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PloS One 2020Fixed-combination (FC) therapy is used in primary open-angle glaucoma (POAG) and ocular hypertension (OHT) patients who require more than one medication to reach their... (Meta-Analysis)
Meta-Analysis
The efficacy of the fixed combination of latanoprost and timolol versus other fixed combinations for primary open-angle glaucoma and ocular hypertension: A systematic review and meta-analysis.
BACKGROUND
Fixed-combination (FC) therapy is used in primary open-angle glaucoma (POAG) and ocular hypertension (OHT) patients who require more than one medication to reach their target intraocular pressure (IOP). Currently, there are several FC therapies available for the treatment of glaucoma. The FC of latanoprost/timolol (LTFC) is a commonly used FC. Here, we conducted systematic review to compare the IOP-lowering effects of LTFC with other FCs for patients with POAG and OHT.
MATERIALS AND METHODS
We searched PubMed, EMBASE, the Cochrane Library, and Web of Science for randomized-controlled clinical trials and cross-over studies. The outcomes were mean IOP and IOP fluctuation after one month of treatment. Meta-analysis was carried out using RevMan (version 5.1) software. After conducting meta-analyses, we rated the quality of each meta-analysis as high, moderate, low, or very low using the "GRADE" system.
RESULTS
We included 16 trials in this meta-analysis. Moderate-quality meta-analysis showed that LTFC had a comparable mean IOP to that of a fixed combination of travoprost and timolol (TTFC) [mean difference (MD): 0.07 mmHg] and a fixed combination of dorzolamide and timolol (DTFC) [MD: -0.31 mmHg], and it also had a comparable IOP-fluctuation effect compared to that of TTFC [MD: 0.13 mm Hg] and DTFC [MD: 0.25 mmHg]. Compared to the fixed combination of bimatoprost and timolol (BiTFC), moderate-quality evidence showed a higher mean IOP in the LTFC group [MD 0.76 mmHg], whereas low-quality meta-analysis showed higher IOP fluctuation [MD 1.09 mmHg] in the LTFC group.
CONCLUSIONS
LTFC is as effective as TTFC and DTFC, but worse than BiTFC in controlling mean IOP and IOP fluctuation for POAG or OHT patients. The quality of our meta-analyses was assessed as moderate, with the exception of one low-quality analysis that compared the IOP fluctuation of LTFC and BiTFC.
Topics: Antihypertensive Agents; Bimatoprost; Drug Combinations; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Ocular Hypertension; Sulfonamides; Thiophenes; Timolol; Travoprost; Treatment Outcome
PubMed: 32106236
DOI: 10.1371/journal.pone.0229682 -
British Journal of Clinical Pharmacology Jun 2020CYP2D6 genetic polymorphisms are associated with metoprolol pharmacokinetics. Whether the clinical response to metoprolol is also affected remains uncertain. (Meta-Analysis)
Meta-Analysis Review
AIMS
CYP2D6 genetic polymorphisms are associated with metoprolol pharmacokinetics. Whether the clinical response to metoprolol is also affected remains uncertain.
METHODS
We conducted a systematic review on the effects of CYP2D6 polymorphism on the clinical response to metoprolol. Searches were conducted using MEDLINE. Meta-analyses were performed on the impact of CYP2D6-inferred phenotypes on heart rate (HR) reduction, diastolic (DBP) and systolic (SBP) blood pressure reduction, average daily doses, all-type adverse events and bradycardia.
RESULTS
Our qualitative assessment indicated inconsistent results in individual studies and endpoints, but CYP2D6 poor metabolizers (PM) generally presented a greater reduction in HR. The meta-analysis of 15 studies, including a total of 1146 individuals, found a reduction in HR of 3 beats/min (P = .017), and of SBP and DBP by 3 mmHg (P = .0048) for PM compared to non-PM individuals using similar metoprolol doses. Bradycardia appeared more frequent by 4-fold for PM, although significant heterogeneity was observed regarding bradycardia, which limits the scope of this finding.
