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Current Problems in Cardiology Feb 2024Postoperative atrial fibrillation (POAF) is the most common arrhythmic complication following cardiac surgery. Current guidelines suggest beta-blockers for the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Postoperative atrial fibrillation (POAF) is the most common arrhythmic complication following cardiac surgery. Current guidelines suggest beta-blockers for the prevention of POAF. In comparing metoprolol succinate with carvedilol, the later has sparked interest in its usage as an important medication for POAF prevention.
METHODS
We considered randomized controlled studies (RCTs) and retrospective studies that evaluated the efficacy of carvedilol versus metoprolol for the prevention of POAF. After literature search, data extraction, and quality evaluation, pooled data were analyzed using either the fixed-effect or random-effect model using Review Manager 5.3. The Cochrane risk of bias tool was used to assess the bias of included studies. The incidence of POAF was the primary endpoint, while mortality rate and bradycardia were secondary outcomes.
RESULTS
In meta-analysis 5 RCTs and 2 retrospective studies with a total of 1000 patients were included. The overall effect did not favor the carvedilol over metoprolol groups in terms of mortality rate [risk ratio 0.45, 95 % CI (0.1-1.97), P=0.29] or incidence of bradycardia [risk ratio 0.63, 95 % CI (0.32-1.23), P=0.17]. However, the incidence of POAF was lower in patients who received carvedilol compared to metoprolol [risk ratio 0.54, 95 % CI (0.42-0.71), P < 0.00001].
CONCLUSION
In patients undergoing cardiac surgery, carvedilol may minimize the occurrence of POAF more effectively than metoprolol. To definitively establish the efficacy of carvedilol compared to metoprolol and other beta-blockers in the prevention of POAF, a large-scale, well-designed randomized controlled trials are required.
Topics: Humans; Metoprolol; Carvedilol; Atrial Fibrillation; Bradycardia; Propanolamines; Carbazoles; Adrenergic beta-Antagonists
PubMed: 37989396
DOI: 10.1016/j.cpcardiol.2023.102220 -
American Journal of Ophthalmology Mar 2024To learn more about the effectiveness of oral propranolol as a therapeutic alternative for preterm newborns with pre-existing retinopathy of prematurity (ROP) as well as... (Meta-Analysis)
Meta-Analysis
PURPOSE
To learn more about the effectiveness of oral propranolol as a therapeutic alternative for preterm newborns with pre-existing retinopathy of prematurity (ROP) as well as an early prevention method for ROP, one of the most common but avoidable causes of juvenile blindness.
STUDY DESIGN
Meta-analysis of relevant literature.
METHODS
A total of 3464 papers were identified, with 2873 from PubMed, 39 from Scopus, 67 from Medline, and 16 from Embase. After screening, finally, a total of 8 studies were deemed suitable for review. Following the PRISMA guidelines, published literature was systematically assessed up to May 10, 2023. Trials and observational studies were included in which beta blockage was used to prevent severe ROP (defined as stage ≥3 or requiring treatment). A total of 3646 papers were identified, with 2873 from PubMed, 39 from Scopus, 67 from Medline, and 16 from Embase. After screening, a total of 8 studies were deemed suitable for review.
RESULTS
The use of propranolol is linked to a lower risk of disease development in ROP compared to other therapies or control groups, according to the overall risk ratio of 0.59 (95% CI = 0.42, 0.82; P = .002, I = 41%). Additionally, the overall risk ratio for plus disease is 0.42 (95% CI = 0.23, 0.78; P = .006, I = 0%), for laser photocoagulation is 0.48 (95% CI = 0.31, 0.74; P = .001; I = 2%), and for intravitreal injection of VEGF is 0.43 (95% CI = 0.24, 0.74; P = 0.003, I = 0%), suggesting that use of propranolol may reduce the likelihood of developing a disease such as plus disease, requiring laser photocoagulation or necessitating intravitreal injection of vascular endothelial growth factor for ROP, respectively. No statistically significant heterogeneity was found in this study (P > .10, I = 50%). It can be concluded from this that the results of the chosen studies were sufficiently comparable and consistent.
CONCLUSION
This study showed that oral propranolol given as a preventive treatment in premature newborns successfully prevented severe ROP. Propranolol dosage and timing must now be carefully considered in the context of the study population, as these factors may have a major impact on the observed outcomes and treatment success.
