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ESC Heart Failure Aug 2022Recent studies have suggested potential sex differences in treatment response to pharmacological therapies in heart failure (HF). We performed a systematic review and... (Meta-Analysis)
Meta-Analysis
AIMS
Recent studies have suggested potential sex differences in treatment response to pharmacological therapies in heart failure (HF). We performed a systematic review and meta-analysis of studies comparing treatment effects between men and women with HF and reduced ejection fraction (HFrEF) using established guideline-directed medical therapy and other emerging pharmacological treatments.
METHODS AND RESULTS
Systematic search was performed on PubMed, Embase, and Cochrane Library for randomized controlled trials published in 1990-2021. Outcomes were all-cause mortality and combined outcome of all-cause mortality and/or hospitalization for HF. Of 618 articles identified, 25 articles and 100 213 patients (mean age 62 ± 1.7 years, women 23.1%, mean left ventricular ejection fraction 26.6 ± 1.3%) were included in the systematic review and meta-analysis. For the outcome of all-cause mortality, there was no evidence of treatment heterogeneity by sex for renin-angiotensin system inhibitors (RASi) [hazard ratio (HR) 0.86 (95% confidence interval 0.75-0.99) in men; HR 0.97 (0.77-1.23) in women; P = 0.288], or for beta-blockers (BB) [HR 0.71 (0.59-0.86) in men; HR 0.87 (0.73-1.03) in women; P = 0.345]. Similarly, for the composite outcome of death or HF hospitalization, there was no evidence of treatment heterogeneity by sex for RASi [HR 0.84 (0.77-0.93) in men; HR 0.94 (0.81-1.08) in women; P = 0.210] or BB [HR 0.76 (0.64-0.90) in men; HR 0.72 (0.60-0.86) in women; P = 0.650]. Results for mineralocorticoid receptor antagonists (MRA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) from previously published meta-analyses were included in the review. For the combined outcome of cardiovascular death or HF hospitalization, no significant interaction for sex was observed for MRA (P = 0.78) or SGLT2i (P = 0.37). Results for emerging pharmacological treatments, such as soluble guanylate cyclase stimulators and cardiac myosin activators, were included in the review and showed consistent treatment effects between men and women.
CONCLUSIONS
Our meta-analysis showed no differences between sex in treatment effect for BB and RASi. Review on previously published trials for MRA, SGLT2i, and emerging therapies presented consistent treatment effects between men and women.
Topics: Female; Humans; Male; Middle Aged; Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Heart Failure; Mineralocorticoid Receptor Antagonists; Sex Characteristics; Sodium-Glucose Transporter 2 Inhibitors; Stroke Volume; Ventricular Function, Left
PubMed: 35603531
DOI: 10.1002/ehf2.13974 -
Respiratory Care Feb 2014The use of β2 agonist as an intervention for acute lung injury (ALI) and ARDS patients is controversial, so we performed a systematic review and meta-analysis of the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The use of β2 agonist as an intervention for acute lung injury (ALI) and ARDS patients is controversial, so we performed a systematic review and meta-analysis of the published randomized controlled trials of using β2 agonists to improve outcomes (mortality and ventilator free days) among patients with ALI/ARDS.
METHODS
A comprehensive search of 7 major databases (Ovid MEDLINE In-Process and other non-indexed citations, Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials (CENTRAL), Ovid Cochrane Database of Systematic Reviews, Web of Science, and Scopus) for randomized controlled trials using β2 agonists for ALI from their origin to March 2013 was conducted. The effect size was measured by relative risk for dichotomous outcomes, and mean difference for continuous outcomes, with 95% CI. The statistical heterogeneity between the studies was assessed with the Cochran Q test and I(2) statistic. The heterogeneity of > 50% was considered significant for the analysis. The Cochrane risk of bias tool was used to ascertain the quality of the included studies.
RESULTS
Out of 219 studies screened, 3 randomized controlled trials reported mortality and ventilator-free days, in 646 ALI/ARDS subjects. Of the 646 subjects, 334 (51.7%) received β2 agonist and 312 (48.3%) received placebo. There was no significant decrease in 28-day mortality or hospital mortality in the β2-agonist group: relative risk 1.04, 95% CI 0.50-2.16, and relative risk 1.22, 95% CI 0.95-1.56, respectively. The ventilator-free days and organ-failure-free days were significantly lower for the ALI subjects who received β2 agonists: mean difference -2.19 days (95% CI -3.68 to -1.99 d) and mean difference -2.04 days (95% CI -3.74 to -0.35 d), respectively.
