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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 -
Advances in Nutrition (Bethesda, Md.) Dec 2022Zinc supplementation reduces morbidity, but evidence suggests that excessive intakes can have negative health consequences. Current guidelines of upper limits (ULs) of... (Meta-Analysis)
Meta-Analysis
Zinc supplementation reduces morbidity, but evidence suggests that excessive intakes can have negative health consequences. Current guidelines of upper limits (ULs) of zinc intake for young children are extrapolated from adult data. This systematic review (PROSPERO; registration no. CRD42020215187) aimed to determine the levels of zinc intake at which adverse effects are observed in young children. Studies reporting potential adverse effects of zinc intake in children aged 0-3 y were identified (from inception to August 2020) in MEDLINE, Embase, and the Cochrane Library, with no limits on study design. Adverse clinical and physical effects of zinc intake were synthesized narratively, and meta-analyses of biochemical outcomes were conducted. Random effects models were used to generate forest plots to examine the evidence by age category, dose, dose duration, chemical formula of zinc, and zinc compared with placebo. The Joanna Briggs Institute Critical Appraisal Checklist, Cochrane Risk of Bias 2, and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guideline were employed to assess risk of bias and to appraise the certainty of evidence. Fifty-eight studies assessed possible adverse effects of zinc doses ranging from 3 to 70 mg/d. Data from 39 studies contributed to meta-analyses. Zinc supplementation had an adverse effect on serum ferritin, plasma/serum copper concentration, serum transferrin receptor, hemoglobin, hematocrit, and the odds of anemia in ≥1 of the subgroups investigated. Lactulose:mannitol ratio was improved with zinc supplementation, and no significant effect was observed on C-reactive protein, erythrocyte superoxide dismutase, zinc protoporphyrin, blood cholesterol, and iron deficiency anemia. The certainty of the evidence, as assessed using GRADE, was very low to moderate. Although possible adverse effects of zinc supplementation were observed in some subgroups, it is unclear whether these findings are clinically important. The synthesized data can be used to undertake a dose-response analysis to update current guidelines of ULs of zinc intake for young children.
Topics: Adult; Child; Humans; Infant; Child, Preschool; Zinc; Nutritional Status
PubMed: 36055780
DOI: 10.1093/advances/nmac088 -
Clinical Endocrinology Jun 2017International and national guidelines on the treatment of chronic nonhypovolaemic hypotonic hyponatraemia differ; therefore, we have undertaken this systematic review... (Meta-Analysis)
Meta-Analysis Review
International and national guidelines on the treatment of chronic nonhypovolaemic hypotonic hyponatraemia differ; therefore, we have undertaken this systematic review and meta-analysis to investigate the efficacy and safety of interventions for the treatment of chronic nonhypovolaemic hypotonic hyponatraemia. Following registration of the review protocol with PROSPERO, systematic literature searches were conducted to identify randomized and quasi-randomized controlled trials assessing any degree of fluid restriction or any drug treatment with the aim of increasing serum sodium concentration in patients with chronic nonhypovolaemic hypotonic hyponatraemia. Where appropriate, outcome data were synthesized in a meta-analysis. A total of 45 716 bibliographic records were identified from the searches and 18 trials (assessing conivaptan, lixivaptan, tolvaptan and satavaptan) met the eligibility criteria. Results suggest that all four vasopressin receptor agonists ("vaptans") significantly improve serum sodium concentration. Lixivaptan, satavaptan and tolvaptan were associated with greater rates of response versus placebo. There was no evidence of a difference between each of the vaptans compared with placebo for mortality, discontinuation and rates of hypernatraemia. No RCT evidence of treatments other than the vaptans for hyponatraemia such as oral urea, salt tablets, mannitol, loop diuretics demeclocycline or lithium was identified. Vaptans demonstrated superiority over placebo for outcomes relating to serum sodium correction. Few trials documented the potential benefit of vaptans on change in health-related quality of life as a result of treatment. There was also a lack of high-quality RCT evidence on the comparative efficacy of the vaptans and other treatment strategies for the treatment of chronic nonhypovolaemic hypotonic hyponatraemia.
