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The Cochrane Database of Systematic... Nov 2020Cardiogenic shock (CS) and low cardiac output syndrome (LCOS) are potentially life-threatening complications of acute myocardial infarction (AMI), heart failure (HF) or... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cardiogenic shock (CS) and low cardiac output syndrome (LCOS) are potentially life-threatening complications of acute myocardial infarction (AMI), heart failure (HF) or cardiac surgery. While there is solid evidence for the treatment of other cardiovascular diseases of acute onset, treatment strategies in haemodynamic instability due to CS and LCOS remains less robustly supported by the given scientific literature. Therefore, we have analysed the current body of evidence for the treatment of CS or LCOS with inotropic and/or vasodilating agents. This is the second update of a Cochrane review originally published in 2014.
OBJECTIVES
Assessment of efficacy and safety of cardiac care with positive inotropic agents and vasodilator agents in CS or LCOS due to AMI, HF or after cardiac surgery.
SEARCH METHODS
We conducted a search in CENTRAL, MEDLINE, Embase and CPCI-S Web of Science in October 2019. We also searched four registers of ongoing trials and scanned reference lists and contacted experts in the field to obtain further information. No language restrictions were applied.
SELECTION CRITERIA
Randomised controlled trials (RCTs) enrolling patients with AMI, HF or cardiac surgery complicated by CS or LCOS.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures according to Cochrane standards.
MAIN RESULTS
We identified 19 eligible studies including 2385 individuals (mean or median age range 56 to 73 years) and three ongoing studies. We categorised studies into 11 comparisons, all against standard cardiac care and additional other drugs or placebo. These comparisons investigated the efficacy of levosimendan versus dobutamine, enoximone or placebo; enoximone versus dobutamine, piroximone or epinephrine-nitroglycerine; epinephrine versus norepinephrine or norepinephrine-dobutamine; dopexamine versus dopamine; milrinone versus dobutamine and dopamine-milrinone versus dopamine-dobutamine. All trials were published in peer-reviewed journals, and analyses were done by the intention-to-treat (ITT) principle. Eighteen of 19 trials were small with only a few included participants. An acknowledgement of funding by the pharmaceutical industry or missing conflict of interest statements occurred in nine of 19 trials. In general, confidence in the results of analysed studies was reduced due to relevant study limitations (risk of bias), imprecision or indirectness. Domains of concern, which showed a high risk in more than 50% of included studies, encompassed performance bias (blinding of participants and personnel) and bias affecting the quality of evidence on adverse events. All comparisons revealed uncertainty on the effect of inotropic/vasodilating drugs on all-cause mortality with a low to very low quality of evidence. In detail, the findings were: levosimendan versus dobutamine (short-term mortality: RR 0.60, 95% CI 0.36 to 1.03; participants = 1701; low-quality evidence; long-term mortality: RR 0.84, 95% CI 0.63 to 1.13; participants = 1591; low-quality evidence); levosimendan versus placebo (short-term mortality: no data available; long-term mortality: RR 0.55, 95% CI 0.16 to 1.90; participants = 55; very low-quality evidence); levosimendan versus enoximone (short-term mortality: RR 0.50, 0.22 to 1.14; participants = 32; very low-quality evidence; long-term mortality: no data available); epinephrine versus norepinephrine-dobutamine (short-term mortality: RR 1.25; 95% CI 0.41 to 3.77; participants = 30; very low-quality evidence; long-term mortality: no data available); dopexamine versus dopamine (short-term mortality: no deaths in either intervention arm; participants = 70; very low-quality evidence; long-term mortality: no data available); enoximone versus dobutamine (short-term mortality RR 0.21; 95% CI 0.01 to 4.11; participants = 27; very low-quality evidence; long-term mortality: no data available); epinephrine versus norepinephrine (short-term mortality: RR 1.81, 0.89 to 3.68; participants = 57; very low-quality evidence; long-term mortality: no data available); and dopamine-milrinone versus dopamine-dobutamine (short-term mortality: RR 1.0, 95% CI 0.34 to 2.93; participants = 20; very low-quality evidence; long-term mortality: no data available). No information regarding all-cause mortality were available for the comparisons milrinone versus dobutamine, enoximone versus piroximone and enoximone versus epinephrine-nitroglycerine.
