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Advances in Therapy Nov 2022Few randomised controlled trials (RCTs) have directly compared long-acting muscarinic antagonist/long-acting β-agonist (LAMA/LABA) dual maintenance therapies for... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Few randomised controlled trials (RCTs) have directly compared long-acting muscarinic antagonist/long-acting β-agonist (LAMA/LABA) dual maintenance therapies for patients with chronic obstructive pulmonary disease (COPD). This systematic literature review and network meta-analysis (NMA) compared the efficacy of umeclidinium/vilanterol (UMEC/VI) versus other dual and mono-bronchodilator therapies in symptomatic patients with COPD.
METHODS
A systematic literature review (October 2015-November 2020) was performed to identify RCTs ≥ 8 weeks long in adult patients with COPD that compared LAMA/LABA combinations against any long-acting bronchodilator-containing dual therapy or monotherapy. Data extracted on changes from baseline in trough forced expiratory volume in 1 s (FEV), St George's Respiratory Questionnaire (SGRQ) total score, Transitional Dyspnoea Index (TDI) focal score, rescue medication use and moderate/severe exacerbation rate were analysed using an NMA in a frequentist framework. The primary comparison was at 24 weeks. Fixed effects model results are presented.
RESULTS
The NMA included 69 full-length publications (including 10 GSK clinical study reports) reporting 49 studies. At 24 weeks, UMEC/VI provided statistically significant greater improvements in FEV versus all dual therapy and monotherapy comparators. UMEC/VI provided similar improvements in SGRQ total score compared with all other LAMA/LABAs, and significantly greater improvements versus UMEC 125 μg, glycopyrronium 50 μg, glycopyrronium 18 μg, tiotropium 18 μg and salmeterol 50 μg. UMEC/VI also provided significantly better outcomes versus some comparators for TDI focal score, rescue medication use, annualised moderate/severe exacerbation rate, and time to first moderate/severe exacerbation.
CONCLUSION
UMEC/VI provided generally better outcomes compared with LAMA or LABA monotherapies, and consistent improvements in lung function (measured by change from baseline in trough FEV at 24 weeks) versus dual therapies. Treatment with UMEC/VI may improve outcomes for symptomatic patients with COPD compared with alternative maintenance treatments.
Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Adult; Benzyl Alcohols; Bronchodilator Agents; Chlorobenzenes; Drug Combinations; Dyspnea; Forced Expiratory Volume; Glycopyrrolate; Humans; Muscarinic Antagonists; Network Meta-Analysis; Pulmonary Disease, Chronic Obstructive; Quinuclidines; Salmeterol Xinafoate; Tiotropium Bromide; Treatment Outcome
PubMed: 35857184
DOI: 10.1007/s12325-022-02234-x -
JAMA Network Open Mar 2024Antipsychotic-induced akathisia (AIA) occurs in 14% to 35% of patients treated with antipsychotics and is associated with increased suicide and decreased adherence in... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Antipsychotic-induced akathisia (AIA) occurs in 14% to 35% of patients treated with antipsychotics and is associated with increased suicide and decreased adherence in patients with schizophrenia. However, no comprehensive review and network meta-analysis has been conducted to compare the efficacy of treatments for AIA.
OBJECTIVE
To compare the efficacy associated with AIA treatments.
DATA SOURCES
Three databases (MEDLINE, Web of Science, and Google Scholar) were systematically searched by multiple researchers for double-blind randomized clinical trials (RCTs) comparing active drugs for the treatment of AIA with placebo or another treatment between May 30 and June 18, 2023.
STUDY SELECTION
Selected studies were RCTs that compared adjunctive drugs for AIA vs placebo or adjunctive treatment in patients treated with antipsychotics fulfilling the criteria for akathisia, RCTs with sample size of 10 patients or more, only trials in which no additional drugs were administered during the study, and RCTs that used a validated akathisia score. Trials with missing data for the main outcome (akathisia score at the end points) were excluded.
DATA EXTRACTION AND SYNTHESIS
Data extraction and synthesis were performed, estimating standardized mean differences (SMDs) through pairwise and network meta-analysis with a random-effects model. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed.
