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BMJ (Clinical Research Ed.) May 2024To determine the efficacy of psilocybin as an antidepressant compared with placebo or non-psychoactive drugs. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine the efficacy of psilocybin as an antidepressant compared with placebo or non-psychoactive drugs.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
Five electronic databases of published literature (Cochrane Central Register of Controlled Trials, Medline, Embase, Science Citation Index and Conference Proceedings Citation Index, and PsycInfo) and four databases of unpublished and international literature (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, ProQuest Dissertations and Theses Global, and PsycEXTRA), and handsearching of reference lists, conference proceedings, and abstracts.
DATA SYNTHESIS AND STUDY QUALITY
Information on potential treatment effect moderators was extracted, including depression type (primary or secondary), previous use of psychedelics, psilocybin dosage, type of outcome measure (clinician rated or self-reported), and personal characteristics (eg, age, sex). Data were synthesised using a random effects meta-analysis model, and observed heterogeneity and the effect of covariates were investigated with subgroup analyses and metaregression. Hedges' g was used as a measure of treatment effect size, to account for small sample effects and substantial differences between the included studies' sample sizes. Study quality was appraised using Cochrane's Risk of Bias 2 tool, and the quality of the aggregated evidence was evaluated using GRADE guidelines.
ELIGIBILITY CRITERIA
Randomised trials in which psilocybin was administered as a standalone treatment for adults with clinically significant symptoms of depression and change in symptoms was measured using a validated clinician rated or self-report scale. Studies with directive psychotherapy were included if the psychotherapeutic component was present in both experimental and control conditions. Participants with depression regardless of comorbidities (eg, cancer) were eligible.
RESULTS
Meta-analysis on 436 participants (228 female participants), average age 36-60 years, from seven of the nine included studies showed a significant benefit of psilocybin (Hedges' g=1.64, 95% confidence interval (CI) 0.55 to 2.73, P<0.001) on change in depression scores compared with comparator treatment. Subgroup analyses and metaregressions indicated that having secondary depression (Hedges' g=3.25, 95% CI 0.97 to 5.53), being assessed with self-report depression scales such as the Beck depression inventory (3.25, 0.97 to 5.53), and older age and previous use of psychedelics (metaregression coefficient 0.16, 95% CI 0.08 to 0.24 and 4.2, 1.5 to 6.9, respectively) were correlated with greater improvements in symptoms. All studies had a low risk of bias, but the change from baseline metric was associated with high heterogeneity and a statistically significant risk of small study bias, resulting in a low certainty of evidence rating.
CONCLUSION
Treatment effects of psilocybin were significantly larger among patients with secondary depression, when self-report scales were used to measure symptoms of depression, and when participants had previously used psychedelics. Further research is thus required to delineate the influence of expectancy effects, moderating factors, and treatment delivery on the efficacy of psilocybin as an antidepressant.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42023388065.
Topics: Humans; Antidepressive Agents; Depression; Hallucinogens; Psilocybin; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 38692686
DOI: 10.1136/bmj-2023-078084 -
Brain & Spine 2024The effectiveness of post-surgical rehabilitation following lumbar disc herniation (LDH) surgery is unclear. (Review)
Review
INTRODUCTION
The effectiveness of post-surgical rehabilitation following lumbar disc herniation (LDH) surgery is unclear.
RESEARCH QUESTION
To investigate the effectiveness and safety of rehabilitation interventions initiated within three months post-surgery for adults treated surgically for LDH.
MATERIAL AND METHODS
This systematic review searched seven databases from inception to November 2023. Independent reviewers screened studies, assessed and extracted data, and rated the certainty of the evidence using the GRADE approach.
RESULTS
This systematic review retrieved 20,531 citations and included 25 randomized controlled trials. The high certainty evidence suggests that adding Pilates exercise to routine care and cognitive behavioral therapy may improve function immediately post-intervention (1 RCT), and that adding whole-body magnetic therapy to exercise, pharmacological and aquatic therapy may reduce low back pain intensity (1 RCT) immediately post-intervention. Compared to placebo, pregabalin did not reduce low back pain or leg pain intensity (1 RCT) (moderate to high certainty evidence). We found no differences between: 1) behavioral graded activity vs. physiotherapy (1 RCT); 2) exercise and education vs. neck massage or watchful waiting (1 RCT); 3) exercise, education, and in-hospital usual care vs. in-hospital usual care (1 RCT); 4) functional or staged exercise vs. usual post-surgical care including exercise (2 RCTs); and 5) supervised exercise with education vs. education (1 RCT). No studies assessed adverse events.
