, 51/1 SAG: Acupressure at Non-Acupoints using Acupressure Band Total: 80/ TAG: Acupressure at 0, TAG: True Acupoints using 40/0, SAG: Acupressure Band, 40/0 SAG: Acupressure at Non-Acupoints using Acupressure Band TAG: Acupressure at True Acupoints using Acupressure Beads, SAG: Acupressure at Non-Acupoints using Acupressure Beads Main Outcome(s) Therapeutic Effects of Acupressure* Pain Intensity (VAS) Postoperative Nausea and/or Vomiting Incidence of Nausea and/or Vomiting Anxiety Level (State Anxiety Inventory for Children) No. of Days of Hospital Stay, and No. of Patients Who Required ≧ 4 Days in the Hospital Parental Anxiety (State Anxiety Inventory) 0 (For No. of Days of Hospital Stay), + + (For No. of Patients Who Required ≧ 4 Days in the Hospital) Acupressurerelated AEs Mild and Transient Bruising or A Rash at the Acupressure Site (n = 10) Discomfort from Band (n = 25) Not Reported2 Erythema and Swelling of the Treated Hand (n = 1) No Discomforts Found in the Study Not Reported2 Time to the Onset of Moderate Nausea Incidence of Nausea and Vomiting Therapeutic Effects of Acupressure* +, Mean Time to Moderate Nausea was Statistically Longer in TAG than That in CG, SCG was also Longer than CG but There was no Statistical Significance Acupressurerelated AEs Not Reported2 Study & Setting(s) Alkaissi et al. 2005 [45], Department of Otolaryngology, University Hospital of Linköping, Sweden Tolerance to Nauseogenic Motion Stimulation Samad et al. 2003 [46], Aga Khan University Hospital, Pakistan Postoperative Nausea and Vomiting Alkaissi et al. 2002 Postoperative [47], University Nausea and Hospital of Linköping, Vomiting Sweden Agarwal et al. 2000 [48], Setting not Described, India Postoperative Nausea and Vomiting Harmon et al. 2000 [49], Rotunda Hospital, Ireland Nausea and Vomiting during and after Surgery Harmon et al. 1999 [50], Rotunda Hospital, Ireland Postoperative Nausea and Vomiting Alkaissi et al. 1999 Postoperative [51], University Nausea and Hospital of Linköping, Vomiting Sweden Main Outcome(s) Total: 60/ TAG: Acupressure at 0, TAG: True Acupoints using 20/0, SAG: Acupressure Band, 20/0, CG: SAG: Acupressure at 20/0 Non-Acupoints using Acupressure Band, CG: No Acupressure TAG: Acupressure at True Acupoints using Wrist-Band with Plastic Bead, SAG: Acupressure at NonAcupoints using Wrist Band with Plastic Bead Total: 410/ TAG: Acupressure at 30, TAG: True Acupoints using 135/NR, Acupressure Band SAG: 139/ + Routine Anesthesia, NR, CG: SAG: Acupressure at 136/NR Non-Acupoints using Acupressure Band + Routine Anesthesia, CG: Routine Anesthesia Total: 200/ TAG: Acupressure at 0, TAG: True Acupoints using 100/0, Acupressure Bands, SAG: 100/ SAG: Acupressure at 0 Non-Acupoints using Acupressure Bands TAG: Acupressure at True Acupoints using Acupressure Band, SAG: Acupressure at Non-Acupoints using Acupressure Band Total: 104/ TAG: Acupressure at 0, TAG: True Acupoints using 52/0, SAG: Acupressure Band, 52/0 SAG: Acupressure at Non-Acupoints using Acupressure Band TAG: Acupressure at True Acupoints using Acupressure Band + Routine Anesthesia, SAG: Acupressure at Non-Acupoints using Acupressure Band + Routine Anesthesia, CG: Routine Anesthesia Postoperative Nausea and Vomiting Postoperative Nausea and Vomiting Complete Response 0, Both TAG and of Postoperative SAG were Better Nausea and Vomiting than CG, but There (No Report of were No Statistical Nausea, Vomiting or Significances Rescue Medication) Discomforts, Red Indentation or Itching (n = 15), Headache and Dizziness (n = 1), Deep Marks, Blistering or Swelling (n = 45) No AEs Found in the Study Not Reported2 No AEs Found in the Study Not Reported2 Total: 200/ TAG: Acupressure at 0, TAG: True Acupoints using 108/0, Acupressure Band, SAG: 92/0 SAG: Acupressure at Non-Acupoints using Acupressure Band TAG: Acupressure at True Acupoints using Acupressure Band, SAG: Acupressure at Non-Acupoints using Acupressure Band, CG: No Acupressure TAG: Acupressure at True Acupoints using A Dentist’s Tool, SAG: Acupressure at NonAcupoints using A Dentist’s Tool Total: 23/ TAG: Acupressure at 8, TAG: True Acupoints using 11/4, SAG: Acupressure Band, 12/4 SAG: Acupressure at Non-Acupoints using Acupressure Band Total: 100/ TAG: Manual 0, TAG: Acupressure at True 50/0, SAG: Acupoints, SAG: Light 50/0 Touch on the Same Acupoints Total: 30/ TAG: Manual 0, TAG: Acupressure at True 15/0, SAG: Acupoints, SAG: Light 15/0 Touch on the Same Acupoints Total: 50/ TAG: Manual 6, TAG: Acupressure at True 25/2, SAG: Acupoints, SAG: Light 25/4 Touch on the Same Acupoints Total: 120/ TAG: Manual 0, TAG: Acupressure at True 60/0, SAG: Acupoints, SAG: Light 60/0 Touch on the Same Acupoints Total: 213/ TAG: Manual 1, TAG: Acupressure at True 71/0, SAG: Acupoints + Usual 71/0, Care, SAG: Light Touch CG:71/1 on the Same Acupoints + Usual Care, CG: Usual Care Postoperative Nausea and Vomiting Nausea and Vomiting (The Rhodes Index of Nausea, Vomiting, and Retching) Intensity of Labor Pain (VAS) Severity of Dysmenorrhea (VAS) Severity of Labor Pain (VAS) and Duration of Active Phase Intensity of Labor Pain (VAS) Felhendler & Lisander 1996 [54], An Ambulatory Unit in Linköping University Hospital, Sweden Hamidzadeh et al. 2012 [56], Fatemiyeh Educational and Research Hospital in Shahroud, Iran Mirbagher-Ajorpaz et al. 2011 [57], Dormitories of Kashan University of Medical Science, Iran Hjelmstedt et al. 2010 [60], Sree Avittom Thirunal Hospital in Trivandrum, India Primary Dysmenorrhea Duration and Pain of the Active Phase of Labor Study & Setting(s) Fan et al. 1997 [52], Maimonides Medical Center, United States Postoperative Nausea and Vomiting O’Brien et al. 1996 [53], Setting Not Described, Canada Nausea and Vomiting During Pregnancy Early Morning Sickness Main Outcome(s) Therapeutic Effects of Acupressure* 0, No Difference was Detected Across Groups ++, TAG was Significantly Better than CG; SAG was Better than CG but There was no Statistical Significance Acupressurerelated AEs No AEs Found in the Study Not Reported2 Not Reported2 Not Reported2 No AEs Found in the Study Not Reported2 Not Reported2 Not Reported2 Not Reported2 Study & Setting(s) Hsu et al. 2006 [61], Insomnia Two Long-Term Care Facilities, Taiwan Main Outcome(s) Therapeutic Effects of Acupressure* Insomnia (Pittsburgh Sleep Quality Index) Severity of Labor Pain (VAS) and Duration of Labor to Delivery Postoperative Nausea (NRS) Lee et al. 2004 [62], Delivery Room in A University Hospital, South Korea Nilsson et al. 2015 [63], Department of Neurosurgery of Umeå University Hospital, Sweden Molassiotis et al. 2013 [64], Christie NHS Foundation Trust, Clatterbridge Centre for Oncology, Southport General Infirmary, and Several Hospitals, United Kingdom Noroozinia et al. 2013 [65], Imam Khomeini General Hospital of Urmia, Iran Soltanzadeh et al. 2012 [66], Hospital (Details not Described), Iran Postoperative Nausea and Vomiting ChemotherapyInduced Acute and Delayed Nausea Postoperative Nausea and Vomiting Postoperative Nausea and Vomiting Total: 50/ TAG: Manual 0, TAG: Acupressure at True 25/0, SAG: Acupoints, SAG: Light 25/0 Touch on the Same Acupoints TAG: Manual Acupressure at True Acupoints, SAG: Light Touch on the Same Acupoints Total: 120/ TAG: Acupressure at 25, TAG: True Acupoints using 52/9, SAG: Acupressure Band, 68/16 SAG: Sham Acupressure at the Same Acupoints using A Placebo Acupressure Band Total: 152/ TAG: Acupressure at 0, TAG: True Acupoints using 76/0, SAG: Acupressure Band, 76/0 SAG: Sham Acupressure at the Same Acupoints using A Placebo Acupressure Band Total: 120/ TAG: Acupressure at 0, TAG: True Acupoints using 40/0, SAG Acupressure Band, 1: 40/0, SAG 1: Sham SAG 2: 40/ Acupressure at the 0 Same Acupoints using A Dummy Band, SAG 2: Sham Acupressure at the Same Acupoints using A Dummy Band + Metoclopramide Acupressurerelated AEs Not Reported2 Not Reported2 Transient AEs (n = 6): Minor Swelling and Tightness in the Area of Wristbands, and Discomfort when Wearing the Wristbands Not Reported2 TAG: Acupressure at ChemotherapyTrue Acupoints using Induced Nausea (The Acupressure Band Nausea Experience + Standard Antiemetics, Subscale of The SAG: Sham Rhodes Index of Acupressure at the Nausea, Vomiting, Same Acupoints using and Retching) A Placebo Acupressure Band+ Standard Antiemetics, CG: Standard Antiemetics Incidence of Postoperative Nausea and Vomiting ++ (For Nausea), + (For Vomiting) No AEs Found in the Study Main Outcome(s) Therapeutic Effects of Acupressure* Study & Setting(s) White et al. 2012 [67], Cedars Sinai Medical Center in Los Angeles, United States Ho et al. 2006 [68], Taipei Veterans General Hospital, Taiwan Postoperative Nausea and Vomiting Klein et al. 2004 Postoperative [69], Toronto General Nausea and Hospital, Canada Vomiting Schultz et al. 2003 [70], A Tertiary Care Hospital in Northern New England, Portland Postoperative Nausea and Vomiting Dent et al. 2003 [71], The Coronary Care Unit of A District Hospital, United Kingdom Acute Myocardial Infarction-Related Nausea and Vomiting Norheim et al. 2001 [72], A University Hospital, Norway Morning Sickness in Pregnancy Total: 100/ TAG: Acupressure at 0, TAG: True Acupoints using 50/0, SAG: Acupressure Strip, 50/0 SAG: Sham Acupressure at the Same Acupoints using A Placebo Acupressure Strip Total: 110/ TAG: Acupressure at 0, TAG: True Acupoints using 55/0, SAG: Acupressure Band, 55/0 SAG: Sham Acupressure at the Same Acupoints using A Placebo Acupressure Band Total: 152/ TAG: Acupressure at 0, TAG: True Acupoints using 75/0, SAG: Acupressure Band, 77/0 SAG: Sham Acupressure at the Same Acupoints using A Placebo Acupressure Band Total: 143/ TAG 1: Acupressure 40, TAG Band at True Acupoints 1:30, TAG + Droperidol, TAG 2: 2:24, SAG Acupressure Band at 1:24, SAG True Acupoints 2:25 + Placebo Drug, SAG 1: Placebo Band at the Same Acupoints + Droperidol, SAG 2: Placebo Band at the Same Acupoints + Placebo Drug Total: 301/ TAG: Acupressure at 0, TAG: True