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Clinical Toxicology (Philadelphia, Pa.) Jan 2021Clinicians utilize lipid emulsion to treat local anesthetic toxicity and non-local anesthetic toxicities, a practice supported by animal experimentation and clinical... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Clinicians utilize lipid emulsion to treat local anesthetic toxicity and non-local anesthetic toxicities, a practice supported by animal experimentation and clinical experience. Prior meta-analysis confirmed a mortality benefit of lipid emulsion in animal models of local anesthetic toxicity but the benefit of lipid emulsion in models of non-local anesthetic toxicity remains unanswered. Further, swine suffer an anaphylactoid reaction from lipid emulsions calling into question their role as a model system to study lipid, so we examined swine and non-swine dependent outcomes in models of intravenous lipid emulsion.
METHODS
We conducted a systematic review and meta-analysis examining the use of lipid emulsion therapy in animal models of cardiac toxicity. We quantified mortality using a random-effects odds-ratio method. Secondary outcomes included survival in the following subgroups: local-anesthetic systemic toxicity, non-local anesthetic toxicity, swine-based models, and non-swine models (e.g., rat, rabbit and dog). We assessed for heterogeneity with Cochran's Q and I. We examined bias with Egger's test & funnel plot analysis.
RESULTS
Of 2784 references screened, 58 met criteria for inclusion. Treatment with lipid emulsion reduced chance of death in all models of toxicity with an odds ratio of death of 0.26 (95% CI 0.16-0.44, Z-5.21, < 0.00001, Cohen's- = 0.72, = 60). Secondary outcomes confirmed a reduced chance of death in models of local anesthetic toxicity (OR 0.16 {95% CI 0.1-0.33}) and non-local anesthetic toxicity (OR 0.43 {95% CI 0.22-0.83}). Heterogeneity (Cochran's Q 132 {df = 59, < 0.01}, = 0.55) arose primarily from animal-model and disappeared ( < = 0.12) when we analyzed swine and non-swine subgroups independently. Swine only benefited in models of local anesthetic toxicity (OR 0.28 {95% CI 0.11-0.7}, = 0.0033) whereas non-swine models experienced a homogeneous benefit across all toxins (OR 0.1 {95% CI 0.06-0.16}, < 0.00001). Egger's test identified risk of bias with outliers on funnel plot analysis.
DISCUSSION
Lipid emulsion therapy reduces mortality in animal models of toxicity. Heterogeneity arises from the animal-model used. Swine only benefit in models of local anesthetic toxicity, potentially due to lipid dose, experimental design or swine's anaphylactoid reaction to lipid. Outlier analysis reinforced the need for appropriate dosing of lipid emulsion along with airway management and chest compressions in the setting of cardiac arrest.
Topics: Administration, Intravenous; Anaphylaxis; Anesthetics, Local; Animals; Disease Models, Animal; Dogs; Fat Emulsions, Intravenous; Humans; Poisoning; Rabbits; Rats; Risk Assessment; Species Specificity; Sus scrofa
PubMed: 33025830
DOI: 10.1080/15563650.2020.1814316 -
Evidence-based Complementary and... 2018This meta-analysis sought to assess the efficacy and safety of oil emulsion injection (BJOEI) combined with chemotherapy for treating gastric cancer (GC). (Review)
Review
OBJECTIVE
This meta-analysis sought to assess the efficacy and safety of oil emulsion injection (BJOEI) combined with chemotherapy for treating gastric cancer (GC).
METHOD
Randomized controlled trials (RCTs) regarding BJOEI to treat GC were searched in PubMed, the Cochrane Library, Embase, the China National Knowledge Infrastructure Database (CNKI), the Wan-Fang Database, China Science and Technology Journal Database (VIP), and the Chinese Biomedical Literature Database (SinoMed) up to January 9, 2017. The clinical total effective rate, performance status, adverse drug reactions (ADRs), and other outcomes were analyzed with Review Manager 5.3 and Stata12.0 software.
RESULTS
13 RCTs involving 912 patients were included in the present meta-analysis. The results demonstrated that, compared with receiving chemotherapy alone, BJOEI combined with chemotherapy was more effective in improving clinical total effective rate (RR = 1.38, 95% CI: 1.22~1.56, < 0.00001), performance status (RR = 1.63, 95% CI: 1.30~2.04, < 0.00001), and relieving ADRs such as myelosuppression, neutropenia, thrombopenia, and liver damage. Statistically significant difference was observed between the experimental group and control group.