DISCUSSION AND CONCLUSION
Evidence on effective and safe post-surgical rehabilitation interventions is sparse. This review identified two interventions with potential short-term benefits (Pilates exercises, whole-body magnetic therapy) but safety is unclear, and one with an iatrogenic effect (pregabalin).
PubMed: 38690091
DOI: 10.1016/j.bas.2024.102806 -
Frontiers in Immunology 2024Peri-implant diseases (peri-implant mucositis and peri-implantitis) are pathologies of an infectious-inflammatory nature of the mucosa around dental implants. Probiotics... (Meta-Analysis)
Meta-Analysis
The role of probiotic therapy on clinical parameters and human immune response in peri-implant diseases: a systematic review and meta-analysis of randomized clinical studies.
BACKGROUND
Peri-implant diseases (peri-implant mucositis and peri-implantitis) are pathologies of an infectious-inflammatory nature of the mucosa around dental implants. Probiotics are microorganisms that regulate host immunomodulation and have shown positive results in the treatment of peri-implant diseases. The objective of the systematic review and meta-analysis was to evaluate the efficacy of probiotics in the treatment of peri-implant oral diseases.
METHODS
According to the PRISMA guidelines, the research question was established: Are probiotics able to favorably modify clinical and immunological biomarkers determinants of peri-implant pathologies? and an electronic search of the databases MEDLINE/PubMed, Embase, Cochrane Central, Web of Science, (until December 2023) was performed. Inclusion criteria were established for intervention studies (RCTs), according to the PICOs strategy in subjects with peri-implant pathology (participants), treated with probiotics (intervention) compared to patients with conventional treatment or placebo (control) and evaluating the response to treatment (outcomes). Results- 1723 studies were obtained and 10 were selected. Risk of bias was assessed using the Cochrane Risk of Bias Tool and methodological quality using the Joanna Briggs Institute for RCTs. Two meta-analyses were performed, one to evaluate probiotics in mucositis and one for peri-implantitis. All subgroups were homogeneous (I0%), except in the analysis of IL-6 in mucositis (I65%). The overall effect was favorable to the experimental group in both pathologies. The analysis of the studies grouped in peri-implantitis showed a tendency to significance (p=0.09).
CONCLUSION
The use of probiotics, as basic or complementary treatment of peri-implant diseases, showed a statistically significant trend, but well-designed studies are warranted to validate the efficacy of these products in peri-implant pathologies.
Topics: Humans; Probiotics; Peri-Implantitis; Randomized Controlled Trials as Topic; Dental Implants; Treatment Outcome; Stomatitis
PubMed: 38686378
DOI: 10.3389/fimmu.2024.1371072 -
EClinicalMedicine Apr 2024The World Health Organization (WHO) recommends tenofovir disoproxil fumarate (TDF)-based oral pre-exposure prophylaxis (PrEP), the dapivirine vaginal ring, and...
BACKGROUND
The World Health Organization (WHO) recommends tenofovir disoproxil fumarate (TDF)-based oral pre-exposure prophylaxis (PrEP), the dapivirine vaginal ring, and long-acting intramuscular injectable cabotegravir (CAB-LA) for HIV prevention in populations at substantial risk of HIV infection. Pregnancy is a period of elevated risk of maternal HIV infection and transmission to the infant. This systematic review and meta-analysis assessed the risk of adverse perinatal outcomes among HIV-negative pregnant women with exposure to any PrEP modality.
METHODS
We conducted a systematic review by searching Medline, EMBASE, CINAHL, Global Health, the Cochrane Library, WHO ICTR, ISRCTN, PACTR, and ClinicalTrials.gov for studies published between 1 January 2000 and 29 August 2023. We included studies reporting on the association of antenatal exposure to any PrEP modality with 13 perinatal outcomes: preterm birth (PTB), very PTB, spontaneous PTB, spontaneous very PTB, low birthweight (LBW), very LBW, term LBW, preterm LBW, small for gestational age (SGA), very SGA, miscarriage, stillbirth, or neonatal death (NND). Quality assessments of included studies were performed. Fixed-effect meta-analyses were conducted to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). The protocol is registered with PROSPERO, CRD42022339825.
