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Vaccine Feb 2016New adjuvants such as the AS- or the MF59-adjuvants improve vaccine efficacy and facilitate dose-sparing. Their use in influenza and malaria vaccines has resulted in a... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
New adjuvants such as the AS- or the MF59-adjuvants improve vaccine efficacy and facilitate dose-sparing. Their use in influenza and malaria vaccines has resulted in a large body of evidence on their clinical safety in children.
METHODS
We carried out a systematic search for safety data from published clinical trials on newly adjuvanted vaccines in children ≤10 years of age. Serious adverse events (SAEs), solicited AEs, unsolicited AEs and AEs of special interest were evaluated for four new adjuvants: the immuno-stimulants containing adjuvant systems AS01 and AS02, and the squalene containing oil-in-water emulsions AS03 and MF59. Relative risks (RR) were calculated, comparing children receiving newly adjuvanted vaccines to children receiving other vaccines with a variety of antigens, both adjuvanted and unadjuvanted.
RESULTS
Twenty-nine trials were included in the meta-analysis, encompassing 25,056 children who received at least one dose of the newly adjuvanted vaccines. SAEs did not occur more frequently in adjuvanted groups (RR 0.85, 95%CI 0.75-0.96). Our meta-analyses showed higher reactogenicity following administration of newly adjuvanted vaccines, however, no consistent pattern of solicited AEs was observed across adjuvant systems. Pain was the most prevalent AE, but often mild and of short duration. No increased risks were found for unsolicited AEs, febrile convulsions, potential immune mediated diseases and new onset of chronic diseases.
CONCLUSIONS
Our meta-analysis did not show any safety concerns in clinical trials of the newly adjuvanted vaccines in children ≤10 years of age. An unexplained increase of meningitis in one Phase III AS01-adjuvanted malaria trial and the link between narcolepsy and the AS03-adjuvanted pandemic vaccine illustrate that continued safety monitoring is warranted.
Topics: Adjuvants, Immunologic; Adolescent; Child; Child, Preschool; Clinical Trials as Topic; Drug Combinations; Humans; Infant; Likelihood Functions; Lipid A; Polysorbates; Risk; Saponins; Squalene; Vaccines; alpha-Tocopherol
PubMed: 26740250
DOI: 10.1016/j.vaccine.2015.12.024 -
Clinical Toxicology (Philadelphia, Pa.) Jun 2016Cocaine abuse is a major worldwide health problem. Patients with acute cocaine toxicity presenting to the emergency department may require urgent treatment for... (Review)
Review
INTRODUCTION
Cocaine abuse is a major worldwide health problem. Patients with acute cocaine toxicity presenting to the emergency department may require urgent treatment for tachycardia, dysrhythmia, hypertension, and coronary vasospasm, leading to pathological sequelae such as acute coronary syndrome, stroke, and death.
OBJECTIVE
The objective of this study is to review the current evidence for pharmacological treatment of cardiovascular toxicity resulting from cocaine abuse.