MAIN OUTCOMES AND MEASURES
The primary outcome was the severity of akathisia measured by a validated scale at the last available end point.
RESULTS
Fifteen trials involving 492 participants compared 10 treatments with placebo. Mirtazapine (15 mg/d for ≥5 days; SMD, -1.20; 95% CI, -1.83 to -0.58), biperiden (6 mg/d for ≥14 days; SMD, -1.01; 95% CI, -1.69 to -0.34), vitamin B6 (600-1200 mg/d for ≥5 days; SMD, -0.92; 95% CI, -1.57 to -0.26), trazodone (50 mg/d for ≥5 days; SMD, -0.84; 95% CI, -1.54 to -0.14), mianserin (15 mg/d for ≥5 days; SMD, -0.81; 95% CI, -1.44 to -0.19), and propranolol (20 mg/d for ≥6 days; SMD, -0.78; 95% CI, -1.35 to -0.22) were associated with greater efficacy than placebo, with low to moderate heterogeneity (I2 = 34.6%; 95% CI, 0.0%-71.1%). Cyproheptadine, clonazepam, zolmitriptan, and valproate did not yield significant effects. Eight trials were rated as having low risk of bias; 2, moderate risk; and 5, high risk. Sensitivity analyses generally confirmed the results for all drugs except for cyproheptadine and propranolol. No association between effect sizes and psychotic severity was found.
CONCLUSIONS AND RELEVANCE
In this systematic review and network meta-analysis, mirtazapine, biperiden, and vitamin B6 were associated with the greatest efficacy for AIA, with vitamin B6 having the best efficacy and tolerance profile. Trazodone, mianserin, and propranolol appeared as effective alternatives with slightly less favorable efficacy and tolerance profiles. These findings should assist prescribers in selecting an appropriate medication for treating AIA.
Topics: Humans; Antipsychotic Agents; Biperiden; Cyproheptadine; Gallopamil; Mianserin; Mirtazapine; Network Meta-Analysis; Propranolol; Randomized Controlled Trials as Topic; Trazodone; Vitamin B 6; Akathisia, Drug-Induced
PubMed: 38451521
DOI: 10.1001/jamanetworkopen.2024.1527 -
Critical Care Medicine Oct 2022Hepatorenal syndrome (HRS) is associated with high rates of morbidity and mortality. Evidence examining commonly used drug treatments remains uncertain. We assessed the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Hepatorenal syndrome (HRS) is associated with high rates of morbidity and mortality. Evidence examining commonly used drug treatments remains uncertain. We assessed the comparative effectiveness of inpatient treatments for HRS by performing a network meta-analysis of randomized clinical trials (RCTs).
DATA SOURCES
We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Medline In-Process & Other Non-Indexed Citations, Scopus, and Web of Science from inception.
STUDY SELECTION AND DATA EXTRACTION
Pairs of reviewers independently identified eligible RCTs that enrolled patients with type 1 or 2 HRS. Pairs of reviewers independently extracted data.
DATA SYNTHESIS
We assessed risk of bias using the Cochrane tool for RCTs and certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluations approach. Our main outcomes are all-cause mortality, HRS reversal, and serious adverse events. Of 3,079 citations, we included 26 RCTs examining 1,736 patients. Based on pooled analysis, terlipressin increases HRS reversal compared with placebo (142 reversals per 1,000 [95% CI, >87.7 to >210.9]; high certainty). Norepinephrine (112.7 reversals per 1,000 [95% CI, 52.6 to >192.3]) may increase HRS reversal compared with placebo (low certainty). The effect of midodrine+octreotide (67.8 reversals per 1,000 [95% CI, <2.8 to >177.4]; very low) on HRS reversal is uncertain. Terlipressin may reduce mortality compared with placebo (93.7 fewer deaths [95% CI, 168.7 to <12.5]; low certainty). Terlipressin probably increases the risk of serious adverse events compared with placebo (20.4 more events per 1,000 [95% CI, <5.1 to >51]; moderate certainty).
