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Major depressive disorder is the most common mental disorder with significant economic burden and limited treatments. Acupuncture has emerged as a promising non-pharmacological treatment for reducing depressive symptoms. However, the potential mechanisms and clinical effectiveness of acupuncture are not fully understood. This review aimed to: (1) summarize the available evidence on the mechanisms and clinical effectiveness of acupuncture for depression, and then (2) compare with pharmacological interventions, guiding future studies. Studies with animal models of depression and patients have shown that acupuncture could increase hippocampal and network neuroplasticity and decrease brain inflammation, potentially to alleviating depressive disorders. Overall clinical studies indicated that acupuncture could relieve primary depression, particularly milder cases, and was helpful in the management of post-stroke depression, pain-related depression, and postpartum depression both as an isolated and adjunct treatment. It was emphasized that acupuncture combined with antidepressant pharmacological treatment not only enhanced the improvement of primary and secondary depressive symptoms but also reduced the side effects of the medical treatment, which is the main cause for high dropout rates with drug treatment. In summary, substantial evidence from animal and human researches supported the beneficial effect of acupuncture in depression. However, most clinical trials of acupuncture were small, and it is unclear whether their findings can be generalized, so more studies are needed.

Background Research on the effect of acupuncture has been limited. Whether the effect of acupuncture is equivalent to placebo has been the focus of debate in this field. This study will explore the specific and non-specific effects of acupuncture for knee osteoarthritis (KOA) by functional magnetic resonance imaging (fMRI). Methods and design Ninety participants diagnosed with KOA will be randomly divided into the acupuncture group, sham acupuncture group, and waiting list group in a ratio of 1:1:1. Except for the waiting list group, the other participants will receive acupuncture or sham acupuncture three sessions per week for 4 weeks respectively. The primary outcome will be the response rate which is defined on an individual basis as at least a 2-point decrease in the numerical rating scale (NRS) of pain at the end of intervention period compared with the baseline. fMRI scans will be performed at baseline and the end of the intervention period to examine the response of various brain regions. The secondary outcomes will include the Western Ontario and McMaster Osteoarthritis Index (WOMAC), State-Trait Anxiety Scale-State Anxiety Subscale (STAI-S), and Stanford Expectations of Treatment Scale (SETS). Pearson’s correlation coefficient will be performed to investigate the changes in brain activity and clinical variables. Discussion The results of our study will help to evaluate the specific and nonspecific effects of acupuncture combined with clinical and brain function changes based on KOA. Trial registration Chinese Clinical Trial Registry ChiCTR1900025799. Registered on 9 September 2019.

Objective: We aimed to explore the feasibility of evaluating the comparative effectiveness and safety of electroacupuncture (EA) relative to manual acupuncture (MA) for the treatment of knee osteoarthritis (KOA). Methods: A multicenter randomized controlled clinical trial was conducted in Beijing from September 2017 to January 2018. A total of 60 participants with KOA were randomly allocated to either EA ( n = 30) or MA ( n = 30) groups. Participants in the EA group were treated with EA at six to seven local traditional acupuncture points or ah shi points, and two to three distal points. Participants in the MA group had the same schedule as the EA group except that the electrical apparatus featured a working power indicator without actual current output, constituting a sham EA procedure, in order to blind participants. Both groups received 24 sessions over 8 weeks. The primary outcome was response rate, defined as a change of ⩾50% from baseline in the total scores of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) after 8 weeks. Secondary outcomes included pain, stiffness, function, quality of life, and acupuncture-related adverse events (AEs) at 4 and 8 weeks. Results: Of 60 participants randomized, 53 (88%) completed the study. Response rates were 43% for the EA group and 30% for the MA group by the intention-to-treat analysis. Although significant differences were observed in WOMAC pain, stiffness, and function scores within both groups, between-group differences at 8 weeks did not reach statistical significance (odds ratio = 1.75 (95% confidence interval = 0.593–5.162)). Rates of AEs were low and similarly distributed between groups. Conclusion: Both EA and MA interventions in KOA were feasible and appeared safe. Whether or not EA may have a stronger impact on pain and function requires further evaluation through larger, adequately powered, randomized controlled trials. Trial registration number: NCT03274713.