CONCLUSIONS
In subjects with ALI/ARDS, β2 agonists were not only nonbeneficial in improving the survival, but were harmful and increased morbidity (reduced organ-failure-free days and ventilator-free days). The current evidence discourages the use of β2 agonist in ALI/ARDS patients. (International Prospective Register of Systematic Reviews, http://www.crd.york.ac.uk/prospero, 2012:CRD42012002616.).
Topics: Acute Lung Injury; Adrenergic beta-2 Receptor Antagonists; Humans; Randomized Controlled Trials as Topic; Receptors, Adrenergic, beta-2; Respiratory Distress Syndrome; Treatment Outcome
PubMed: 23777655
DOI: 10.4187/respcare.02571 -
International Journal of Chronic... 2017Randomized controlled trials (RCTs) indicate that long-acting bronchodilator combinations, such as β-agonist (LABA)/muscarinic antagonist (LAMA), have favorable... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Randomized controlled trials (RCTs) indicate that long-acting bronchodilator combinations, such as β-agonist (LABA)/muscarinic antagonist (LAMA), have favorable efficacy compared with commonly used COPD treatments. The objective of this analysis was to compare the efficacy and safety of LABA/LAMA with LAMA or LABA/inhaled corticosteroid (ICS) in adults with stable moderate-to-very-severe COPD.
METHODS
This systematic review and meta-analysis (PubMed/MEDLINE, Embase, Cochrane Library and clinical trial/manufacturer databases) included RCTs comparing ≥12 weeks' LABA/LAMA treatment with LAMA and/or LABA/ICS (approved doses only). Eligible studies were independently selected by two authors using predefined data fields; the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed.
RESULTS
Eighteen studies (23 trials) were eligible (N=20,185). LABA/LAMA significantly improved trough forced expiratory volume in 1 second (FEV) from baseline to week 12 versus both LAMA and LABA/ICS (0.07 L and 0.08 L, <0.0001), with patients more likely to achieve clinically important improvements in FEV of >100 mL (risk ratio [RR]: 1.33, 95% confidence interval [CI]: [1.20, 1.46] and RR: 1.44, 95% CI: [1.33, 1.56], respectively, the number needed to treat being eight and six, respectively). LABA/LAMA improved transitional dyspnea index and St George's Respiratory Questionnaire scores at week 12 versus LAMA (both <0.0001), but not versus LABA/ICS, and reduced rescue medication use versus both (<0.0001 and =0.001, respectively). LABA/LAMA significantly reduced moderate/severe exacerbation rate compared with LABA/ICS (RR 0.82, 95% CI: [0.75, 0.91]). Adverse event (AE) incidence was no different for LABA/LAMA versus LAMA treatment, but it was lower versus LABA/ICS (RR 0.94, 95% CI: [0.89, 0.99]), including a lower pneumonia risk (RR 0.59, 95% CI: [0.43, 0.81]). LABA/LAMA presented a lower risk for withdrawals due to lack of efficacy versus LAMA (RR: 0.66, 95% CI: [0.51, 0.87]) and due to AEs versus LABA/ICS (RR: 0.83, 95% CI: [0.69, 0.99]).
CONCLUSION
The greater efficacy and comparable safety profiles observed with LABA/LAMA combinations versus LAMA or LABA/ICS support their potential role as first-line treatment options in COPD. These findings are of direct relevance to clinical practice because we included all currently available LABA/LAMAs and comparators, only at doses approved for clinical use.
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Bronchodilator Agents; Chi-Square Distribution; Disease Progression; Drug Combinations; Forced Expiratory Volume; Humans; Lung; Muscarinic Antagonists; Odds Ratio; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Recovery of Function; Risk Factors; Time Factors; Treatment Outcome
PubMed: 28360514
DOI: 10.2147/COPD.S130482 -
Europace : European Pacing,... Jul 2022Vasovagal syncope (VVS) is a common clinical condition that lacks effective medical therapies despite being associated with significant morbidity. Current guidelines... (Meta-Analysis)
Meta-Analysis
AIMS
Vasovagal syncope (VVS) is a common clinical condition that lacks effective medical therapies despite being associated with significant morbidity. Current guidelines suggest that midodrine, a prodrug for an α1-adrenergic receptor agonist, might suppress VVS but supporting studies have utilized heterogeneous methods and yielded inconsistent results. To evaluate the efficacy of midodrine to prevent syncope in patients with recurrent VVS by conducting a systematic review and meta-analysis of published studies.