AUTHORS' CONCLUSIONS
At present, there are no convincing data supporting any specific inotropic or vasodilating therapy to reduce mortality in haemodynamically unstable patients with CS or LCOS. Considering the limited evidence derived from the present data due to a high risk of bias and imprecision, it should be emphasised that there is an unmet need for large-scale, well-designed randomised trials on this topic to close the gap between daily practice in critical care of cardiovascular patients and the available evidence. In light of the uncertainties in the field, partially due to the underlying methodological flaws in existing studies, future RCTs should be carefully designed to potentially overcome given limitations and ultimately define the role of inotropic agents and vasodilator strategies in CS and LCOS.
Topics: Aged; Cardiac Output, Low; Cardiotonic Agents; Cause of Death; Dobutamine; Enoximone; Epinephrine; Humans; Hydrazones; Middle Aged; Myocardial Infarction; Nitric Oxide; Placebos; Pyridazines; Randomized Controlled Trials as Topic; Shock, Cardiogenic; Simendan; Vasodilator Agents
PubMed: 33152122
DOI: 10.1002/14651858.CD009669.pub4 -
International Journal of Molecular... Mar 2023According to the EU Early Warning System (EWS), synthetic cathinones (SCs) are the second largest new psychoactive substances (NPS) class, with 162 synthetic cathinones... (Review)
Review
According to the EU Early Warning System (EWS), synthetic cathinones (SCs) are the second largest new psychoactive substances (NPS) class, with 162 synthetic cathinones monitored by the EU EWS. They have a similar structure to cathinone, principally found in Catha Edulis; they have a phenethylamine related structure but also exhibit amphetamine-like stimulant effects. Illegal laboratories regularly develop new substances and place them on the market. For this reason, during the last decade this class of substances has presented a great challenge for public health and forensic toxicologists. Acting on different systems and with various mechanisms of action, the spectrum of side effects caused by the intake of these drugs of abuse is very broad. To date, most studies have focused on the substances' cardiac effects, and very few on their associated neurotoxicity. Specifically, synthetic cathinones appear to be involved in different neurological events, including increased alertness, mild agitation, severe psychosis, hyperthermia and death. A systematic literature search in PubMed and Scopus databases according to PRISMA guidelines was performed. A total of 515 studies published from 2005 to 2022 (350 articles from PubMed and 165 from Scopus) were initially screened for eligibility. The papers excluded, according to the criteria described in the Method Section (n = 401) and after full text analyses (n = 82), were 483 in total. The remaining 76 were included in the present review, as they met fully the inclusion criteria. The present work provides a comprehensive review on neurotoxic mechanisms of synthetic cathinones highlighting intoxication cases and fatalities in humans, as well as the toxic effects on animals (in particular rats, mice and zebrafish larvae). The reviewed studies showed brain-related adverse effects, including encephalopathy, coma and convulsions, and sympathomimetic and hallucinogenic toxidromes, together with the risk of developing excited/agitated delirium syndrome and serotonin syndrome.
Topics: Mice; Rats; Humans; Animals; Synthetic Cathinone; Zebrafish; Central Nervous System Stimulants; Fever; Amphetamine; Neurotoxicity Syndromes; Psychotropic Drugs
PubMed: 37047201
DOI: 10.3390/ijms24076230 -
The Journal of Maternal-fetal &... Dec 2023Antidepressant medications are used by increasing numbers of pregnant women. The evidence on the relationship between antidepressant use during pregnancy and the risk... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Antidepressant medications are used by increasing numbers of pregnant women. The evidence on the relationship between antidepressant use during pregnancy and the risk for gestational diabetes mellitus (GDM) is inconsistent. We perform a systematic review and meta-analysis to assess the GDM risk associated with antidepressant exposure during pregnancy.