Background: Acupuncture is a widely used treatment for knee osteoarthritis, but evidence of its effectiveness from randomised controlled trials (RCTs) is contradictory. Objective: To systematically review RCTs to determine whether the effect of acupuncture is dose dependent for symptom management in knee osteoarthritis. Methods: Seven English/Chinese databases were searched through January 2017. Study quality was assessed using the Cochrane Collaboration tool. Slavin’s qualitative best-evidence synthesis approach was used to provide methodological rigour. Included RCTs were separated into three categories according to the dose of acupuncture treatment: high dosage (HD), medium dosage (MD) and low dosage (LD). Correlation between dose and effect of treatment was analysed. Results: Eight RCTs with a total of 2106 subjects met the eligibility criteria. Numbers of studies using the various doses of acupuncture were 1 for LD, 1 for MD and 6 for HD, respectively. Compared with LD and MD acupuncture treatments, strong evidence showed that there was a positive correlation between HD acupuncture treatment and positive outcomes. Conclusion: The effect of acupuncture may be associated with dose of acupuncture, with a higher dosage related to better treatment outcomes in terms of relief of pain and dysfunction in patients with knee osteoarthritis.

OBJECTIVES: This study aimed to assess the clinical benefit of device therapy on controlling the symptoms of Meniere’s disease (MD). MATERIALS AND METHODS: We searched PubMed, Embase, the Cochrane Library, China National Knowledge Internet, and Wanfang Data before January 13, 2018. We selected randomized controlled clinical trials, case-controlled studies, and cohort studies that dealt with outcomes of device therapy for the treatment of MD. RESULTS: Sixteen trials met our inclusion criteria. The use of device therapy resulted in improved vertigo control, which was described as a reduction in the number of vertigo days by month (weighted mean difference [WMD]: 3.15, 95% confidence interval [CI]: 2.00–4.31), in the number of vertigo episodes by month (WMD: 7.37, 95% CI: 2.40–12.35), and in the vertigo visual analog score (WMD: 41.51, 95% CI: 34.68–48.34). In addition, the overall complete vertigo control (class A) rate was 50% (95% CI: 37%–64%). The device therapy also reduced the number of sick days by month (WMD: 4.56, 95% CI: 2.15–6.97), and the functional level improved (WMD: 2.66, 95% CI: 2.15–3.17). The electrocochleographic parameters decreased. The device therapy proved beneficial for hearing changes (WMD: 3.19, 95% CI: 0.66–5.71). No publication bias was found in the funnel plot and the results of Egger’s test. CONCLUSION: This study showed that the device therapy might reduce vertigo attacks and sick days in patients with MD. Additionally, the function level and hearing level may improve after the device therapy. In addition, the decrease in electrocochleographic parameters showed that inner ear electrophysiology improved after device therapy.

Objective: To evaluate the effectiveness of acupuncture in patients with vascular cognitive impairment no dementia (VCIND) in comparison with citicoline, an agent for cognitive disturbances associated with chronic cerebral disorders. Design: A randomized controlled multicenter trial. Setting: In three hospitals in Beijing, China. Subjects: A total of 216 patients with VCIND were recruited. Interventions: Patients with VCIND (mean age of 65.4 years) were randomized to receive acupuncture (two sessions per week) or oral citicoline (100 mg three times daily) over three months. Main measures: The primary outcome was the change from baseline to three months in cognitive symptom, measured by Alzheimer’s disease Assessment Scale, cognitive subscale (ADAS-cog). Secondary outcomes included changes from baseline to six months in ADAS-cog, executive function measured by the Clock Drawing Test (CDT), and functional disability measured by the Ability of Daily Living (ADL) scale at three and six months. Results: At three months, the acupuncture group had a greater decrease in mean ADAS-cog score (−2.33 ± 0.31) than the citicoline group (−1.38 ± 0.34) with a mean difference of −0.95 (95% CI, −1.84 to −0.07, P = 0.035). The mean change from baseline to six months in ADAS-cog also significantly favored acupuncture treatments (acupuncture change −2.61 vs citicoline −1.25, difference: −1.36 points; 95% CI, −2.20 to −0.51; P = 0.002). There was no difference between the two groups on CDT and ADL scores at either time point. Conclusion: Compared with citicoline, acupuncture has comparable and even superior efficacy with improved cognitive and daily living performance as a complementary and alternative medicine treatment for VCIND.