METHODS AND RESULTS
Relevant randomized controlled trials were identified from the MEDLINE, Embase, CENTRAL, and CINAHL databases without language restriction from inception to June 2021. All studies were conducted in clinical syncope populations and compared the benefit of midodrine vs. placebo or non-pharmacological standard care. Weighted relative risks (RRs) were estimated using random effects meta-analysis techniques. Seven studies (n = 315) met inclusion criteria. Patients were 33 ± 17 years of age and 31% male. Midodrine was found to substantially reduce the likelihood of positive head-up-tilt (HUT) test outcomes [RR = 0.37 (0.23-0.59), P < 0.001]. In contrast, the pooled results of single- and double-blind clinical trials (I2 = 54%) suggested a more modest benefit from midodrine for the prevention of clinical syncope [RR = 0.51 (0.33-0.79), P = 0.003]. The two rigorous double-blind, randomized, placebo-controlled clinical trials included 179 VVS patients with minimal between-study heterogeneity (I2 = 0%) and reported a risk reduction with midodrine [RR = 0.71 (0.53-0.95), P = 0.02].
CONCLUSIONS
Midodrine is effective in preventing syncope induced by HUT testing and less, but still significant, RR reduction in randomized, double-blinded clinical trials.
Topics: Double-Blind Method; Female; Humans; Male; Midodrine; Randomized Controlled Trials as Topic; Syncope; Syncope, Vasovagal; Tilt-Table Test
PubMed: 35025999
DOI: 10.1093/europace/euab323 -
The Cochrane Database of Systematic... Jan 2014Awake fibreoptic intubation (AFOI) frequently requires sedation, anxiolysis and relief of discomfort without impairing ventilation and depressing cardiovascular... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Awake fibreoptic intubation (AFOI) frequently requires sedation, anxiolysis and relief of discomfort without impairing ventilation and depressing cardiovascular function. The goal is to allow the patient to be responsive and co-operative. Medications such as fentanyl, remifentanil, midazolam and propofol have been reported to assist AFOI; however,these agents are associated with cardiovascular or respiratory adverse effects. Dexmedetomidine has been proposed as an alternative to facilitate AFOI.
OBJECTIVES
The primary objective of this review is to evaluate and compare the efficacy and safety of dexmedetomidine in the management of patients with a difficult or unstable airway undergoing awake fibreoptic intubation (AFOI).
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2012, Issue 5), MEDLINE (1966 to May 2012) through Ovid, EMBASE (1980 to May 2012) and Web of Science (1945 to May 2012); we screened the reference lists of all eligible trials and reviews to look for further trials and contacted authors of trials to ask for additional information. We searched for ongoing trials at http://www.controlledtrials.com/ and http://clinicaltrials.gov/ . We reran our search of all databases listed above on 21 November 2013.
SELECTION CRITERIA
We included published and unpublished randomized controlled trials, regardless of blinding or language of publication, in participants 18 years of age or older who were scheduled for an elective AFOI because of an anticipated difficult airway. Participants received dexmedetomidine or control medications.
DATA COLLECTION AND ANALYSIS
Three review authors independently extracted data on study design, participants, interventions and outcomes. We assessed risk of bias using The Cochrane Collaboration's tool. We estimated risk ratios (RRs) or mean differences (MDs) with 95% confidence internals (CIs) for outcomes with sufficient data; for other outcomes, we performed a qualitative analysis.
MAIN RESULTS
We identified four randomized controlled trials (RCTs), which included 211 participants. The four trials compared dexmedetomidine with midazolam, fentanyl, propofol or a sodium chloride placebo, respectively. The trials showed low or unclear risk of bias primarily because information provided on allocation concealment and other potential sources of bias was inadequate. Owing to clinical heterogeneity and potential methodological heterogeneity, it was impossible to conduct a full meta-analysis. We described findings from individual studies or presented them in tabular form. Limited evidence was available for assessment of the outcomes of interest for this review. Results of the limited included trials showed that dexmedetomidine significantly reduced participants' discomfort with no significant differences in airway obstruction, low oxygen levels or treatment-emergent cardiovascular adverse events noted during AFOI compared with control groups. When the search was rerun (from May 2012 to November 2013), it was noted that four studies are awaiting assessment. We will deal with these studies when we update the review.
AUTHORS' CONCLUSIONS
Small, limited trials provide weak evidence to support dexmedetomidine as an option for patients with an anticipated difficult airway who undergo AFOI. The findings of this review should be further corroborated by additional controlled investigations.