CONCLUSION
The pooled analysis showed that using BJOEI on the basis of the chemotherapy had a remarkable therapeutic effect for patients with GC, whereas more evidence-based medical researches were required to further support our study.
PubMed: 29853964
DOI: 10.1155/2018/6350782 -
Vaccine May 2017Cross-clade immunogenic stockpiled H5N1 vaccines may decrease the morbidity and transmission of infection during the initial phase of influenza pandemic. Meta-analysis... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cross-clade immunogenic stockpiled H5N1 vaccines may decrease the morbidity and transmission of infection during the initial phase of influenza pandemic. Meta-analysis of cross-reactive antibodies induced by oil-in-water emulsion adjuvanted (OWEA) influenza H5N1 virus monovalent vaccines with circulating heterologous H5N1 virus strains, isolated from human infections was performed.
METHODS
Literature search of MEDLINE, EMBASE, Web of Knowledge, The Cochrane Library, ClinicalTrials.gov, and International Standard Randomised Controlled Trial Number registry was conducted up through December 1, 2015. Methodologically qualified studies were included for (1) use of two doses of licensed OWEA (AS03 or MF59) egg-derived, inactivated influenza H5N1 virus monovalent vaccine, (2) participant age between 18 and 64years, and (3) evaluation of immunogenicity outcome for one or more subclade. Meta-analysis assessed the cross-reactivity of antibodies elicited by clade 1 adjuvanted vaccine strain against clade 2.1 virus strain (A/Vietnam/1194/2004 vs. A/Indonesia/05/2005); and separately against clade 2.2 virus strain (A/Vietnam/1194/2004 vs. A/turkey/Turkey/1/05); and clade 2.1 adjuvanted vaccine strain against clade 1 virus strain (A/Indonesia/05/2005 vs. A/Vietnam/1194/2004). Quantitative publication bias and influence analysis was conducted to evaluate potential impact of unpublished or new studies on the robustness of meta-analysis.
RESULTS
Of 960 articles, 53 qualified for quality assessment and 15 studies met the inclusion criteria. All assessed clade pairs elicited cross-reactive antibodies (clade 1 against clade 2.1 and 2.2; clade 2.1 against clade 1, 2.2, and 2.3). Heterologous strains of same sub-clade are likely to elicit higher cross-reactive antibodies.
CONCLUSIONS
OWEA influenza H5N1 virus monovalent vaccines exhibit broad cross-clade immunogenicity, a desired feature for vaccine stockpiling not yet demonstrated by unadjuvanted vaccines. In case of an impending H5N1 virus pandemic, stockpiled OWEA influenza H5N1 virus monovalent vaccines may allow population priming that could slow down the course of pandemic and could offer additional time needed for development of an effective strain specific vaccine supply.
Topics: Adjuvants, Immunologic; Adolescent; Adult; Antibodies, Viral; Cross Reactions; Emulsions; Female; Hemagglutination Inhibition Tests; Humans; Immunogenicity, Vaccine; Influenza A Virus, H5N1 Subtype; Influenza Vaccines; Influenza, Human; Male; Middle Aged; Oils; Pandemics; Water; Young Adult
PubMed: 28483200
DOI: 10.1016/j.vaccine.2017.04.029 -
The Cochrane Database of Systematic... Mar 2011Rosacea is a common chronic skin condition affecting the face, characterised by flushing, redness, pimples, pustules, and dilated blood vessels. The eyes are often... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Rosacea is a common chronic skin condition affecting the face, characterised by flushing, redness, pimples, pustules, and dilated blood vessels. The eyes are often involved and thickening of the skin with enlargement (phymas), especially of the nose, can occur in some patients. A range of treatment options are available but it is unclear which are the most effective.
OBJECTIVES
To assess the evidence for the efficacy and safety of treatments for rosacea.
SEARCH STRATEGY
In February 2011 we updated our searches of the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (Clinical Trials) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index, and Ongoing Trials Registers.
SELECTION CRITERIA
Randomised controlled trials in people with moderate to severe rosacea.
DATA COLLECTION AND ANALYSIS
Study selection, data extraction, assessment of risk of bias, and analyses were carried out by two independent review authors.