Acupoints using 95/0, SAG: Acupressure Band, 98/0, CG: SAG: Sham 108/0 Acupressure at the Same Acupoints using A Placebo Acupressure Band, CG: No Additional Intervention TAG: Acupressure at True Acupoints using Acupressure Band, SAG: Sham Acupressure at the Same Acupoints using A Placebo Acupressure Band Incidence of Postoperative Nausea and Vomiting Incidence of Nausea and Vomiting During Surgery Incidence of Postoperative Nausea and Vomiting Incidence of Postoperative Nausea and Vomiting Incidence of Nausea and Vomiting Incidence and Duration of Nausea and Vomiting Acupressurerelated AEs No AEs Found in the Study No AEs Found in the Study —(For Nausea),— (For Vomiting) 6 Not Reported2 +,TAG was Better than SAG and CG, No Difference was Found between SAG and CG Not Reported2 + (For Incidence of Nausea and Vomiting), ++ (For Duration of Nausea and Vomiting) Pain, Numbness, Soreness, and Swelling (No. not Given); Worse Symptoms (n = 3) Main Outcome(s) Type 5—Acupressure at Non-Therapeutic Acupoints (Irrelevant Acupoints): Manual Acupressure Study & Setting(s) Steele et al. 2001 [73], Seventeen Medical Clinics or Offices in Southern Michigan, United States Woods 1999 [74], Malcolm Grow Air Force Medical Center, United States Nausea and Vomiting During Pregnancy Postoperative Nausea and Vomiting Postoperative Nausea and Vomiting Lewis et al. 1991 [76], Hospital (Details not Described), United States Postoperative Nausea and Vomiting Suh 2012 [77], A University Cancer Center in Seoul, South Korea ChemotherapyInduced Nausea and Vomiting Lang et al. 2007 [78], A ParamedicBased Rescue System, Austria Pre-Hospital Analgesia Total: 138/ TAG: Acupressure at 28, TAG: True Acupoints using 85/17, Acupressure Band, SAG: 53/ SAG: Sham 11 Acupressure at the Same Acupoints using A Placebo Acupressure Band TAG: Acupressure at True Acupoints using Acupressure Band, SAG: Sham Acupressure at the Same Acupoints using A Placebo Acupressure Band Total: 263/ TAG: Acupressure at 19, TAG: True Acupoints using 122, SAG: Acupressure Band, 122 SAG: Sham Acupressure at the Same Acupoints using A Placebo Acupressure Band Total: 66/ TAG: Acupressure at 2, TAG: True Acupoints using 33/2, SAG: Acupressure Band, 33/0 SAG: Sham Acupressure at the Same Acupoints using A Placebo Acupressure Band TAG 1: Acupressure at Therapeutic Acupoints using Acupressure Band, TAG 2: Acupressure at Therapeutic Acupoints using Acupressure Band + Counseling, SAG: Manual Acupressure at Irrelevant Acupoints, CG: Counseling Only Total: 32/ TAG: Manual 1, TAG: Acupressure at 16/1, SAG: Therapeutic Acupoints, 16/0 SAG: Manual Acupressure at Irrelevant Acupoints Severity and Frequency of Nausea and Vomiting Incidence of Nausea and Vomiting Incidence of Postoperative Nausea and Vomiting ChemotherapyInduced Nausea and Vomiting (The Index of Nausea, Vomiting, and Retching) Therapeutic Effects of Acupressure* Acupressurerelated AEs Not Reported2 Not Reported2 Tightness (n = 22), Swollen Hands (n = 43), Infusion Problem (n = 4), and Itching Wrists (n = 9) Bands were Well Tolerated ++ (For Acute and Delayed Vomiting) 7 Not Reported2 Intensity of Pain and Anxiety (VAS), and Blood Pressure and Heart Rate ++ (For Pain, Anxiety and Heart Rate), 0 (Blood Pressure) Not Reported2 Study & Setting(s) Wu et al. 2007 [79], Wu et al. 2004 [80], A Medical Center and Three Regional Hospitals in Taipei, Taiwan TAG: Acupressure at Therapeutic Acupoints using Wrist Acupressure Device, SAG: Acupressure at Irrelevant Acupoints using Wrist Acupressure Device Main Outcome(s) Depression (The Geriatric Depression Scale), Anxiety (The State Anxiety Inventory), Chronic Dyspnea (Pulmonary Function Status and Dyspnea Questionnaire Modified and VAS), and Six-Minute Walking Tests Therapeutic Effects of Acupressure* Acupressurerelated AEs Not Reported2 Nordio & Romanelli 2008 [81], Setting not Described, Italy No AEs Found in the Study SGRQ: The Saint George Respiratory Questionnaire, NRS: Numerical Rating Scale 1: For true acupressure group 1 and sham acupressure group 2: The study did not assess acupressure-related adverse events 3: Statistical analysis was not conducted for vomiting 4: For true acupressure group and sham acupressure group 1 6: For true acupressure group 1 and sham acupressure group 1 7: For true acupressure group 1 and sham acupressure group. is significantly better than true acupressure group for the main outcome. Methodological Quality and Risk of Bias of the Included Studies Results of the risk of bias assessment for all the included trials can be seen in S3 Table. Methodological quality of the included trials was generally satisfactory, as already all studies of high risk of bias were excluded. Forty-nine trials adequately described the method of randomization. Twenty-six studies appropriately described the allocation concealment. Blinding of participants was adopted in 45 trials. Outcome assessor was blinded to the intervention in the majority of studies (51 studies), but there were only 17 studies which reported blinding for the care provider. Eighteen studies employed a single-blind design for either participant, or care provider, or outcome assessor. Double-blinding for both participant and outcome assessor was utilized in 26 trials, and blinding for both the care provider and the outcome assessor was used in four studies. There were 11 trials that incorporated a triple-blind design. No trial tested the credibility of blinding during the study period. Dropout of study subjects was mentioned and acceptable in 89.4% of the included studies. Thirty-two trials reported that all randomized participants were included for analysis. Selective outcome reporting was detected in only one study, and baseline data were similar between groups in most of the studies. Co-intervention (e.g. intra-operative anesthesia or standard care, etc.) was similar or avoidable in more than half of the articles (42 studies). Participants’ compliance to treatment was mentioned and satisfactorily achieved in seven studies. The timing of outcome assessment was found similar among groups in 96.97% of the included trials. Description of Acupressure Protocols True acupressure protocols used in the included trials are presented in Table 3. Among the analyzed trials, 30 adopted manual acupressure while another 36 chose acupressure equipment to provide constant pressure on the targeted acupoints. The majority (52 studies) described the person conducting acupressure, being an acupuncturist, acupressure practitioner, anesthetist, nurse, paramedic and study investigator, etc. For studies where acupressure was administered by non-acupuncture/acupressure professionals, 60% (27/45) specified that the intervention operator had received training in acupressure or application of the acupressure device. Length of acupressure therapy varied significantly among studies due to the nature of the treated conditions. The shortest intervention (three minutes) emerged in one study focusing on pre-hospital analgesia [33] while the longest treatment was five months for cancer-related fatigue [16]. Fifty studies reported the intensity for acupressure, 24 claimed equal intensity between groups, while sham groups received only light acupressure or no stimulation in the other 26 studies. For the types of acupressure, 61 articles employed Chinese acupuncture theory to guide the acupressure protocol, and three adopted the Japanese Jin Shin acupressure [20, 24, 27], while the other two used Korean hand acupressure [30,66]. Bilateral acupoints were stimulated in both groups in 38 studies, and eight trials only employed unilateral stimulation, while in the other 20 studies, both bilateral and unilateral acupoints were used or such information were not reported. The number of selected acupoints ranged from one to 15 in the true treatment groups, and the majority (50 studies) only applied one acupoint (bilateral or unilateral) for acupressure. In one study on postoperative pain [54], 15 acupoints were chosen for stimulation. Selection of the acupoints was based on the targeted health issue, and neiguan (P6) was frequently used for controlling nausea and/or vomiting, sanyinjiao (SP6) and hegu (LI4) were used for treating various types of pain such as peri-operative pain, primary dysmenorrheal and labor pain, shenmen (HT7) was mainly used for sleep disorders, and yintang (EX-NH3) was used for anxiety relief. Description of Sham Acupressure Procedures Sham acupressure protocols are also summarized in Table 3. Six types of sham acupressure were identified. Non-acupoint was used in 40 studies, of which, 19 manually stimulated the non-acupoint (type 1). For studies with type 1 sham mode, 12 described the definite location of the selected non-acupoints and most of them were near the real acupoints used in the true intervention groups. More specifically, three studies [25, 26, 32] indicated that the non-acupoints should be away from the nearby meridians, with 0.5 cun (a traditional Chinese term that translates to "anatomical inch") in one study [26], and one cm in another [32]. In addition, there was one study [31] stating that the non-acupoints should be three to four cm away from the targeted active acupoints. Total duration of treatment as well as duration of each session were similar between groups. In terms of the acupressure intensity, three studies [19, 22, 25] applied equal pressure between groups, and one [23] only exerted light pressure on non-acupoints, while this information was not reported in the other 15 articles. Twenty-one studies used acupressure devices at the non-acupoints (type 2). Both true and sham study arms utilized the same equipment. Wrist bands such as sea-bands or vital-bands, etc. were adopted in 16 studies and these tools usually possess a plastic/metal button located at True Acupressure (TA) Sham Acupressure (SA) Intervention Duration Type 1—Sham Acupressure at Non-Acupoints: Manual Acupressure (19 Studies) Tang et al. 