Placebo and nocebo responses in restless legs syndrome

Neurology ◽  
2017 ◽  
Vol 88 (23) ◽  
pp. 2216-2224 ◽  
Author(s):  
Maria A. Silva ◽  
Gonçalo S. Duarte ◽  
Raquel Camara ◽  
Filipe B. Rodrigues ◽  
Ricardo M. Fernandes ◽  
...  
Keyword(s):  
Adverse Events ◽  
Restless Legs Syndrome ◽  
Meta Analysis ◽  
Placebo Response ◽  
Controlled Trials ◽  
Pool Data ◽  
Double Blind ◽  
Restless Legs ◽  
Statistical Heterogeneity ◽  
Registration Number

Objective:To estimate the placebo and nocebo responses in restless legs syndrome (RLS) and explore their determinants.Methods:Databases were searched up to October 2015. Randomized, double-blind, placebo-controlled trials of patients with RLS were included if quantitative data were extractable in the placebo arm. Placebo response was defined as the within-group change from baseline, using any scale measuring RLS severity or disability. Nocebo response was defined as the proportion of patients experiencing adverse events in the placebo arm. Random-effects meta-analysis was used to pool data. Statistical heterogeneity was assessed with I2 statistic. Several predetermined subgroup and sensitivity analysis were performed. PROSPERO registration number is CRD42015027992.Results:We included 85 randomized controlled trials (5,046 participants). Pooled placebo response effect size was −1.41 (95% confidence interval [CI] −1.56 to −1.25, 64 trials, I2 = 88.1%), corresponding to −6.58 points in the International RLS Study Group Scale (IRLS). Pooled nocebo response was 45.36% (95% CI 40.47%–50.29%, 72 trials; I2 = 89.8%). The placebo and nocebo responses were greater in trials with longer duration, evaluating pharmacologic interventions and idiopathic RLS, and in industry-funded and unpublished studies. The placebo response was considerably smaller in objective as compared to subjective outcomes. In addition, the nocebo response increases proportionally with the placebo response, and has the same predictors.Conclusions:The magnitude of the placebo response in RLS is above the threshold of minimal clinical important difference, and the frequency of adverse events is also considerable. These results are relevant to inform the design and interpretation of future clinical trials.

Pharmacological Treatment of Osteoporosis in Elderly People: A Systematic Review and Meta-Analysis

Gerontology ◽  
2021 ◽  
pp. 1-11
Author(s):  
Qin-Yi Wang ◽  
Na Ding ◽  
Yi-He Dong ◽  
Zhang-Xin Wen ◽  
Rong Chen ◽  
...  
Keyword(s):  
Adverse Events ◽  
Elderly Patients ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Anabolic Agents ◽  
Double Blind ◽  
Antiresorptive Agents ◽  
Statistical Heterogeneity ◽  
Post Hoc

<b><i>Background:</i></b> The evidence supporting the use of antiresorptive and anabolic agents for fracture prevention in elderly patients is still inconclusive. Whether it is too late to alter the course of the disease in this age-group has remained uncertain. <b><i>Objectives:</i></b> The objective of this study was to determine the efficacy and safety of antiresorptive and anabolic agents in elderly patients. <b><i>Methods:</i></b> PubMed, Web of Science, MEDLINE, and the Cochrane Central Register of Controlled Trials were searched for randomized controlled trials (RCTs) and post hoc analyses of RCTs reporting efficacy outcomes or adverse events of antiresorptive and anabolic agents in elderly patients. Statistical heterogeneity was assessed with the Cochran <i>Q</i> χ<sup>2</sup> test and <i>I</i><sup>2</sup> statistic. All results were expressed as relative risk (RR) with 95% confidence intervals (CIs). <b><i>Results:</i></b> The meta-analysis included 1 RCT and 11 post hoc analyses of data from 10 double-blind placebo-controlled RCTs. Antiresorptive therapy significantly reduced the pooled incidence of vertebral fractures (RR = 0.43; 95% CI = 0.35–0.53; and <i>p</i> &#x3c; 0.001). It was also associated with lower risk of nonvertebral and hip fractures (RR = 0.84; 95% CI = 0.74–0.96; and <i>p</i> = 0.009 and RR = 0.75; 95% CI = 0.58–0.97; and <i>p</i> = 0.028, respectively). For any adverse events, no difference was observed between antiresorptive agents and placebo groups (RR = 1.01; 95% CI = 1.00–1.02; and <i>p</i> = 0.23). <b><i>Conclusions:</i></b> Both antiresorptive and anabolic agents represented potentially important osteoporosis treatments, showing significant effects on reducing vertebral, nonvertebral, or hip fracture risk, and were well-tolerated by elderly patients. Even in the elderly, maybe it is not too late to alter the course of the disease.

