Sham-controlled Randomized Controlled Trials Research Articles

Efficacy of neurofeedback training for improving attentional performance in healthy adults: A systematic review and meta-analysis

Abstract This systematic review and meta-analysis examined the neurofeedback training (NFT) effects on attentional performance in healthy adults. Six databases were searched until June 2022 to identify parallel randomized controlled trials (RCTs) evaluating attentional improvements after NFT. Risk of bias was assessed using the Cochrane Collaboration tool. We identified 41 RCTs for qualitative synthesis and 15 RCTs (569 participants) for meta-analysis. The overall NFT effect on attentional performance was significant (standardized mean difference = 0.27, 95% confidence interval = 0.10–0.44). However, no significant pooled effect was found within the trials comparing its effect with sham-NFT (eight RCTs). Additionally, variable effects were observed on individual subsets of attentional performance. Further sham-controlled RCTs are required to validate the improvement of attentional performance with NFT.

Clinical Evidence for Association of Electroacupuncture with Improved Colorectal Postoperative Gastrointestinal Function Recovery: A Systematic Review and Meta-Analysis

Background: Studies on the efficacy of electroacupuncture (EA) on postoperative gastrointestinal function (PGIF) recovery in colorectal cancer (CRC) patients have been increasing, but the findings are inconsistent. To evaluate the effectiveness and safety of EA on PGIF recovery in patients with CRC based on existing randomized controlled trials (RCTs) and assess whether the current evidence is conclusive by trial sequential analysis (TSA). Materials and Methods: PubMed, Embase (Ovid), Medline, Cochrane Library, Chinese Biomedical Literature Database, VIP Database for Chinese Technical Periodicals, China National Knowledge Infrastructure, and Wanfang) were searched for RCTs published from inception to November 6, 2022. RCTs in which EA was compared with sham control (sham electroacupuncture, SA) or usual care (UC) for managing PGIF recovery in patients with CRC were included. Following the preferred reporting items for systematic reviews and meta-analyses, two reviewers independently extracted data as well as assessed the risk of bias using the cochrane risk of bias tool (ROB 2.0) and the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Data were screened and extracted independently using predesigned forms. Data were pooled using a random-effects model. Results: Sixteen studies, including 1290 patients with CRC that showed PGIF recovery met the inclusion criteria. The meta-analysis revealed that compared with the UC group, EA + UC group showed a significant improvement in the time to first flatus (MD: -14.59, 95% CI: -22.75 to -6.43, P < 0.01), time to first defecation (MD: -20.28, 95% CI: -28.14 to -12.42, P < 0.01), and time to first bowel sounds (MD: -11.79, 95% CI: -18.97 to -4.60, P < 0.01). The TSA confirmed the better treatment outcomes of EA compared with UC. Compared with the SA group, EA + UC group showed a significant improvement in the time to first flatus (MD: -10.48, 95% CI: [-13.74, -7.21], P < 0.01) and time to first defecation (MD: -10.72, 95% CI: [-20.14, -1.30], P = 0.03), and the improvement in time to first bowel sounds (MD: -5.41, 95% CI -12.43 to 1.60, P = 0.13) was similar. The TSA indicated there might be false positive results and further studies with a larger overall sample size are deemed necessary. The reported adverse events related to acupuncture were less serious. Conclusion: EA has great potential to accelerate the recovery of PGIF for patients with CRC. RCTs with usual care control was sufficient. Additional pre-registered and sham-controlled RCTs are still needed to validate the safety and efficacy of EA.

Massage Therapy for Fatigue Management in Breast Cancer Survivors: A Systematic Review and Descriptive Analysis of Randomized Controlled Trials

