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Medicina (Kaunas, Lithuania) Jun 2021: Over the past twenty years a large number of new psychoactive substances (NPS) have entered and modified the recreational drug scene. Their intake has been associated... (Review)
Review
: Over the past twenty years a large number of new psychoactive substances (NPS) have entered and modified the recreational drug scene. Their intake has been associated with health-related risks, especially so for vulnerable populations such as people with severe mental illness, who might be at higher risk of suicidality or self-injurious behavior. This paper aims at providing an overview of NPS abuse and the effects on mental health and suicidality issues, by performing a literature review of the current related knowledge, thereby identifying those substances that, more than others, are linked to suicidal behaviors. : A comprehensive and updated overview of the literature regarding suicidality and NPS categories has been undertaken. An electronic search was performed, including all papers published up to March 2021, using the following keywords "NPS" OR "new psychoactive substances" OR "novel psychoactive substances" OR "synthetic cannabinoids" OR "phenethylamines" OR "synthetic cathinones" OR "tryptamines" OR "piperazines" OR "new synthetic opioids" OR "designer benzodiazepines" AND ("suicide" OR "suicidality") NOT review NOT animal on the PubMed, Cochrane Library, and Web of Science online databases. : Suicidality and self-injurious behavior appear to be frequently associated with some NPS such as cathinones, synthetic cannabinoids, and new synthetic opioids. The results are organized according to the substances recorded. : The growing use of NPS has become a significant clinical issue, causing increasing concern and challenges for clinicians working in both mental health and emergency departments. Thus, considering the associations between NPS and suicidality or self-injurious behaviors, areas where suicide-prevention efforts and strategies might be focused are the early detection, monitoring, and restriction of NPS.
Topics: Analgesics, Opioid; Humans; Illicit Drugs; Mental Disorders; Psychotropic Drugs; Substance-Related Disorders; Suicide
PubMed: 34204131
DOI: 10.3390/medicina57060580 -
The Korean Journal of Internal Medicine Jan 2024There may be many predictors of anticoagulation-related gastrointestinal bleeding (GIB), but until now, systematic reviews and assessments of the certainty of the... (Meta-Analysis)
Meta-Analysis
BACKGROUND/AIMS
There may be many predictors of anticoagulation-related gastrointestinal bleeding (GIB), but until now, systematic reviews and assessments of the certainty of the evidence have not been published. We conducted a systematic review to identify all risk factors for anticoagulant-associated GIB to inform risk prediction in the management of anticoagulation- related GIB.
METHODS
A systematic review and meta-analysis were conducted to search PubMed, EMBASE, Web of Science, and Cochrane Library databases (from inception through January 21, 2022) using the following search terms: anticoagulants, heparin, warfarin, dabigatran, rivaroxaban, apixaban, DOACs, gastrointestinal hemorrhage, risk factors. According to inclusion and exclusion criteria, studies of risk factors for anticoagulation-related GIB were identified. Risk factors for anticoagulant-associated GIB were used as the outcome index of this review.
RESULTS
We included 34 studies in our analysis. For anticoagulant-associated GIB, moderate-certainty evidence showed a probable association with older age, kidney disease, concomitant use of aspirin, concomitant use of the antiplatelet agent, heart failure, myocardial infarction, hematochezia, renal failure, coronary artery disease, helicobacter pylori infection, social risk factors, alcohol use, smoking, anemia, history of sleep apnea, chronic obstructive pulmonary disease, international normalized ratio (INR), obesity et al. Some of these factors are not included in current GIB risk prediction models. such as anemia, co-administration of gemfibrozil, co-administration of verapamil or diltiazem, INR, heart failure, myocardial infarction, etc.
CONCLUSION
The study found that anemia, co-administration of gemfibrozil, co-administration of verapamil or diltiazem, INR, heart failure, myocardial infarction et al. were associated with anticoagulation-related GIB, and these factors were not in the existing prediction models. This study informs risk prediction for anticoagulant-associated GIB, it also informs guidelines for GIB prevention and future research.
