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European Review For Medical and... Jun 2020Intravenous lipid emulsions (ILE) were developed many decades ago to supply nutritional requirements to patients unable to obtain adequate enteral nutrition. The utility...
OBJECTIVE
Intravenous lipid emulsions (ILE) were developed many decades ago to supply nutritional requirements to patients unable to obtain adequate enteral nutrition. The utility of ILE was extended to therapeutics, facilitating the delivery of drugs. More recently, the potential for ILE to act as an antidote for inversion of drug toxicity has been recognized. This review aims to summarize the literature on ILE therapy as an antidote. Suggested mechanisms of action, safety profile, and recommendations on the administration of ILE in cases of drug intoxication are highlighted.
MATERIALS AND METHODS
A complete literature survey was performed using the PubMed database search to collect available information regarding mechanisms of ILE action as an antidote, ILE administration for drug toxicity, and presentation of adverse events.
RESULTS
A total of 102 studies met the selection criteria for inclusion in the review. Mainly used for local anesthetics toxicity, ILE therapy has been expanded in clinical toxicology involving overdose treatment of drugs other than local anesthetics. Partitioning in a lipid phase of fat droplets is a mechanism named the lipid sink phenomenon that has primarily been described to explain this action of ILE and remains the most widely accepted. At the same time, recent research has also revealed several molecular mechanisms that may contribute to ILE efficacy.
CONCLUSIONS
ILE therapy comprises a recognized approach in clinical toxicology. Due to the lack of randomized clinical trials, recommendations on administration are based on animal studies and published cases. Thus, the constantly increased knowledge about ILE therapy supports the need for a detailed appraisal.
Topics: Anesthetics, Local; Animals; Antidotes; Drug-Related Side Effects and Adverse Reactions; Fat Emulsions, Intravenous; Humans
PubMed: 32633409
DOI: 10.26355/eurrev_202006_21708 -
Critical Reviews in Food Science and... Jun 2017Drug delivery systems, accompanied by nanoparticle technology, have recently emerged as prominent solutions to improve the pharmacokinetic properties, namely... (Review)
Review
Drug delivery systems, accompanied by nanoparticle technology, have recently emerged as prominent solutions to improve the pharmacokinetic properties, namely bioavailability, of therapeutic and nutraceutical agents. Solid lipid nanoparticles (SLNs) have received much attention from researchers due to their potential to protect or improve drug properties. SLNs have been reported to be an alternative system to traditional carriers, such as emulsions, liposomes, and polymeric nanoparticles. Phenolic compounds are widespread in plant-derived foodstuffs and therefore abundant in our diet. Over the last decades, phenolic compounds have received considerable attention due to several health promoting properties, mostly related to their antioxidant activity, which can have important implications for health. However, most of these compounds have been associated with poor bioavailability being poorly absorbed, rapidly metabolized and eliminated, which compromises its biological and pharmacological benefits. This paper provides a systematic review of the use of SLNs as oral delivery systems of phenolic compounds, in order to overcome pharmacokinetic limitations of these compounds and improved nutraceutical potential. In vitro studies, as well as works describing topical and oral treatments will be revisited and discussed. The classification, synthesis, and clinical application of these nanomaterials will be also considered in this review article.
Topics: Administration, Oral; Dietary Supplements; Drug Delivery Systems; Lipids; Nanoparticles; Phenols
PubMed: 26192708
DOI: 10.1080/10408398.2015.1031337 -
Systematic review of topical diclofenac for the treatment of acute and chronic musculoskeletal pain.Current Medical Research and Opinion Apr 2020The objective was to systematically review the efficacy and safety of topical diclofenac in both acute and chronic musculoskeletal pain in adults. We used standard...
