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European Journal of Internal Medicine Oct 2022Portal vein thrombosis (PVT) may be associated with negative outcomes in patients with liver cirrhosis. However, the prevalence and incidence of PVT in liver cirrhosis... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Portal vein thrombosis (PVT) may be associated with negative outcomes in patients with liver cirrhosis. However, the prevalence and incidence of PVT in liver cirrhosis are heterogeneous among studies and have not been sufficiently determined yet.
METHODS
The PubMed, EMBASE, and Cochrane Library databases were searched. Eligible studies would explore the prevalence and/or incidence of PVT in liver cirrhosis without hepatocellular carcinoma or abdominal surgery. Pooled proportion with 95% confidence interval (CI) was calculated using a random-effect model. Factors associated with the presence/occurrence of PVT were also extracted.
RESULTS
Among the 8549 papers initially identified, 74 were included. Fifty-four studies explored the prevalence of PVT in liver cirrhosis with a pooled prevalence of 13.92% (95%CI=11.18-16.91%). Based on cross-sectional data, Child-Pugh class B/C, higher D-dimer, ascites, and use of non-selective beta-blockers (NSBBs) were associated with the presence of PVT in liver cirrhosis. Twenty-three studies explored the incidence of PVT in liver cirrhosis with a pooled incidence of 10.42% (95%CI=8.16-12.92%). Based on cohort data, Child-Pugh class B/C, higher model of end-stage liver disease score, higher D-dimer, lower platelets count, decreased portal flow velocity, ascites, use of NSBBs, and moderate or high-risk esophageal varices could predict the occurrence of PVT in liver cirrhosis.
CONCLUSION
Approximately one seventh of cirrhotic patients have PVT, and one tenth will develop PVT. Progression of liver cirrhosis and portal hypertension seems to be in parallel with the risk of PVT. Prospective studies with detailed information about classification and extension of PVT in liver cirrhosis are needed.
Topics: Adrenergic beta-Antagonists; Ascites; Cross-Sectional Studies; Humans; Liver Cirrhosis; Portal Vein; Prospective Studies; Venous Thrombosis
PubMed: 35688747
DOI: 10.1016/j.ejim.2022.05.032 -
The Cochrane Database of Systematic... Jul 2023Different first-line drug classes for patients with hypertension are often assumed to have similar effectiveness with respect to reducing mortality and morbidity... (Review)
Review
BACKGROUND
Different first-line drug classes for patients with hypertension are often assumed to have similar effectiveness with respect to reducing mortality and morbidity outcomes, and lowering blood pressure. First-line low-dose thiazide diuretics have been previously shown to have the best mortality and morbidity evidence when compared with placebo or no treatment. Head-to-head comparisons of thiazides with other blood pressure-lowering drug classes would demonstrate whether there are important differences.
OBJECTIVES
To compare the effects of first-line diuretic drugs with other individual first-line classes of antihypertensive drugs on mortality, morbidity, and withdrawals due to adverse effects in patients with hypertension. Secondary objectives included assessments of the need for added drugs, drug switching, and blood pressure-lowering.
SEARCH METHODS
Cochrane Hypertension's Information Specialist searched the Cochrane Hypertension Specialized Register, CENTRAL, MEDLINE, Embase, and trials registers to March 2021. We also checked references and contacted study authors to identify additional studies. A top-up search of the Specialized Register was carried out in June 2022.
SELECTION CRITERIA
Randomized active comparator trials of at least one year's duration were included. Trials had a clearly defined intervention arm of a first-line diuretic (thiazide, thiazide-like, or loop diuretic) compared to another first-line drug class: beta-blockers, calcium channel blockers, alpha adrenergic blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, direct renin inhibitors, or other antihypertensive drug classes. Studies had to include clearly defined mortality and morbidity outcomes (serious adverse events, total cardiovascular events, stroke, coronary heart disease (CHD), congestive heart failure, and withdrawals due to adverse effects).
