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Critical Care (London, England) Feb 2023Ethylene glycol (EG) is metabolized into glycolate and oxalate and may cause metabolic acidemia, neurotoxicity, acute kidney injury (AKI), and death. Historically,...
Ethylene glycol (EG) is metabolized into glycolate and oxalate and may cause metabolic acidemia, neurotoxicity, acute kidney injury (AKI), and death. Historically, treatment of EG toxicity included supportive care, correction of acid-base disturbances and antidotes (ethanol or fomepizole), and extracorporeal treatments (ECTRs), such as hemodialysis. With the wider availability of fomepizole, the indications for ECTRs in EG poisoning are debated. We conducted systematic reviews of the literature following published EXTRIP methods to determine the utility of ECTRs in the management of EG toxicity. The quality of the evidence and the strength of recommendations, either strong ("we recommend") or weak/conditional ("we suggest"), were graded according to the GRADE approach. A total of 226 articles met inclusion criteria. EG was assessed as dialyzable by intermittent hemodialysis (level of evidence = B) as was glycolate (Level of evidence = C). Clinical data were available for analysis on 446 patients, in whom overall mortality was 18.7%. In the subgroup of patients with a glycolate concentration ≤ 12 mmol/L (or anion gap ≤ 28 mmol/L), mortality was 3.6%; in this subgroup, outcomes in patients receiving ECTR were not better than in those who did not receive ECTR. The EXTRIP workgroup made the following recommendations for the use of ECTR in addition to supportive care over supportive care alone in the management of EG poisoning (very low quality of evidence for all recommendations): i) Suggest ECTR if fomepizole is used and EG concentration > 50 mmol/L OR osmol gap > 50; or ii) Recommend ECTR if ethanol is used and EG concentration > 50 mmol/L OR osmol gap > 50; or iii) Recommend ECTR if glycolate concentration is > 12 mmol/L or anion gap > 27 mmol/L; or iv) Suggest ECTR if glycolate concentration 8-12 mmol/L or anion gap 23-27 mmol/L; or v) Recommend ECTR if there are severe clinical features (coma, seizures, or AKI). In most settings, the workgroup recommends using intermittent hemodialysis over other ECTRs. If intermittent hemodialysis is not available, CKRT is recommended over other types of ECTR. Cessation of ECTR is recommended once the anion gap is < 18 mmol/L or suggested if EG concentration is < 4 mmol/L. The dosage of antidotes (fomepizole or ethanol) needs to be adjusted during ECTR.
Topics: Humans; Antidotes; Fomepizole; Ethanol; Renal Dialysis; Glycolates; Ethylene Glycol; Poisoning
PubMed: 36765419
DOI: 10.1186/s13054-022-04227-2 -
Therapeutic Advances in Neurological... 2023Intravenous thrombolysis (IVT) is standard of care for disabling acute ischemic stroke (AIS) within a time window of ⩽ 4.5 h. Some AIS patients cannot be treated...
BACKGROUND AND AIMS
Intravenous thrombolysis (IVT) is standard of care for disabling acute ischemic stroke (AIS) within a time window of ⩽ 4.5 h. Some AIS patients cannot be treated with IVT due to limiting contraindications, including heparin usage in an anticoagulating dose within the past 24 h or an elevated activated prothrombin time (aPTT) > 15 s. Protamine is a potent antidote to unfractionated heparin.
OBJECTIVES
The objective of this study was to investigate the safety and efficacy of IVT in AIS patients after antagonization of unfractionated heparin with protamine.
METHODS
Patients from our stroke center (between January 2015 and September 2021) treated with IVT after heparin antagonization with protamine were analyzed. National Institutes of Health Stroke Scale (NIHSS) was used for stroke severity and modified Rankin Scale (mRS) for outcome assessment. Substantial neurological improvement was defined as the difference between admission and discharge NIHSS of ⩾8 or discharge NIHSS of ⩽1. Good outcome at follow-up after 3 months was defined as mRS 0-2. Safety data were obtained for mortality, symptomatic intracerebral hemorrhage (sICH), and for adverse events due to protamine. Second, a systematic review was performed searching PubMed and Scopus for studies and case reviews presenting AIS patients treated with IVT after heparin antagonization with protamine. The search was limited from January 1, 2011 to September 29, 2021. Furthermore, we conducted a propensity score matching comparing protamine-treated patients to a control IVT group without protamine (ratio 2:1, match tolerance 0.2).