Topics: Adrenergic alpha-2 Receptor Agonists; Anti-Anxiety Agents; Dexmedetomidine; Fentanyl; Humans; Hypnotics and Sedatives; Intubation, Intratracheal; Midazolam; Propofol; Randomized Controlled Trials as Topic; Wakefulness
PubMed: 24442817
DOI: 10.1002/14651858.CD009798.pub2 -
The Journal of Clinical Pediatric... 2015Dexmedetomidine is a central α-2 agonist, similar to Clonidine, but 8 times more specific for the central α-2 receptor which causes sedation with minimal depression of... (Review)
Review
UNLABELLED
Dexmedetomidine is a central α-2 agonist, similar to Clonidine, but 8 times more specific for the central α-2 receptor which causes sedation with minimal depression of respiration, making it safe for sedation during procedures. It is widely used in the field of medicine for many procedures especially premedication, awake intubation, and sedation of patients in intensive care units and pediatric procedural sedation.
OBJECTIVE
To do a systematic review of the pharmacology, pharmacodynamics, as well as the usage of newer sedative drug- Dexmedetomidine in dentistry.
STUDY DESIGN
The search for articles was conducted in Pub Med, including the articles published in English until Oct 2014. Both animal and human studies were included using the key words, "Dexmedetomidine", "Dexmedetomidine in sedation", "Dexmedetomidine in Dentistry", and "Dexmedetomidine in Pediatric dentistry". The Articles obtained were checked for their quality methodology and inference of the studies and selected for review.
RESULTS
Initial search retrieved 2436 articles, out of which 44 articles were on the subject of Dexmedetomidine in dentistry. Five of which articles were on the usage of Dexmedetomidine in pediatric dentistry. These studies were included in systematic review.
CONCLUSION
The study revealed that Dexmedetomidine being a new drug with its added advantages makes a better choice for sedation in dentistry. But with limited studies on Dexmedetomidine, the recommendation to use the drug exclusively is still under debate.
Topics: Adrenergic alpha-2 Receptor Agonists; Anesthesia, Dental; Conscious Sedation; Dexmedetomidine; Humans; Hypnotics and Sedatives
PubMed: 26551360
DOI: 10.17796/1053-4628-39.5.401 -
Prostate International Jun 2023To compare the effects of different alpha-blocker regimes on acute urinary retention (AUR) and the success rate of trial without catheter (TWOC) among patients with...
BACKGROUND
To compare the effects of different alpha-blocker regimes on acute urinary retention (AUR) and the success rate of trial without catheter (TWOC) among patients with AUR secondary to benign prostatic hyperplasia (BPH) to determine the most effective regime.
METHODS
A comprehensive literature search was performed using PubMed/Medline, Embase, and Cochrane Library up to June 2021. Studies that compared successful TWOC rates between each alpha-blocker regime in patients with AUR secondary to BPH were included. The outcome was the odds ratio of successful TWOC after AUR between groups (each regime of alpha blocker or placebo). To indirectly compare the effect of each alpha-blocker regime on the outcome (successful TWOC rate), a network meta-analysis was conducted using a Bayesian hierarchical random effects model for dichotomous outcomes.
RESULTS
In total, 13 randomized controlled trials were included in the present study. There were six nodes (five alpha-blocker regimes and placebo) and eight comparisons in the evidence network plot. Compared to placebo, alfuzosin, silodosin, tamsulosin, and alfuzosin plus tamsulosin resulted in significantly higher TWOC success rates, whereas doxazosin did not show a significant difference in TWOC success rate compared to placebo. Alfuzosin plus tamsulosin was ranked first, followed in order by tamsulosin, silodosin, alfuzosin, and doxazosin. There was no significant inconsistency in the results of this analysis.
CONCLUSIONS
Alpha blockers may increase the success rate of TWOC. This study evaluated the priority of the effect of several alpha-blocker regimens on AUR related to BPH, which is expected to be helpful in selecting the best medication for patients with AUR.
PubMed: 37409094
DOI: 10.1016/j.prnil.2022.12.002 -
British Journal of Anaesthesia May 2022New onset atrial fibrillation (NOAF) is the most common arrhythmia affecting critically unwell patients. NOAF can lead to worsening haemodynamic compromise, heart... (Review)
Review
BACKGROUND
New onset atrial fibrillation (NOAF) is the most common arrhythmia affecting critically unwell patients. NOAF can lead to worsening haemodynamic compromise, heart failure, thromboembolic events, and increased mortality. The aim of this systematic review and narrative synthesis is to evaluate the non-pharmacological and pharmacological management strategies for NOAF in critically unwell patients.
METHODS
Of 1782 studies, 30 were eligible for inclusion, including 4 RCTs and 26 observational studies. Efficacy of direct current cardioversion, amiodarone, β-adrenergic receptor antagonists, calcium channel blockers, digoxin, magnesium, and less commonly used agents such as ibutilide are reported.
