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Molecular Psychiatry Jan 2023A systematic review and random-effects model network meta-analysis were conducted to compare the efficacy, acceptability, tolerability, and safety of antidepressants to... (Meta-Analysis)
Meta-Analysis
A systematic review and random-effects model network meta-analysis were conducted to compare the efficacy, acceptability, tolerability, and safety of antidepressants to treat adults with major depressive disorder (MDD) in the maintenance phase. This study searched the PubMed, Cochrane Library, and Embase databases and included only double-blind, randomized, placebo-controlled trials with an enrichment design: patients were stabilized on the antidepressant of interest during the open-label study and then randomized to receive the same antidepressant or placebo. The outcomes were the 6-month relapse rate (primary outcome, efficacy), all-cause discontinuation (acceptability), discontinuation due to adverse events (tolerability), and the incidence of individual adverse events. The risk ratio with a 95% credible interval was calculated. The meta-analysis comprised 34 studies (n = 9384, mean age = 43.80 years, and %females = 68.10%) on 20 antidepressants (agomelatine, amitriptyline, bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, levomilnacipran, milnacipran, mirtazapine, nefazodone, paroxetine, reboxetine, sertraline, tianeptine, venlafaxine, vilazodone, and vortioxetine) and a placebo. In terms of the 6-month relapse rate, amitriptyline, citalopram, desvenlafaxine, duloxetine, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, reboxetine, sertraline, tianeptine, venlafaxine, and vortioxetine outperformed placebo. Compared to placebo, desvenlafaxine, paroxetine, sertraline, venlafaxine, and vortioxetine had lower all-cause discontinuation; however, sertraline had a higher discontinuation rate due to adverse events. Compared to placebo, venlafaxine was associated with a lower incidence of dizziness, while desvenlafaxine, sertraline, and vortioxetine were associated with a higher incidence of nausea/vomiting. In conclusion, desvenlafaxine, paroxetine, venlafaxine, and vortioxetine had reasonable efficacy, acceptability, and tolerability in the treatment of adults with stable MDD.
Topics: Female; Humans; Adult; Depressive Disorder, Major; Duloxetine Hydrochloride; Sertraline; Citalopram; Venlafaxine Hydrochloride; Vortioxetine; Fluoxetine; Paroxetine; Mirtazapine; Amitriptyline; Desvenlafaxine Succinate; Fluvoxamine; Reboxetine; Network Meta-Analysis; Antidepressive Agents; Randomized Controlled Trials as Topic
PubMed: 36253442
DOI: 10.1038/s41380-022-01824-z -
The American Journal of Medicine Oct 2022Studies evaluating alcohol consumption and cardiovascular diseases have shown inconsistent results.
BACKGROUND
Studies evaluating alcohol consumption and cardiovascular diseases have shown inconsistent results.
METHODS
We performed a systematic review of peer-reviewed publications from an extensive query of Ovid MEDLINE, Ovid Embase, Ovid Cochrane Database of Systematic Reviews, Scopus, and Web of Science from database inception to March 2022 for all studies that reported the association between alcohol consumption in terms of quantity (daily or weekly amounts) and type of beverage (wine, beer or spirit) and cardiovascular disease events.
RESULTS
The study population included a total of 1,579,435 individuals based on 56 cohorts from several countries. We found that moderate wine consumption defined as 1-4 drinks per week was associated with a reduction in risk for cardiovascular mortality when compared with beer or spirits. However, higher risk for cardiovascular disease mortality was typically seen with heavier daily or weekly alcohol consumption across all types of beverages.
CONCLUSIONS
It is possible that the observational studies may overestimate the benefits of alcohol for cardiovascular disease outcomes. Although moderate wine consumption is probably associated with low cardiovascular disease events, there are many confounding factors, in particular, lifestyle, genetic, and socioeconomic associations with wine drinking, which likely explain much of the association with wine and reduced cardiovascular disease events. Further prospective study of alcohol and all-cause mortality, including cancer, is needed.