Accumulating evidence supports an association between chronic pain and psychological disorders, a connection that seems to be bidirectional. Treating both the pain and psychological conditions together is essential for effective treatment outcomes. Acupuncture is a somatosensory-guided mind–body therapy that can tackle the multidimensional nature of pain with fewer or no serious adverse effects. In this review, we discuss the use of acupuncture in some conditions with a high incidence of psychological disorders caused by chronic pain: headache, musculoskeletal pain, low back pain, and cancer pain, focusing on the effect and potential mechanisms of acupuncture. Overall clinical studies indicated that acupuncture might effectively contribute to management of psychological disorders caused by chronic pain. Mechanistic studies showed that acupuncture significantly alleviated such psychological disorders by regulating the activity of amygdala and insula, and regulating functional connectivity of insular and limbic regions/medial prefrontal cortex in humans and the corresponding animal models. In addition, 5-HT in the dorsal raphe nucleus, opioid receptors in the cingulate cortex, and plasma met-enkephalin are involved in acupuncture relief of pain and psychological symptoms. Substantial evidences from animal and human research support a beneficial effect of acupuncture in psychological disorders caused by chronic pain.

White matter lesions induced by chronic cerebral hypoperfusion are associated with cognitive impairment in vascular dementia (VaD). Previous studies have shown that acupuncture can ameliorate the cognitive deficits of individuals with VaD. However, the neuroimaging mechanisms of acupuncture on white matter perfusion and integrity remain elusive. In this study, the VaD model was induced by bilateral common carotid arteries occlusion (BCCAO) in rats. Novel object recognition task and Morris water maze were performed to evaluate short-term memory and spatial learning and memory. Arterial spin labeling and diffusion tensor imaging (DTI) were used to measure the cerebral blood flow (CBF) and the white matter integrity. Pathological examinations detected the myelin loss and concomitant neuroinflammation. The results demonstrate that BCCAO rats with reduced CBF exhibited worse performance and altered DTI parameters, including decreased fractional anisotropy, increased radial diffusivity, and axial diffusivity in white matter regions. Acupuncture ameliorated cognitive impairment, increased CBF, and protected the myelin sheath integrity but not the axons of BCCAO rats. These protective effects of acupuncture on white matter were significantly correlated with improved CBF. Pathological examination confirmed that the loss of myelin basic protein and microglial accumulation associated IL-1β and IL-6 production were attenuated by acupuncture treatment. Our findings suggest that acupuncture protects cognitive function of BCCAO rats by improving white matter perfusion and integrity.

