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Pain Medicine (Malden, Mass.) Apr 2012To compare placebo responses in neuropathic pain syndromes. (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVE
To compare placebo responses in neuropathic pain syndromes.
DESIGN
Systematic literature review and meta-analysis.
SETTING AND PATIENTS
Randomized placebo-controlled trials assessing pain intensity or pain relief in any neuropathic pain syndrome published since 1995 with ≥5days follow-up.
INTERVENTIONS
Placebo response.
OUTCOME MEASURES
Pain intensity and responder rates (proportion reporting ≥50% pain relief). Meta-regression models were built.
RESULTS
Ninety-four studies (N=5,317) were included in the pain intensity analysis; 47 studies (N=3,087) were included in the responder analysis. After controlling for potential confounders (e.g., subject characteristics, study design characteristics), the placebo response was found to be large and varied with the pain syndrome. Compared with diabetic neuropathic/polyneuropathic pain (DPN), the placebo response for a decline in pain intensity and responder rate was smaller in trials that assessed central pain and postherpetic neuralgia (PHN) and larger in trials that assessed HIV pain. The model-predicted mean decrease (95% confidence interval [CI]) from baseline in pain intensity (0-10 scale) was as follows: DPN, 1.45 (1.35 to 1.55); PHN, 1.16 (1.03 to 1.29); central pain, 0.44 (-0.41 to 1.30); HIV pain, 1.82 (1.51 to 2.12). The predicted responder rates (95% CI) were as follows: DPN, 20% (14.6 to 25.8); PHN, 11.5% (8.4 to 14.5); central pain, 7.2% (2.1 to 12.3); HIV pain, 42.8% (34.9 to 50.7). The type of treatment in the active arm also influenced the placebo response.
CONCLUSIONS
Placebo response is influenced by the pain syndrome evaluated. These differences should be considered when evaluating novel compounds for the treatment of neuropathic pain conditions.
Topics: Diabetic Neuropathies; Humans; Neuralgia; Neuralgia, Postherpetic; Pain Perception; Placebos; Randomized Controlled Trials as Topic
PubMed: 22390269
DOI: 10.1111/j.1526-4637.2012.01340.x -
The Cochrane Database of Systematic... Oct 2013Progesterone, a female sex hormone, is known to induce secretory changes in the lining of the uterus essential for successful implantation of a fertilized egg. It has... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Progesterone, a female sex hormone, is known to induce secretory changes in the lining of the uterus essential for successful implantation of a fertilized egg. It has been suggested that a causative factor in many cases of miscarriage may be inadequate secretion of progesterone. Therefore, progestogens have been used, beginning in the first trimester of pregnancy, in an attempt to prevent spontaneous miscarriage.
OBJECTIVES
To determine the efficacy and safety of progestogens as a preventative therapy against miscarriage.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (1 August 2013), reference lists from relevant articles, attempting to contact authors where necessary, and contacted experts in the field for unpublished works.
SELECTION CRITERIA
Randomized or quasi-randomized controlled trials comparing progestogens with placebo or no treatment given in an effort to prevent miscarriage.
DATA COLLECTION AND ANALYSIS
Two review authors assessed trial quality and extracted data.
MAIN RESULTS
Fourteen trials (2158 women) are included. The meta-analysis of all women, regardless of gravidity and number of previous miscarriages, showed no statistically significant difference in the risk of miscarriage between progestogen and placebo or no treatment groups (Peto odds ratio (Peto OR) 0.99; 95% confidence interval (CI) 0.78 to 1.24) and no statistically significant difference in the incidence of adverse effect in either mother or baby.A subgroup analysis of placebo controlled trials did not find a difference in the rate of miscarriage with the use of progestogen (10 trials, 1028 women; Peto OR 1.15; 95% CI 0.88 to 1.50).In a subgroup analysis of four trials involving women who had recurrent miscarriages (three or more consecutive miscarriages; four trials, 225 women), progestogen treatment showed a statistically significant decrease in miscarriage rate compared to placebo or no treatment (Peto OR 0.39; 95% CI 0.21 to 0.72). However, these four trials were of poorer methodological quality. No statistically significant differences were found between the route of administration of progestogen (oral, intramuscular, vaginal) versus placebo or no treatment. No significant differences in the rates of preterm birth, neonatal death, or fetal genital anomalies/virilization were found between progestogen therapy versus placebo/control.
