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Annals of Internal Medicine Jan 2015The relative efficacy of available treatments of knee osteoarthritis (OA) must be determined for rational treatment algorithms to be formulated. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The relative efficacy of available treatments of knee osteoarthritis (OA) must be determined for rational treatment algorithms to be formulated.
PURPOSE
To examine the efficacy of treatments of primary knee OA using a network meta-analysis design, which estimates relative effects of all treatments against each other.
DATA SOURCES
MEDLINE, EMBASE, Web of Science, Google Scholar, Cochrane Central Register of Controlled Trials from inception through 15 August 2014, and unpublished data.
STUDY SELECTION
Randomized trials of adults with knee OA comparing 2 or more of the following: acetaminophen, diclofenac, ibuprofen, naproxen, celecoxib, intra-articular (IA) corticosteroids, IA hyaluronic acid, oral placebo, and IA placebo.
DATA EXTRACTION
Two reviewers independently abstracted study data and assessed study quality. Standardized mean differences were calculated for pain, function, and stiffness at 3-month follow-up.
DATA SYNTHESIS
Network meta-analysis was performed using a Bayesian random-effects model; 137 studies comprising 33,243 participants were identified. For pain, all interventions significantly outperformed oral placebo, with effect sizes from 0.63 (95% credible interval [CrI], 0.39 to 0.88) for the most efficacious treatment (hyaluronic acid) to 0.18 (CrI, 0.04 to 0.33) for the least efficacious treatment (acetaminophen). For function, all interventions except IA corticosteroids were significantly superior to oral placebo. For stiffness, most of the treatments did not significantly differ from one another.
LIMITATION
Lack of long-term data, inadequate reporting of safety data, possible publication bias, and few head-to-head comparisons.
CONCLUSION
This method allowed comparison of common treatments of knee OA according to their relative efficacy. Intra-articular treatments were superior to nonsteroidal anti-inflammatory drugs, possibly because of the integrated IA placebo effect. Small but robust differences were observed between active treatments. All treatments except acetaminophen showed clinically significant improvement from baseline pain. This information, along with the safety profiles and relative costs of included treatments, will be helpful for individualized patient care decisions.
PRIMARY FUNDING SOURCE
Agency for Healthcare Research and Quality.
Topics: Acetaminophen; Adrenal Cortex Hormones; Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Steroidal; Celecoxib; Cyclooxygenase 2 Inhibitors; Diclofenac; Humans; Hyaluronic Acid; Ibuprofen; Injections, Intra-Articular; Naproxen; Osteoarthritis, Knee; Pain; Pyrazoles; Sulfonamides; Treatment Outcome; Viscosupplements
PubMed: 25560713
DOI: 10.7326/M14-1231 -
Medicine Aug 2016Placebo, defined as "false treatment," is a common gold-standard method to assess the validity of a therapy both in pharmacological trials and manual medicine research... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Placebo, defined as "false treatment," is a common gold-standard method to assess the validity of a therapy both in pharmacological trials and manual medicine research where placebo is also referred to as "sham therapy." In the medical literature, guidelines have been proposed on how to conduct robust placebo-controlled trials, but mainly in a drug-based scenario. In contrast, there are not precise guidelines on how to conduct a placebo-controlled in manual medicine trials (particularly osteopathy). The aim of the present systematic review was to report how and what type of sham methods, dosage, operator characteristics, and patient types were used in osteopathic clinical trials and, eventually, assess sham clinical effectiveness.
METHODS
A systematic Cochrane-based review was conducted by analyzing the osteopathic trials that used both manual and nonmanual placebo control. Searches were conducted on 8 databases from journal inception to December 2015 using a pragmatic literature search approach. Two independent reviewers conducted the study selection and data extraction for each study. The risk of bias was evaluated according to the Cochrane methods.
