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Clinical Toxicology (Philadelphia, Pa.) Dec 2020Paracetamol (acetaminophen) remains a leading cause of poisoning in Europe, North America, and Australia. For over four decades, acetylcysteine has been the antidote of...
BACKGROUND
Paracetamol (acetaminophen) remains a leading cause of poisoning in Europe, North America, and Australia. For over four decades, acetylcysteine has been the antidote of choice. However, despite the use of acetylcysteine, some patients who ingest very large doses of paracetamol or who reach hospital late in the course of their poisoning, develop acute liver failure. Some will develop metabolic acidosis indicating mitochondrial toxicity.
OBJECTIVE
We review the experimental and clinical data reported with the use of cimetidine, fomepizole, and calmangafodipir in the treatment of paracetamol toxicity to determine if these treatments alone or in combination with acetylcysteine might be of benefit.
METHODS
We searched Ovid Medline 1946-2020, Embase 1947-2020, Scopus 2004-2020, Cochrane Databases of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), and clinicaltrials.gov 1997-2020 for records including the concepts of paracetamol poisoning and cimetidine, fomepizole, calmangafodipir, and acetylcysteine. We included basic science studies in animals and all available study types in humans. We reviewed the reference lists of included articles to search for references missed in the original search. We registered the protocol in PROSPERO.
RESULTS
We completed all search strategies on 20 August 2019, 27 January 2020, and 15 June 2020. These produced 6,826 citations. We identified and deleted 2,843 duplicate resulting in a total of 3,856 unique citations. After applying inclusion and exclusion criteria, 89 studies remained. The largest numbers of studies described the past use of cimetidine, and the more recent use of fomepizole. There is good animal evidence that cimetidine blocks CYP 2E1 with the potential to inhibit the toxic metabolism of paracetamol. Early case reports were inconclusive regarding the benefit to humans in paracetamol poisoning. Two comparative trials found no benefit of cimetidine in paracetamol poisoning, but few patients had severe poisoning. There is good animal evidence that fomepizole blocks CYP 2E1 with the potential to inhibit the toxic metabolism of paracetamol. There are no comparative trials of fomepizole for acute paracetamol poisoning. Case reports are inconclusive due to multiple other interventions including the use of acetylcysteine in all cases. The benefit of fomepizole as adjunct treatment has not been demonstrated. Calmangafodipir, a drug mimicking superoxide dismutase, has emerged as a potential treatment for severe paracetamol toxicity because the formation of superoxide free radicals appears to explain part of the mitochondrial toxicity of extremely large paracetamol overdoses. Calmangafodipir has reached Phase I/II trial of safety in humans with acute paracetamol overdose. Planning for a Phase III study of efficacy is currently underway.
CONCLUSIONS
The vast majority of patients with acute paracetamol overdose enjoy excellent outcomes with acetylcysteine alone. Although cimetidine and fomepizole inhibit CYP 2E1 in animals, there is insufficient evidence to recommend their use either as a primary treatment or adjunct therapy in paracetamol poisoning. Calmangafodipir remains investigational.
Topics: Acetaminophen; Acetylcysteine; Acidosis; Animals; Antidotes; Cimetidine; Drug Overdose; Edetic Acid; Fomepizole; Humans; Mitochondria; Pyridoxal Phosphate
PubMed: 32762579
DOI: 10.1080/15563650.2020.1798979 -
Evidence-based Complementary and... 2022Due to the limited treatment options in antibiotic-associated diarrhea (AAD) in children, more effective treatments should be explored. Traditional Chinese medicine... (Review)
Review
BACKGROUND
Due to the limited treatment options in antibiotic-associated diarrhea (AAD) in children, more effective treatments should be explored. Traditional Chinese medicine (TCM) has a long history in China, which has produced a pretty effect in clinical practice. Many randomized clinical trials (RCTs) have explored the effect of traditional Chinese medicine on treating AAD in children. However, there has been no systematic review or meta-analysis on the impact of TCM on AAD in children. The aim of this study was to systematically review RCTs on the effect of TCM in children with AAD.