RESULTS
A total of 16 patients, 5 treated in our hospital and 11 from literature, [65.2 ± 13.1 years, 37.5% female, median premorbid mRS (pmRS) 1 (IQR 1, 4)] treated with IVT after heparin antagonization using protamine were included and compared to 31 IVT patients [76.2 ± 10.9 years, 45% female, median pmRS 1 (IQR 0, 2)]. Substantial neurological improvement was evident in 68.8% of protamine-treated patients 38.7% of control patients ( = 0.028). Good clinical outcome at follow-up was observed in 56.3% 58.1% of patients ( = 0.576). No adverse events due to protamine were reported, one patient suffered sICH after secondary endovascular thrombectomy of large vessel occlusion. Mortality was 6.3% 22.6% ( = 0.236).
CONCLUSION
IVT after heparin antagonization with protamine seems to be safe and, prospectively, may extend the number of AIS patients who can benefit from reperfusion treatment using IVT. Further prospective registry trials would be helpful to further investigate the clinical applicability of heparin antagonization.
PubMed: 36710724
DOI: 10.1177/17562864221149249 -
Cancer Treatment Reviews Feb 2023The aim of this review was to characterize the second- and later-line (≥2L) treatment landscape for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). (Review)
Review
INTRODUCTION
The aim of this review was to characterize the second- and later-line (≥2L) treatment landscape for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC).
METHODS
This systematic literature review (PROSPERO: CRD42021279753) involved searches of MEDLINE® and Embase to identify results from prospective studies of ≥2L treatment options for metastatic pancreatic cancer published from 2016 to 2021. Publications were screened according to predetermined eligibility criteria; population-level data were extracted using standardized data fields. Publication quality was assessed according to Grading of Recommendations Assessment, Development and Evaluation (GRADE). The data were analyzed descriptively, grouped by drug class.
RESULTS
Sixty publications were identified, including 23 relating to comparative trials. GRADE assessment found that, of these 23 trials, 83% reported high or moderate-quality evidence. Of the publications relating to comparative trials, nine (three trials) reported favorable results: the pivotal phase 3 NAPOLI-1 trial for liposomal irinotecan; a phase 3 trial of non-liposomal irinotecan within the FOLFIRINOX regimen; and a phase 2 trial of eryaspase plus chemotherapy.
CONCLUSIONS
The level of unmet need for ≥2L treatment options for mPDAC remains high. Irinotecan-based regimens currently offer the greatest promise. Investigations into paradigm-changing agents and combination approaches continue.
Topics: Humans; Pancreatic Neoplasms; Irinotecan; Fluorouracil; Antineoplastic Combined Chemotherapy Protocols; Prospective Studies; Leucovorin; Adenocarcinoma; Carcinoma, Pancreatic Ductal
PubMed: 36641880
DOI: 10.1016/j.ctrv.2022.102502 -
Environmental Pollution (Barking, Essex... Feb 2023Over the last several decades, extensive and inefficient use of contemporary technologies has resulted in substantial environmental pollution, predominantly caused by...
