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Journal of Cardiothoracic and Vascular... Mar 2024The potential risks associated with the use of levosimendan in the pediatric population has not been systematically evaluated. This study aimed to review the available... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The potential risks associated with the use of levosimendan in the pediatric population has not been systematically evaluated. This study aimed to review the available evidence regarding the safety of this treatment.
METHODS
Bio Med Central, PubMed, Embase, and the Cochrane Central Register of clinical trials were searched for studies describing levosimendan administration in the pediatric population in any setting. Relevant studies were independently screened, selected, and their data extracted by two investigators. The authors excluded: reviews, meta-analyses, as well as basic research and trials involving patients >18 years old. The primary outcome was the number and the type of adverse side effects reported during levosimendan administration.
RESULTS
The updated systematic review included 48 studies, enrolling a total of 1,271 pediatric patients who received levosimendan as treatment (790 patients in the 11 studies that reported side effects). The primary adverse effects of levosimendan administration were hypotension and cardiac arrhythmias, particularly tachycardia. Hypotension occurred in approximately 28.9% of patients, while arrhythmia occurred in about 12.3% of patients. Meta analysis of RCTs revealed a rate of all-cause mortality of 2.0% (8 out of 385) in the levosimendan group compared to 3.9% (15 out of 378) in the control group (dobutamine, milrinone or placebo) (risk ratio [RR] = 0.55; 95% confidence interval [CI] = 0.25-1.21; P = 0.14; I = 0%) CONCLUSIONS: Hypotension and cardiac arrhythmia are the most reported side effects of levosimendan in pediatric patients. However, adverse events remain underreported, especially in randomized trials.
Topics: Humans; Child; Adolescent; Simendan; Hydrazones; Pyridazines; Dobutamine; Arrhythmias, Cardiac; Hypotension
PubMed: 38135567
DOI: 10.1053/j.jvca.2023.11.020 -
Toxicology Letters Jan 2024This systematic review aimed to assess the association between neuropsychiatric effects of substance use and occurrence of ER stress and unfolded protein response (UPR)...
INTRODUCTION
This systematic review aimed to assess the association between neuropsychiatric effects of substance use and occurrence of ER stress and unfolded protein response (UPR) through comprehensive electronic search of existing literature and review of their findings.
METHODS
A comprehensive electronic literature search was carried out on research articles published between 1950 to July 2023 through major databases, such as Scopus, Web of Science, Google Scholar, PubMed, PsycINFO, EMBASE, Medline and Cochrane Library.
RESULTS
A total of 21 research articles were selected for review, which were comprised of sixteen animal studies, four human studies and one study on postmortem human brain samples. The selected studies revealed that alcohol, methamphetamine, cocaine, opioid and kratom exposures contributed to neuropsychiatric effects: such as decline in learning and memory function, executive dysfunction, alcohol, methamphetamine, opioid, and kratom dependence. These effects were associated with activation and persistent of ER stress and UPR with elevation of BiP and CHOP expression and the direction of ER stress is progressing towards the PERK-eIF2α-ATF4-CHOP pathway and neuronal apoptosis and neurodegeneration at various regions of the brain. In addition, regular kratom use in humans also contributed to elevation of p-JNK expression, denoting progress of ER stress towards the IRE1-ASK1-JNK-p-JNK pathway which was linked to kratom use disorder. However, treatment with certain compounds or biological agents could reverse the activation of ER stress.
CONCLUSIONS
The neuropsychiatric effects of alcohol, methamphetamine, cocaine, opioid and kratom use may be associated with persistent ER stress and UPR.