Topics: Humans; Infant, Newborn; Adrenergic beta-Antagonists; Angiogenesis Inhibitors; Infant, Premature; Propranolol; Retinopathy of Prematurity; Vascular Endothelial Growth Factor A
PubMed: 37979602
DOI: 10.1016/j.ajo.2023.11.012 -
Anaesthesia Jan 2024We conducted a systematic review of the literature reporting phenylephrine-induced changes in blood pressure, cardiac output, cerebral blood flow and cerebral tissue... (Review)
Review
We conducted a systematic review of the literature reporting phenylephrine-induced changes in blood pressure, cardiac output, cerebral blood flow and cerebral tissue oxygen saturation as measured by near-infrared spectroscopy in humans. We used the proportion change of the group mean values reported by the original studies in our analysis. Phenylephrine elevates blood pressure whilst concurrently inducing a reduction in cardiac output. Furthermore, despite increasing cerebral blood flow, it decreases cerebral tissue oxygen saturation. The extent of phenylephrine's influence on cardiac output (r = -0.54 and p = 0.09 in awake humans; r = -0.55 and p = 0.007 in anaesthetised humans), cerebral blood flow (r = 0.65 and p = 0.002 in awake humans; r = 0.80 and p = 0.003 in anaesthetised humans) and cerebral tissue oxygen saturation (r = -0.72 and p = 0.03 in awake humans; r = -0.24 and p = 0.48 in anaesthetised humans) appears closely linked to the magnitude of phenylephrine-induced blood pressure changes. When comparing the effects of phenylephrine in awake and anaesthetised humans, we found no evidence of a significant difference in cardiac output, cerebral blood flow or cerebral tissue oxygen saturation. There was also no evidence of a significant difference in effect on systemic and cerebral circulations whether phenylephrine was given by bolus or infusion. We explore the underlying mechanisms driving the phenylephrine-induced cardiac output reduction, cerebral blood flow increase and cerebral tissue oxygen saturation decrease. Individualised treatment approaches, close monitoring and consideration of potential risks and benefits remain vital to the safe and effective use of phenylephrine in acute care.
Topics: Humans; Phenylephrine; Vasoconstrictor Agents; Oxygen; Blood Pressure; Cerebrovascular Circulation
PubMed: 37948131
DOI: 10.1111/anae.16172 -
Journal of Neurochemistry Dec 2023The aim of this study was to systematically review prior research investigating the effects of contact/collision sport participation on neurometabolite levels in the... (Meta-Analysis)
Meta-Analysis Review
The effect of contact/collision sport participation without concussion on neurometabolites: A systematic review and meta-analysis of magnetic resonance spectroscopy studies.
The aim of this study was to systematically review prior research investigating the effects of contact/collision sport participation on neurometabolite levels in the absence of concussion. Four online databases were searched to identify studies that measured neurometabolite levels in contact/collision sport athletes (without concussion) using proton ( H) or phosphorus ( P) magnetic resonance spectroscopy (MRS). All study designs were acceptable for inclusion. Meta-analytic procedures were used to quantify the effect of contact/collision sport participation on neurometabolite levels and explore the impact of specific moderating factors (where sufficient data were available). Narrative synthesis was used to describe outcomes that could not be meta-analysed. Nine observational studies involving 300 contact/collision sport athletes were identified. Six studies (providing 112 effect estimates) employed longitudinal (cohort) designs and three (that could not be meta-analysed) employed case-control designs. N-acetylaspartate (NAA; g = -0.331, p = 0.013) and total creatine (tCr; creatine + phosphocreatine; g = -0.524, p = 0.029), but not glutamate-glutamine (Glx), myo-inositol (mI) or total choline (tCho; choline-containing compounds; p's > 0.05), decreased between the pre-season and mid-/post-season period. Several moderators were statistically significant, including: sex (Glx: 6 female/23 male, g = -0.549, p = 0.013), sport played (Glx: 22 American football/4 association football [soccer], g = 0.724, p = 0.031), brain region (mI: 2 corpus callosum/9 motor cortex, g = -0.804, p = 0.015), and the MRS quantification approach (mI: 18 absolute/3 tCr-referenced, g = 0.619, p = 0.003; and tCho: 18 absolute/3 tCr-referenced, g = 0.554, p = 0.005). In case-control studies, contact/collision sport athletes had higher levels of mI, but not NAA or tCr compared to non-contact sport athletes and non-athlete controls. Overall, this review suggests that contact/collision sport participation has the potential to alter neurometabolites measured via H MRS in the absence of concussion. However, further research employing more rigorous and consistent methodologies (e.g. interventional studies with consistent H MRS pulse sequences and quantifications) is required to confirm and better understand the clinical relevance of observed effects.