Topics: Antidiuretic Hormone Receptor Antagonists; Benzamides; Benzazepines; Humans; Hyponatremia; Morpholines; Osmotic Pressure; Pyrroles; Randomized Controlled Trials as Topic; Receptors, Vasopressin; Spiro Compounds; Tolvaptan
PubMed: 28214374
DOI: 10.1111/cen.13315 -
Anaesthesia Sep 2014Ischaemia of the extremity from the use of a tourniquet and the subsequent reperfusion contribute to the release of reactive oxygen species. This release may result in... (Review)
Review
Ischaemia of the extremity from the use of a tourniquet and the subsequent reperfusion contribute to the release of reactive oxygen species. This release may result in injury to remote organs. We performed a qualitative systematic review exploring the interventions used to prevent tourniquet-related oxidative damage in adults undergoing orthopaedic surgery, and the possible relationship between biochemical oxidative stress markers and postoperative clinical outcomes. Seventeen randomised controlled studies were included in the qualitative synthesis. Most trials were of low methodological quality and only two studies reported postoperative clinical outcomes. Nine studies tested anaesthetics (propofol, dexmedetomidine, ketamine, and spinal anaesthesia); four studies tested antioxidants (N-acetyl-cysteine, vitamin C, and mannitol); and four studies tested ischaemic pre-conditioning. Fifteen studies showed a significant reduction in biochemical oxidative stress markers. We conclude that propofol and ischaemic pre-conditioning, in particular, appear to show some benefit at reducing oxidative stress following operations under tourniquet; the correlation between a reduction in oxidative stress and postoperative clinical outcomes should be further investigated in the future.
Topics: Adolescent; Adult; Aged; Anesthesia; Antioxidants; Female; Humans; Ischemia; Ischemic Preconditioning; Male; Middle Aged; Orthopedic Procedures; Oxidative Stress; Randomized Controlled Trials as Topic; Research Design; Tourniquets; Treatment Outcome; Young Adult
PubMed: 24800642
DOI: 10.1111/anae.12664 -
The Oncologist Feb 2024Cisplatin-induced nephrotoxicity (CIN) can be prevented by fluid hydration, electrolyte supplementation, or forced diuresis; however, the best way to prevent CIN is...
INTRODUCTION
Cisplatin-induced nephrotoxicity (CIN) can be prevented by fluid hydration, electrolyte supplementation, or forced diuresis; however, the best way to prevent CIN is still unknown. The aim of this study was to provide objective evidence on the optimal design of hydration schemes to prevent CIN based on an update of the literature.
METHODS
A Pubmed and Embase search were conducted in December 2021 and repeated in April 2022 and March 2023. Two independent reviewers screened the articles. The included articles were categorized and reviewed per category.
RESULTS
Twenty-seven articles met the inclusion criteria. The included studies varied widely. Four out of seven studies investigating diuretics found a protective effect of adding mannitol to the hydration scheme. All six studies investigating duration and amount of volume of hydration found that a short-hydration scheme resulted in less CIN than a longer hydration scheme. Seven out of nine articles evaluating the role of electrolytes found that magnesium supplementation reduced the risk of nephrotoxicity. Three studies investigated the safety of oral hydration and concluded that nephrotoxicity did not occur more frequently after oral hydration.
CONCLUSION
The hydration scheme of cisplatin should be short and consist of a relatively small amount of volume. The scheme should include mannitol and magnesium supplementation. Head-to-head studies are needed to investigate the safety of furosemide compared with mannitol and the dose of mannitol and magnesium.
Topics: Humans; Cisplatin; Antineoplastic Agents; Magnesium; Mannitol; Renal Insufficiency
PubMed: 37995306
DOI: 10.1093/oncolo/oyad297 -
International Endodontic Journal Jul 2022Incorporating an additive into lidocaine is a method to enhance the efficacy of the inferior alveolar nerve block (IANB) in mandibular posterior teeth. (Meta-Analysis)
Meta-Analysis Review
Anaesthetic efficacy of incorporating different additives into lidocaine for the inferior alveolar nerve block: A systematic review with meta-analysis and trial sequential analysis.
BACKGROUND
Incorporating an additive into lidocaine is a method to enhance the efficacy of the inferior alveolar nerve block (IANB) in mandibular posterior teeth.
OBJECTIVES
To assess the efficacy of incorporating additives into lidocaine in the success rate of IANB for teeth with the diagnosis of normal pulp (NP) or symptomatic irreversible pulpitis (SIP).
METHODS
Randomized controlled trials (RCTs) assessing the incorporation of additives into lidocaine on the pulpal anaesthesia success rate of mandibular posterior teeth were searched in PubMed, Scopus, Web of Science, Ovid, EBSCO, Embase, and Cochrane databases up to 1 December 2021. The risk of bias (RoB) was assessed by the Cochrane Risk of Bias Tool. A random-effects model was employed to calculate the pooled risk ratio (RR) with a 95% confidence interval (CI), using STATA 16. The trial sequential analysis (TSA) was applied to calculate the required information size (RIS). The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach was used to assess the certainty of the evidence.