Topics: Alcohol Drinking; Alcoholic Beverages; Beer; Cardiovascular Diseases; Ethanol; Humans; Prospective Studies; Risk Factors; Wine
PubMed: 35580715
DOI: 10.1016/j.amjmed.2022.04.021 -
The Lancet. Psychiatry Jul 2019Depression is the single largest contributor to non-fatal health loss worldwide. Second-generation antidepressants are the first-line option for pharmacological... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Depression is the single largest contributor to non-fatal health loss worldwide. Second-generation antidepressants are the first-line option for pharmacological management of depression. Optimising their use is crucial in reducing the burden of depression; however, debate about their dose dependency and their optimal target dose is ongoing. We have aimed to summarise the currently available best evidence to inform this clinical question.
METHODS
We did a systematic review and dose-response meta-analysis of double-blind, randomised controlled trials that examined fixed doses of five selective serotonin reuptake inhibitors (SSRIs; citalopram, escitalopram, fluoxetine, paroxetine, and sertraline), venlafaxine, or mirtazapine in the acute treatment of adults (aged 18 years or older) with major depression, identified from the Cochrane Central Register of Controlled Trials, CINAHL, Embase, LILACS, MEDLINE, PsycINFO, AMED, PSYNDEX, websites of drug licensing agencies and pharmaceutical companies, and trial registries. We imposed no language restrictions, and the search was updated until Jan 8, 2016. Doses of SSRIs were converted to fluoxetine equivalents. Trials of antidepressants for patients with depression and a serious concomitant physical illness were excluded. The main outcomes were efficacy (treatment response defined as 50% or greater reduction in depression severity), tolerability (dropouts due to adverse effects), and acceptability (dropouts for any reasons), all after a median of 8 weeks of treatment (range 4-12 weeks). We used a random-effects, dose-response meta-analysis model with flexible splines for SSRIs, venlafaxine, and mirtazapine.
FINDINGS
28 554 records were identified through our search (24 524 published and 4030 unpublished records). 561 published and 121 unpublished full-text records were assessed for eligibility, and 77 studies were included (19 364 participants; mean age 42·5 years, SD 11·0; 7156 [60·9%] of 11 749 reported were women). For SSRIs (99 treatment groups), the dose-efficacy curve showed a gradual increase up to doses between 20 mg and 40 mg fluoxetine equivalents, and a flat to decreasing trend through the higher licensed doses up to 80 mg fluoxetine equivalents. Dropouts due to adverse effects increased steeply through the examined range. The relationship between the dose and dropouts for any reason indicated optimal acceptability for the SSRIs in the lower licensed range between 20 mg and 40 mg fluoxetine equivalents. Venlafaxine (16 treatment groups) had an initially increasing dose-efficacy relationship up to around 75-150 mg, followed by a more modest increase, whereas for mirtazapine (11 treatment groups) efficacy increased up to a dose of about 30 mg and then decreased. Both venlafaxine and mirtazapine showed optimal acceptability in the lower range of their licensed dose. These results were robust to several sensitivity analyses.
INTERPRETATION
For the most commonly used second-generation antidepressants, the lower range of the licensed dose achieves the optimal balance between efficacy, tolerability, and acceptability in the acute treatment of major depression.
FUNDING
Japan Society for the Promotion of Science, Swiss National Science Foundation, and National Institute for Health Research.
Topics: Depressive Disorder, Major; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Mirtazapine; Randomized Controlled Trials as Topic; Serotonin Agents; Selective Serotonin Reuptake Inhibitors; Venlafaxine Hydrochloride
PubMed: 31178367
DOI: 10.1016/S2215-0366(19)30217-2 -
Ophthalmology Jun 2022This systematic review and meta-analysis summarizes the existing evidence for the association of alcohol use with intraocular pressure (IOP) and open-angle glaucoma... (Meta-Analysis)
Meta-Analysis Review
TOPIC
This systematic review and meta-analysis summarizes the existing evidence for the association of alcohol use with intraocular pressure (IOP) and open-angle glaucoma (OAG).