Topics: Humans; Anemia; Anticoagulants; Diltiazem; Gastrointestinal Hemorrhage; Gemfibrozil; Heart Failure; Helicobacter Infections; Helicobacter pylori; Myocardial Infarction; Risk Factors; Verapamil
PubMed: 38062723
DOI: 10.3904/kjim.2023.098 -
Drugs in R&D Sep 2023At present, the therapies of dilated cardiomyopathy concentrated on the symptoms of heart failure and related complications. The study is to evaluate the clinical... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
At present, the therapies of dilated cardiomyopathy concentrated on the symptoms of heart failure and related complications. The study is to evaluate the clinical efficacy of a combination of various conventional and adjuvant drugs in treating dilated cardiomyopathy via network meta-analysis.
METHODS
The study was reported according to the PRISMA 2020 statement. From inception through 27 June 2022, the PubMed, Embase, Cochrane library, and Web of Science databases were searched for randomized controlled trials on medicines for treating dilated cardiomyopathy. The quality of the included studies was evaluated according to the Cochrane risk of bias assessment. R4.1.3 and Revman5.3 software were used for analysis.
RESULTS
There were 52 randomized controlled trials in this study, with a total of 25 medications and a sample size of 3048 cases. The network meta-analysis found that carvedilol, verapamil, and trimetazidine were the top three medicines for improving left ventricular ejection fraction (LVEF). Ivabradine, bucindolol, and verapamil were the top 3 drugs for improving left ventricular end-diastolic dimension (LVEDD). Ivabradine, L-thyroxine, and atorvastatin were the top 3 drugs for improving left ventricular end-systolic dimension (LVESD). Trimetazidine, pentoxifylline, and bucindolol were the top 3 drugs for improving the New York Heart Association classification (NYHA) cardiac function score. Ivabradine, carvedilol, and bucindolol were the top 3 drugs for reducing heart rate (HR).
CONCLUSION
A combination of different medications and conventional therapy may increase the clinical effectiveness of treating dilated cardiomyopathy. Beta-blockers, especially carvedilol, can improve ventricular remodeling, cardiac function, and clinical efficacy in patients with dilated cardiomyopathy (DCM). Hence, they can be used if patients tolerate them. If LVEF and HR do not meet the standard, ivabradine can also be used in combination with other treatments. However, since the quality and number of studies in our research were limited, large sample size, multi-center, and high-quality randomized controlled trials are required to corroborate our findings.
Topics: Humans; Cardiomyopathy, Dilated; Carvedilol; Ivabradine; Stroke Volume; Trimetazidine; Network Meta-Analysis; Ventricular Function, Left; Verapamil; Randomized Controlled Trials as Topic
PubMed: 37556093
DOI: 10.1007/s40268-023-00435-5 -
The Cochrane Database of Systematic... Sep 2022Fatigue is a common and disabling symptom in people with a primary brain tumour (PBT). The effectiveness of interventions for treating clinically significant levels of... (Review)
Review
BACKGROUND
Fatigue is a common and disabling symptom in people with a primary brain tumour (PBT). The effectiveness of interventions for treating clinically significant levels of fatigue in this population is unclear. This is an updated version of the original Cochrane Review published in Issue 4, 2016.
OBJECTIVES
To assess the effectiveness and safety of pharmacological and non-pharmacological interventions for adults with PBT and clinically significant (or high levels) of fatigue.
SEARCH METHODS
For this updated review, we searched CENTRAL, MEDLINE and Embase, and checked the reference lists of included studies in April 2022. We also searched relevant conference proceedings, and ClinicalTrials.gov for ongoing trials.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that investigated any pharmacological or non-pharmacological intervention in adults with PBT and fatigue, where fatigue was the primary outcome measure. We restricted inclusion specifically to studies that enrolled only participants with clinically significant levels of fatigue to improve the clinical utility of the findings.
DATA COLLECTION AND ANALYSIS
Two review authors (JD, DC) independently evaluated search results for the updated search. Two review authors (JD, SYK) extracted data from selected studies, and carried out a risk of bias assessment. We extracted data on fatigue, mood, cognition, quality of life and adverse events outcomes.