Background Fatigue is one of the most common symptoms among breast cancer survivors. Although massage therapy has been commonly used for fatigue management, relevant evidence on the effectiveness of massage therapy for the reduction of fatigue in breast cancer survivors is still unclear. Objective To identify the research evidence on the effectiveness and safety of massage therapy to manage fatigue in breast cancer survivors and summarize the characteristics of massage therapy protocols utilized for fatigue management in breast cancer survivors. Methods Randomized controlled trials (RCTs) using massage therapy to manage cancer-related fatigue were searched in PubMed, Medline, Web of Science, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL), ScienceDirect, PsycINFO, Wan Fang Data, and China National Knowledge Infrastructure (CNKI) from the inception of each database to March 2021. The Cochrane Back Review Group Risk of Bias Assessment Criteria was used to assess the methodological quality of the included studies. Descriptive analysis was applied for a summary and synthesis of the findings. The primary outcome was fatigue measured by any patient-reported questionnaires, and the secondary outcomes were quality of life and massage-therapy-related adverse events. Results Ten RCTs were included. Massage therapy was found to have a positive effect on fatigue management compared with routine care/wait list control groups and sham massage. Despite these encouraging findings, the review concluded that most of the included studies exhibited an unsatisfactory experimental design, particularly, inadequate blinding and allocation concealment. The duration and frequency of the massage therapy interventions varied across the studies. Adverse events were reported in three included studies, with no study conducting causality analysis. Conclusion This systematic review provides the latest research evidence to support massage therapy as an encouraging complementary and alternative medicine approach to managing fatigue in breast cancer survivors. More rigorously designed, large-scale, sham-controlled RCTs are needed to further conclude the specific therapeutic effectiveness and safety issues of massage therapy for fatigue management.

Use of Sham Interventions in Randomized Controlled Trials in Neurosurgery.

The use of sham interventions in randomized controlled trials (RCTs) is essential to minimize bias. However, their use in surgical RCTs is rare and subject to ethical concerns. To date, no studies have looked at the use of sham interventions in RCTs in neurosurgery. This study evaluated the frequency, type, and indication of sham interventions in RCTs in neurosurgery. RCTs using sham interventions were also characterized in terms of design and risk of bias. From a total of 1,102 identified RCTs in neurosurgery, 82 (7.4%) used sham interventions. The most common indication for the RCT was the treatment of pain (67.1%), followed by the treatment of movement disorders and other clinical problems (18.3%) and brain injuries (12.2%). The most used sham interventions were saline injections into spinal structures (31.7%) and peripheral nerves (10.9%), followed by sham interventions in cranial surgery (26.8%), and spine surgery (15.8%). Insertion of probes or catheters for a sham lesions was performed in 14.6%.In terms of methodology, most RCTs using sham interventions were double blinded (76.5%), 9.9% were single blinded, and 13.6% did not report the type of blinding. Sham-controlled RCTs in neurosurgery are feasible. Most aim to minimize bias and to evaluate the efficacy of pain management methods, especially in spinal disorders. The greatest proportion of sham-controlled RCTs involves different types of substance administration routes, with sham surgery the less commonly performed.

S43. ASSESSING THE VARIABILITY OF RESPONSE TO NON-INVASIVE BRAIN STIMULATION IN PSYCHOSIS

BackgroundNon-invasive brain stimulation has been introduced as add-on treatment for psychotic symptoms, not least because transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) have a low risk profile. Yet, the initial excitement is wearing off and there is a lack of consistent evidence from randomized controlled trials (RCT) for the efficacy of brain stimulation. It is often claimed that this is because patients respond very differently to brain stimulation, with some benefiting much more than others. However, is there really strong evidence from RCTs that patients do respond differently? This question can be assessed by comparing the overall variability under active stimulation with the variability under sham stimulation across studies.MethodsWe included all double-blinded, sham-controlled RCTs and crossover studies of adults with a diagnosis of a schizophrenia spectrum disorder that used TMS or tDCS for the treatment of psychotic symptoms. We extracted a measure of variability (standard deviation, standard error, or confidence interval) of the primary outcome for active and sham stimulation, computed variance-weighted variability ratios for each study, and entered them into a random-effects model. In the case of individual differences in response to TMS or tDCS, we expected that the overall variability under active stimulation would be increased compared to sham stimulation (as evidenced by an overall variability ratio significantly larger than 1).ResultsA total of 39 RCTs and crossover trials with 1 352 patients were included. We found that the variability under active stimulation was not significantly larger than under sham stimulation (variability ratio = 1.07; 95% CI: 0.99, 1.16; P = 0.098).DiscussionThese results do not provide strong evidence for the presence of individual differences in response to non-invasive brain stimulation in patients with schizophrenia spectrum disorders. The search for subgroups and prognostic biomarkers may require more complex study designs including N-of-1 trials.

Acupuncture for hip osteoarthritis.