Topics: Humans; Male; Female; Creatine; Brain Concussion; Magnetic Resonance Spectroscopy; Choline; Receptors, Antigen, T-Cell; Aspartic Acid; Inositol
PubMed: 37908148
DOI: 10.1111/jnc.16000 -
Semergen 2024Pregnancy is one of the most important and difficult moments that a woman goes through throughout her life. It is a period of great need for macro and micronutrients to... (Review)
Review
Pregnancy is one of the most important and difficult moments that a woman goes through throughout her life. It is a period of great need for macro and micronutrients to meet the demands of the developing fetus and avoid deficiencies, in order to obtain the best possible result. Nowadays, most women who are pregnant or planning to become pregnant know the importance of getting the required amount of certain types of nutrients (proteins, fats, folate, etc.), as well as avoiding certain compounds (alcohol, tobacco, drugs, etc.) to avoid possible complications during pregnancy. In recent years, with the greatest scientific evidence available, it has been shown how some of these nutrients could have a more relevant role than previously believed in the optimal outcome of pregnancy. One of these nutrients being choline. Choline supplementation during pregnancy has been shown to be a non-pharmacological treatment capable of improving both physical (growth) and mental (memory) qualities of the new individual. Choline has been known as an essential nutrient since 1998 and several studies have shown its effectiveness in rodent models. The existence of recent publications that deal with its application in humans makes it necessary to carry out a systematic review. In this systematic review of the scientific evidence available from 2012 to the present that deals with the application of a higher intake of choline through supplementation as a treatment to improve pregnancy outcomes, its main objetive is to determine the effects that a nutritional intervention through choline supplementation in pregnant mothers can have on children's cognition. For this, 9studies have been analyzed where the treatment given to pregnant women is revealed, this being choline supplementation in different modalities (choline chloride, choline bitartrate, and phosphatidylcholine) and the different effects produced in the children of these mothers who have resulted from these treatment modalities. We conclude by stating that choline supplementation during pregnancy appears to be effective in improving or increasing cognition in children.
Topics: Child; Female; Humans; Pregnancy; Choline; Dietary Supplements; Pregnant Women; Lactation; Micronutrients
PubMed: 37862810
DOI: 10.1016/j.semerg.2023.102089 -
Psychopharmacology Feb 2024The selective serotonin and norepinephrine reuptake inhibitor venlafaxine is among the most prescribed antidepressant drugs worldwide and, according to guidelines, its... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The selective serotonin and norepinephrine reuptake inhibitor venlafaxine is among the most prescribed antidepressant drugs worldwide and, according to guidelines, its dose titration should be guided by drug-level monitoring of its active moiety (AM) which consists of venlafaxine (VEN) plus active metabolite O-desmethylvenlafaxine (ODV). This indication of therapeutic drug monitoring (TDM), however, assumes a clear concentration/effect relationship for a drug, which for VEN has not been systematically explored yet.
OBJECTIVES
We performed a systematic review and meta-analysis to investigate the relationship between blood levels, efficacy, and adverse reactions in order to suggest an optimal target concentration range for VEN oral formulations for the treatment of depression.
METHODS
Four databases (MEDLINE (PubMed), PsycINFO, Web of Science Core Collection, and Cochrane Library) were systematically searched in March 2022 for relevant articles according to a previously published protocol. Reviewers independently screened references and performed data extraction and critical appraisal.
RESULTS
High-quality randomized controlled trials investigating concentration/efficacy relationships and studies using a placebo lead-in phase were not found. Sixty-eight articles, consisting mostly of naturalistic TDM studies or small noncontrolled studies, met the eligibility criteria. Of them, five cohort studies reported a positive correlation between blood levels and antidepressant effects after VEN treatment. Our meta-analyses showed (i) higher AM and (ii) higher ODV concentrations in patients responding to VEN treatment when compared to non-responders (n = 360, k = 5). AM concentration-dependent occurrence of tremor was reported in one study. We found a linear relationship between daily dose and AM concentration within guideline recommended doses (75-225 mg/day). The population-based concentration ranges (25-75% interquartile) among 11 studies (n = 3200) using flexible dosing were (i) 225-450 ng/ml for the AM and (ii) 144-302 ng/ml for ODV. One PET study reported an occupancy of 80% serotonin transporters for ODV serum levels above 85 ng/ml. Based on our findings, we propose a therapeutic reference range for AM of 140-600 ng/ml.