CONCLUSION
Patients without any CYP2D6 metabolic capacities appear to have increased reduction in DBP, HR and SBP during metoprolol treatment and may be at a higher risk of bradycardia compared to patients with active CYP2D6 phenotypes. Further prospective data are required to determine whether CYP2D6 is associated with clinical events in patients treated with metoprolol, as well as to demonstrate the clinical utility of an individualized approach of prescribing metoprolol using CYP2D6-inferred phenotypes.
Topics: Cytochrome P-450 CYP2D6; Genotype; Humans; Metoprolol; Phenotype; Polymorphism, Genetic
PubMed: 32090368
DOI: 10.1111/bcp.14247 -
JAMA Pediatrics Apr 2020Migraine is one of the most common neurologic disorders in children and adolescents. However, a quantitative comparison of multiple preventive pharmacologic treatments... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Migraine is one of the most common neurologic disorders in children and adolescents. However, a quantitative comparison of multiple preventive pharmacologic treatments in the pediatric population is lacking.
OBJECTIVE
To examine whether prophylactic pharmacologic treatments are more effective than placebo and whether there are differences between drugs regarding efficacy, safety, and acceptability.
DATA SOURCES
Systematic review and network meta-analysis of studies in MEDLINE, Cochrane, Embase, and PsycINFO published through July 2, 2018.
STUDY SELECTION
Randomized clinical trials of prophylactic pharmacologic treatments in children and adolescents diagnosed as having episodic migraine were included. Abstract, title, and full-text screening were conducted independently by 4 reviewers.
DATA EXTRACTION AND SYNTHESIS
Data extraction was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis network meta-analysis guidelines. Quality was assessed with the Cochrane Risk of Bias tool. Effect sizes, calculated as standardized mean differences for primary outcomes and risk ratios for discontinuation rates, were assessed in a random-effects model.
MAIN OUTCOMES AND MEASURES
Primary outcomes were efficacy (ie, migraine frequency, number of migraine days, number of headache days, headache frequency, or headache index), safety (ie, treatment discontinuation owing to adverse events), and acceptability (ie, treatment discontinuation for any reason).
RESULTS
Twenty-three studies (2217 patients) were eligible for inclusion. Prophylactic pharmacologic treatments included antiepileptics, antidepressants, calcium channel blockers, antihypertensive agents, and food supplements. In the short term (<5 months), propranolol (standard mean difference, 0.60; 95% CI, 0.03-1.17) and topiramate (standard mean difference, 0.59; 95% CI, 0.03-1.15) were significantly more effective than placebo. However, the 95% prediction intervals for these medications contained the null effect. No significant long-term effects for migraine prophylaxis relative to placebo were found for any intervention.
CONCLUSIONS AND RELEVANCE
Prophylactic pharmacologic treatments have little evidence supporting efficacy in pediatric migraine. Future research could (1) identify factors associated with individual responses to pharmacologic prophylaxis, (2) analyze fluctuations of migraine attack frequency over time and determine the most clinically relevant length of probable prophylactic treatment, and (3) identify nonpharmacologic targets for migraine prophylaxis.
Topics: Adolescent; Anticonvulsants; Antidepressive Agents; Antihypertensive Agents; Calcium Channel Blockers; Child; Dietary Supplements; Humans; Migraine Disorders; Propranolol; Topiramate; Vasodilator Agents
PubMed: 32040139
DOI: 10.1001/jamapediatrics.2019.5856 -
BioMed Research International 2019The present study aims to investigate whether intravenous dexmedetomidine shows superiority to esmolol for hemodynamic response to tracheal intubation after rapid... (Comparative Study)
Comparative Study Meta-Analysis
Comparison of Intravenous Dexmedetomidine versus Esmolol for Attenuation of Hemodynamic Response to Tracheal Intubation after Rapid Sequence Induction: A Systematic Review and Meta-Analysis.
