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Journal of the National Cancer Institute Aug 2019FOLFIRINOX is a standard treatment for metastatic pancreatic cancer patients. The effectiveness of neoadjuvant FOLFIRINOX in patients with borderline resectable... (Meta-Analysis)
Meta-Analysis
BACKGROUND
FOLFIRINOX is a standard treatment for metastatic pancreatic cancer patients. The effectiveness of neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer (BRPC) remains debated.
METHODS
We performed a systematic review and patient-level meta-analysis on neoadjuvant FOLFIRINOX in patients with BRPC. Studies with BRPC patients who received FOLFIRINOX as first-line neoadjuvant treatment were included. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival, resection rate, R0 resection rate, and grade III-IV adverse events. Patient-level survival outcomes were obtained from authors of the included studies and analyzed using the Kaplan-Meier method.
RESULTS
We included 24 studies (8 prospective, 16 retrospective), comprising 313 (38.1%) BRPC patients treated with FOLFIRINOX. Most studies (n = 20) presented intention-to-treat results. The median number of administered neoadjuvant FOLFIRINOX cycles ranged from 4 to 9. The resection rate was 67.8% (95% confidence interval [CI] = 60.1% to 74.6%), and the R0-resection rate was 83.9% (95% CI = 76.8% to 89.1%). The median OS varied from 11.0 to 34.2 months across studies. Patient-level survival data were obtained for 20 studies representing 283 BRPC patients. The patient-level median OS was 22.2 months (95% CI = 18.8 to 25.6 months), and patient-level median progression-free survival was 18.0 months (95% CI = 14.5 to 21.5 months). Pooled event rates for grade III-IV adverse events were highest for neutropenia (17.5 per 100 patients, 95% CI = 10.3% to 28.3%), diarrhea (11.1 per 100 patients, 95% CI = 8.6 to 14.3), and fatigue (10.8 per 100 patients, 95% CI = 8.1 to 14.2). No deaths were attributed to FOLFIRINOX.
CONCLUSIONS
This patient-level meta-analysis of BRPC patients treated with neoadjuvant FOLFIRINOX showed a favorable median OS, resection rate, and R0-resection rate. These results need to be assessed in a randomized trial.
Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug-Related Side Effects and Adverse Reactions; Female; Fluorouracil; Humans; Irinotecan; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Oxaliplatin; Pancreatic Neoplasms; Progression-Free Survival; Treatment Outcome
PubMed: 31086963
DOI: 10.1093/jnci/djz073 -
World Journal of Gastrointestinal... Dec 2019Propofol is commonly used for sedation during endoscopic procedures. Data suggests its superiority to traditional sedatives used in endoscopy including benzodiazepines...
BACKGROUND
Propofol is commonly used for sedation during endoscopic procedures. Data suggests its superiority to traditional sedatives used in endoscopy including benzodiazepines and opioids with more rapid onset of action and improved post-procedure recovery times for patients. However, Propofol requires administration by trained healthcare providers, has a narrow therapeutic index, lacks an antidote and increases risks of cardio-pulmonary complications.
AIM
To compare, through a systematic review of the literature and meta-analysis, sedation with propofol to traditional sedatives with or without propofol during endoscopic procedures.
METHODS
A literature search was performed using MEDLINE, Scopus, EMBASE, the Cochrane Library, Scopus, LILACS, BVS, Cochrane Central Register of Controlled Trials, and The Cumulative Index to Nursing and Allied Health Literature databases. The last search in the literature was performed on March, 2019 with no restriction regarding the idiom or the year of publication. Only randomized clinical trials with full texts published were included. We divided sedation therapies to the following groups: (1) Propofol versus benzodiazepines and/or opiate sedatives; (2) Propofol versus Propofol with benzodiazepine and/or opioids; and (3) Propofol with adjunctive benzodiazepine and opioid versus benzodiazepine and opioid. The following outcomes were addressed: Adverse events, patient satisfaction with type of sedation, endoscopists satisfaction with sedation administered, dose of propofol administered and time to recovery post procedure. Meta-analysis was performed using RevMan5 software version 5.39.