CONCLUSIONS
Terlipressin increases HRS reversal compared with placebo. Terlipressin may reduce mortality. Until access to terlipressin improves, initial norepinephrine administration may be more appropriate than initial trial with midodrine+octreotide. Our review has the potential to inform future guideline and practice in the treatment of HRS.
Topics: Hepatorenal Syndrome; Humans; Midodrine; Network Meta-Analysis; Norepinephrine; Octreotide; Terlipressin; Treatment Outcome; Vasoconstrictor Agents
PubMed: 35777925
DOI: 10.1097/CCM.0000000000005595 -
The Lancet. Psychiatry Mar 2024There are no recommendations based on the efficacy of specific drugs for the treatment of psychotic depression. To address this evidence gap, we did a network... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There are no recommendations based on the efficacy of specific drugs for the treatment of psychotic depression. To address this evidence gap, we did a network meta-analysis to assess and compare the efficacy and safety of pharmacological treatments for psychotic depression.
METHODS
In this systematic review and network meta-analysis, we searched ClinicalTrials.gov, CENTRAL, Embase, PsycINFO, PubMed, Scopus, and Web of Science from inception to Nov 23, 2023 for randomised controlled trials published in any language that assessed pharmacological treatments for individuals of any age with a diagnosis of a major depressive episode with psychotic features, in the context of major depressive disorder or bipolar disorder in any setting. We excluded continuation or maintenance trials. We screened the study titles and abstracts identified, and we extracted data from relevant studies after full-text review. If full data were not available, we requested data from study authors twice. We analysed treatments for individual drugs (or drug combinations) and by grouping them on the basis of mechanisms of action. The primary outcomes were response rate (ie, the proportion of participants who responded to treatment) and acceptability (ie, the proportion who discontinued treatment for any reason). We calculated risk ratios and did separate frequentist network meta-analyses by using random-effects models. The risk of bias of individual studies was assessed with the Cochrane risk-of-bias tool and the confidence in the evidence with the Confidence-In-Network-Meta-Analysis (CINeMA). This study was registered with PROSPERO, CRD42023392926.
FINDINGS
Of 6313 reports identified, 16 randomised controlled trials were included in the systematic review, and 14 were included in the network meta-analyses. The 16 trials included 1161 people with psychotic depression (mean age 50·5 years [SD 11·4]). 516 (44·4%) participants were female and 422 (36·3%) were male; sex data were not available for the other 223 (19·2%). 489 (42·1%) participants were White, 47 (4·0%) were African American, and 12 (1·0%) were Asian; race or ethnicity data were not available for the other 613 (52·8%). Only the combination of fluoxetine plus olanzapine was associated with a higher proportion of participants with a treatment response compared with placebo (risk ratio 1·91 [95% CI 1·27-2·85]), with no differences in terms of safety outcomes compared with placebo. When treatments were grouped by mechanism of action, the combination of a selective serotonin reuptake inhibitor with a second-generation antipsychotic was associated with a higher proportion of treatment responses than was placebo (1·89 [1·17-3·04]), with no differences in terms of safety outcomes. In head-to-head comparisons of active treatments, a significantly higher proportion of participants had a response to amitriptyline plus perphenazine (3·61 [1·23-10·56]) and amoxapine (3·14 [1·01-9·80]) than to perphenazine, and to fluoxetine plus olanzapine compared with olanzapine alone (1·60 [1·09-2·34]). Venlafaxine, venlafaxine plus quetiapine (2·25 [1·09-4·63]), and imipramine (1·95 [1·01-3·79]) were also associated with a higher proportion of treatment responses overall. In head-to-head comparisons grouped by mechanism of action, antipsychotic plus antidepressant combinations consistently outperformed monotherapies from either drug class in terms of the proportion of participants with treatment responses. Heterogeneity was low. No high-risk instances were identified in the bias assessment for our primary outcomes.
INTERPRETATION
According to the available evidence, the combination of a selective serotonin reuptake inhibitor and a second-generation antipsychotic-and particularly of fluoxetine and olanzapine-could be the optimal treatment choice for psychotic depression. These findings should be taken into account in the development of clinical practice guidelines. However, these conclusions should be interpreted cautiously in view of the low number of included studies and the limitations of these studies.
