基于CONSORT与TIDieR-Placebo评价安慰针刺治疗偏头痛随机对照试验的文献报告质量

目的应用试验报告统一标准(Consolidated Standards for Reporting of Trials,CONSORT)与安慰措施描述规范清单(Template for Intervention Description and Replication-Placebo,TIDieR-Placebo)评价安慰针刺治疗偏头痛随机对照试验(Randomized controlled trials,RCT)的文献报告质量。通过评价结果讨论目前安慰针刺的运用现状,并为今后安慰针刺的试验设计提供参考。方法计算机检索中国期刊全文数据库(CNKI)、维普数据库(VIP)、万方数据资源系统(WF)、中国生物医学文献数据库(SinoMed)、PubMed、Embase、Web of Science(WOS),收集近10年使用单纯针刺与安慰针刺进行对比的针灸治疗偏头痛RCT研究,检索时限为2011年7月20日-2021年7月20日。应用CONSORT与TIDieR-Placebo评价文献报告的规范性,并对结果进行分析讨论。结果共纳入59篇文献。CONSORT评价结果显示报告率低于10%的条目为条目3b、6b、11b、12b、14b、16、17b、18、24。TIDieR-Placebo评价结果显示报告率低于10%的条目为条目6、7、9、10、13。安慰针刺的方式主要为“假穴假刺”、“假穴真刺”、“假穴浅刺”及“非治疗穴真刺”4种。结论目前安慰针刺治疗偏头痛RCT的文献报告质量总体不高,研究者未来应重视使用此两项清单对自身研究进行规范报告。大部分研究的安慰针刺设计方式尚缺合理性,亟需国内外在安慰针刺的设计和选择方面形成共识,以推动针灸临床研究的规范化。

Systematic review: The placebo effect of psychological interventions in the treatment of irritable bowel syndrome

AIM To determine the placebo response rate associated with different types of placebo interventions used in psychological intervention studies for irritable bowel syndrome. METHODS Randomized controlled trials comparing psychological interventions(stress management/relaxation therapy(cognitive) behavioral therapy, short-term psychodynamic therapy, and hypnotherapy) for the treatment of adult patients with irritable bowel syndrome(IBS) diagnosed with the Manning or Rome criteria with an adequate placebo control treatment and reporting data on IBS symptom severity were identified by searching Pub Med, Embase, the Cochrane Library, CINAHL and Psyc INFO databases. Full-text articles that were written in English and published between 1966 and February 2016 in peer-reviewed journals were selected for the present review. Placebo interventions were considered to be adequate if the number of sessions and the amount of time spent with the therapist were the same as in the active treatment. The placebo response rate(PRR) was computed for IBS symptom severity(primary outcome measure) as well as for anxiety, depression and quality of life(secondary outcome measures). RESULTS Six studies, with a total of 555 patients met the inclusion criteria. Four studies used an educational intervention, whereas two studies used a form of supportive therapy as the placebo intervention. The PRR for IBS symptom severity ranged from 25% to 59%, with a pooled mean of 41.4%. The relative PRR for the secondary outcome measures ranged from 0% to 267% for anxiety, 6% to 52% for depression 20% to 125% for quality of life. The PRR associated with pharmacological treatments, treatment with dietary bran and complementary medicine ranged from 37.5% to 47%. Contrary to our expectations, the PRR in studies on psychological interventions was comparable to that in studies on pharmacological, dietary and alternative medical interventions.CONCLUSION The PRR is probably determined to a larger extent by patient-related factors, such as expectations and desire for the treatment to be effective, than the content of the placebo intervention.