METHODS
MEDLINE, PsycINFO, Database of Abstracts of Reviews of Effects (DARE), OpenGrey, Google Scholar, and the Cochrane Library were searched from inception to November 2015. Articles on pharmacological treatment involving human subjects and cocaine were selected and reviewed. Evidence was graded using Oxford Centre for Evidence-Based Medicine guidelines. Treatment recommendations were compared to current American College of Cardiology/American Heart Association guidelines. Special attention was given to adverse drug events or treatment failure. The search resulted in 2376 articles with 120 eligible involving 2358 human subjects. Benzodiazepines and other GABA-active agents: There were five high-quality (CEBM Level I/II) studies, three retrospective (Level III), and 25 case series/reports (Level IV/V) supporting the use of benzodiazepines and other GABA-active agents in 234 subjects with eight treatment failures. Benzodiazepines may not always effectively mitigate tachycardia, hypertension, and vasospasm from cocaine toxicity. Calcium channel blockers: There were seven Level I/II, one Level III, and seven Level IV/V studies involving 107 subjects and one treatment failure. Calcium channel blockers may decrease hypertension and coronary vasospasm, but not necessarily tachycardia. Nitric oxide-mediated vasodilators: There were six Level I/II, one Level III, and 25 Level IV/V studies conducted in 246 subjects with 11 treatment failures and two adverse drug events. Nitroglycerin may lead to severe hypotension and reflex tachycardia. Alpha-adrenoceptor blocking drugs: There were two Level I studies and three case reports. Alpha-1 blockers may improve hypertension and vasospasm, but not tachycardia, although evidence is limited. Alpha-2-adrenoceptor agonists: There were two high-quality studies and one case report detailing the successful use of dexmedetomidine. Beta-blockers and β/α-blockers: There were nine Level I/II, seven Level III, and 34 Level IV/V studies of β-blockers, with 1744 subjects, seven adverse drug events, and three treatment failures. No adverse events were reported for use of combined β/α-blockers such as labetalol and carvedilol, which were effective in attenuating both hypertension and tachycardia. Antipsychotics: Seven Level I/II studies, three Level III studies, and seven Level IV/V case series and reports involving 168 subjects have been published. Antipsychotics may improve agitation and psychosis, but with inconsistent reduction in tachycardia and hypertension and risk of extrapyramidal adverse effects. Other agents: There was only one high level study of morphine, which reversed cocaine-induced coronary vasoconstriction but increased heart rate. Other agents reviewed included lidocaine, sodium bicarbonate, amiodarone, procainamide, propofol, intravenous lipid emulsion, propofol, and ketamine.
CONCLUSIONS
High-quality evidence for pharmacological treatment of cocaine cardiovascular toxicity is limited but can guide acute management of associated tachycardia, dysrhythmia, hypertension, and coronary vasospasm. Future randomized prospective trials are needed to evaluate new agents and further define optimal treatment of cocaine-toxic patients.
Topics: Benzodiazepines; Calcium Channel Blockers; Cardiovascular System; Cocaine; Cocaine-Related Disorders; Evidence-Based Medicine; Heart Rate; Humans; Hypertension; Nitric Oxide; Randomized Controlled Trials as Topic; Tachycardia; Vasodilator Agents
PubMed: 26919414
DOI: 10.3109/15563650.2016.1142090 -
Clinical Toxicology (Philadelphia, Pa.) Dec 2017Intraosseous (IO) access is an established route of administration in resuscitation situations. Patients with serious poisoning presenting to the emergency department... (Review)
Review
CONTEXT
Intraosseous (IO) access is an established route of administration in resuscitation situations. Patients with serious poisoning presenting to the emergency department may require urgent antidote therapy. However, intravenous (IV) access is not always readily available.
OBJECTIVE
This study reviews the current evidence for IO administration of antidotes that could be used in poisoning. The primary outcome was mortality as a surrogate of efficacy. Secondary outcomes included hemodynamic variables, electrocardiographic variables, neurological status, pharmacokinetics outcomes, and adverse effects as defined by each article.
METHODS
A medical librarian created a systematic search strategy for Medline, subsequently translated to Embase, BIOSIS, PubMed, Web of Science, Cochrane, Database of Abstracts of Reviews of Effects (DARE), and the CENTRAL clinical trial register, all of which we searched from inception to 30 June 2016. Interventions included IO administration of selected antidotes. Articles included volunteer studies, poisoning, or other resuscitation contexts such as cardiac arrest, burns, dehydration, seizure, hemorrhagic shock, or undifferentiated shock. We considered all human studies and animal experiments to the exception of in vitro studies. Two reviewers independently selected studies, and a third adjudicated in case of disagreement. Three reviewers extracted all relevant data. Three reviewers evaluated the risk of bias and quality of the articles using specific scales according to each type of study design.