METHODS
RCTs in the past ten years on TCM for AAD in children were included. We searched Electronic databases as much as possible. This paper was registered in PROSPERO (CRD42022301034).
RESULTS
26 studies were included in this systematic review. 25 studies reported the effects of TCM interventions on the total effective rate (RR = 1.20, CI 1.16 to 1.24; < 0.001). 7 studies reported the effects of TCM interventions on the time to change the shape of feces (MD = -1.37, CI -1.67 to -1.07; < 0.001). 17 studies reported the effects of TCM interventions (MD = -1.43, CI -1.71 to -1.15; < 0.001). The pooled results showed that there were no significant differences between the two groups in CD3+, CD4+, CD8+, CD4 : CD8, time for bowel sounds to return to normal, hs-CRP, and IgM. There was a significant difference between the two groups in frequency of diarrhea on the third day after TCM intervention, vomiting improvement time, diamine oxidase, IL-8, TNF, IgA, IgG, and average hospital stay.
CONCLUSIONS
TCM interventions combined with conventional therapy can improve the therapeutic effect of AAD in children. However, future studies are still needed for the low methodological quality.
PubMed: 36185092
DOI: 10.1155/2022/6108772 -
PloS One 2021Silver diamine fluoride (SDF) is used in minimally invasive dentistry for arresting dental caries. However, discoloration of teeth is a significant side effect that has...
The effect of the combined use of silver diamine fluoride and potassium iodide in disrupting the plaque biofilm microbiome and alleviating tooth discoloration: A systematic review.
Silver diamine fluoride (SDF) is used in minimally invasive dentistry for arresting dental caries. However, discoloration of teeth is a significant side effect that has limited the use of SDF. Hence, the application of potassium iodide (KI) following SDF has been proposed to ameliorate the staining. Although antimicrobial activity is one of the major mechanisms of the caries-arresting effect of SDF, the antimicrobial potency of SDF/KI combination is unclear. Thus, the primary objective of this systematic review was to appraise the studies on the antimicrobial efficacy of SDF/KI combination on cariogenic microbes. The secondary objective was to summarize the evidence on the potential of KI in reducing the discoloration associated with the application of SDF. Electronic databases of Medline via PubMed, Cochrane Library, Web of Science, and EBSCO host were searched for English language manuscripts from January 2005 to 15th November 2020. The reference lists of these manuscripts were manually searched for additional studies. Twelve studies were included in the final analysis, seven of which have investigated the antimicrobial efficacy of SDF/KI, and the rest have examined the anti-staining potential of KI. The exploratory findings from the reviewed articles revealed the promising antimicrobial potential of SDF/KI on cariogenic microbes associated with dentine caries. There is, however, contradictory evidence on the effect of SDF/KI on tooth color. The reviewed in-vitro studies indicated significant effectiveness of KI in preventing staining. A clinical trial on primary dentition showed 25% reduction in the incidence of staining by SDF after applying KI, while a clinical study on root caries in adults showed no significant effect. Within the methodological limitations of this review, we conclude that for arresting dental caries, SDF could be combined with KI, as there may be a lower likelihood of staining. Further, well-designed clinical trials on the antimicrobial and anti-staining effect of SDF/KI are needed to obtain more robust evidence.
Topics: Biofilms; Dental Plaque; Drug Combinations; Fluorides, Topical; Humans; Microbiota; Potassium Iodide; Quaternary Ammonium Compounds; Silver Compounds; Tooth Discoloration
PubMed: 34115788
DOI: 10.1371/journal.pone.0252734 -
Hormones (Athens, Greece) Jun 2019Thyroid incidentaloma is defined as a thyroid lesion incidentally and newly detected by imaging techniques performed for an unrelated purpose and especially for a...
INTRODUCTION
Thyroid incidentaloma is defined as a thyroid lesion incidentally and newly detected by imaging techniques performed for an unrelated purpose and especially for a non-thyroid disease. The aim of this review is to evaluate the prevalence and clinical significance of focal incidental radiolabelled prostate-specific membrane antigen (PSMA) uptake in the thyroid gland [PSMA thyroid incidentaloma (PTI)] revealed by PET/CT or PET/MRI.