RESULTS
Of 6966 records retrieved initially, 14 trials (8 for NP and 6 for SIP groups) were included in qualitative and quantitative syntheses. All trials were categorized as low and unclear RoB for NP and SIP groups, respectively. In the NP group, with 307 participants, no significant effect was observed for additives incorporated into lidocaine (RR: 0.84; 95% CI: 0.53-1.32; I = 98%). Subgroup analysis revealed that adding mannitol led to a higher success rate (RR = 1.24; 95% CI: 1.15-1.34; I = 7.16%). In the SIP group, with 434 participants, no significant effect was shown when the additives were incorporated (RR = 1.22; 95% CI: 0.98-1.52; I = 0%). Likewise, in subgroup analysis, incorporating mannitol or sodium bicarbonate demonstrated no significant effect (RR = 1.76; 95% CI: 0.93-3.32; I = 18.41% and RR = 1.06; 95% CI: 0.65-1.72; I = 53.5%, respectively).
DISCUSSION
TSA revealed that the outcome was "inconclusive" for each group. The certainty of the evidence was graded as "very low" and "low" for NP and SIP groups, respectively.
CONCLUSIONS
The very low to low certainty of evidence indicated that incorporating additives into lidocaine did not increase the efficacy of IANB and supplemental injections are still necessary to help practitioners achieve painless dentistry.
REGISTRATION
PROSPERO database (CRD42020132585).
Topics: Anesthesia, Dental; Anesthetics; Anesthetics, Local; Double-Blind Method; Humans; Lidocaine; Mandibular Nerve; Mannitol; Nerve Block; Pulpitis
PubMed: 35398916
DOI: 10.1111/iej.13746 -
Artificial Organs May 2016Organ preservation solution has been designed to attenuate the detrimental effects during the ischemic period. The aim of this study was to systematically evaluate the... (Meta-Analysis)
Meta-Analysis Review
Organ preservation solution has been designed to attenuate the detrimental effects during the ischemic period. The aim of this study was to systematically evaluate the evidence comparing preservation solutions for heart preservation. Studies were searched in PubMed, Embase, the Cochrane Library, the Transplant Library, and the International Clinical Trials Registry Platform. The primary outcomes were patient survival and donor heart dysfunction. The secondary outcomes were in-hospital mortality and enzyme gene expression. The University of Wisconsin solution (UW) was associated with a significantly improved survival at 30 days and 90 days (hazard ratio = 1.16, 95% confidence interval [CI] = 1.11-1.22, P < 0.00001; risk difference [RD] = 0.03, 95% CI = 0.01-0.05, P = 0.002), compared with Celsior. Hearts preserved with UW exhibited less ischemic necrosis than those preserved with Celsior (RD = -0.07, 95% CI = -0.08 to 0.05, P < 0.00001). UW was associated with better survival compared with histidine-tryptophan-ketoglutarate solution (HTK). There was no statistical difference in donor heart dysfunction and in-hospital mortality outcomes when comparing HTK with Celsior solution. During static cold storage preservation, this study suggests that UW solution has better clinical outcomes for heart transplantation compared with the other two organ preservation solutions. Besides, the protective effect of Celsior solution is similar to HTK solution in donor heart preservation.
Topics: Adenosine; Allografts; Allopurinol; Disaccharides; Electrolytes; Glucose; Glutamates; Glutathione; Heart; Heart Transplantation; Histidine; Humans; Insulin; Mannitol; Organ Preservation; Organ Preservation Solutions; Potassium Chloride; Procaine; Raffinose
PubMed: 26526678
DOI: 10.1111/aor.12585 -
Burns & Trauma 2015We aimed to systematically review the efficacy of mannitol (MTL) on patients with acute severe traumatic brain injury (TBI).
BACKGROUND
We aimed to systematically review the efficacy of mannitol (MTL) on patients with acute severe traumatic brain injury (TBI).
METHODS
Databases such as PubMed (US National Library of Medicine), CENTRAL (The Cochrane Library 2014, Issue 3), ISI (Web of Science: Science Citation Index Expanded), Chinese Biomedicine Database (CBM), and China Knowledge Resource Integrated Database (CNKI) have been searched for relevant studies published between 1 January 2003 and 1 October 2014. We have established inclusion and exclusion criteria to identify RCTs, which were suitable to be enrolled in the systematic review. The comparison group could be hypertonic saline (HS), hydroxyethyl starch, or others. The quality assessment was based on the Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.1 and modified Jadad score scale. The major outcome was mortality, followed by the secondary outcomes such as neurological outcome, days on intensive care unit (ICU), and ventilator day. In addition, intracranial pressure (ICP), cerebral perfusion pressure (CPP), and mean arterial pressure (MAP) were used as the surrogate endpoints. Data synthesis and meta-analysis was conducted by using R (version 3.7-0.).