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodological procedures.
MAIN RESULTS
We included 20 trials with 26 comparator arms randomizing over 90,000 participants. The findings are relevant to first-line use of drug classes in older male and female hypertensive patients (aged 50 to 75) with multiple co-morbidities, including type 2 diabetes. First-line thiazide and thiazide-like diuretics were compared with beta-blockers (six trials), calcium channel blockers (eight trials), ACE inhibitors (five trials), and alpha-adrenergic blockers (three trials); other comparators included angiotensin II receptor blockers, aliskiren (a direct renin inhibitor), and clonidine (a centrally acting drug). Only three studies reported data for total serious adverse events: two studies compared diuretics with calcium channel blockers and one with a direct renin inhibitor. Compared to first-line beta-blockers, first-line thiazides probably result in little to no difference in total mortality (risk ratio (RR) 0.96, 95% confidence interval (CI) 0.84 to 1.10; 5 trials, 18,241 participants; moderate-certainty), probably reduce total cardiovascular events (5.4% versus 4.8%; RR 0.88, 95% CI 0.78 to 1.00; 4 trials, 18,135 participants; absolute risk reduction (ARR) 0.6%, moderate-certainty), may result in little to no difference in stroke (RR 0.85, 95% CI 0.66 to 1.09; 4 trials, 18,135 participants; low-certainty), CHD (RR 0.91, 95% CI 0.78 to 1.07; 4 trials, 18,135 participants; low-certainty), or heart failure (RR 0.69, 95% CI 0.40 to 1.19; 1 trial, 6569 participants; low-certainty), and probably reduce withdrawals due to adverse effects (10.1% versus 7.9%; RR 0.78, 95% CI 0.71 to 0.85; 5 trials, 18,501 participants; ARR 2.2%; moderate-certainty). Compared to first-line calcium channel blockers, first-line thiazides probably result in little to no difference in total mortality (RR 1.02, 95% CI 0.96 to 1.08; 7 trials, 35,417 participants; moderate-certainty), may result in little to no difference in serious adverse events (RR 1.09, 95% CI 0.97 to 1.24; 2 trials, 7204 participants; low-certainty), probably reduce total cardiovascular events (14.3% versus 13.3%; RR 0.93, 95% CI 0.89 to 0.98; 6 trials, 35,217 participants; ARR 1.0%; moderate-certainty), probably result in little to no difference in stroke (RR 1.06, 95% CI 0.95 to 1.18; 6 trials, 35,217 participants; moderate-certainty) or CHD (RR 1.00, 95% CI 0.93 to 1.08; 6 trials, 35,217 participants; moderate-certainty), probably reduce heart failure (4.4% versus 3.2%; RR 0.74, 95% CI 0.66 to 0.82; 6 trials, 35,217 participants; ARR 1.2%; moderate-certainty), and may reduce withdrawals due to adverse effects (7.6% versus 6.2%; RR 0.81, 95% CI 0.75 to 0.88; 7 trials, 33,908 participants; ARR 1.4%; low-certainty). Compared to first-line ACE inhibitors, first-line thiazides probably result in little to no difference in total mortality (RR 1.00, 95% CI 0.95 to 1.07; 3 trials, 30,961 participants; moderate-certainty), may result in little to no difference in total cardiovascular events (RR 0.97, 95% CI 0.92 to 1.02; 3 trials, 30,900 participants; low-certainty), probably reduce stroke slightly (4.7% versus 4.1%; RR 0.89, 95% CI 0.80 to 0.99; 3 trials, 30,900 participants; ARR 0.6%; moderate-certainty), probably result in little to no difference in CHD (RR 1.03, 95% CI 0.96 to 1.12; 3 trials, 30,900 participants; moderate-certainty) or heart failure (RR 0.94, 95% CI 0.84 to 1.04; 2 trials, 30,392 participants; moderate-certainty), and probably reduce withdrawals due