Hip osteoarthritis (OA) is a major cause of pain and functional limitation. Few hip OA treatments have been evaluated for safety and effectiveness. Acupuncture is a traditional Chinese medical therapy which aims to treat disease by inserting very thin needles at specific points on the body. To assess the benefits and harms of acupuncture in patients with hip OA. We searched Cochrane CENTRAL, MEDLINE, and Embase all through March 2018. We included randomized controlled trials (RCTs) that compared acupuncture with sham acupuncture, another active treatment, or no specific treatment; and RCTs that evaluated acupuncture as an addition to another treatment. Major outcomes were pain and function at the short term (i.e. < 3 months after randomization) and adverse events. We used standard methodological procedures expected by Cochrane. Six RCTs with 413 participants were included. Four RCTs included only people with OA of the hip, and two included a mix of people with OA of the hip and knee. All RCTs included primarily older participants, with a mean age range from 61 to 67 years, and a mean duration of hip OA pain from two to eight years. Approximately two-thirds of participants were women. Two RCTs compared acupuncture versus sham acupuncture; the other four RCTs were not blinded. All results were evaluated at short term (i.e. four to nine weeks after randomization).In the two RCTs that compared acupuncture to sham acupuncture, the sham acupuncture control interventions were judged believable, but each sham acupuncture intervention was also judged to have a risk of weak acupuncture-specific effects, due to placement of non-penetrating needles at the correct acupuncture points in one RCT, and the use of penetrating needles not inserted at the correct points in the other RCT. For these two sham-controlled RCTs, the risk of bias was low for all outcomes.The combined analysis of two sham-controlled RCTs gave moderate quality evidence of little or no effect in reduction in pain for acupuncture relative to sham acupuncture. Due to the small sample sizes in the studies, the confidence interval includes both the possibility of moderate benefit and the possibility of no effect of acupuncture (120 participants; Standardized Mean Difference (SMD) -0.13, (95% Confidence Interval (CI) -0.49 to 0.22); 2.1 points greater improvement with acupuncture compared to sham acupuncture on 100 point scale (i.e., absolute percent change -2.1% (95% CI -7.9% to 3.6%)); relative percent change -4.1% (95% CI -15.6% to 7.0%)). Estimates of effect were similar for function (120 participants; SMD -0.15, (95% CI -0.51 to 0.21)). No pooled estimate, representative of the two sham-controlled RCTs, could be calculated or reported for the quality of life outcome.The four other RCTs were unblinded comparative effectiveness RCTs, which compared (additional) acupuncture to four different active control treatments.There was low quality evidence that addition of acupuncture to the routine primary care that RCT participants were receiving from their physicians was associated with statistically significant and clinically relevant benefits, compared to the routine primary physician care alone, in pain (1 RCT; 137 participants; mean percent difference -22.9% (95% CI -29.2% to -16.6%); relative percent difference -46.5% (95% CI -59.3% to -33.7%)) and function (mean percent difference -19.0% (95% CI -24.41 to -13.59); relative percent difference -38.6% (95% CI -49.6% to -27.6%)). There was no statistically significant difference for mental quality of life and acupuncture showed a small, significant benefit for physical quality of life.The effects of acupuncture compared with either advice plus exercise or NSAIDs are uncertain.We are also uncertain whether acupuncture plus patient education improves pain, function, and quality of life, when compared to patient education alone.In general, the overall quality of the evidence for the four comparative effectiveness RCTs was low to very low, mainly due to the potential for biased reporting of patient-assessed outcomes due to lack of blinding and sparse data.Information on safety was reported in four RCTs. Two RCTs reported minor side effects of acupuncture, which were primarily minor bruising, bleeding, or pain at needle insertion sites. Four RCTs reported on adverse events, and none reported any serious adverse events attributed to acupuncture. Acupuncture probably has little or no effect in reducing pain or improving function relative to sham acupuncture in people with hip osteoarthritis. Due to the small sample size in the studies, the confidence intervals include both the possibility of moderate benefits and the possibility of no effect of acupuncture. One unblinded trial found that acupuncture as an addition to routine primary physician care was associated with benefits on pain and function. However, these reported benefits are likely due at least partially to RCT participants' greater expectations of benefit from acupuncture. Possible side effects associated with acupuncture treatment were minor.