The objective was to systematically review the efficacy and safety of topical diclofenac in both acute and chronic musculoskeletal pain in adults. We used standard Cochrane methods. Searches were conducted in MEDLINE, EMBASE and The Cochrane Register of Studies; date of the final search was November 2018. Included studies were randomized, double blinded, with ten or more participants per treatment arm. The primary outcome of "clinical success" was defined as participant-reported reduction in pain of at least 50%. Details of adverse events (AEs) were recorded. For acute pain, 23 studies (5170 participants) were included. Compared to placebo, number needed to treat (NNT) for different formulations were as follows: diclofenac plaster, 4.7 (95% CI 3.7-6.5); diclofenac plaster with heparin, 7.4 (95% CI 4.6-19); and diclofenac Emulgel, 1.8 (95% CI 1.5-2.1). 4.1% (78/1919) reported a local AE. For chronic pain, 21 studies (26 publications) with 5995 participants were included. Formulations included gel, solution with or without DMSO, emulsion and plaster. A clinical success rate of ∼60% (NNT 9.5 [95% CI 7-14.7]) was achieved with a variety of formulations. Local AEs (∼14%) were similar for both diclofenac and placebo. This systematic review of 11,000+ participants demonstrates that topical diclofenac is effective for acute pain, such as sprains, with minimal AEs. The effectiveness of topical diclofenac was also demonstrated in chronic musculoskeletal pain but with a higher NNT (worse) compared with acute pain. Formulation does play a part in effectiveness but needs further studies.
Topics: Acute Pain; Administration, Topical; Anti-Inflammatory Agents, Non-Steroidal; Chronic Pain; Diclofenac; Humans; Musculoskeletal Pain; Randomized Controlled Trials as Topic
PubMed: 31944135
DOI: 10.1080/03007995.2020.1716703 -
Emergency Medicine Australasia : EMA Apr 2011Intravenous lipid emulsion (ILE) has been demonstrated to be effective in amelioration of cardiovascular and central nervous system sequelae of local-anaesthetic and... (Review)
Review
Intravenous lipid emulsion (ILE) has been demonstrated to be effective in amelioration of cardiovascular and central nervous system sequelae of local-anaesthetic and non-local-anaesthetic drug toxicity in animal models. Sequestration of lipophilic toxins to an expanded plasma lipid phase is credited as the predominant beneficial mechanism of action of ILE. Systematic review of published human experience is however lacking. We determined to report a comprehensive literature search of all human reports of ILE application in drug poisoning. Forty-two cases of ILE use (19 local-anaesthetic, 23 non-local-anaesthetic) were identified, with anecdotal reports of successful resuscitation from cardiovascular collapse and central nervous system depression associated with ILE administration in lipophilic toxin overdose. Although significant heterogeneity was observed in both agents of intoxication, and reported outcomes; case report data suggest a possible benefit of ILE in potentially life-threatening cardio-toxicity from bupivacaine, mepivacaine, ropivacaine, haloperidol, tricyclic antidepressants, lipophilic beta blockers and calcium channel blockers. Further controlled study and systematic evaluation of human cases is required to define the clinical role of ILE in acute poisonings.
Topics: Anesthetics, Local; Antidotes; Drug Overdose; Fat Emulsions, Intravenous; Humans; Intraoperative Complications
PubMed: 21489160
DOI: 10.1111/j.1742-6723.2011.01398.x -
The Cochrane Database of Systematic... Aug 2016Various hormone therapies (HT) are available to treat menopausal vasomotor symptoms. Bioidentical hormones are chemically identical to those produced by the human body,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Various hormone therapies (HT) are available to treat menopausal vasomotor symptoms. Bioidentical hormones are chemically identical to those produced by the human body, and several types are well-tested and available on prescription. Many women have opted for bioidentical hormone therapy (BHT) on the assumption that it is safer than other forms of HT. We evaluated the evidence.
OBJECTIVES
To determine the effectiveness and safety of bioidentical hormones compared to placebo or non-bioidentical hormones for the relief of vasomotor symptoms.