METHODS
A comprehensive literature search of the PubMed/MEDLINE, Scopus, and Embase databases was conducted to find relevant published articles about the prevalence and clinical significance of PTIs detected by PET/CT or PET/MRI in patients studied for other oncologic purposes.
RESULTS
Twelve articles were included in the systematic review. Among 23 PTIs, 6 were malignant (5 primary thyroid tumors and one metastasis from renal cell carcinoma), one was a follicular lesion of undetermined significance, and the rest were benign.
CONCLUSION
Despite being very rare, though probably underestimated, PTIs frequently signal the presence of unexpected lesions in the thyroid which differ from the indicated reason for which the patient was initially scanned and concerning which the risk of malignancy is not negligible.
Topics: Adenoma; Edetic Acid; Gallium Isotopes; Gallium Radioisotopes; Humans; Incidental Findings; Male; Oligopeptides; Positron Emission Tomography Computed Tomography; Prostatic Neoplasms; Thyroid Neoplasms
PubMed: 30989578
DOI: 10.1007/s42000-019-00106-8 -
Contact Dermatitis May 2011Multiple studies have evaluated diverse allergens in paediatric populations. Consensus is still lacking on which allergens are most commonly implicated in allergic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Multiple studies have evaluated diverse allergens in paediatric populations. Consensus is still lacking on which allergens are most commonly implicated in allergic contact dermatitis.
OBJECTIVES
To evaluate the proportion of positive reactions for allergens tested in children and to identify allergens with positive reactions in at least 1% of them.
METHODS
This was a systematic review of studies in PubMed (1966-2010) investigating allergens in at least 100 enrolled children. Proportions of positive reactions for each allergen were combined with random effects models across studies.
RESULTS
We included 49 studies with available data on 170 allergens. Each study tested a median of two allergens. Among the 94 allergens evaluated by at least two studies, 58 had estimates of positive reactions of at least 1% by random effects calculations, and for 21 of them the 95% confidence interval ensured that the proportion of positive reactions was at least 1%. The top five allergens tested by at least two studies included nickel sulfate, ammonium persulfate, gold sodium thiosulfate, thimerosal, and toluene-2,5-diamine (p-toluenediamine). For most allergens, the proportion of positive reactions was higher in studies published after 1995 than in earlier studies (p = 0.0065).
CONCLUSIONS
This meta-analysis offers guidance on which allergens are most prevalent in the paediatric population and should have priority for inclusion in standardized allergen series.
Topics: Allergens; Child; Dermatitis, Allergic Contact; Humans; Patch Tests
PubMed: 21480911
DOI: 10.1111/j.1600-0536.2010.01860.x -
Clinical Chemistry and Laboratory... Oct 2013Parathyroid hormone (PTH) is relatively unstable: optimisation of pre-analytical conditions, including specimen type, sampling time and storage conditions, is essential.... (Review)
Review
Parathyroid hormone (PTH) is relatively unstable: optimisation of pre-analytical conditions, including specimen type, sampling time and storage conditions, is essential. We have undertaken a systematic review of these pre-analytical conditions. An electronic search of the PubMed, Embase, Cochrane, Centre for Research and Dissemination and Bandolier databases was undertaken. Of 5511 papers identified, 96 underwent full text review, of which 83 were finally included. At room temperature PTH was stable in ethylenediaminetetraacetic acid (EDTA) preserved whole blood for at least 24 h and in EDTA plasma for at least 48 h after venepuncture. Losses were observed in clotted blood samples after 3 h and in serum after 2 h. At 4°C PTH was more stable in EDTA plasma (at least 72 h) than serum (at least 24 h). Central venous PTH concentrations were higher than peripheral venous concentrations. In the northern hemisphere, PTH concentrations were higher in winter than summer. PTH has a circadian rhythm characterised by a nocturnal acrophase and mid-morning nadir. Data related to frozen storage of PTH (-20°C and -80°C) were limited and contradictory. We recommend that blood samples for PTH measurement should be taken into tubes containing EDTA, ideally between 10:00 and 16:00, and plasma separated within 24 h of venepuncture. Plasma samples should be stored at 4°C and analysed within 72 h of venepuncture. Particular regard must be paid to the venepuncture site when interpreting PTH concentration. Further research is required to clarify the suitability of freezing samples prior to PTH measurement.