to adverse effects (3.9% versus 2.9%; RR 0.73, 95% CI 0.64 to 0.84; 3 trials, 25,254 participants; ARR 1.0%; moderate-certainty). Compared to first-line alpha-blockers, first-line thiazides probably result in little to no difference in total mortality (RR 0.98, 95% CI 0.88 to 1.09; 1 trial, 24,316 participants; moderate-certainty), probably reduce total cardiovascular events (12.1% versus 9.0%; RR 0.74, 95% CI 0.69 to 0.80; 2 trials, 24,396 participants; ARR 3.1%; moderate-certainty) and stroke (2.7% versus 2.3%; RR 0.86, 95% CI 0.73 to 1.01; 2 trials, 24,396 participants; ARR 0.4%; moderate-certainty), may result in little to no difference in CHD (RR 0.98, 95% CI 0.86 to 1.11; 2 trials, 24,396 participants; low-certainty), probably reduce heart failure (5.4% versus 2.8%; RR 0.51, 95% CI 0.45 to 0.58; 1 trial, 24,316 participants; ARR 2.6%; moderate-certainty), and may reduce withdrawals due to adverse effects (1.3% versus 0.9%; RR 0.70, 95% CI 0.54 to 0.89; 3 trials, 24,772 participants; ARR 0.4%; low-certainty). For the other drug classes, data were insufficient. No antihypertensive drug class demonstrated any clinically important advantages over first-line thiazides.
AUTHORS' CONCLUSIONS
When used as first-line agents for the treatment of hypertension, thiazides and thiazide-like drugs likely do not change total mortality and likely decrease some morbidity outcomes such as cardiovascular events and withdrawals due to adverse effects, when compared to beta-blockers, calcium channel blockers, ACE inhibitors, and alpha-blockers.
Topics: Aged; Female; Humans; Male; Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium Channel Blockers; Coronary Disease; Diabetes Mellitus, Type 2; Diuretics; Heart Failure; Hypertension; Stroke; Thiazides; Middle Aged
PubMed: 37439548
DOI: 10.1002/14651858.CD008161.pub3 -
European Journal of Psychotraumatology 2021: Pharmacological approaches are widely used for post-traumatic stress disorder (PTSD) despite uncertainty over efficacy. : To determine the efficacy of all... (Meta-Analysis)
Meta-Analysis
: Pharmacological approaches are widely used for post-traumatic stress disorder (PTSD) despite uncertainty over efficacy. : To determine the efficacy of all pharmacological approaches, including monotherapy, augmentation and head-to-head approaches (drug versus drug, drug versus psychotherapy), in reducing PTSD symptom severity. : A systematic review and meta-analysis of randomised controlled trials were undertaken; 115 studies were included. : Selective serotonin reuptake inhibitors (SSRIs) were found to be statistically superior to placebo in reduction of PTSD symptoms but the effect size was small (standardised mean difference -0.28, 95% CI -0.39 to -0.17). For individual monotherapy agents compared to placebo in two or more studies, we found small statistically significant evidence for the antidepressants fluoxetine, paroxetine, sertraline, venlafaxine and the antipsychotic quetiapine. For pharmacological augmentation, we found small statistically significant evidence for prazosin and risperidone. : Some medications have a small positive effect on reducing PTSD symptom severity and can be considered as potential monotherapy treatments; these include fluoxetine, paroxetine, sertraline, venlafaxine and quetiapine. Two medications, prazosin and risperidone, also have a small positive effect when used to augment pharmacological monotherapy. There was no evidence of superiority for one intervention over another in the small number of head-to-head comparison studies.