RESULTS
Cardioversion rates of 48% were reported for direct current cardioversion; however, re-initiation of NOAF was as high as 23.4%. Amiodarone was the most commonly reported intervention with cardioversion rates ranging from 18% to 96% followed by β-antagonists with cardioversion rates from 40% to 92%. Amiodarone was more effective than diltiazem (odds ratio [OR]=1.91, P=0.32) at cardioversion. Short-acting β-antagonists esmolol and landiolol were more effective compared with diltiazem for cardioversion (OR=3.55, P=0.04) and HR control (OR=3.2, P<0.001).
CONCLUSION
There was significant variation between studies with regard to the definition of successful cardioversion and heart rate control, making comparisons between studies and interventions difficult. Future RCTs comparing individual anti-arrhythmic agents, in particular magnesium, amiodarone, and β-antagonists, and studying the role of anticoagulation in critically unwell patients are required. There is also an urgent need for a core outcome dataset for studies of new onset atrial fibrillation to allow comparisons between different anti-arrhythmic strategies.
CLINICAL TRIAL REGISTRATION
PROSPERO CRD42019121739.
Topics: Adult; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Diltiazem; Electric Countershock; Humans; Magnesium
PubMed: 34916053
DOI: 10.1016/j.bja.2021.11.016 -
Psychopharmacology Bulletin Oct 2020This evidence-based systematic review will focus on the use of dexmedetomidine and its role as adjuvant anesthetics in regional blocks to help better guide physicians in... (Review)
Review
PURPOSE OF REVIEW
This evidence-based systematic review will focus on the use of dexmedetomidine and its role as adjuvant anesthetics in regional blocks to help better guide physicians in their practice. This review will cover background and mechanism of dexmedetomidine as well as the use in various regional blocks.
RECENT FINDINGS
Local anesthetics are preferred for nerve blocks over opioids; however, both due come with its own side effects. Local anesthetics may be toxic as they disrupt cell membrane and proteins, but by using adjuvants such as dexmedetomidine, that can prolong sensory and motor blocks can reduce total amount of local anesthetics needed. Dexmedetomidine is an alpha-2-adrenergic agonist used as additive for regional nerve block. It has a relatively low side effect profile and have been researched in various regional blocks (intrathecal, paravertebral, axillary, infraclavicular brachial plexus, interscalene). Dexmedetomidine shows promising results as adjuvant anesthetics in most regional blocks.
SUMMARY
Many studies have been done and many show promising results for the use of dexmedetomidine in regional blocks. It may significantly increase in duration of sensory and motor blocks that correlates with lower pain scores and less need of morphine in various regional blocks.
Topics: Adrenergic alpha-2 Receptor Agonists; Anesthesia, Conduction; Anesthetics, Local; Brachial Plexus Block; Dexmedetomidine
PubMed: 33633422
DOI: No ID Found -
British Journal of Clinical Pharmacology Nov 2014Platelets play an important role in cardiovascular disease, and β-blockers are often prescribed for cardiovascular disease prevention. β-Blockers may directly affect... (Meta-Analysis)
Meta-Analysis Review
AIMS
Platelets play an important role in cardiovascular disease, and β-blockers are often prescribed for cardiovascular disease prevention. β-Blockers may directly affect platelet aggregation, because β-adrenergic receptors are present on platelets. There is uncertainty about the existence and magnitude of an effect of β-blockers on platelet aggregation. The aim of this study was to perform a systematic review and meta-analysis of the effect of β-blockers on platelet aggregation.
METHODS
MEDLINE and EMBASE were searched until April 2014. Two reviewers independently performed data extraction and risk of bias assessment. Type of β-blocker, population, treatment duration and platelet aggregation were extracted. Standardized mean differences were calculated for each study and pooled in a random-effects meta-analysis.
RESULTS
We retrieved 31 studies (28 clinical trials and three observational studies). β-Blockers decreased platelet aggregation (standardized mean difference -0.54, 95% confidence interval -0.85 to -0.24, P < 0.0001). This corresponds to a reduction of 13% (95% confidence interval 8-17%). Nonselective lipophilic β-blockers decreased platelet aggregation more than selective nonlipophilic β-blockers.
CONCLUSIONS
Clinically used β-blockers significantly reduce platelet aggregation. Nonselective lipophilic β-blockers seem to reduce platelet aggregation more effectively than selective nonlipophilic β-blockers. These findings may help to explain why some β-blockers are more effective than others in preventing cardiovascular disease.
Topics: Adrenergic beta-Antagonists; Cardiovascular Diseases; Clinical Trials as Topic; Humans; Observational Studies as Topic; Platelet Aggregation
PubMed: 24730697
DOI: 10.1111/bcp.12404