Topics: Animals; Humans; Endoplasmic Reticulum Stress; eIF-2 Kinase; Analgesics, Opioid; Unfolded Protein Response; Endoplasmic Reticulum; Apoptosis; Methamphetamine; Substance-Related Disorders; Cocaine
PubMed: 38101493
DOI: 10.1016/j.toxlet.2023.12.008 -
Scientific Reports Jun 2024Classic psychedelics and MDMA have a colorful history of recreational use, and both have recently been re-evaluated as tools for the treatment of psychiatric disorders.... (Meta-Analysis)
Meta-Analysis
Classic psychedelics and MDMA have a colorful history of recreational use, and both have recently been re-evaluated as tools for the treatment of psychiatric disorders. Several studies have been carried out to assess potential long-term effects of a regular use on cognition, delivering distinct results for psychedelics and MDMA. However, to date knowledge is scarce on cognitive performance during acute effects of those substances. In this systematic review and meta-analysis, we investigate how cognitive functioning is affected by psychedelics and MDMA during the acute drug effects and the sub-acute ("afterglow") window. Our quantitative analyses suggest that acute cognitive performance is differentially affected by psychedelics when compared to MDMA: psychedelics impair attention and executive function, whereas MDMA primarily affects memory, leaving executive functions and attention unaffected. Our qualitative analyses reveal that executive functioning and creativity may be increased during a window of at least 24 h after the acute effects of psychedelics have subsided, whereas no such results have been observed for MDMA. Our findings may contribute to inform recommendations on harm reduction for recreational settings and to help fostering differential approaches for the use of psychedelics and MDMA within a therapeutic framework.
Topics: Humans; Hallucinogens; N-Methyl-3,4-methylenedioxyamphetamine; Cognition; Executive Function; Attention; Memory
PubMed: 38926480
DOI: 10.1038/s41598-024-65391-9 -
International Journal of Chronic... 2024To comparison of the application of Vibrating Mesh Nebulizer and Jet Nebulizer in chronic obstructive pulmonary disease (COPD). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To comparison of the application of Vibrating Mesh Nebulizer and Jet Nebulizer in chronic obstructive pulmonary disease (COPD).
RESEARCH METHODS
This systematic review and meta-analysis was conducted following the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) statements. The primary outcome measures analyzed included: The amount of inhaler in the urine sample at 30 minutes after inhalation therapy (USAL0.5), The total amount of inhaler in urine sample within 24 hours (USAL24), Aerosol emitted, Forced expiratory volume in 1 second (FEV), Forced vital capacity (FVC).
RESULTS
Ten studies were included with a total of 314 study participants, including 157 subjects in the VMN group and 157 subjects in the JN group. The data analysis results of USAL0.5, MD (1.88 [95% CI, 0.95 to 2.81], P = 0.000), showed a statistically significant difference. USAL24, MD (1.61 [95% CI, 1.14 to 2.09], P = 0.000), showed a statistically significant difference. The results of aerosol emitted showed a statistically significant difference in MD (3.44 [95% CI, 2.84 to 4.04], P = 0.000). The results of FEV showed MD (0.05 [95% CI, -0.24 to 0.35], P=0.716), the results were not statistically significant. The results of FVC showed MD (0.11 [95% CI, -0.18 to 0.41], P=0.459), the results were not statistically significant. It suggests that VMN is better than JN and provides higher aerosols, but there is no difference in improving lung function between them.
CONCLUSION
VMN is significantly better than JN in terms of drug delivery and utilization in the treatment of patients with COPD. However, in the future use of nebulizers, it is important to select a matching nebulizer based on a combination of factors such as mechanism of action of the nebulizer, disease type and comorbidities, ventilation strategies and modes, drug formulations, as well as cost-effectiveness, in order to achieve the ideal treatment of COPD.
Topics: Humans; Administration, Inhalation; Albuterol; Bronchodilator Agents; Drug Delivery Systems; Equipment Design; Nebulizers and Vaporizers; Pulmonary Disease, Chronic Obstructive; Respiratory Aerosols and Droplets
PubMed: 38562440
DOI: 10.2147/COPD.S452191 -
Orthopaedic Surgery Dec 2023Hip fractures are the most common fractures among older adults, with most patients undergoing surgery. The debate regarding the type of anesthetic technique for hip... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Hip fractures are the most common fractures among older adults, with most patients undergoing surgery. The debate regarding the type of anesthetic technique for hip fracture surgery is still ongoing. This meta-analysis aimed to compare the intraoperative and postoperative outcomes of spinal and general anesthesia in older patients undergoing hip fracture surgery.