Topics: Adrenergic alpha-1 Receptor Antagonists; Antipsychotic Agents; Drug Synergism; Drug Therapy, Combination; Humans; Selective Serotonin Reuptake Inhibitors; Stress Disorders, Post-Traumatic
PubMed: 34992738
DOI: 10.1080/20008198.2020.1802920 -
JAMA Network Open Feb 2021Combining 2 first-line treatments for erectile dysfunction (ED) or initiating other modalities in addition to a first-line therapy may produce beneficial outcomes. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Combining 2 first-line treatments for erectile dysfunction (ED) or initiating other modalities in addition to a first-line therapy may produce beneficial outcomes.
OBJECTIVE
To assess whether different ED combination therapies were associated with improved outcomes compared with first-line ED monotherapy in various subgroups of patients with ED.
DATA SOURCES
Studies were identified through a systematic search in MEDLINE, Cochrane Library, and Scopus from inception of these databases to October 10, 2020.
STUDY SELECTION
Randomized clinical trials or prospective interventional studies of the outcomes of combination therapy vs recommended monotherapy in men with ED were identified. Only comparative human studies, which evaluated the change from baseline of self-reported erectile function using validated questionnaires, that were published in any language were included.
DATA EXTRACTION AND SYNTHESIS
Data extraction and synthesis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline.
MAIN OUTCOMES AND MEASURES
A meta-analysis was conducted that included randomized clinical trials that compared outcomes of combination therapy with phosphodiesterase type 5 (PDE5) inhibitors plus another agent vs PDE5 inhibitor monotherapy. Separate analyses were performed for the mean International Index of Erectile Function (IIEF) score change from baseline and the number of adverse events (AEs) by different treatment modalities and subgroups of patients.
RESULTS
A total of 44 studies included 3853 men with a mean (SD) age of 55.8 (11.9) years. Combination therapy compared with monotherapy was associated with a mean IIEF score improvement of 1.76 points (95% CI, 1.27-2.24; I2 = 77%; 95% PI, -0.56 to 4.08). Adding daily tadalafil, low-intensity shockwave therapy, vacuum erectile device, folic acid, metformin hydrochloride, or angiotensin-converting enzyme inhibitors was associated with a significant IIEF score improvement, but each measure was based on only 1 study. Specifically, the weighted mean difference (WMD) in IIEF score was 1.70 (95% CI, 0.79-2.61) for the addition of daily tadalafil, 3.50 (95% CI, 0.22-6.78) for the addition of low-intensity shockwave therapy, 8.40 (95% CI, 4.90-11.90) for the addition of a vacuum erectile device, 3.46 (95% CI, 2.16-4.76) for the addition of folic acid, 4.90 (95% CI, 2.82-6.98) for the addition of metformin hydrochloride and 2.07 (95% CI, 1.37-2.77) for the addition of angiotensin-converting enzyme inhibitors. The addition of α-blockers to PDE5 inhibitors was not associated with improvement in IIEF score (WMD, 0.80; 95% CI, -0.06 to 1.65; I2 = 72%). Compared with monotherapy, combination therapy was associated with improved IIEF score in patients with hypogonadism (WMD, 1.61; 95% CI, 0.99-2.23; I2 = 0%), monotherapy-resistant ED (WMD, 4.38; 95% CI, 2.37-6.40; I2 = 52%), or prostatectomy-induced ED (WMD, 5.47; 95% CI, 3.11-7.83; I2 = 53%). The treatment-related AEs did not differ between combination therapy and monotherapy (odds ratio, 1.10; 95% CI, 0.66-1.85; I2 = 78%). Despite multiple subgroup and sensitivity analyses, the levels of heterogeneity remained high.
CONCLUSIONS AND RELEVANCE
This study found that combination therapy of PDE5 inhibitors and antioxidants was associated with improved ED without increasing the AEs. Treatment with PDE5 inhibitors and daily tadalafil, shockwaves, or a vacuum device was associated with additional improvement, but this result was based on limited data. These findings suggest that combination therapy is safe, associated with improved outcomes, and should be considered as a first-line therapy for refractory, complex, or difficult-to-treat cases of ED.