Radiofrequency ablation for chronic low back pain: a systematic review of randomized controlled trials.

Radiofrequency ablation (RFA), a procedure using heat to interrupt pain signals in spinal nerves, is an emerging treatment option for chronic low back pain. Its clinical efficacy has not yet been established. To determine the efficacy of RFA for chronic low back pain associated with lumbar facet joints, sacroiliac joints, discogenic low back pain and the coccyx. A systematic review was conducted. Medline, EMBASE, PubMed, SPORTDiscus, CINAHL and the Cochrane Library were searched up to August 2013. Abstracts and full-text articles were reviewed in duplicate. Included articles were sham-controlled randomized controlled trials (RCTs), assessed the efficacy of RFA, reported at least one month of follow-up and included participants who had experienced back pain for at least three months. Data were extracted in duplicate and quality was assessed using the Cochrane Risk of Bias tool. Due to heterogeneity, as well as a lack of reported mean differences and SDs, meta-analysis was not possible using these data. The present systematic review retrieved 1063 abstracts. Eleven sham-controlled RCTs were included: three studies involving discogenic back pain; six studies involving lumbar facet joint pain; and two studies involving sacroiliac joint pain. No studies were identified assessing the coccyx. The evidence supports RFA as an efficacious treatment for lumbar facet joint and sacroiliac joint pain, with five of six and both of the RCTs demonstrating statistically significant pain reductions, respectively. The evidence supporting RFA for the treatment of discogenic pain is mixed. While the majority of the studies focusing on lumbar facet joints and sacroiliac joints suggest that RFA significantly reduces pain in short-term follow-up, the evidence base for discogenic low back pain is mixed. There is no RCT evidence for RFA for the coccyx. Future studies should examine the clinical significance of the achieved pain reduction and the long-term efficacy of RFA.

Acupuncture for treatment of irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a common, costly, and difficult to treat disorder that impairs health-related quality of life and work productivity. Evidence-based treatment guidelines have been unable to provide guidance on the effects of acupuncture for IBS because the only previous systematic review included only small, heterogeneous and methodologically unsound trials. The primary objectives were to assess the efficacy and safety of acupuncture for treating IBS. MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE, the Cumulative Index to Nursing and Allied Health, and the Chinese databases Sino-Med, CNKI, and VIP were searched through November 2011. Randomized controlled trials (RCTs) that compared acupuncture with sham acupuncture, other active treatments, or no (specific) treatment, and RCTs that evaluated acupuncture as an adjuvant to another treatment, in adults with IBS were included. Two authors independently assessed the risk of bias and extracted data. We extracted data forthe outcomes overall IBS symptom severity and health-related quality of life. For dichotomous data (e.g. the IBS Adequate Relief Question), we calculated a pooled relative risk (RR) and 95% confidence interval (CI) for substantial improvement in symptom severity after treatment. For continuous data (e.g. the IBS Severity Scoring System), we calculated the standardized mean difference (SMD) and 95% CI in post-treatment scores between groups. Seventeen RCTs (1806 participants) were included. Five RCTs compared acupuncture versus sham acupuncture. The risk of bias in these studies was low. We found no evidence of an improvement with acupuncture relative to sham (placebo) acupuncture for symptom severity (SMD -0.11, 95% CI -0.35 to 0.13; 4 RCTs; 281 patients) or quality of life (SMD = -0.03, 95% CI -0.27 to 0.22; 3 RCTs; 253 patients). Sensitivity analyses based on study quality did not change the results. A GRADE analysis indicated that the overall quality of the evidence for the primary outcomes in the sham controlled trials was moderate due to sparse data. The risk of bias in the four Chinese language comparative effectiveness trials that compared acupuncture with drug treatment was high due to lack of blinding. The risk of bias in the other studies that did not use a sham control was high due to lack of blinding or inadequate methods used for randomization and allocation concealment or both. Acupuncture was significantly more effective than pharmacological therapy and no specific treatment. Eighty-four per cent of patients in the acupuncture group had improvement in symptom severity compared to 63% of patients in the pharmacological treatment group (RR 1.28, 95% CI 1.12 to 1.45; 5 studies, 449 patients). A GRADE analysis indicated that the overall quality of the evidence for this outcome was low due to a high risk of bias (no blinding) and sparse data. Sixty-three per cent of patients in the acupuncture group had improvement in symptom severity compared to 34% of patients in the no specific therapy group (RR 2.11, 95% CI 1.18 to 3.79; 2 studies, 181 patients). There was no statistically significant difference between acupuncture and Bifidobacterium (RR 1.07, 95% CI 0.90 to 1.27; 2 studies; 181 patients) or between acupuncture and psychotherapy (RR 1.05, 95% CI 0.87 to 1.26; 1 study; 100 patients). Acupuncture as an adjuvant to another Chinese medicine treatment was significantly better than the other treatment alone. Ninety-three per cent of patients in the adjuvant acupuncture group improved compared to 79% of patients who received Chinese medicine alone (RR 1.17, 95% CI 1.02 to 1.33; 4 studies; 466 patients). There was one adverse event (i.e. acupuncture syncope) associated with acupuncture in the 9 trials that reported this outcome, although relatively small sample sizes limit the usefulness of these safety data. Sham-controlled RCTs have found no benefits of acupuncture relative to a credible sham acupuncture control for IBS symptom severity or IBS-related quality of life. In comparative effectiveness Chinese trials, patients reported greater benefits from acupuncture than from two antispasmodic drugs (pinaverium bromide and trimebutine maleate), both of which have been shown to provide a modest benefit for IBS. Future trials may help clarify whether or not these reportedly greater benefits of acupuncture relative to pharmacological therapies are due entirely to patients' preferences for acupuncture or greater expectations of improvement on acupuncture relative to drug therapy.