AUTHORS' CONCLUSIONS
There is no evidence to support the routine use of progestogen to prevent miscarriage in early to mid-pregnancy. However, there seems to be evidence of benefit in women with a history of recurrent miscarriage. Treatment for these women may be warranted given the reduced rates of miscarriage in the treatment group and the finding of no statistically significant difference between treatment and control groups in rates of adverse effects suffered by either mother or baby in the available evidence. Larger trials are currently underway to inform treatment for this group of women.
Topics: Abortion, Habitual; Abortion, Spontaneous; Female; Humans; Pregnancy; Pregnancy Trimester, Second; Progestins; Randomized Controlled Trials as Topic
PubMed: 24173668
DOI: 10.1002/14651858.CD003511.pub3 -
Anesthesiology Oct 2013Epidural steroid injection is the most frequently performed pain procedure. This study of epidural steroid "control" injections aimed to determine whether epidural... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Epidural steroid injection is the most frequently performed pain procedure. This study of epidural steroid "control" injections aimed to determine whether epidural nonsteroid injections constitute a treatment or true placebo in comparison with nonepidural injections for back and neck pain treatment.
METHODS
This systematic review with direct and indirect meta-analyses used PubMed and EMBASE searches from inception through October 2012 without language restrictions. Study selection included randomized controlled trials with a treatment group receiving epidural injections of corticosteroids or another analgesic and study control groups receiving either an epidural injection devoid of treatment drug or a nonepidural injection. Two reviewers independently extracted data including short-term (up to 12 weeks) pain scores and pain outcomes. All reviewers evaluated studies for eligibility and quality.
RESULTS
A total of 3,641 patients from 43 studies were included in this systematic review and meta-analysis. Indirect comparisons suggested epidural nonsteroid were more likely than nonepidural injections to achieve positive outcomes (risk ratio, 2.17; 95% CI, 1.87-2.53) and provide greater pain score reduction (mean difference, -0.15; 95% CI, -0.55 to 0.25). In the very limited direct comparisons, no significant differences were noted between epidural nonsteroid and nonepidural injections for either outcome (risk ratio [95% CI], 1.05 [0.88-1.25]; mean difference [95% CI], 0.22 [-0.50 to 0.94]).
CONCLUSION
Epidural nonsteroid injections may provide improved benefit compared with nonepidural injections on some measures, though few, low-quality studies directly compared controlled treatments, and only short-term outcomes (≤12 weeks) were examined.
Topics: Adrenal Cortex Hormones; Analgesics; Back Pain; Humans; Injections; Injections, Epidural; Neck Pain; Placebos; Randomized Controlled Trials as Topic
PubMed: 24195874
DOI: 10.1097/ALN.0b013e31829c2ddd -
Value in Health : the Journal of the... May 2022Emergence of severe acute respiratory syndrome coronavirus 2 infections and the resultant disease, COVID-19 led the world into 238 million cases and 4.8 million deaths...
OBJECTIVES
Emergence of severe acute respiratory syndrome coronavirus 2 infections and the resultant disease, COVID-19 led the world into 238 million cases and 4.8 million deaths over the first 22 months of the pandemic. While numerous vaccines have been developed to combat this pandemic, limited literature is available regarding the comparison of these vaccines. This study aims to systematically review and evaluate the immunogenicity and safety of COVID-19 vaccines compared with control arms in the healthy adult population.