FUNDING
None.
Topics: Male; Female; Humans; Middle Aged; Depressive Disorder, Major; Fluoxetine; Perphenazine; Network Meta-Analysis; Bipolar Disorder; Venlafaxine Hydrochloride; Selective Serotonin Reuptake Inhibitors; Depression; Antipsychotic Agents; Olanzapine
PubMed: 38360024
DOI: 10.1016/S2215-0366(24)00006-3 -
Nutrients Dec 2021l-Carnitine (l-C) and any of its forms (glycine-propionyl l-Carnitine (GPL-C) or l-Carnitine l-tartrate (l-CLT)) has been frequently recommended as a supplement to...
l-Carnitine (l-C) and any of its forms (glycine-propionyl l-Carnitine (GPL-C) or l-Carnitine l-tartrate (l-CLT)) has been frequently recommended as a supplement to improve sports performance due to, among others, its role in fat metabolism and in maintaining the mitochondrial acetyl-CoA/CoA ratio. The main aim of the present systematic review was to determine the effects of oral l-C supplementation on moderate- (50-79% V˙O) and high-intensity (≥80% V˙O) exercise performance and to show the effective doses and ideal timing of its intake. A structured search was performed according to the PRISMA statement and the PICOS guidelines in the Web of Science (WOS) and Scopus databases, including selected data obtained up to 24 October 2021. The search included studies where l-C or glycine-propionyl l-Carnitine (GPL-C) supplementation was compared with a placebo in an identical situation and tested its effects on high and/or low-moderate performance. The trials that used the supplementation of l-C together with additional supplements were eliminated. There were no applied filters on physical fitness level, race, or age of the participants. The methodological quality of studies was evaluated by the McMaster Critical Review Form. Of the 220 articles obtained, 11 were finally included in this systematic review. Six studies used l-C, while three studies used l-CLT, and two others combined the molecule propionyl l-Carnitine (PL-C) with GPL-C. Five studies analyzed chronic supplementation (4-24 weeks) and six studies used an acute administration (<7 days). The administration doses in this chronic supplementation varied from 1 to 3 g/day; in acute supplementation, oral l-C supplementation doses ranged from 3 to 4 g. On the one hand, the effects of oral l-C supplementation on high-intensity exercise performance variables were analyzed in nine studies. Four of them measured the effects of chronic supplementation (lower rating of perceived exertion (RPE) after 30 min at 80% V˙O on cycle ergometer and higher work capacity in "all-out" tests, peak power in a Wingate test, and the number of repetitions and volume lifted in leg press exercises), and five studies analyzed the effects of acute supplementation (lower RPE after graded exercise test on the treadmill until exhaustion and higher peak and average power in the Wingate cycle ergometer test). On the other hand, the effects of l-C supplementation on moderate exercise performance variables were observed in six studies. Out of those, three measured the effect of an acute supplementation, and three described the effect of a chronic supplementation, but no significant improvements on performance were found. In summary, l-C supplementation with 3 to 4 g ingested between 60 and 90 min before testing or 2 to 2.72 g/day for 9 to 24 weeks improved high-intensity exercise performance. However, chronic or acute l-C or GPL-C supplementation did not present improvements on moderate exercise performance.
Topics: Administration, Oral; Athletic Performance; Carnitine; Dietary Supplements; Exercise; Female; Humans; Male; Sports Nutritional Physiological Phenomena; Time Factors
PubMed: 34959912
DOI: 10.3390/nu13124359 -
European Journal of Clinical... Dec 2020To investigate the comparative effectiveness of dopamine agonists and monoamine oxidase type-B (MAO-B) inhibitors available for treatment of Parkinson's disease. (Comparative Study)
Comparative Study Meta-Analysis
PURPOSE
To investigate the comparative effectiveness of dopamine agonists and monoamine oxidase type-B (MAO-B) inhibitors available for treatment of Parkinson's disease.