The present study aims to investigate whether intravenous dexmedetomidine shows superiority to esmolol for hemodynamic response to tracheal intubation after rapid sequence induction. In the present meta-analysis, PubMed, EMBASE, and the Cochrane Library were searched for trials comparing dexmedetomidine with esmolol for the attenuation of the hemodynamic response to intubation. Ten trials were selected in the present meta-analysis. Compared to esmolol, the use of dexmedetomidine maintains stable heart rates (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) at 1 min, 3 min, and 5 min after tracheal intubation. Dexmedetomidine causes less hemodynamic response to tracheal intubation after rapid sequence induction compared with esmolol.
Topics: Administration, Intravenous; Adult; Blood Pressure; Dexmedetomidine; Diastole; Hemodynamics; Humans; Intubation, Intratracheal; Middle Aged; Propanolamines; Publication Bias; Systole; Young Adult
PubMed: 31139645
DOI: 10.1155/2019/6791971 -
BMJ Open Apr 2019Esmolol is an ultra-short-acting β antagonist that has been shown to attenuate the corrected QT (QTc) interval prolongation associated with laryngoscopy and...
INTRODUCTION AND AIMS
Esmolol is an ultra-short-acting β antagonist that has been shown to attenuate the corrected QT (QTc) interval prolongation associated with laryngoscopy and endotracheal intubation (LTI). Prolongation of the QTc interval can precipitate arrhythmias, the most serious of which is torsades de pointes . The aim of this systematic review was to compare esmolol and placebo on QTc changes occurring during LTI.
MATERIALS AND METHODS
PubMed, EMBASE, Cochrane Registry of Clinical Trials and CINAHL databases (up to August 2018) were screened for randomised controlled trials comparing esmolol and placebo on QTc changes during LTI in cardiac and non-cardiac surgeries. The primary outcome was QTc changes during LTI and secondary outcome was related to adverse effects from esmolol such as bradycardia and hypotension.
RESULTS
Seven trials were identified involving 320 patients, 160 patients receiving esmolol or placebo apiece. A shortening of the QTc post-LTI was evident in the esmolol group compared with the placebo in four studies. Compared with the baseline, the QTc was reduced post-LTI in the esmolol group. In the placebo group, the QTc was prolonged compared with the baseline post LTI. Nonetheless, esmolol did not prevent QTc prolongation in the remaining three studies, and much of this was attributed to employing QTc prolonging agents for premedication and anaesthetic induction. No significant adverse events were noted.
CONCLUSION
Compared with placebo, esmolol reduced the LTI-induced QTc prolongation when current non-QTc prolonging agents were chosen for tracheal intubation. Future studies should explore whether transmural dispersion (a marker of torsadogenicity) is also affected during LTI by analysing parameters such as the Tp-e interval (interval between the peak to the end of the T-wave) and Tp-e/QTc (rate corrected Tp-e interval).
TRIAL REGISTRATION NUMBER
CRD42018090282.
Topics: Adrenergic beta-1 Receptor Antagonists; Arrhythmias, Cardiac; Electrocardiography; Heart Rate; Humans; Intubation, Intratracheal; Propanolamines
PubMed: 31023764
DOI: 10.1136/bmjopen-2018-028111 -
The Cochrane Database of Systematic... Mar 2019Panic disorder is characterised by recurrent unexpected panic attacks consisting of a wave of intense fear that reaches a peak within a few minutes. Panic disorder is a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Panic disorder is characterised by recurrent unexpected panic attacks consisting of a wave of intense fear that reaches a peak within a few minutes. Panic disorder is a common disorder, with an estimated lifetime prevalence of 1% to 5% in the general population and a 7% to 10% prevalence in primary care settings. Its aetiology is not fully understood and is probably heterogeneous.Panic disorder is treated with psychological and pharmacological interventions, often used in combination. Although benzodiazepines are frequently used in the treatment of panic disorder, guidelines recommend antidepressants, mainly selective serotonin reuptake inhibitors (SSRIs), as first-line treatment for panic disorder, particularly due to their lower incidence of dependence and withdrawal reaction when compared to benzodiazepines. Despite these recommendations, benzodiazepines are widely used in the treatment of panic disorder, probably because of their rapid onset of action.