RESULTS
A total of 23 clinical trials were included ( = 3854) from the initial search of 6410 articles. For Group I (Propofol benzodiazepine and/or opioids): The incidence of bradycardia was not statistically different between both sedation arms (RD: -0.01, 95%CI: -0.03-+0.01, : 22%). In 10 studies, the incidence of hypotension was not statistically difference between sedation arms (RD: 0.01, 95%CI: -0.02-+0.04, : 0%). Oxygen desaturation was higher in the propofol group but not statistically different between groups (RD: -0.03, 95%CI: -0.06-+0.00, : 25%). Patients were more satisfied with their sedation in the benzodiazepine + opioid group compared to those with monotherapy propofol sedation (MD: +0.89, 95%CI: +0.62-+1.17, : 39%). The recovery time after the procedure showed high heterogeneity even after outlier withdrawal, there was no statistical difference between both arms (MD: -15.15, 95%CI: -31.85-+1.56, : 99%). For Group II (Propofol propofol with benzodiazepine and/or opioids): Bradycardia had a tendency to occur in the Propofol group with benzodiazepine and/or opioid-associated (RD: -0.08, 95%CI: -0.13--0.02, : 59%). There was no statistical difference in the incidence of bradycardia (RD: -0.00, 95%CI: -0.08-+0.08, : 85%), desaturation (RD: -0.00, 95%CI: -0.03-+0.02, : 44%) or recovery time (MD: -2.04, 95%CI: -6.96-+2.88, : 97%) between sedation arms. The total dose of propofol was higher in the propofol group with benzodiazepine and/or opiates but with high heterogeneity. (MD: 70.36, 95%CI: +53.11-+87.60, : 61%). For Group III (Propofol with benzodiazepine and opioid benzodiazepine and opioid): Bradycardia and hypotension was not statistically significant between groups (RD: -0.00, 95%CI: -0.002-+0.02, : 3%; RD: 0.04, 95%CI: -0.05-+0.13, : 77%). Desaturation was evaluated in two articles and was higher in the propofol + benzodiazepine + opioid group, but with high heterogeneity (RD: 0.15, 95%CI: 0.08-+0.22, : 95%).
CONCLUSION
This meta-analysis suggests that the use of propofol alone or in combination with traditional adjunctive sedatives is safe and does not result in an increase in negative outcomes in patients undergoing endoscopic procedures.
PubMed: 31839876
DOI: 10.4253/wjge.v11.i12.573 -
Toxins Oct 2021Uremic pruritus is a distressful complication of chronic kidney disease and results in impaired quality of life and higher mortality rates. Intravenous sodium... (Meta-Analysis)
Meta-Analysis
Uremic pruritus is a distressful complication of chronic kidney disease and results in impaired quality of life and higher mortality rates. Intravenous sodium thiosulfate has been reported to alleviate pruritus in hemodialysis patients. We performed a systematic review and meta-analysis to estimate the efficacy of intravenous sodium thiosulfate in patients with uremic pruritus. A systematic search of electronic databases up to June 2021 was conducted for randomized controlled trials that evaluated the clinical effects of sodium thiosulfate in the management of patients with uremic pruritus. Two reviewers selected eligible articles and evaluated the risk of bias; the results of pruritus assessment and uremic pruritus-related laboratory parameters in selected studies were analyzed. There are four trials published between 2018 and 2021, which include 222 participants. The sodium thiosulfate group displayed significant decrease in the pruritus score (standardized mean difference = -3.52, 95% confidence interval = -5.63 to -1.41, = 0.001), without a significant increase in the adverse effects (risk ratio = 2.44, 95% confidence interval = 0.37 to 15.99, = 0.35) compared to the control group. Administration of sodium thiosulfate is found to be a safe and efficacious complementary therapy in improving uremic pruritus in patients with chronic kidney disease.