METHODS
We performed a systematic literature search identifying randomized controlled trials investigating 4 dopamine agonists (cabergoline, pramipexole, ropinirole, rotigotine) and 3 MAO-B inhibitors (selegiline, rasagiline, safinamide) for Parkinson's disease. We extracted and pooled data from included clinical trials in a joint model allowing both direct and indirect comparison of the seven drugs. We considered dopamine agonists and MAO-B inhibitors given as monotherapy or in combination with levodopa. Selected endpoints were change in the Unified Parkinson's Disease Rating Scale (UPDRS) score, serious adverse events and withdrawals. We estimated the relative effectiveness of each dopamine agonist and MAO-B inhibitor versus comparator drug.
RESULTS
Altogether, 79 publications were included in the analysis. We found all the investigated drugs to be effective compared with placebo when given as monotherapy except safinamide. When considering combination treatment, the estimated relative effects of selegiline, pramipexole, ropinirole, rotigotine, cabergoline, rasagiline and safinamide were 2.316 (1.819, 2.951), 2.091 (1.889, 2.317), 2.037 (1.804, 2.294), 1.912 (1.716, 2.129), 1.664 (1.113, 2.418), 1.584 (1.379, 1.820) and 1.179 (1.031, 1.352), respectively, compared with joint placebo and levodopa treatment.
CONCLUSIONS
Dopamine agonists were found to be effective as treatment for Parkinson's disease, both when given as monotherapy and in combination with levodopa. Selegiline and rasagiline were also found to be effective for treating Parkinson's disease, and selegiline was the best option in combination with levodopa among all the drugs investigated.
Topics: Dopamine Agonists; Drug Therapy, Combination; Humans; Indans; Levodopa; Monoamine Oxidase Inhibitors; Parkinson Disease; Randomized Controlled Trials as Topic; Selegiline; Treatment Outcome
PubMed: 32710141
DOI: 10.1007/s00228-020-02961-6 -
The Cochrane Database of Systematic... Apr 2023Attention deficit hyperactivity disorder (ADHD) is a major problem in children and adolescents, characterised by age-inappropriate levels of inattention, hyperactivity,... (Review)
Review
BACKGROUND
Attention deficit hyperactivity disorder (ADHD) is a major problem in children and adolescents, characterised by age-inappropriate levels of inattention, hyperactivity, and impulsivity, and is associated with long-term social, academic, and mental health problems. The stimulant medications methylphenidate and amphetamine are the most frequently used treatments for ADHD, but these are not always effective and can be associated with side effects. Clinical and biochemical evidence suggests that deficiencies of polyunsaturated fatty acids (PUFA) could be related to ADHD. Research has shown that children and adolescents with ADHD have significantly lower plasma and blood concentrations of PUFA and, in particular, lower levels of omega-3 PUFA. These findings suggest that PUFA supplementation may reduce the attention and behaviour problems associated with ADHD. This review is an update of a previously published Cochrane Review. Overall, there was little evidence that PUFA supplementation improved symptoms of ADHD in children and adolescents.
OBJECTIVES
To compare the efficacy of PUFA to other forms of treatment or placebo in treating the symptoms of ADHD in children and adolescents.
SEARCH METHODS
We searched 13 databases and two trials registers up to October 2021. We also checked the reference lists of relevant studies and reviews for additional references.
SELECTION CRITERIA
We included randomised and quasi-randomised controlled trials that compared PUFA with placebo or PUFA plus alternative therapy (medication, behavioural therapy, or psychotherapy) with the same alternative therapy alone in children and adolescents (aged 18 years and under) diagnosed with ADHD.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcome was severity or improvement of ADHD symptoms. Our secondary outcomes were severity or incidence of behavioural problems; quality of life; severity or incidence of depressive symptoms; severity or incidence of anxiety symptoms; side effects; loss to follow-up; and cost. We used GRADE to assess the certainty of evidence for each outcome.