OBJECTIVES
To assess the efficacy and acceptability of benzodiazepines versus placebo in the treatment of panic disorder with or without agoraphobia in adults.
SEARCH METHODS
We searched the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR Studies and References), the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1950-), Embase (1974-), and PsycINFO (1967-) up to 29 May 2018. We handsearched reference lists of relevant papers and previous systematic reviews. We contacted experts in the field for supplemental data.
SELECTION CRITERIA
All double-blind (blinding of patients and personnel) controlled trials randomising adults with panic disorder with or without agoraphobia to benzodiazepine or placebo.
DATA COLLECTION AND ANALYSIS
Two review authors independently checked the eligibility of studies and extracted data using a standardised form. Data were then entered data into Review Manager 5 using a double-check procedure. Information extracted included study characteristics, participant characteristics, intervention details, settings, and outcome measures in terms of efficacy, acceptability, and tolerability.
MAIN RESULTS
We included 24 studies in the review with a total of 4233 participants, of which 2124 were randomised to benzodiazepines and 1475 to placebo. The remaining 634 participants were randomised to other active treatments in three-arm trials. We assessed the overall methodological quality of the included studies as poor. We rated all studies as at unclear risk of bias in at least three domains. In addition, we judged 20 of the 24 included studies as having a high risk of bias in at least one domain.Two primary outcomes of efficacy and acceptability showed a possible advantage of benzodiazepines over placebo. The estimated risk ratio (RR) for a response to treatment was 1.65 (95% confidence interval (CI) 1.39 to 1.96) in favour of benzodiazepines, which corresponds to an estimated number needed to treat for an additional beneficial outcome (NNTB) of 4 (95% CI 3 to 7). The dropout rate was lower among participants treated with benzodiazepines (RR 0.50, 95% CI 0.39 to 0.64); the estimated NNTB was 6 (95% CI 5 to 9). We rated the quality of the evidence as low for both primary outcomes. The possible advantage of benzodiazepine was also seen for remission (RR 1.61, 95% CI 1.38 to 1.88) and the endpoint data for social functioning (standardised mean difference (SMD) -0.53, 95% CI -0.65 to -0.42), both with low-quality evidence. We assessed the evidence for the other secondary outcomes as of very low quality. With the exception of the analyses of the change score data for depression (SMD -0.22, 95% CI -0.48 to 0.04) and social functioning (SMD -0.32, 95% CI -0.88 to 0.24), all secondary outcome analyses showed an effect in favour of benzodiazepines compared to placebo. However, the number of dropouts due to adverse effects was higher with benzodiazepines than with placebo (RR 1.58, 95% CI 1.16 to 2.15; low-quality evidence). Furthermore, our analyses of adverse events showed that a higher proportion of participants experienced at least one adverse effect when treated with benzodiazepines (RR 1.18, 95% CI 1.02 to 1.37; low-quality evidence).
AUTHORS' CONCLUSIONS
Low-quality evidence shows a possible superiority of benzodiazepine over placebo in the short-term treatment of panic disorders. The validity of the included studies is questionable due to possible unmasking of allocated treatments, high dropout rates, and probable publication bias. Moreover, the included studies were only short-term studies and did not examine the long-term efficacy nor the risks of dependency and withdrawal symptoms. Due to these limitations, our results regarding the efficacy of benzodiazepines versus placebo provide only limited guidance for clinical practice. Furthermore, the clinician's choice is not between benzodiazepines and placebo, but between benzodiazepines and other agents, notably SSRIs, both in terms of efficacy and adverse effects. The choice of treatment should therefore be guided by the patient's preference and should balance benefits and harms from treatment in a long-term perspective.