CONCLUSION
VEN TDM within a range of 140 to 600 ng/ml (AM) will increase the probability of response in nonresponders. A titration within the proposed reference range is recommended in case of non-response at lower drug concentrations as a consequence of VEN's dual mechanism of action via combined serotonin and norepinephrine reuptake inhibition. Drug titration towards higher concentrations will, however, increase the risk for ADRs, in particular with supratherapeutic drug concentrations.
Topics: Humans; Antidepressive Agents; Depression; Desvenlafaxine Succinate; Norepinephrine; Reference Values; Serotonin; Venlafaxine Hydrochloride
PubMed: 37857898
DOI: 10.1007/s00213-023-06484-7 -
American Journal of Cardiovascular... Jan 2024Atrial fibrillation (AF) and/or atrial flutter (AFL) with rapid ventricular response (RVR) is a condition that often requires urgent treatment. Although guidelines have... (Meta-Analysis)
Meta-Analysis
Intravenous Diltiazem Versus Metoprolol in Acute Rate Control of Atrial Fibrillation/Flutter and Rapid Ventricular Response: A Meta-Analysis of Randomized and Observational Studies.
BACKGROUND
Atrial fibrillation (AF) and/or atrial flutter (AFL) with rapid ventricular response (RVR) is a condition that often requires urgent treatment. Although guidelines have recommendations regarding chronic rate control therapy, recommendations on the best choice for acute heart rate (HR) control in RVR are unclear.
METHODS
A systematic search across multiple databases was performed for studies evaluating the outcome of HR control (defined as HR less than 110 bpm and/or 20% decrease from baseline HR). Included studies evaluated AF and/or AFL with RVR in a hospital setting, with direct comparison between intravenous (IV) diltiazem and metoprolol and excluded cardiac surgery and catheter ablation patients. Hypotension (defined as systolic blood pressure less than 90 mmHg) was measured as a secondary outcome. Two authors performed full-text article review and extracted data, with a third author mediating disagreements. Random effects models utilizing inverse variance weighting were used to calculate odds ratios (OR) and 95% confidence intervals (CI). Heterogeneity was assessed using the I test.
RESULTS
A total of 563 unique titles were identified through the systematic search, of which 16 studies (7 randomized and 9 observational) were included. In our primary analysis of HR control by study type, IV diltiazem was found to be more effective than IV metoprolol for HR control in randomized trials (OR 4.75, 95% CI 2.50-9.04 with I = 14%); however, this was not found for observational studies (OR 1.26, 95% CI 0.89-1.80 with I = 55%). In an analysis of observational studies, there were no significant differences between the two drugs in odds of hypotension (OR 1.12, 95% CI 0.51-2.45 with I = 18%).
CONCLUSION
While there was a trend toward improved HR control with IV diltiazem compared with IV metoprolol in randomized trials, this was not seen in observational studies, and there was no observed difference in hypotension between the two drugs.
Topics: Humans; Atrial Fibrillation; Atrial Flutter; Diltiazem; Hypotension; Metoprolol; Observational Studies as Topic
PubMed: 37856044
DOI: 10.1007/s40256-023-00615-3 -
Drug Metabolism Reviews Nov 2023Nebivolol is a beta-1 receptor blocker used to treat hypertension, heart failure, erectile dysfunction, vascular disease, and diabetes mellitus. This review investigated... (Review)
Review
Nebivolol is a beta-1 receptor blocker used to treat hypertension, heart failure, erectile dysfunction, vascular disease, and diabetes mellitus. This review investigated the data regarding pharmacokinetic (PK) parameters, drug-drug interactions, dextrorotatory (D), and levorotatory (L) stereoisomers of nebivolol. The articles related to the PK of nebivolol were retrieved by searching the five databases; Google Scholar, PubMed, Cochrane Library, ScienceDirect, and EBSCO. A total of 20 studies comprising plasma concentration-time profile data following the nebivolol's oral and intravenous (IV) administration were included. The area under the concentration-time curve from zero to infinity (AUC) was 15 times greater in poor metabolizers (PMs) than in extensive metabolizers (EMs). In hypertensive patients, L-nebivolol expressed a higher maximum plasma concentration (C) than D-nebivolol, i.e. 2.5 ng/ml vs 1.2 ng/ml. The AUC of nebivolol was 3-fold greater in chronic kidney disease (CKD). The clearance (CL) was increased in obese than in controls from 51.6 ± 11.6 L/h to 71.6 ± 17.4 L/h when 0.5 mg/ml IV solution was infused. Nebivolol showed higher C, AUC and half-life (t) when co-administered with bupropion, duloxetine, fluvoxamine, paroxetine, lansoprazole, and fluoxetine. This concise review of nebivolol would be advantageous in assessing all PK parameters, which may be crucial for clinicians to avoid drug-drug interactions, prevent adverse drug events and optimize the dosage regimen in diseased patients diagnosed with hypertension and cardiovascular disorders.