RESULTS
When 176 potential relevant literatures and abstracts have been screened, four RCTs met all the inclusion criteria and were enrolled for the meta-analysis. Amongst all the enrolled studies, two trials have provided the primary outcome data. There was no heterogeneity between two studies (I (2) = 0 %) and a fixed model was used for meta-analysis (n = 53), pooled result indicated that the mortality was similar in mannitol intervention and control treatment, OR = 0.80, 95 % CI [0.27, 2.37], P = 0.38. We found that both mannitol and HS were efficient in decreasing the ICP. Furthermore, the effect of the HS on the ICP appeared to be more effective in the patients with diffuse brain injuries than mannitol did.
CONCLUSIONS
As a conclusion, the mannitol therapy cannot reduce the mortality risk of acute severe traumatic brain injury. Current evidence does not support the mannitol as an effective treatment of acute severe traumatic brain injury. The well-designed randomized controlled trials are in urgent need to demonstrate the adoption of mannitol to acute severe traumatic brain injury.
PubMed: 27574654
DOI: 10.1186/s41038-015-0006-8 -
Clinical Infectious Diseases : An... Nov 2014Childhood gut dysfunction (enteropathy) is common in resource-poor environments. Stunting is its presumed major consequence. Identification of biomarkers of gut... (Review)
Review
Childhood gut dysfunction (enteropathy) is common in resource-poor environments. Stunting is its presumed major consequence. Identification of biomarkers of gut dysfunction could identify the presence of, and, ideally, assess interventions for, enteropathy. Classically, enteropathy has been identified histopathologically. However, less invasive assays may be more sensitive for detecting earlier perturbations reflecting specific functional derangements. The most commonly used test has been the urinary lactulose to mannitol ratio (L:M), which primarily assesses gut leakiness, and which also measures absorption. We systematically reviewed the L:M literature published from 2000 to 2010 pertinent to children in developing country settings, and identified 25 relevant publications representing heterogeneous studies. We conclude that the L:M test has many attributes, including reflecting 2 physiologic processes (absorption and permeability) and likely correlation with growth failure consequent to child gut dysfunction. However, improved test technical performance, data reporting, and correlation with host phenotypes are needed to maximize the utility of this test.
Topics: Biomarkers; Child, Preschool; Developing Countries; Diagnostic Techniques, Digestive System; Environment; Humans; Infant; Infant, Newborn; Intestinal Diseases; Lactulose; Mannitol; Nutrition Disorders; Poverty
PubMed: 25305289
DOI: 10.1093/cid/ciu541 -
CJEM Sep 2016As part of the Canadian Journal of Emergency Medicine's (CJEM) developing social media strategy, 1 we are collaborating with the Skeptics' Guide to Emergency Medicine... (Meta-Analysis)
Meta-Analysis Review
As part of the Canadian Journal of Emergency Medicine's (CJEM) developing social media strategy, 1 we are collaborating with the Skeptics' Guide to Emergency Medicine (SGEM) to summarize and critically appraise the current emergency medicine (EM) literature using evidence-based medicine principles. In the "Hot Off the Press" series, we select original research manuscripts published in CJEM to be featured on the SGEM website/podcast and discussed by the study authors and the online EM community. A similar collaboration is under way between the SGEM and Academic Emergency Medicine. What follows is a summary of the selected article, the immediate post-publication synthesis from the SGEM podcast, commentary by the first author, and the subsequent discussion from the SGEM blog and other social media. Through this series, we hope to enhance the value, accessibility, and application of important, clinically relevant EM research. In this, the second SGEM HOP hosted collaboratively with CJEM, we discuss a systematic review evaluating the use of hypertonic saline in the treatment of severe traumatic brain injury. 2.
Topics: Brain Injuries, Traumatic; Canada; Emergency Medicine; Emergency Service, Hospital; Evidence-Based Medicine; Female; Glasgow Coma Scale; Hospital Mortality; Humans; Injury Severity Score; Male; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic; Risk Assessment; Saline Solution, Hypertonic; Survival Analysis
PubMed: 27618977
DOI: 10.1017/cem.2016.374