MAIN RESULTS
We included 37 trials with more than 2374 participants, of which 24 trials were new to this update. Five trials (seven reports) used a cross-over design, while the remaining 32 trials (52 reports) used a parallel design. Seven trials were conducted in Iran, four each in the USA and Israel, and two each in Australia, Canada, New Zealand, Sweden, and the UK. Single studies were conducted in Brazil, France, Germany, India, Italy, Japan, Mexico, the Netherlands, Singapore, Spain, Sri Lanka, and Taiwan. Of the 36 trials that compared a PUFA to placebo, 19 used an omega-3 PUFA, six used a combined omega-3/omega-6 supplement, and two used an omega-6 PUFA. The nine remaining trials were included in the comparison of PUFA to placebo, but also had the same co-intervention in the PUFA and placebo groups. Of these, four trials compared a combination of omega-3 PUFA plus methylphenidate to methylphenidate. One trial each compared omega-3 PUFA plus atomoxetine to atomoxetine; omega-3 PUFA plus physical training to physical training; and an omega-3 or omega-6 supplement plus methylphenidate to methylphenidate; and two trials compared omega-3 PUFA plus dietary supplement to dietary supplement. Supplements were given for a period of between two weeks and six months. Although we found low-certainty evidence that PUFA compared to placebo may improve ADHD symptoms in the medium term (risk ratio (RR) 1.95, 95% confidence interval (CI) 1.47 to 2.60; 3 studies, 191 participants), there was high-certainty evidence that PUFA had no effect on parent-rated total ADHD symptoms compared to placebo in the medium term (standardised mean difference (SMD) -0.08, 95% CI -0.24 to 0.07; 16 studies, 1166 participants). There was also high-certainty evidence that parent-rated inattention (medium-term: SMD -0.01, 95% CI -0.20 to 0.17; 12 studies, 960 participants) and hyperactivity/impulsivity (medium-term: SMD 0.09, 95% CI -0.04 to 0.23; 10 studies, 869 participants) scores were no different compared to placebo. There was moderate-certainty evidence that overall side effects likely did not differ between PUFA and placebo groups (RR 1.02, 95% CI 0.69 to 1.52; 8 studies, 591 participants). There was also moderate-certainty evidence that medium-term loss to follow-up was likely similar between groups (RR 1.03, 95% CI 0.77 to 1.37; 13 studies, 1121 participants).
AUTHORS' CONCLUSIONS
Although we found low-certainty evidence that children and adolescents receiving PUFA may be more likely to improve compared to those receiving placebo, there was high-certainty evidence that PUFA had no effect on total parent-rated ADHD symptoms. There was also high-certainty evidence that inattention and hyperactivity/impulsivity did not differ between PUFA and placebo groups. We found moderate-certainty evidence that overall side effects likely did not differ between PUFA and placebo groups. There was also moderate-certainty evidence that follow-up was similar between groups. It is important that future research addresses the current weaknesses in this area, which include small sample sizes, variability of selection criteria, variability of the type and dosage of supplementation, and short follow-up times.
Topics: Child; Humans; Adolescent; Attention Deficit Disorder with Hyperactivity; Atomoxetine Hydrochloride; Quality of Life; Fatty Acids, Unsaturated; Methylphenidate; Fatty Acids, Omega-3; Amphetamine
PubMed: 37058600
DOI: 10.1002/14651858.CD007986.pub3 -
Shock (Augusta, Ga.) Dec 2023Background: Septic shock is a distributive shock with decreased systemic vascular resistance and MAP. Septic shock contributes to the most common causes of death in the... (Meta-Analysis)
Meta-Analysis
Background: Septic shock is a distributive shock with decreased systemic vascular resistance and MAP. Septic shock contributes to the most common causes of death in the intensive care unit (ICU). Current guidelines recommend the use of norepinephrine as the first-line vasopressor, whereas adrenergic agonists and vasopressin analogs are also commonly used by physicians. To date, very few studies have synthetically compared the effects of multiple types of vasoactive medications. The aim of this study was to systemically evaluate the efficacy of vasoactive agents both individually and in combination to treat septic shock. Methods: The PubMed, MEDLINE, Embase, Web of Science, and Cochrane Central Register for Controlled Trials (CENTRAL) were searched up