METHODS
Eligible studies that compared the effects of spinal and general anesthesia were systematically searched from PubMed, Embase, and the Cochrane Library until May 27, 2022. The intraoperative and postoperative outcomes of the two anesthesia techniques were compared. Quality assessment, heterogeneity analysis, and publication bias of the studies were also assessed.
RESULTS
Nine articles of methodological quality were included in the meta-analysis. The pooled results revealed that there were significant differences in hypotension (risk ratio [RR] (95% confidence interval [CI]) = 0.81 (0.68, 0.97), p = 0.02) and ephedrine dose (weighted mean difference [WMD] [95%CI] = -20.94 [-37.50, -4.37] mg, p = 0.01) between the spinal and general anesthesia groups. However, no significant differences were observed in the use of ephedrine (RR [95% CI] = 0.77 [0.19, 3.05]), blood loss (WMD [95%CI] = -34.38 [-89.56, 20.80) mL], myocardial infarction (RR [95% CI] = 0.78 [0.31, 1.94] mL), heart failure (RR [95% CI] = 0.87 [0.17, 4.36] mL), stroke (RR [95%CI) = 0.65 [0.22, 1.95] mL), postoperative nausea and vomiting (RR [95% CI] = 0.88 [0.17, 4.35] mL), delirium (RR [95% CI] = 1.08 [0.89, 1.31] mL), and mortality (RR [95% CI] = 1.10 [0.72, 1.68] mL) (all p < 0.05). No publication bias was observed in any of the included studies.
CONCLUSION
Compared to general anesthesia, spinal anesthesia was associated with a lower risk of intraoperative hypotension and lower doses of ephedrine in older patients undergoing hip fracture surgery.
Topics: Humans; Aged; Ephedrine; Randomized Controlled Trials as Topic; Anesthesia, General; Hip Fractures; Hypotension; Anesthesia, Spinal
PubMed: 37753546
DOI: 10.1111/os.13895 -
COPD Dec 2024To compare the efficacy of budesonide/formoterol (BF) versus fluticasone/salmeterol (FS) in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). (Meta-Analysis)
Meta-Analysis
Comparative Efficacy of Budesonide/Formoterol Versus Fluticasone/Salmeterol in Patients With Moderate-to-Severe Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.
BACKGROUND/OBJECTIVE
To compare the efficacy of budesonide/formoterol (BF) versus fluticasone/salmeterol (FS) in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).
METHODS
The PubMed, Embase, Cochrane Library, and Web of Science databases were searched for studies comparing BF versus FS in the treatment of COPD from inception to July 17, 2023. Outcomes, including exacerbations, hospitalizations, pneumonia, emergency department (ED) visits for COPD, length of hospitalization, and number of exacerbations, were compared using risk ratio (RR) with corresponding 95% confidence interval (CI) or weighted mean difference (WMD) with 95% CI. All statistical analyses were performed using Stata version 12.0.
RESULTS
Ten studies comprising a total of 136,369 participants were included. Compared with those treated with FS, patients with COPD treated with BF experienced a reduced number of exacerbations (RR 0.91 [95% CI 0.83-1.00]; = 0.040), hospitalizations (RR 0.77 [95% CI 0.67-0.88]; < 0.001), and frequency of pneumonia (RR 0.77 [95% CI 0.64-0.92]; = 0.05). However, no significant difference was observed between BF and FS in terms of ED visits for COPD (RR 0.87 [95% CI 0.69-1.10]; = 0.243), length of hospitalization (WMD -0.18 [95% CI -0.62-0.27]; = 0.437), and number of exacerbations (WMD -0.06 [95% CI -0.28-0.16]; = 0.602). Notably, no significant heterogeneity was noted in length of hospitalization between the two groups, whereas clear heterogeneity was observed in other outcomes ( > 50%, < 0.05).
CONCLUSION
Compared with FS, BF therapy appears to be a more promising treatment strategy for patients with moderate-to-severe COPD; however, this should be verified in further high-quality studies.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Fluticasone-Salmeterol Drug Combination; Patients; Budesonide, Formoterol Fumarate Drug Combination; Pneumonia
PubMed: 38573085
DOI: 10.1080/15412555.2024.2328708 -
Journal of Studies on Alcohol and Drugs Mar 2024This study aims to review applications of immersive, head-mounted display (HMD)-delivered virtual reality (VR) technology for the assessment and modification of...