METHODS
A literature search was conducted in PubMed, MEDLINE, Embase, and Cochrane up to July 4, 2021. Randomized controlled trials assessing the immunogenicity of any dose of COVID-19 vaccine in adults by anti-severe acute respiratory syndrome coronavirus 2 immunoglobulin G antibodies geometric mean titers (GMTs) and neutralizing antibodies GMT response at 28 days postimmunization compared with the control groups in the healthy adults were considered for inclusion. Groups at day 28 with the highest GMT were further examined for their adverse events.
RESULTS
Of the 341 citations retrieved, 19 were included. This covered a total of 16 vaccines involving 8342 subjects aged between 30.8 and 69.7 years, comprising 52.13% females. All studies reported GMT at or close to 28 days postvaccination compared with placebo and comparator, and 13 of 19 studies reported seroconversion rates. While 15 of 16 vaccines reported adverse events that ranged from mild to severe, 1 of 16 (AD26.COV2.S) noted 1 case of a vaccine-related serious adverse event-high fever 6 hours after vaccination. Local reactions (such as redness, pain, and swelling) and systematic reactions (such as fatigue, fever, and headache) were commonly noted. Safety between vaccines was similar; however, higher rates of severe adverse events were noted in Ad5-vectored COVID-19, AD26.COV2.S, ChAdOx nCoV-19, and mRNA-1273. No all-cause mortality was documented in any vaccines.
CONCLUSIONS
All 16 vaccines elicited an immune response substantially higher than the control groups while maintaining tolerable safety profiles.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Ad26COVS1; COVID-19; COVID-19 Vaccines; Vaccination; Vaccines; Randomized Controlled Trials as Topic
PubMed: 35500945
DOI: 10.1016/j.jval.2021.09.003 -
Journal of Trace Elements in Medicine... Apr 2013Impaired zinc metabolism is prominent in chronic disorders including cardiovascular disease and diabetes. Zinc has the potential to affect glucose homeostasis in animals... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Impaired zinc metabolism is prominent in chronic disorders including cardiovascular disease and diabetes. Zinc has the potential to affect glucose homeostasis in animals and humans and hence impact the risk of type 2 diabetes mellitus.
METHODS
A systematic review and meta-analysis of randomised placebo controlled trials was conducted to determine the effect of zinc supplementation on fasting blood glucose, HbA1c, serum insulin and serum zinc concentrations. Relevant studies for inclusion were identified from a literature search of electronic databases up to July 2011.
RESULTS
Fourteen reports (n=3978 subjects) were included in the meta-analysis. In the overall analysis, a small but statistically significant reduction in fasting glucose concentrations was observed (-0.19±0.08mmol/L, P=0.013) after zinc supplementation. HbA1c tended to decrease in zinc-supplemented individuals (-0.64±0.36%, P=0.072). No significant effect was observed for serum insulin concentrations. Plasma zinc concentrations increased significantly following supplementation (+4.03±0.81μmol/L, P=0.001). In secondary analyses of participants with chronic metabolic disease (types 1 and 2 diabetes mellitus, metabolic syndrome and obesity), zinc supplementation produced a greater reduction in glucose concentrations (-0.49±0.11mmol/L, P=0.001) compared to the effect that was observed in healthy participants.
CONCLUSION
The significant albeit modest reduction in glucose concentrations and tendency for a decrease in HbA1c following zinc supplementation suggest that zinc may contribute to the management of hyperglycemia in individuals with chronic metabolic disease.
Topics: Biomarkers; Blood Glucose; Dietary Supplements; Humans; Hyperglycemia; Models, Biological; Placebos; Randomized Controlled Trials as Topic; Zinc
PubMed: 23137858
DOI: 10.1016/j.jtemb.2012.08.001 -
JAMA Network Open Jan 2022Adverse events (AEs) after placebo treatment are common in randomized clinical drug trials. Systematic evidence regarding these nocebo responses in vaccine trials is... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Adverse events (AEs) after placebo treatment are common in randomized clinical drug trials. Systematic evidence regarding these nocebo responses in vaccine trials is important for COVID-19 vaccination worldwide especially because concern about AEs is reported to be a reason for vaccination hesitancy.