Over the last several decades, extensive and inefficient use of contemporary technologies has resulted in substantial environmental pollution, predominantly caused by potentially hazardous elements (PTEs), like heavy metals that severely harm living species. To combat the presence of heavy metals (HMs) in the agrarian system, biochar becomes an attractive approach for stabilizing and limiting availability of HMs in soils due to its high surface area, porosity, pH, aromatic structure as well as several functional groups, which mostly rely on the feedstock and pyrolysis temperature. Additionally, agricultural waste-derived biochar is an effective management option to ensure carbon neutrality and circular economy while also addressing social and environmental concerns. Given these diverse parameters, the present systematic evaluation seeks to (i) ascertain the effectiveness of heavy metal immobilization by agro waste-derived biochar; (ii) examine the presence of biochar on soil physico-chemical, and thermal properties, along with microbial diversity; (iii) explore the underlying mechanisms responsible for the reduction in heavy metal concentration; and (iv) possibility of biochar implications to advance circular economy approach. The collection of more than 200 papers catalogues the immobilization efficiency of biochar in agricultural soil and its impacts on soil from multi-angle perspectives. The data gathered suggests that pristine biochar effectively reduced cationic heavy metals (Pb, Cd, Cu, Ni) and Cr mobilization and uptake by plants, whereas modified biochar effectively reduced As in soil and plant systems. However, the exact mechanism underlying is a complex biochar-soil interaction. In addition to successfully immobilizing heavy metals in the soil, the application of biochar improved soil fertility and increased agricultural productivity. However, the lack of knowledge on unfavorable impacts on the agricultural systems, along with discrepancies between the use of biochar and experimental conditions, impeded a thorough understanding on a deeper level.
Topics: Ecosystem; Soil Pollutants; Metals, Heavy; Charcoal; Soil
PubMed: 36608723
DOI: 10.1016/j.envpol.2022.120937 -
Clinical Toxicology (Philadelphia, Pa.) Dec 2022Dexmedetomidine is an alpha-2 adrenoceptor agonist which is widely used for sedation. Dexmedetomidine does not suppress the respiratory drive and produces a state of...
INTRODUCTION
Dexmedetomidine is an alpha-2 adrenoceptor agonist which is widely used for sedation. Dexmedetomidine does not suppress the respiratory drive and produces a state of cooperative sedation; it may be associated with beneficial outcomes in the general critical care population. The role of dexmedetomidine in the treatment of toxicologic conditions (excluding alcohol withdrawal) is unclear.
OBJECTIVES
To critically assess and summarize the literature regarding the use of dexmedetomidine in toxicologic conditions other than alcohol withdrawal.
METHODS
We performed a systematic review of the medical literature to identify all existing evidence regarding the use of dexmedetomidine for toxicologic conditions. We excluded reviews and commentary, studies reporting exclusively on alcohol withdrawal, and studies reporting the use of dexmedetomidine to treat iatrogenic sedative withdrawal in the intensive care unit. We also performed a review of the Toxicology Investigators Consortium (ToxIC) database for patients treated with dexmedetomidine.
RESULTS
We identified 98 studies meeting inclusion criteria; 87 of these were case reports or case series, representing 99 unique cases. Eleven articles with other designs were identified, which included 138 patients treated with dexmedetomidine for toxicologic conditions. Ninety-three cases from the ToxIC registry met inclusion criteria. Common indications for dexmedetomidine included stimulant intoxication, sedative withdrawal, serotonin syndrome, antimuscarinic toxidrome, opioid withdrawal, and cannabinoid intoxication. Dexmedetomidine was usually administered by continuous infusion; bolus administration was reported in a minority of cases. Adverse effects were uncommon. The quality of evidence was generally low, given the preponderance of case reports, the rate of missing or poorly reported data, and the near-universal co-administration of other sedatives.
TREATMENT OF STIMULANT POISONING
Fifty-nine patients with stimulant poisoning were treated with dexmedetomidine. There was reasonably good evidence that dexmedetomidine was helpful in the treatment of stimulant poisoning.
TREATMENT OF SEDATIVE WITHDRAWAL
Twenty-two patients with sedative withdrawal were treated with dexmedetomidine. Several case reports of very high-quality suggested efficacy of dexmedetomidine for this indication, particularly for baclofen withdrawal.
TREATMENT OF SEROTONIN SYNDROME
Twenty-six patients with serotonin syndrome were treated with dexmedetomidine. This evidence was of lower quality due to missing clinical details, potential overdiagnosis of serotonin syndrome, and near-universal concomitant treatment with other sedatives.
TREATMENT OF ANTIMUSCARINIC POISONING
Forty-two patients with antimuscarinic poisoning were treated with dexmedetomidine. This evidence was of low quality and was limited by infrequent use of the preferred antidote, physostigmine.