Topics: Adult; Aged; Agoraphobia; Benzodiazepines; Buspirone; Humans; Imipramine; Middle Aged; Numbers Needed To Treat; Panic Disorder; Paroxetine; Patient Dropouts; Placebos; Propranolol; Randomized Controlled Trials as Topic; Remission Induction; Young Adult
PubMed: 30921478
DOI: 10.1002/14651858.CD010677.pub2 -
PloS One 2019Headaches are a common source of pain and suffering. The study's purpose was to assess beta-blockers efficacy in preventing migraine and tension-type headache. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Headaches are a common source of pain and suffering. The study's purpose was to assess beta-blockers efficacy in preventing migraine and tension-type headache.
METHODS
Cochrane Register of Controlled Trials; MEDLINE; EMBASE; ISI Web of Science, clinical trial registries, CNKI, Wanfang and CQVIP were searched through 21 August 2018, for randomized trials in which at least one comparison was a beta-blocker for the prevention of migraine or tension-type headache in adults. The primary outcome, headache frequency per month, was extracted in duplicate and pooled using random effects models.
DATA SYNTHESIS
This study included 108 randomized controlled trials, 50 placebo-controlled and 58 comparative effectiveness trials. Compared to placebo, propranolol reduced episodic migraine headaches by 1.5 headaches/month at 8 weeks (95% CI: -2.3 to -0.65) and was more likely to reduce headaches by 50% (RR: 1.4, 95% CI: 1.1-1.7). Trial Sequential Analysis (TSA) found that these outcomes were unlikely to be due to a Type I error. A network analysis suggested that beta-blocker's benefit for episodic migraines may be a class effect. Trials comparing beta-blockers to other interventions were largely single, underpowered trials. Propranolol was comparable to other medications known to be effective including flunarizine, topiramate and valproate. For chronic migraine, propranolol was more likely to reduce headaches by at least 50% (RR: 2.0, 95% CI: 1.0-4.3). There was only one trial of beta-blockers for tension-type headache.
CONCLUSIONS
There is high quality evidence that propranolol is better than placebo for episodic migraine headache. Other comparisons were underpowered, rated as low-quality based on only including single trials, making definitive conclusions about comparative effectiveness impossible. There were few trials examining beta-blocker effectiveness for chronic migraine or tension-type headache though there was limited evidence of benefit.
REGISTRATION
Prospero (ID: CRD42017050335).
Topics: Adrenergic beta-Antagonists; Adult; Clinical Trials as Topic; Female; Humans; Male; Migraine Disorders; Propranolol; Tension-Type Headache; Topiramate; Valproic Acid
PubMed: 30893319
DOI: 10.1371/journal.pone.0212785 -
Revista Da Associacao Medica Brasileira... Aug 2018This study aimed at assessing the role of beta-blockers on preventing anthracycline-induced cardiotoxicity in adults.
OBJECTIVES
This study aimed at assessing the role of beta-blockers on preventing anthracycline-induced cardiotoxicity in adults.
METHODS
A systematic review was performed on electronic databases, including relevant studies that analysed beta-blockers as cardioprotective agents before the use of anthracyclines by adult oncologic patients.
RESULTS
After application of eligibility and selection criteria, eight articles were considered as high quality, complying with the proposed theme; all eight clinical trials, four of them placebo-controlled, with a total number of 655 patients included. From this sample, 281 (42.9%) used beta-blocker as intervention, and carvedilol was the most frequent (167 patients - 25.5%). Six studies were considered positive regarding the cardioprotection role played by beta-blockers, although only four demonstrated significant difference on left ventricle ejection fraction after chemotherapy on groups that used beta-blockers compared to control groups. Carvedilol and nebivolol, but not metoprolol, had positive results regarding cardioprotection. Other beta-blockers were not analysed in the selected studies.