MAIN RESULTS
Fifty-eight trials, including 27 from the original review, comprising 6633 participants were included in this updated review. Interventions included topical metronidazole, oral antibiotics, topical azelaic cream or gel, topical benzoyl peroxide and/or combined with topical antibiotics, sulphacetamide/sulphur, and others. Only two studies assessed our primary outcome 'quality of life'.Pooled data from physician assessments in three trials provided some evidence that metronidazole was more effective compared to placebo (RR 1.95, 95% CI 1.48 to 2.56). Three trials provided data, based on participants' assessments, illustrating azelaic acid was more effective than placebo (RR 1.52, 95% CI 1.32 to 1.76).Physician-based assessments in two trials indicated that doxycycline appeared to be significantly more effective than placebo (RR 1.59, 95% CI 1.02 to 2.47 and RR 2.37, 95% CI 1.12 to 4.99). There was no statistically significant difference in effectiveness between 100 mg and 40 mg doses of doxycycline, but there was evidence of less adverse effects with the lower dose (RR 0.25, 95% CI 0.11 to 0.54).One study reported that cyclosporine ophthalmic emulsion was significantly more effective than artificial tears for treating ocular rosacea (for all outcomes).
AUTHORS' CONCLUSIONS
Although the majority of included studies were assessed as being at high or unclear risk of bias there was some evidence to support the effectiveness of topical metronidazole, azelaic acid, and doxycycline (40 mg) in the treatment of moderate to severe rosacea, and cyclosporine 0.5% ophthalmic emulsion for ocular rosacea. Further well-designed, adequately-powered randomised controlled trials are required.
Topics: Anti-Infective Agents; Cyclosporine; Dermatologic Agents; Dicarboxylic Acids; Doxycycline; Humans; Metronidazole; Ophthalmic Solutions; Randomized Controlled Trials as Topic; Rosacea
PubMed: 21412882
DOI: 10.1002/14651858.CD003262.pub4 -
Current Opinion in Anaesthesiology Oct 2017Enthusiasm for regional anesthesia has been driven by multimodal benefits to patient outcomes. Despite widespread awareness and improved techniques (including the... (Review)
Review
PURPOSE OF REVIEW
Enthusiasm for regional anesthesia has been driven by multimodal benefits to patient outcomes. Despite widespread awareness and improved techniques (including the increasing use of ultrasound guidance for block placement), intravascular sequestration and the attendant risk of local anesthetic systemic toxicity (LAST) remains. Intravenous lipid emulsion (ILE) for the treatment of LAST has been endorsed by anesthetic regulatory societies on the basis of animal study and human case report data. The accumulated mass of reporting now permits objective interrogation of published literature.
RECENT FINDINGS
Although incompletely elucidated the mechanism of action for ILE in LAST seemingly involves beneficial effects on initial drug distribution (i.e., pharmacokinetic effects) and positive cardiotonic and vasoactive effects (i.e., pharmacokinetic effects) acting in concert. Recent systematic review by collaborating international toxicologic societies have provided reserved endorsement for ILE in bupivacaine-induced toxicity, weak support for ILE use in toxicity from other local anesthetics, and largely neutral recommendation for all other drug poisonings. Work since publication of these recommendations has concluded that there is a positive effect on survival for ILE when animal models of LAST are meta-analyzed and evidence of a positive pharmacokinetic effect for lipid in human models of LAST.
SUMMARY
Lipid emulsion remains first-line therapy (in conjunction with standard resuscitative measures) in LAST. Increasing conjecture as to the clinical efficacy of ILE in LAST, however, calls for high-quality human data to refine clinical recommendations.
