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Anais Da Academia Brasileira de Ciencias 2024Cyanotoxins pose a health threat when present in the drinking water supply since conventional water treatment processes are not effective in removing extracellular...
Cyanotoxins pose a health threat when present in the drinking water supply since conventional water treatment processes are not effective in removing extracellular metabolites hence, advanced treatment techniques are usually applied. Powdered activated carbon (PAC) is an effective adsorbent for removing toxins. However, since a high volume is necessary, alternative adsorbents have been investigated. Biochar, especially from renewable sources, is a potential adsorbent material that could replace PAC for removing toxins. This paper aimed to investigate which PAC properties play key roles in cyanotoxin adsorption by a systematic review addressing the adsorption of toxins such as microcystins-LR (MC-LR), cylindrospermopsin (CYL), and saxitoxins (STXs). As a result, the review showed that some commonly adopted indices (i.e. total surface area) are not relevant to cyanotoxin adsorption, especially if appraised alone. Along with a multi-barrier approach, PAC has to be applied taking into account the complexity of the water system, which includes a better understanding of the characteristics of the adsorbent, the target toxin, and the aqueous medium. The biochar systematic review showed that no studies have yet been designed specifically for the removal of toxins. Since biochar has not yet been applied to water treatment processes, the knowledge gap is even greater than for PAC.
Topics: Charcoal; Adsorption; Cyanobacteria Toxins; Knowledge; Powders
PubMed: 38198398
DOI: 10.1590/0001-3765202320230061 -
JAMA Network Open Jan 2024The NAPOLI 3 trial showed the superiority of fluorouracil, leucovorin, liposomal irinotecan, and oxaliplatin (NALIRIFOX) over the combination of gemcitabine and... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The NAPOLI 3 trial showed the superiority of fluorouracil, leucovorin, liposomal irinotecan, and oxaliplatin (NALIRIFOX) over the combination of gemcitabine and nab-paclitaxel (GEM-NABP) as first-line treatment of metastatic pancreatic ductal adenocarcinoma (PDAC). Analyses comparing NALIRIFOX and GEM-NABP with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) have not yet been reported.
OBJECTIVE
To derive survival, response, and toxic effects data from phase 3 clinical trials and compare NALIRIFOX, FOLFIRINOX, and GEM-NABP.
DATA SOURCES
After a systematic search of PubMed, Scopus, Embase, and American Society of Clinical Oncology and European Society for Medical Oncology meetings' libraries, Kaplan-Meier curves were extracted from phase 3 clinical trials conducted from January 1, 2011, until September 12, 2023.
STUDY SELECTION
Phase 3 clinical trials that tested NALIRIFOX, FOLFIRINOX, or GEM-NABP as first-line treatment of metastatic PDAC and reported overall survival (OS) and progression-free survival (PFS) curves were selected. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses of Individual Participant Data reporting guidelines.
DATA EXTRACTION AND SYNTHESIS
Individual patient OS and PFS data were extracted from Kaplan-Meier plots of original trials via a graphic reconstructive algorithm. Overall response rates (ORRs) and grade 3 or higher toxic effects rates were also collected. A pooled analysis was conducted, and results were validated via a network meta-analysis.
MAIN OUTCOMES AND MEASURES
The primary end point was OS. Secondary outcomes included PFS, ORR, and toxic effects rates.
RESULTS
A total of 7 trials with data on 2581 patients were analyzed, including 383 patients treated with NALIRIFOX, 433 patients treated with FOLFIRINOX, and 1756 patients treated with GEM-NABP. Median PFS was longer in patients treated with NALIRIFOX (7.4 [95% CI, 6.1-7.7] months) or FOLFIRINOX (7.3 [95% CI, 6.5-7.9] months; [HR], 1.21 [95% CI, 0.86-1.70]; P = .28) compared with patients treated with GEM-NABP (5.7 [95% CI, 5.6-6.1] months; HR vs NALIRIFOX, 1.45 [95% CI, 1.22-1.73]; P < .001). Similarly, GEM-NABP was associated with poorer OS (10.4 [95% CI, 9.8-10.8]; months) compared with NALIRIFOX (HR, 1.18 [95% CI, 1.00-1.39]; P = .05], while no difference was observed between FOLFIRINOX (11.7 [95% CI, 10.4-13.0] months) and NALIRIFOX (11.1 [95% CI, 10.1-12.3] months; HR, 1.06 [95% CI, 0.81-1.39]; P = .65). There were no statistically significant differences in ORR among NALIRIFOX (41.8%), FOLFIRINOX (31.6%), and GEM-NABP (35.0%). NALIRIFOX was associated with lower incidence of grade 3 or higher hematological toxic effects (eg, platelet count decreased 1.6% vs 11.8% with FOLFIRINOX and 10.8% with GEM-NABP), but higher rates of severe diarrhea compared with GEM-NABP (20.3% vs 15.7%).