Effect of probiotics on length of hospitalization in mild acute pancreatitis:A randomized,double-blind,placebo-controlled trial

BACKGROUND Acute pancreatitis is the leading cause of hospitalization for acute gastrointestinal disease worldwide.The effects of probiotics in mild acute pancreatitis have not been studied.We hypothesized that the administration of probiotics may accelerate the recovery of intestinal function and shorten the length of hospital stay(LOS)in patients with mild pancreatitis.AIM To investigate the value of probiotics in reducing the LOS in patients with mild acute pancreatitis.METHODS We conducted a double-blind randomized clinical trial to evaluate the effects of probiotics administered to patients with mild acute pancreatitis at a tertiary medical center.The patients were given probiotics capsules(a mixed preparation of Bacillus subtilis and Enterococcus faecium)or placebo.The primary study endpoint was the LOS.The secondary endpoints included time to abdominal pain relief,recurrent abdominal pain,and time to successful oral feeding.RESULTS A total of 128 patients were included,with 64 patients in each arm.The severity of illness and the etiological distribution of disease were similar in the two groups.There was a significant reduction in the LOS in the probiotics treatment group vs the placebo group(5.36±0.15 vs 6.02±0.17 d,P<0.05).The probiotics group was associated with a shorter time to abdominal pain relief and time to successful oral feeding(P<0.01 for both)than the placebo group.No statistical difference was found in recurrent abdominal pain between the two groups.CONCLUSION The study results showed that the administration of probiotics capsules is associated with a shorter duration of hospitalization in patients with mild acute pancreatitis.

Early mortality of alcoholic hepatitis: A review of data from placebo-controlled clinical trials

AIM: To investigate the early mortality of placebo-treated alcoholic hepatitis patients. METHODS: Mortality data about alcoholic hepatitis patients who participated in randomized placebo-controlled trials were searched from PubMed, EMBASE, and Cochrane Library, extracted and analyzed. RESULTS: A total of 661 placebo-treated patients in 19 trials were included. The overall mortality rate was 34.19% with a median observation time of 160 d (range 21-720 d). Hepatic failure, gastrointestinal bleeding and infection were the three main causes of death, accounting for 55.47%, 21.17% and 7.30% of all deaths, respectively. One-month mortality data about 324 placebo-treated alcoholic hepatitis patients in 10 trials were reported with a pooled mortality rate of 20.37%. The one-month mortality rate of patients with moderate to severe alcoholic hepatitis tended to be higherthan that of general patients (22.69% vs 10.93%, P < 0.05), whereas no signifi cant difference was observed between the patients from North America or Europe (22.43% vs 18.45%, P > 0.05), neither any difference was found between the studies published before and after 1990 (18.18% vs 21.88%, P > 0.05). CONCLUSION: Alcoholic hepatitis is a severe liver disease with a high mortality rate, and hepatic failure, gastrointestinal bleeding and infection are the three main causes of death.

Efficacy of Chinese herbal medicine in functional dyspepsia: A meta-analysis of randomized, double-blind, placebo-controlled trials

Objective:To evaluate the efficacy and safety of Chinese herbal medicine(CHM)for the treatment of functional dyspepsia(FD).Methods:Web of Science,PubMed,EMBASE,Cochrane Library,and four other Chinese electronic databases,including China National Knowledge Infrastructure(CNKI),Chinese Biological Medical Database(CBM),Chinese Scientific Journals Database(VIP),and WanFang Database were used to search(up to Feb,2016)for randomized,double-blind,placebocontrolled trials recruiting adults with FD treated with CHM.Study selection,data extraction,quality assessment,and data analyses were conducted based on Cochrane standards using Review Manager software.Results:Fourteen publications(1424 patients)were included.Evidence revealed that CHM was more efficacious than the placebo in improving global dyspepsia symptoms(RR,1.45;95%CI,1.31e1.60),Chinese medicine syndrome(CMS)(RR,1.36;95%CI,1.23e1.50),and quality of life(SMD,0.30;95%CI,0.15e0.45)in FD patients.Furthermore,the difference in the incidence of adverse events between CHM and placebo groups had no statistical significance(RR,1.06;95%CI,0.66e1.70).Conclusion:This meta-analysis demonstrates that CHM has a therapeutic potential in treating FD with a certain safety.However,due to the restricted number of trials included,wellplanned,long-term studies are necessary to provide credible evidence.