OBJECTIVE
This study aims to review applications of immersive, head-mounted display (HMD)-delivered virtual reality (VR) technology for the assessment and modification of clinically relevant factors (e.g., craving, electrophysiological reactions, brain activation) present in illicit substance use.
METHOD
A PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses)-guided systematic review was conducted and retrieved articles from four databases. Articles included were peer-reviewed, empirical studies and were screened on criteria pertaining to sample using (or with a history of using) substances and measurement of substance-related factors.
RESULTS
Eighteen articles met inclusion criteria. Applications of immersive, HMD-delivered VR in assessment and modification were most prevalent among individuals using (or with a history of using) methamphetamine and targeted subjective craving, electrophysiological biomarkers (e.g., heart rate variability, skin conductance), and brain activity. Environments presented through VR involved substance-relevant cues (e.g., paraphernalia) and neuropsychological assessments. The majority of assessment studies elicited clinically relevant factor(s) present in illicit substance use through VR and all reviewed modification studies effectively reduced clinically relevant factors in methamphetamine and opioid use (e.g., craving, subjective pain).
CONCLUSIONS
There is evidence to support the use of immersive, HMD-delivered VR in the assessment and modification of clinically relevant factors in methamphetamine use, as well as preliminary evidence to support its effectiveness for clinically relevant factors in opioid use. Future research should further examine the effectiveness of HMD-delivered VR in modifying illicit substance use and triangulate biomarkers measured in individuals using illicit substances.
Topics: Humans; Analgesics, Opioid; Virtual Reality; Pain; Opioid-Related Disorders; Biomarkers; Methamphetamine
PubMed: 38206672
DOI: 10.15288/jsad.23-00189 -
Therapeutic Drug Monitoring Apr 2024Compared with antipsychotics, the relationship between antidepressant blood (plasma or serum) concentrations and target engagement is less well-established.
BACKGROUND
Compared with antipsychotics, the relationship between antidepressant blood (plasma or serum) concentrations and target engagement is less well-established.
METHODS
We have discussed the literature on the relationship between plasma concentrations of antidepressant drugs and their target occupancy. Antidepressants reviewed in this work are citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine, duloxetine, milnacipran, tricyclic antidepressants (amitriptyline, nortriptyline, and clomipramine), bupropion, tranylcypromine, moclobemide, and vortioxetine. Four electronic databases were systematically searched.
RESULTS
We included 32 articles published 1996-2022. A strong relationship between serotonin transporter (SERT) occupancy and drug concentration is well established for selective serotonin reuptake inhibitors. Lower limits of recommended therapeutic reference ranges largely corroborate with the findings from positron emission tomography studies (80% SERT occupancy). Only a few novel studies have investigated alternative targets, that is, norepinephrine transporters (NETs), dopamine transporters (DATs), or monoamine oxidase A (MAO-A). For certain classes of drugs, positron emission tomography study data are inconclusive. Low DAT occupancy after bupropion treatment speculates its discussed mechanism of action. For MAO inhibitors, a correlation between drug concentration and MAO-A occupancy could not be established.
CONCLUSIONS
Neuroimaging studies are critical in TDM-guided therapy for certain antidepressants, whereas for bupropion and MAO inhibitors, the available evidence offers no further insight. Evidence for selective serotonin reuptake inhibitors is strong and justifies a titration toward suggested ranges. For SNRIs, duloxetine, and venlafaxine, NETs are sufficiently occupied, well above the SERT efficacy threshold. For these drugs, a titration toward higher concentrations (within the recommended range) should be considered in case of no response at lower concentrations.
Topics: Humans; Selective Serotonin Reuptake Inhibitors; Venlafaxine Hydrochloride; Bupropion; Duloxetine Hydrochloride; Monoamine Oxidase Inhibitors; Antidepressive Agents; Positron-Emission Tomography; Monoamine Oxidase
PubMed: 38287888
DOI: 10.1097/FTD.0000000000001142 -
International Journal of Cardiology Nov 2023The aims of this study were to provide an overview of the cardiac stress response in Fontan patients and of the use, safety and clinical value of stress imaging in...