CONCLUSIONS
Despite the potential cardioprotective effect of beta-blockers, as demonstrated in small and unicentric clinical trials, its routine use on prevention of anthracycline-associated cardiotoxicity demands greater scientific evidence.
Topics: Adrenergic beta-Antagonists; Adult; Anthracyclines; Cardiotonic Agents; Cardiotoxicity; Carvedilol; Heart Diseases; Humans; Reproducibility of Results; Stroke Volume
PubMed: 30673046
DOI: 10.1590/1806-9282.64.08.745 -
Psychosomatics 2019Traumatic brain injury (TBI) is an increasingly common cause of behavioral and emotional dysregulation among hospitalized patients. While consultation-liaison...
BACKGROUND
Traumatic brain injury (TBI) is an increasingly common cause of behavioral and emotional dysregulation among hospitalized patients. While consultation-liaison psychiatrists are often called to help manage these behaviors, acute pharmacological management guidelines are limited.
OBJECTIVE
Conduct a systematic review to determine which pharmacological measures are supported by the literature for targeting agitation and aggression in the acute time period following a TBI.
METHODS
In a systematic review of MEDLINE, Embase, PsycInfo, ClinicalTrials.gov and the Cochrane Library, we identified and then analyzed publications that investigated the pharmacological management of behavioral and emotional dysregulation following a TBI during the acute time period following injury.
RESULTS
There were a limited number of high quality studies that met our inclusion criteria, including only five randomized controlled trials. The majority of the literature identified consisted of case reports or case series. Trends identified in the literature reviewed suggested that amantadine, propranolol, and anti-epileptics were the best supported medications to consider. For many medication classes, the time of medication initiation and duration of treatment, relative to the time of injury, may impact the effect observed.
CONCLUSIONS
The pharmacological management of agitated patients immediately following a TBI is still an area of much-needed research, as there is limited data-driven guidance in the literature.
Topics: Acute Disease; Adrenergic beta-Antagonists; Aggression; Amantadine; Anticonvulsants; Brain Injuries, Traumatic; Dopamine Agents; Emotional Regulation; Humans; Practice Guidelines as Topic; Problem Behavior; Propranolol
PubMed: 30665668
DOI: 10.1016/j.psym.2018.11.009 -
Advances in Nutrition (Bethesda, Md.) Mar 2019Human brown adipose tissue (BAT) has attracted clinical interest not only because it dissipates energy but also for its potential capacity to counteract obesity and...
Human brown adipose tissue (BAT) has attracted clinical interest not only because it dissipates energy but also for its potential capacity to counteract obesity and related metabolic disorders (e.g., insulin resistance and dyslipidemia). Cold exposure is the most powerful stimulus for activating and recruiting BAT, and this stimulatory effect is mediated by the transient receptor potential (TRP) channels. BAT can also be activated by other receptors such as the G-protein-coupled bile acid receptor 1 (GPBAR1) or β-adrenergic receptors. Interestingly, these receptors also interact with several dietary components; in particular, capsinoids and tea catechins appear to mimic the effects of cold through a TRP-BAT axis, and they consequently seem to decrease body fat and improve metabolic blood parameters. This systematic review critically addresses the evidence behind the available human studies analyzing the effect of several dietary components (e.g., capsinoids, tea catechins, and ephedrine) on BAT activity. Even though the results of these studies are consistent with the outcomes of preclinical models, the lack of robust study designs makes it impossible to confirm the BAT-activation capacity of the specified dietary components. Further investigation into the effects of dietary components on BAT is warranted to clarify to what extent these components could serve as a powerful strategy to treat obesity and related metabolic disorders.
Topics: Adipose Tissue, Brown; Capsaicin; Catechin; Ephedrine; Humans; Phytochemicals; Receptors, Adrenergic, beta; Receptors, G-Protein-Coupled; Tea; Transient Receptor Potential Channels
PubMed: 30624591
DOI: 10.1093/advances/nmy067