A Double-Blind, Randomized, Placebo-Controlled Nutritional Study Using an Insoluble Yeast Beta-Glucan to Improve the Immune Defense System

Purpose: In a placebo-controlled, double-blind, randomized clinical trial, the effect of an insoluble yeast beta-glucan preparation on the incidences of common colds and its effect on common cold symptoms were compared to placebo. Methods: 100 healthy participants with recurring infections were randomly assigned to receive either placebo or yeast beta-glucan (Yestimun?;n = 50 each group) over a period of 26 weeks. The subjects had to document each common cold episode in a diary, and rate 6 predefined infections symptoms on a 3-point rating scale during an infection period, resulting in an infection score. The common cold episodes were confirmed by the investigators. Results: A total of 171 common cold episodes were documented. Of these, 76 were experienced by 38 subjects in the beta-glucan group and 96 were experienced by 48 subjects in the placebo group (p = 0.406). The beta-glucan group had significantly more subjects without incidences of common cold than the placebo group (15.6% vs 2.0%;p = 0.019). During the most intense infection season (first 13 weeks of the study), the beta-glucan group had significantly less infections compared to placebo (p = 0.02). Beta-glucan significantly reduced the typical cold symptoms (“sore throat and/or difficulty swallowing”, “hoarseness and/or cough” and “runny nose”) as opposed to placebo. Conclusion: The present study demonstrates a prophylactic effect of yeast beta-glucan on the occurrence of common colds as opposed to placebo. In addition, when these episodes occurred, they were from the beginning less pronounced and subsided faster.

Efficacy and Safety of Vortioxetine and Duloxetine 60 mg Compared Placebo for the Treatment of Major Depressive Disorder: A Systematic Review and Meta-Analysis

Background: Major depressive disorder is a serious public health problem affecting the lives of millions in the worldwide and leading causes of disability and disease. This study aimed to evaluate the efficacy and safety of Vortioxetine and Duloxetine 60 mg compared to placebo for the treatment of major depressive disorder. Method: We searched the Cochrane library, Pub Med, CRD, Scopus, and Central Register of Controlled Trials to January 2015. We also searched ClinicalTrials.gov, International depressive disorder Conference and the Anxiety Disorders and Depression Conference. We identified that five randomized clinical trials were ultimately included in a Meta analysis. Data analysis was conducted by Standardized Mean Differences (SMD) for Montgomery-&Aring;sberg Depression Rating Scale (MADRS), and Odds Ratio (OR) for adverse events. The SMD and OR reported by 95% CI. Results: Results showed statistical significance in the MADRS for Vortioxetine (SMD = ﹣3.29;95% CI ﹣4.47 to ﹣2.10;I2 = 99.3%) and for Duloxetine 60 mg (SMD = ﹣6.35;95% CI ﹣8.84, ﹣3.87;I2 = 99.3%). Results showed that the Vortioxetine 2.5, 5, 10, 15, 20 mg and overall compared to placebo showed a significance for Nausea and no significance for diarrhea, dry mouth, dizziness, fatigue and headache. Also results of Duloxetine 60 mg showed a significant effect for dry mouth, dizziness, fatigue and nausea. Conclusion: It is necessary to do more studies so as to better assess and much more powerful than the evidence for the use of this drug in the treatment of depression.

Placebo effect in osteoarthritis: Why not use it to our advantage?

Osteoarthritis is a major cause of pain and reduced quality of life in the elderly, as well as a major economic burden. Unfortunately, there is no currently effective therapeutic strategy to prevent the progression of Osteoarthritis, and its treatment poses a great challenge to the medical community. Most of the treatment modalities currently available for osteoarthritis have small to moderate effect sizes, according to main metaanalyses and treatment guidelines. On the other hand, literature has demonstrated that placebo is considerablyeffective. The present article discusses the history of placebo effect and its scientific evidence, comments on ethical issues and provides insights about how it may be used to our advantage when treating osteoarthritic patients.