Topics: Male; Humans; Nebivolol; Hypertension; Fluvoxamine; Lansoprazole; Drug Interactions
PubMed: 37849071
DOI: 10.1080/03602532.2023.2271195 -
The Clinical Respiratory Journal Dec 2023Salbutamol has been used to alleviate bronchospasm in airway disease for decades, while its potential risks have not been systematically investigated yet. The risk of... (Meta-Analysis)
Meta-Analysis
PURPOSE
Salbutamol has been used to alleviate bronchospasm in airway disease for decades, while its potential risks have not been systematically investigated yet. The risk of any potential adverse events (AEs) in patients treated with salbutamol was assessed through systematic review and meta-analysis.
METHODS
A systematic search of the literature was conducted, using EMBASE, PubMed and Cochrane library, until 3 April 2023. Once the AE incidence was evaluated, randomized controlled trials (RCTs) were eligible for review. The endpoints included the incidence of total AEs, severe AEs, treatment discontinuation and specific AEs. The pooled AEs incidence was analysed via random-effects model in a single-arm meta-analysis. A subgroup study was carried out to examine whether the pooled incidence of AE differed by indications or formulations.
RESULTS
Of the 8912 studies that were identified, 58 RCTs met the inclusion criteria and involved 12 961 participants. The analysis showed the pooled incidences of total AEs, severe AEs and treatment discontinuation in patients treated with salbutamol were 34%, 2% and 3%, respectively. Subgroup analysis indicated that premature labour users and intravenous salbutamol users were more likely associated with total AEs. The most frequently observed specific AEs were palpitations or tachycardia.
CONCLUSION
This meta-analysis indicated that salbutamol was associated with a very common risk of palpitations or tachycardia. Clinical vigilance and research efforts are needed to optimize the safe use of salbutamol.
Topics: Humans; Albuterol; Tachycardia
PubMed: 37844914
DOI: 10.1111/crj.13711 -
Biology Direct Oct 2023The social impact of glaucoma is worth of note: primary open-angle glaucoma (POAG) is one of the leading causes of irreversible blindness worldwide, affecting some 68.56... (Meta-Analysis)
Meta-Analysis Review
The social impact of glaucoma is worth of note: primary open-angle glaucoma (POAG) is one of the leading causes of irreversible blindness worldwide, affecting some 68.56 million people with overall prevalence of 2.4%. Since one of the main risk factors for the development of POAG is the increase of intraocular pressure (IOP) causing retinal ganglion cells death, the medical treatment of POAG consists in the use of drugs endowed with neuroprotective effect and able to reduce IOP. These drugs include beta-blockers, prostaglandin analogues, carbonic anhydrase inhibitors, alpha or cholinergic agonists and rho kinase inhibitors. However, not all the patients respond to the same extent to the therapy in terms of efficacy and safety. Genetics and genome wide association studies have highlighted the occurrence of mutations and polymorphisms influencing the predisposition to develop POAG and its phenotype, as well as affecting the response to pharmacological treatment. The present systematic review and meta-analysis aims at identifying genetic variants and at verifying whether these can influence the responsiveness of patients to therapy for efficacy and safety. It follows the most updated Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 recommendations. The literature search was conducted consulting the most relevant scientific databases, i.e. PubMed/MEDLINE, Scopus, Web of Science and Public Health Genomics and Precision Health Knowledge Base up to June 14th, 2023. The search retrieved 1026 total records, among which eight met the eligibility criteria for inclusion in the analysis. The results demonstrated that the most investigated pharmacogenetic associations concern latanoprost and timolol, and that efficacy was studied more in depth than safety. Moreover, the heterogeneity of design and paucity of studies prompt further investigation in randomized clinical trials. In fact, adequately powered and designed pharmacogenetic association studies are needed to provide body of evidence with good certainty for a more appropriate use of medical therapy in POAG.PROSPERO registration: CRD42023434867.
Topics: Humans; Glaucoma, Open-Angle; Antihypertensive Agents; Genome-Wide Association Study; Timolol; Genotype
PubMed: 37833756
DOI: 10.1186/s13062-023-00423-4