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The Cochrane Database of Systematic... May 2018Many people with schizophrenia do not reach a satisfactory clinical response with a standard dose of an initially prescribed antipsychotic drug. In such cases,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Many people with schizophrenia do not reach a satisfactory clinical response with a standard dose of an initially prescribed antipsychotic drug. In such cases, clinicians face the dilemma of increasing the antipsychotic dose in order to enhance antipsychotic efficacy.
OBJECTIVES
To examine the efficacy of increasing antipsychotic dose compared to keeping the same dose in the treatment of people with schizophrenia who have not responded (as defined in the individual studies) to an initial antipsychotic drug trial. We also examine the adverse effects associated with such a procedure.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group Trials Register (10 June 2014, 6 October 2015, and 30 March 2017). We examined references of all included studies for further trials.
SELECTION CRITERIA
All relevant randomised controlled trials (RCTs), reporting useable data, comparing increasing the antipsychotic dose rather than maintaining the original dose for people with schizophrenia who do not respond to their initial antipsychotic treatment.
DATA COLLECTION AND ANALYSIS
At least two review authors independently extracted data . We analysed dichotomous data using relative risks (RR) and the 95% confidence intervals (CI). We analysed continuous data using mean differences (MD) and their 95% CI. We assessed risk of bias for included studies and used GRADE to create a 'Summary of findings' table.
MAIN RESULTS
Ten relevant RCTs with 675 participants are included in this review. All trials were double blind except one single blind. All studies had a run-in phase to confirm they did not respond to their initial antipsychotic treatment. The trials were published between 1980 and 2016. In most studies the methods of randomisation, allocation and blinding were poorly reported. In addition sample sizes were often small, limiting the overall quality of the evidence. Overall, no clear difference was found between groups in terms of the number of participants who showed clinically relevant response (RR 1.09, 95% CI 0.86 to 1.40, 9 RCTs, N = 533, low-quality evidence), or left the study early due to adverse effects (RR 1.63, 95% CI 0.52 to 5.07, very low quality evidence), or due to any reason (RR 1.30, 95% CI 0.89 to 1.90, 5 RCTs, N = 353, low-quality evidence). Similarly, no clear difference was found in general mental state as measured by PANSS total score change (MD -1.44, 95% CI -6.85 to 3.97, 3 RCTs, N = 258, very low quality evidence). At least one adverse effect was equivocal between groups (RR 0.91, 95% CI 0.55 to 1.50, 2 RCTs, N = 191, very low quality evidence). Data were not reported for time in hospital or quality-of-life outcomes. Finally, subgroup and sensitivity analyses did not show any effect on the primary outcome but these analyses were clearly underpowered.
AUTHORS' CONCLUSIONS
Current data do not show any clear differences between increasing or maintaining the antipsychotic dose for people with schizophrenia who do not respond to their initial antipsychotic treatment. Adverse effect reporting was limited and poor. There is an urgent need for further trials in order to determine the optional treatment strategy in such cases.
Topics: Antipsychotic Agents; Double-Blind Method; Humans; Randomized Controlled Trials as Topic; Schizophrenia; Single-Blind Method; Treatment Outcome
PubMed: 29750432
DOI: 10.1002/14651858.CD011883.pub2 -
Journal of the Royal Society of Medicine Oct 2016To quantify the risk of suicidality and violence when selective serotonin and serotonin-norepinephrine reuptake inhibitors are given to adult healthy volunteers with no... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To quantify the risk of suicidality and violence when selective serotonin and serotonin-norepinephrine reuptake inhibitors are given to adult healthy volunteers with no signs of a mental disorder.
DESIGN
Systematic review and meta-analysis.
MAIN OUTCOME MEASURE
Harms related to suicidality, hostility, activation events, psychotic events and mood disturbances.
SETTING
Published trials identified by searching PubMed and Embase and clinical study reports obtained from the European and UK drug regulators.
PARTICIPANTS
Double-blind, placebo-controlled trials in adult healthy volunteers that reported on suicidality or violence or precursor events to suicidality or violence.