This 16-week randomised controlled trial (8-week treatment followed by 8-week follow-up) evaluated the symptomatic improvement in patients with knee osteoarthritis on 3 sessions per week of acupuncture (TSWA) compared to 1 session per week of acupuncture (OSWA). Sixty participants were randomised to either the TSWA or the OSWA group in a 1:1 ratio. The primary outcome was response rate, defined as the percentage of participants achieving ≥2 points decrease on the numerical rating scale (NRS) and ≥6 points decrease in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function score at week 8 compared with baseline. Additional outcomes included response rates at weeks 4 and 16, NRS, WOMAC, Patient Global Assessment, 12-item Short Form Health Survey (SF-12), and treatment credibility and expectancy. No significant difference was seen in response rate between TSWA and OSWA groups at week 8 (64.7% vs 50.0%; difference, 14.7 percentage points [95% CI, -10.1 to 39.4 percentage points], P = 0.435). At weeks 4 and 16, the TSWA group had higher response rates than the OSWA group (week-4: difference, 44.7 percentage points [95% CI, 23.2-66.1 percentage points], P = 0.001; week-16: difference, 46.0 percentage points [95% CI, 24.4-67.6 percentage points], P < 0.001). Participants in the TSWA group experienced significantly greater improvements in NRS, WOMAC function, and Patient Global Assessment than those in the OSWA group. There were no significant between-group differences in WOMAC stiffness and SF-12. In summary, TSWA immediately improved knee pain and dysfunction compared with OSWA. In addition, the benefit of TSWA persists throughout follow-up.

BACKGROUND: The survival of early placement (within 72h after admission) of transjugular intrahepatic portosystemic shunts (early-TIPS) in patients with cirrhosis and acute variceal bleeding (AVB) is controversial. OBJECTIVES: We performed a systemic review and meta-analysis to assess whether early-TIPS could improve survival in patients with cirrhosis and acute variceal bleeding. METHODS: Systematic search of the literature was conducted from PubMed, EMBASE, and Cochrane Library published before June 25, 2019 for eligible studies that compared early-TIPS with a combination of endoscopic variceal ligation (EVL) or endoscopic injection sclerotherapy (EIS) plus pharmacotherapy in the therapeutic effect in AVB patients. RESULTS: A total of 5 studies with 1,754 participants were enrolled. The early-TIPS demonstrated a significant improvement in prevention of treatment failure (OR=0.11,95%CI=0.05-0.23), 6-weeks mortality (OR=0.24,95%CI=0.13-0.46), rebleeding within 6 weeks (OR=0.21,95%CI=0.12-0.36), rebleeding within 1 year (OR=0.16,95%CI=0.07-0.36), new or worsening ascites (OR=0.33,95%CI=0.21-0.53), except in encephalopathy (OR=1.29,95%CI=0.996-1.67). For 1-year mortality, significant prior effect was also observed in early-TIPS (OR=0.64,95%CI=0.46-0.90), and the beneficial effect in Child-Pugh C patients (OR=0.35,95%CI=0.18-0.68) was equal to Child-Pugh B patients (OR=0.34,95%CI=0.25-0.58). No difference in liver transplantation and mortality caused by liver failure was observed. CONCLUSSIONS: Early covered-TIPS could be recommended for the management of AVB patients in cirrhosis with demonstrating a significant improvement in treatment failure, both short- and long-term mortality, rebleeding risk, and new or worsening ascites compared to standard therapy, especially for the high-risk AVB patients. It will also apply to patients in Child-Pugh A until the solutions to prevent hepatic encephalopathy in future researches were found.