RESULTS
A total of 47 publications (46 articles and one abstract) met our inclusion criteria and described IO administration of 13 different antidotes. These included one case series and 21 case reports describing 26 patients, and 25 animal experiments. Of those, seven human case reports and four animal experiments specifically reported the use of antidotes in poisoning. Human case reports suggested favorable outcomes with IO use of atropine, diazepam, hydroxocobalamin, insulin, lipid emulsion, methylene blue, phentolamine, prothrombin complex concentrate, and sodium bicarbonate. Clinical outcomes varied according to the antidote used. The only reported adverse event was ventricular tachycardia following IO naloxone. Regarding the animal experiments, IO administration of lipid emulsion and of hydroxocobalamin showed improved survival in bupivacaine-poisoned rats and in cyanide-intoxicated swine, respectively. Animal data also suggested an equivalent bio-availability between IO and IV administration for atropine, calcium chloride, dextrose 50%, diazepam, methylene blue, pralidoxime, and sodium bicarbonate. Adverse effect reporting of fat emboli after IO administration of sodium bicarbonate, for example, was conflicting due to the significant heterogeneity in the timing of lung examination across studies.
CONCLUSION
The evidence supporting the use of IO route for the administration of antidotes in a context of poisoning is scarce. The majority of the evidence consists of case reports and animal experiments. Common antidotes such as acetylcysteine, fomepizole, and digoxin-specific antibody fragments have not been studied or reported with the use of the IO route. Despite the low-quality evidence available, IO access is a potential option for antidotal treatments in toxicological resuscitation when IV access is unavailable.
Topics: Animals; Antidotes; Humans; Infusions, Intraosseous; Poisoning; Resuscitation
PubMed: 28644688
DOI: 10.1080/15563650.2017.1337122 -
Journal of Alternative and... May 2019This meta-analysis aimed to assess the clinical effectiveness and safety of Javanica oil emulsion injection (JOEI) combined with the radiotherapy (RT) for treating... (Meta-Analysis)
Meta-Analysis
This meta-analysis aimed to assess the clinical effectiveness and safety of Javanica oil emulsion injection (JOEI) combined with the radiotherapy (RT) for treating esophageal cancer (EC). A literature search was conducted for collecting the randomized controlled trials (RCTs) on EC treated by JOEI in the Cochrane Library, PubMed, Embase, the Chinese Biomedical Literature Database (SinoMed), the China National Knowledge Infrastructure Database, the China Science and Technology Journal Database (VIP), and the Wanfang Database from inception to February 4, 2017. The quality of the RCTs was evaluated by the Cochrane risk of bias assessment tool, and objective remission rate, performance status, adverse drug reactions (ADRs), 1-year survival rate, and 2-year survival rate were analyzed by Review Manager 5.3 and Stata 13.0 software. A total of 11 RCTs with 909 participants were involved in this meta-analysis. The results showed that in comparison with RT alone, the JOEI combined with RT was associated with the better effects on improving objective remission rate (relative risk [RR] = 1.33, 95% confidence interval [CI 1.17-1.52], = 4.44, < 0.00001), performance status (RR = 1.52, 95% CI [1.25-1.85], = 4.24, < 0.00001), 1-year survival rate (RR = 1.37, 95% CI [1.17-1.60], = 3.86, < 0.0001), and 2-year survival rate (RR = 1.36, 95% CI [1.09-1.70], = 2.68, = 0.007). The differences between the two groups in objective remission rate, performance status, 1-year survival rate, and 2-year survival rate were statistically significant. Besides, the JOEI combined with RT could reduce the incidence of ADRs. Specifically, the statistically significant difference was detected between these two groups about leukopenia (RR = 0.39, 95% CI [0.25-0.61], = 4.19, < 0.0001), radiation esophagitis (RR = 0.68, 95% CI [0.50-0.93], = 2.42, = 0.02), thrombocytopenia (RR = 0.92, 95% CI [0.12-0.66], = 2.95, = 0.003), and hemoglobin reduction (RR = 0.53, 95% CI [0.35-0.79], = 3.14, = 0.002); however, there was no statistically significant difference for the outcome of nausea and vomiting (RR = 0.61, 95% CI [0.36-1.03], = 1.85, = 0.06) between two groups. This meta-analysis indicated that the combination of JOEI and RT was associated with the more beneficial treatment for patients with EC compared with only receiving RT. However, more well-designed and multicenter RCTs should be carried out to confirm this finding because of the limitations of enrolled 11 RCTs.