scholarly journals Efficacy and Safety of Remdesivir for COVID-19 Treatment: An Analysis of Randomized, Double-Blind, Placebo-Controlled Trials

2020 ◽  
Author(s):  
Yun Zhu ◽  
Zhaowei Teng ◽  
Lirong Yang ◽  
Shuanglan Xu ◽  
Jie Liu ◽  
...  
Keyword(s):  
Adverse Events ◽  
Discharge Rate ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Randomized Controlled ◽  
Central Register ◽  
Registration Number

AbstractBACKGROUNDRemdesivir, an inhibitor of viral RNA-dependent RNA polymerases, has been identified as a candidate for COVID-19 treatment. However, the therapeutic effect of remdesivir is controversial.METHODSWe searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials, from inception to June 11, 2020 for randomized controlled trials on the clinical efficacy of remdesivir. The main outcomes were discharge rate, mortality, and adverse events. This study is registered at INPLASY (INPLASY202060046).RESULTSData of 1075 subjects showed that remdesivir significantly increased the discharge rate of patients with COVID-19 compared with the placebo (50.4% vs. 45.29%; relative risk [RR] 1.19 [95% confidence interval [CI], 1.05–1.34], I2 = 0.0%, P = 0.754). It also significantly decreased mortality (8.18% vs. 12.70%; RR 0.64 [95% CI, 0.44–0.92], I2 = 45.7%, P = 0.175) compared to the placebo. Data of 1296 subjects showed that remdesivir significantly decreased the occurrence of serious adverse events (RR 0.77 [95% CI, 0.63–0.94], I2 = 0.0%, P = 0.716).CONCLUSIONRemdesivir is efficacious and safe for the treatment of COVID-19.TRIAL REGISTRATION NUMBERThis study is registered at the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY202060046).

scholarly journals Efficacy and safety of guselkumab for the treatment of patients with moderate-to-severe plaque psoriasis: A metaanalysis of randomized clinical trials

2020 ◽  
Vol 19 (2) ◽  
pp. 433-440
Author(s):  
Xing-Bao Tao ◽  
Yin-Qiu Huang ◽  
Yi-Hong Zhou ◽  
Lv-Lang Zhang ◽  
Yao-Kai Chen
Keyword(s):  
Quality Of Life ◽  
Clinical Trials ◽  
Adverse Events ◽  
Plaque Psoriasis ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Double Blind ◽  
Severe Plaque Psoriasis ◽  
Central Registry

Purpose: To conduct a systematic analysis on data from randomized controlled trials (RCTs) on different doses of guselkumab, and provide high-quality evidence for its use in the treatment of patients with moderate-to-severe plaque psoriasis (PsO). Methods: Related studies were searched using online search engines including MEDLINE, PubMed, and central registry of Cochrane controlled trials from January 2001 to October 2017. Only randomized, placebo-controlled, double-blind clinical trials involving guselkumab- and placebo-treated PsO subjects were included. Results: Five eligible double-blind, randomized, and placebo-controlled trials involving patients with moderate-to-severe PsO subjects treated with guselkumab were included. Compared with the placebo groups, the proportion of patients with improvements in Psoriasis Area and Severity Index (PASI) 75 (RR= 12.14; 95% CI= 9.11-16.16; p < 0.001); PASI 90 (RR= 23.26; 95% CI =14.57-37.13; p < 0.001), and PASI 100 (RR = 37.66; 95% CI = 15.81-89.69; p < 0.001) were significantly higher than those in guselkumab-treated groups. Furthermore, the guselkumab-treated groups showed significant decreases in Physician’s Global Assessment (PGA) score (RR = 10.46; 95% CI = 7.96-13.83; p < 0.001) and the Dermatology Life Quality Index (DLQI) score (SMD = -1.3; 95% CL = -1.4 to -1.19; p < 0.001), when compared with the placebo groups. However, there were no significant differences in adverse events (AEs) (RR = 1.01; 95% CL = 0.93-1.11; p > 0.05); severe adverse events (SAEs) (RR = 1.32; 95% CI =0.69-2.54; p > 0.05) and study discontinuations (RR = 0.79; 95% CI = 0.42-1.48; p > 0.05) between the two groups. Conclusion: This meta-analysis summarizes available evidence for the use of guselkumab in psoriasis. The results suggest that guselkumab is superior to placebo in moderate-to-severe psoriasis, and is welltolerated, effective, and safe in improving the severity of disease and quality of life. Keywords: Guselkumab, Effectiveness, Safety, Plaque psoriasis, Meta-analysis, Quality of life