Topics: Anesthesia, Conduction; Anesthetics, Local; Fat Emulsions, Intravenous; Humans
PubMed: 28692439
DOI: 10.1097/ACO.0000000000000498 -
Mycoses Mar 2017Invasive fungal infections, an important cause of mortality, are primarily treated using amphotericin B, which is available in different formulations, both conventional... (Meta-Analysis)
Meta-Analysis Review
Invasive fungal infections, an important cause of mortality, are primarily treated using amphotericin B, which is available in different formulations, both conventional and lipid-based (liposomal, lipid complex, colloidal dispersion and Intralipid infusion). The aim of our study was to determine the efficacy and safety of conventional amphotericin B vs its lipid-based formulations. A systematic review followed by pairwise meta-analysis was performed, including randomised controlled trials (RCTs) that evaluated the use of lipid-based amphotericin B in patients with any degree of immunosuppression and susceptibility to invasive fungal infection. An electronic search was conducted using PubMed, Scopus, Web of Science and Scielo databases. Extracted outcomes were related to efficacy (cure) and safety (incidence of adverse events). Results were evaluated and meta-analyses were performed. Twenty-three RCTs were identified (n=2677 participants) for meta-analysis. No significant differences between conventional amphotericin B and any of the five formulations evaluated were observed, with regard to the efficacy analysis. With respect to the adverse events of nephrotoxicity, fever, chills and vomiting, all lipid formulations presented better profiles than the conventional formulation. The present systematic review and meta-analysis showed that conventional amphotericin B presents the same efficacy profile as lipid-based formulations, although the latter were associated with a safer profile.
Topics: Amphotericin B; Antifungal Agents; Clinical Trials as Topic; Colloids; Drug Compounding; Emulsions; Fever; Humans; Invasive Fungal Infections; Lipids; Phospholipids; Soybean Oil
PubMed: 27878878
DOI: 10.1111/myc.12585 -
Journal Der Deutschen Dermatologischen... Feb 2024Rosacea is a common chronic skin disease distributed primarily around the central face. Ocular manifestations of rosacea are poorly studied, and estimates of prevalence... (Review)
Review
Rosacea is a common chronic skin disease distributed primarily around the central face. Ocular manifestations of rosacea are poorly studied, and estimates of prevalence vary widely, ranging from 6% to 72% in the rosacea population. Treatment options for ocular rosacea include lid hygiene, topical and oral antibiotics, cyclosporine ophthalmic emulsion, oral vitamin A derivatives, and intense pulsed light; however, a direct comparison of treatment methods for ocular rosacea is lacking. This review aims to compare treatment efficacy and adverse events for different treatment modalities in ocular rosacea. We performed a systematic review by searching Cochrane, MEDLINE and Embase. Title, abstract, full text screening, and data extraction were done in duplicate. Sixty-six articles met the inclusion criteria, representing a total of 1,275 patients. The most effective treatment modalities were topical antimicrobials and oral antibiotics, which achieved complete or partial response in 91% (n = 82/90) and 89% (n = 525/580) of patients respectively, followed by intense pulsed light (89%, n = 97/109 partial response), cyclosporine ophthalmic emulsion (87% n = 40/46), and lid hygiene (65%, n = 67/105). Combination treatments achieved a complete or partial response in 90% (n = 69/77). Results suggest that topical antimicrobials, oral antibiotics, intense pulsed light. and cyclosporine were the most efficacious single modality treatments.
Topics: Humans; Emulsions; Rosacea; Anti-Bacterial Agents; Cyclosporine; Skin Diseases
PubMed: 38243868
DOI: 10.1111/ddg.15290 -
Academic Emergency Medicine : Official... Sep 2009The objective was to asses the efficacy of lipid emulsion as antidotal therapy outside the accepted setting of local anesthetic toxicity. (Review)
Review
OBJECTIVES
The objective was to asses the efficacy of lipid emulsion as antidotal therapy outside the accepted setting of local anesthetic toxicity.
METHODS
Literature was accessed through PubMed, OVID (1966-February 2009), and EMBASE (1947-February 2009) using the search terms "intravenous" AND ["fat emulsion" OR "lipid emulsion" OR "Intralipid"] AND ["toxicity" OR "resuscitation" OR "rescue" OR "arrest" OR "antidote"]. Additional author and conference publication searches were undertaken. Publications describing the use of lipid emulsion as antidotal treatment in animals or humans were included.
RESULTS
Fourteen animal studies, one human study, and four case reports were identified. In animal models, intravenous lipid emulsion (ILE) has resulted in amelioration of toxicity associated with cyclic antidepressants, verapamil, propranolol, and thiopentone. Administration in human cases has resulted in successful resuscitation from combined bupropion/lamotrigine-induced cardiac arrest, reversal of sertraline/quetiapine-induced coma, and amelioration of verapamil- and beta blocker-induced shock.