OBJECTIVE
To compare the frequencies of AEs reported in the placebo groups of COVID-19 vaccine trials with those reported in the vaccine groups.
DATA SOURCES
For this systematic review and meta-analysis, the Medline (PubMed) and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched systematically using medical subheading terms and free-text keywords for trials of COVID-19 vaccines published up to July 14, 2021.
STUDY SELECTION
Randomized clinical trials of COVID-19 vaccines that investigated adults aged 16 years or older were selected if they assessed solicited AEs within 7 days of injection, included an inert placebo arm, and provided AE reports for both the vaccine and placebo groups separately. Full texts were reviewed for eligibility by 2 independent reviewers.
DATA EXTRACTION AND SYNTHESIS
Data extraction and quality assessment were performed independently by 2 reviewers, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline and using the Cochrane risk-of-bias tool. Meta-analyses were based on random-effects models.
MAIN OUTCOMES AND MEASURES
The primary outcomes were the proportions of placebo recipients reporting overall, systemic, and local (injection-site) AEs as well as logarithmic odds ratios (ORs) to evaluate group differences. Outcomes were tested for significance using z tests with 95% CIs.
RESULTS
Twelve articles with AE reports for 45 380 participants (22 578 placebo recipients and 22 802 vaccine recipients) were analyzed. After the first dose, 35.2% (95% CI, 26.7%-43.7%) of placebo recipients experienced systemic AEs, with headache (19.3%; 95% CI, 13.6%-25.1%) and fatigue (16.7%; 95% CI, 9.8%-23.6%) being most common. After the second dose, 31.8% (95% CI, 28.7%-35.0%) of placebo recipients reported systemic AEs. The ratio between placebo and vaccine arms showed that nocebo responses accounted for 76.0% of systemic AEs after the first COVID-19 vaccine dose and for 51.8% after the second dose. Significantly more vaccine recipients reported AEs, but the group difference for systemic AEs was small after the first dose (OR, -0.47; 95% CI, -0.54 to -0.40; P < .001; standardized mean difference, -0.26; 95% CI, -0.30 to -0.22) and large after the second dose (OR, -1.36; 95% CI, -1.86 to -0.86; P < .001; standardized mean difference, -0.75; 95% CI, -1.03 to -0.47).
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis, significantly more AEs were reported in vaccine groups compared with placebo groups, but the rates of reported AEs in the placebo arms were still substantial. Public vaccination programs should consider these high rates of AEs in placebo arms.
Topics: Arm Injuries; COVID-19; COVID-19 Vaccines; Fatigue; Headache; Humans; Injections, Intramuscular; Placebos; SARS-CoV-2
PubMed: 35040967
DOI: 10.1001/jamanetworkopen.2021.43955 -
The Cochrane Database of Systematic... Oct 2014Stroke affects 15 million people per year worldwide. Despite recent developments in acute stroke treatment, prevention remains very important. Stroke has a high rate of... (Review)
Review
BACKGROUND
Stroke affects 15 million people per year worldwide. Despite recent developments in acute stroke treatment, prevention remains very important. Stroke has a high rate of recurrence; therefore secondary prevention is also important. Many clinical approaches to control risk factors have been proposed. One of these approaches is the prescription of beta-blockers that have effects beyond the reduction of blood pressure, which can reduce the recurrence of stroke.
OBJECTIVES
To evaluate the efficacy of beta-blockers for preventing stroke recurrence and for reducing death and major vascular events in people with a previous stroke or transient ischaemic attack (TIA), and to determine their safety, particularly with regard to the development of diabetes mellitus.