Topics: Adrenergic alpha-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antioxidants; Combined Modality Therapy; Drug Therapy, Combination; Equipment and Supplies; Erectile Dysfunction; Extracorporeal Shockwave Therapy; Folic Acid; Humans; Hypoglycemic Agents; Male; Metformin; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate; Tadalafil; Treatment Outcome; Vitamin B Complex
PubMed: 33599772
DOI: 10.1001/jamanetworkopen.2020.36337 -
Advances in Therapy Jun 2021In patients with chronic obstructive pulmonary disease (COPD) who experience further exacerbations or symptoms, despite being prescribed dual long-acting muscarinic... (Meta-Analysis)
Meta-Analysis
In patients with chronic obstructive pulmonary disease (COPD) who experience further exacerbations or symptoms, despite being prescribed dual long-acting muscarinic antagonist (LAMA)/long-acting β-agonist (LABA) or inhaled corticosteroid (ICS)/LABA therapies, triple ICS/LAMA/LABA therapy is recommended. A previous network meta-analysis showed comparable efficacy of the ICS/LAMA/LABA, budesonide/glycopyrronium bromide/formoterol fumarate (BUD/GLY/FOR) 320/18/9.6 µg, to other fixed-dose and open combination triple therapies at 24 weeks in COPD. Subsequently, the ETHOS study was published, including data for 8509 patients, assessing the efficacy and safety of BUD/GLY/FOR over 52 weeks. This network meta-analysis (NMA) was conducted to compare the relative efficacy, safety, and tolerability of BUD/GLY/FOR 320/18/9.6 µg with other fixed-dose and open combination triple therapies in COPD over 52 weeks, including data from ETHOS. A systematic literature review was conducted to identify ≥ 10-week randomized controlled trials, including ≥ 1 fixed-dose or open combination triple-therapy arm, in patients with moderate-to-very severe COPD. The methodologic quality and risk of bias of included studies were assessed. Study results were combined using a three-level hierarchical Bayesian NMA model to assess efficacy and safety outcomes at or over 24 and 52 weeks. Meta-regression and sensitivity analyses were used to assess heterogeneity across studies. Nineteen studies (n = 37,741 patients) met the inclusion criteria of the review; 15 contributed to the base case network. LAMA/LABA dual combinations were combined as a single treatment group to create a connected network. Across all outcomes for exacerbations, lung function, symptoms, health-related quality of life, safety, and tolerability, the efficacy and safety of BUD/GLY/FOR were comparable to those of other triple ICS/LAMA/LABA fixed-dose (fluticasone furoate/umeclidinium/vilanterol and beclomethasone dipropionate/glycopyrronium bromide/formoterol fumarate) and open combinations at or over 24 and 52 weeks. Sensitivity analyses and meta-regression results for exacerbation outcomes were broadly in line with the base case NMA. In this NMA, BUD/GLY/FOR 320/18/9.6 μg showed comparable efficacy versus other ICS/LAMA/LABA fixed-dose or open combination therapies in terms of reducing exacerbation rates and improving lung function, symptoms and health-related quality of life in patients with moderate-to-very-severe COPD, in line with previously published meta-analysis results of triple combinations in COPD. The safety and tolerability profile of BUD/GLY/FOR was also found to be comparable to other triple combination therapies.
Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Bayes Theorem; Bronchodilator Agents; Budesonide; Drug Combinations; Formoterol Fumarate; Fumarates; Glycopyrrolate; Humans; Muscarinic Antagonists; Network Meta-Analysis; Pulmonary Disease, Chronic Obstructive; Quality of Life
PubMed: 33929661
DOI: 10.1007/s12325-021-01703-z -
Current Problems in Cardiology Mar 2024While beta-blockers are considered the cornerstone of treatment for heart failure with reduced ejection fraction, the same may not apply to patients with heart failure... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
While beta-blockers are considered the cornerstone of treatment for heart failure with reduced ejection fraction, the same may not apply to patients with heart failure with preserved ejection fraction (HFpEF). To date, the benefit of beta-blockers remains uncertain, and there is no current consensus on their effectiveness. This study sought to evaluate the efficacy of beta-blockers on mortality and rehospitalization among patients with HFpEF.
