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Clinical Toxicology (Philadelphia, Pa.) Oct 2020Beta-adrenoreceptor antagonist (beta-blocker) poisoning is a common overdose which can lead to significant morbidity and mortality. To evaluate the effects of...
Beta-adrenoreceptor antagonist (beta-blocker) poisoning is a common overdose which can lead to significant morbidity and mortality. To evaluate the effects of treatments for beta-adrenoreceptor antagonist poisoning. Searches were conducted across MEDLINE (1946-26 November 2019, Ovid); Embase (1974-26 November 2019, Ovid); and the Cochrane Central Register of Controlled Trials (CENTRAL, to 26 November 2019) utilising a combination of subject headings and free text. The search strategy identified 15, 553 citations. Two reviewers screened titles and abstracts prior to selecting 141 articles (Kappa on articles included = 0.982, 95% CI 0.980-0.985). Primary outcomes included mortality and improvement in haemodynamic parameters (e.g., heart rate, blood pressure or a composite measure able to quantitate a haemodynamic response). The risk of bias was high for all interventions. Fifteen case reports described the administration of activated charcoal and five detailed the use of gastric lavage. As there was concurrent utilisation of multiple interventions, it was difficult to draw definitive conclusions regarding the relative contribution of these interventions to mortality or survival. The use of catecholamines in treating beta-blocker toxicity was reported in 16 case reports, 3 case series and 2 animal studies. These agents most likely provided a survival benefit and improved haemodynamics. Multiple intravenous boluses of atropine were associated with improvement in heart rate and blood pressure in one case report. Intravenous calcium was associated with an improvement in haemodynamics in three out of six case reports but in association with multiple other therapies as well as in two animal studies. The use of this therapy was associated with mortality benefit in 10 case series. Two case reports showed clear haemodynamic improvement in a timeframe consistent with insulin administration (bolus then continuous infusion). Maintenance dosing ranged from 1 to 10 units/kg/h of insulin. However, it is unclear whether high-dose insulin euglycaemic therapy improved haemodynamic response above catecholamines and other inotropic agents in humans. Hypoglycaemia and hypokalemia were commonly observed adverse effects. Glucagon was associated with minor improvements in haemodynamics through an increase in heart rate in two cases series, nine case reports and five animal studies. Four case reports reported an association with improvement in haemodynamics following administration of methylene blue but in the setting of co-ingestion with amlodipine. There was variable response to intravenous lipid emulsion therapy reported in 10 case series, 5 animal studies and 21 case reports. There were four case reports showing variable response to lignocaine in arrhythmias secondary to beta-blocker toxicity. Fructose diphosphate, levosimendan and amrinone did not provide a mortality or significant haemodynamic benefit in three animal studies and nine case reports. . Veno-arterial extracorporeal membrane oxygenation was associated with improved survival in patients with severe cardiogenic shock or cardiac arrest in an observational study and four cases series. The evidence of four case reports suggest haemodialysis may assist in the management of massive overdose of specific water-soluble beta-blockers (e.g., atenolol) by improving elimination; however, a survival or haemodynamic benefit was not established. One case series and a single case report showed the utility of temporary overdrive cardiac pacing to prevent arrhythmias in sotalol toxicity. Catecholamines, vasopressors, high-dose insulin euglycaemic therapy and veno-arterial extracorporeal membrane oxygenation were associated with reduced mortality. However, it must be acknowledged that multiple treatments were often given simultaneously. Haemodynamic improvements in blood pressure and cardiac output were seen with the use of catecholamines, vasopressin and high-dose insulin euglycaemic therapy. Evidence for treatment recommendations is almost entirely drawn from very low- to low-quality studies and subject to bias. However, it is reasonable to have a graduated response to cardiovascular instability beginning with intravenous fluids, commencement of a single or a combination of catecholamine inotropes and vasopressors depending upon the type of haemodynamic compromise (bradycardia, left ventricular dysfunction, vasodilation). High-dose insulin euglycaemic therapy can be introduced as an adjunctive inotrope and lastly, more invasive methods such as veno-arterial extracorporeal membrane oxygenation should be considered in cases unresponsive to other therapies.