2014 [16] Atrian et al. 2013 [17] Researcher with Acupressure Training Research Assistant with Acupressure Training Chao et al. 2013 [19] Research Nurse with Acupressure Training McFadden et al. 2012 [20] Acupressure Practitioner Valiee et al. 2012 [21] Researcher with Acupressure Training Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): (Bilateral) Hegu (LI4), Zusanli (ST36), and Sanyinjiao (SP6) Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): (Bilateral) Taichong (LR3) Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): (Bilateral) Sanyinjiao (SP6), and Hegu (LI4) Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): (Bilateral) Zusanli (ST36) Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): True Acupoints (Details not Described) Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): Yintang (or Extra-1, EX-NH3), and Shenmen (Ear) Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): (Bilateral) Youmen (KI21) Acupressure Intensity Method(s): Manual Acupressure at Non-Acupoints, Selected Acupoint(s): (Bilateral) Non-Acupoints at Inner Ankle, Patella, and the First Metacarpal Head Method(s): Manual Acupressure at Non-Acupoints, Selected Acupoint(s): (Bilateral) Non-Acupoints located 2 cm above the Distance between the Third and Fourth Toes Method(s): Manual Acupressure at Non-Acupoints, Selected Acupoint(s): (Bilateral) Non-Acupoints on the Legs and Hands (Details not Described) Method(s): Manual Acupressure at Non-Acupoints, Selected Acupoint(s): (Bilateral) Non-Acupoint located at the Tibia Method(s): Manual Acupressure at Non-Acupoints, Selected Acupoint(s): NonAcupoints which cannot be Found on Established Acupressure Point Charts (Details not Described) Method(s): Manual Acupressure at Non-Acupoints, Selected Acupoint(s): NonAcupoints located at the External Corner of the Left Eyebrow, and the Entrance of the Cavity of the Ear Method(s): Manual Acupressure at Non-Acupoints, Selected Acupoint(s): (Unilateral) No-Acupoint (Details Not Described) Total Duration: Daily Treatment for Consecutive 5 Months, Each Treatment: 6 Min with 1 Min for Each Acupoint Total Duration: NR (3 Treatments in Total), Each Treatment: 16 Mins (Each Acupoint on Each Leg for 2 Min Pressure and 2 Min Resting, Repeated Twice) Total Duration: Four Treatments in Total, Each Treatment: 20 Min Total Duration: 3 Treatments Per Day for 5 Days, Each Treatment: 5 Continuous 1-second Press followed by a 2-Second Rest, Repeated for 3 Min Total Duration: 40 Min (Only One Treatment) Total Duration: Daily Treatment for 4 Consecutive Days, Each Treatment: 2 Min Acupressure followed by 2 more Min Massage at the Acupoints, Repeated for 20 Min Total Duration: 10 Min (Only One Treatment) Chang et al. 2011 [23] Researcher with Acupressure Training McFadden et al. 2011 [24] Acupressure Practitioner Researcher with Acupressure Training Reza et al. 2010 [26] Investigator with Acupressure Training McFadden & Hernández 2010 [27] Acupressure Practitioner Maa et al. 2007 Investigator Skilled [28] in Acupressure Shin et al. 2007 [29] Nurse with Acupressure Training True Acupressure (TA) Sham Acupressure (SA) Intervention Duration Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): Zhongji (CV3), Guanyuan (CV4), Qihai (CV6), Shenshu (BL23), Pangguangshu (BL28), Ciliao (BL32), Sanyinjiao (SP6), and Zusanli (ST36) Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): True Acupoints (Details not Described) Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): (Bilateral) Sanyinjiao (SP6) Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): (Bilateral) Neiguan (P6), Shenmen (Hand, HT7), Shenmen (Ear), Yungchuan (KI1), Sanyinjiao (SP6), and Anmian (EX-HN22) Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): True Acupoints (Details not Described) Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): (Bilateral) Zhongfu(LU1), Chize (LU5), Yuji (LU10), Fenglong (ST40), and Zusanli (ST36) Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): Neiguan (P6) Method(s): Manual Acupressure at Non-Acupoints, Selected Acupoint(s): NonAcupoints (Details Not Described) Total Duration: 3 Treatments Per Week for 10 Weeks, Each Treatment: 30 Min Method(s): Manual Acupressure at Non-Acupoints, Selected Acupoint(s): NonAcupoints which cannot be Found on Established Acupressure Point Charts (Details not Described) Method(s): Manual Acupressure at Non-Acupoints, Selected Acupoint(s): (Bilateral) Non-Acupoint located at the Dorsal Side of the Leg, Away from Meridians and is not Stimulated upon the Achilles Tendon Method(s): Manual Acupressure at Non-Acupoints, Selected Acupoint(s): NonAcupoints Located 0.5 cun Away from Meridian Method(s): Manual Acupressure at Non-Acupoints, Selected Acupoint(s): NonAcupoints which cannot be Found on Established Acupressure Point Charts (Details not Described) Method(s): Manual Acupressure at Non-Acupoints, Selected Acupoint(s): (Bilateral) Non-Acupoints located near Real Acupoints (where no Acupoints are Known to Exist) Method(s): Manual Acupressure at Non-Acupoints, Selected Acupoint(s): NonAcupoint located at a Bony Part around the Radial Pulse at the Wrist Total Duration: 2 Treatments Per week for 4 Weeks, Each Treatment: 40 Min 4 Weeks Total Duration: One Treatment Per Week for 8 Weeks, Each Treatment: 40 Min Total Duration: Daily Treatment (at Least) for 8 Weeks, Each Treatment: 30 Seconds to 2 Min Acupressure for Each Acupoint (Total Duration for Each Treatment not Mentioned) Total Duration: 3 Treatments Per Day, From the Second Day of Hospitalization to the Day before Discharge, Each Treatment: 10 Min (7 Seconds Acupressure Followed by 2 Seconds Rest, Repeated for 10 Min) Acupressure Intensity Unequal (Less in SA, Only Light Pressure) Method(s): Manual Total Duration: 4 Days in Acupressure at Non-Acupoints, Hospital and SelfSelected Acupoint(s): Non- Acupressure at Home in Acupoints located at the Tibia or the Following Days Radial Bone Surface (Details Not Described), Approximately 3–4 cm from the Each Treatment: 9 Min Selected True Acupoints (3 Min for Each Acupoint) Total Duration: From the Time of Randomization to Arrival at the Hospital Total Duration: 3 Treatments Per Week for 4 Weeks, Each Treatment: 14 Min Total Duration: 3 Min Acupressure Intensity Bertalanffy et al. 2004 [30] Chen et al. 2003 [31] Tsay & Chen 2003 [32] Kober et al. 2002 [33] Research Assistant with Acupressure Training Investigator and Research Assistant with Acupressure Training Paramedic with Acupressure Training Belluomini et al. 1994 [34] Researcher with Acupressure Training Alessandrini et al. 2012 [36] True Acupressure (TA) Sham Acupressure (SA) Intervention Duration Method(s): Manual Acupressure at True Acupoints using A Hard Plastic Ball, Selected Acupoint(s): (Bilateral) Korean Hand Acupressure Point located at the Middle Phalanx of the Fourth Finger (K-K9) Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): Neiguan (P6), Zusanli (ST36), and Sanyinjiao (SP6) Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): (Bilateral) Shenmen (Hand, HT7), Shenmen (Ear), Yungchuan (KI1) Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): Zhongchong (PC9), Neiguan (P6), Kunlun (BL60), Hegu (LI4), and Baihui (GV20) Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): Neiguan (P6) Method(s): Acupressure at True Acupoints using Acupressure Band (PsiBand), Selected Acupoint(s): (Unilateral) Lanwei (EX-LE7) Method(s): Acupressure at True Acupoints using Acupressure Band (SeaBand), Selected Acupoint(s): (Bilateral) Neiguan (P6) Method(s): Manual Acupressure at Non-Acupoints using A Hard Plastic Ball, Selected Acupoint(s): (Bilateral) Non-Acupoint located at the Middle Phalanx of the Second Finger Method(s): Manual Acupressure at Non-Acupoints, Selected Acupoint(s): NonAcupoints located at the Middle of Dorsal Wrist, Middle of Clavicle, Middle of Patella, Lateral Metacarpophalangeal Junction of the Second Finger, and Middle of Lateral Malleolus Method(s): Manual Acupressure at Non-Acupoints, Selected Acupoint(s): NonAcupoint located at the Palmar Surface of the Hand, Proximal to the Head of the Fifth Metacarpal Joint Method(s): Acupressure at Non-Acupoints using Acupressure Band (PsiBand), Selected Acupoint(s): (Unilateral) Non-Acupoint located at the Opposite Site of the Lanwei (EX-LE7) Point Method(s): Acupressure at Non-Acupoints using Acupressure Band (Sea-Band), Selected Acupoint(s): (Bilateral) Non-Acupoint located at the Dorsal Part of the Carpus Type 2—Sham Acupressure at Non-Acupoints: Acupressure Bands or Other Devices (21 Studies) Total Duration: 4 Times Per Day for Consecutive 7 Days, Each Treatment: 10 Min Total Duration: 7 Hours (Loosened for 10 Min every 2 Hours and then Tightened) Total Duration: 30 Min True Acupressure (TA) Sham Acupressure (SA) Intervention Duration Acupressure Intensity Soltani et al. 2011 [37] Acupressure Operator Sinha et al. 2011 [40] Wang et al. 2008 [41] Turgut et al. 2007 [42] Nursing Assistant Heazell et al. 2006 [43] Wang et al. 2005 [44] Method(s): Using Acupressure Wrist Band at True Acupoints, Selected Acupoint(s): (Bilateral) Neiguan (P6) Method(s): Acupressure at True Acupoints using Magnetic Acupressure Suction Cups + Standard Local Analgesics, Selected Acupoint(s): (Bilateral) Hegu (LI4) Method(s): Acupressure at True Acupoints using Acupressure Band (VitalBand), Selected Acupoint(s): (Unilateral) Neiguan (P6) Method(s): Acupressure at True Acupoints using Acupressure Band (Pressure RightTM), Selected Acupoint(s): (Bilateral) Neiguan (P6) Method(s): Acupressure at True Acupoints using Acupressure Beads, Selected Acupoint(s): Yintang (or Extra-1, EX-NH3) Method(s): Acupressure at True Acupoints using Acupressure Band (SeaBand), Selected Acupoint(s): (Bilateral) Neiguan (P6) Method(s): Acupressure at True Acupoints using Acupressure Band (SeaBand), Selected Acupoint(s): (Bilateral) Neiguan (P6) Method(s): Acupressure at True Acupoints using Acupressure Beads, Selected Acupoint(s): Yintang (or Extra-1, EX-NH3) Method(s): Using Acupressure Wrist Band at Non-Acupoints, Selected Acupoint(s): (Bilateral) Non-Acupoint located at the Posterior Surface of Both Forearms Method(s): Acupressure at Non-Acupoints using Magnetic Acupressure Suction Cups, Selected Acupoint(s): (Bilateral) Non-Acupoint located at the Proximal Dorsum of the Fourth Interosseus Space of the Hand Method(s): Acupressure at Non-Acupoints using Acupressure Band (Vital-Band), Selected Acupoint(s): (Unilateral) Non-Acupoint located at the Dorsum of the Forearm Method(s): Acupressure at Non-Acupoints using Placebo Acupressure Band, Selected Acupoint(s): (Bilateral) NonAcupoint located at A Distance of 3 of the Parturient’s FingerBreadths from the Proximal Palmar Crease Method(s): Acupressure at Non-Acupoints using Acupressure Beads, Selected Acupoint(s): Non-Acupoint (Above the Lateral Boarder of the Left Eyebrow) Method(s): Acupressure at Non-Acupoints using Acupressure Band (Sea-Band), Selected Acupoint(s): (Bilateral) Non-Acupoint located at the Dorsal Surface of the Forearm Method(s): Acupressure at Non-Acupoints using Acupressure Band (Sea-Band), Selected Acupoint(s): (Bilateral) Non-Acupoint located at the Dorsal Aspect of the Forearm Method(s): Acupressure at Non-Acupoints using Acupressure Beads, Selected Acupoint(s): Non-Acupoint (Above the Lateral Boarder of the Left Eyebrow) Total Duration: Applied Equal for Both TA 30 Min before Induction of and SA Anesthesia and Removed 6 Hours Later Total Duration: The Entire BMAB Procedure Total Duration: Applied just before Induction of Anesthesia and Kept for 24 Hours after Surgery Total Duration: From the Time of Randomization to 2 Hours after Vaginal Delivery or the Time of A Decision of Caesarean Delivery Total Duration: Entire Anesthesia Period (Applied before Enter the Operation Room and Removed at the Completion of the Procedure) Total Duration: Applied 30 Min before Anesthesia and Kept for 24 Hours after Surgery Unequal (No Pressure was Applied for SA) Total Duration: More than 20 Min Alkaissi et al. 2005 [45] Samad et al. 2003 [46] Alkaissi et al. 2002 [47] Agarwal et al. 2000 [48] Harmon et al. 2000 [49] Individual who was Trained in the Application of Acupressure Band Harmon et al. 1999 [50] Alkaissi et al. 1999 [51] Individual who was Trained in the Application of Acupressure Band True Acupressure (TA) Sham Acupressure (SA) Intervention Duration Method(s): Acupressure at True Acupoints using Acupressure Band (SeaBand), Selected Acupoint(s): (Bilateral) Neiguan (P6) Method(s): Acupressure at True Acupoints using Wrist-Band with Plastic Bead, Selected Acupoint (s): (Unilateral) Neiguan (P6) Method(s): Acupressure at True Acupoints using Acupressure Band (SeaBand), Selected Acupoint(s): (Bilateral) Neiguan (P6) Method(s): Acupressure at True Acupoints using Acupressure Bands, Selected Acupoint(s): (Bilateral) Neiguan (P6) Method(s): Acupressure at True Acupoints using Acupressure Band (SeaBand), Selected Acupoint(s): (Unilateral) Neiguan (P6) Method(s): Acupressure at True Acupoints using Acupressure Band (SeaBand), Selected Acupoint(s): (Unilateral) Neiguan (P6) Method(s): Acupressure at True Acupoints using Acupressure Band (SeaBand), Selected Acupoint(s): (Bilateral) Neiguan (P6) Method(s): Acupressure at True Acupoints using Acupressure Band (AcuBand), Selected Acupoint(s): (Bilateral) Neiguan (P6) Method(s): Acupressure at Non-Acupoints using Acupressure Band (Sea-Band), Selected Acupoint(s): (Bilateral) Non-Acupoint located at the Dorsal Side of both Forearms, 4 Fingers Breadth Proximal to the Proximal Flexor Palmar Crease Method(s): Acupressure at Non-Acupoints using WristBand with Plastic Bead, Selected Acupoint(s): (Unilateral) Non-Acupoint located at the Dorsum of the Right Forearm away from P6 Acupoint Method(s): Acupressure at Non-Acupoints using Acupressure Band (Sea-Band), Selected Acupoint(s): (Bilateral) Non-Acupoint located at the Dorsal Site of the Forearm, 4 Fingers Breadth Proximal to the Flexor Palmar Crease Method(s): Acupressure at Non-Acupoints using Acupressure Bands, Selected Acupoint(s): (Bilateral) NonAcupoint located at the Posterior Surface of the Wrist Method(s): Acupressure at Non-Acupoints using Acupressure Band (Sea-Band), Selected Acupoint(s): (Unilateral) Non-Acupoint located at the Dorsal Site of the Right Forearm Method(s): Acupressure at Non-Acupoints using Acupressure Band (Sea-Band), Selected Acupoint(s): (Unilateral) Non-Acupoint (Details Not Described) Method(s): Acupressure at Non-Acupoints using Acupressure Band (Sea-Band), Selected Acupoint(s): (Bilateral) Non-Acupoint located at the Dorsal Site of Both Forearms, 4 Fingers Breadth Proximal to the Proximal Flexor Palmar Crease Method(s): Acupressure at Non-Acupoints using Acupressure Band (AcuBand), Selected Acupoint(s): (Bilateral) Non-Acupoint located at the Dorsum of Both Wrists Total Duration: Not Reported Acupressure Intensity Total Duration: Applied Equal for Both TA 30 Min before Induction of and SA Anesthesia, and Kept for 6 Hours after Surgery Total Duration: 24 Hours Total Duration: Applied 5 Min before Induction of Anesthesia, and Removed 6 Hours after Discharge to the Ward Total Duration: Applied immediately before Induction of Anesthesia, and Removed 20 Min after Induction of Anesthesia Total Duration: Applied just before Surgery, and Removed after Discharge to Home (Details not Described) Total Duration: Applied before Induction of Anesthesia, and Removed 6 Hours after Surgery Unequal (AcuBands were Tied Loosely in SA) O’Brien et al. 1996 [53] Bayreuther et al. 1994 [55] Hamidzadeh et al. 2012 [56] Researcher with Acupressure Training MirbagherAjorpaz et al. 2011 [57] Researcher with Acupressure Training Research Assistant with Acupressure Training Hjelmstedt et al. 2010 [60] A Person with Acupressure Training Method(s): Acupressure at True Acupoints using Acupressure Band (SeaBand), Selected Acupoint(s): (Bilateral) Neiguan (P6) Method(s): Acupressure at True Acupoints using A Dentist’s Tool (A 15-cm Handle with A Ball at the End), Selected Acupoint (s): (Unilateral) Chengqi (ST1), Lidui (ST45), Yinbai (SP1), Dabao (SP21), Gongsun (SP4), Jingming (BL1), Zhiyin (BL67), Yungchuan (KI1), Youmen (KI27), Dazhong (KI4), Ligou (LR5), Tongziliao (GB1), Zuqiaoyin (GB44), Dadun (LR1), and Qimen (LR14) Method(s): Acupressure at True Acupoints using Acupressure Band (SeaBand), Selected Acupoint(s): Neiguan (P6) Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): (Bilateral) Hegu (LI4) Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): Sanyinjiao (SP6) Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): (Bilateral) Shenmen (HT7) Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): Sanyinjiao (SP6) Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): (Bilateral) Sanyinjiao (SP6) Method(s): Acupressure at Non-Acupoints using Acupressure Band (Sea-Band), Selected Acupoint(s): (Bilateral) Non-Acupoint located at the Radius of Both Forearms Method(s): Acupressure at Non-Acupoints using A Dentist’s Tool (A 15-cm Handle with A Ball at the End), Selected Acupoint(s): (Unilateral) NonAcupoints Situated 2 cm from the Nearest True Acupoints Method(s): Acupressure at Non-Acupoints using Acupressure Band (Sea-Band), Selected Acupoint(s): NonAcupoint located Above or Below the Elbow Total Duration: 3 Days (From the Morning of Study Day 3 to The Morning of Study Day 6) Total Duration: 30 Min after Patients Awoke from Anesthesia Acupressure Intensity Total Duration: 7 Days True Acupressure (TA) Sham Acupressure (SA) Intervention Duration Method(s): Light Touch (without Total Duration: 20 Min (5 Acupressure) on the Same Pressure Per Min) Acupoints, Selected Acupoint (s): (Bilateral) Hegu (LI4) Method(s): Light Touch (without Total Duration: 20 Min Acupressure) on the Same (10 Second-Cycle Acupoints, Selected Acupoint repeated 120 Times) (s): Sanyinjiao (SP6) Method(s): Light Touch (without Total Duration: Daily Acupressure) on the Same Treatment for Acupoints, Selected Acupoint Consecutive 5 Weeks, (s): (Bilateral) Shenmen (HT7) Each Treatment: 5-Second Pressure Followed by 1-Second Rest, Repeated for 5 Min Method(s): Light Touch (without Total Duration: 30 Min Acupressure) on the Same Acupoints, Selected Acupoint (s): Sanyinjiao (SP6) Method(s): Light Touch (without Total Duration: 30 Min Acupressure) on the Same Acupoints, Selected Acupoint (s): (Bilateral) Sanyinjiao (SP6) No Pressure was Applied for SA No Pressure was Applied for SA No Pressure was Applied for SA No Pressure was Applied for SA No Pressure was Applied for SA True Acupressure (TA) Sham Acupressure (SA) Intervention Duration Researcher with TCM Training Nilsson et al. 2015 [63] Nurse Anesthetist Molassiotis et al. 2013 [64] Noroozinia et al. 2013 [65] Soltanzadeh et al. 2012 [66] White et al. 2012 [67] Klein et al. 2004 [69] Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): (Bilateral) Shenmen (HT7) Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): (Bilateral) Sanyinjiao (SP6) Method(s): Acupressure at True Acupoints using Acupressure Band (SeaBand), Selected Acupoint(s): (Unilateral) Neiguan (P6) Method(s): Acupressure at True Acupoints using Acupressure Band (SeaBand), Selected Acupoint(s): (Bilateral) Neiguan (P6) Method(s): Acupressure at True Acupoints using Acupressure Band, Selected Acupoint(s): Neiguan (P6) Method(s): Acupressure at True Acupoints using Acupressure Band, Selected Acupoint(s): (Bilateral) Korean Hand Acupressure Point (K-K9) located at the Middle Phalanx of the Fourth Finger on Both Hands Method(s): Acupressure at True Acupoints using Acupressure Strip, Selected Acupoint(s): (Bilateral) Neiguan (P6) Method(s): Acupressure at True Acupoints using Acupressure Band (SeaBand), Selected Acupoint(s): (Bilateral) Neiguan (P6) Method(s): Acupressure at True Acupoints using Acupressure Band (SeaBand), Selected Acupoint(s): (Bilateral) Neiguan (P6) Method(s): Light Touch (without Total