METHODS
A systematic review and meta-analysis of randomized or observational cohort studies examined the efficacy of beta-blocker therapy in comparison with placebo, control, or standard medical care in patients with HFpEF, defined as left ventricular ejection fraction ≥50 %. The main endpoints were mortality (i.e., all-cause and cardiovascular), rehospitalization (i.e., all-cause and for heart failure) and a composite of the two.
RESULTS
Out of the 13,189 records initially identified, 16 full-text records met the inclusion criteria and were analyzed recruiting a total of 27,188 patients. The mean age range was 62-84 years old, predominantly female, with HFpEF in which 63.4 % of patients received a beta-blocker and 36.6 % did not. The pooled analysis of included cohort studies, of variable follow-up durations, showed a significant reduction in all-cause mortality by 19 % (odds ratio (OR) 0.81; 95 % confidence interval (CI): 0.65-0.99, p = 0.044) whereas rehospitalization for heart failure (OR 1.13; 95 % CI: 0.91-1.41, p = 0.27) or its composite with all-cause mortality (OR 1.01; 95 % CI: 0.78-1.32, p = 0.92) were similar between the beta-blocker and control groups.
CONCLUSION
This meta-analysis showed that beta-blocker therapy has the potential to reduce all-cause mortality in patients with HFpEF based on observational studies. Nevertheless, it did not affect rehospitalization for heart failure or its composite with all-cause mortality. Large scale randomized trials are needed to clarify this uncertainty.
Topics: Humans; Female; Middle Aged; Aged; Aged, 80 and over; Male; Stroke Volume; Heart Failure; Ventricular Function, Left; Patient Readmission; Hospitalization; Adrenergic beta-Antagonists; Observational Studies as Topic
PubMed: 38184132
DOI: 10.1016/j.cpcardiol.2024.102376 -
International Journal of Environmental... Dec 2022Nightmares are highly prevalent and distressing for the sufferer, which underlines the need for well-documented treatments. A comprehensive literature review and... (Meta-Analysis)
Meta-Analysis Review
Nightmares are highly prevalent and distressing for the sufferer, which underlines the need for well-documented treatments. A comprehensive literature review and meta-analysis of the effects of different pharmacological placebo-controlled randomized clinical trials, covering the period up to 1 December 2022, was performed. Searches were conducted in PubMed, Embase, Web of Science, PsychInfo, Cinahl, and Google Scholar, resulting in the identification of 1762 articles, of which 14 met the inclusion criteria: pharmacological intervention of nightmares, based on a placebo-controlled randomized trial published in a European language, reporting outcomes either/or in terms of nightmare frequency, nightmare distress, or nightmare intensity, and reporting sufficient information enabling calculation of effect sizes. Most studies involved the effect of the α-adrenergic antagonist prazosin in samples of veterans or soldiers suffering from posttraumatic stress disorder. Other medications used were hydroxyzine, clonazepam, cyproheptadine, nabilone, and doxazosin. The vast majority of studies were conducted in the USA. The studies comprised a total of 830 participants. The Clinician-Administered PTSD Scale was the most frequently used outcome measure. The results showed an overall effect size of Hedges' = 0.50 (0.42 after adjustment for publication bias). The synthetic cannabinoid nabilone (one study) showed the highest effect size ( = 1.86), followed by the histamine H-antagonist hydroxyzine (one study), and prazosin (10 studies), with effect sizes of = 1.17 and = 0.54, respectively. Findings and limitations are discussed, and recommendations for future studies are provided.