METHODS
We systematically searched the PubMed and EMBASE databases until December 2021. We sought observational studies assessing the association between gestational antidepressant use and GDM.
RESULTS
Five observational studies were included in the analysis. Mothers exposed to antidepressants during pregnancy were at a significantly increased risk for GDM (relative risk [RR] 1.20, 95% confidence interval [CI] 1.11-1.30; < .001). However, after considering confounding by indication, we observed no significant effect of antidepressant use during pregnancy on the risk of GDM (RR 1.13, 95% CI 1-1.28; = .054; = 0%). Independent of clinical indication, subgroup analysis based on individual antidepressants suggested that the risk was increased by venlafaxine or amitriptyline use, but not by selective serotonin reuptake inhibitors.
CONCLUSIONS
The significant association between antidepressant exposure during pregnancy and GDM may be overestimated due to confounding by indication. However, the evidence remains insufficient, particularly for specific drug classes.
Topics: Pregnancy; Female; Humans; Diabetes, Gestational; Antidepressive Agents; Selective Serotonin Reuptake Inhibitors; Venlafaxine Hydrochloride; Amitriptyline
PubMed: 36599445
DOI: 10.1080/14767058.2022.2162817 -
BMJ Clinical Evidence Jan 2015Changes in air pressure during flying can cause ear-drum pain and perforation, vertigo, and hearing loss. It has been estimated that 10% of adults and 22% of children... (Review)
Review
INTRODUCTION
Changes in air pressure during flying can cause ear-drum pain and perforation, vertigo, and hearing loss. It has been estimated that 10% of adults and 22% of children might have changes to the ear drum after a flight, although perforation is rare. Symptoms usually resolve spontaneously.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of interventions to prevent middle-ear pain during air travel? We searched: Medline, Embase, The Cochrane Library and other important databases up to July 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found three studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: nasal balloon inflation, nasal decongestants (topical), and oral pseudoephedrine.
Topics: Air Travel; Earache; Humans; Nasal Decongestants; Pseudoephedrine
PubMed: 25599243
DOI: No ID Found -
Neuroscience and Biobehavioral Reviews Oct 2023Methamphetamine use typically starts in adolescence, and early onset is associated with worse outcomes. Yet, health, functional, and cognitive outcomes associated with... (Meta-Analysis)
Meta-Analysis Review
Methamphetamine use typically starts in adolescence, and early onset is associated with worse outcomes. Yet, health, functional, and cognitive outcomes associated with methamphetamine use in young people are not well understood. The aim of this study was to comprehensively assess the evidence on health, functional, and cognitive outcomes in young people (10-25 years-old) who use methamphetamine. Sixty-six studies were included. The strongest association observed was with conduct disorder, with young people who use methamphetamine some 13 times more likely to meet conduct disorder criteria than controls. They were also more likely to have justice system involvement and to perpetrate violence against others. Educational problems were consistently associated with youth methamphetamine use. The cognitive domain most reliably implicated was inhibitory control. Key limitations in the literature were identified, including heterogenous measurement of exposure and outcomes, lack of adequate controls, and limited longitudinal evidence. Outcomes identified in the present review - suggesting complex and clinically significant behavioural issues in this population - are informative for the development of future research and targeted treatments.
Topics: Adolescent; Humans; Child; Young Adult; Adult; Methamphetamine; Violence; Cognition
PubMed: 37678571
DOI: 10.1016/j.neubiorev.2023.105380 -
Respiratory Medicine Nov 2022This network meta-analysis (NMA) compared fixed-dose, twice daily fluticasone propionate/salmeterol (FP/Sal) vs. inhaled corticosteroid (ICS) and other ICS/long-acting... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This network meta-analysis (NMA) compared fixed-dose, twice daily fluticasone propionate/salmeterol (FP/Sal) vs. inhaled corticosteroid (ICS) and other ICS/long-acting beta-agonists (LABA) treatments, including when administered using maintenance and reliever therapy (MART) regimens, in terms of improvements in health-related quality of life (HRQoL). The relationship between changes in asthma control and HRQoL was assessed.