CLINICAL RELEVANCE
Understanding and quantifying these associations may aid clinical guidelines or treatment strategies and shed light on disease pathogenesis. The role of alcohol, a modifiable factor, in determining IOP and OAG risk also may be of interest from an individual or public health perspective.
METHODS
The study protocol was preregistered in the Open Science Framework Registries (https://osf.io/z7yeg). Eligible articles (as of May 14, 2021) from 3 databases (PubMed, Embase, Scopus) were independently screened and quality assessed by 2 reviewers. All case-control, cross-sectional, and cohort studies reporting a quantitative effect estimate and 95% confidence interval (CI) for the association between alcohol use and either IOP or OAG were included. The evidence for the associations with both IOP and OAG was qualitatively summarized. Effect estimates for the association with OAG were pooled using random effects meta-analysis. Studies not meeting formal inclusion criteria for systematic review, but with pertinent results, were also appraised and discussed. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework.
RESULTS
Thirty-four studies were included in the systematic review. Evidence from 10 studies reporting an association with IOP suggests that habitual alcohol use is associated with higher IOP and prevalence of ocular hypertension (IOP > 21 mmHg), although absolute effect sizes were small. Eleven of 26 studies, comprising 173 058 participants, that tested for an association with OAG met inclusion criteria for meta-analysis. Pooled effect estimates indicated a positive association between any use of alcohol and OAG (1.18; 95% confidence interval [CI], 1.02-1.36; P = 0.03; I = 40.5%), with similar estimates for both prevalent and incident OAG. The overall GRADE certainty of evidence was very low.
CONCLUSIONS
Although this meta-analysis suggests a harmful association between alcohol use and OAG, our results should be interpreted cautiously given the weakness and heterogeneity of the underlying evidence base, the small absolute effect size, and the borderline statistical significance. Nonetheless, these findings may be clinically relevant, and future research should focus on improving the quality of evidence.
Topics: Cross-Sectional Studies; Ethanol; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Ocular Hypertension; Tonometry, Ocular
PubMed: 35101531
DOI: 10.1016/j.ophtha.2022.01.023 -
The Western Journal of Emergency... Feb 2021Most experts recommend norepinephrine as the first-line agent in septic shock. Our objective was to determine the effectiveness and safety of norepinephrine in patients... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Most experts recommend norepinephrine as the first-line agent in septic shock. Our objective was to determine the effectiveness and safety of norepinephrine in patients with septic shock.
METHODS
We searched the Cochrane Central Register of Controlled Trials and Epistemonikos, as well as MEDLINE from 1966 till August 2019. Screening of full texts, evaluation for eligibility, and data extraction were done by four independent reviewers. We estimated risk ratios (RR) and mean differences (MD) using a random-effects model with 95% confidence intervals (CI). The primary outcomes included the number of participants who achieved the target mean arterial pressure (MAP), time to achieve the target MAP, and number of participants with all-cause 28-day mortality. The secondary outcomes included the length of stay in the intensive care unit, length of hospital stay, incidence of arrhythmia and myocardial infarction, vasopressor-free days, and number of participants with all-cause 90-day mortality.
RESULTS
We identified 11 randomized controlled trials with a total of 4,803 participants. There was no difference in the number of participants who achieved the target MAP between those patients receiving norepinephrine and other vasopressors (RR 1.44; 95% CI, 0.32 to 6.54; P = 0.640; I = 94%; two trials, 116 participants). There was no significant difference in time to achieve the target MAP (MD -0.05; 95%, CI, -0.32 to 0.21; P = 0.690; I = 26%; two trials, 1763 participants) and all-cause 28-day mortality (RR 0.95; 95% CI, 0.89 to 1.02; P = 0.160; I = 0%; seven trials, 4,139 participants). Regarding the secondary outcome, norepinephrine may significantly reduce the incidence of arrhythmia as compared to other vasopressors (RR 0.64; 95% CI, 0.42 to 0.97; P = 0.030; I = 64%; six trials, 3974 participants). There was no difference in the incidence of myocardial infarction (RR 1.28; 95% CI, 0.79 to 2.09), vasopressor-free day (RR 0.46; 95% CI, -1.82 to 2.74) and all-cause 90-day mortality (RR 1.08; 95% CI, 0.96 to 1.21) between norepinephrine and vasopressors.