RESULTS
A total of 64 studies were eligible for analysis collecting a total of 5024 participants. More than half (43 studies) used a manual placebo; 9 studies used a nonmanual placebo; and 12 studies used both manual and nonmanual placebo. Data showed lack of reporting sham therapy information across studies. Risk of bias analysis demonstrated a high risk of bias for allocation, blinding of personnel and participants, selective, and other bias. To explore the clinical effects of sham therapies used, a quantitative analysis was planned. However, due to the high heterogeneity of sham approaches used no further analyses were performed.
CONCLUSION
High heterogeneity regarding placebo used between studies, lack of reporting information on placebo methods and within-study variability between sham and real treatment procedures suggest prudence in reading and interpreting study findings in manual osteopathic randomized controlled trials (RCTs). Efforts must be made to promote guidelines to design the most reliable placebo for manual RCTs as a means of increasing the internal validity and improve external validity of findings.
Topics: Controlled Clinical Trials as Topic; Humans; Osteopathic Medicine; Placebo Effect
PubMed: 27583913
DOI: 10.1097/MD.0000000000004728 -
PloS One 2015The tolerability of oral iron supplementation for the treatment of iron deficiency anemia is disputed. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The tolerability of oral iron supplementation for the treatment of iron deficiency anemia is disputed.
OBJECTIVE
Our aim was to quantify the odds of GI side-effects in adults related to current gold standard oral iron therapy, namely ferrous sulfate.
METHODS
Systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating GI side-effects that included ferrous sulfate and a comparator that was either placebo or intravenous (i.v.) iron. Random effects meta-analysis modelling was undertaken and study heterogeneity was summarised using I2 statistics.
RESULTS
Forty three trials comprising 6831 adult participants were included. Twenty trials (n = 3168) had a placebo arm and twenty three trials (n = 3663) had an active comparator arm of i.v. iron. Ferrous sulfate supplementation significantly increased risk of GI side-effects versus placebo with an odds ratio (OR) of 2.32 [95% CI 1.74-3.08, p<0.0001, I2 = 53.6%] and versus i.v. iron with an OR of 3.05 [95% CI 2.07-4.48, p<0.0001, I2 = 41.6%]. Subgroup analysis in IBD patients showed a similar effect versus i.v. iron (OR = 3.14, 95% CI 1.34-7.36, p = 0.008, I2 = 0%). Likewise, subgroup analysis of pooled data from 7 RCTs in pregnant women (n = 1028) showed a statistically significant increased risk of GI side-effects for ferrous sulfate although there was marked heterogeneity in the data (OR = 3.33, 95% CI 1.19-9.28, p = 0.02, I2 = 66.1%). Meta-regression did not provide significant evidence of an association between the study OR and the iron dose.
CONCLUSIONS
Our meta-analysis confirms that ferrous sulfate is associated with a significant increase in gastrointestinal-specific side-effects but does not find a relationship with dose.
Topics: Anemia, Iron-Deficiency; Clinical Trials as Topic; Databases, Factual; Dietary Supplements; Ferrous Compounds; Gastrointestinal Diseases; Humans; Odds Ratio; Placebo Effect
PubMed: 25700159
DOI: 10.1371/journal.pone.0117383 -
Homeopathy : the Journal of the Faculty... Apr 2010Like other forms of medicine, including Complementary and Alternative Medicine (CAM), homeopathy elicits expectations in patients. The physician-patient relationship,... (Review)
Review
BACKGROUND
Like other forms of medicine, including Complementary and Alternative Medicine (CAM), homeopathy elicits expectations in patients. The physician-patient relationship, personal and comprehensive treatment and lack of adverse effects are elements in creating positive expectations. Other elements may be associated with negative expectations.
METHODS
We conducted a systematic literature review on placebo and nocebo effects in acupuncture and homeopathy using Medline.
RESULTS
Findings on the psychophysiological and neuromediating mechanisms of the placebo-nocebo phenomenon are reviewed. Studies of these effects reveal how expectations and unconscious conditioning can be measured by imaging and EEG methods. They result in significant, non-specific therapeutic effects, which may confuse the evaluation of the specific therapeutic effects treatment, hampering selection of the simillimum.