Duration: Daily Acupressure) on the Same Treatment (5 Min) for Acupoints, Selected Acupoint Consecutive 5 Weeks (s): (Bilateral) Shenmen (HT7) Method(s): Light Touch (without Total Duration: 30 Min Acupressure) on the Same During Each Uterine Acupoints, Selected Acupoint Contraction (s): (Bilateral) Sanyinjiao (SP6) Method(s): Sham Acupressure at the Same Acupoints using A Placebo Acupressure Band without the Plastic Button, Selected Acupoint(s): (Unilateral) Neiguan (P6) Method(s): Sham Acupressure at the Same Acupoints using A Placebo Acupressure Band with the Plastic Button located at the Exterior of the Wrist Band, Selected Acupoint(s): (Bilateral) Neiguan (P6) Method(s): Sham Acupressure at the Same Acupoints using A Placebo Acupressure Band without the Pressure Button, Selected Acupoint(s): Neiguan (P6) Method(s): Sham Acupressure at the Same Acupoints using A Dummy Band (Details not Described), Selected Acupoint (s): (Bilateral) Korean Hand Acupressure Point (K-K9) located at the Middle Phalanx of the Fourth Finger on Both Hands Method(s): Sham Acupressure at the Same Acupoints using A Placebo Acupressure Strip without the Pressure Button, Selected Acupoint(s): (Bilateral) Neiguan (P6) Method(s): Sham Acupressure at the Same Acupoints using A Placebo Acupressure Band with A Blunted Plastic Button, Selected Acupoint(s): (Bilateral) Neiguan (P6) Method(s): Sham Acupressure at the Same Acupoints using A Placebo Acupressure Band without the Plastic Button, Selected Acupoint(s): (Bilateral) Neiguan (P6) Total Duration: 2 Days Total Duration: 7 Days Total Duration: Applied 15 Min Prior to Induction of Anesthesia and Kept for 24 Hours Total Duration: Applied 30 to 60 Min before Induction of Anesthesia and Kept for 72 Hours after Surgery Total Duration: Applied More than 30 Min before Induction of Anesthesia and Removed after Arrival in the Post-Anesthesia Care Unit Total Duration: Applied before Induction of Anesthesia and Removed 24 Hours after Extubation Total Duration: 30 Min Prior to Spinal Anesthesia No Pressure was Applied for SA Acupressure Intensity No Pressure was Applied for SA No Pressure was Applied for SA No Pressure was Applied for SA No Pressure was Applied for SA No Pressure was Applied for SA No Pressure was Applied for SA No Pressure was Applied for SA True Acupressure (TA) Sham Acupressure (SA) Intervention Duration Schultz et al. 2003 [70] Dent et al. 2003 [71] Norheim et al. 2001 [72] Steele et al. 2001 [73] Preoperative Nurse Nurse who was Trained in Accurate Location of Targeted Acupoints Study Assistant Nurse who was Trained in the Application of Acupressure Band Anesthesia Provider Duggal et al. 1998 [75] Lewis et al. 1991 [76] Suh 2012 [77] Researcher and Research Assistant Lang et al. 2007 [78] Paramedic with Acupressure Training Method(s): Acupressure Band (Sea-Band) at True Acupoints + Droperidol, Selected Acupoint(s): Neiguan (P6) Method(s): Acupressure at True Acupoints using Acupressure Band (SeaBand), Selected Acupoint(s): (Bilateral) Neiguan (P6) Method(s): Acupressure at True Acupoints using Acupressure Band (SeaBand), Selected Acupoint(s): (Bilateral) Neiguan (P6) Method(s): Acupressure at True Acupoints using Acupressure Band (SeaBand), Selected Acupoint(s): (Bilateral) Neiguan (P6) Method(s): Acupressure at True Acupoints using Acupressure Band (SeaBand), Selected Acupoint(s): (Bilateral) Neiguan (P6) Method(s): Acupressure at True Acupoints using Acupressure Band (SeaBand), Selected Acupoint(s): (Bilateral) Neiguan (P6) Method(s): Acupressure at True Acupoints using Acupressure Band (SeaBand), Selected Acupoint(s): (Bilateral) Neiguan (P6) Method(s): Acupressure at Therapeutic Acupoints using Acupressure Band (Sea-Band), Selected Acupoint(s): (Bilateral) Neiguan (P6) Method(s): Manual Acupressure at Therapeutic Acupoints, Selected Acupoint(s): Baihui (GV20) and Hegu (LI4, Unilateral) Method(s): Placebo Band (with A Flat Button) at the Same Acupoints, Selected Acupoint (s): Neiguan (P6) Method(s): Sham Acupressure at the Same Acupoints using A Placebo Acupressure Band without the Plastic Button, Selected Acupoint(s): (Bilateral) Neiguan (P6) Method(s): Sham Acupressure at the Same Acupoints using A Placebo Acupressure Band without the Plastic Button, Selected Acupoint(s): (Bilateral) Neiguan (P6) Method(s): Sham Acupressure at the Same Acupoints using A Placebo Acupressure Band without the Plastic Button, Selected Acupoint(s): (Bilateral) Neiguan (P6) Method(s): Sham Acupressure at the Same Acupoints using A Placebo Acupressure Band without the Plastic Button, Selected Acupoint(s): (Bilateral) Neiguan (P6) Method(s): Sham Acupressure at the Same Acupoints using A Placebo Acupressure Band without the Plastic Button, Selected Acupoint(s): (Bilateral) Neiguan (P6) Method(s): Sham Acupressure at the Same Acupoints using A Placebo Acupressure Band without the Stud, Selected Acupoint(s): (Bilateral) Neiguan (P6) Method(s): Manual Acupressure at NonTherapeutic (Irrelevant) Acupoints, Selected Acupoint (s): (Bilateral) Houxi (SI3) Method(s): Manual Acupressure at NonTherapeutic (Irrelevant) Acupoints, Selected Acupoint (s): Geshu (BL17) and Jianliao (TE14, Unilateral) Total Duration: Not Reported Total Duration: 24 Hours Total Duration: 4 Days Total Duration: 4 Days Total Duration: Applied at Least 15 Min before Induction of Anesthesia and Kept for 24 Hours after Surgery Total Duration: Applied 1 Hour before Operation and Kept until Discharge from Hospital on the same Day Total Duration: 5 Days Total Duration: Not Reported (3 Min Acupressure for Each Acupoint) No Pressure was Applied for SA Acupressure Intensity No Pressure was Applied for SA No Pressure was Applied for SA No Pressure was Applied for SA No Pressure was Applied for SA No Pressure was Applied for SA No Pressure was Applied for SA True Acupressure (TA) Sham Acupressure (SA) Intervention Duration Acupressure Intensity the interior surface which can exert constant pressure at the targeted acupoint. However, in one study [40], the button was replaced by a backing square in the sham group. In two trials where the non-acupoints located at the forehead, adhesive beads were applied [41, 44]. Special band was also adopted on the non-acupoint located below the knee in one study [35], and magnetic suction cup was utilized in another trial to stimulate the non-acupoints on both hands [38]. Particularly, a dentist’s tool was employed for acupressure in one trial which selected more than ten non-acupoints [54]. Twenty studies described the definite locations of the nonacupoints. Most of the studies with type 2 design adopted equal acupressure intensity between groups, while it was unequal in four trials [35, 40, 52, 54] with sham groups receiving lowerintensity pressure or no stimulation at all. In 21 articles, the sham study arms employed the same acupoints as in the true acupressure arms. Manual light touch was applied in seven trials without any pressure (type 3) whereas the other 14 used a placebo device but also no pressure was exerted (type 4). The intervention protocols were all similar between groups except for the acupressure intensity. For studies utilizing type 4 sham procedures, pseudo devices used in the control groups were identical from those applied in true acupressure with the only exception that the pressure button was missing, or was replaced by a blunted/flat one, or was located at the exterior of the equipment. One study stated that a dummy band was applied but no detailed information was given [66]. Non-therapeutic acupoints were chosen as sham intervention in five trials. Of which, four utilized manual acupressure (type 5) [77–80] and one employed a wrist acupressure device (type 6) [81]. In studies with type 5 sham method, the intervention protocol was similar between groups in 3 studies [78–80], but in another trial [77], the acupressure intensity was unequal between groups with the true intervention group applying a wrist band to create constant pressure while the sham comparison received manual acupressure with discontinuous stimulation. The only one article with type 6 sham procedure focused on insomnia [81]. Unfortunately, this study failed to specify the selected sham acupoints but only stated that the irrelevant acupoints were “known as not to interfere with” the treated condition [81]. Results of Therapeutic Effects Type 1: Sham acupressure at non-acupoints by manual pressure; Type 2: Sham acupressure at non-acupoints by employing acupressure devices; Type 3: Pseudo-intervention at the same acupoints as true treatment arm by manual light-touch; Type 4: Pseudo-intervention at the same acupoints as true treatment arm by using placebo devices; Type 5: Manual acupressure at non-therapeutic (irrelevant) acupoints; Type 6: Sham acupressure at nontherapeutic (irrelevant) acupoints by adopting acupressure devices 1: For studies reporting multiple main outcomes, at least one “++” were identified 2: For studies reporting multiple main outcomes, no “++” but at least one “+” were identified 3: “0” for all main outcome(s) 4: “−” or “− −”for all main outcome(s) #: Sham acupressure control type 1 was applied in 19 studies, but comparison between groups was not performed (or not clearly reported) in one study ##: Sham acupressure control type 2 was applied in 21 studies, but comparison between groups was not performed (or not clearly reported) in one study Therapeutic Effects of Acupressure Therapeutic outcomes of acupressure are summarized in Tables 4 and 5. Meanwhile, results of the responder rate ratio calculation are presented in Table 6. Overall Assessment. Sixty-four studies reported treatment outcomes between the true and sham acupressure groups. For the main outcomes, 64.1% (41/64) reported that true acupressure was significantly superior to sham intervention, and 12.5% favored the true procedure but the difference did not reach statistical significance, while there were 13 studies (20.3%) which found no