Acupuncture for Irritable Bowel Syndrome: Systematic Review and Meta-Analysis

Evidence-based treatment guidelines have been unable to provide evidence-based guidance on the effects of acupuncture for irritable bowel syndrome (IBS) because the only previous systematic review included only small, heterogeneous, and methodologically unsound trials. We conducted a new systematic review and meta-analysis of randomized controlled trials (RCTs) to estimate the effects of acupuncture for treating IBS. MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE, Cumulative Index to Nursing and Allied Health, and the Chinese databases Sino-Med, CNKI, and VIP were searched through November 2011. Eligible RCTs compared acupuncture with sham acupuncture, other active treatments, or no (specific) treatment, and evaluated acupuncture as an adjuvant to another treatment. Our outcomes were overall IBS symptom severity and health-related quality of life. Dichotomous data were pooled to provide a relative risk (RR) of substantial improvement after treatment, and continuous data were pooled to provide a standardized mean difference (SMD) in post-treatment scores between groups. A total of 17 RCTs (N=1,806) were included. We found no evidence of an improvement with acupuncture relative to sham acupuncture on symptom severity (SMD=-0.11, 95% confidence interval (95% CI): -0.35 to 0.13; 4 RCTs) or quality of life (SMD=-0.03, 95% CI: -0.27 to 0.22; 3 RCTs). Because of the homogeneity of the results of the sham-controlled trials, results were unaffected by restriction to the four sham-controlled RCTs that used adequate randomization, blinding, and had few withdrawals/dropouts. Among RCTs that did not use a placebo control, acupuncture was more effective than pharmacological therapy (RR of symptom improvement=1.28, 95% CI: 1.12 to 1.45; 5 RCTs) and no (specific) treatment (RR = 2.11, 95% CI: 1.18 to 3.79; 2 RCTs). There was no difference between acupuncture and Bifidobacterium (RR=1.07, 95% CI: 0.90 to 1.27; 2 RCTs) or between acupuncture and psychotherapy (RR=1.05, 95% CI: 0.87 to 1.26; 1 RCT). Acupuncture as an adjuvant to another Chinese medicine treatment was statistically significantly better than the other treatment alone, in trials with a high risk of bias (RR=1.17, 95% CI: 1.02 to 1.33; 4 RCTs). Sham-controlled RCTs have found no benefits of acupuncture relative to a credible sham acupuncture control on IBS symptom severity or IBS-related quality of life. In comparative effectiveness Chinese trials, patients reported greater benefits from acupuncture than from pharmacological therapies. Future trials may help clarify whether or not these reportedly greater benefits of acupuncture relative to pharmacological therapies are due entirely to patients' preferences for acupuncture or patients' greater expectations of improvement on acupuncture relative to drugs.