CONCLUSIONS
Directions for future research on non-specific therapeutic effects of homeopathy to improve clinical practice and clinical research are discussed.
Topics: Acupuncture Therapy; Brain; Clinical Trials as Topic; Depressive Disorder, Major; Homeopathy; Humans; Pain; Parkinson Disease; Placebo Effect
PubMed: 20471615
DOI: 10.1016/j.homp.2010.02.001 -
Complementary Therapies in Clinical... Nov 2023To understand the placebo response of acupuncture and its effect on migraine and optimize the design of future acupuncture clinical trials on migraine treatment. (Meta-Analysis)
Meta-Analysis Review
AIM
To understand the placebo response of acupuncture and its effect on migraine and optimize the design of future acupuncture clinical trials on migraine treatment.
METHODS
Randomized controlled trials with sham acupuncture as a control in migraine treatment were searched in four English databases from inception to September 1, 2022. The primary outcome was placebo response rate. Secondary outcomes were migraine symptoms, emotional condition, and quality of life. Factors associated with placebo response were also explored. Results were combined using risk difference (RD) or standardized mean difference (SMD) and 95% confidence interval (CI) with a random effects model.
RESULTS
The final analysis included 21 studies involving 1177 patients. The pooled response rate of sham acupuncture was 0.34 (RD, 95% CI 0.23-0.45, I 89.8%). The results (SMD [95% CI]) showed significant improvements in migraine symptoms (pain intensity -0.56 [-0.73 to -0.38], and episode conditions -0.55 [-0.75 to -0.35]); emotional condition (anxiety scale -0.49 [-0.90 to -0.08] and depression scale -0.21 [-0.40 to -0.03]); and quality of life on the Migraine-Specific Quality-of-Life Questionnaire (restrictive 0.78 [0.61-0.95]; preventive 0.52 [0.35-0.68]; and emotional 0.45 [0.28-0.62]) and on the Medical Outcomes Study Short-Form (physical 0.48 [0.34-0.62] and mental 0.21 [0.02-0.41]). Only acupuncture treatment frequency had a significant impact on the placebo response rate (RD 0.49 vs. 0.14; p = 0.00).
CONCLUSIONS
The effect sizes for placebo response of sham acupuncture varied across migraine treatment trials. Further studies should routinely consider adjusting for a more complete set of treatment factors.
Topics: Humans; Quality of Life; Acupuncture Therapy; Migraine Disorders; Outcome Assessment, Health Care; Placebo Effect; Randomized Controlled Trials as Topic
PubMed: 37793307
DOI: 10.1016/j.ctcp.2023.101800 -
Journal of Clinical Epidemiology Apr 2015It has been suggested that some placebo interventions might be associated with larger clinical effects than others. In a systematic review, we investigated whether there... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
It has been suggested that some placebo interventions might be associated with larger clinical effects than others. In a systematic review, we investigated whether there is evidence from direct comparisons in randomized clinical trials including two or more placebo groups supporting this hypothesis.
STUDY DESIGN AND SETTING
Eligible trials were identified through electronic database searches and citation tracking up to February 2013. Placebo interventions in a trial were categorized into a more intense and a less intense intervention based on complexity, invasiveness, or route of administration and time needed for application.
RESULTS
Twelve studies with 1,059 patients receiving placebo met the eligibility criteria. Studies were highly heterogeneous regarding patients, interventions, outcomes, and risk of bias. Seven studies did not find any significant differences between the more intense and the less intense placebo intervention, four studies found differences for single outcomes, and one study consistently reported significantly larger effects of the more intense placebo. An explorative meta-analysis yielded a standardized mean difference -0.22 (95% confidence interval: -0.46, 0.02; P = 0.07; I(2) = 68%).
CONCLUSION
In the studies included in this review, more intense placebos were not consistently associated with larger effects than less intense placebos.
Topics: Humans; Placebo Effect; Placebos; Randomized Controlled Trials as Topic
PubMed: 25639981
DOI: 10.1016/j.jclinepi.2014.11.018 -
Nutrients Nov 2019Isoflavones have gained popularity as an alternative treatment for menopausal symptoms for people who cannot or are unwilling to take hormone replacement therapy....