PAID study design on the role of PKC activation in immune/inflammation-related depression:a randomised placebo-controlled trial protocol

Background Inflammation that is mediated by microglia activation plays an important role in the pathogenesis of depression.Microglia activation can lead to an increase in the levels of proinflammatory cytokines,including TNF-α,which leads to neuronal apoptosis in the specific neural circuits of some brain regions,abnormal cognition and treatment-resistant depression(TRD).Protein kinase C(PKC)is a key regulator of the microglia activation process.We assume that the abnormality in PKC might result in abnormal microglia activation,neuronal apoptosis,significant changes in emotional and cognitive neural circuits,and TRD.In the current study,we plan to target at the PKC signal pathway to improve the TRD treatment outcome.Methods and analysis This is a 12-week,ongoing,randomised,placebo-controlled trial.Patients with TRD(N=180)were recruited from Shanghai Mental Health Center,Shanghai Jiao Tong University.Healthy control volunteers(N=60)were recruited by advertisement.Patients with TRD were randomly assigned to‘escitalopram+golimumab(TNF-αinhibitor)’,‘escitalopram+calcium tablet+vitamin D(PKC activator)’or‘escitalopram+placebo’groups.We define the primary outcome as changes in the 17-item Hamilton Depression Rating Scale(HAMD-17).The secondary outcome is defined as changes in anti-inflammatory effects,cognitive function and quality of life.Discussion This study might be the first randomised,placebo-controlled trial to target at the PKC signal pathway in patients with TRD.Our study might help to propose individualised treatment strategies for depression.Trial registration number The trial protocol is registered with ClinicalTrials.gov under protocol ID 81930033 and ClinicalTrials.gov ID NCT04156425.

The effects of traditional medicine in health care:placebo or body-mind therapy?

Chronic diseases such as Alzheimer's disease (AD), diabetes and scapulohumeral periarthritis present a special challenge to clinicians because of high incidence, lethality and disability which directly result in the economical and family burden. The current special issue of'health care and rehabilitation'mainly focuses on the area of traditional medicine therapy to chronic diseases. The following six papers cover three different methods of traditional medicine therapy including drug therapy, non-drug therapy and manipulation therapy.

Misunderstanding of a New Approach to Drug-Placebo Difference Calculation in Short Term Antidepressant-Drug Trials

In clinical trials, drug effect is measured by a difference between subjects who are treated by experimental drug against placebo-treated subjects. In case of binary data, with observing YES/NO on each subject in certain period of time, it is the proportion of subjects who respond in treatment group minus the proportion of responders in placebo group (for example, 50% vs. 30%). However, a greater difference was proposed by Rihmer et al. (2011) [1] with their supporting arguments, in that antidepressant response and placebo response had different mechanisms and there were equal chances for antidepressant responder to be responding to placebo and not responding to placebo at all. Therefore, the authors proposed 50% - 30% * 50% when the response rate in the treatment group and the placebo group are 50% and 30% respectively, resulting in higher drug-placebo difference than traditional understanding of 50% - 30%. In this article, we tried to explain why the authors misunderstood the drug-placebo concept for evaluating drug superiority, their misunderstanding of assumptions of traditional calculation, as well as their wrong reasoning on their proposed approach. All in all, we conclude the traditional approach of 50% - 30% is the right way of evaluating drug-placebo difference and the possible methods to control impact of placebo effect are briefly discussed at the end of this article.

The ethical dilemma of placebo use in clinical practice

The clinical use of placebo that involves some ethical issues has led to much controversy.From the standpoint of both supporters and opponents,this article discusses this topic from three ethical principles such as beneficence,justice,and autonomy and also gives the recommendations.Finally,the moral dilemma caused by the different views between nurses and doctors in clinical practice is discussed.

Scalp Psoriasis: Systematic Review Comparing Topical Treatments and Placebo

Patients with scalp psoriasis suffered from a lower quality of life relating to the highly visible site of their psoriatic lesions. In consequence this fact stimulates investigations involving treatments of this dermatologic disease. The aim of this review is to evaluate the topical treatments for scalp psoriasis compared with placebos. Methods: A systematic review was performed using searches in the database LILACS, MEDLINE, Cochrane Library, and Embase. As selection criteria were chosen eligible publications involving randomized controlled trials, patients with scalp psoriasis diagnosed clinically or by biopsy, interventions with topical treatments for scalp psoriasis compared with placebo. Outcome related to the reduction in severity of psoriasis of the scalp, assessed by physicians and patients, and assessment of adverse effects that required discontinuation of treatment. The results have shown that the patients were aged 12 to 97 years, including 3441 patients. Ten of the fifteen studies included reported gender data. Patients were mostly female. Twelve studies were about psoriasis’s severity. These studies in which the severity has been described, the classification of severity was mild (0 study), mild to moderate (1 study), moderate to severe (11 studies) and severe (0 study). In conclusion, topical corticosteroids, calcipotriol, ciclopirox olamine and associations between them are effective in the treatment of scalp psoriasis. Clobetasol propionate (0.05%) was the most effective active ingredient in several vehicles in the induction treatment of scalp psoriasis.