SEARCH METHODS
We searched the Cochrane Stroke Group Trials Register (May 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Database of Systematic Reviews (CDSR) (The Cochrane Library 2014, Issue 5), the Database of Abstracts of Reviews of Effects (DARE) (May 2014), MEDLINE (1966 to May 2014), EMBASE (1980 to May 2014), and Latin American and Caribbean Health Sciences Literature (LILACS) (1982 to May 2014). We also searched ongoing trials registers and reference lists.
SELECTION CRITERIA
Randomised controlled trials (RCTs) that included participants with previous stroke or TIA due to arterial thrombosis or embolism. The intervention was any beta-blocker versus control, or beta-blocker plus other treatment versus other treatment.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the trials identified, appraised quality, and extracted data.
MAIN RESULTS
We included two RCTs involving 2193 participants in the review. Both studies randomised participants to either beta-blocker (atenolol 5 mg) or placebo and were of a high methodological quality. We noted no statistical differences among the groups in risks of fatal and non-fatal stroke (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.76 to 1.18). For other outcomes analysed (major vascular events, death from all causes, death from cardiovascular causes) , we observed no significant differences between the groups. There were minor blood pressure reductions in the intervention group. Neither of the included studies reported the occurrence of diabetes among their outcomes or assessed quality of life. Adverse events were significantly more frequent in participants taking atenolol than in those given placebo, and were the most common reason given for discontinuing treatment (RR 1.85, 95% CI 1.45 to 2.35).
AUTHORS' CONCLUSIONS
To date, no available evidence supports the routine use of beta-blockers for secondary prevention after stroke or TIA. More studies with larger samples are needed.
Topics: Adrenergic beta-1 Receptor Antagonists; Atenolol; Humans; Ischemic Attack, Transient; Randomized Controlled Trials as Topic; Recurrence; Secondary Prevention; Stroke
PubMed: 25317988
DOI: 10.1002/14651858.CD007890.pub3 -
Acta Anaesthesiologica Scandinavica Nov 2014While post-operative pain routinely resolves, persistent post-surgical pain (PPSP) is common in certain surgeries; it causes disability, lowers quality of life and has... (Meta-Analysis)
Meta-Analysis Review
While post-operative pain routinely resolves, persistent post-surgical pain (PPSP) is common in certain surgeries; it causes disability, lowers quality of life and has economic consequences. The objectives of this systematic review and meta-analysis were to evaluate the effectiveness of ketamine in reducing the prevalence and severity of PPSP and to assess safety associated with its use. We searched the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE through December 2012 for articles in any language. We included randomized, controlled trials in adults in which ketamine was administered perioperatively via any route. Seventeen studies, the majority of which administered ketamine intravenously, met all inclusion criteria. The overall risk of developing PPSP was not significantly reduced at any time point in the ketamine group vs. placebo, nor did comparisons of pain severity scores reach statistical significance. Sensitivity analysis of exclusively intravenous ketamine studies included in this meta-analysis demonstrated statistically significant reductions in risk of developing PPSP at 3 and 6 months (P = 0.01 and P = 0.04, respectively). Adverse event rates were similar between ketamine and placebo groups. The study data from our review are heterogeneous and demonstrate efficacy of intravenously administered ketamine only in comparison with placebo. Highly variable timing and dosing of ketamine in these studies suggest that no unifying effective regimen has emerged. Future research should focus on clinically relevant outcomes, should stratify patients with pre-existing pain and possible central sensitization and should enroll sufficiently large numbers to account for loss to follow-up in long-term studies.
Topics: Anesthetics, Dissociative; Chronic Pain; Humans; Ketamine; Pain, Postoperative
PubMed: 25060512
DOI: 10.1111/aas.12377 -
BMJ (Clinical Research Ed.) Jan 2009To study the analgesic effect of acupuncture and placebo acupuncture and to explore whether the type of the placebo acupuncture is associated with the estimated effect... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To study the analgesic effect of acupuncture and placebo acupuncture and to explore whether the type of the placebo acupuncture is associated with the estimated effect of acupuncture.
DESIGN
Systematic review and meta-analysis of three armed randomised clinical trials.