METHODS
Articles published between 2001 and 2021, reporting change from baseline (CFB) in Asthma Quality of Life Questionnaire (AQLQ) in patients with moderate-to-severe asthma, were identified by a systematic review. Random effects Bayesian NMAs derived estimates of the mean difference in CFB in AQLQ vs. other interventions connected to the network (included 15 studies). Sensitivity analyses explored the impacts of differences in follow-up duration, baseline asthma control, the inclusion of observational studies, adjusting for baseline FEV, and low-medium ICS dose arms only. Linear regression analysis compared CFBs in AQLQ and Asthma Control Questionnaire (ACQ) score.
RESULTS
Mean CFB in AQLQ with FP/Sal vs. comparators demonstrated expected ranked effects: mean difference 0.65 [95% credible interval: 0.54, 0.78] versus placebo, 0.58 [ 0.33, 0.84] versus LABA, 0.21 [ 0.13, 0.31] versus ICS alone, 0.06 [-0.04, 0.19] versus other ICS/LABA, and 0.00 [-0.13, 0.14] versus ICS/formoterol MART. Sensitivity analyses largely showed consistent results. Improvements in AQLQ and ACQ were strongly correlated (R = 0.94).
CONCLUSIONS
This NMA demonstrates that HRQoL is responsive to treatment, is strongly related to asthma control and that it can be well-managed in patients with moderate-to-severe asthma using regular treatment with inhaled FP/Sal.
Topics: Humans; Fluticasone-Salmeterol Drug Combination; Quality of Life; Bronchodilator Agents; Network Meta-Analysis; Bayes Theorem; Administration, Inhalation; Asthma; Formoterol Fumarate; Adrenal Cortex Hormones; Fluticasone; Drug Combinations
PubMed: 36257125
DOI: 10.1016/j.rmed.2022.106993 -
CNS Drugs Sep 2023Although one of the major presentations of vestibular migraine is dizziness with/without unsteady gait, it is still classified as one of the migraine categories.... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Although one of the major presentations of vestibular migraine is dizziness with/without unsteady gait, it is still classified as one of the migraine categories. However, in contrast to ordinary migraine, vestibular migraine patients have distinct characteristics, and the detailed treatment strategy for vestibular migraine is different and more challenging than ordinary migraine treatment. Currently, there is no conclusive evidence regarding its management, including vestibular migraine prophylaxis.
AIM
The objective of this current network meta-analysis (NMA) was to compare the efficacy and acceptability of individual treatment strategies in patients with vestibular migraine.
METHODS
The PubMed, Embase, ScienceDirect, ProQuest, Web of Science, ClinicalKey, Cochrane Central, and ClinicalTrials.gov databases were systematically searched for randomized controlled trials (RCTs), with a final literature search date of 30 December 2022. Patients diagnosed with vestibular migraine were included. The PICO of the current study included (1) patients with vestibular migraine; (2) intervention: any active pharmacologic or non-pharmacologic intervention; (3) comparator: placebo-control, active control, or waiting list; and (4) outcome: changes in migraine frequency or severity. This NMA of RCTs of vestibular migraine treatment was conducted using a frequentist model. We arranged inconsistency and similarity tests to re-examine the assumption of NMA, and also conducted a subgroup analysis focusing on RCTs of pharmacological treatment for vestibular migraine management. The primary outcome was changes in the frequency of vestibular migraines, while the secondary outcomes were changes in vestibular migraine severity and acceptability. Acceptability was set as the dropout rate, which was defined as the participant leaving the study before the end of the trial for any reason. Two authors independently evaluated the risk of bias for each domain using the Cochrane risk-of-bias tool.
RESULTS
Seven randomized controlled trials (N = 828, mean age 37.6 years, 78.4% female) and seven active regimens were included. We determined that only valproic acid (standardized mean difference [SMD] -1.61, 95% confidence interval [CI] -2.69, -0.54), propranolol (SMD -1.36, 95% CI -2.55, -0.17), and venlafaxine (SMD -1.25, 95% CI -2.32, -0.18) were significantly associated with better improvement in vestibular migraine frequency than the placebo/control groups. Furthermore, among all the investigated pharmacologic/non-pharmacologic treatments, valproic acid yielded the greatest decrease in vestibular migraine frequency among all the interventions. In addition, most pharmacologic/non-pharmacologic treatments were associated with similar acceptability (i.e. dropout rate) as those of the placebo/control groups.