Topics: Humans; Dreams; Randomized Controlled Trials as Topic; Prazosin; Adrenergic alpha-1 Receptor Antagonists; Stress Disorders, Post-Traumatic; Hydroxyzine
PubMed: 36613097
DOI: 10.3390/ijerph20010777 -
Asian Journal of Psychiatry Jan 2023To integrate all evidence derived from randomized controlled trials (RCTs) of both pharmacological and nonpharmacological augmentation interventions for... (Meta-Analysis)
Meta-Analysis
Pharmacological and nonpharmacological augmentation treatments for clozapine-resistant schizophrenia: A systematic review and network meta-analysis with normalized entropy assessment.
OBJECTIVE
To integrate all evidence derived from randomized controlled trials (RCTs) of both pharmacological and nonpharmacological augmentation interventions for clozapine-resistant schizophrenia (CRS).
METHODS
Six major electronic databases were systematically searched for RCTs published until July 10, 2021. The primary outcome was change in overall symptoms, and the secondary outcomes were positive and negative symptoms and acceptability. We performed random-effects network meta-analysis. Normalized entropy was calculated to examine the uncertainty of treatment ranking.
RESULTS
We identified 35 RCTs (1472 patients with 23 active augmentation treatments) with a mean daily clozapine dose of 440.80 (91.27) mg for 1168.22 (710.28) days. Network meta-analysis of overall symptoms (reported as standardized mean difference; 95 % confidence interval) with consistent results indicated that mirtazapine (-4.41; -5.61, -3.21), electroconvulsive therapy (ECT) (-4.32; -5.43, -3.21), and memantine (-2.02; -3.14, -0.91) were ranked as the best three treatments. For positive symptoms, ECT (-5.18; -5.86, -4.49) was ranked the best with less uncertainty. For negative symptoms, memantine (-3.38; -4.50, -2.26), duloxetine (-3.27; -4.25, -2.29), and mirtazapine (-1.73; -2.71, -0.74) were ranked the best three treatments with less uncertainty. All antipsychotics, N-methyl d-aspartate receptor agonists, and antiepileptics were not associated with more efficacy than placebo. Compared to placebo, only amisulpride had statistically significant lower discontinuation rate (risk ratio: 0.21; 95 % CI: 0.05, 0.93).
CONCLUSION
Add-on mirtazapine, ECT, and memantine were the most efficacious augmentation options for CRS. Data on other important outcomes such as cognitive functioning or quality of life were rarely reported, making further large-scale, well-designed RCTs necessary. (PROSPERO number, CRD42021262197.).
Topics: Humans; Clozapine; Network Meta-Analysis; Entropy; Memantine; Mirtazapine; Antipsychotic Agents; Schizophrenia
PubMed: 36470132
DOI: 10.1016/j.ajp.2022.103375 -
Advances in Therapy Nov 2022Few randomised controlled trials (RCTs) have directly compared long-acting muscarinic antagonist/long-acting β-agonist (LAMA/LABA) dual maintenance therapies for... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Few randomised controlled trials (RCTs) have directly compared long-acting muscarinic antagonist/long-acting β-agonist (LAMA/LABA) dual maintenance therapies for patients with chronic obstructive pulmonary disease (COPD). This systematic literature review and network meta-analysis (NMA) compared the efficacy of umeclidinium/vilanterol (UMEC/VI) versus other dual and mono-bronchodilator therapies in symptomatic patients with COPD.
METHODS
A systematic literature review (October 2015-November 2020) was performed to identify RCTs ≥ 8 weeks long in adult patients with COPD that compared LAMA/LABA combinations against any long-acting bronchodilator-containing dual therapy or monotherapy. Data extracted on changes from baseline in trough forced expiratory volume in 1 s (FEV), St George's Respiratory Questionnaire (SGRQ) total score, Transitional Dyspnoea Index (TDI) focal score, rescue medication use and moderate/severe exacerbation rate were analysed using an NMA in a frequentist framework. The primary comparison was at 24 weeks. Fixed effects model results are presented.