RESULTS
A total of 5787 publications were screened and 130 trials fulfilled our inclusion criteria. The trials were generally uninformative; 97 trials did not report the randomisation method, 75 trials did not report any discontinuations and 63 trials did not report any adverse events or lack thereof. Eleven of the 130 published trials and two of 29 clinical study reports we received from the regulatory agencies presented data for our meta-analysis. Treatment of adult healthy volunteers with antidepressants doubled their risk of harms related to suicidality and violence, odds ratio 1.85 (95% confidence interval 1.11 to 3.08, p = 0.02, I= 18%). The number needed to treat to harm one healthy person was 16 (95% confidence interval 8 to 100; Mantel-Haenszel risk difference 0.06). There can be little doubt that we underestimated the harms of antidepressants, as we only had access to the published articles for 11 of our 13 trials.
CONCLUSIONS
Antidepressants double the occurrence of events in adult healthy volunteers that can lead to suicide and violence.
Topics: Adult; Antidepressive Agents; Female; Healthy Volunteers; Humans; Male; Risk; Selective Serotonin Reuptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors; Suicide; Violence
PubMed: 27729596
DOI: 10.1177/0141076816666805 -
Nutrients Jan 2021Recent systematic reviews and meta-analyses of randomized, double-blind, placebo-controlled trials (double-blind, placebo-controlled RCTs) have reported controversial... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Recent systematic reviews and meta-analyses of randomized, double-blind, placebo-controlled trials (double-blind, placebo-controlled RCTs) have reported controversial findings regarding the associations between calcium supplements on the risk of cardiovascular disease (CVD). This meta-analysis aimed to investigate the association between them.
METHODS
We searched PubMed, EMBASE, the Cochrane Library, and the bibliographies of relevant articles for double-blind, placebo-controlled RCTs in November, 2020. Relative risks (RRs) with 95% confidence intervals (CIs) for the risk of cardiovascular disease were calculated using a random effects model. The main outcomes were CVD, coronary heart disease (CHD), and cerebrovascular disease.
RESULTS
A total of 13 double-blind, placebo-controlled RCTs ( = 28,935 participants in an intervention group and 14,243 in a control group)) were included in the final analysis. Calcium supplements significantly increased the risk of CVD (RR 1.15, 95% CI 1.06-1.25], I2 = 0.0%, = 14) and CHD (RR 1.16, 95% CI 1.05-1.28], I2 = 0.0%, = 9) in double-blind, placebo-controlled RCTs, specifically in healthy postmenopausal women. In the subgroup meta-analysis, dietary calcium intake of 700-1000 mg per day or supplementary calcium intake of 1000 mg per day significantly increased the risk of CVD and CHD.
CONCLUSIONS
The current meta-analysis found that calcium supplements increased a risk of CVD by about 15% in healthy postmenopausal women.
Topics: Calcium; Calcium, Dietary; Cardiovascular Diseases; Clinical Trials as Topic; Coronary Disease; Databases, Factual; Dietary Supplements; Double-Blind Method; Eating; Female; Humans; Randomized Controlled Trials as Topic
PubMed: 33530332
DOI: 10.3390/nu13020368 -
The Cochrane Database of Systematic... Oct 2015This is an updated version of the original Cochrane review published in Issue 3, 2012. That review considered both fibromyalgia and neuropathic pain, but the efficacy of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an updated version of the original Cochrane review published in Issue 3, 2012. That review considered both fibromyalgia and neuropathic pain, but the efficacy of milnacipran for neuropathic pain is now dealt with in a separate review.Milnacipran is a serotonin-norepinephrine (noradrenaline) reuptake inhibitor (SNRI) that is licensed for the treatment of fibromyalgia in some countries, including Canada, Russia, and the United States.
OBJECTIVES
To assess the analgesic efficacy of milnacipran for pain in fibromyalgia in adults and the adverse events associated with its use in clinical trials.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE to 18 May 2015, together with reference lists of retrieved papers and reviews, and two clinical trial registries. For the earlier review, we also contacted the manufacturer.