Topics: Adrenergic beta-Antagonists; Animals; Atropine; Catecholamines; Drug Overdose; Extracorporeal Membrane Oxygenation; Fat Emulsions, Intravenous; Hemodynamics; Humans; Insulin; Practice Guidelines as Topic
PubMed: 32310006
DOI: 10.1080/15563650.2020.1752918 -
The Cochrane Database of Systematic... Sep 2019Topical cyclosporine A (also known as ciclosporin A) (CsA) is an anti-inflammatory that has been widely used to treat inflammatory ocular surface diseases. Two CsA...
BACKGROUND
Topical cyclosporine A (also known as ciclosporin A) (CsA) is an anti-inflammatory that has been widely used to treat inflammatory ocular surface diseases. Two CsA eyedrops have been approved by US Food and Drug Administration for managing dry eye: Restasis (CsA 0.05%, Allergan Inc, Irvine, CA, USA), approved in 2002, and Cequa (CsA 0.09%, Sun Pharma, Cranbury, NJ, USA), approved in 2018. Numerous clinical trials have been performed to assess the effectiveness and safety of CsA for dry eye; however, there is no universal consensus with regard to its effect.
OBJECTIVES
To assess the effectiveness and safety of topical CsA in the treatment of dry eye.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2018, Issue 2); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature Database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 16 February 2018.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) of people with dry eye regardless of age, sex, severity, etiology, or classification of dry eye. We included RCTs in which different concentrations of topical CsA were compared with one another or with artificial tears, placebo, or vehicle. We also included RCTs in which CsA in combination with artificial tears was compared to artificial tears alone.
DATA COLLECTION AND ANALYSIS
We followed the standard Cochrane methodology and assessed the certainty of the evidence using GRADE.
MAIN RESULTS
We included 30 RCTs (4009 participants) with follow-up periods ranging from 6 weeks to 12 months. We studied dry eye of various severity and underlying causes. The interventions investigated also varied across RCTs: CsA versus artificial tears; CsA with artificial tears versus artificial tears alone; and in some studies, more than one concentration of CsA. Artificial tears were used as adjunctive to study medication in all but five trials. Almost all trials had deficiencies in the reporting of results (e.g. reporting P values or direction only), precluding the calculation of between-group estimates of effect or meta-analysis.Eighteen trials compared topical CsA 0.05% plus artificial tears versus vehicle plus artificial tears or artificial tears alone. One trial reported subjective symptoms of dry eye at 6 months and the results were in favor of CsA (mean difference (MD) -4.80, 95% confidence interval (CI) -6.41 to -3.19; low-certainty evidence). Two trials reported MD in ocular surface dye staining at 6 months, but the results were inconsistent in these two trials (MD -0.35, 95% CI -0.69 to -0.01 in one and MD 0.58, 95% CI 0.06 to 1.10 in the other; low-certainty evidence). Four trials reported MD in Schirmer test scores at 6 months and the estimates ranged from -4.05 (95% CI -6.67 to -1.73) to 3.26 (95% CI -1.52 to 5.00) (low-certainty evidence). Three trials reported risk ratio (RR) of improved Schirmer test scores at 6 months; estimates ranged from 0.98 (95% CI 0.83 to 1.17) to 3.50 (95% CI 2.09 to 5.85) (low-certainty evidence). Four trials reported MD in tear film stability measured by tear break-up time at 6 months and the estimates ranged from -1.98 (95% CI -3.59 to -0.37) to 1.90 (95% CI 1.44 to 2.36) (low-certainty evidence). Three trials reported RR of improved tear break-up time at 6 months and the estimates ranged from 0.90 (95% CI 0.77 to 1.04) to 4.00 (95% CI 2.25 to 7.12) (low-certainty evidence). Three trials reported frequency of artificial tear usage at 6 months without providing any estimates of effect; the direction of effect seem to be in favor of CsA (low-certainty evidence). Because of incomplete reporting of the results data or considerable statistical heterogeneity, we were only able to perform a meta-analysis on mean conjunctival goblet cell density. Mean conjunctival goblet cell density in the CsA treated group may be greater than that in the control group at the end of follow-up at four and 12 months (MD 22.5 cells per unit, 95% CI 16.3 to 