TREATMENT OF OPIOID WITHDRAWAL
Forty-four patients with opioid withdrawal were treated with dexmedetomidine. This evidence was of low quality due to missing clinical details and near-universal concomitant treatment with other agents. The one high-quality trial reported the use of dexmedetomidine in ultra-rapid opioid detoxification, which is not indicated in modern practice.
TREATMENT OF CANNABINOID INTOXICATION
Five patients with cannabinoid intoxication were treated with dexmedetomidine. No definite conclusion can be drawn from the limited available evidence.
DISCUSSION
It is important to distinguish between the use of dexmedetomidine as a general sedative, which is likely to increase as the overall utilization of dexmedetomidine in critical care settings increases, and the use of dexmedetomidine as a specific pharmacologic treatment for a toxicologic condition. Well-established pharmacologic data from animal and human studies suggest dexmedetomidine counteracts stimulant-induced norepinephrine release. The mechanism by which dexmedetomidine treats sedative withdrawal is unclear. Some animal data show that dexmedetomidine may indirectly suppress serotonin release, which may suggest a role for dexmedetomidine in this condition.
CONCLUSIONS
There is a small and generally low-quality body of evidence which suggests that dexmedetomidine may be helpful in the treatment of certain toxicologic conditions, particularly stimulant intoxication and sedative withdrawal. Further high-quality research is needed to clarify the role of dexmedetomidine in patients with toxicologic conditions.
Topics: Humans; Dexmedetomidine; Analgesics, Opioid; Alcoholism; Muscarinic Antagonists; Serotonin Syndrome; Substance Withdrawal Syndrome; Hypnotics and Sedatives; Narcotics
PubMed: 36346349
DOI: 10.1080/15563650.2022.2138761 -
International Journal of Environmental... Oct 2022Occupational exposure may involve a variety of toxic compounds. A mutagenicity analysis using the Ames test can provide valuable information regarding the toxicity of... (Review)
Review
Occupational exposure may involve a variety of toxic compounds. A mutagenicity analysis using the Ames test can provide valuable information regarding the toxicity of absorbed xenobiotics. Through a search of relevant databases, this systematic review gathers and critically discusses the published papers (excluding other types of publications) from 2001-2021 that have assessed urinary mutagenicity (Ames test with ) in an occupational exposure context. Due to the heterogeneity of the study methods, a meta-analysis could not be conducted. The characterized occupations were firefighters, traffic policemen, bus drivers, mail carriers, coke oven and charcoal workers, chemical laboratory staff, farmers, pharmacy workers, and professionals from several other industrial sectors. The genetically modified bacterial strains (histidine dependent) TA98, TA100, YG1041, YG1021, YG1024 and YG1042 have been used for the health risk assessment of individual (e.g., polycyclic aromatic hydrocarbons) and mixtures of compounds (e.g., diesel engine exhaust, fire smoke, industrial fumes/dyes) in different contexts. Although comparison of the data between studies is challenging, urinary mutagenicity can be very informative of possible associations between work-related exposure and the respective mutagenic potential. Careful interpretation of results and their direct use for occupational health risk assessment are crucial and yet complex; the use of several strains is highly recommended since individual and/or synergistic effects of complex exposure to xenobiotics can be overlooked. Future studies should improve the methods used to reach a standardized protocol for specific occupational environments to strengthen the applicability of the urinary mutagenicity assay and reduce inter- and intra-individual variability and exposure source confounders.
Topics: Humans; Mutagens; Mutagenicity Tests; Coke; Charcoal; Histidine; Vehicle Emissions; Polycyclic Aromatic Hydrocarbons; Smoke; Coloring Agents
PubMed: 36293654
DOI: 10.3390/ijerph192013074 -
Annals of Anatomy = Anatomischer... Jan 2023Tooth whitening is currently one of the most requested treatments to change the color of teeth. There are different types of whitening in the dental office and at home....