to May 12, 2022, to identify relevant randomized controlled trials. A network meta-analysis was performed to evaluate the effect of different types of vasopressors. The primary outcome was 28-day all-cause mortality. The secondary outcome was the ICU length of stay. Adverse events are defined as any undesirable outcomes, including myocardial infarction, cardiac arrhythmia, peripheral ischemia, or stroke and cerebrovascular events. Findings: Thirty-three randomized controlled trials comprising 4,966 patients and assessing 8 types of vasoactive treatments were included in the network meta-analysis. The surface under the cumulative ranking curve provided a ranking of vasoactive medications in terms of 28-day all-cause mortality from most effective to least effective: norepinephrine plus dobutamine, epinephrine, vasopressin, terlipressin, norepinephrine, norepinephrine plus vasopressin, dopamine, and dobutamine. Dopamine was associated with a significantly shorter ICU stay than norepinephrine, terlipressin, and vasopressin, whereas other vasoactive medications showed no definite difference in ICU length of stay. Regarding adverse events, norepinephrine was associated with the highest incidences of myocardial infarction and peripheral ischemia. Dopamine was associated with the highest incidence of cardiac arrhythmia. Epinephrine and terlipressin were associated with the highest incidences of myocardial infarction and peripheral ischemia. Interpretation: The results of this network meta-analysis suggest that norepinephrine plus dobutamine is associated with a lower risk of 28-day mortality in septic shock patients than other vasoactive medications, and the use of dopamine is associated with a higher risk of 28-day mortality due to septic shock than norepinephrine, terlipressin, and vasopressin.
Topics: Humans; Shock, Septic; Dopamine; Terlipressin; Dobutamine; Network Meta-Analysis; Vasoconstrictor Agents; Epinephrine; Norepinephrine; Vasopressins; Arrhythmias, Cardiac; Ischemia; Myocardial Infarction
PubMed: 37548686
DOI: 10.1097/SHK.0000000000002193 -
Critical Care (London, England) May 2020The use of the furosemide stress test (FST) as an acute kidney injury (AKI) severity marker has been described in several trials. However, the diagnostic performance of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The use of the furosemide stress test (FST) as an acute kidney injury (AKI) severity marker has been described in several trials. However, the diagnostic performance of the FST in predicting AKI progression has not yet been fully discussed.
METHODS
In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched the PubMed, Embase, and Cochrane databases up to March 2020. The diagnostic performance of the FST (in terms of sensitivity, specificity, number of events, true positive, false positive) was extracted and evaluated.
RESULTS
We identified eleven trials that enrolled a total of 1366 patients, including 517 patients and 1017 patients for whom the outcomes in terms of AKI stage progression and renal replacement therapy (RRT), respectively, were reported. The pooled sensitivity and specificity results of the FST for AKI progression prediction were 0.81 (95% CI 0.74-0.87) and 0.88 (95% CI 0.82-0.92), respectively. The pooled positive likelihood ratio (LR) was 5.45 (95% CI 3.96-7.50), the pooled negative LR was 0.26 (95% CI 0.19-0.36), and the pooled diagnostic odds ratio (DOR) was 29.69 (95% CI 17.00-51.85). The summary receiver operating characteristics (SROC) with pooled diagnostic accuracy was 0.88. The diagnostic performance of the FST in predicting AKI progression was not affected by different AKI criteria or underlying chronic kidney disease. The pooled sensitivity and specificity results of the FST for RRT prediction were 0.84 (95% CI 0.72-0.91) and 0.77 (95% CI 0.64-0.87), respectively. The pooled positive LR and pooled negative LR were 3.16 (95% CI 2.06-4.86) and 0.25 (95% CI 0.14-0.44), respectively. The pooled diagnostic odds ratio (DOR) was 13.59 (95% CI 5.74-32.17), and SROC with pooled diagnostic accuracy was 0.86. The diagnostic performance of FST for RRT prediction is better in stage 1-2 AKI compared to stage 3 AKI (relative DOR 5.75, 95% CI 2.51-13.33).
CONCLUSION
The FST is a simple tool for the identification of AKI populations at high risk of AKI progression and the need for RRT, and the diagnostic performance of FST in RRT prediction is better in early AKI population.
