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Cureus Mar 2023The opioid overdose epidemic is exacerbated by the emergence of Xylazine as an illicit drug adulterant. Xylazine, a veterinary sedative, can potentiate opioid effects... (Review)
Review
INTRODUCTION AND OBJECTIVES
The opioid overdose epidemic is exacerbated by the emergence of Xylazine as an illicit drug adulterant. Xylazine, a veterinary sedative, can potentiate opioid effects while also causing toxic and potentially fatal side effects. This systematic review aims to assess the impact of Xylazine use and overdoses within the opioid epidemic context.
METHOD
A systematic search was conducted following PRISMA guidelines to identify relevant case reports, and case series related to Xylazine use. A comprehensive literature search included databases like Web of Science, PubMed, Embase, and Google Scholar, utilizing keywords and Medical Subject Headings (MeSH) terms related to Xylazine. Thirty-four articles met the inclusion criteria for this review.
RESULTS
Intravenous (IV) administration was a common route for Xylazine use among various methods, including subcutaneous (SC), intramuscular (IM), and inhalation, with overall doses ranging from 40 mg to 4300 mg. The average dose in fatal cases was 1,200 mg, compared to 525 mg in non-fatal cases. Concurrent administration of other drugs, primarily opioids, occurred in 28 cases (47.5%). Intoxication was identified as a notable concern in 32 out of 34 studies, and treatments varied, with the majority experiencing positive outcomes. Withdrawal symptoms were documented in one case study, but the low number of cases with withdrawal symptoms may be attributed to factors such as a limited number of cases or individual variation. Naloxone was administered in eight cases (13.6%), and all patients recovered, although it should not be misconstrued as an antidote for Xylazine intoxication. Of the 59 cases, 21 (35.6%) resulted in fatal outcomes, with 17 involving Xylazine use in conjunction with other drugs. The IV route was a common factor in six out of the 21 fatal cases (28.6%).
CONCLUSION
This review highlights the clinical challenges associated with Xylazine use and its co-administration with other substances, particularly opioids. Intoxication was identified as a major concern, and treatments varied across the studies, including supportive care, naloxone, and other medications. Further research is needed to explore the epidemiology and clinical implications of Xylazine use. Understanding the motivations and circumstances leading to Xylazine use, as well as its effects on users, is essential for developing effective psychosocial support and treatment interventions to address this public health crisis.
PubMed: 37009344
DOI: 10.7759/cureus.36864 -
Pharmacotherapy Sep 2019Hyperlactatemia and lactic acidosis are two syndromes that are associated with morbidity and mortality. Medication-induced hyperlactatemia and lactic acidosis are...
Hyperlactatemia and lactic acidosis are two syndromes that are associated with morbidity and mortality. Medication-induced hyperlactatemia and lactic acidosis are diagnoses of exclusion and have the potential to be overlooked. The purposes of this systematic review are to identify published reports of medication-induced lactate level elevations to aid clinicians in diagnosing and comprehending the underlying mechanism of this rare adverse drug effect and to provide management strategies. The PubMed database was searched for case reports, case series, retrospective studies, and prospective studies describing cases of medication-induced lactate level elevation, including lactic acidosis and hyperlactatemia, published between January 1950 and June 2017. A standardized search strategy was used, and the articles identified underwent two rounds of independent evaluation by two reviewers to assess for inclusion. Articles were included if they described at least one patient older than 12 years with hyperlactatemia or lactic acidosis caused by a medication with United States Food and Drug Administration (FDA) approval and if alternative etiologies for an elevated lactate level were ruled out. Metformin and nucleoside/nucleotide reverse transcriptase inhibitors were excluded since the pathophysiology and incidence of lactic acidosis have been well established for these agents. Overall, 1918 articles were identified, and 101 met inclusion criteria. A total of 286 patients experienced medication-induced lactate level elevations, from which 59 unique medications were identified. The most commonly identified agents were epinephrine and albuterol. Medication-induced lactate level elevation was classified as lactic acidosis (64.0%), hyperlactatemia (31.1%), or not specified (4.9%). The doses ingested included FDA-labeled doses (86%), intentional overdoses (10.8%), or prescribed doses exceeding the FDA-labeled dose (3.1%). Medications were continued without a change (40.8%), were permanently discontinued (34.4%), were continued with a dosage reduction (11.6%), or were initially withheld then resumed after lactate level normalized (2.9%); medication management for the remaining 10.0% was not reported. Forty-six patients died (16%). Six deaths were attributed by treating clinicians to be secondary to medication-induced lactic acidosis. Management strategies were heterogeneous, and treatment included supportive care, exogenous bicarbonate therapy, medication specific antidotes, and decontamination strategies. Unexplained lactate level elevations should prompt clinicians to assess for medication-induced lactate level elevations. Pharmacists are members of the health care team that are well positioned to serve as experts in the diagnosis and management of medication-induced lactate level elevations.