CONCLUSIONS
The current study provides evidence that only valproic acid, propranolol, and venlafaxine might be associated with beneficial efficacy in vestibular migraine treatment.
TRIAL REGISTRATION
CRD42023388343.
Topics: Adult; Female; Humans; Male; Migraine Disorders; Network Meta-Analysis; Propranolol; Valproic Acid; Venlafaxine Hydrochloride
PubMed: 37676473
DOI: 10.1007/s40263-023-01037-0 -
Addiction Biology Nov 2022Classic psychedelics refer to substances such as lysergic acid diethylamide (LSD), psilocybin, ayahuasca, and mescaline, which induce altered states of consciousness by...
Classic psychedelics refer to substances such as lysergic acid diethylamide (LSD), psilocybin, ayahuasca, and mescaline, which induce altered states of consciousness by acting mainly on 5-HT receptors. Recently, the interest of psychedelics as pharmacological treatment for psychiatric disorders has increased significantly, including their use on problematic use of alcohol. This systematic review is aimed to analyse the last two decades of studies examining the relationship between classic psychedelics and alcohol consumption. We searched PubMed and PsycInfo for human and preclinical studies published between January 2000 to December 2021. The search identified 639 publications. After selection, 27 studies were included. Human studies (n = 20) generally show promising data and seem to indicate that classic psychedelics could help reduce alcohol consumption. Nevertheless, some of these studies present methodological concerns such as low number of participants, lack of control group or difficulty in determining the effect of classic psychedelics in isolation. On the other hand, preclinical studies (n = 7) investigating the effect of these compounds on voluntary alcohol consumption are scarce and show some conflicting data. Among these compounds, psilocybin seems to show the most consistent data indicating that this compound could be a potential candidate to treat alcohol use disorders. In the absence of understanding the biological and/or psychological mechanisms, more studies including methodological quality parameters are needed to finally determine the effects of classic psychedelics on alcohol consumption.
Topics: Animals; Humans; Hallucinogens; Psilocybin; Alcoholism; Lysergic Acid Diethylamide; Mescaline
PubMed: 36301215
DOI: 10.1111/adb.13229 -
Drug Design, Development and Therapy 2014Recent studies have promised that lisdexamfetamine (LDX) is effective in the treatment of adults with attention-deficit hyperactivity disorder (ADHD). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Recent studies have promised that lisdexamfetamine (LDX) is effective in the treatment of adults with attention-deficit hyperactivity disorder (ADHD).
OBJECTIVES
This systematic review was undertaken to summarize LDX efficacy, acceptability, and tolerability in adult ADHD. All randomized controlled trials (RCTs) of lisdexamfetamine compared with placebo were included for synthesis. Clinical trials published between January 1991 and January 2014 were evaluated.
METHODS
The database of MEDLINE(®), EMBASE™, CINAHL(®), PsycINFO(®) and Cochrane Controlled Trials Register were searched in January 2014. Studies were also searched in ClinicalTrials.gov and the EU Clinical Trials Register database. Study eligibility criteria, participants, and interventions were considered. All RCTs of LDX vs placebo reporting final results of: 1) severity of ADHD symptoms and executive function deficit, 2) response or remission rates, 3) overall discontinuation rate, or 4) discontinuation rate due to adverse events were included. The language of the papers was not restricted. All abstracts of studies gathered from the database were examined. After excluding irrelevant trials, the full text version of relevant studies were assessed and extracted for outcomes of interest. Examination of risks of bias, based on the Cochrane bias assessment, was carried out. The efficacy outcomes consisted of the mean end point or change scores for ADHD rating scales, the response rate, and the remission rate. The overall discontinuation rate and the discontinuation rate due to adverse events were measured for acceptability and tolerability, respectively. A random effect model was applied for the synthesis of relative risks (RRs), and weighted mean differences or standardized mean differences (SMDs) with 95% confidence intervals (CIs).