28.8; low-certainty evidence). All but two trials reported adverse events that included burning and stinging. Participants treated with CsA may be more likely to have treatment-related adverse events than those who treated with vehicle (RR 1.33, 95% CI 1.00 to 1.78; low-certainty evidence).Other comparisons evaluated were CsA 0.05% plus artificial tears versus higher concentrations of CsA plus artificial tears (4 trials); CsA 0.05% versus placebo or vehicle (4 trials); CsA 0.1% plus artificial tears versus placebo or vehicle plus artificial tears (2 trials);CsA 0.1% cationic emulsion plus artificial tears versus vehicle plus artificial tears (2 trials); CsA 1% plus artificial tears versus placebo plus artificial tears (3 trials); and CsA 2% plus artificial tears versus placebo plus artificial tears (3 trials). Almost all of these trials reported P value or direction of effect only (mostly in favor of CsA), precluding calculation of between-group effect estimates or meta-analyses.
AUTHORS' CONCLUSIONS
Despite the widespread use of topical CsA to treat dry eye, we found that evidence on the effect of CsA on ocular discomfort and ocular surface and tear film parameters such as corneal fluorescein staining, Schirmer's test, and TBUT is inconsistent and sometimes may not be different from vehicle or artificial tears for the time periods reported in the trials. There may be an increase in non-serious, treatment-related adverse effects (particularly burning) in the CsA group. Topical CsA may increase the number of conjunctival goblet cells. However, current evidence does not support that improvements in conjunctival mucus production (through increased conjunctival goblet cells) translate to improved symptoms or ocular surface and tear film parameters. All published trials were short term and did not assess whether CsA has longer-term disease-modifying effects. Well-planned, long-term, large clinical trials are needed to better assess CsA on long-term dry eye-modifying effects. A core outcome set, which ideally includes both biomarkers and patient-reported outcomes in the field of dry eye, is needed.
Topics: Cyclosporine; Dry Eye Syndromes; Humans; Lubricant Eye Drops; Randomized Controlled Trials as Topic
PubMed: 31517988
DOI: 10.1002/14651858.CD010051.pub2 -
The British Journal of Dermatology Jul 2019Rosacea is a common chronic facial dermatosis. Classification of rosacea has evolved from subtyping to phenotyping.
BACKGROUND
Rosacea is a common chronic facial dermatosis. Classification of rosacea has evolved from subtyping to phenotyping.
OBJECTIVES
To update our systematic review on interventions for rosacea.
METHODS
We searched CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index and ongoing trials registers (March 2018) for randomized controlled trials. Study selection, data extraction, risk-of-bias assessment and analyses were carried out independently by two authors. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) was used to assess certainty of evidence.
RESULTS
We included 152 studies (46 were new), comprising 20 944 participants. Topical interventions included brimonidine, oxymetazoline, metronidazole, azelaic acid, ivermectin and other topical treatments. Systemic interventions included oral antibiotics, combinations with topical treatments or other systemic treatments. Several studies evaluated laser or light-based treatment. We present the most current evidence for rosacea management based on a phenotype-led approach.
CONCLUSIONS
For reducing temporarily persistent erythema there was high-certainty evidence for topical brimonidine and moderate certainty for topical oxymetazoline; for erythema and mainly telangiectasia there was low-to-moderate-certainty evidence for laser and intense pulsed light therapy. For reducing papules/pustules there was high-certainty evidence for topical azelaic acid and topical ivermectin; moderate-to-high-certainty evidence for doxycycline 40 mg modified release (MR) and isotretinoin; and moderate-certainty evidence for topical metronidazole, and topical minocycline and oral minocycline being equally effective as doxycycline 40 mg MR. There was low-certainty evidence for tetracycline and low-dose minocycline. For ocular rosacea, there was moderate-certainty evidence that oral omega-3 fatty acids were effective and low-certainty evidence for ciclosporin ophthalmic emulsion and doxycycline.