RESULTS
The NMA included 69 full-length publications (including 10 GSK clinical study reports) reporting 49 studies. At 24 weeks, UMEC/VI provided statistically significant greater improvements in FEV versus all dual therapy and monotherapy comparators. UMEC/VI provided similar improvements in SGRQ total score compared with all other LAMA/LABAs, and significantly greater improvements versus UMEC 125 μg, glycopyrronium 50 μg, glycopyrronium 18 μg, tiotropium 18 μg and salmeterol 50 μg. UMEC/VI also provided significantly better outcomes versus some comparators for TDI focal score, rescue medication use, annualised moderate/severe exacerbation rate, and time to first moderate/severe exacerbation.
CONCLUSION
UMEC/VI provided generally better outcomes compared with LAMA or LABA monotherapies, and consistent improvements in lung function (measured by change from baseline in trough FEV at 24 weeks) versus dual therapies. Treatment with UMEC/VI may improve outcomes for symptomatic patients with COPD compared with alternative maintenance treatments.
Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Adult; Benzyl Alcohols; Bronchodilator Agents; Chlorobenzenes; Drug Combinations; Dyspnea; Forced Expiratory Volume; Glycopyrrolate; Humans; Muscarinic Antagonists; Network Meta-Analysis; Pulmonary Disease, Chronic Obstructive; Quinuclidines; Salmeterol Xinafoate; Tiotropium Bromide; Treatment Outcome
PubMed: 35857184
DOI: 10.1007/s12325-022-02234-x -
The American Journal of Emergency... Jan 2022Intravenous diltiazem and metoprolol are both commonly used to treat atrial fibrillation (AF) with rapid ventricular rate (RVR) in the emergency department (ED), but the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Intravenous diltiazem and metoprolol are both commonly used to treat atrial fibrillation (AF) with rapid ventricular rate (RVR) in the emergency department (ED), but the advantages and disadvantages of these drugs cannot be verified. This meta-analysis aimed to assess the efficacy and safety of intravenous diltiazem versus metoprolol for AF with RVR.
METHOD
We systematically searched PubMed, Web of Science, Embase, Cochrane library, the China National Knowledge Infrastructure (CNKI), Wanfang, China Biology Medicine disc (CBM) and the WeiPu (VIP). Meta-analysis was performed using weighted mean difference (WMD), relative risk (RR) and 95% confidence interval (CI). Statistical analysis was performed using Review Manager 5.4.1.
RESULTS
Seventeen studies involving 1214 patients in nine randomized controlled trials (RCTs) and eight cohort studies were included in meta-analysis, including 643 patients in the intravenous diltiazem group and 571 patients group in the intravenous metoprolol. The results of the meta-analysis showed that compared with intravenous metoprolol, intravenous diltiazem was found higher efficacy (RR =1.11; 95% CI = 1.06 to 1.16, p < 0.00001), shorter average onset time (RR = -1.13; 95% CI = -1.97 to -0.28, p = 0.009), lower ventricular rate (RR = -9.48; 95% CI = -12.13 to -6.82, p<0.00001), less impact on systolic blood pressure (WMD = 3.76; 95% CI: 0.20 to 7.33, P = 0.04), and no significant difference in adverse events (RR = 0.80, 95% CI = 0.55 to 1.14, P = 0.22) and diastolic blood pressure (WMD = -1.20; 95% CI: -3.43 to 1.04, P = 0.29) was found between intravenous diltiazem and metoprolol.
CONCLUSION
Intravenous diltiazem has higher efficacy, shorter average onset time, lower ventricular rate, less impact on blood pressure, and with no increase in adverse events compared to intravenous metoprolol.
Topics: Administration, Intravenous; Atrial Fibrillation; Blood Pressure; Diltiazem; Heart Rate; Humans; Metoprolol; Randomized Controlled Trials as Topic
PubMed: 34781150
DOI: 10.1016/j.ajem.2021.08.082