MAIN RESULTS
The original review identified one study and this update identified a further two for inclusion. One study investigated the use of modafinil, one study the use of armodafinil and one study the use of dexamfetamine. We identified three ongoing studies. In the original review, the single eligible trial compared modafinil to placebo for 37 participants with a high- or low-grade PBT. One new study compared two doses of armodafinil (150 mg and 250 mg) to placebo for 297 people with a high-grade glioma. The second new study compared dexamfetamine sulfate to placebo for 46 participants with a low- or high-grade PBT. The evidence was uncertain for both modafinil and dexamfetamine regarding fatigue outcome measures, compared to controls, at study endpoint. Two trials did not reach the planned recruitment target and therefore may not, in practice, have been adequately powered to detect a difference. These trials were at a low risk of bias across most areas. There was an unclear risk of bias related to the use of mean imputation for one study because the investigators did not analyse the impact of imputation on the results and information regarding baseline characteristics and randomisation were not clear. The certainty of the evidence measured using GRADE was very low across all three studies. There was one identified study awaiting classification once data are available, which investigated the feasibility of 'health coaching' for people with a PBT experiencing fatigue. There were three ongoing studies that may be eligible for an update of this review, all investigating a non-pharmacological intervention for fatigue in people with PBT.
AUTHORS' CONCLUSIONS
There is currently insufficient evidence to draw reliable and generalisable conclusions regarding potential effectiveness or harm of any pharmacological or non-pharmacological treatments for fatigue in people with PBT. More research is needed on how best to treat people with brain tumours with high fatigue.
Topics: Adult; Brain Neoplasms; Dextroamphetamine; Fatigue; Glioma; Humans; Modafinil
PubMed: 36094728
DOI: 10.1002/14651858.CD011376.pub3 -
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 -
Journal of Psychopharmacology (Oxford,... Oct 2022Small-scale clinical studies with psychedelic drugs have shown promising results for the treatment of several mental disorders. Before psychedelics become registered... (Review)
Review
INTRODUCTION
Small-scale clinical studies with psychedelic drugs have shown promising results for the treatment of several mental disorders. Before psychedelics become registered medicines, it is important to know the full range of adverse events (AEs) for making balanced treatment decisions.
OBJECTIVE
To systematically review the presence of AEs during and after administration of serotonergic psychedelics and 3,4-methyenedioxymethamphetamine (MDMA) in clinical studies.
METHODS
We systematically searched PubMed, PsycINFO, Embase, and ClinicalTrials.gov for clinical trials with psychedelics since 2000 describing the results of quantitative and qualitative studies.
RESULTS
We included 44 articles (34 quantitative + 10 qualitative), describing treatments with MDMA and serotonergic psychedelics (psilocybin, lysergic acid diethylamide, and ayahuasca) in 598 unique patients. In many studies, AEs were not systematically assessed. Despite this limitation, treatments seemed to be overall well tolerated. Nausea, headaches, and anxiety were commonly reported acute AEs across diagnoses and compounds. Late AEs included headaches (psilocybin, MDMA), fatigue, low mood, and anxiety (MDMA). One serious AE occurred during MDMA administration (increase in premature ventricular contractions requiring brief hospitalization); no other AEs required medical intervention. Qualitative studies suggested that psychologically challenging experiences may also be therapeutically beneficial. Except for ayahuasca, a large proportion of patients had prior experience with psychedelic drugs before entering studies.
CONCLUSIONS
AEs are poorly defined in the context of psychedelic treatments and are probably underreported in the literature due to study design (lack of systematic assessment of AEs) and sample selection. Acute challenging experiences may be therapeutically meaningful, but a better understanding of AEs in the context of psychedelic treatments requires systematic and detailed reporting.
Topics: Banisteriopsis; Hallucinogens; Headache; Humans; Lysergic Acid Diethylamide; N-Methyl-3,4-methylenedioxyamphetamine; Psilocybin
PubMed: 36017784
DOI: 10.1177/02698811221116926 -
Epilepsia Open Apr 2024Stiripentol, fenfluramine, and cannabidiol are licensed add-on therapies to treat seizures in Dravet Syndrome (DS). There are no direct or indirect comparisons assessing... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Stiripentol, fenfluramine, and cannabidiol are licensed add-on therapies to treat seizures in Dravet Syndrome (DS). There are no direct or indirect comparisons assessing their full licensed dose regimens, across different jurisdictions, as first-line add-on therapies in DS.
METHODS
We conducted a systematic review and frequentist network meta-analysis (NMA) of randomized controlled trial (RCT) data for licensed add-on DS therapies. We compared the proportions of patients experiencing: reductions from baseline in monthly convulsive seizure frequency (MCSF) of ≥50% (clinically meaningful), ≥75% (profound), and 100% (seizure-free); serious adverse events (SAEs); discontinuations due to AEs.