SEARCH METHODS
In July 2015 we searched the Cochrane Central Register of Controlled Trials, PubMed, Embase, Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), registers of ongoing trials and the reference lists of articles retrieved.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing bioidentical hormone therapy (BHT) versus placebo or non-bioidentical hormones.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by the Cochrane Collaboration. Our primary outcome was vasomotor symptoms (hot flushes and night sweats). We evaluated the overall quality of the evidence using Grading of Recommendations Assessment, Development and Evaluation criteria (GRADE).
MAIN RESULTS
We included 23 RCTs (5779 participants). Most studies (20/23) included only women with moderate to severe hot flushes. All studies compared unopposed 17 beta-estradiol (beta-estradiol) versus placebo or conjugated equine estrogens (CEE). None of the studies reported night sweats as a separate outcome. BHT patch versus placebo Frequency of hot flushesFour RCTs reported data suitable for analysis. There were fewer hot flushes in the BHT group, with a moderate to large effect size (SMD -0.68, 95% CI -0.83 to -0.53, four RCTs, 793 women, I(2) = 67%, low quality evidence). There was moderate heterogeneity, but a consistent direction of effect. Seven RCTs reported data unsuitable for analysis; all reported a benefit in the intervention group. Symptom intensityTwo RCTs reported analysable data. Measured on a 0-100 visual analogue scale (VAS), hot flush intensity was lower in the BHT group (MD -19.94 points, 95% CI -24.86 to -15.02, two RCTs, 393 women, I(2) = 54%, low quality evidence). There was moderate heterogeneity, but a consistent direction of effect. Adverse effectsAdverse events (such as headache, vaginal bleeding, breast tenderness and skin reactions) were more common in the intervention group (odds ratio (OR) 2.14, 95% CI 1.29 to 3.54, 9 RCTs, 1822 women, I(2) = 73%, low quality evidence). There was moderate heterogeneity, but a consistent direction of effect. In one study, five women in the intervention group developed endometrial hyperplasia. BHT gel versus placebo Hot flush frequencyThree RCTs reported this outcome, but the data were unsuitable for analysis. All reported a benefit in the BHT group. Adverse effectsAdverse events were more common in the BHT group (OR 1.41, 95% CI 1.09 to 1.83, 3 RCTs, 1086 women, I(2) = 0%, moderate quality evidence). Oral BHT versus placebo Hot flush frequencyTwo studies reported analysable data. There were fewer hot flushes in the BHT group, with a moderate to large effect size (SMD -0.80, 95% CI -1.03 to -0.57, two RCTs, 356 women, I(2) = 14%, low quality evidence). Adverse effectsThere was no evidence of a difference between the groups (OR 1.28, 95% CI 0.84 to 1.96, 3 RCTs, 433 women, I(2) = 0%, low quality evidence). Topical BHT emulsion versus placebo Hot flush frequencyOne study with data unsuitable for analysis reported a benefit in the intervention group. Adverse effectsThere was no evidence of a difference between the groups (OR 1.46, 95% CI 0.80 to 2.66, one RCT, 200 women, low quality evidence). Intranasal BHT versus placebo Hot flush frequencyOnly one study reported analysable data. There were fewer hot flushes per day in the BHT group (MD -3.04 95% CI -4.05 to -2.03, one study, 458 women, moderate quality evidence) Adverse effectsAdverse events (such as headache, breast tenderness, arthralgia and nausea) were more common in the intervention group (OR 1.96, 95% CI 1.26 to 3.03, one RCT, 458 women, moderate quality evidence). Subgroup analysesSubgroup analyses by dose of BHT suggested that higher doses of BHT may be associated with more effectiveness but also higher risk of adverse effects. BHT patch versus 0.625 mg CEETwo RCTs reported this comparison, but the data were unsuitable for analysis. Hot flush frequencyBoth RCTs reported no evidence of a difference between the groups. Adverse effectsFindings were inconsistent. In one comparison (0.1 mg BHT versus CEE), breast pain and vaginal bleeding were more frequent in the BHT group. Oral BHT versus 0.625 mg CEE Hot flush frequencyOne study with data unsuitable for analysis reported no evidence of a difference between the groups. Adverse effectsThere was no evidence of a difference between the groups (OR 1.20, 95% CI 0.50 to 2.87, one RCT, 103 women, very low quality evidence).