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis, NALIRIFOX and FOLFIRINOX were associated with similar PFS and OS as first-line treatment of advanced PDAC, although NALIRIFOX was associated with a different toxicity profile. Careful patient selection, financial toxic effects consideration, and direct comparison between FOLFIRINOX and NALIRIFOX are warranted.
Topics: Humans; Pancreatic Neoplasms; Irinotecan; Antineoplastic Combined Chemotherapy Protocols; Leucovorin; Oxaliplatin; Gemcitabine; Fluorouracil; Adenocarcinoma
PubMed: 38190183
DOI: 10.1001/jamanetworkopen.2023.50756 -
The Western Journal of Emergency... Nov 2023Acetaminophen poisoning is commonly treated by emergency physicians. First-line therapy is N-acetylcysteine (NAC), traditionally administered intravenously via a US Food...
INTRODUCTION
Acetaminophen poisoning is commonly treated by emergency physicians. First-line therapy is N-acetylcysteine (NAC), traditionally administered intravenously via a US Food and Drug Administration (FDA)-approved three-bag protocol in which each bag has a unique concentration and infusion duration. Recently, simplified, off-label two-bag NAC infusion protocols have become more common. The purpose of this review is to summarize the effectiveness and safety of two-bag NAC.
METHODS
We undertook a comprehensive search of PubMed, EMBASE, and MEDLINE from inception to December 13, 2022, for articles describing human acetaminophen poisonings treated with two-bag NAC, defined as any regimen involving two discrete infusions in two separate bags. Outcomes included effectiveness (measured by incidence of liver injury); incidence of non-allergic anaphylactoid reactions (NAAR); gastrointestinal, cutaneous, and systemic reactions; treatments for NAARs; incidence of NAC-related medication errors; and delays or interruptions in NAC administration.
RESULTS
Twelve articles met final inclusion, 10 of which compared two-bag NAC to the three-bag regimen. Nine articles evaluated the two-bag/20-hour regimen, a simplified version of the FDA-approved three-bag regimen in which the traditional first and second bags are combined into a single four-hour infusion. Nine articles assessed comparative effectiveness of two-bag NAC in terms of liver injury, most commonly assessed for by incidence of hepatotoxicity (aspartate aminotransferase or alanine aminotransferase >1,000 international units per liter). No difference in liver injury was observed between two-bag and three-bag regimens. Of nine articles comparing incidence of NAARs, eight demonstrated statistically fewer NAARs with two-bag regimens, and one showed no difference. In seven articles evaluating treatment for NAARs (antihistamines, corticosteroids, epinephrine), all showed that patients received fewer medications for NAARs with two-bag NAC. Three articles evaluated NAC-related medication errors; two demonstrated no difference, while one study evaluating only children showed fewer errors with two-bag NAC. Two studies evaluated delays and/or interruptions in NAC infusions; both favored two-bag NAC.
CONCLUSION
For patients with acetaminophen poisoning, two-bag NAC regimens appear to have similar outcomes to the traditional three-bag regimen in terms of liver injury. Two-bag NAC regimens are associated with fewer adverse events and fewer treatments for those events than the three-bag regimen and fewer interruptions in antidotal therapy.
Topics: Child; Humans; Acetaminophen; Acetylcysteine; Analgesics, Non-Narcotic; Antidotes; Drug Overdose; Drug-Related Side Effects and Adverse Reactions; Infusions, Intravenous
PubMed: 38165196
DOI: 10.5811/westjem.59099 -
Waste Management (New York, N.Y.) Feb 2024Biochar obtained from sewage sludge serves as a valuable soil amendment in agriculture, enhancing soil properties by increasing the nutrient content, cation exchange...