difference between groups. In addition, the sham acupressure was found to be more effective than true intervention in two trials (3.1%) [70, 74] with one even reaching statistical significance [70]. Among all the included studies, 12 compared the effects of acupressure (true/sham) with the study arms using standard methods of care. In four trials [23, 29, 32, 71], true acupressure was shown to be more effective than sham treatment and/or standard care, while no difference was found between sham acupressure and standard care. In another seven studies [26, 28, 45, 47, 51, 60, 64], both true and sham procedures were found to be superior to conventional care with or without statistical significance, while one trial [53] found no difference among groups. Thirty-four articles which provided dichotomous data were included for calculating responder rate ratio, and the majority (27 studies) supported the superiority of true acupressure compared with sham intervention, with the responder rate ratio (as measured by RR) greater than 1.0. Subgroup Analysis. Subgroup analysis was performed based on different sham alternatives (Table 4). Fourteen out of 18 studies (77.8%) employing type 1 sham procedure favored true acupressure. For type 2 studies, 70% (14/20) supported the superiority of the true intervention. Of the 14 studies using pseudo-acupressure devices (type 4), nine (64.3%) reported that true acupressure was more effective than sham control, three (21.4%) found no difference between groups, and two (14.3%) favored sham acupressure. Number of studies for sham type Results of Therapeutic Effects TAG is Significantly Superior to SAG1 No Difference between TAG and SAG3 1: For studies reporting multiple main outcomes, at least one “++” were identified 2: For studies reporting multiple main outcomes, no “++” but at least one “+” were identified 3: “0” for all main outcome(s) 4: “−” or “− −”for all main outcome(s); MI: Myocardial infarction # Twenty studies for postoperative nausea and vomiting and one study for intra-operative nausea and vomiting ## Perioperative/prehospital pain was observed in 5 studies, but comparison between groups was not performed (or not clearly reported) in 1 study ### Motion sickness was observed in 3 studies, but comparison between groups was not performed (or not clearly reported) in 2 studies #### Acupressure durations were less than 1 hour in 14 studies, but comparison between groups was not performed (or not clearly reported) in 2 studies 3, 5 and 6 were limited, but all supported the superiority of true intervention. Responder rate ratios were also separately analyzed for different sham acupressure types and the true intervention groups were found to be more effective than the sham comparisons in the majority of the analyzed trials within each sham acupressure control (Table 6). Outcome# Definition of Response Type 1 Sham Acupressure at Non-Acupoints: Manual Acupressure Bertalanffy et al. 2004 Sympathetic Activity Peripheral Vasodilation Kober et al. 2002 Pre-Hospital Anxiety Anxiety Reduction Type 2 Sham Acupressure at Non-Acupoints: Acupressure Bands or Other Devices Adib-Hajbaghery & Etri Postoperative Nausea Absence of Nausea 2013 Adib-Hajbaghery & Etri Postoperative Vomiting Absence of Vomiting 2013 Alessandrini et al. 2012 Soltani et al. 2011 Soltani et al. 2011 Bao et al. 2011 Majholm & Møller 2011 Majholm & Møller 2011 Sinha et al. 2011 23.00 [5.90, 89.64] 1.37 [0.80, 2.33] 0.94 [0.59, 1.51] 0.95 [0.63, 1.44] 1.17 [0.85, 1.60] 1.89 [1.25, 2.86] 1.76 [1.22, 2.54] 1.32 [0.94, 1.85] 1.00 [0.93, 1.08] 1.08 [0.90, 1.29] 1.02 [0.90, 1.17] 1.02 [0.94, 1.11] 1.88 [1.19, 2.95] 1.40 [1.07, 1.83] 1.00 [0.57, 1.75] 1.31 [1.07, 1.60] 2.00 [0.90, 4.45] 1.54 [1.23, 1.94] 0.97 [0.71, 1.34] 1.16 [0.92, 1.45] 0.94 [0.66, 1.33] 1.07 [0.74, 1.55] 1.00 [0.84, 1.18] 1.06 [1.00, 1.12] Outcome# Definition of Response TAG: True acupressure group; SAG: Sham acupressure group; MI: Myocardial infarction #: Outcome used for response rate estimation 1.06 [0.49, 2.33] 2.17 [1.00, 4.68] Types of Sham Control No. of Studies# Subgroup analyses were also applied for different types of health conditions and treatment duration (Table 5). Descriptive analysis showed that true acupressure can be an effective approach in managing postoperative and pregnancy-related nausea and/or vomiting, perioperative/prehospital pain, labor pain, sleep disturbances, respiratory disorders, anxiety, postoperative gastrointestinal dysfunctions and motion sickness. Studies on primary dysmenorrhea and chemotherapy-induced nausea and vomiting reported contradictory findings, where two studies [57, 77] supported the superiority of true acupressure, while another two [17, 64] stated no difference between groups. Results from a single study indicated that the true intervention was Number of Dropout/Sample Size (Dropout Rate, %) Chi-Squared Test χ² = 2.233, df = 1, P = 0.135 χ² = 0.435, df = 1, P = 0.509 χ² = 0.169, df = 1, P = 0.681 χ² = 1.013, df = 1, P = 0.314 χ² = 0.090, df = 1, P = 0.765 χ² = 0.693, df = 1, P = 0.405 χ² = 0.234, df = 1, P = 0.629 better than sham control in treating urodynamic stress incontinence [23], traumatic brain injury [24], cancer-related fatigue [16] and myocardial infarction-related nausea and vomiting [71], and in maintaining women’s general health [25] and stroke survivors’ cardiovascular functions [27]. The only study on stress reduction failed to prove the superiority of true acupressure [20]. For each subgroup under “treatment duration”, more than half (68.75% to 83.3%) supported that true acupressure was more effective than sham intervention (Table 5). Further investigation on acupressure frequency and intensity was not feasible due to insufficient information and absence of available data. Dropout Rates and Adverse Events associated with Acupressure In 26 studies, all the randomized subjects completed the study. Thirty-four studies reported participants’ dropout, however, 11 of them only provided the total dropout number but failed to specify the number in each study arm [19, 32, 47, 51, 53, 62, 70, 72, 75, 79, 80]. Reasons for dropout were diverse and included changing treatment protocol, refusing to continue with the study, suffering from adverse events, or death, etc. The total dropout rate was 6.2%, with the true intervention groups 6.1% and the sham groups 6.4%. Dropout rates also varied significantly among different sham alternatives. The lowest was found in type 3 trials, with the total dropout rate being 1.22% (true acupressure 0.8% and sham comparison 1.6%). Chi-square tests showed that there was no difference of the dropout rates between groups (Table 7). There were 24 studies that observed potential adverse events associated with acupressure, among which, 13 reported no adverse events, and the other 11 reported acupressure devicerelated harm data including local swelling and redness, discomfort and tenderness at the wrist, and paresthesia, etc. No serious adverse events were noted. There was one study [67] that detected adverse events such as constipation, headache, fatigue and drowsiness, but information was insufficient to judge whether these were caused by acupressure. No study assessed the causality between the acupressure and the reported adverse events. This study analyzed 66 trials with six sham acupressure types. The findings indicated that “non-acupoint” was the most frequently selected sham acupoint and an acupressure device was the commonly adopted approach for sham intervention. Meanwhile, our findings supported that acupressure was a beneficial method in managing a variety of health problems, and the effect was found to be more effective in true acupressure than that in sham procedure. Because of the significant clinical heterogeneity among the included studies, the relationship between sham acupressure methods and the treatment outcomes is not fully conclusive at this stage. Our findings showed that true acupressure was more effective than sham acupressure, and the effect of sham intervention was somewhat better than that in the standard care arms. These results support the specific benefits of true acupoint stimulation, but also indicate that sham acupressure more or less produces some specific or non-specific treatment effects. Sham acupressure may be associated with larger effects than control groups adopting standard methods of care. Placebo effects of sham acupoint stimulation may be related to patients’ expectation of treatment, and ventral striatum and prefrontal cortex are commonly believed to be involved in the activation of the reward system which contributes to a feeling of symptom improvement during intervention [82]. Previous studies indicated that “physical placebos”, including sham acupoint stimulation (e.g. acupuncture), could result in larger effects over non-treatment arms than drug placebos [83, 84]. Reasons for the relatively larger effects in sham acupoint stimulation are complicated, and from a psychological perspective, any forms of acupoint stimulation could be viewed as an emotional focused therapy which more or less produces some treatment effects [82]. However, whether the effects produced by sham acupoint stimulation are only non-specific placebo effects or are mixed with any specific therapeutic benefits, we still cannot reach a definite conclusion at present. Similar to the results from the descriptive analysis, the exploratory analysis of the responder rate ratios also showed that true acupressure was more effective than sham comparisons regardless of the sham acupressure types. However, these findings should be interpreted prudently because the responder rate ratio only provides a rough summary of the study results, and the dichotomous data we used were not the main measures in some of the analyzed trials. Meanwhile, even within the subgroup of each sham acupressure method, clinical heterogeneities (e.g. differences in the health conditions, patient