AUTHORS' CONCLUSIONS
There was low to moderate quality evidence that BHT in various forms and doses is more effective than placebo for treating moderate to severe menopausal hot flushes. There was low to moderate quality evidence of higher rates of adverse effects such as headache, vaginal bleeding, breast tenderness and skin reactions in the BHT group. There was some evidence to suggest that higher doses of BHT are associated with greater effectiveness but also with higher risk of adverse effects. Although all the included studies used unopposed estrogen, it is recommended best practice to use progestogen therapy in women with a uterus taking estrogen in order to avoid endometrial hyperplasia, regardless of the source of the estrogen. No data are yet available about the safety of BHT with regard to long-term outcomes such as heart attack, stroke and breast cancer.There was no good evidence of a difference in effectiveness between BHT and CEE, and findings with regard to adverse effects were inconsistent. The quality of the evidence was too low to reach any firm conclusions.The main limitations in the quality of the evidence were study risk of bias (mainly due to poor reporting of methods), imprecision and lack of data suitable for analysis.
Topics: Estradiol; Estrogens; Estrogens, Conjugated (USP); Female; Hot Flashes; Humans; Randomized Controlled Trials as Topic
PubMed: 27479272
DOI: 10.1002/14651858.CD010407.pub2 -
The British Journal of Dermatology Dec 2001Many different therapies are available for treating guttate psoriasis; however, there appears to be little objective evidence for their efficacy (Review)
Review
BACKGROUND
Many different therapies are available for treating guttate psoriasis; however, there appears to be little objective evidence for their efficacy
OBJECTIVES
This review aims to assess the evidence for the effectiveness of treatments for guttate psoriasis. Antistreptococcal interventions for guttate psoriasis are addressed in a separate review.
METHODS
Studies were identified by searching the Cochrane Clinical Trials Register (Cochrane Library, Issue 3, 1999), Medline (1966-September 1999), Embase (1988-September 1999), Salford Database of Psoriasis Trials (to November 1999) and the European Dermato-Epidemiology Network (EDEN) Psoriasis Trials Database (to November 1999) for terms GUTTATE and PSORIASIS. We also searched 100 unselected randomized controlled trials of psoriasis therapy and all 112 randomized controlled trials of phototherapy for psoriasis in the Salford Database of Psoriasis Trials for separate stratification of guttate psoriasis.
RESULTS
No published report could be found to support or to challenge current commonly used methods of management. Only one trial that met the selection criteria was identified. In this small study of 21 hospitalized patients with guttate psoriasis, intravenous infusion of an n-3 fatty acid rich lipid emulsion was compared with placebo emulsion containing n-6 fatty acids. The n-3 preparation appeared to be of some benefit for patients with guttate psoriasis.
CONCLUSION
There is currently no firm evidence on which to base treatment of acute guttate psoriasis. Studies comparing standard treatment modalities, including phototherapy and topical regimens, are required to enable informed decisions on treatment choices to be made.
Topics: Acute Disease; Dermatologic Agents; Evidence-Based Medicine; Fatty Acids, Omega-3; Humans; Psoriasis; Randomized Controlled Trials as Topic
PubMed: 11899141
DOI: 10.1046/j.1365-2133.2001.04505.x -
The Journal of Emergency Medicine Mar 2015Intravenous lipid emulsion (ILE) has been broadly attempted in the resuscitation of neurologic and cardiac toxic drug overdoses, however, the role of ILE in the... (Review)
Review
BACKGROUND
Intravenous lipid emulsion (ILE) has been broadly attempted in the resuscitation of neurologic and cardiac toxic drug overdoses, however, the role of ILE in the emergency department is poorly defined.