Topics: Anticoagulants; Blood Specimen Collection; Circadian Rhythm; Databases, Bibliographic; Edetic Acid; Humans; Immunoassay; Parathyroid Hormone; Refrigeration; Seasons; Sensitivity and Specificity; Temperature; Time Factors
PubMed: 24072573
DOI: 10.1515/cclm-2013-0315 -
Journal of Public Health Dentistry Jun 2024This systematic review aimed to review the safety and effectiveness of professionally applied fluorides for preventing and arresting dental caries in low- and... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This systematic review aimed to review the safety and effectiveness of professionally applied fluorides for preventing and arresting dental caries in low- and middle-income countries (LMICs).
METHODS
Randomized controlled trials conducted in LMICs, in which professionally applied fluorides were compared with placebo/no treatment/health education only or usual care with a minimum one-year follow-up period, were included. Any topically applied fluoride agents such as sodium fluoride (NaF), acidulated phosphate fluoride, silver diamine fluoride (SDF), and nano silver fluoride (NSF) were included. Five databases (PubMed, Embase, Scopus, Web of Science, and Cochrane Library) were searched in May 2022. Meta-analysis was conducted using a random effect model.
RESULTS
This review included 33 studies for qualitative synthesis, encompassing 16,375 children aged between 1.5 and 14 years. Nevertheless, the meta-analysis focused on only 17 studies, involving 4067 children. Fourteen papers assessed potential adverse events, none of which was reported as major adverse events. SDF and NSF were identified as effective in arresting caries on primary teeth (p < 0.05) compared with a placebo or no treatment. Fluoride varnish and gel were identified as effective in reducing new caries development on primary teeth (p < 0.05) but not on permanent teeth (p > 0.05). The certainty of the generated evidence obtained is low.
CONCLUSION
The review provides valuable insights into the use of professionally applied fluorides in LMICs and contributes to recommendations for their use. However, the limited rigorous evidence suggests the need for further research to strengthen these findings and draw more robust conclusions.
Topics: Humans; Dental Caries; Developing Countries; Fluorides, Topical; Child; Child, Preschool; Adolescent; Cariostatic Agents; Infant; Fluorides; Silver Compounds; Randomized Controlled Trials as Topic; Quaternary Ammonium Compounds
PubMed: 38623701
DOI: 10.1111/jphd.12617 -
AJR. American Journal of Roentgenology Mar 2021Early diagnosis is important in the overall management of prostate cancer (PCa). Gallium-68-labeled prostate-specific membrane antigen (PSMA) PET/CT has an established... (Meta-Analysis)
Meta-Analysis
Early diagnosis is important in the overall management of prostate cancer (PCa). Gallium-68-labeled prostate-specific membrane antigen (PSMA) PET/CT has an established role in the detection of recurrent disease and staging of patients with intermediate- to high-risk PCa. However, only a small number of studies have evaluated its role in the initial diagnosis of PCa. This systematic review was conducted to evaluate the diagnostic performance of Ga-PSMA PET/CT in the initial detection of PCa in patients with clinical or biochemical findings suspicious for PCa. This systematic review followed PRISMA guidelines. Searches in PubMed, Scopus, and Embase were conducted using relevant keywords, and articles published through April 30, 2020, were included. Using histopathology results as the reference standard, the numbers of true- and false-positives and true- and false-negatives were extracted. Pooled estimates of diagnostic test accuracy-including sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and summary ROC (SROC) curve-were generated using bivariate random-effects meta-analysis. Seven studies comprising 389 patients were included in the systematic review and meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio for the initial diagnosis of PCa using Ga-PSMA PET/CT were 0.97 (95% CI, 0.90-0.99), 0.66 (95% CI, 0.52-0.78), 2.86 (95% CI, 1.95-4.20), and 0.05 (95% CI, 0.01-0.15), respectively. The test had high accuracy; the area under the SROC curve was 0.91 (95% CI, 0.88-0.93). Gallium-68-labeled PSMA PET/CT had excellent sensitivity and negative likelihood ratio in the initial diagnosis of PCa in patients with clinical or biochemical findings suspicious for PCa. Gallium-68-labeled PSMA PET/CT had high diagnostic accuracy for the initial detection of PCa in patients with clinical or biochemical findings suspicious for PCa and has potential utility as a rule-out test for these patients.