Topics: Antioxidants; Humans; Pruritus; Randomized Controlled Trials as Topic; Thiosulfates; Uremia; Vasodilator Agents
PubMed: 34822553
DOI: 10.3390/toxins13110769 -
BMC Cancer Jul 2020Pancreatic cancer has a poor prognosis and few choices of therapy. For patients with adequate performance status, FOLFIRINOX or gemcitabine plus nab-paclitaxel are... (Comparative Study)
Comparative Study Meta-Analysis
Meta-analysis examining overall survival in patients with pancreatic cancer treated with second-line 5-fluorouracil and oxaliplatin-based therapy after failing first-line gemcitabine-containing therapy: effect of performance status and comparison with other regimens.
BACKGROUND
Pancreatic cancer has a poor prognosis and few choices of therapy. For patients with adequate performance status, FOLFIRINOX or gemcitabine plus nab-paclitaxel are preferred first-line treatment. 5-Fluorouracil (5-FU)-based therapy (e.g. FOLFIRI, OFF, or FOLFOX) are often used in patients who previously received gemcitabine-based regimens. A systematic review was conducted of the safety and efficacy of FOLFOX for metastatic pancreatic cancer following prior gemcitabine-based therapy. A Bayesian fixed-effect meta-analysis with adjustment of patient performance status (PS) was conducted to evaluate overall survival (OS) and compare outcomes with nanoliposomal irinotecan combination therapy.
METHODS
PubMed.gov , FDA.gov , ClinicalTrials.gov , congress abstracts, Cochrane.org library, and EMBASE database searches were conducted to identify randomized controlled trials of advanced/metastatic disease, prior gemcitabine-based therapy, and second-line treatment with 5-FU and oxaliplatin. The database search dates were January 1, 1990-June 30, 2019. Endpoints were OS and severe treatment-related adverse events (TRAEs). Trial-level PS scores were standardized by converting Karnofsky grade scores to Eastern Cooperative Oncology Group (ECOG) Grade, and overall study-weighted PS was calculated based on weighted average of all patients.
RESULTS
Of 282 studies identified, 11 randomized controlled trials (N = 454) were included in the meta-analysis. Baseline weighted PS scores predicted OS in 10 of the 11 studies, and calculated PS scores of 1.0 were associated with a median OS of 6.3 months (95% posterior interval, 5.4-7.4). After adjusting for baseline PS, FOLFOX had a similar treatment effect profile (median OS, range 2.6-6.7 months) as 5-FU/leucovorin plus nanoliposomal irinotecan therapy (median OS, 6.1 months; 95% confidence interval 4.8-8.9). Neutropenia and fatigue were the most commonly reported Grade 3-4 TRAEs associated with FOLFOX.
CONCLUSIONS
Baseline PS is a strong prognostic factor when interpreting the efficacy of 5-FU and oxaliplatin-based therapy of pancreatic cancer after progression on first-line gemcitabine-based regimens. When baseline PS is considered, FOLFOX has a similar treatment effect as 5-FU and nanoliposomal irinotecan therapy and a comparable safety profile. These findings suggest that 5-FU and oxaliplatin-based therapies remain an acceptable and alternative second-line treatment option for patients with pancreatic cancer and adequate PS (e.g. ECOG 0-1) following gemcitabine treatment.