SELECTION CRITERIA
We included randomised, double-blind studies of eight weeks' duration or longer, comparing milnacipran with placebo or another active treatment in fibromyalgia in adults.
DATA COLLECTION AND ANALYSIS
We extracted efficacy and adverse event data, and two review authors examined issues of study quality independently.
MAIN RESULTS
We identified one new study with 100 participants for the pooled analysis. We identified two additional reports of a study using an enriched enrolment randomised withdrawal (EERW) design that included participants from earlier randomised controlled trials and an open-label study. Because this study used the same participants already included in our main analysis, and a different design, we dealt with it separately.The main analysis included six studies (five from the earlier review; 4238 participants in total), all of which were placebo-controlled, and used titration to a target dose of milnacipran 100 or 200 mg, with assessment after 8 to 24 weeks of stable treatment. There were no studies with active comparators. Study quality was generally good, although the imputation method used in analyses of the primary outcomes could overestimate treatment effect.Both doses of milnacipran provided moderate levels of pain relief (at least 30% pain intensity reduction) to about 40% of participants treated, compared to 30% with placebo, giving a number needed to treat for an additional beneficial outcome (NNT) of 6 to 10 (high quality evidence). Using a stricter definition for responder and a more conservative method of analysis gave lower levels of response (while maintaining a 10% difference between milnacipran and placebo) and increased the NNT to 11 (high quality evidence). One EERW study was broadly supportive.Adverse events were common in both milnacipran (86%) and placebo (78%) groups (high quality evidence), but serious adverse events did not differ between groups (less than 2%) (low quality evidence). Nausea, constipation, and headache were the most common events showing the greatest difference between groups (number needed to treat for an additional harmful outcome (NNH) of 5.7 for nausea, 13 for constipation, and 29 for headache) (moderate quality evidence).Withdrawals for any reason were more common with milnacipran than placebo, and more common with 200 mg (NNH 9) than 100 mg (NNH 23), compared with placebo. This was largely driven by adverse event withdrawals, where the NNH compared with placebo was 14 for 100 mg and 7.0 for 200 mg (high quality evidence). Withdrawals due to lack of efficacy were less common with milnacipran than placebo but did not differ between doses (number needed to treat to prevent an additional unwanted outcome (NNTp) of 41) (moderate quality evidence).
AUTHORS' CONCLUSIONS
The evidence available indicates that milnacipran 100 mg or 200 mg is effective for a minority in the treatment of pain due to fibromyalgia, providing moderate levels of pain relief (at least 30%) to about 40% of participants, compared with about 30% with placebo. There were insufficient data to assess substantial levels of pain relief (at least 50%), and the use of last observation carried forward imputation may overestimate drug efficacy. Using stricter criteria for 'responder' and a more conservative method of analysis gave lower response rates (about 26% with milnacipran versus 17% with placebo). Milnacipran was associated with increased adverse events and adverse event withdrawals, which were significantly greater for the higher dose.
Topics: Adult; Analgesics; Chronic Disease; Cyclopropanes; Fibromyalgia; Humans; Milnacipran; Neuralgia; Selective Serotonin Reuptake Inhibitors
PubMed: 26482422
DOI: 10.1002/14651858.CD008244.pub3 -
JAMA Network Open Apr 2024Psilocybin has been studied in the treatment of depression and anxiety disorders. Clinical studies have mainly focused on efficacy, with systematic reviews showing... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Psilocybin has been studied in the treatment of depression and anxiety disorders. Clinical studies have mainly focused on efficacy, with systematic reviews showing favorable efficacy; however, none have primarily focused on psilocybin safety.
OBJECTIVE
To evaluate the acute adverse effects of psilocybin at therapeutic doses in the treatment of depression and anxiety.
DATA SOURCES
MEDLINE via PubMed, Web of Science, and ClinicalTrials.gov were searched for publications available between 1966 and November 30, 2023.