Tolerability of a Proprietary Larch Arabinogalactan Extract: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial in Healthy Subjects

In a placebo-controlled, double-blind, randomized clinical trial, the tolerability of a proprietary larch arabinogalactan preparation (ResistAidTM) was investigated. METHODS: 199 healthy participants were randomly assigned to receive either placebo (n = 98) or an arabinogalactan preparation (n = 101) over a period of 12 weeks. As safety parameters the total number of adverse events, changes in various biochemical and laboratory parameters as well as the global evaluation of tolerability by investigator and subjects compared to placebo were evaluated. RESULTS: In total 16 adverse events were observed in 16 subjects, with no difference between the arabinogalactan and the placebo group (p = 0.935). There were no differences in the mean changes of the measured biochemical and laboratory parameters. The tolerability of the arabinogalactan extract was rated as “very good” or “good” by the investigators for 99% of the subjects and by 98% subjects in self-assessment with no statistical differences to placebo. CONCLUSION: The measured parameters as well as the evaluation of the tolerability by the investigators and the subjects demonstrate a very good tolerance profile of the proprietary arabinogalactan extract with no differences to placebo when taken for 12 weeks.

Effect of <i>Lactobacillus brevis</i>SBC8803 on Gamma-Glutamyl Transferase in Japanese Habitual Drinkers: A Double-Blind, Placebo-Controlled Study

A randomized, double-blind, placebo-controlled clinical trial in Japanese habitual drinkers was conducted to evaluate the efficacy of Lactobacillus brevis SBC8803 to alleviate adverse effect of alcohol. Subjects who drank habitually and had moderately higher levels of gamma-glutamyl transferase (GGT) (50 - 100 IU/L) were enrolled. The levels of transaminases in these subjects were almost within normal levels (aspartate transaminase (AST) <30 IU/L and alanine transaminase (ALT) <40 IU/L). Either the capsules containing placebo (n = 23) or 130 mg (4.0 × 1010 colony-forming units) of live L. brevis SBC8803 (n = 22) per day were administered for the continuous eight weeks (56 days). During the period, the subjects both in test group and placebo groups have kept each drinking behavior as usual. Regarding lipid metabolism, triacylglycerol (TG) levels in the male test group significantly decreased at week 4 as compared with week 0. Biomarkers of hepatocytes-damage;AST and ALT levels showed no significant differences between the pla- cebo and test groups at both weeks 4 and 8. Oxidative stress marker;GGT at weeks 4 was significantly lower in the test group than that in the placebo group (p = 0.017), but not at weeks 8. However, taking a reduced rate of GGT at weeks 8 comparing with that at week 0, that in the test group showed larger value comparing with that in the placebo group. These data about TG and GGT suggest that, although efficacy of L. brevis SBC8803 is limited in this study, intake of the probiotic may alleviate alcoholic influence in lipid metabolism and oxidative stress.

Efficacy of the adjuvanted subunit protein COVID-19 vaccine,SCB-2019:a phase 2 and 3 multicentre,double-blind,randomised,placebo-controlled trial

Background:A range of safe and effective vaccines against SARS CoV 2 are needed to address the COVID 19 pandemic.We aimed to assess the safety and efficacy of the COVID-19 vaccine SCB-2019.Methods:This ongoing phase 2 and 3 double-blind,placebo-controlled trial was done in adults aged 18 years and older who were in good health or with a stable chronic health condition,at 31 sites in five countries(Belgium,Brazil,Colombia,Philippines.