RESULTS
We identified relevant data from two placebo-controlled RCTs for each drug. Stiripentol 50 mg/kg/day and fenfluramine 0.7 mg/kg/day had similar efficacy in achieving ≥50% (clinically meaningful) and ≥75% (profound) reductions from baseline in MCSF (absolute risk difference [RD] for stiripentol versus fenfluramine 1% [95% confidence interval: -20% to 22%; p = 0.93] and 6% [-15% to 27%; p = 0.59], respectively), and both were statistically superior (p < 0.05) to licensed dose regimens of cannabidiol (10 or 20 mg/kg/day, with/irrespective of clobazam) for these outcomes. Stiripentol was statistically superior in achieving seizure-free intervals compared to fenfluramine (RD = 26% [CI: 8% to 44%; p < 0.01]) and licensed dose regimens of cannabidiol. There were no significant differences in the proportions of patients experiencing SAEs. The risk of discontinuations due to AEs was lower for stiripentol, although the stiripentol trials were shorter.
SIGNIFICANCE
This NMA of RCT data indicates stiripentol, as a first-line add-on therapy in DS, is at least as effective as fenfluramine and both are more effective than cannabidiol in reducing convulsive seizures. No significant difference in the incidence of SAEs between the three add-on agents was observed, but stiripentol may have a lower risk of discontinuations due to AEs. These results may inform clinical decision-making and the continued development of guidelines for the treatment of people with DS.
PLAIN LANGUAGE SUMMARY
This study compared three drugs (stiripentol, fenfluramine, and cannabidiol) used alongside other medications for managing seizures in a severe type of epilepsy called DS. The study found that stiripentol and fenfluramine were similarly effective in reducing seizures and both were more effective than cannabidiol. Stiripentol was the best drug for stopping seizures completely based on the available clinical trial data. All three drugs had similar rates of serious side effects, but stiripentol had a lower chance of being stopped due to side effects. This information can help guide treatment choices for people with DS.
Topics: Humans; Cannabidiol; Anticonvulsants; Fenfluramine; Network Meta-Analysis; Seizures; Epilepsies, Myoclonic; Randomized Controlled Trials as Topic; Dioxolanes
PubMed: 38427284
DOI: 10.1002/epi4.12923 -
Journal of Psychopharmacology (Oxford,... Jan 2024Classic psychedelics, including lysergic acid diethylamide (LSD), psilocybin, mescaline, N,N-dimethyltryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT),... (Review)
Review
Classic psychedelics, including lysergic acid diethylamide (LSD), psilocybin, mescaline, N,N-dimethyltryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), are potent psychoactive substances that have been studied for their physiological and psychological effects. However, our understanding of the potential interactions and outcomes when using these substances in combination with other drugs is limited. This systematic review aims to provide a comprehensive overview of the current research on drug-drug interactions between classic psychedelics and other drugs in humans. We conducted a thorough literature search using multiple databases, including PubMed, PsycINFO, Web of Science and other sources to supplement our search for relevant studies. A total of 7102 records were screened, and studies involving human data describing potential interactions (as well as the lack thereof) between classic psychedelics and other drugs were included. In total, we identified 52 studies from 36 reports published before September 2, 2023, encompassing 32 studies on LSD, 10 on psilocybin, 4 on mescaline, 3 on DMT, 2 on 5-MeO-DMT and 1 on ayahuasca. These studies provide insights into the interactions between classic psychedelics and a range of drugs, including antidepressants, antipsychotics, anxiolytics, mood stabilisers, recreational drugs and others. The findings revealed various effects when psychedelics were combined with other drugs, including both attenuated and potentiated effects, as well as instances where no changes were observed. Except for a few case reports, no serious adverse drug events were described in the included studies. An in-depth discussion of the results is presented, along with an exploration of the potential molecular pathways that underlie the observed effects.
Topics: Humans; Hallucinogens; Psilocybin; Mescaline; N,N-Dimethyltryptamine; Drug Interactions; Lysergic Acid Diethylamide
PubMed: 37982394
DOI: 10.1177/02698811231211219 -
Orphanet Journal of Rare Diseases Jan 2024The aetiology of gastroschisis is considered multifactorial. We conducted a systematic review and meta-analysis to assess whether the use of medications during... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The aetiology of gastroschisis is considered multifactorial. We conducted a systematic review and meta-analysis to assess whether the use of medications during pregnancy, is associated with the risk of gastroschisis in offspring.