Topics: Adult; Aged; Aged, 80 and over; Chemoradiotherapy; Drugs, Chinese Herbal; Esophageal Neoplasms; Female; Humans; Male; Middle Aged
PubMed: 30785303
DOI: 10.1089/acm.2018.0096 -
Nutrition Research (New York, N.Y.) Aug 2021Clinical trials have reported that a four-oil intravenous lipid emulsion (SMOFlipid) play a positive role in immune function, but showed inconsistent outcomes compared... (Meta-Analysis)
Meta-Analysis
A four-oil intravenous lipid emulsion improves markers of liver function, triglyceride levels and shortens length of hospital stay in adults: a systematic review and meta-analysis.
Clinical trials have reported that a four-oil intravenous lipid emulsion (SMOFlipid) play a positive role in immune function, but showed inconsistent outcomes compared to other lipid emulsions. A systematic review and meta-analysis was conducted to evaluate the effect of SMOFlipid on liver function, triglycerides (TG), inflammatory markers, and clinical outcomes in hospitalized adults after short-term use compared to others. A search of the PubMed, Medline, Embase, China National Knowledge Infrastructure, and Wanfang databases was performed to identify the included randomized controlled trials. Trials with adults who were administrated a short-term course of SMOFlipid were included. A meta-analysis on liver function markers, TG, inflammatory markers, and clinical outcomes was conducted. A total of 18 randomized controlled trials with 1188 patients were included. Compared to other lipid emulsions, SMOFlipid was associated with a significant reduction in ALT, AST, γ-glutamyltransferase, total bilirubin, TG, C-reactive protein and length of hospital stay. No effect on serum interleukin-6 levels or adverse events were observed. For adult patients, our meta-analysis indicated that SMOFlipid may be beneficial to the liver and prone to prevent hyperlipidemia. The SMOFlipid also shortened length of hospital stay.
Topics: Adult; Fat Emulsions, Intravenous; Fatty Acids, Omega-3; Fish Oils; Humans; Hyperlipidemias; Inflammation; Length of Stay; Liver; Olive Oil; Parenteral Nutrition; Plant Oils; Soybean Oil; Triglycerides
PubMed: 34157593
DOI: 10.1016/j.nutres.2021.05.003 -
BMJ (Clinical Research Ed.) Mar 2011To systematically determine the most efficacious approach for preventing pain on injection of propofol. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To systematically determine the most efficacious approach for preventing pain on injection of propofol.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
PubMed, Embase, Cochrane Library, www.clinicaltrials.gov, and hand searching from the reference lists of identified papers.
STUDY SELECTION
Randomised controlled trials comparing drug and non-drug interventions with placebo or another intervention to alleviate pain on injection of propofol in adults.
RESULTS
Data were analysed from 177 randomised controlled trials totalling 25,260 adults. The overall risk of pain from propofol injection alone was about 60%. Using an antecubital vein instead of a hand vein was the most effective single intervention (relative risk 0.14, 95% confidence interval 0.07 to 0.30). Pretreatment using lidocaine (lignocaine) in conjunction with venous occlusion was similarly effective (0.29, 0.22 to 0.38). Other effective interventions were a lidocaine-propofol admixture (0.40, 0.33 to 0.48); pretreatment with lidocaine (0.47, 0.40 to 0.56), opioids (0.49, 0.41 to 0.59), ketamine (0.52, 0.46 to 0.57), or non-steroidal anti-inflammatory drugs (0.67, 0.49 to 0.91); and propofol emulsions containing medium and long chain triglycerides (0.75, 0.67 to 0.84). Statistical testing of indirect comparisons showed that use of the antecubital vein and pretreatment using lidocaine along with venous occlusion to be more efficacious than the other interventions.
CONCLUSIONS
The two most efficacious interventions to reduce pain on injection of propofol were use of the antecubital vein, or pretreatment using lidocaine in conjunction with venous occlusion when the hand vein was chosen. Under the assumption of independent efficacy a third practical alternative could be pretreatment of the hand vein with lidocaine or ketamine and use of a propofol emulsion containing medium and long chain triglycerides. Although not the most effective intervention on its own, a small dose of opioids before induction halved the risk of pain from the injection and thus can generally be recommended unless contraindicated.