Topics: Acute Kidney Injury; Disease Progression; Exercise Test; Furosemide; Humans; Predictive Value of Tests; Renal Replacement Therapy; Severity of Illness Index
PubMed: 32381019
DOI: 10.1186/s13054-020-02912-8 -
Clinical Toxicology (Philadelphia, Pa.) Dec 2021The use of activated charcoal in poisoning remains both a pillar of modern toxicology and a source of debate. Following the publication of the joint position statements...
INTRODUCTION
The use of activated charcoal in poisoning remains both a pillar of modern toxicology and a source of debate. Following the publication of the joint position statements on the use of single-dose and multiple-dose activated charcoal by the American Academy of Clinical Toxicology and the European Association of Poison Centres and Clinical Toxicologists, the routine use of activated charcoal declined. Over subsequent years, many new pharmaceuticals became available in modified or alternative-release formulations and additional data on gastric emptying time in poisoning was published, challenging previous assumptions about absorption kinetics. The American Academy of Clinical Toxicology, the European Association of Poison Centres and Clinical Toxicologists and the Asia Pacific Association of Medical Toxicology founded the Clinical Toxicology Recommendations Collaborative to create a framework for evidence-based recommendations for the management of poisoned patients. The activated charcoal workgroup of the Clinical Toxicology Recommendations Collaborative was tasked with reviewing systematically the evidence pertaining to the use of activated charcoal in poisoning in order to update the previous recommendations.
OBJECTIVES
The main objective was: Does oral activated charcoal given to adults or children prevent toxicity or improve clinical outcome and survival of poisoned patients compared to those who do not receive charcoal? Secondary objectives were to evaluate pharmacokinetic outcomes, the role of cathartics, and adverse events to charcoal administration. This systematic review summarizes the available evidence on the efficacy of activated charcoal.
METHODS
A medical librarian created a systematic search strategy for Medline (Ovid), subsequently translated for Embase ( Ovid), CINAHL ( EBSCO), BIOSIS Previews ( Ovid), Web of Science, Scopus, and the Cochrane Library/DARE. All databases were searched from inception to December 31, 2019. There were no language limitations. One author screened all citations identified in the search based on predefined inclusion/exclusion criteria. Excluded citations were confirmed by an additional author and remaining articles were obtained in full text and evaluated by at least two authors for inclusion. All authors cross-referenced full-text articles to identify articles missed in the searches. Data from included articles were extracted by the authors on a standardized spreadsheet and two authors used the GRADE methodology to independently assess the quality and risk of bias of each included study.
RESULTS
From 22,950 titles originally identified, the final data set consisted of 296 human studies, 118 animal studies, and 145 studies. Also included were 71 human and two animal studies that reported adverse events. The quality was judged to have a Low or Very Low GRADE in 469 (83%) of the studies. Ninety studies were judged to be of Moderate or High GRADE. The higher GRADE studies reported on the following drugs: paracetamol (acetaminophen), phenobarbital, carbamazepine, cardiac glycosides (digoxin and oleander), ethanol, iron, salicylates, theophylline, tricyclic antidepressants, and valproate. Data on newer pharmaceuticals not reviewed in the previous American Academy of Clinical Toxicology/European Association of Poison Centres and Clinical Toxicologists statements such as quetiapine, olanzapine, citalopram, and Factor Xa inhibitors were included. No studies on the optimal dosing for either single-dose or multiple-dose activated charcoal were found. In the reviewed clinical data, the time of administration of the first dose of charcoal was beyond one hour in 97% ( = 1006 individuals), beyond two hours in 36% ( = 491 individuals), and beyond 12 h in 4% ( = 43 individuals) whereas the timing of the first dose in controlled studies was within one hour of ingestion in 48% ( = 2359 individuals) and beyond two hours in 36% ( = 484) of individuals.
CONCLUSIONS
This systematic review found heterogenous data. The higher GRADE data was focused on a few select poisonings, while studies that addressed patients with unknown and or mixed ingestions were hampered by low rates of clinically meaningful toxicity or death. Despite these limitations, they reported a benefit of activated charcoal beyond one hour in many clinical scenarios.
Topics: Acetaminophen; Animals; Carbamazepine; Charcoal; Decontamination; Drug Overdose; Humans
PubMed: 34424785
DOI: 10.1080/15563650.2021.1961144