characteristics, intervention duration and outcome measures, etc.) were still considerable in the analyzed trials. In addition, the number of studies included within each subgroup was quite imbalanced among the sham types, with type 2 and 4 respectively gathering more than 10 studies, whereas other sham modalities only including no more than three studies. In the analyzed studies, non-acupoint was the most frequently adopted sham acupoint approach used. Non-acupoint is a popular sham modality because generally it would not create any therapeutic effects. However, we are not sure whether all the so-called “non-acupoints” in our analyzed trials are real non-acupoints because only few of them pointed out that the selected non-acupoints were situated away from the meridians, while in the remaining studies, the relation between the non-acupoints and their nearest active acupoints and/or meridians was not provided. Meanwhile, researchers should prudently select the non-acupoints because currently there are more than 2000 established extra-points which are not linked with meridians, and this cannot exclude the possibility that the so called “non-acupoints” in some trials may be unintentionally therapeutic points in nature [85]. In addition to the non-acupoints, true acupoints were also commonly used as sham acupressure. The acupoints were the same as the active intervention groups but were only provided with light tough or totally received no stimulation. It is believed that light stimulation on the true acupoints would not activate the deqi sensation, and thus, avoid the generation of specific treatment effects [6, 85]. But recent studies on pain concluded that light stimulation on the skin could evoke the activity of the cutaneous afferent nerves and/or the insular region of the brain, and may result in some augmented therapeutic benefits [4, 86]. Also, patients with pain conditions could experience similar treatment effects when the selected true and sham acupoints located at the same or nearby myotome [4, 87]. Light touch may not be a proper sham approach for studies on pain management. Also, light stimulation was deemed inadequate to maintain blinding of the participants, especially for those with previous acupressure experience. Light touch does not exert additional pressure and avoids evoking the deqi sensation. When the intervention is observed by participants, it may be easy for them to judge that they are not receiving the “true” acupressure. Non-therapeutic acupoints were used as the sham intervention in five of the included studies. Regarding to the location of the non-therapeutic acupoint, it is recommended to be situated near the selected active acupoint to achieve proper blinding, but is also required to avoid being on the same meridian as in the true intervention. In one trial which focused on pre-hospital analgesia for patients with distal radius fracture, jianliao (TE14) was employed as one of the sham acupoints, and acupressure intensity was equal in both groups [78]. However, this kind of sham design might not be adequate enough because acupressure at any of the body acupoints could contribute to some pain relieving effects. In the meantime, jianliao is mainly used for treating shoulder and back pain, although not specific for distal radius fracture, stimulation of jianliao might somewhat produce some positive impact on the pain management of the whole body. According to the “holism concept” of acupuncture theory, every single stimulation of the acupoint could result in comprehensive responses of the human body and subsequently generate specific and/or non-specific effects [85]. That is to say, pressing irrelevant acupoints may also create some treatment effects for the targeted condition, especially when the sham intervention receives the same acupressure intensity as in the active intervention arm. Acupressure devices can be an adequate method for retaining blinding. In our analyzed studies, acupressure bands with or without the pressure button were commonly incorporated as sham interventions. The same or identical equipment used in both groups makes the blinding of participants and outcome assessors possible, and blinding of care providers can also be achieved if they are not involved in the application of the acupressure devices. In type 2 sham designs, most of the trials employed acupressure equipment on non-acupoints and used the same acupressure intensity as in the true intervention arms. However, as mentioned above, acupressure at non-acupoints might induce some unexpected treatment effects, and thus makes the type 2 design more effective than its own placebo effects. Type 4 designs with pseudo-devices could be viewed as a good sham mode because those do not apply additional pressure to the selected acupoints which could minimize the potential therapeutic effects at a greater extend. Also, the appearance looks indistinguishable from the true acupressure tools which could keep the blinding at a satisfactory level, particularly for acupressure-naive participants. Unfortunately, tools such as acupressure bands currently are only applicable for acupoints located on the arms or legs, and when a study adopts too many acupoints, using acupressure equipment nearly becomes impossible. Participants’ dropout rates were similar between groups. Although reasons for dropout varied among trials, no participants were reported dropping out because of being allocated to sham group. Meanwhile, this review found that the type 3 control had the lowest dropout rate. However, the low rate seemed not to be caused by the sham intervention itself but by the nature of the included health problems. Among the six studies with the type 3 sham approach, more than half were studying pregnant women preparing for delivery and the acupressure only lasted several minutes. For studies that observed potential adverse events associated with acupressure, no such events were found in more than half of the studies. Adverse events related to acupressure identified in the remaining trials were generally mild and transient. Reported adverse events were associated with acupressure devices, which were mostly attributed to wearing of the equipment for a longer time. Loosening the bands temporarily during the intervention could help to reduce the side effects to some extent. Acupressure seems to be a relatively safe approach for acupoints-stimulation. However, it is noted that none of the included trials assessed the causality between the acupressure and the reported adverse events, and standard causality assessment tools (e.g. The WHO-Uppsala Monitoring Centre System for Standardized Case Causality Assessment) were failed to be applied in the analyzed studies, which make it difficult to judge whether these adverse events are really caused by the acupressure intervention or not. Some limitations were identified in the analyzed studies which could affect the reliability of our results. Firstly, true and sham acupressure protocols were described unclearly in some studies. Relationship and distance between the non-acupoint and the nearest meridian were seldom reported. Information on intervention frequency and intensity were also provided insufficiently in some trials, which made the subgroup analyses on the acupressure frequency and intensity impossible. Secondly, subjective outcomes were utilized in more than half of the articles, which produced a possibility for exaggerating the treatment effects of the intervention, especially for studies with inadequate blinding and/or allocation concealment [88]. Thirdly, methodological flaws still existed among studies. Assessment of the credibility of blinding is essential in clinical trials for evaluating the successfulness of blinding design, especially for trials with a placebo/sham control arm, as inadequate blinding could contribute to performance and/or detection biases, which could exaggerate the potential specific/non-specific treatment effects of the placebo/sham intervention. However, credibility of blinding was not tested in all the trials, and for some studies to which the blinding of care providers could have been achieved (e.g. studies using identical acupressure bands), such a design also failed to be incorporated. Moreover, Chinese syndrome differentiation was not employed to guide subject recruitment, acupoint identification, and acupressure-technique selection in studies using Chinese acupressure, which may downgrade the feasibility and reliability of the intervention protocols to some degree. The study objective which focused on whether different types of sham procedure yield different therapeutic outcomes was difficult to achieve in this review as limited homogeneous data could be accessed for conducting subgroup analysis on the same health condition within each sham acupressure modality. Descriptive analysis only provided a preliminary summary of the therapeutic effects of acupressure. The exploratory analysis of the responder rate ratio was unable to always be consistent with the finding drawn from the study main outcomes with continuous variables as responder rate ratio was only a rough estimation and dichotomous data were not the main outcomes for some studies. Meanwhile, even within single sham alternative, trials still showed heterogeneity in a number of aspects, such as the differences in patient characteristics, treatment duration and the outcome measures, etc., all of which made the interpretation of results a difficult task. In addition, our findings at the current stage could not evaluate whether there were any sham designs that had produced additional treatment effects over and above their own placebo effects. Finally, although we have made efforts to locate as much eligible studies as possible, the final included studies were only in English and Chinese. Several articles written in languages other than English or Chinese were excluded, inevitably leading to some