CONCLUSION
In minimizing the occurrence of an arrhythmia, norepinephrine is superior to other vasopressors, making it safe to be used in septic shock. However, there was insufficient evidence concerning mortality and achievement of the target MAP outcomes.
Topics: Humans; Intensive Care Units; Length of Stay; Norepinephrine; Shock, Septic; Vasoconstrictor Agents
PubMed: 33856300
DOI: 10.5811/westjem.2020.10.47825 -
Drug and Alcohol Review May 2022Alcohol consumption during pregnancy and breastfeeding cause adverse health outcomes to the mother and child, including Fetal Alcohol Spectrum Disorder (FASD). (Review)
Review
ISSUE
Alcohol consumption during pregnancy and breastfeeding cause adverse health outcomes to the mother and child, including Fetal Alcohol Spectrum Disorder (FASD).
APPROACH
Systematic literature review and thematic synthesis. Original studies that contained reasons for alcohol consumption in pregnancy and while breastfeeding were included. The Mixed Methods Appraisal Tool (MMAT) and the Confidence in the Evidence of Reviews of Qualitative Research (CerQUAL) approach were utilised. The review protocol is available on PROSPERO (registration number: CRD42018116998).
KEY FINDINGS
Forty-two eligible studies comprising women from 16 countries were included. Most commonly reported reasons of alcohol use in pregnancy were societal pressure and the belief that only "strong" alcohol and alcohol in large quantities is harmful. Other reasons were: a lack of awareness of adverse effects on the fetus; coping with adverse life experiences; consumption based on intuitive decision-making and influenced by personal/peer experiences; belief in the beneficial properties of alcohol; advice from medical practitioners; unwanted or unplanned pregnancy; alcohol dependence; and consumption as a cultural/traditional custom. Reasons for alcohol use during breastfeeding included the belief that alcohol stimulates breast milk production, unclear advice from medical practitioners, unawareness of the risks of infant exposure and to improve mood and celebrate events.
IMPLICATIONS
Understanding the context of reasons for alcohol use in pregnancy is crucial for implementing prenatal health education, and preventing FASD and other adverse maternal and child health outcomes.
CONCLUSION
Individual beliefs, knowledge/advice, culture and personal circumstances influence alcohol use in pregnancy. Data are limited for reasons surrounding alcohol use while breastfeeding.
Topics: Alcohol Drinking; Breast Feeding; Child; Ethanol; Female; Fetal Alcohol Spectrum Disorders; Humans; Infant; Mothers; Pregnancy
PubMed: 34963039
DOI: 10.1111/dar.13425 -
Pain Physician Jul 2017Palmitoylethanolamide (PEA) is a cannabimimetic compound that has been investigated as an analgesic agent in animal models and clinical trials. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Palmitoylethanolamide (PEA) is a cannabimimetic compound that has been investigated as an analgesic agent in animal models and clinical trials.
OBJECTIVES
We conducted a meta-analysis to examine the efficacy of PEA for treating pain in randomized, controlled trials.
STUDY DESIGN
Systematic review and meta-analysis.
SETTING
This meta-analysis examined all randomized, controlled trials involving the effect of PEA on pain score.
METHODS
We searched PubMed and Embase for randomized, active or placebo-controlled trials of PEA for the treatment of acute or chronic pain. Our primary outcome was the weighted mean difference in visual analog pain scales of PEA treatment compared to inactive controls.
RESULTS
We identified 10 studies including data from 786 patients who received PEA and 512 controls for inclusion in our systematic review. Eight trials included an inactive control group and were included in the meta-analysis. PEA was associated with significantly greater pain reduction compared to inactive control conditions (WMD = 2.03, 95% CI: 1.19 - 2.87, z = 4.75, P < 0.001). Use of placebo control, presence of blinding, allowance for concomitant treatments, and duration or dose of PEA treatment did not affect the measured efficacy of PEA. All-cause dropout was non-significantly reduced in the PEA group compared to inactive control conditions (RR = 0.36, 95% CI: 0.10 - 1.26, z = -1.60, P = 0.11).