STUDY SELECTION
Randomized, double-blind clinical trials that reported adverse effects of psilocybin in patients treated for depression and anxiety were screened.
DATA EXTRACTION AND SYNTHESIS
Data were independently extracted by 2 authors and verified by 2 additional authors following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. The inverse variance method with the Hartung-Knapp adjustment for the random-effects model was used, with a continuity correction of 0.5 for studies with 0 cell frequencies. Sensitivity analysis was conducted by sequentially removing 1 study at a time to assess the robustness of the results.
MAIN OUTCOMES AND MEASURES
The primary outcome was considered as the adverse effects of psilocybin at high and moderate (ie, therapeutic) dose regimens and compared with placebo, low-dose psilocybin, or other comparator in the treatment of depression and/or anxiety.
RESULTS
Six studies met the inclusion criteria with a total sample of 528 participants (approximately 51% female; median age 39.8 years; IQR, 39.8-41.2). Seven adverse effects were reported in multiple studies and included in the analysis. Among these, headache (relative risk [RR], 1.99; 95% CI 1.06-3.74), nausea (RR, 8.85; 95% CI, 5.68-13.79), anxiety (RR, 2.27; 95% CI, 1.11-4.64), dizziness (RR, 5.81; 95% CI, 1.02-33.03), and elevated blood pressure (RR, 2.29; 95% CI, 1.15- 4.53) were statistically significant. Psilocybin use was not associated with risk of paranoia and transient thought disorder.
CONCLUSIONS AND RELEVANCE
In this meta-analysis, the acute adverse effect profile of therapeutic single-dose psilocybin appeared to be tolerable and resolved within 48 hours. However, future studies need to more actively evaluate the appropriate management of adverse effects.
Topics: Humans; Female; Adult; Male; Psilocybin; Drug-Related Side Effects and Adverse Reactions; Anxiety Disorders; Anxiety; Dizziness; Randomized Controlled Trials as Topic
PubMed: 38598236
DOI: 10.1001/jamanetworkopen.2024.5960 -
Journal of Prosthodontic Research Jan 2023The efficacy of etch-and-rinse, selective enamel-etching, and self-etching protocols for universal adhesives in follow-ups of over 12 months was compared in a network... (Meta-Analysis)
Meta-Analysis
Efficacy of adhesive strategies for restorative dentistry: A systematic review and network meta-analysis of double-blind randomized controlled trials over 12 months of follow-up.
PURPOSE
The efficacy of etch-and-rinse, selective enamel-etching, and self-etching protocols for universal adhesives in follow-ups of over 12 months was compared in a network meta-analysis.
STUDY SELECTION
Randomized controlled trials (RCTs) published from 1998 to 2022 that compared marginal staining, marginal adaptation, retention and fractures, post-operative sensitivity, or recurrence of caries that took place over 12-months post-restoration were selected. A network meta-analysis determined the performance of each adhesive protocol.
RESULTS
After screening 981 articles, 16 RCTs were subjected to data extraction. Of which, 674 patients with 2816 restorations, were included in the network meta-analysis. The pooled risk of marginal discoloration following self-etching was significantly higher than that following etch-and-rinse at over 12, 24, and 36 months, which was time-dependent. The pooled risks of unfavorable marginal adaptation and unfavorable retention and fractures following self-etching were also significantly higher than that following etch-and-rinse, with the rates of unfavorable retention and fractures in non-carious cervical lesions increasing in a time-dependent manner. The pooled risks of marginal discoloration, unfavorable marginal adaptation, retention and fractures were similar between etch-and-rinse and selective enamel-etching protocols. Post-operative hypersensitivity and recurrence of caries were not significantly different among etch-and-rinse, selective enamel-etching, and self-etching protocols.
CONCLUSIONS
In follow-ups over 12 months, esthetic and functional outcomes of restorations completed with an etch-and-rinse adhesive protocol were superior to the ones achieved with a self-etching strategy without selective enamel-etching. Selective enamel etching is recommended for self-etching systems. Biological responses were similar for all three adhesive strategies.