Biochar obtained from sewage sludge serves as a valuable soil amendment in agriculture, enhancing soil properties by increasing the nutrient content, cation exchange capacity, water retention, and oxygen transmission. However, its utilisation is hampered by the presence of micropollutants such as polycyclic aromatic hydrocarbons (PAHs), polychlorinated dibenzodioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), polychlorinated biphenyls (PCBs), and volatile organic compounds (VOCs). Previous studies indicate that the type and amount of micropollutants can be significantly adjusted by selecting the right process parameters. This literature review provides an overview of how (1) pyrolysis temperature, (2) carrier gas flow and type, (3) heating rate, and (4) residence time affect the concentration of micropollutants in biochar produced from sewage sludge. The micropollutants targeted are those listed by the European Biochar Certificate (EBC) and by the International Biochar Institution (IBI), including PAHs, PCDD/Fs, PCBs and VOCs. In addition, per- and poly-fluoroalkyl substances (PFAS) are also considered due to their presence in sewage sludge. The findings suggest that higher pyrolysis temperatures reduce micropollutant levels. Moreover, the injection of a carrier gas (N or CO) during the pyrolysis and cooling processes effectively lowers PAHs and PCDD/Fs, by reducing the contact of biochar with oxygen, which is crucial in mitigating micropollutants. Nevertheless, limited available data impedes an assessment of the impact of these parameters on PFAS in biochar. In addition, further research is essential to understand the effects of carrier gas type, heating rate, and residence time in order to determine the optimal pyrolysis process parameters for generating clean biochar.
Topics: Sewage; Polychlorinated Dibenzodioxins; Polychlorinated Biphenyls; Dibenzofurans; Pyrolysis; Charcoal; Polycyclic Aromatic Hydrocarbons; Soil; Oxygen; Fluorocarbons
PubMed: 38154418
DOI: 10.1016/j.wasman.2023.12.036 -
Clinical Oncology (Royal College of... Feb 2024The combination of 5-fluorouracil/leucovorin (5-FU/LV) plus oxaliplatin (FOLFOX) is widely acknowledged as the standard regimen for second-line treatment in patients... (Meta-Analysis)
Meta-Analysis
AIMS
The combination of 5-fluorouracil/leucovorin (5-FU/LV) plus oxaliplatin (FOLFOX) is widely acknowledged as the standard regimen for second-line treatment in patients with advanced biliary tract cancer. Nanoliposomal irinotecan (nal-IRI) has demonstrated its activity in patients with advanced pancreatic cancer. Recent studies have investigated the activity of nal-IRI in combination with 5-FU/LV for biliary tract cancer. However, the results have been contradictory. We conducted a meta-analysis to assess survival outcomes and response rates in randomised trials investigating the activity of nal-IRI in previously treated biliary tract cancer patients.
MATERIALS AND METHODS
We systematically collected potentially relevant findings from PubMed/Medline, the Cochrane library and EMBASE. Abstracts presented at major international oncological meetings were also reviewed. We extracted hazard ratios and 95% confidence intervals for progression-free survival and overall survival, as well as odds ratios and 95% confidence intervals for objective response rate. The outcomes of the accessible randomised studies evaluating the activity of nal-IRI plus 5-FU/LV were analysed.
RESULTS
The combination therapy exhibited a statistically significant decrease in the risk of progression (hazard ratio 0.70; 95% confidence interval 0.50-0.97) when compared with 5-FU/LV alone. Additionally, the dual regimen yielded longer overall survival and a higher objective response rate.
CONCLUSION
Our meta-analysis showed that nal-IRI plus 5-FU/LV had a superior activity in comparison with 5-FU/LV. Further investigations are required to elucidate the role of nal-IRI in this setting and to identify subgroups of patients who could derive the greatest benefit from its administration.
Topics: Humans; Antineoplastic Combined Chemotherapy Protocols; Biliary Tract Neoplasms; Fluorouracil; Irinotecan; Leucovorin; Liposomes; Pancreatic Neoplasms
PubMed: 38129199
DOI: 10.1016/j.clon.2023.12.005 -
Environmental Science and Pollution... Jan 2024Pyrolysis has become an interesting waste valorization method leading to an increasing number of research studies in this field in the last decade. The present study...