Topics: Acidosis, Lactic; Dose-Response Relationship, Drug; Drug Overdose; Humans; Hyperlactatemia; Prescription Drug Misuse; Prescription Drugs; United States
PubMed: 31361914
DOI: 10.1002/phar.2316 -
The Lancet. Oncology Jun 201635% of patients with pancreatic cancer have unresectable locally advanced disease at diagnosis. Several studies have examined systemic chemotherapy with FOLFIRINOX... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
35% of patients with pancreatic cancer have unresectable locally advanced disease at diagnosis. Several studies have examined systemic chemotherapy with FOLFIRINOX (leucovorin and fluorouracil plus irinotecan and oxaliplatin) in patients with locally advanced pancreatic cancer. We aimed to assess the effectiveness of FOLFIRINOX as first-line treatment in this patient population.
METHODS
We systematically searched Embase, MEDLINE (OvidSP), Web of Science, Scopus, PubMed Publisher, Cochrane, and Google Scholar from July 1, 1994, to July 2, 2015, for studies of treatment-naive patients of any age who received FOLFIRINOX as first-line treatment of locally advanced pancreatic cancer. Our primary outcome was overall survival. Secondary outcomes were progression-free survival; rates of grade 3 or 4 adverse events; and the proportion of patients who underwent radiotherapy or chemoradiotherapy, surgical resection after FOLFIRINOX, and R0 resection. We evaluated survival outcomes with the Kaplan-Meier method with patient-level data. Grade 3 or 4 adverse events, and the proportion of patients who underwent subsequent radiotherapy or chemoradiotherapy or resection, were pooled in a random-effects model.
FINDINGS
We included 13 studies comprising 689 patients, of whom 355 (52%) patients had locally advanced pancreatic cancer. 11 studies, comprising 315 patients with locally advanced disease, reported survival outcomes and were eligible for patient-level meta-analysis. Median overall survival from the start of FOLFIRINOX ranged from 10·0 months (95% CI 4·0-16·0) to 32·7 months (23·1-42·3) across studies with a pooled patient-level median overall survival of 24·2 months (95% CI 21·7-26·8). Median progression-free survival ranged from 3·0 months (95% CI not calculable) to 20·4 months (6·5-34·3) across studies with a patient-level median progression-free survival of 15·0 months (95% 13·8-16·2). In ten studies comprising 490 patients, 296 grade 3 or 4 adverse events were reported (60·4 events per 100 patients). No deaths were attributed to FOLFIRINOX toxicity. The proportion of patients who underwent radiotherapy or chemoradiotherapy ranged from 31% to 100% across studies. In eight studies, 154 (57%) of 271 patients received radiotherapy or chemoradiotherapy after FOLFIRINOX. The pooled proportion of patients who received any radiotherapy treatment was 63·5% (95% CI 43·3-81·6, I(2) 90%). The proportion of patients who underwent surgical resection for locally advanced pancreatic cancer ranged from 0% to 43%. The proportion of patients who had R0 resection of those who underwent resection ranged from 50% to 100% across studies. In 12 studies, 91 (28%) of 325 patients underwent resection after FOLFIRINOX. The pooled proportion of patients who had resection was 25·9% (95% CI 20·2-31·9, I(2) 24%). R0 resection was reported in 60 (74%) of 81 patients. The pooled proportion of patients who had R0 resection was 78·4% (95% CI 60·2-92·2, I(2) 64%).
INTERPRETATION
Patients with locally advanced pancreatic cancer treated with FOLFIRINOX had a median overall survival of 24·2 months-longer than that reported with gemcitabine (6-13 months). Future research should assess these promising results in a randomised controlled trial, and should establish which patients might benefit from radiotherapy or chemoradiotherapy or resection after FOLFIRINOX.
FUNDING
None.
Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Deoxycytidine; Fluorouracil; Humans; Irinotecan; Leucovorin; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Pancreatic Neoplasms; Prognosis; Survival Rate; Gemcitabine
PubMed: 27160474
DOI: 10.1016/S1470-2045(16)00172-8 -
Annals of Surgical Oncology Jul 2023Pancreatic cancer often presents as locally advanced (LAPC) or borderline resectable (BRPC). Neoadjuvant systemic therapy is recommended as initial treatment. It is... (Meta-Analysis)
Meta-Analysis Review
FOLFIRINOX or Gemcitabine-based Chemotherapy for Borderline Resectable and Locally Advanced Pancreatic Cancer: A Multi-institutional, Patient-Level, Meta-analysis and Systematic Review.