RESULTS
A total of 806 final study or safety participants were included. The dosage of lisdexamfetamine was 30 to 70 mg/day. The pooled mean scores of mean change and mean end point scores between LDX- and placebo-treated groups also had a significant difference (SMD [95% CI] of -0.97 [-1.15, -0.78], I(2)=18%). The pooled response rates for adult ADHD between the two groups had a significant difference (RR [95% CI] of 1.99 [1.50, 2.63], I(2)=0%). Based on the Behavior Rating Inventory of Executive Function - Adult version (BRIEF-A), the pooled end point mean scores for the Global Executive Composite (GEC) for the LDX-treated groups was greater than that of placebo-treated groups (MD [95% CI] of -9.20 [-14.11, -4.29], I(2)=34%). The pooled overall discontinuation rates between the two groups had no significant difference (RR [95% CI] of 0.82 [0.59, 1.14], I(2)=0%). Similarly, the pooled discontinuation rates due to adverse events between the two groups was not significantly different (RR [95% CI] of 1.77 [0.71, 4.40], I(2)=0%).
CONCLUSION
The number of included studies was limited (five RCTs), but based on this meta-analysis, LDX is efficacious and well tolerated in the treatment of adult ADHD. Additionally, it also improved the executive function deficits in this population. However, its acceptability is no higher than placebo. These findings should be carefully interpreted and considered as preliminary outcomes. To confirm these results, further studies are warranted. LDX is a viable alternative psychostimulant for adult ADHD.
Topics: Attention Deficit Disorder with Hyperactivity; Databases, Factual; Dextroamphetamine; Humans; Lisdexamfetamine Dimesylate; Placebos; Registries
PubMed: 25336914
DOI: 10.2147/DDDT.S68393 -
PLoS Neglected Tropical Diseases Apr 2023Scorpion envenomation is associated with several complications. One of the most serious complications is the cardiac involvement in the form of myocarditis that remains...
BACKGROUND
Scorpion envenomation is associated with several complications. One of the most serious complications is the cardiac involvement in the form of myocarditis that remains the main reason for mortalities associated with scorpion envenomation. The present review aims to elucidate clinical and paraclinical findings associated with scorpion-related myocarditis, and to explore different management strategies and subsequent outcomes.
METHODS
We searched PubMed, Web of Science, Scopus, and Google Scholar for articles related to keywords of myocarditis associated with scorpion envenomation up to May 1, 2022. Each article was carefully reviewed by two independent researchers. In case of disagreement for inclusion, we sought a third researcher opinion.
RESULTS
A total of 703 cases from 30 case reports and 34 case series were included in our review. Myocarditis associated with scorpion envenomation was usually reported in children presenting with cardiopulmonary symptoms including pulmonary edema (60.7%) and shock or hypotension (45.8%). The most common ECG findings are sinus tachycardia (82%) followed by ST-T changes (64.6%). The management typically included inotropes (especially dobutamine), prazosin, diuretics, nitroglycerine and digoxin, when indicated. Mechanical ventilation was required in 36.7% of the patients. Mortality in confirmed scorpion-related myocarditis cases is estimated at 7.3%. Almost all survived cases showed rapid recovery and improvement in the left ventricular function.
CONCLUSION
Even though myocarditis associated with scorpion envenomation is rare, it remains a serious and in some of cases a fatal consequence of scorpion sting. In case of relative presentations, particularly in envenomed children, diagnosis of myocarditis should be considered. Early screening using serial cardiac markers and echocardiography can guide the treatment. Prompt treatment that focuses on cardiogenic shock and pulmonary edema usually results in a favorable outcome.
Topics: Child; Humans; Animals; Scorpion Stings; Myocarditis; Pulmonary Edema; Dobutamine; Respiration, Artificial; Scorpions
PubMed: 37018229
DOI: 10.1371/journal.pntd.0011219