Topics: Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Drug Resistance, Neoplasm; Drug-Related Side Effects and Adverse Reactions; Fluorouracil; Humans; Karnofsky Performance Status; Leucovorin; Organoplatinum Compounds; Oxaliplatin; Pancreatic Neoplasms; Prognosis; Randomized Controlled Trials as Topic; Risk Factors; Survival Analysis; Treatment Outcome; Gemcitabine
PubMed: 32641104
DOI: 10.1186/s12885-020-07110-x -
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 -
Journal of Environmental Management Feb 2024Biofiltration utilizes natural mechanisms including biodegradation and biotransformation along with other physical processes for the removal of organic micropollutants... (Review)
Review
Biofiltration utilizes natural mechanisms including biodegradation and biotransformation along with other physical processes for the removal of organic micropollutants (OMPs) such as pharmaceuticals, personal care products, pesticides and industrial compounds found in (waste)water. In this systematic review, a total of 120 biofiltration studies from 25 countries were analyzed, considering various biofilter configurations, source water types, biofilter media and scales of operation. The study also provides a bibliometric analysis to identify the emerging research trends in the field. The results show that granular activated carbon (GAC) either alone or in combination with another biofiltration media can remove a broad range of OMPs efficiently. The impact of pre-oxidation on biofilter performance was investigated, revealing that pre-oxidation significantly improved OMP removal and reduced the empty bed contact time (EBCT) needed to achieve a consistently high OMP. Biofiltration with pre-oxidation had median removals ranging between 65% and >90% for various OMPs at 10-45 min EBCT with data variability drastically reducing beyond 20 min EBCT. Biofiltration without pre-oxidation had lower median removals with greater variability. The results demonstrate that pre-oxidation greatly enhances the removal of adsorptive and poorly biodegradable OMPs, while its impact on other OMPs varies. Only 19% of studies we reviewed included toxicity testing of treated effluent, and even fewer measured transformation products. Several studies have previously reported an increase in effluent toxicity because of oxidation, although it was successfully abated by subsequent biofiltration in most cases. Therefore, the efficacy of biofiltration treatment should be assessed by integrating toxicity testing into the assessment of overall removal.
Topics: Filtration; Water Purification; Water Pollutants, Chemical; Charcoal; Water
PubMed: 38325285
DOI: 10.1016/j.jenvman.2024.120203 -
BMC Nephrology Jan 2024Up to now, there is no unequivocal intervention to mitigate vascular calcification (VC) in patients with hemodialysis. This network meta-analysis aimed to systematically... (Meta-Analysis)
Meta-Analysis
Comparative efficacy of sodium thiosulfate, bisphosphonates, and cinacalcet for the treatment of vascular calcification in patients with haemodialysis: a systematic review and network meta-analysis.
BACKGROUND
Up to now, there is no unequivocal intervention to mitigate vascular calcification (VC) in patients with hemodialysis. This network meta-analysis aimed to systematically evaluate the clinical efficacy of sodium thiosulfate, bisphosphonates, and cinacalcet in treating vascular calcification.
METHODS
A comprehensive study search was performed using PubMed, Web of Science, the Cochrane Library, EMBASE and China National Knowledge Internet (CNKI) to collect randomized controlled trials (RCTs) of sodium thiosulfate, bisphosphonates, and cinacalcet for vascular calcification among hemodialysis patients. Then, network meta-analysis was conducted using Stata 17.0 software.
RESULTS
In total, eleven RCTs including 1083 patients were qualified for this meta-analysis. We found that cinacalcet (SMD - 0.59; 95% CI [-0.95, -0.24]) had significant benefit on vascular calcification compared with conventional therapy, while sodium thiosulfate or bisphosphonates did not show such efficiency. Furthermore, as for ranking the efficacy assessment, cinacalcet possessed the highest surface under the cumulative ranking curve (SUCRA) value (88.5%) of lessening vascular calcification and was superior to sodium thiosulfate (50.4%) and bisphosphonates (55.4%). Thus, above results suggested that cinacalcet might be the most promising drug for vascular calcification treatment in hemodialysis patients. Mechanistically, our findings illustrated that cinacalcet reduced serum calcium (SMD - 1.20; 95% CI [-2.08, - 0.33]) and showed the tendency in maintaining the balance of intact Parathyroid Hormone (iPTH) level.
CONCLUSIONS
This network meta-analysis indicated that cinacalcet appear to be more effective than sodium thiosulfate and bisphosphonates in mitigating vascular calcification through decreasing serum calcium and iPTH. And cinacalcet might be a reasonable option for hemodialysis patients with VC in clinical practice.
SYSTEMATIC REVIEW REGISTRATION
[ http://www.crd.york.ac.uk/PROSPERO ], identifier [CRD42022379965].