Topics: Administration, Cutaneous; Administration, Oral; Anti-Bacterial Agents; Brimonidine Tartrate; Combined Modality Therapy; Dermatologic Agents; Dermatology; Drug Therapy, Combination; Evidence-Based Medicine; Facial Dermatoses; Humans; Intense Pulsed Light Therapy; Low-Level Light Therapy; Oxymetazoline; Randomized Controlled Trials as Topic; Rosacea; Severity of Illness Index; Treatment Outcome
PubMed: 30585305
DOI: 10.1111/bjd.17590 -
Clinical Nutrition (Edinburgh, Scotland) Apr 2023Accumulating scientific evidence supports the benefits of parenteral nutrition (PN) with fish oil (FO) containing intravenous lipid emulsions (ILEs) on clinical... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
Accumulating scientific evidence supports the benefits of parenteral nutrition (PN) with fish oil (FO) containing intravenous lipid emulsions (ILEs) on clinical outcomes. Yet, the question of the most effective ILE remains controversial. We conducted a network meta-analysis (NMA) to compare and rank different types of ILEs in terms of their effects on infections, sepsis, ICU and hospital length of stay, and in-hospital mortality in adult patients.
METHODS
MEDLINE, EMBASE, and Web of Science databases were searched for randomized controlled trials (RCTs) published up to May 2022, investigating ILEs as a part of part of PN covering at least 70% of total energy provision. Lipid emulsions were classified in four categories: FO-ILEs, olive oil (OO)-ILEs, medium-chain triglyceride (MCT)/soybean oil (SO)-ILEs, and pure SO-ILEs. Data were statistically combined through Bayesian NMA and the Surface Under the Cumulative RAnking (SUCRA) was calculated for all outcomes.
RESULTS
1651 publications were retrieved in the original search, 47 RCTs were included in the NMA. For FO-ILEs, very highly credible reductions in infection risk versus SO-ILEs [odds ratio (OR) = 0.43 90% credibility interval (CrI) (0.29-0.63)], MCT/soybean oil-ILEs [0.59 (0.43-0.82)], and OO-ILEs [0.56 (0.33-0.91)], and in sepsis risk versus SO-ILEs [0.22 (0.08-0.59)], as well as substantial reductions in hospital length of stay versus SO-ILEs [mean difference (MD) = -2.31 (-3.14 to -1.59) days] and MCT/SO-ILEs (-2.01 (-2.82 to -1.22 days) were shown. According to SUCRA score, FO-ILEs were ranked first for all five outcomes.
CONCLUSIONS
In hospitalized patients, FO-ILEs provide significant clinical benefits over all other types of ILEs, ranking first for all outcomes investigated.
REGISTRATION NO
PROSPERO 2022 CRD42022328660.
Topics: Humans; Soybean Oil; Network Meta-Analysis; Parenteral Nutrition; Fat Emulsions, Intravenous; Fish Oils; Olive Oil; Fatty Acids, Omega-3; Sepsis
PubMed: 36878111
DOI: 10.1016/j.clnu.2023.02.008 -
The Cochrane Database of Systematic... Feb 2021Eczema and food allergy are common health conditions that usually begin in early childhood and often occur together in the same people. They can be associated with an... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Eczema and food allergy are common health conditions that usually begin in early childhood and often occur together in the same people. They can be associated with an impaired skin barrier in early infancy. It is unclear whether trying to prevent or reverse an impaired skin barrier soon after birth is effective in preventing eczema or food allergy.
OBJECTIVES
Primary objective To assess effects of skin care interventions, such as emollients, for primary prevention of eczema and food allergy in infants Secondary objective To identify features of study populations such as age, hereditary risk, and adherence to interventions that are associated with the greatest treatment benefit or harm for both eczema and food allergy.