Pyrolysis has become an interesting waste valorization method leading to an increasing number of research studies in this field in the last decade. The present study aims to provide a comprehensive knowledge map of scientific production in pyrolysis, discuss the current state of research, and identify the main research hotspots and trends in recent years. The systematic review, supported by analysis of countries and institutions, keyword co-occurrence analysis, analysis of keyword trends, journal analysis, and article impact, was carried out on 6234 journal articles from the Science Citation Index Expanded database of the Web of Science Core Collection. As a result, four main research hotspots were identified: 1) characterization techniques and pyrolysis kinetic models, 2) biochar production and its main applications, 3) bio-oil production and catalytic pyrolysis, and 4) co-pyrolysis, which has become a consolidated research hotspot since 2018. Additionally, the main challenges and opportunities for future research have been identified, such as 1) the development of multi-step kinetic models for studying complex wastes, 2) the integration of biochar into other valorization processes, such as anaerobic digestion, and 3) the development of catalytic hydropyrolysis for the valorization of organic waste. This bibliometric analysis provides a visualization of the current context and future trends in pyrolysis, facilitating future collaborative research and knowledge exchange.
Topics: Bibliometrics; Catalysis; Charcoal; Pyrolysis
PubMed: 38036906
DOI: 10.1007/s11356-023-31186-0 -
Cureus Oct 2023In recent times, novel oral anticoagulants (NOACs)/direct oral anticoagulants (DOACs) have emerged as an alternative to the traditionally used Vitamin K oral... (Review)
Review
In recent times, novel oral anticoagulants (NOACs)/direct oral anticoagulants (DOACs) have emerged as an alternative to the traditionally used Vitamin K oral antagonists (VKA) like warfarin for the treatment of atrial fibrillation (AF). This systematic review and meta-analysis aims to evaluate the efficacy and safety of NOACs in patients with AF and, thus, the related thromboembolic risks and sequelae. Of the 131 published articles we examined, 11 were included in an in-depth systematic review. The articles we reviewed were from the past ten years, from 2013 onward. The analysis derived the efficacy and safety of NOACs in patients with AF and also included different patients' baseline characteristics and subgroups. This systematic review reiterates previous research findings of superior efficacy and safety of the use of NOACs in the AF population and also illuminates certain head-to-head comparisons of individual NOACs with warfarin. It digressed into subgroups of patients with different baseline characteristics to provide evidence and support the existing guidelines for the use of NOACs in the treatment of AF. Overall, there is marked efficacy and safety of NOACs in patients with AF, be they elderly or Asian, with decreased renal function, or with other comorbidities. Adherence to NOACs was also satisfactory. Despite such a review, there needs to be more research on vast subgroups and also on reversal antidotes like andexanet alfa and idarucizumab, as well as more head-to-head analysis between NOACs over a long duration of study, which would provide more answers and pinpoint reasons as to the differences that exist between demographics and subgroups in the usage of NOACs.
PubMed: 37927673
DOI: 10.7759/cureus.46385 -
BMC Pharmacology & Toxicology Nov 2023Aluminum phosphide toxicity is a serious problem in many countries. Unfortunately, there is no specific antidote. N-acetylcysteine has been used in some studies as... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Aluminum phosphide toxicity is a serious problem in many countries. Unfortunately, there is no specific antidote. N-acetylcysteine has been used in some studies as adjuvant therapy depending on to its antioxidant properties. We hypothesized that IV N-acetylcysteine is effective in reducing mortality rate compared to supportive treatment alone.
METHODS
We searched in PubMed, Scopus, Web of Science, and Cochrane Library databases. We only included randomized controlled trials that assessed the efficacy of IV N-acetylcysteine and supportive treatment versus supportive treatment alone in acute aluminum phosphide poisoning. Four investigators independently screened the studies' results and designed the data extraction sheet. The primary and secondary outcomes were mortality and the need for mechanical ventilation rates. Random effects estimators with weights were used to result in the pooled risk ratios.
RESULTS
We included four randomized controlled trials with 177 patients. 91 patients were distributed in N-acetylcysteine group and 86 patients in the control group. Mortality rates in N-acetylcysteine group and in the control group were 43.95% 66.27% respectively. There was a statistically significant reduction in mortality rate after leave out test (pooled risk ratio, 0.5; 95% confidence interval, 0.32-0.77). Regarding the need for mechanical ventilation, it was measured only in three RCTs. It was assessed in 67 patients in N-acetylcysteine group and 60 patients in the control group. 24 patients were ventilated in N-acetylcysteine group (35.8%) and 29 patients in the control group (48.3%). But it was statistically nonsignificant (pooled risk ratio, 0.71; 95% confidence interval, 0.48-1.04).