Isoflavones have gained popularity as an alternative treatment for menopausal symptoms for people who cannot or are unwilling to take hormone replacement therapy. However, there is still no consensus on the effects of isoflavones despite over two decades of vigorous research. This systematic review aims to summarize the current literature on isoflavone supplements, focusing on the active ingredients daidzein, genistein, and S-equol, and provide a framework to guide future research. We performed a literature search in Ovid Medline using the search terms "isoflavone" and "menopause", which yielded 95 abstracts and 68 full-text articles. We found that isoflavones reduce hot flashes even accounting for placebo effect, attenuate lumbar spine bone mineral density (BMD) loss, show beneficial effects on systolic blood pressure during early menopause, and improve glycemic control in vitro. There are currently no conclusive benefits of isoflavones on urogenital symptoms and cognition. Due to the lack of standardized research protocols including isoflavone component and dosage, outcomes, and trial duration, it is difficult to reach a conclusion at this point in time. Despite these limitations, the evidence thus far favors the use of isoflavones due to their safety profile and benefit to overall health.
Topics: Dietary Supplements; Female; Humans; Isoflavones; Menopause
PubMed: 31689947
DOI: 10.3390/nu11112649 -
Acta Neurologica Belgica Jun 2019Nocebo refers to the adverse events (AEs) experienced when taking a placebo drug and is believed to be a centrally mediated process. We sought to examine the AEs... (Meta-Analysis)
Meta-Analysis
Nocebo refers to the adverse events (AEs) experienced when taking a placebo drug and is believed to be a centrally mediated process. We sought to examine the AEs following placebo administration in Randomised Controlled Trials (RCTs) for Myasthenia Gravis (MG) patients. A systematic literature search was performed on Medline and Web of Science for RCTs for MG pharmacological treatments. We assessed the number of placebo-treated patients reporting at least one AE and the number of dropouts because of AEs. Data were extracted from six RCTs fulfilling the search criteria. Four out of five placebo-treated participants (80.1%) reported at least one AE and one in 40 (2.4%) discontinued placebo treatment because of AE. All patients participating in the MG trials reported similar AEs independent of the study arm to which they belonged (placebo or active treatment). This meta-analysis demonstrates a low nocebo dropout rate in MG compared to central nervous system disorders.
Topics: Clinical Trials as Topic; Drug-Related Side Effects and Adverse Reactions; Humans; MEDLINE; Myasthenia Gravis; Nocebo Effect; Placebos
PubMed: 31004288
DOI: 10.1007/s13760-019-01143-1 -
The Journal of Sexual Medicine Jun 2014It is not known if statins will improve symptoms in patients with established erectile dysfunction (ED). (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
It is not known if statins will improve symptoms in patients with established erectile dysfunction (ED).
AIM
We carried out a systematic review and meta-analysis to assess the effect of statins on ED.
METHODS
A literature review was performed to identify all published randomized double-blind, placebo-controlled trials of statins for the treatment of ED. The search included the following databases: MEDLINE, Embase, and the Cochrane Controlled Trials Register. The reference lists of the retrieved studies were also investigated. A systematic review and meta-analysis were conducted.
MAIN OUTCOME MEASURES
Six publications involving a total of 462 patients were used in the analysis, including three randomized controlled trials (RCTs) that compared statins with placebo and three RCTs that compared statins plus sildenafil with placebo plus sildenafil.