Background: The current clinical guidelines on post-traumatic stress disorder (PTSD) recommend selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) of drugs. However, there is uncertainty about the efficacy of other drugs and selecting which treatments work best for which patients. Therefore, we aimed to estimate efficacy and acceptability of pharmaceutical management for adults with PTSD. Methods: We searched the Ovid Medline, EMBase, CENTRAL, PsycINFO, Ovid Health and Psychosocial Instruments, and ISIWeb of Science for randomized controlled trials (RCTs) until June 21, 2019. We included placebo-controlled and active-comparators trials of pharmaceutical management for adults with PTSD diagnosed according to standard operationalized criteria. The outcomes were defined as efficacy (improvement in symptoms of PTSD, based on evaluation results of clinician rating scales or interview instruments; core symptoms, including re-experiencing, avoidance, and hyperarousal; other symptoms, including depression and anxiety) and acceptability (all-cause discontinuation, and discontinuation due to adverse effects). Findings: 66 studies with 78 trials comprising of 8,083 patients diagnosed with PTSD were identified. There were two kind of comparisons in included studies, one of them was the comparison between 31 active drugs and placebo, another comparison was active-comparator between 12 active drugs aiming at exploring the differences among different drugs. In terms of efficacy, all active drugs demonstrated superior effect than placebo (SMD = -0.33, 95%CI: -0.43 to -0.23). The medications were superior to placebo in reducing the symptom of re-experiencing, avoidance, hyperarousal, depression, and anxiety. For acceptability, medicine interventions for PTSD showed no increase in all-cause discontinuation compared with placebo (RR = 0.95, 95%CI: 0.88 to 1.03). Nevertheless, in terms of safety, medicine interventions indicated a higher risk of adverse effect compared with placebo (RR = 1.47, 95%CI: 1.24 to 1.75). Compared with placebo, the SSRIs and atypical antipsychotics drugs had significant efficacy whether in patients with severe or extremely severe PTSD status. However, only atypical antipsychotics (SMD = -0.29, 95%CI: -0.48 to -0.10) showed superior efficacy than placebo in veterans. Interpretation: Medication management could be effective in intervention of PTSD, which demonstrated a sufficient improvement in the core symptoms. This meta-analysis supports the status of SSRIs and SNRIs as recommended pharmacotherapy for PTSD. However, patients with different clinical characteristics of PTSD should consider individualized drug management. Furthermore, more high-quality researches are required to confirm these findings. Funding Statement: The authors stated that no funding was received for this research. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The authors used the guidelines from the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement.

Background: White matter lesions induced by chronic cerebral hypoperfusion (CCH) are common pathological changes, and are associated with cognitive impairment in vascular dementia (VaD). It has been reported that acupuncture can improve cognitive deficits of VaD rats through increasing cortical cerebral blood flow and attenuating neuroinflammation. However, the effects of acupuncture on white matter perfusion and white matter structural integrity have been not investigated. Methods: VaD was induced by bilateral common carotid arteries occlusion (BCCAO) in Wistar rats. Morris water maze (MWM) was used to evaluated the spatial learning and memory of rats. Arterial spin labeling imaging (ASL) and diffusion tensor imaging (DTI) were performed to measure the cerebral blood flow and white matter integrity in corpus callosum, external capsule, internal capsule, optic nerve and optic tract. Pathological staining was also applied to detect the myelin loss and neuroinflammation. Results: BCCAO rats with declined cerebral blood flow exhibited significant worse MWM performance, and altered DTI parameters including decreased fractional anisotropy, elevated radial diffusivity and axial diffusivity in white matter regions. After acupuncture treatment at GV20 and ST36, cognitive dysfunction, disruption of white matter perfusion and integrity were reversed. Pathological results supported that acupuncture could attenuate the loss of myelin sheath and microglia activation. Conclusions: Our findings suggest that acupuncture treatment protects cognitive impairment of BCCAO rats through increasing subcortical white matter perfusion and improving white matter lesions. Keywords: Acupuncture; ASL; DTI; cerebral blood flow; white matter; microglia activation