Efficacy and safety of extended-release amantadine in levodopa-induced dyskinesias: a meta-analysis

2019 ◽  
Vol 9 (4) ◽  
pp. 205-215 ◽  
Author(s):  
Azalea T Pajo ◽  
Adrian I Espiritu ◽  
Roland Dominic G Jamora
Keyword(s):  
Adverse Events ◽  
Extended Release ◽  
Meta Analysis ◽  
Mean Difference ◽  
Controlled Trials ◽  
Visual Hallucinations ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Parallel Group ◽  
Troublesome Dyskinesia

Aim: To determine the effectiveness and safety of extended-release amantadine (ADS-5102) for levodopa-induced dyskinesias (LID) in patients with Parkinson disease (PD) by conducting a meta-analysis of relevant trials. Methods: The electronic databases were searched on or before March 1, 2019 for relevant trials. Only randomized, double-blind, parallel-group, placebo-controlled trials using ADS-5102 for LID in PD were included. Results: The ADS-5102 showed a reduction in the dyskinesia scores (mean difference: -9.56: CI: -10.05 to -9.07; p < 0.00001) and in the on time without troublesome dyskinesia (mean difference 2.50: CI 2.38 to 2.63; p < 0.00001). The adverse events identified in ADS-5102 were visual hallucinations, constipation, dry mouth and fall. Conclusion: ADS-5102 can be used as an adjunct therapy for LID.

Effect of Aerobic Exercise on Dialysis-Related Symptoms in Individuals Undergoing Maintenance Hemodialysis

2021 ◽  
Vol 16 (4) ◽  
pp. 560-574
Author(s):  
Nicholas Hargrove ◽  
Nada El Tobgy ◽  
Olivia Zhou ◽  
Mark Pinder ◽  
Brittany Plant ◽  
...  
Keyword(s):  
Aerobic Exercise ◽  
Randomized Controlled Trials ◽  
Beck Depression Inventory ◽  
Restless Legs Syndrome ◽  
Meta Analysis ◽  
Maintenance Hemodialysis ◽  
Controlled Trials ◽  
Exercise Interventions ◽  
Restless Legs ◽  
Randomized Controlled

BackgroundHemodialysis is associated with a high symptom burden that impairs health-related quality of life and functional status. Effective symptom management is a priority for individuals receiving hemodialysis. Aerobic exercise may be an effective, nonpharmacologic treatment for specific hemodialysis-related symptoms. This systematic review investigated the effect of aerobic exercise on hemodialysis-related symptoms in adults with kidney failure undergoing maintenance hemodialysis.Design, setting, participants, & measurementsWe searched MEDLINE, PubMed, Cochrane CENTRAL, CINAHL, PsycINFO, SPORTDiscus, EMBASE, PEDro, and Scopus databases from 1960 or inception until April 15, 2020 for randomized controlled trials investigating the effect of aerobic exercise on hemodialysis-related symptoms, identified as prespecified primary or secondary outcomes, as compared with controls in adults on maintenance hemodialysis. We identified restless legs syndrome as the primary outcome.ResultsOf 3048 studies identified, 15 randomized controlled trials met the eligibility criteria. These studies investigated the effect of aerobic exercise on restless legs syndrome (two studies), sleep disturbance (four studies), anxiety (four studies), depression (nine studies), muscle cramping (one study), and fatigue (one study). Exercise interventions were intradialytic in ten studies and outside of hemodialysis in five studies. Heterogenous interventions and outcomes and moderate to high risk of bias precluded meta-analysis for most symptoms. Aerobic exercise demonstrated improvement in symptoms of restless legs syndrome, muscle cramping, and fatigue, as compared with nonexercise controls. Meta-analysis of depressive symptoms in studies using the Beck Depression Inventory demonstrated a greater reduction in Beck Depression Inventory score with exercise as compared with control (mean difference −7.57; 95% confidence interval, −8.25 to −6.89).ConclusionsOur review suggests that in adults on maintenance hemodialysis, aerobic exercise improves several hemodialysis-related symptoms, including restless legs syndrome, symptoms of depression, muscle cramping, and fatigue. However, the use of validated outcome measures with demonstrated reliability and responsiveness in more diverse hemodialysis populations is required to fully characterize the effect of this intervention.Clinical Trial registry name and registration number:PROSPERO #CRD42017056658

scholarly journals Effectiveness and adverse events of topical and allergen immunotherapy for atopic dermatitis: a systematic review and network meta-analysis protocol

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Luis Guillermo Gómez-Escobar ◽  
Hansel Mora-Ochoa ◽  
Andrea Vargas Villanueva ◽  
Loukia Spineli ◽  
Gloria Sanclemente ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Systematic Review ◽  
Atopic Dermatitis ◽  
Adverse Events ◽  
Random Effects ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Allergen Specific Immunotherapy ◽  
Statistical Heterogeneity