METHODS
PubMed, EMBASE, and Scopus were searched from 1st January 1990 to 31st December 2020 to identify observational studies examining the association between medication use during pregnancy and the risk of gastroschisis. The Newcastle-Ottawa Scale was used for the quality assessment of the individual studies. We pooled adjusted measures using a random-effect model to estimate relative risk [RR] and the 95% confidence interval [CI]. I statistic for heterogeneity and publication bias was calculated.
RESULTS
Eighteen studies providing data on 751,954 pregnancies were included in the meta-analysis. Pooled RRs showed significant associations between aspirin (RR 1.66, 95% CI 1.16-2.38; I = 58.3%), oral contraceptives (RR 1.52, 95% CI 1.21-1.92; I = 22.0%), pseudoephedrine and phenylpropanolamine (RR 1.51, 95% CI 1.16-1.97; I = 33.2%), ibuprofen (RR 1.42, 95% CI 1.26-1.60; I = 0.0%), and gastroschisis. No association was observed between paracetamol and gastroschisis (RR 1.16, 95% CI 0.96-1.41; I = 39.4%).
CONCLUSIONS
These results suggest that the exposure in the first trimester of pregnancy to over the counter medications (OTC) such as aspirin, ibuprofen, pseudoephedrine and phenylpropanolamine as well as to oral contraceptives, was associated with an increased risk of gastroschisis. However, these associations are significant only in particular subgroups defined by geographic location, adjustment variables and type of control. Therefore, further research is needed to investigate them as potential risk factors for gastroschisis, to assess their safety in pregnancy and to develop treatment strategies to reduce the risk of gastroschisis in offspring. PROSPERO registration number: CRD42021287529.
Topics: Female; Humans; Pregnancy; Aspirin; Contraceptives, Oral; Gastroschisis; Ibuprofen; Phenylpropanolamine; Pseudoephedrine; Observational Studies as Topic
PubMed: 38287353
DOI: 10.1186/s13023-023-02992-z -
Seizure Feb 2021Dravet syndrome (DS) is an infantile-onset developmental and epileptic encephalopathy syndrome with limited treatment options. We aimed to evaluate the efficacy and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dravet syndrome (DS) is an infantile-onset developmental and epileptic encephalopathy syndrome with limited treatment options. We aimed to evaluate the efficacy and tolerability of fenfluramine in patients with Dravet syndrome using meta-analytical techniques.
METHODS
We searched for relevant randomized controlled trials and non-randomized studies involving children with Dravet syndrome on fenfluramine therapy in MEDLINE, CENTRAL, EMBASE, Google Scholar and Web of Science database (31 July 2020). The primary outcome for the efficacy of fenfluramine was reduction in monthly convulsive seizure frequency. We carried out a random effect meta-analysis focusing on efficacy and safety variables. Only Randomized Controlled Trials (RCT) were included in the meta-analysis. The risk of bias was assessed for each study, and GRADE was used to assess the quality of evidence for each outcome.
RESULTS
Of 61 publications initially screened, 12 were reviewed as full-text. Seven articles including 2 RCTs, 4 uncontrolled studies (3 prospective and one retrospective study), and one case report described responses to fenfluramine in 144 DS patients (54 % male, mean age of 8.8 years, median dose of 0.4 mg/kg/day). Fenfluramine was found to be more efficacious than placebo, in terms of mean convulsive and total seizure frequency reduction (mean difference: -45.3 % (95 % CI: -48.1 %, -42.4 %, p < 0.00001) and -39.7 % (-46.7 %, -32.7 %, p < 0.00001)). A greater proportion of patients in the fenfluramine arm achieved >25 %, >50 %, >75 % and 100 % seizure reductions (odds ratios: 6.5 (3.7, 11.5, p < 0.00001), 10.6 (5.3, 21.3, p < 0.00001), 22.7(6.9, 75.3, p < 0.00001) and 9.3(1.7, 51.4, p = 0.01) respectively). The incidence of serious adverse events was not greater in the fenfluramine groups (OR: 1.02 (0.5, 2.19, p = 0.96)).
CONCLUSION
Fenfluramine appears to be a safe and efficacious antiseizure medication in patients with Dravet syndrome.
Topics: Child; Epilepsies, Myoclonic; Female; Fenfluramine; Humans; Infant; Male; Seizures; Spasms, Infantile; Treatment Outcome
PubMed: 33461030
DOI: 10.1016/j.seizure.2020.12.016