Background: With new randomised pieces of evidence and the latest clinical practice guideline from the BMJ emerging in 2018, an updated analysis of best available evidence on the controversial effects of corticosteroids in sepsis is warranted. Objectives: To comprehensively evaluate whether corticosteroids are beneficial in reducing mortality and what cumulative dosage, daily dosage, and duration of corticosteroid treatment would enable adult patients with sepsis to reach the critical point of benefits. Methods: Ovid MEDLINE, Ovid EMbase, Cochrane Library, and LILACS database were searched until March 22, 2019. Results: Thirty RCTs with 8,836 participants were identified. Long course low-dose corticosteroid therapy could improve 28-day mortality (RR = 0.90, 95% CI = 0.84–0.97; high quality), intensive care unit mortality (RR = 0.87; 95% CI = 0.79–0.95; moderate quality), and in-hospital mortality (RR = 0.88, 95% CI = 0.79–0.997; high quality). However, we found no benefits for 90-day, 180-day, and 1-year mortality. Subgroup results of long course corticosteroid treatment in a population with septic shock and vasopressor-dependent septic shock, corticosteroid regimen with hydrocortisone plus fludrocortisone, corticosteroid dosing strategies including bolus dosing and infusion dosing, the strategies of abrupt discontinuation, timing of randomisation ≤24 h, impact factor of ≥10, and sample size ≥500 were associated with a marginally reduction in 28-day mortality. Conclusions: This meta-analysis found that the long course low-dose and not short course high-dose corticosteroid treatment could marginally improve short-term 28-day mortality with high quality, especially septic shock and vasopressor-dependent septic shock, and it is recommended that long course (about 7 days) low-dose (about 200–300mg per day) hydrocortisone (or equivalent) with cumulative dose (at least about 1,000mg) may be a viable management option for overall patients with sepsis, and it can be also adapted to patient with septic shock alone. Early hydrocortisone plus fludrocortisone administration, via continuous infusion or bolus dosing, is also particularly important for the prognosis. Abrupt discontinuation of corticosteroids, as opposed to the conventional tapered discontinuation, may be considered as a desirable option in 28-day mortality. The safety profile of long course low-dose corticosteroid treatment, including adverse hyperglycaemia and hypernatraemia events, remains a concern, although these events could be easily treated. Clinical Trial Registration: PROSPERO, identifier CRD 42018092849.

Background: A host of systematic reviews and meta-analyses were carried out to estimate the role of corticosteroids in sepsis and septic shock. Discordant opinions were investigated to determine whether patients who experienced sepsis and septic shock could benefit from corticosteroids treatment. Our purpose is to perform a systematic review of overlapping meta-analyses, to explore the role of corticosteroids in the treatment of sepsis and septic shock. Method: Ovid MEDLINE, EMBase, Cochrane Database of Systematic Reviews, and LILACS were searched for eligible studies. Two authors individually extracted the relevant data and evaluated the quality of the meta-analysis using A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR 2) and ROBIS. The Jadad decision algorithm was implemented to identify the meta-analyses that offered the optimal level of evidence. Result: Sixteen meta-analyses met the eligibility criteria. None of the studies that reported mortality illustrated a significant improvement on mortality (14-day and 90-day), but a 28-day mortality on a long course of a low dose corticosteroids was described. Only four studies stated that a long course of low-dose corticosteroids had advantageous effect on 28-day mortality. A meta-analysis by Fang et al. was regarded as the highest level of evidence in the Jadad decision algorithm among the meta-analyses that were investigated in this systematic review. Conclusion: The 28-day mortality was reduced, as well as the mortality in the ICU and hospital and the length of stay in the ICU, using a long course of low-dose corticosteroids. This was demonstrated by a meta-analysis of the current optimal available evidence. Additionally, significant improvements on the adverse events of hyperglycemia and hypernatraemia have been made.

Background This study aims to determine whether 3 sessions per week of acupuncture treatment is superior to 1 session per week of acupuncture treatment for symptomatic outcomes in knee osteoarthritis. Methods/design This is a two parallel-group, assessor-blinded, randomized controlled trial. Sixty patients with knee osteoarthritis (Kellgren–Lawrence grade II or III) will be recruited and randomly allocated to receive 24 or 8 sessions (group M or group L) of acupuncture treatment in a 1:1 ratio. Patients in group M will receive 3 sessions per week of acupuncture for 8 weeks. Patients in group L will receive acupuncture once per week for 8 weeks. The primary outcome is the response rate—the percentage of patients achieving a decrease ≥ 2 points on a numerical rating pain scale and a decrease ≥ 6 points in the Western Ontario and McMaster Universities Osteoarthritis Index function score at 8 weeks compared with baseline. Secondary outcomes include pain, function, overall effect, quality of life, and treatment credibility and expectancy. Discussion Three sessions per week of acupuncture treatment may be superior to 1 session per week of acupuncture treatment for symptomatic outcomes in knee osteoarthritis. Results of the study will be of great importance for the guidelines of clinical therapy. Trial registration Clinicaltrials.gov, NCT03359603. Registered on 1 December 2017. Electronic supplementary material The online version of this article (10.1186/s13063-019-3528-8) contains supplementary material, which is available to authorized users.