OBJECTIVE
This review aims to identify recent literature on the use of ILE in humans as an antidote and to familiarize emergency providers with the indications, availability, dosing recommendations, and adverse reactions associated with ILE use.
METHODS
A systemic literature search of MEDLINE, EMBASE, and major toxicology conference abstracts was performed for human cases using ILE as an antidote with documented clinical outcomes through January 2014.
RESULTS
Ninety-four published articles and 40 conference abstracts were identified, 85% of which had positive outcomes. The most common indication for ILE was for local anesthetic systemic toxicity (LAST). The most common nonlocal anesthetic xenobiotics were tricyclic-antidepressants and verapamil.
DISCUSSION
No standard of care is defined for the use of ILE, although the American Heart Association recommends use in LAST, and the American College of Medical Toxicology recommends consideration for circumstances of hemodynamic instability resultant from lipid-soluble xenobiotics. ILE should be administered per American Society of Regional Anesthesia and Pain Medicine dosing recommendations. Laboratory interference, pancreatitis, respiratory distress syndrome, and interference with vasopressors should be considered as risks but are uncommon.
CONCLUSIONS
In the setting of severe hemodynamic compromise by lipid-soluble xenobiotics, ILE may be considered for resuscitation by emergency physicians. As such, ILE may be stocked in emergency departments in close proximity to resuscitation rooms and areas where local nerve blocks are performed.
Topics: Adult; Anesthetics, Local; Anti-Arrhythmia Agents; Antidepressive Agents, Tricyclic; Antidotes; Emergency Service, Hospital; Fat Emulsions, Intravenous; Female; Humans; Poisoning; Practice Guidelines as Topic; Verapamil
PubMed: 25534900
DOI: 10.1016/j.jemermed.2014.10.009 -
Drug Design, Development and Therapy 2020Microemulsions drug delivery systems (MDDS) have been known to increase the bioavailability of hydrophobic drugs. The main challenge of the MDDS is the development of an... (Comparative Study)
Comparative Study
BACKGROUND
Microemulsions drug delivery systems (MDDS) have been known to increase the bioavailability of hydrophobic drugs. The main challenge of the MDDS is the development of an effective and safe system for drug carriage and delivery. Biosurfactants are preferred surface-active molecules because of their lower toxicity and safe characteristics when compared to synthetic surfactants. Glycolipid and lipopeptide are the most common biosurfactants that were tested for MDDS. The main goal of the present systematic review was to estimate the available evidence on the role of biosurfactant in the development of MDDS.
SEARCH STRATEGY
Literature searches involved the main scientific databases and were focused on the period from 2005 until 2017. The Search filter composed of two items: "Biosurfactant" and/or "Microemulsion."
INCLUSION CRITERIA
Twenty-four studies evaluating the use of biosurfactant in MDDS were eligible for inclusion. Among these 14 were related to the use of glycolipid biosurfactants in the MDDS formulations, while four reported using lipopeptide biosurfactants and six other related review articles.
RESULTS
According to the output study parameters, biosurfactants acted as active stabilizers, hydrophilic or hydrophobic linkers and safety carriers in MDDS, and among them glycolipid biosurfactants had the most application in MDDS formulations.
CONCLUSION
Synthetic surfactants could be replaced by biosurfactants as an effective bio-source for MDDS due to their excellent self-assembling and emulsifying activity properties.