Topics: Humans; Dental Caries; Dental Marginal Adaptation; Dental Restoration, Permanent; Follow-Up Studies; Network Meta-Analysis; Randomized Controlled Trials as Topic; Treatment Outcome; Adhesives; Denture Retention; Double-Blind Method; Dental Etching
PubMed: 35691823
DOI: 10.2186/jpr.JPR_D_21_00279 -
Iranian Journal of Nursing and... 2022Blinding is one of the critical criteria of clinical trials that prevents probable bias. Judgment regarding results of an intervention significantly depends on the... (Review)
Review
BACKGROUND
Blinding is one of the critical criteria of clinical trials that prevents probable bias. Judgment regarding results of an intervention significantly depends on the quality of such studies, one of which is blinding. This study aimed to investigate blinding and its quality in clinical trials in patients with breast cancer.
MATERIALS AND METHODS
A systematic review was conducted on the online databases of PubMed, ScienceDirect and ProQuest using keywords, MeSH terms and grey literature. Articles were screened by predefined inclusion and exclusion criteria. They were evaluated based on the checklists introduced by Cochrane database.
RESULTS
From 22519 articles obtained at the initial stage, 20 articles remained after screening for the inclusion and exclusion criteria. Fifteen articles had used single, five: double and none had used triple or quadruple blinding. Seventeen studies had described the details of blinding. Of the 15 single blind articles, the blinded subjects were patients in five, patients and research assistants in three, research assistants in five studies, and two had not given any details.
CONCLUSIONS
The majority of researchers had used the single blind method, though using double, triple or quadruple blinding increases the trustworthiness of results and increases the quality of clinical trials. The details of blinding should be explained to other researchers and for a better understanding of the method if it is to be repeated. Thereafter, nurses can apply new interventions and earn their patients' trust and help those with breast cancer by relieving them of their disease symptoms and its treatment complications.
PubMed: 35280192
DOI: 10.4103/ijnmr.IJNMR_49_20 -
Brazilian Journal of Anesthesiology... 2021Dexmedetomidine (DEX) has been associated with a decrease in postoperative cognitive and behavioral dysfunction in patients submitted to general anesthesia, whether... (Meta-Analysis)
Meta-Analysis Review
Dexmedetomidine reduces postoperative cognitive and behavioral dysfunction in adults submitted to general anesthesia for non-cardiac surgery: meta-analysis of randomized clinical trials.
INTRODUCTION AND OBJECTIVES
Dexmedetomidine (DEX) has been associated with a decrease in postoperative cognitive and behavioral dysfunction in patients submitted to general anesthesia, whether inhalation or total intravenous anesthesia. Consequently, the DEX effects on postoperative agitation and delirium in patients submitted to general anesthesia for non-cardiac surgery have been investigated.
METHOD
A systematic review and meta-analysis of randomized and double-blind clinical trials (RCTs) was undertaken assessing adults submitted to elective procedures under general anesthesia receiving DEX or placebo. The search included articles published in English in the Pubmed and Web of Science databases using keywords such as dexmedetomidine, delirium, and agitation. Duplicate publications, studies involving cardiac surgery or using active control (other than saline solution) were included. A random effects model was adopted using the DerSimonian-Laird method and estimate of Odds Ratio (OR) for dichotomous variables, and weighted mean difference for continuous variables, with their respective 95% Confidence Intervals (95% CI).
RESULTS
Of the 484 articles identified, 15 were selected comprising 2,183 patients (1,079 and 1,104 patients in the DEX and control group, respectively). The administration of DEX was considered a protective factor for postoperative cognitive and behavioral dysfunction (OR=0.36; 95% CI 0.23-0.57 and p<0.001), regardless of the anesthesia technique used.
CONCLUSION
Dexmedetomidine administration reduced by at least 43% the likelihood of postoperative cognitive and behavioral dysfunction in adult patients submitted to general anesthesia for non-cardiac surgery.