INTRODUCTION
The aims of this study were to provide an overview of the cardiac stress response in Fontan patients and of the use, safety and clinical value of stress imaging in Fontan patients.
METHODS
Studies evaluating cardiac function using stress imaging in Fontan patients published up until 12 December 2021 were included in this review.
RESULTS
From 1603 potential studies, 32 studies met the inclusion criteria. In total, stress imaging tests of 728 Fontan patients were included. Cardiac function was most often measured using physical stress (61%), all other studies used dobutamine-induced stress. Stroke volume (SV) increased in most studies (71%), mean SV at rest ranged from 27 mL/m to 60 mL/m versus 27 mL/m to 101 mL/m during stress, and increased with an average of 4%. Ejection fraction increased in almost all studies, whereas both end-systolic volume and end-diastolic volume decreased during stress. Higher heart rates were obtained with physical stress (82-180) compared to dobutamine induced stress (73-128). Compared to controls, increases in heartrate and SV were lower and end-diastolic volume decreased abnormally in 75% of reporting studies. No major adverse events were reported. Poorer cardiac stress response was related to decreased exercise capacity and higher risk for long-term (adverse) outcomes in Fontan patients.
DISCUSSION
Cardiac stress response in Fontan patients differs from healthy subjects, reflected by lower increases in heart rate, diminished preload and decreased cardiac output, especially during higher levels of exercise. Stress imaging is safe, however the added clinical value needs to be investigated in more detail.
Topics: Humans; Fontan Procedure; Dobutamine; Heart; Heart Defects, Congenital; Magnetic Resonance Imaging, Cine
PubMed: 37479147
DOI: 10.1016/j.ijcard.2023.131192 -
BMJ Paediatrics Open May 2024There exists limited agreement on the recommendations for the treatment of transitional circulatory instability (TCI) in preterm neonates OBJECTIVE: To compare the... (Meta-Analysis)
Meta-Analysis Comparative Study
Comparative efficacy of volume expansion, inotropes and vasopressors in preterm neonates with probable transitional circulatory instability in the first week of life: a systematic review and network meta-analysis.
BACKGROUND
There exists limited agreement on the recommendations for the treatment of transitional circulatory instability (TCI) in preterm neonates OBJECTIVE: To compare the efficacy of various interventions used to treat TCI METHODS: Medline and Embase were searched from inception to 21 July 2023. Two authors extracted the data independently. A Bayesian random effects network meta-analysis was used. Recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework.
INTERVENTIONS
Dopamine, dobutamine, epinephrine, hydrocortisone, vasopressin, milrinone, volume and placebo.
MAIN OUTCOME MEASURES
Mortality, major brain injury (MBI) (intraventricular haemorrhage > grade 2 or cystic periventricular leukomalacia), necrotising enterocolitis (NEC) ≥stage 2 and treatment response (as defined by the author).
RESULTS
15 Randomized Controlled Trials (RCTs) were included from the 1365 titles and abstracts screened. Clinical benefit or harm could not be ruled out for the critical outcome of mortality. For the outcome of MBI, epinephrine possibly decreased the risk when compared to dobutamine and milrinone (very low certainty). Epinephrine was possibly associated with a lesser risk of NEC when compared with dopamine, dobutamine, hydrocortisone and milrinone (very low certainty). Dopamine was possibly associated with a lesser risk of NEC when compared with dobutamine (very low certainty). Vasopressin possibly decreased the risk of NEC compared with dopamine, dobutamine, hydrocortisone and milrinone (very low certainty). Clinical benefit or harm could not be ruled out for the outcome response to treatment.
CONCLUSIONS
Epinephrine may be used as the first-line drug in preterm neonates with TCI, the evidence certainty being very low. We suggest future trials evaluating the management of TCI with an emphasis on objective criteria to define it.
Topics: Humans; Infant, Newborn; Cardiotonic Agents; Vasoconstrictor Agents; Infant, Premature; Network Meta-Analysis; Infant, Premature, Diseases; Randomized Controlled Trials as Topic; Dobutamine
PubMed: 38769048
DOI: 10.1136/bmjpo-2024-002500