CONCLUSION
Our meta-analysis revealed that IV N-acetylcysteine may be effective in reducing mortality of severe aluminum phosphide poisoning cases.
TRIAL REGISTRATION
Registration number in Prospero CRD42022375344 on 25 NOVEMBER 2022, retrospectively registered.
Topics: Humans; Acetylcysteine; Antioxidants; Aluminum Compounds; Phosphines
PubMed: 37924139
DOI: 10.1186/s40360-023-00699-2 -
Clinical Otolaryngology : Official... Jan 2024Ototoxicity is a common disabling side effect of platinum-based chemotherapy. This study aimed to assess the evidence on the management of platinum-induced ototoxicity... (Review)
Review
OBJECTIVES
Ototoxicity is a common disabling side effect of platinum-based chemotherapy. This study aimed to assess the evidence on the management of platinum-induced ototoxicity in adult cancer patients.
METHODS
Four databases were searched up to 1 November 2022. Original studies were included if they reported on a pharmacologic or non-pharmacologic intervention to prevent or treat platinum ototoxicity in adults. The articles' quality was assessed via two grading scales.
RESULTS
Nineteen randomised controlled trials and five quasi-experimental studies with 1673 patients were analysed. Eleven interventions were identified, nine pharmacological and two non-pharmacological. Six of the interventions (sodium thiosulphate, corticoids, sertraline, statins, multivitamins and D-methionine) showed mild benefits in preventing cisplatin-induced ototoxicity. Only one trial assessed corticoids as a potential treatment. Overall, only six trials were deemed with a low risk of bias. The majority of studies inadequately documented intervention-related adverse effects, thereby limiting safety conclusions.
CONCLUSIONS
Current interventions have mild benefits in preventing cisplatin-induced ototoxicity in adult cancer patients. Sodium thiosulphate is the most promising intervention as a preventive strategy. Rigorous, high-quality research is warranted, encompassing an evaluation of all potential symptoms and innovative treatment modalities.
Topics: Adult; Humans; Cisplatin; Antineoplastic Agents; Carboplatin; Ototoxicity; Hearing Loss; Neoplasms; Adrenal Cortex Hormones; Randomized Controlled Trials as Topic
PubMed: 37818931
DOI: 10.1111/coa.14106 -
European Journal of Cardio-thoracic... Oct 2023Literature is scarce on the management of patients using direct oral anticoagulants (DOACs) undergoing elective, urgent and emergency surgery. Therefore, we summarize... (Review)
Review
OBJECTIVES
Literature is scarce on the management of patients using direct oral anticoagulants (DOACs) undergoing elective, urgent and emergency surgery. Therefore, we summarize the current evidence and provide literature-based recommendations for the management of patients on DOACs in the perioperative phase.
METHODS
A general literature review was conducted on the pharmacology of DOACs and for recommendations on the management of cardiac surgical patients on DOACs. Additionally, we performed a systematic review for studies on the use of direct DOAC reversal agents in the emergency cardiac surgical setting.
RESULTS
When surgery is elective, the DOAC cessation strategy is relatively straightforward and should be adapted to the renal function. The same approach applies to urgent cases, but additional DOAC activity drug level monitoring tests may be useful. In emergency cases, idarucizumab can be safely administered to patients on dabigatran in any of the perioperative phases. However, andexanet alfa, which is not registered for perioperative use, should not be administered in the preoperative phase to reverse the effect of factor Xa inhibitors, as it may induce temporary heparin resistance. Finally, the administration of (activated) prothrombin complex concentrate may be considered in all patients on DOACs, and such concentrates are generally readily available.
CONCLUSIONS
DOACs offer several advantages over vitamin K antagonists, but care must be taken in patients undergoing cardiac surgery. Although elective and urgent cases can be managed relatively straightforwardly, the management of emergency cases requires particular attention.
Topics: Humans; Administration, Oral; Anticoagulants; Cardiac Surgical Procedures; Dabigatran; Hemorrhage; Heparin
PubMed: 37812245
DOI: 10.1093/ejcts/ezad340