FINDINGS
Of 18,598 citations identified, 13 studies (eight randomised controlled trials (RCTs) and five cohort studies), assessing 8712 pregnant women in Africa, were included. Oral PrEP, compared to no PrEP, was not associated with PTB in meta-analyses of six RCTs (OR 0.73, 95% CI 0.43-1.26; = 0.0%) or five unadjusted cohort studies (OR 0.84, 95% CI 0.69-1.03; = 0.0%), but was associated with a reduced risk of PTB in three adjusted cohort studies (aOR 0.67; 95% CI 0.52-0.88, = 0.0%). There was no association of oral PrEP with LBW, vLBW, SGA, or NND, compared to no PrEP. There was no association with PTB when oral TDF/emtricitabine (FTC) PrEP, oral TDF PrEP, and tenofovir vaginal gel were compared to each other. There was no association of the dapivirine vaginal ring with PTB or NND, compared to placebo or oral TDF/FTC PrEP. We found no data on CAB-LA.
INTERPRETATION
We found no evidence of adverse perinatal outcomes associated with PrEP exposure during pregnancy. Our findings support the WHO recommendation to provide oral PrEP to women of reproductive age and pregnant women. More data is needed to assess the safety of all PrEP modalities in pregnancy.
FUNDING
None.
PubMed: 38685925
DOI: 10.1016/j.eclinm.2024.102532 -
Biomedical Reports Jun 2024Lurasidone is an atypical anti-psychotic approved by the US Food and Drug Administration. It is mainly used to treat schizophrenia in adults through its antagonistic...
Efficacy and safety of lurasidone for schizophrenia: A systematic review and meta‑analysis of eight short‑term, randomized, double‑blind, placebo‑controlled clinical trials.
Lurasidone is an atypical anti-psychotic approved by the US Food and Drug Administration. It is mainly used to treat schizophrenia in adults through its antagonistic action on dopamine and 5-hydroxytryptamine receptors. The present study systematically assessed the efficacy and safety of lurasidone in the treatment of schizophrenia. Clinical, double-blind, parallel, randomized controlled trials (RCTs) of lurasidone in the treatment of schizophrenia were retrieved from PubMed\Medline, EBSCO, Embase, Cochrane Library, OVID, Web of Science and related clinical trial registration websites up to May 2023. A total of two investigators independently screened the included references and evaluated their quality. RevMan 5.3 software was used for meta-analysis of each measure outcome. The present systematic review was registered in PROSPERO (ID=CRD42018108178). A total of eight RCTs were included in the present study, including a total of 2,456 patients with schizophrenia. All eight references were randomized, double-blind and parallel control trials. All eight references were evaluated as high quality. The meta-analysis results demonstrated that there were no significant change in total Positive and Negative Syndrome Scale (PANSS) score, Clinical Global Impression of Severity (CGI-S) score and Montgomery-Asberg Depression Rating Scale (MADRS) between the 40 mg lurasidone group and the placebo group (P>0.05). However, as the dosage increased, the 80, 120 and 160 mg lurasidone groups had significant changes in total PANSS score, CGI-S score and MADRS Compared with placebo (P<0.05), although changes in MADRS in the 120 mg lurasidone group were not statistically significant (P>0.05). In terms of safety, the changes in the incidence of agitation in the 40 mg lurasidone group (P<0.05), vomiting in the 80 mg group (P<0.05) and akathisia in the 160 mg group (P<0.05) were statistically significant and there were also statistically significant changes in the incidence of akathisia, nausea, somnolence and extrapyramidal disorder among the 40, 80 and 120 mg lurasidone groups (P<0.05); No statistically significant changes in the in the incidence of other adverse reactions (P>0.05). In conclusion, existing evidence suggests that the initial dose of lurasidone for schizophrenia can be adjusted to 80 mg. As the condition aggravates, the dose can be incrementally increased to 160 mg. A dose of 160 mg lurasidone is recommended as the most efficacious and safe dose for acute schizophrenia and the risk of occurrence of akathisia, nausea, somnolence and extrapyramidal disorder is still high when lurasidone is administered at a dose of 80-120 mg. The dose should be promptly adjusted or the drug should be withdrawn if the aforementioned adverse reactions worsen. Multi-center, high-quality and long-term clinical RCTs influenced by the included references are still necessary to support the aforementioned conclusions.
PubMed: 38682090
DOI: 10.3892/br.2024.1779 -
Osteoarthritis and Cartilage Jul 2024To examine the pain relief effects of comparators (placebos and untreated control groups) in hand osteoarthritis trials and the impact of contextual factors. (Meta-Analysis)
Meta-Analysis
Comparative effectiveness of different placebos and comparator groups for hand osteoarthritis exploring the impact of contextual factors: A systematic review and meta-analysis of randomised trials.
OBJECTIVE
To examine the pain relief effects of comparators (placebos and untreated control groups) in hand osteoarthritis trials and the impact of contextual factors.