Topics: Adult; Anesthetics, Intravenous; Bias; Humans; Hypnotics and Sedatives; Injections, Intravenous; Pain; Propofol; Randomized Controlled Trials as Topic
PubMed: 21406529
DOI: 10.1136/bmj.d1110 -
Human Vaccines & Immunotherapeutics 2016Montanide ISA™51 (ISA 51) is a vaccine adjuvant which has been tested in therapeutic and prophylactic vaccine trials. The aim of this review is to present a... (Review)
Review
Montanide ISA™51 (ISA 51) is a vaccine adjuvant which has been tested in therapeutic and prophylactic vaccine trials. The aim of this review is to present a comprehensive examination of the safety and tolerability of ISA 51 containing vaccines. A systematic literature search was conducted in PubMed, EMBASE and clinicaltrials.gov . Eligible studies were categorized into: (A) uncontrolled studies with non-healthy subjects, (B) controlled studies with non-healthy subjects, and (C) controlled studies with healthy subjects. Reported adverse events (AEs) were assessed. 91 studies were included in our review. Generally observed AEs included injection site reaction; injection site pain; myalgia; headache; gastro-intestinal disorders; fatigue and fever - regardless of the administration route and subject characteristic. Specific AEs, e.g. injection site reactions and rash, were more frequently reported from subjects receiving ISA 51-adjuvanted vaccines than from subjects receiving antigen or ISA 51 only. The reported AEs were mainly mild to moderate in intensity. Serious AEs (SAEs) were reported in 27% of the uncontrolled trials and 2 trials conducted with healthy subjects. Notably, 2 other trials conducted with healthy subjects were stopped due to unacceptable AEs. Some studies indicate that the mixing procedure of antigen and adjuvant might influence the occurrence of AEs. Reports on SAEs and premature termination of 2 trials advise caution when using ISA 51. Yet, AEs might be preventable by proper mixing of vaccine and adjuvant to a stable emulsion. Trials including an active control group are needed for a fair evaluation of adjuvant safety.
Topics: Adjuvants, Immunologic; Drug-Related Side Effects and Adverse Reactions; Fatigue; Fever; Gastrointestinal Diseases; Headache; Humans; Mannitol; Oleic Acids; Pain; Skin Diseases; Vaccines
PubMed: 26378866
DOI: 10.1080/21645515.2015.1071455 -
Recent Patents on Nanotechnology 2020Pharmaceutical nanotechnology represents an efficient alternative for the delivery of pharmacologically active plant-derived compounds, considering their protective...
BACKGROUND
Pharmaceutical nanotechnology represents an efficient alternative for the delivery of pharmacologically active plant-derived compounds, considering their protective capacity, oral bioavailability and drug vectorization capacity. In this context, butters obtained from plant seeds have emerged as promising products for the development of pharmacologically active nanostructures. They possess a complex lipid composition, allowing the formation of different emulsion systems with solid cores, since this mixture of different triglycerides is solid at room temperature and body temperature. Therefore, the systematic mapping around the technological development of nanostructures produced from plant-derived butters is potentially valuable for researchers interested in novel alternative formulations for pharmacological therapy, with potential industrial, economic, health and societal impacts.
METHODS
Systematic review was carried out by the search of scientific papers and patents deposited in official databases concerning the development of nanostructured pharmaceutical products using plantderived butters as starting material. The publications obtained were subjected to sorting and analysis by applying the following inclusion/exclusion criteria.
RESULTS
The Solid Lipid Nanoparticle (SLN) was the type of nanostructure produced in all the analyzed scientific papers, due to the physicochemical characteristics of the lipid constituents of plantderived butters. In this sense, 54% of the articles have reported the use of Cocoa Butter for the production of nanostructures; 28% for Shea Butter; 6% for Cupuacu Butter, 6% for Murumuru Butter and 6% for Bacuri Butter.