Topics: Adult; Aged; Aged, 80 and over; Edetic Acid; False Negative Reactions; False Positive Reactions; Gallium Isotopes; Gallium Radioisotopes; Humans; Likelihood Functions; Male; Middle Aged; Oligopeptides; Positron Emission Tomography Computed Tomography; Prostatic Neoplasms; Publication Bias; Radiopharmaceuticals; Sensitivity and Specificity
PubMed: 32755196
DOI: 10.2214/AJR.20.23912 -
The Cochrane Database of Systematic... Nov 2015In cardiac ischaemia, the accumulation of adenosine may lead to or exacerbate bradyasystole and diminish the effectiveness of catecholamines administered during... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In cardiac ischaemia, the accumulation of adenosine may lead to or exacerbate bradyasystole and diminish the effectiveness of catecholamines administered during resuscitation. Aminophylline is a competitive adenosine antagonist. Case studies suggest that aminophylline may be effective for atropine-resistant bradyasystolic arrest.
OBJECTIVES
To determine the effects of aminophylline in the treatment of patients in bradyasystolic cardiac arrest, primarily survival to hospital discharge. We also considered survival to admission, return of spontaneous circulation, neurological outcomes and adverse events.
SEARCH METHODS
For this updated review, we searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, LILACS, ClinicalTrials.gov and WHO International Clinical Trials Registry Platform in November 2014. We checked the reference lists of retrieved articles, reviewed conference proceedings, contacted experts and searched further using Google.
SELECTION CRITERIA
All randomised controlled trials comparing intravenous aminophylline with administered placebo in adults with non-traumatic, normothermic bradyasystolic cardiac arrest who were treated with standard advanced cardiac life support (ACLS).
DATA COLLECTION AND ANALYSIS
Two review authors independently reviewed the studies and extracted the included data. We contacted study authors when needed. Pooled risk ratio (RR) was estimated for each study outcome. Subgroup analysis was predefined according to the timing of aminophylline administration.
MAIN RESULTS
We included five trials in this analysis, all of which were performed in the prehospital setting. The risk of bias was low in four of these studies (n = 1186). The trials accumulated 1254 participants. Aminophylline was found to have no effect on survival to hospital discharge (risk ratio (RR) 0.58, 95% confidence interval (CI) 0.12 to 2.74) or on secondary survival outcome (survival to hospital admission: RR 0.92, 95% CI 0.61 to 1.39; return of spontaneous circulation: RR 1.15, 95% CI 0.89 to 1.49). Survival was rare (6/1254), making data about neurological outcomes and adverse events quite limited. The planned subgroup analysis for early administration of aminophylline included 37 participants. No one in the subgroup survived to hospital discharge.
AUTHORS' CONCLUSIONS
The prehospital administration of aminophylline in bradyasystolic arrest is not associated with improved return of circulation, survival to admission or survival to hospital discharge. The benefits of aminophylline administered early in resuscitative efforts are not known.
Topics: Aged; Aminophylline; Bradycardia; Cardiotonic Agents; Female; Humans; Injections, Intravenous; Male; Out-of-Hospital Cardiac Arrest; Randomized Controlled Trials as Topic; Survival Analysis
PubMed: 26593309
DOI: 10.1002/14651858.CD006781.pub3