METHODS
We systematically searched PubMed, EMBASE and CENTRAL from inception to December 26, 2021. We included randomised controlled trials of people with hand osteoarthritis with a placebo or an untreated control group. We assessed the Risk of Bias with Cochrane Risk-of-Bias tool version 2. Each comparator was contrasted with a null-arm, imputed as having a zero change from baseline with the same standard deviation as the comparator. We combined the standardised mean differences with a random effects meta-analysis. The contextual factors' effect was explored in meta-regression and stratified models with pain as the dependent variable.
RESULTS
84 trials (7262 participants) were eligible for quantitative synthesis, of which 76 (6462 participants) were eligible for the stratified analyses. Placebos were superior to their matched null-arms in relieving pain with an effect size of -0.51 (95% confidence interval -0.61 to -0.42), while untreated control groups were not. When analysing all comparators, blinded trial designs and low risk of bias were associated with higher pain relief compared to an open-label trial design and some concern or high risk of bias.
CONCLUSION
The placebo response on pain for people with hand osteoarthritis was increased by appropriate blinding and a lower risk of bias assessment. Placebos were superior to a null-arm, while untreated control groups were not. Results emphasise the importance of using appropriate comparators in clinical trials.
PROSPERO REGISTRATION ID
CRD42022298984.
Topics: Humans; Control Groups; Hand Joints; Osteoarthritis; Placebos; Randomized Controlled Trials as Topic
PubMed: 38679284
DOI: 10.1016/j.joca.2024.02.947 -
Systematic Reviews Apr 2024Chronic postsurgical pain (CPSP) is common following musculoskeletal and orthopedic surgeries and is associated with impairment and reduced quality of life. Several... (Meta-Analysis)
Meta-Analysis
Comparative benefits and harms of perioperative interventions to prevent chronic pain after orthopedic surgery: a systematic review and network meta-analysis of randomized trials.
BACKGROUND
Chronic postsurgical pain (CPSP) is common following musculoskeletal and orthopedic surgeries and is associated with impairment and reduced quality of life. Several interventions have been proposed to reduce CPSP; however, there remains uncertainty regarding which, if any, are most effective. We will perform a systematic review and network meta-analysis of randomised trials to assess the comparative benefits and harms of perioperative pharmacological and psychological interventions directed at preventing chronic pain after musculoskeletal and orthopedic surgeries.
METHODS
We will search MEDLINE, Embase, PsycINFO, CINAHL, and the Cochrane Central Register of Controlled Trials from inception to present, without language restrictions. We will include randomised controlled trials that as follows: (1) enrolled adult patients undergoing musculoskeletal or orthopedic surgeries; (2) randomized them to any pharmacological or psychological interventions, or their combination directed at reducing CPSP, placebo, or usual care; and (3) assessed pain at 3 months or more after surgery. Screening for eligible trials, data extraction, and risk-of-bias assessment using revised Cochrane risk-of-bias tool (RoB 2.0) will be performed in duplicate and independently. Our main outcome of interest will be the proportion of surgical patients reporting any pain at ≥ 3 months after surgery. We will also collect data on other patient important outcomes, including pain severity, physical functioning, emotional functioning, dropout rate due to treatment-related adverse event, and overall dropout rate. We will perform a frequentist random-effects network meta-analysis to determine the relative treatment effects. When possible, the modifying effect of sex, surgery type and duration, anesthesia type, and veteran status on the effectiveness of interventions will be investigated using network meta-regression. We will use the GRADE approach to assess the certainty evidence and categorize interventions from most to least beneficial using GRADE minimally contextualised approach.
DISCUSSION
This network meta-analysis will assess the comparative effectiveness of pharmacological and psychological interventions directed at preventing CPSP after orthopedic surgery. Our findings will inform clinical decision-making and identify promising interventions for future research.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42023432503.
Topics: Humans; Orthopedic Procedures; Chronic Pain; Randomized Controlled Trials as Topic; Pain, Postoperative; Network Meta-Analysis; Perioperative Care; Quality of Life
PubMed: 38671531
DOI: 10.1186/s13643-024-02528-x -
Nutricion Hospitalaria Jun 2024Caffeine is a widely used ergogenic aid in society, which has made it a topic of interest due to its various benefits at cognitive, physiological, and sports levels,...