Topics: Drug Carriers; Drug Delivery Systems; Emulsions; Glycolipids; Humans; Hydrophobic and Hydrophilic Interactions; Lipopeptides; Pharmaceutical Preparations; Surface-Active Agents
PubMed: 32103896
DOI: 10.2147/DDDT.S232325 -
Scientific Reports Oct 2017Corneal endothelium morphological abnormalities result in fluid imbalance, stromal swelling, and loss of transparency, thus impairing visual function. Recently, growing... (Meta-Analysis)
Meta-Analysis
Corneal endothelium morphological abnormalities result in fluid imbalance, stromal swelling, and loss of transparency, thus impairing visual function. Recently, growing number of studies have focused on diabetic corneal abnormalities after cataract surgery and its comparison with non-diabetic patients, the results remain conflicting. Thus, to evaluate the effect of phacoemulsification on the corneal properties in diabetic and non-diabetic patients, prospective studies were comprehensively searched through PubMed, EMBASE, and Cochrane databases updated to Jan 2017. A meta-analysis of the 13 identified studies was performed using weighted mean difference (WMD) and 95% confidence interval (CI). For the dynamic changes between preoperative and postoperative values, significant differences were identified between the two groups in endothelial cell density (ECD) and hexagon cells (HC%) at 1 day, 1 week, 1 month, and 3 months postoperatively, in central corneal thickness (CCT) at 1 month postoperatively, and in coefficient variation (CV) at 1 week and 1 month postoperatively. However, no significant differences were observed in CCT at 1 day, 1 week and 3 months postoperatively or in CV at 1 day and 3 months postoperatively. Diabetic corneas are more vulnerable to stress and trauma, resulting in greater morphological abnormalities and longer recovery time.
Topics: Cataract; Cornea; Diabetes Complications; Emulsions; Humans
PubMed: 29074989
DOI: 10.1038/s41598-017-14656-7 -
Intensive Care Medicine Oct 2013Parenteral lipid emulsions (LEs) are commonly rich in long-chain triglycerides derived from soybean oil (SO). SO-containing emulsions may promote systemic inflammation... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Parenteral lipid emulsions (LEs) are commonly rich in long-chain triglycerides derived from soybean oil (SO). SO-containing emulsions may promote systemic inflammation and therefore may adversely affect clinical outcomes. We hypothesized that alternative oil-based LEs (SO-sparing strategies) may improve clinical outcomes in critically ill adult patients compared to products containing SO emulsion only. The purpose of this systematic review was to evaluate the effect of parenteral SO-sparing strategies on clinical outcomes in intensive care unit (ICU) patients.
METHODS
We searched computerized databases from 1980 to 2013. We included randomized controlled trials (RCTs) conducted in critically ill adult patients that evaluated SO-sparing strategies versus SO-based LEs in the context of parenteral nutrition.
RESULTS
A total of 12 RCTs met the inclusion criteria. When the results of these RCTs were statistically aggregated, SO-sparing strategies were associated with clinically important reductions in mortality (risk ratio, RR 0.83; 95 % confidence intervals, CI 0.62, 1.11; P = 0.20), in duration of ventilation (weighted mean difference, WMD -2.57; 95 % CI -5.51, 0.37; P = 0.09), and in ICU length of stay (LOS) (WMD -2.31; 95 % CI -5.28, 0.66; P = 0.13) but none of these differences were statistically significant. SO-sparing strategies had no effect on infectious complications (RR 1.13; 95 % CI 0.87, 1.46; P = 0.35).
CONCLUSION
Alternative oil-based LEs may be associated with clinically important reductions in mortality, duration of ventilation, and ICU LOS but lack of statistical precision precludes any clinical recommendations at this time. Further research is warranted to confirm these potential positive treatment effects.
Topics: Adult; Critical Illness; Databases, Bibliographic; Emulsions; Fat Emulsions, Intravenous; Fish Oils; Humans; Immune System; Inflammation; Intensive Care Units; Lecithins; Oxidative Stress; Parenteral Nutrition; Phospholipids; Plant Oils; Randomized Controlled Trials as Topic; Safflower Oil; Soybean Oil; Treatment Outcome; Triglycerides
PubMed: 23812404
DOI: 10.1007/s00134-013-2999-4