Knee osteoarthritis (KOA) is one of the most common musculoskeletal disorders. Although the available evidence for its efficacy is inconclusive, acupuncture is used as an alternative therapy for KOA. The aim of this trial is to determine the efficacy of electro-acupuncture and manual acupuncture versus sham acupuncture for KOA.This is a study protocol for a randomised, three-arm, multicentre, clinical trial. A total of 480 patients with KOA will be randomly assigned to the electro-acupuncture group, the manual acupuncture group or the sham acupuncture group in a 1:1:1 ratio. All patients will receive 24 sessions over 8 weeks. Participants will complete the trial by visiting the research centre at week 26 for a follow-up assessment. The primary outcome is the success rate: the proportion of patients achieving a minimal clinically important improvement, which is defined as ≥2 points on the numerical rating scale and ≥6 points on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function score at week 8 compared with baseline. Secondary outcomes include the numerical rating scale, WOMAC score, global patient assessment and quality of life at weeks 4, 8, 16 and 26 after randomisation.This trial may provide high-quality evidence for the efficacy of acupuncture in the treatment of KOA. The results of this study will be published in peer-reviewed journals.ClinicalTrials.gov, NCT03274713 . Registered on 20 November 2017.

Background: Acupuncture therapies are widely used for knee osteoarthritis (KOA), despite contradictory evidences. Current study is designed to determine the efficacy of electro-acupuncture and manual acupuncture versus sham acupuncture for KOA. Methods/design: Current study is a multi-center, three-arm, randomized controlled trial which will enroll 480 participants with KOA in China. Participants will be randomly assigned (1:1:1) to receive 24 sessions of electro-acupuncture, manual acupuncture, or sham acupuncture over 8 weeks. The primary outcome is the response rate - the proportion of patients who simultaneously achieve minimal clinically important improvement in pain and function domains at 8 weeks. The primary outcome will be analyzed using Z-test with intention-to-treat set. Secondary outcomes contain pain, function, global patient assessment and quality of life. Full details of the statistical analysis plan for the primary and secondary outcomes will be described in this article. The statistical analysis plan was written and submitted without knowledge of the study data. Discussion: The data will be analyzed according to this pre-specified statistical analysis plan to avoid data-driven analysis and enhance the transparency of current trial. The trial will provide high-quality evidence on the efficacy of acupuncture for KOA. Trial registration: Clinicaltrials.gov, NCT03366363. Registered on 20 November 2017. (https://clinicaltrials.gov/show/NCT03366363)

Background Knee osteoarthritis (KOA) is one of the most common musculoskeletal disorders. Although the available evidence for its efficacy is inconclusive, acupuncture is used as an alternative therapy for KOA. The aim of this trial is to determine the efficacy of electro-acupuncture and manual acupuncture versus sham acupuncture for KOA. Methods/design This is a study protocol for a randomised, three-arm, multicentre, clinical trial. A total of 480 patients with KOA will be randomly assigned to the electro-acupuncture group, the manual acupuncture group or the sham acupuncture group in a 1:1:1 ratio. All patients will receive 24 sessions over 8 weeks. Participants will complete the trial by visiting the research centre at week 26 for a follow-up assessment. The primary outcome is the success rate: the proportion of patients achieving a minimal clinically important improvement, which is defined as ≥2 points on the numerical rating scale and ≥6 points on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function score at week 8 compared with baseline. Secondary outcomes include the numerical rating scale, WOMAC score, global patient assessment and quality of life at weeks 4, 8, 16 and 26 after randomisation. Discussion This trial may provide high-quality evidence for the efficacy of acupuncture in the treatment of KOA. The results of this study will be published in peer-reviewed journals. Trial registration ClinicalTrials.gov, NCT03274713. Registered on 20 November 2017. Electronic supplementary material The online version of this article (10.1186/s13063-018-3138-x) contains supplementary material, which is available to authorized users.