Caffeine is a widely used ergogenic aid in society, which has made it a topic of interest due to its various benefits at cognitive, physiological, and sports levels, among others. This review aims to investigate the potential benefits of caffeine supplementation in psychophysiological performance through a structured search in the SportsDiscus/Scopus/MEDLINE and Web of Science databases (October 2022). This review followed the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guideline, and the inclusion criteria were defined based on the PICOS model. Double-blind, randomized/semi-randomized crossover articles comparing caffeine intake with an identical placebo condition were included. Filters by age or gender of the participants were not applied. The initial search gave a result of 201 articles, which after eliminating duplicates and applying the inclusion and exclusion criteria, the final sample for this review was 8 studies. The review concluded that 3 (37.5 %) found favorable ergogenic effects, 4 (50 %) found partial effects, and 1 (12.5 %) found no effects of caffeine supplementation on variables related to psychophysiological performance. In general, both partial and negative results could be linked to insufficient doses to produce any change, likewise, habitual caffeine consumption is also a variable that could be attenuating its potential ergogenic effect. In conclusion, moderate doses of caffeine 3-6 mg/kg seem to be an effective strategy to improve the psychophysiological response in various contexts without generating detrimental effects on performance, as long as the intervention designs consider the variables that could condition its effect.
Topics: Caffeine; Humans; Athletic Performance; Performance-Enhancing Substances; Dietary Supplements; Psychophysiology; Central Nervous System Stimulants; Randomized Controlled Trials as Topic
PubMed: 38666339
DOI: 10.20960/nh.04820 -
Cureus Mar 2024Tirzepatide is a novel once-a-week dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, recently approved for... (Review)
Review
Tirzepatide is a novel once-a-week dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, recently approved for type 2 diabetes mellitus (T2DM) and obesity. A systematic review of the literature published in multiple meta-analyses on Tirzepatide with emphasis on its effect on glycaemic and non-glycaemic parameters was conducted. We systematically searched the electronic databases PubMed and Google Scholar up to August 2023 for meta-analyses that compared Tirzepatide with placebo or active antihyperglycaemic drugs in subjects with T2DM. Various parameters for efficacy and safety, with their point estimates and confidence intervals, such as glycated haemoglobin (HbA1c), fasting serum glucose (FSG), body weight, lipid, and cardiovascular outcomes were assessed. Six meta-analyses fulfilled the pre-specified criteria and were included in the study. In all the studies, Tirzepatide treatment at different doses resulted in a significant reduction in HbA1c and FSG levels along with a significant reduction in weight compared with active control and placebo groups. Tirzepatide significantly reduced levels of triglycerides and increased high-density lipoprotein (HDL) cholesterol, whether used as monotherapy or add-on therapy. The studies suggested the cardiovascular safety of Tirzepatide as there was no increase in major adverse cardiovascular events (MACE). The drug shows lesser hypoglycemia but predominant gastrointestinal adverse effects such as nausea, vomiting, and diarrhoea. In conclusion, Tirzepatide shows superior glycaemic control and weight loss in patients with T2DM with beneficial effects on lipids, without an increased risk of hypoglycemia and cardiovascular events.
PubMed: 38665722
DOI: 10.7759/cureus.56939 -
International Journal of Exercise... 2024The objective of this study was to systematically review the literature on the effect of CGs versus non-CGs (such as regular socks) or versus placebo garments on 1) the... (Review)
Review
The objective of this study was to systematically review the literature on the effect of CGs versus non-CGs (such as regular socks) or versus placebo garments on 1) the incidence of lower extremity sports injuries and 2) subjective ratings of fatigue and biomechanical variables in athletes at participating in any sport that required any level of running performance, given that fatigue-related biomechanical alterations may increase the risk of sports injuries. This study was a systematic review with meta-analyses. PubMed, Embase, CINAHL, Cochrane, PEDro, and Scopus were searched for eligible studies until 7 July 2021. Two reviewers independently assessed the risk of bias using the Cochrane Collaboration's tool for risk of bias. Meta-analyses were performed using a random-effects model. The Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of evidence for all outcome measures. Twenty-three studies, all with a high risk of bias, were included. Nineteen studies were used in the meta-analyses. No studies focused on the effect of CGs on the incidence of lower extremity sports injuries in athletes. Seventeen studies investigated the effect of CGs on subjective ratings of fatigue, but meta-analysis showed no difference in effectiveness between CGs versus non-CGs (such as regular socks) and versus placebo CGs (low certainty evidence). Because of heterogeneity, pooling of the results was not possible for the biomechanical variables. Nonetheless, low certainty evidence showed no effect of CGs. We identified no evidence for a beneficial or detrimental effect of lower leg CGs on the occurrence of lower extremity sports injuries, subjective ratings of fatigue, or biomechanical variables in athletes at any level of running performance. Based on the variable use of running tests, definitions used for biomechanical variables, and reporting of CG characteristics and more standardized reporting is recommended for future studies evaluating CGs.
PubMed: 38665681
DOI: No ID Found