Abstract Background Atopic dermatitis (AD) is an inflammatory chronic condition that affects the skin of children and adults and has an important impact on the quality of life. Treatments for AD are based on environmental controls, topical and systemic therapies, and allergen-specific immunotherapy (AIT). However, it remains unclear the effectiveness and adverse events of AIT and all conventional topical treatments compared with placebo and each other for AD. Methods We will search five electronic databases [Central Cochrane register of controlled trials (CENTRAL), MEDLINE, EMBASE, CINAHL, and LILACS] from inception until November 2019 with no language restriction, and we will include experimental studies [randomized controlled trials (RCTs), and quasi-RCTs]. The primary outcome is global and specific skin symptoms assessment. Secondary outcomes are hospital length of stay, quality of life, and adverse events. Reviewers independently will extract data from the studies that meet our inclusion criteria and will assess the risk of bias of individual primary studies. We will conduct random effects pairwise meta-analyses for the observed pairwise comparisons with at least two trials. Then, we will perform random-effects Bayesian network meta-analysis (NMA) to obtain treatment effects for all possible comparisons and to provide a hierarchy of all interventions for each outcome. Possible incoherence between direct and indirect sources of evidence will be investigated locally (if possible) and globally. To investigate sources of statistical heterogeneity, we will perform a series of meta-regression analyses based on pre-specified important effect modifiers. Two authors will appraise the certainty of the evidence for each outcome applying the GRADE’s framework for NMA. Discussion The findings of this systematic review will shed the light on the effectiveness and adverse events of all possible comparisons for treating AD and on the quality of the collated evidence for recommendations. It will also provide critical information to health care professionals to comprehend and manage this disease at different age stages, treatment type, duration, and severity of atopic dermatitis. Systematic review registration PROSPERO Protocol ID CRD42019147106

scholarly journals Intranasal Ketamine for Depression in Adults: A Systematic Review and Meta-Analysis of Randomized, Double-Blind, Placebo-Controlled Trials

2021 ◽  
Vol 12 ◽  
Author(s):  
Dongjiao An ◽  
Changwei Wei ◽  
Jing Wang ◽  
Anshi Wu
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Clinical Response ◽  
Clinical Remission ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Major Depressive ◽  
Double Blind ◽  
Madrs Score ◽  
Randomized Controlled

BackgroundThere is growing interest in glutamatergic agents as a treatment for depression, especially intranasal ketamine, which has become a hot topic in recent years. We aim to assess the efficacy and safety of intranasal ketamine in the treatment of major depressive disorder (MDD), especially treatment-resistant depression (TRD).MethodsWe searched Medline, EMBASE, and the Cochrane Library until April 1, 2020 to identify double-blind, randomized controlled trials with allocation concealment evaluating intranasal ketamine in major depressive episodes. Clinical remission, response, and depressive symptoms were extracted by two independent raters. The outcome measures were Montgomery–Asberg Depression Rating Scale (MADRS) score improved from baseline, clinical response and remission, dissociative symptoms, and common adverse events. The analyses employed a random-effects model.ResultsData were synthesized from five randomized controlled trials (RCTs) employing an intranasal esketamine and one RCT employing intranasal ketamine, representing 840 subjects in parallel arms, and 18 subjects in cross-over designs (n = 858 with MDD, n = 792 with TRD). The weighted mean difference of MADRS score was observed to decrease by 6.16 (95% CI 4.44–7.88) in 2–4 h, 9.96 (95% CI 8.97–10.95) in 24 h, and 4.09 (95% CI 2.18–6.00) in 28 day. The pooled relative risk (RR) was 3.55 (95% CI 1.5–8.38, z = 2.89, and p &lt; 0.001) for clinical remission and 3.22 (95% CI 1.85–5.61, z = 4.14, and p &lt; 0.001) for clinical response at 24 h, while the pooled RR was 1.7 (95% CI 1.28–2.24, z = 3.72, and p &lt; 0.001) for clinical remission and 1.48 (95% CI 1.17–1.86, z = 3.28, and p &lt; 0.001) for clinical response at 28 day. Intranasal ketamine was associated with the occurrence of transient dissociative symptoms and common adverse events, but no persistent psychoses or affective switches.ConclusionOur meta-analysis suggests that repeated intranasal ketamine conducted a fast-onset antidepression effect in unipolar depression, while the mild and transient adverse effects were acceptable.Systematic Review RegistrationPROSPERO, CRD42020196856.

Sign in / Sign up

Export Citation Format

Share Document