DISCUSSION
In the technological prospection, only two patents exhibited SLN as an invention based on cocoa butter and on shea butter, respectively. The production methods employed have included: phase inversion temperature, microemulsion, hot high pressure homogenization, high shear homogenization and ultrasonication.
CONCLUSION
In light of this prospective review, the encouragement of novel studies in lipids-based nanotechnology is evident, considering the small number of findings so far, in order to stimulate new research involving plant-derived butters from easily cultivated fruits in tropical regions, then stimulating the pharmaceutical development of new therapeutic alternatives using biocompatible and sustainable raw materials.
Topics: Butter; Drug Carriers; Emulsions; Lipids; Liposomes; Nanoparticles; Plants; Publications
PubMed: 32442090
DOI: 10.2174/1872210514666200522213144 -
Bioactive Materials Dec 2019Atopic dermatitis is a chronic, relapsing, non-contiguous, exudative eczema/dermatitis, which represents a complex, multi-factorial disorder, due to an impairment of the... (Review)
Review
Atopic dermatitis is a chronic, relapsing, non-contiguous, exudative eczema/dermatitis, which represents a complex, multi-factorial disorder, due to an impairment of the barrier. Currently available drugs have a low skin bioavailability and may give rise to severe adverse events. Nanotechnologies, including nano-particles, liposomes, nano-gels, nano-mixtures, nano-emulsions and other nano-carriers, offer unprecedented solutions to these issues, enabling: i) the management of different clinical forms of atopic dermatitis, especially the recalcitrant ones, i) a better bio-availability and trans-dermal drug targeted delivery at the inflammation site, ii) dose control, iii) significant improvements both in clinical symptoms and immune responses, iv) with less adverse events being reported and a better safety profile. However, some nano-sized structures could amplify and even worsen symptoms in particularly susceptible individuals. Furthermore, most studies included in the present systematic review have been conducted or , with few randomized controlled clinical trials (RCTs). Future investigations should adopt this design in order to enable scholars achieving robust findings and evidence. Therefore, given the above-mentioned shortcomings, further research in the field is urgently warranted.
PubMed: 31872162
DOI: 10.1016/j.bioactmat.2019.11.003 -
Clinical Toxicology (Philadelphia, Pa.) Aug 2017The Lipid Emulsion Therapy workgroup, organized by the American Academy of Clinical Toxicology, recently conducted a systematic review, which subjectively evaluated... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The Lipid Emulsion Therapy workgroup, organized by the American Academy of Clinical Toxicology, recently conducted a systematic review, which subjectively evaluated lipid emulsion as a treatment for local anesthetic toxicity. We re-extracted data and conducted a meta-analysis of survival in animal models.
METHODS
We extracted survival data from 26 publications and conducted a random-effect meta-analysis based on odds ratio weighted by inverse variance. We assessed the benefit of lipid emulsion as an independent variable in resuscitative models (16 studies). We measured Cochran's Q for heterogeneity and I to determine variance contributed by heterogeneity. Finally, we conducted a funnel plot analysis and Egger's test to assess for publication bias in studies.
RESULTS
Lipid emulsion reduced the odds of death in resuscitative models (OR =0.24; 95%CI: 0.1-0.56, p = .0012). Heterogeneity analysis indicated a homogenous distribution. Funnel plot analysis did not indicate publication bias in experimental models.
DISCUSSION
Meta-analysis of animal data supports the use of lipid emulsion (in combination with other resuscitative measures) for the treatment of local anesthetic toxicity, specifically from bupivacaine. Our conclusion differed from the original review. Analysis of outliers reinforced the need for good life support measures (securement of airway and chest compressions) along with prompt treatment with lipid.
Topics: Anesthetics, Local; Animals; Bupivacaine; Combined Modality Therapy; Disease Models, Animal; Dogs; Drug Compounding; Emulsions; Fat Emulsions, Intravenous; Odds Ratio; Poisoning; Rabbits; Rats; Resuscitation; Risk Assessment; Risk Factors; Swine; Time Factors
PubMed: 28346007
DOI: 10.1080/15563650.2017.1288911