language bias. Implications for Future Research and Practice Verbal and non-verbal interactions between practitioners/researchers and participants should be pre-standardized to avoid increasing participants’ expectations to the treatment which may exaggerate the non-specific psychological effects of the treatment [89, 90]. In studies utilizing an acupressure device, it is suggested that researchers and care providers are not involved in the application of acupressure equipment in order to retain satisfactory blinding. Furthermore, it would be better for future studies to recruit participants without any previous experience in acupressure. Acupressure-naive subjects do not have any experience of deqi sensation, which may increase the chance of reaching successful blinding of participants [6]. To equalize the treatment expectations among participants, if possible, participants’ characteristics such as educational background, religion, and lifestyle, etc. should be kept similar at the baseline, as these elements are considered to be potential social-psychological factors that could affect participants’ expectations to treatment [85]. Selection of the sham methods should be in accordance with the study objectives and the actual requirements of the intervention and participants, as well as the nature of the disease being treated. For example, if a study intends to test the specificity of some particular acupoints, the true and sham acupressure protocols should be the same with the only difference in the selected acupoints. To minimize potential therapeutic effects of sham interventions and to maintain a satisfactory blinding design, non-acupoints located near the targeted true acupoints are generally recommended but the definite locations should be identified with caution, and an acupoint detector (a commonly utilized device for accurately locating effective body/auricular acupoints) could be considered to distinguish ineffective non-acupoints from active true acupoints. For acupressure intensity, future studies are suggested to exert only light or no stimulation to the sham acupoints to prevent the generation of the deqi sensation. Particularly, acupoint stimulation should be avoided in pain studies adopting sham acupressure. While for studies using single sham acupoints on hands or legs, it is suggested to apply identical acupressure devices on the same acupoints as in the true intervention groups without any stimulation. To facilitate the blinding of participants and/or care providers, some methods could be considered to prevent them from observing the treatment procedure, for instance, letting participants wear eye patches when administering the intervention [91], or using bandages to cover the wrist bands during surgical acupressure trials. Moreover, some studies also pointed out that the effects of acupoint stimulation can be reflected on the neural activities in the limbic system and subcortical structures which provides a possible direction for future research to use the functional magnetic resonance imaging (fMRI) to adequately evaluate sham procedures based on the neural activities of the brain [92,93]. As subjective outcomes (e.g. questionnaire and visual analogue scale, etc.) could be affected by the participants’ expectations to treatment, which subsequently exaggerates therapeutic effects, future studies could consider including some objective measures. Some scholars point out that instead of using the word of “sham” or “placebo”, informing participants that the aim of study is to compare two different treatment procedures would be more credible to reach a successful blinding of study subjects [2, 94]. This kind of incomplete informed consent may be in debate for ethical reasons [2]. However, according to the results of a nested qualitative study within a RCT using acupressure (both true and sham) for controlling chemotherapy-induced nausea, it was acceptable for the study participants to receive this kind of consent process [94]. Meanwhile, from the findings of this review as well as other studies on sham acupoint stimulation [92, 95], sham interventions can also contribute to symptom improvement, and thus, it seems plausible to view the sham acupressure as a non-specific treatment approach in nature. Finally, the methodological quality of future trial needs to be improved. More detailed information on the theoretical background of the selection and identification of true and sham acupoints should be provided. Treatment duration, number of sessions, and acupressure intensity should be described in detail in the acupressure protocols. Even if it is difficult to incorporate blinding of the practitioner in manual acupressure trials, a double-blind design for both participants and outcome assessors is still possible. Credibility of blinding should also be tested to investigate the successfulness of blinding design and subsequent to identify the potential risk of performance and/or detection biases. Related guidelines such as the CONSORT [96] and STRICTA [97] guidelines should be followed in the development and reporting of acupressure trials. Conclusions A great diversity of sham acupressure controls have been used in the literature. A solid conclusion whether different sham alternatives are related to different treatment outcomes cannot be derived because of the significant clinical heterogeneity among the analyzed trials. Based on the findings of this systematic review, non-acupoints are generally recommended but the definite locations should be identified with caution. For studies using single sham acupoints on hands or legs, it is suggested to apply identical acupressure devices on the same acupoint as in the active intervention without any stimulation. While for studies on pain, stimulation of sham acupoints should be avoided. Supporting Information S2 Table. Excluded Acupressure Trials due to High Risk of Bias. (PDF) S3 Table. Risk of Bias Assessment of the Included Trials. (PDF) Conceived and designed the experiments: JYT LKPS AM. Performed the experiments: JYT TW. Analyzed the data: JYT AM. Contributed reagents/materials/analysis tools: TW. Wrote the paper: JYT. Revised the manuscript: JYT AM LKPS WT. References Urodynamic Stress Total: 81/ TAG: Manual Pelvic Muscle Incontinence 4, TAG: Acupressure at True Strength 27 /1, SAG: Acupoints + Pelvic Floor (Perineometry 27/1, CG: Muscle Training, SAG: through Measuring 27/2 Manual Acupressure at Vaginal Squeeze Non-Acupoints + Pelvic Pressure) Floor Muscle Training , CG: Pelvic Floor Muscle Training Wu et al. 2007 Investigator with Method(s): Manual Method(s): Manual Total Duration : 5 [79] Wu et al . Acupressure Acupressure at Acupressure at Non- Treatments Per Week for 2004 [80] Training Therapeutic Acupoints , Therapeutic (Irrelevant) Consecutive 4 Weeks, Selected Acupoint(s): Acupoints, Selected Acupoint Each Treatment: 16 Min Dazhui (GV14), Tiantu (s): Shangqiu (SP5), Taibai (CV22), Feishu (B13, (SP3), and Dadun (LR1) Bilateral) , Shenshu ( B23 , Bilateral), and Yuji ( L10 , Unilateral) Type 6-Acupressure at Non-Therapeutic Acupoints (Irrelevant Acupoints): Acupressure Bands or Other Devices (1 Study) Nordio & Not Reported Method(s): Acupressure Method(s): Acupressure at Total Duration: 20 Days Romanelli at Therapeutic Acupoints Non-Therapeutic (Irrelevant) 2008 [81] using Wrist Acupressure Acupoints using Wrist Device, Selected Acupressure Device, Selected Acupoint(s): (Bilateral): Acupoint(s): (Bilateral ): Shenmen (HT7) Acupoint Known as not to Interfere with Insomnia and/or Anxiety (Details not Described) Neurovegetative Symptom Symptom Improvement Postoperative Nausea Absence of Nausea Postoperative Vomiting Absence of Vomiting Pain Intensity Less Severity Pain Postoperative Nausea Absence of Nausea Postoperative Vomiting Absence of Vomiting Nausea and Vomiting in Absence of Nausea and/or Vomiting Delivery Wang et al. 2008 Postoperative Nausea and Absence of Nausea and Vomiting 21/26 Vomiting Turgut et al. 2007 Postoperative Nausea Absence of Nausea 34/50 Turgut et al. 2007 Postoperative Vomiting Absence of Vomiting 37/50 Heazell et al. 2006 Length of Hospitalization Less than 4 Days in the Hospital 29/40 Samad et al. 2003 Postoperative Nausea and Absence of Nausea and Vomiting 25/25 Vomiting Alkaissi et al. 2002 Postoperative Nausea and Absence of Nausea, Vomiting or Rescue Vomiting Medicine Agarwal et al. 2000 Postoperative Nausea Absence of Nausea Agarwal et al. 2000 Postoperative Vomiting Absence of Vomiting Harmon et al. 2000 Postoperative Nausea and Absence of Nausea and Vomiting Vomiting Harmon et al. 1999 Postoperative Nausea and Absence of Nausea and/or Vomiting 42/52 Vomiting Alkaissi et al. 1999 Postoperative Nausea and Absence of Nausea , Vomiting or Rescue 11/20 Vomiting Medicine Fan et al. 1997 Postoperative Nausea and Absence of Nausea and Vomiting Vomiting Bayreuther et al. 1994 Morning Sickness Symptom Reduction 10/15 Type 3 Pseudo-Intervention at the Same Acupoints as Intervention Group: Manual Light-Touch without Acupressure Kashanian & Shahali Cesarean Delivery No Need for Cesarean Delivery 54/60 2010 Hjelmstedt et al. 2010 Use of Analgesics No Need for Analgesics 36/71 Lee et al. 2004 Use of Analgesics No Need for Analgesics 31/36 Type 4 Pseudo-Intervention at the Same Acupoints as Intervention Group: Placebo Acupressure Devices Nilsson et al. 2015 Postoperative Nausea and Absence of Nausea and Vomiting 24/43 Vomiting Molassiotis et al. 2013 Chemotherapy-induced Nausea No Nausea Experience Molassiotis et al. 2013 Chemotherapy-induced No Vomiting Experience Vomiting Noroozinia et al. 2013 Postoperative Nausea and Absence of Nausea and Vomiting 76/76 Vomiting 1. 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Jing-Yu Tan, Lorna K. P. Suen, Tao Wang, Alexander Molassiotis. Sham Acupressure Controls Used in Randomized Controlled Trials: A Systematic Review and Critique, PLOS ONE, 2015, DOI: 10.1371/journal.pone.0132989