CONCLUSIONS
Management of overdose with highly lipophilic cardiotoxic medications should proceed in accord with established antidotal guidelines and early poisons center consultation. Data from animal experiments and human cases are limited, but suggestive that ILE may be helpful in potentially lethal cardiotoxicity or developed cardiac arrest attributable to such agents. Use of lipid emulsion as antidote remains a nascent field warranting further preclinical study and systematic reporting of human cases of use.
Topics: Adrenergic beta-Antagonists; Animals; Antidepressive Agents; Antidotes; Cardiotoxins; Drug Overdose; Fat Emulsions, Intravenous; Heart Arrest; Humans
PubMed: 19845549
DOI: 10.1111/j.1553-2712.2009.00499.x -
Nature Communications Jan 2020Standard inactivated influenza vaccines are poorly immunogenic in immunologically naive healthy young children, who are particularly vulnerable to complications from... (Meta-Analysis)
Meta-Analysis
Standard inactivated influenza vaccines are poorly immunogenic in immunologically naive healthy young children, who are particularly vulnerable to complications from influenza. For them, there is an unmet need for better influenza vaccines. Oil-in-water emulsion-adjuvanted influenza vaccines are promising candidates, but clinical trials yielded inconsistent results. Here, we meta-analyze randomized controlled trials with efficacy data (3 trials, n = 15,310) and immunogenicity data (17 trials, n = 9062). Compared with non-adjuvanted counterparts, adjuvanted influenza vaccines provide a significantly better protection (weighted estimate for risk ratio of RT-PCR-confirmed influenza: 0.26) and are significantly more immunogenic (weighted estimates for seroprotection rate ratio: 4.6 to 7.9) in healthy immunologically naive young children. Nevertheless, in immunologically non-naive children, adjuvanted and non-adjuvanted vaccines provide similar protection and are similarly immunogenic. These results indicate that oil-in-water emulsion adjuvant improves the efficacy of inactivated influenza vaccines in healthy young children at the first-time seasonal influenza vaccination.
Topics: Adjuvants, Immunologic; Antibodies, Viral; Antibody Formation; Child; Databases, Factual; Emulsions; Humans; Immunity; Influenza Vaccines; Influenza, Human; Oils; Orthomyxoviridae; Vaccination; Water
PubMed: 31949137
DOI: 10.1038/s41467-019-14230-x -
Clinical Toxicology (Philadelphia, Pa.) Mar 2016The use of intravenous lipid emulsion (ILE) therapy for the treatment of lipophilic drug toxicity is increasing. Despite this, the evidence for its effect in non-local... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The use of intravenous lipid emulsion (ILE) therapy for the treatment of lipophilic drug toxicity is increasing. Despite this, the evidence for its effect in non-local anesthetic toxicity remains sparse. Furthermore, many case reports describe ILE use for substances in which no clear efficacy data exists. The American Academy of Clinical Toxicology established a lipid emulsion workgroup. The aim of this group is to review the available evidence regarding the effect of ILE in non-LA drug poisoning and develop consensus-based recommendations on the use of this therapy.
METHODS
A systematic review of the literature was performed to capture articles through 15 December 2014. Relevant articles were determined based upon a predefined methodology. Articles involving pre-treatment experiments, pharmacokinetic studies not involving toxicity, and studies not addressing antidotal use of ILE met pre-defined exclusion criteria. Agreement of at least two members of the subgroup was required before an article could be excluded.
RESULTS
The final analysis included 203 articles: 141 for humans and 62 for animals. These include 40 animal experiments and 22 case reports involving animal toxicity. There were three human randomized control trials (RCT): one RCT examined ILE in TCA overdose, one RCT examined ILE in various overdoses, and one study examined ILE in reversal of sedation after therapeutic administration of inhaled anesthesia. One observational study examined ILE in glyphosate overdose. In addition, 137 human case reports or case series were identified. Intravenous lipid emulsion therapy was used in the management of overdose with 65 unique substances.
CONCLUSIONS
Despite the use of ILE for multiple substances in the treatment of patients with poisoning and overdose, the effect of ILE in various non-local anesthetic poisonings is heterogenous, and the quality of evidence remains low to very low.
Topics: Anesthetics; Anesthetics, Inhalation; Antidotes; Drug Overdose; Fat Emulsions, Intravenous; Humans; Male; Randomized Controlled Trials as Topic
PubMed: 26852931
DOI: 10.3109/15563650.2015.1126286