LIMITATIONS
This meta-analysis relied on a relatively small number of trials across a variety of conditions causing pain with differing trial designs. Overall quality of the underlying studies and assessment of side effects were often poor.
CONCLUSIONS
PEA may be a useful treatment for pain and is generally well tolerated in research populations. Further, well-designed, randomized, placebo-controlled trials are needed to provide reliable estimates of its efficacy and to identify less serious adverse events associated with this compound.
KEY WORDS
PEA, palmidrol, palmitoylethanolamide, efficacy, pain, pain management, meta-analysis.
Topics: Acute Pain; Amides; Analgesics; Chronic Pain; Ethanolamines; Humans; Outcome Assessment, Health Care; Palmitic Acids
PubMed: 28727699
DOI: No ID Found -
Advances in Therapy Sep 2022Randomized controlled trials (RCTs) comparing triple therapies (inhaled corticosteroid [ICS], long-acting β-agonist [LABA], and long-acting muscarinic antagonist... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Randomized controlled trials (RCTs) comparing triple therapies (inhaled corticosteroid [ICS], long-acting β-agonist [LABA], and long-acting muscarinic antagonist [LAMA]) for the treatment of chronic obstructive pulmonary disease (COPD) are limited. This network meta-analysis (NMA) investigated the comparative efficacy of single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus any triple (ICS/LABA/LAMA) combinations and dual therapies in patients with COPD.
METHODS
This NMA was conducted on the basis of a systematic literature review (SLR), which identified RCTs in adults aged at least 40 years with COPD. The RCTs compared different ICS/LABA/LAMA combinations or an ICS/LABA/LAMA combination with any dual therapy (ICS/LABA or LAMA/LABA). Outcomes of interest included forced expiratory volume in 1 s (FEV), annualized rate of combined moderate and severe exacerbations, St George's Respiratory Questionnaire (SGRQ) total score and SGRQ responders, transition dyspnea index focal score, and rescue medication use (RMU). Analyses were conducted at 24 weeks (primary endpoint), and 12 and 52 weeks (if feasible).
RESULTS
The NMA was informed by five trials reporting FEV at 24 weeks. FF/UMEC/VI was statistically significantly more effective at increasing trough FEV (based on change from baseline) than all triple comparators in the network apart from UMEC + FF/VI. The NMA was informed by 17 trials reporting moderate or severe exacerbation endpoints. FF/UMEC/VI demonstrated statistically significant improvements in annualized rate of combined moderate or severe exacerbations versus single-inhaler budesonide/glycopyrronium bromide/formoterol fumarate (BUD/GLY/FOR). At 24 weeks, the NMA was informed by five trials. FF/UMEC/VI showed statistically significant improvements in annualized rate of combined moderate or severe exacerbations versus UMEC + FF/VI and BUD/GLY/FOR. FF/UMEC/VI also demonstrated improvements in mean SGRQ score versus other triple therapy comparators at 24 weeks, and a significant reduction in RMU compared with BUD/GLY/FOR (160/18/9.6).
CONCLUSION
The findings of this NMA suggest favorable efficacy with single-inhaler triple therapy comprising FF/UMEC/VI. Further analysis is required as additional evidence becomes available.
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Androstadienes; Benzyl Alcohols; Bronchodilator Agents; Budesonide, Formoterol Fumarate Drug Combination; Chlorobenzenes; Drug Combinations; Fluticasone; Humans; Muscarinic Antagonists; Network Meta-Analysis; Pulmonary Disease, Chronic Obstructive; Quinuclidines
PubMed: 35849317
DOI: 10.1007/s12325-022-02231-0 -
Circulation Mar 2016Although considerable research describes the cardiovascular effects of habitual moderate and heavy alcohol consumption, the immediate risks following alcohol intake have... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Although considerable research describes the cardiovascular effects of habitual moderate and heavy alcohol consumption, the immediate risks following alcohol intake have not been well characterized. Based on its physiological effects, alcohol may have markedly different effects on immediate and long-term risk.