INTRODUCTION
Tooth whitening is currently one of the most requested treatments to change the color of teeth. There are different types of whitening in the dental office and at home. There are also many whitening agents on the market. Nowadays, the public has shown great interest in a new natural compound: activated charcoal. It has an abrasive effect and it is included in toothpastes to whiten teeth quickly and easily.
OBJECTIVES
The main objective of the systematic review is to perform a qualitative synthesis of the available literature on the use of activated charcoal-based toothpaste for tooth whitening.
MATERIAL AND METHODS
An electronic search was carried out in PubMed, Web of Science, and Scopus databases. The search included the terms (charcoal-based OR activated charcoal OR charcoal OR soot) AND (toothpaste OR dentifrices OR bleaching OR oral hygiene OR enamel OR teeth). Inclusion criteria were articles that were published in English, that included activated charcoal toothpastes, that assessed the efficacy of activated charcoal bleaching and/or the safety of using activated charcoal toothpastes, that were conducted on humans or extracted teeth regardless of their origin and the year of publication.
RESULTS
Out of 208 articles, 11 met the inclusion criteria, the Risk of Bias of the selected studies was determined as medium-high. Regarding the whitening effect, there is a variety of results depending on the study: in some there are no significant differences between the proposed treatments and in others activated charcoal is not the most whitening agent. Regarding the abrasive effect, most studies agree that activated charcoal toothpaste has a higher abrasive potential.
CONCLUSION
Toothpastes based on activated charcoal possess a lower whitening effect than other alternatives and can be considered as less safe due to its high abrasive potential.
Topics: Humans; Toothpastes; Bleaching Agents; Charcoal; Tooth Bleaching; Tooth
PubMed: 36183933
DOI: 10.1016/j.aanat.2022.151998 -
Farmacia Hospitalaria : Organo Oficial... Jul 2022The purpose of this systematic review is to analyze the published data on the efficacy and safety of doses higher than 180 mg/m2 of irinotecan recommended in the...
Efficacy and safety of high doses of irinotecan in patients with metastatic colorectal cancer treated with the FOLFIRI regimen based on the UGT1A1 genotype: A systematic review.
OBJECTIVE
The purpose of this systematic review is to analyze the published data on the efficacy and safety of doses higher than 180 mg/m2 of irinotecan recommended in the drug's summary of product characteristics in metastatic colorectal cancer patients with genotypes UGT1A1*1/*1 or *1/*28 who are treated with the FOLFIRI regimen.
METHOD
A systematic review of the literature was carried out in Medline and Embase searching for articles published up to December 2021. The methods used were based on the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The criteria for the inclusion of studies were previously defined based on the two secondary goals addressed in this review: 1) To analyze the magnitude of the differences in clinical responses and 2) To study the magnitude of the differences in adverse effects of irinotecan at high doses, as compared to the doses described in the summary of product characteristics corresponding to the FOLFIRI regimen in patients with metastatic colorectal cancer with genotypes UGT1A1*1/* 1 or *1/*28.
RESULTS
The search yielded a total of 985 references, of which 13 were selected for analysis. Seven evaluated both efficacy and safety and six only safety. With regard to the studies that evaluated both efficacy and safety, six out of seven (85.7%) were in favor of increasing irinotecan dose according to the objective response rate and progression-free survival. Two of them even recommended dose increases based on overall survival. Irinotecan safety studies suggest that doses higher than 180 mg/m2 are tolerated by most UGT1A1*1/*1 and *1/*28 patients.
CONCLUSIONS
The present systematic review shows the advisability of considering adjusting the dose of irinotecan when used as part of the FOLFIRI regimen based on the polymorphisms of the UGT1A1 gene as this may increase the likelihood of an adequate clinical response.
Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Fluorouracil; Genotype; Glucuronosyltransferase; Humans; Irinotecan; Leucovorin
PubMed: 36183220
DOI: No ID Found -
European Review For Medical and... Sep 2022Multi-agent regimens such as Folfirinox and gemcitabine plus nab-paclitaxel have shown significant improvements compared with single-agent gemcitabine as neoadjuvant... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of neoadjuvant Folfirinox and Gemcitabine plus Nab-Paclitaxel for borderline resectable and locally advanced pancreatic cancer: a systematic review and meta-analysis.