RESULTS
For the comparison of statins (+/- sildenafil) with placebo (+/- sildenafil), the mean International Index of Erectile Function (IIEF-5) (the standardized mean difference [SMD] = 3.23, 95% confidence interval [CI] = -1.65 to 4.80, P < 0.0001) indicated that statins (+/- sildenafil) showed statistically significantly greater improvements in the mean IIEF-5 compared with placebo (+/- sildenafil). For the comparison of statins with placebo, the mean IIEF-5 (SMD = 2.13, 95% CI = -1.46 to 5.73, P = 0.24) indicated that there was no significant difference in erectile function between the statins and placebo. For the comparison of statins plus sildenafil with placebo plus sildenafil, the mean IIEF-5 (SMD = 3.60, 95% CI = 2.64 to 4.56, P < 0.00001), the IIEF domain (SMD = 4.88, 95%CI = 3.01 to 6.74, P < 0.00001), and the global efficacy question (odds ratio = 6.44, 95% CI = 2.92 to 14.23, P < 0.00001) showed that compared with placebo plus sildenafil, statins plus sildenafil clearly improved erectile function.
CONCLUSIONS
This meta-analysis indicates that statins (+/- sildenafil) may improve ED compared with placebo (+/- sildenafil).
Topics: Adult; Aged; Double-Blind Method; Drug Therapy, Combination; Erectile Dysfunction; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Randomized Controlled Trials as Topic; Sildenafil Citrate; Sulfones; Treatment Outcome
PubMed: 24628781
DOI: 10.1111/jsm.12497 -
EClinicalMedicine Aug 2023Refractory chronic cough (RCC) has a significant impact on patient's health-related quality of life and represents a challenge in clinical management. However, the...
BACKGROUND
Refractory chronic cough (RCC) has a significant impact on patient's health-related quality of life and represents a challenge in clinical management. However, the optimal treatment for RCC remains controversial. This study aimed to investigate and compare the efficacy and safety of the current pharmacological therapeutic options for RCC.
METHODS
A systematic review was performed by searching PubMed, Web of Science, Embase, and Ovid databases from January 1, 2008 to March 1, 2023. All randomised control trials (RCTs) reporting outcomes of efficacy or/and safety were included in the Bayesian network meta-analysis. Here, we compared the effects on Leicester Cough Questionnaire (LCQ), Visual Analogue Scale (VAS), and objective cough frequency of patients with RCC. Besides, we also compared the incidence of adverse events (AEs) for analysis of safety. PROSPERO registration: CRD42022345940.
FINDINGS
19 eligible RCTs included 3326 patients and 7 medication categories: P2X3 antagonist, GABA modulator, Transient Receptor Potential (TRP) modulator, NK-1 agonist, opioid analgesic, macrolide, and sodium cromoglicate. Compared with placebo, mean difference (MD) of LCQ and 24 h cough frequency for P2X3 antagonist relief were 1.637 (95% CI: 0.887-2.387) and -11.042 (P = 0.035). Compared with placebo, effect sizes (MD for LCQ and cough severity VAS) for GABA modulator were 1.347 (P = 0.003) and -7.843 (P = 0.003). In the network meta-analysis, gefapixant is the most effective treatment for patients with RCC (The Surface Under the Cumulative Ranking Curves (SUCRA) is 0.711 in LCQ, 0.983 in 24 h cough frequency, and 0.786 in cough severity VAS). Lesogaberan had better efficacy than placebo (SUCRA: 0.632 vs. 0.472) in 24 h cough frequency. Eliapixant and lesogaberan had better efficacy than placebo in cough severity VAS. However, TRP modulator had worse efficacy than placebo. In the meta-analysis of AEs, the present study found P2X3 antagonist had a significant correlation to AEs (RR: 1.129, 95% CI: 1.012-1.259), especially taste-related AEs (RR: 6.216, P < 0.05).
INTERPRETATION
In this network meta-analysis, P2X3 antagonist showing advantages in terms of efficacy is currently the most promising medication for treatment of RCC. GABA modulator also showed potential efficacy for RCC but with AEs of the central system. Nevertheless, the role of TRP modulator needed to be revisited. Further research is needed to determine the potential beneficiary population for optimizing the pharmacological management of chronic cough.
FUNDING
National Natural Science Foundation of China (81870079), Guangdong Science and Technology Project (2021A050520012), Incubation Program of National Science Foundation for Distinguished Young Scholars (GMU2020-207).
PubMed: 37538538
DOI: 10.1016/j.eclinm.2023.102100