METHODS AND RESULTS
We searched CINAHL, Embase, and PubMed from inception to March 12, 2015, supplemented with manual screening for observational studies assessing the association between alcohol intake and cardiovascular events in the following hours and days. We calculated pooled relative risks and 95% confidence intervals for the association between alcohol intake and myocardial infarction, ischemic stroke, and hemorrhagic stroke using DerSimonian and Laird random-effects models to model any alcohol intake or dose-response relationships of alcohol intake and cardiovascular events. Among 1056 citations and 37 full-text articles reviewed, 23 studies (29 457 participants) were included. Moderate alcohol consumption was associated with an immediately higher cardiovascular risk that was attenuated after 24 hours, and even protective for myocardial infarction and hemorrhagic stroke (≈2-4 drinks: relative risk=30% lower risk) and protective against ischemic stroke within 1 week (≈6 drinks: 19% lower risk). In contrast, heavy alcohol drinking was associated with higher cardiovascular risk in the following day (≈6-9 drinks: relative risk=1.3-2.3) and week (≈19-30 drinks: relative risk=2.25-6.2).
CONCLUSIONS
There appears to be a consistent finding of an immediately higher cardiovascular risk following any alcohol consumption, but, by 24 hours, only heavy alcohol intake conferred continued risk.
Topics: Alcohol Drinking; Cardiovascular Diseases; Case-Control Studies; Dose-Response Relationship, Drug; Ethanol; Humans; Observational Studies as Topic; Risk Factors; Time Factors
PubMed: 26936862
DOI: 10.1161/CIRCULATIONAHA.115.019743 -
Acta Psychiatrica Scandinavica Oct 2022Rapid cycling is a common and disabling phenomenon in individuals with bipolar disorders. In the absence of a recent literature examination, this systematic review and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Rapid cycling is a common and disabling phenomenon in individuals with bipolar disorders. In the absence of a recent literature examination, this systematic review and meta-analysis aimed to synthesise the evidence of efficacy, acceptability and tolerability of treatments for individuals with rapid cycling bipolar disorder (RCBD).
METHOD
A systematic search was conducted to identify randomised controlled trials assigning participants with RCBD to pharmacological and/or non-pharmacological interventions. Study inclusion and data extraction were undertaken by two reviewers independently. The primary outcome was continuous within-subject RCBD illness severity before and after treatment. Pre-post random effects meta-analyses were conducted for each outcome/intervention arm studied, generating a standardised effect size (hedge's g) and 95% confidence interval (CI).
RESULTS
A total of 34 articles describing 30 studies were included. A total of 16 separate pharmacological treatments were examined in contrast to 1 psychological therapy study. Only quetiapine and lamotrigine were assessed in >5 studies. By assessing 95% CI overlap of within-subject efficacy effects compared to placebo, the only interventions suggesting significant depression benefits (placebo g = 0.60) were olanzapine (with/without fluoxetine; g = 1.01), citalopram (g = 1.10) and venlafaxine (g = 2.48). For mania, benefits were indicated for quetiapine (g = 1.01), olanzapine (g = 1.19) and aripiprazole (g = 1.09), versus placebo (g = 0.33). Most of these effect sizes were from only one trial per treatment. Heterogeneity between studies was variable, and 20% were rated to have a high risk of bias.
CONCLUSIONS
While many interventions appeared efficacious, there was a lack of robust evidence for most treatments. Given the limited and heterogeneous evidence base, the optimal treatment strategies for people with RCBD are yet to be established.
Topics: Aripiprazole; Bipolar Disorder; Citalopram; Fluoxetine; Humans; Lamotrigine; Olanzapine; Quetiapine Fumarate; Venlafaxine Hydrochloride
PubMed: 35778967
DOI: 10.1111/acps.13471