DATA SOURCES
Cochrane Library, Medline, Embase, Biological Abstracts, and PsycLIT. Data extraction and analysis Standardised mean differences from each trial were used to estimate the effect of acupuncture and placebo acupuncture. The different types of placebo acupuncture were ranked from 1 to 5 according to assessment of the possibility of a physiological effect, and this ranking was meta-regressed with the effect of acupuncture.
DATA SYNTHESIS
Thirteen trials (3025 patients) involving a variety of pain conditions were eligible. The allocation of patients was adequately concealed in eight trials. The clinicians managing the acupuncture and placebo acupuncture treatments were not blinded in any of the trials. One clearly outlying trial (70 patients) was excluded. A small difference was found between acupuncture and placebo acupuncture: standardised mean difference -0.17 (95% confidence interval -0.26 to -0.08), corresponding to 4 mm (2 mm to 6 mm) on a 100 mm visual analogue scale. No statistically significant heterogeneity was present (P=0.10, I(2)=36%). A moderate difference was found between placebo acupuncture and no acupuncture: standardised mean difference -0.42 (-0.60 to -0.23). However, considerable heterogeneity (P<0.001, I(2)=66%) was also found, as large trials reported both small and large effects of placebo. No association was detected between the type of placebo acupuncture and the effect of acupuncture (P=0.60).
CONCLUSIONS
A small analgesic effect of acupuncture was found, which seems to lack clinical relevance and cannot be clearly distinguished from bias. Whether needling at acupuncture points, or at any site, reduces pain independently of the psychological impact of the treatment ritual is unclear.
Topics: Acupuncture Analgesia; Acupuncture Therapy; Humans; Pain; Placebos; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 19174438
DOI: 10.1136/bmj.a3115 -
Journal of Pharmacy & Pharmaceutical... 2012Recent investigations in finding new drugs in the treatment of diabetes have led to the discovery of several pathological pathways involved in diabetes. Exenatide a drug... (Comparative Study)
Comparative Study Meta-Analysis Review
Recent investigations in finding new drugs in the treatment of diabetes have led to the discovery of several pathological pathways involved in diabetes. Exenatide a drug with incretin mimetic activity was studied in several in vivo and in vitro as well as human studies. It has shown promising results in controlling metabolic indices in type-2 diabetes and was approved by FDA but still there is an active safety alert on it. In this study we aimed to meta-analyze all placebo-controlled clinical trials on the efficacy or tolerability of exenatide in type 2 diabetes. The literature search provided 1016 articles while only 14 articles were eligible to be included in the meta-analysis with a total of 2583 patients enrolled in the study. According to the wide variation in design of various studies, the study duration of 16 weeks and less or more and dose (5 μg bid versus 10 μg bid) were considered and analyzed. The results of this meta-analysis show that exenatide decreases fasting plasma glucose and HbA1C significantly regardless of dose and study duration. The effect of exenatide on weight reduction was more prominent at the dose of 10 μg bid regardless of the study duration, however at the dose of 5 μg bid, significant results were observed after drug administration for more than 16 weeks. Exenatide usage decreased serum triglycerides indifferent to dose and study duration while its effect on cholesterol was not prominent. Along with these impacts, exenatide changed LDL and HDL cholesterol at the lower dose. The hemodynamic effect of exenatide was observed as significant decrements in systolic and diastolic blood pressure at the higher dose. The risk of nausea, vomiting and hypoglycemia was significant and indifferent to dose while headache and nasopharyngaitis were seen more at lower dose. It is concluded that exenatide can be considered as a good hypoglycemic agent in type-2 diabetic patients with benefits on lipid profile and blood pressure with partially questionable tolerability.
Topics: Blood Glucose; Body Weight; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 2; Exenatide; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Peptides; Placebos; Randomized Controlled Trials as Topic; Systole; Venoms
PubMed: 22365085
DOI: 10.18433/j3g883