OBJECTIVE
Multi-agent regimens such as Folfirinox and gemcitabine plus nab-paclitaxel have shown significant improvements compared with single-agent gemcitabine as neoadjuvant chemotherapy for patients with borderline resectable or locally advanced pancreatic cancer. However, the efficacy and safety of Folfirinox and GNP as NAC for BRPC and LAPC is still controversial.
MATERIALS AND METHODS
The eligible studies including prospective, retrospective, and randomized controlled trial related to Folfirinox and GNP as NAC for patients with BRPC or LAPC up to March 2022 were searched and assessed. Pooled analysis for chemotherapy response rate, resection rate, R0 resection rate, progress free survival, overall survival, and grade 3/4 events of toxicity were performed in the study.
RESULTS
Eight studies were included in this meta-analysis. Compared with GNP, Folfirinox had higher resection rate (HR=0.82; 95% CI 0.59-1.14) and R0 resection rate (HR=0.77; 95% CI 0.60-0.97), better PFS (HR=0.78; 95% CI 0.55-1.12) and OS (HR=0.68; 95% CI 0.46-0.99), and without increasing severe toxicity rate (HR=0.95; 95% CI 0.71-1.28). There are no differences in rate of stable disease (HR=1.06; 95% CI 0.92-1.22) and partial/complete regression (HR=0.85; 95% CI 0.59-1.23) between two groups.
CONCLUSIONS
Higher resection and R0 resection rate and better PFS and OS results were obtained in Folfirinox group compared with GNP group for patients with BRPC and LAPC. There was no increased severe toxicity rate for Folfirinox compared with GNP.
Topics: Albumins; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Fluorouracil; Humans; Irinotecan; Leucovorin; Neoadjuvant Therapy; Oxaliplatin; Paclitaxel; Pancreatic Neoplasms; Prospective Studies; Retrospective Studies; Gemcitabine
PubMed: 36111933
DOI: 10.26355/eurrev_202209_29656 -
Journal of Clinical Pharmacy and... Oct 2022Nadolol is a non-selective beta-adrenergic antagonist that is used for the treatment of hypertension and angina. The primary route for its administration is oral. It is... (Review)
Review
WHAT IS KNOWN AND OBJECTIVE
Nadolol is a non-selective beta-adrenergic antagonist that is used for the treatment of hypertension and angina. The primary route for its administration is oral. It is given once daily as it has a longer half-life (t½). The purpose of conducting this systematic review is to provide a comprehensive view of all the available pharmacokinetic (PK) data on nadolol in humans. This review aimed to systematically collate and analyze publish data on the clinical PK of nadolol in humans and this can be beneficial for the clinicians in dosage adjustments.
METHODS
Two electronic databases PubMed and Google Scholar were used for conducting a systematic literature search. All the relevant articles containing PK data of nadolol in humans were retrieved. A total of 1275 articles were searched from both databases and after applying eligibility criteria finally, 22 articles were included for conducting the systematic review.
RESULTS AND DISCUSSION
The area under the plasma concentration curve (AUC) and maximum plasma concentration (C ) of nadolol increased in a dose-dependent manner. The t½ of nadolol was increased to double (18.2-68.6 h) in the patients with chronic kidney disease while the serum t½ became shorter (3.2-4.3 h) when administered to the children. The bioavailability of nadolol was greatly reduced by the coadministration of green tea. Nadolol can be effectively removed by hemodialysis. It undergoes enterohepatic circulation thus activated charcoal decreased its bioavailability.
WHAT IS NEW AND CONCLUSION
Since, there is no previous report of a systematic review on the PK of nadolol, the current review encompasses all the relevant published articles on nadolol in humans. The analysis and understanding of PK parameters (AUC, C , and t½) of nadolol may be helpful in the development and evaluation of PK models.
Topics: Adrenergic beta-Antagonists; Antihypertensive Agents; Charcoal; Child; Humans; Nadolol; Tea
PubMed: 36040016
DOI: 10.1111/jcpt.13764