SEARCH METHODS
We searched the following databases up to July 2020: Cochrane Skin Specialised Register, CENTRAL, MEDLINE, and Embase. We searched two trials registers and checked reference lists of included studies and relevant systematic reviews for further references to relevant randomised controlled trials (RCTs). We contacted field experts to identify planned trials and to seek information about unpublished or incomplete trials.
SELECTION CRITERIA
RCTs of skin care interventions that could potentially enhance skin barrier function, reduce dryness, or reduce subclinical inflammation in healthy term (> 37 weeks) infants (0 to 12 months) without pre-existing diagnosis of eczema, food allergy, or other skin condition were included. Comparison was standard care in the locality or no treatment. Types of skin care interventions included moisturisers/emollients; bathing products; advice regarding reducing soap exposure and bathing frequency; and use of water softeners. No minimum follow-up was required.
DATA COLLECTION AND ANALYSIS
This is a prospective individual participant data (IPD) meta-analysis. We used standard Cochrane methodological procedures, and primary analyses used the IPD dataset. Primary outcomes were cumulative incidence of eczema and cumulative incidence of immunoglobulin (Ig)E-mediated food allergy by one to three years, both measured by the closest available time point to two years. Secondary outcomes included adverse events during the intervention period; eczema severity (clinician-assessed); parent report of eczema severity; time to onset of eczema; parent report of immediate food allergy; and allergic sensitisation to food or inhalant allergen.
MAIN RESULTS
This review identified 33 RCTs, comprising 25,827 participants. A total of 17 studies, randomising 5823 participants, reported information on one or more outcomes specified in this review. Eleven studies randomising 5217 participants, with 10 of these studies providing IPD, were included in one or more meta-analysis (range 2 to 9 studies per individual meta-analysis). Most studies were conducted at children's hospitals. All interventions were compared against no skin care intervention or local standard care. Of the 17 studies that reported our outcomes, 13 assessed emollients. Twenty-five studies, including all those contributing data to meta-analyses, randomised newborns up to age three weeks to receive a skin care intervention or standard infant skin care. Eight of the 11 studies contributing to meta-analyses recruited infants at high risk of developing eczema or food allergy, although definition of high risk varied between studies. Durations of intervention and follow-up ranged from 24 hours to two years. We assessed most of this review's evidence as low certainty or had some concerns of risk of bias. A rating of some concerns was most often due to lack of blinding of outcome assessors or significant missing data, which could have impacted outcome measurement but was judged unlikely to have done so. Evidence for the primary food allergy outcome was rated as high risk of bias due to inclusion of only one trial where findings varied when different assumptions were made about missing data. Skin care interventions during infancy probably do not change risk of eczema by one to two years of age (risk ratio (RR) 1.03, 95% confidence interval (CI) 0.81 to 1.31; moderate-certainty evidence; 3075 participants, 7 trials) nor time to onset of eczema (hazard ratio 0.86, 95% CI 0.65 to 1.14; moderate-certainty evidence; 3349 participants, 9 trials). It is unclear whether skin care interventions during infancy change risk of IgE-mediated food allergy by one to two years of age (RR 2.53, 95% CI 0.99 to 6.47; 996 participants, 1 trial) or allergic sensitisation to a food allergen at age one to two years (RR 0.86, 95% CI 0.28 to 2.69; 1055 participants, 2 trials) due to very low-certainty evidence for these outcomes. Skin care interventions during infancy may slightly increase risk of parent report of immediate reaction to a common food allergen at two years (RR 1.27, 95% CI 1.00 to 1.61; low-certainty evidence; 1171 participants, 1 trial). However, this was only seen for cow's milk, and may be unreliable due to significant over-reporting of cow's milk allergy in infants. Skin care interventions during infancy probably increase risk of skin infection over the intervention period (RR 1.34, 95% CI 1.02 to 1.77; moderate-certainty evidence; 2728 participants, 6 trials) and may increase risk of infant slippage over the intervention period (RR 1.42, 95% CI 0.67 to 2.99; low-certainty evidence; 2538 participants, 4 trials) or stinging/allergic reactions to moisturisers (RR 2.24, 95% 0.67 to 7.43; low-certainty evidence; 343 participants, 4 trials), although confidence intervals for slippages and stinging/allergic reactions are wide and include the possibility of no effect or reduced risk. Preplanned subgroup analyses show that effects of interventions were not influenced by age, duration of intervention, hereditary risk, FLG mutation, or classification of intervention type for risk of developing eczema. We could not evaluate these effects on risk of food allergy. Evidence was insufficient to show whether adherence to interventions influenced the relationship between skin care interventions and risk of developing eczema or food allergy.