Placebo responses in patients with gastrointestinal disorders

Over the last several years there has been a growing interest in placebo, not only as an inert control in clinical trials, but also in the placebo effect as a group effect as well as a reaction in individual subjects. Methodological factors such as regression to the mean and natural history of the disease play a role in the evaluation of a possible placebo effect. In this report, we discuss several factors including Pavlovian conditioning, beliefs outcome, expectations, and other factors as potential mediators of the placebo response. Placebo effects are common in gastrointestinal diseases and there seems to be no clear difference between placebo effects in functional gastrointestinal diseases (functional dyspepsia and irritable bowel syndrome) and organic gastrointestinal disease (duodenal ulcer and inflammatory bowel disease).

Comparison of exogenous melatonin versus placebo on sleep efficiency in emergency medicine residents working night shifts： A randomized trial

BACKGROUND: Sleep deprivation resulting from night shifts, is a major cause of burnout among physicians. Exogenous melatonin may improve sleep quality in night-shift workers. The study aims to compare the effectiveness of melatonin versus placebo on sleep effi ciency in emergency medicine(EM) residents. METHODS: A randomized, double-blind, replicated crossover trial was performed on EM residents. This study consisted of 4 phases within a month with intervention periods of 2 nights and washouts of 6 days. In our study, EM residents had nine-hour shifts on 6 consecutive days, 2 mornings, 2 evenings and 2 nights and then 2 days off. At the end of shifts' cycle, 24 EM residents were given 3 mg melatonin or placebo(12 in each arm of the study) for 2 consecutive nights after the second night shift with crossover to the other arm after a six-day off drug. This crossover intervention was repeated for two more another time. Finally, we created 48 cases and comparisons in each arm. Different items related to sleep quality were assessed and compared both within the same group and between the two groups. RESULTS: In the melatonin group, daytime sleepiness(calculated by Karolinska Sleep Scale) had a signifi cant reduction after taking the second dose of drug(P=0.003) but the same result was not observed when comparing the 2 groups. Mood status(calculated by Profile of Mood States) showed no remarkable difference between the 2 groups. CONCLUSION: Melatonin might have a limited benefi t on sleep quality in EM residents working night shifts.

Rotigotine in the Treatment of Primary Restless Legs Syndrome:A Meta-analysis of Randomized Placebo-controlled Trials

The aim of this study was to summarize the efficacy and tolerability of rotigotine in the treatment of primary restless legs syndrome(RLS). Pub Med, EMBASE, and Cochrane Central Register of Controlled Trials(CENTRAL) were searched for English-language randomized controlled trials(RCTs) that assessed the effectiveness of rotigotine for RLS. The pooled mean change from baseline in International RLS(IRLS) Study Group Rating Scalescore and relative risk(RR) of response based on the Clinical Global Impression-Improvement(CGI-I) scale score were applied to evaluate the outcomes. The pooled proportions of adverse events(AEs) were also estimated. Six RCTs were included. The meta-analysis showed a favorable effectiveness of rotigotine versus placebo on RLS [mean change on IRLS score: mean difference(MD)=–4.80; 95% confidence interval(CI): –5.90 to –3.70; P<0.00001 and RR of response on CGI-I was 2.19; 95% CI: 1.86 to 2.58, P<0.00001]. The most common AEs were application site reactions, nausea, headache and fatigue. In general, rotigotine was well-tolerated in patients with primary RLS. Based on the findings from the meta-analysis, rotigotine was more significantly efficacious in the treatment of RLS than placebo. Nevertheless, long-term studies and more evidence of comparisons of rotigotine with other dopamine agonists are needed.

Design flaws in randomized, placebo controlled, double blind clinical trials

The hypothesis in drug clinical trials is that the drug is better than a placebo in patients suffering from a disease. The unstated assumption is that the drug cures the disease or is a powerful treatment for the disease. This is an incorrect assumption. Drugs do not cure or treat diseases. The body heals itself; drugs promote this ability of the body to heal itself. Placebos are assumed to be inactive; however, placebos can also promote the ability of the body to heal itself. Placebos are actually treatments that can stimulate endogenous healing mechanisms. The possible place of placebos in health management is controversial. Clinical trial design should be altered. The hypothesis of clinical trials should be that the drug speeds up or improves the healing of the patient, putting patient healing as the first objective. Placebos should not be used as controls but could be tested as drugs in their own right. The control in clinical trials should be no treatment. Alternatively, new drugs could be compared to existing drugs in clinical trials.