Objective: To evaluate the effectiveness of acupuncture for pain relief and function improvement in patients with knee osteoarthritis and to determine the feasibility of an eight-week acupuncture intervention. Design: Pilot randomized controlled trial. Setting: Three teaching hospitals in China. Subjects: Patients with knee osteoarthritis (Kellgren grade II or III). Interventions: Patients were randomly assigned to an eight-week (three sessions per week) intervention of either traditional Chinese acupuncture or sham acupuncture. Main measures: The primary outcome was response rate—the proportion of patients achieving score ⩾36% decrease in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function at week 8 compared with baseline. Secondary outcomes included pain, function and quality of life. Results: Of 42 patients randomized, 36 (85.7%) completed the study. There was no significant difference in response rate between the traditional Chinese acupuncture and control groups: 61.9% (13 of 21) versus 42.9% (9 of 21) achieved score ⩾36% decrease in WOMAC pain and function at week 8 ( P = 0.217). The sum of WOMAC pain and function scores at week 8 was 11.6 (9.1) in the traditional Chinese acupuncture group compared with 16.3 (10.9) in the control group ( P = 0.183). There was no significant difference between groups. Three adverse events were recorded and were classified as mild. Conclusion: It showed that three sessions per week acupuncture intervention of knee osteoarthritis was feasible and safe. No difference was observed between groups due to small sample size. Larger (sample size ⩾ 296) randomized controlled trials of this intervention appear justified.

Patients with liver cirrhosis and variceal hemorrhage are at increased risk of rebleeding. We performed a meta-analysis toassess the clinical efficacy of combination therapy (pharmacotherapy and endoscopic variceal ligation (EVL)) compared with pharmacotherapy, EVL, or transjugular intrahepatic portosystemic shunt (TIPS) alone in the prevention of rebleeding and mortality. A literature search of MEDLINE, EMBASE, and the Cochrane Controlled Trials Register, up until November 2016, identified relevant randomized controlled trials. Data analysis was performed using Stata 12.0. Regarding overall mortality, combination therapy was as effective as EVL, pharmacotherapy, and TIPS (relative risk (RR) = 0.62, 95% confidence interval (CI): 0.36-1.08, RR=1.05, 95% CI: 0.68-1.63, and RR=1.39, 95% CI: 0.92-2.09, respectively). Combination therapy was as effective as EVL and pharmacotherapy alone in reducing blood-related mortality (RR=0.43, 95% CI: 0.15-1.25, and RR=0.42, 95% CI: 0.17-1.06), whereas TIPS was more effective than combination therapy (RR=5.66, 95% CI: 1.02-31.40). This was also the case for rebleeding; combination therapy was more effective than EVL and pharmacotherapy alone (RR=0.57, 95% CI: 0.41-0.79, and RR=0.65, 95% CI: 0.48-0.88), whereas TIPS was more effective than combination therapy (RR=9.42, 95% CI: 2.99-29.65). Finally, regarding rebleeding from esophageal varices, combination therapy was as effective as EVL alone (RR=0.59, 95% CI: 0.33-1.06) and was more effective than pharmacotherapy alone (RR=0.58, 95% CI: 0.40-0.85), although was less effective than TIPS (RR=2.20, 95% CI: 1.22-3.99). TIPS was recommended as the first choice of therapy in the secondary prevention of esophageal variceal bleeding.