AUTHORS' CONCLUSIONS
Skin care interventions such as emollients during the first year of life in healthy infants are probably not effective for preventing eczema, and probably increase risk of skin infection. Effects of skin care interventions on risk of food allergy are uncertain. Further work is needed to understand whether different approaches to infant skin care might promote or prevent eczema and to evaluate effects on food allergy based on robust outcome assessments.
Topics: Bias; Eczema; Emollients; Female; Filaggrin Proteins; Food Hypersensitivity; Humans; Hypersensitivity, Immediate; Immunoglobulin E; Infant; Infant, Newborn; Male; Milk Hypersensitivity; Skin Care; Skin Diseases, Infectious; Soaps
PubMed: 33545739
DOI: 10.1002/14651858.CD013534.pub2 -
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 -
Frontiers in Nutrition 2021Gastric cancer (GC) is one of the most common digestive tract cancers and ranks fifth in the incidence of malignant tumors worldwide. oil emulsion injection (BJOEI), a... (Review)
Review
Gastric cancer (GC) is one of the most common digestive tract cancers and ranks fifth in the incidence of malignant tumors worldwide. oil emulsion injection (BJOEI), a Chinese patent medicine extracted from (Yadanzi in Chinese Pinyin), is widely used as an adjuvant treatment for GC in China. This systematic review and meta-analysis aimed to evaluate the available data on the efficacy and safety of BJOEI in the treatment of GC and assess the quality of the synthesized evidence. A comprehensive search was performed on PubMed, EMBASE, CENTRAL, Web of Science, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Wanfang database and Chinese Scientific Journals Database (VIP database), and other potential resources, such as the Chinese Clinical Trial Registry (ChiCTR) and ClinicalTrials.gov from their inception to July 31, 2021. Randomized controlled trials (RCTs) comparing the therapeutic effects of BJOEI combined with conventional therapy to those of conventional therapy alone were included. We used RevMan 5.3 for data analysis and quality evaluation of the included studies and assessed the evidence quality based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. Eighteen RCTs involving 1,210 patients were included, and the meta-analysis results demonstrated that compared with the control group (conventional therapy), the experimental group (BJOEI combined with conventional therapy) showed a significantly improved overall response rate (ORR) (risk ratio [RR] = 1.52, 95% CI: 1.36-1.69, < 0.00001), clinical benefit rate (CBR) (RR = 1.17, 95% CI: 1.11-1.23, < 0.00001), performance status (RR = 1.72, 95% CI: 1.46-2.01, < 0.00001), and reduced incidence of the following adverse drug reactions (ADRs): neutropenia, leukopenia, nausea and vomiting, diarrhea, liver damage, hand-foot syndrome, and peripheral sensory nerve toxicity. Subgroup analysis showed that the BJOEI intervention could significantly improve the ORR and CBR in patients with GC when combined with FOLFOX4, XELOX, and other chemotherapeutics. The evidence presented in this study supports the fact that BJOEI combined with conventional chemotherapy provides a statistically significant and clinically important effect in the improvement of ORR, CBR, performance status, and ADR reduction in patients with GC. To further support this conclusion, more rigorously designed, large-scale, and multicenter RCTs are needed in the future.
PubMed: 34957186
DOI: 10.3389/fnut.2021.784164 -
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 -
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 -
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