Topics: Humans; Diphosphonates; Cinacalcet; Network Meta-Analysis; Calcium; Vascular Calcification; Randomized Controlled Trials as Topic; Thiosulfates
PubMed: 38254024
DOI: 10.1186/s12882-024-03460-x -
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 -
Nature Communications Nov 2021FOLFIRINOX, a combination of chemotherapy drugs (Fluorouracil, Oxaliplatin, Irinotecan -FOI), provides the best clinical benefit in pancreatic ductal adenocarcinoma... (Meta-Analysis)
Meta-Analysis
FOLFIRINOX, a combination of chemotherapy drugs (Fluorouracil, Oxaliplatin, Irinotecan -FOI), provides the best clinical benefit in pancreatic ductal adenocarcinoma (PDAC) patients. In this study we explore the role of miRNAs (MIR) as modulators of chemosensitivity to identify potential biomarkers of response. We find that 41 and 84 microRNA inhibitors enhance the sensitivity of Capan1 and MiaPaCa2 PDAC cells respectively. These include a MIR1307-inhibitor that we validate in further PDAC cell lines. Chemotherapy-induced apoptosis and DNA damage accumulation are higher in MIR1307 knock-out (MIR1307KO) versus control PDAC cells, while re-expression of MIR1307 in MIR1307KO cells rescues these effects. We identify binding of MIR1307 to CLIC5 mRNA through covalent ligation of endogenous Argonaute-bound RNAs cross-linking immunoprecipitation assay. We validate these findings in an in vivo model with MIR1307 disruption. In a pilot cohort of PDAC patients undergoing FOLFIRONX chemotherapy, circulating MIR1307 correlates with clinical outcome.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; DNA Damage; Fluorouracil; Gene Expression Regulation, Neoplastic; Humans; Irinotecan; Kaplan-Meier Estimate; Leucovorin; MicroRNAs; Neoadjuvant Therapy; Outcome Assessment, Health Care; Oxaliplatin; Pancreatic Neoplasms
PubMed: 34795259
DOI: 10.1038/s41467-021-27099-6 -
Scientific Reports Oct 2021Treatment outcomes between FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) and GNP (gemcitabine with albumin-bound paclitaxel) as first-line... (Meta-Analysis)
Meta-Analysis
Treatment outcomes between FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) and GNP (gemcitabine with albumin-bound paclitaxel) as first-line chemotherapy regimens for metastatic pancreatic cancer (PC) were assessed according to ethnic groups categorized as Western or Asian subgroups. PubMed, EMBASE, and Cochrane library were searched. Thirteen studies were eligible in this meta-analysis. Overall survival was not significantly different between FOLFIRINOX and GNP (HR 1.00, 95% CI 0.83-1.20, P = 0.990). However, the Western subgroup showed a higher survival benefit for FOLFIRINOX over GNP (HR 0.84, 95% CI 0.74-0.95, P = 0.006) whereas the Asian subgroup showed the survival benefit for GNP over FOLFIRINOX (HR 1.29, 95% CI 1.03-1.60, P = 0.030). Progression free survival was not significantly different between the two regimens in the Western subgroup (HR 1.01, 95% CI 0.84-1.20, P = 0.950) and the Asian subgroup (HR 1.13, 95% CI 0.97-1.33, P = 0.110). Occurrence of febrile neutropenia was significantly higher in FOLFIRINOX at both ethnic subgroups; however, that of peripheral neuropathy was significantly higher only in GNP of the Asian subgroup. Therefore, pharmacoethnicity might be a factor worth considering when deciding on a frontline chemotherapeutic regimen although the overall survival was not significantly different between FOLFIRINOX and GNP for metastatic PCs.
Topics: Albumins; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Ethnicity; Fluorouracil; Humans; Irinotecan; Leucovorin; Neoplasm Metastasis; Oxaliplatin; Paclitaxel; Pancreatic Neoplasms; Treatment Outcome; Gemcitabine
PubMed: 34635731
DOI: 10.1038/s41598-021-99647-5