Topics: Adult; Anesthesia, General; Cardiac Surgical Procedures; Cognition; Dexmedetomidine; Humans; Hypnotics and Sedatives; Randomized Controlled Trials as Topic
PubMed: 33685760
DOI: 10.1016/j.bjane.2021.02.020 -
International Journal of Environmental... Mar 2020The aim of this systematic review was to investigate the effectiveness of various disinfection methods available for stethoscopes. In March 2019, we performed a search...
The aim of this systematic review was to investigate the effectiveness of various disinfection methods available for stethoscopes. In March 2019, we performed a search in PubMed and Scopus using the search terms: "reducing stethoscopes contamination" and "disinfection stethoscopes"; the Mesh terms used in PubMed were "Decontamination/methods" or "Disinfection/methods" and "Stethoscopes/microbiology". Selection criteria were: English language; at least one disinfection method tested. A total of 253 publications were screened. After title, abstract, and full-text analysis, 17 papers were included in the systematic review. Ethanol at 90%, Ethanol-Based Hands Sanitizer (EBHS), triclosan, chlorhexidine, isopropyl alcohol, 66% ethyl alcohol, sodium hypochlorite, and benzalkonium chloride have been proven to lower the presence of bacteria on stethoscopes' surfaces. In addition, alcohol wipes show effective results. A wearable device emitting ultraviolet C by Light-Emitting Diode (LED) resulted efficacious against common microorganisms involved in Healthcare Associated Infections. The cover impregnated with silver ions seemed to be associated with significantly higher colony counts. Instead, copper stethoscopes surface reduced bacterial load. The disinfection of stethoscopes appears to be essential. There are many valid methods available; the choice depends on various factors, such as the cost, availability, and practicality.
Topics: Aged; Child; Cohort Studies; Cross-Sectional Studies; Disinfection; Double-Blind Method; Escherichia coli; Humans; Methicillin-Resistant Staphylococcus aureus; Pilot Projects; Prospective Studies; Staphylococcus aureus; Stethoscopes
PubMed: 32182989
DOI: 10.3390/ijerph17061856 -
Gynecologic and Obstetric Investigation 2015In recent years, acupuncture has become more and more popular in the management of subfertility. The aim of this study was to evaluate the impact of acupuncture during... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND/AIMS
In recent years, acupuncture has become more and more popular in the management of subfertility. The aim of this study was to evaluate the impact of acupuncture during in vitro fertilization (IVF) treatment on the outcomes of clinical pregnancy in published randomized studies.
METHODS
This is a systematic review and meta-analysis. Data sources used were MEDLINE, Embase, Web of Knowledge and the Chinese Biomedical Database.
RESULTS
There was no statistically significant difference between the acupuncture group and no acupuncture (intervention) controls around the time of embryo transfer (ET; risk ratio, RR, 1.24, 95% confidence interval, CI, 1.02-1.50) or in unblinded trials, trials blinded to physicians and double-blind trials (95% CI 1.26-1.88, 0.82-1.33 and 0.89-1.25, respectively). This was also the case when comparing acupuncture with sham acupuncture controls around the time of ET (RR, 1.03, 95% CI 0.87-1.22) or when restricting to unblinded trials, trials blinded to physicians and double-blind trials (95% CI 0.80-2.02, 0.82-1.18 and 0.77-1.17, respectively). There was a statistically significant difference when performed at 30 min after ET and implantation phase (RR 1.76, 95% CI 1.22-2.55). There was also a statistically significant difference when performed at follicle phase and 25 min before and after ET (RR 1.56, 95% CI 1.04-2.33).
CONCLUSION
Our study showed that acupuncture did not significantly improve the IVF clinical pregnancy rate when performed only at the time of ET, while we found pooled benefit of acupuncture for IVF when performed at follicle phase and 25 min before and after ET, as well as 30 min after ET and implantation phase.
Topics: Acupuncture; Double-Blind Method; Embryo Transfer; Female; Fertilization in Vitro; Follicular Phase; Humans; MEDLINE; Pregnancy; Pregnancy Outcome; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome
PubMed: 24854767
DOI: 10.1159/000362231