BACKGROUND
Pancreatic cancer often presents as locally advanced (LAPC) or borderline resectable (BRPC). Neoadjuvant systemic therapy is recommended as initial treatment. It is currently unclear what chemotherapy should be preferred for patients with BRPC or LAPC.
METHODS
We performed a systematic review and multi-institutional meta-analysis of patient-level data regarding the use of initial systemic therapy for BRPC and LAPC. Outcomes were reported separately for tumor entity and by chemotherapy regimen including FOLFIRINOX (FIO) or gemcitabine-based.
RESULTS
A total of 23 studies comprising 2930 patients were analyzed for overall survival (OS) calculated from the beginning of systemic treatment. OS for patients with BRPC was 22.0 months with FIO, 16.9 months with gemcitabine/nab-paclitaxel (Gem/nab), 21.6 months with gemcitabine/cisplatin or oxaliplatin or docetaxel or capecitabine (GemX), and 10 months with gemcitabine monotherapy (Gem-mono) (p < 0.0001). In patients with LAPC, OS also was higher with FIO (17.1 months) compared with Gem/nab (12.5 months), GemX (12.3 months), and Gem-mono (9.4 months; p < 0.0001). This difference was driven by the patients who did not undergo surgery, where FIO was superior to other regimens. The resection rates for patients with BRPC were 0.55 for gemcitabine-based chemotherapy and 0.53 with FIO. In patients with LAPC, resection rates were 0.19 with Gemcitabine and 0.28 with FIO. In resected patients, OS for patients with BRPC was 32.9 months with FIO and not different compared to Gem/nab, (28.6 months, p = 0.285), GemX (38.8 months, p = 0.1), or Gem-mono (23.1 months, p = 0.083). A similar trend was observed in resected patients converted from LAPC.
CONCLUSIONS
In patients with BRPC or LAPC, primary treatment with FOLFIRINOX compared with Gemcitabine-based chemotherapy appears to provide a survival benefit for patients that are ultimately unresectable. For patients that undergo surgical resection, outcomes are similar between GEM+ and FOLFIRINOX when delivered in the neoadjuvant setting.
Topics: Humans; Gemcitabine; Antineoplastic Combined Chemotherapy Protocols; Oxaliplatin; Pancreatic Neoplasms; Fluorouracil; Leucovorin; Neoadjuvant Therapy; Paclitaxel; Multicenter Studies as Topic
PubMed: 37020094
DOI: 10.1245/s10434-023-13353-2 -
The Cochrane Database of Systematic... Feb 2018Paracetamol (acetaminophen) is the most widely used non-prescription analgesic in the world. Paracetamol is commonly taken in overdose either deliberately or... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Paracetamol (acetaminophen) is the most widely used non-prescription analgesic in the world. Paracetamol is commonly taken in overdose either deliberately or unintentionally. In high-income countries, paracetamol toxicity is a common cause of acute liver injury. There are various interventions to treat paracetamol poisoning, depending on the clinical status of the person. These interventions include inhibiting the absorption of paracetamol from the gastrointestinal tract (decontamination), removal of paracetamol from the vascular system, and antidotes to prevent the formation of, or to detoxify, metabolites.
OBJECTIVES
To assess the benefits and harms of interventions for paracetamol overdosage irrespective of the cause of the overdose.
SEARCH METHODS
We searched The Cochrane Hepato-Biliary Group Controlled Trials Register (January 2017), CENTRAL (2016, Issue 11), MEDLINE (1946 to January 2017), Embase (1974 to January 2017), and Science Citation Index Expanded (1900 to January 2017). We also searched the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov database (US National Institute of Health) for any ongoing or completed trials (January 2017). We examined the reference lists of relevant papers identified by the search and other published reviews.
SELECTION CRITERIA
Randomised clinical trials assessing benefits and harms of interventions in people who have ingested a paracetamol overdose. The interventions could have been gastric lavage, ipecacuanha, or activated charcoal, or various extracorporeal treatments, or antidotes. The interventions could have been compared with placebo, no intervention, or to each other in differing regimens.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data from the included trials. We used fixed-effect and random-effects Peto odds ratios (OR) with 95% confidence intervals (CI) for analysis of the review outcomes. We used the Cochrane 'Risk of bias' tool to assess the risks of bias (i.e. systematic errors leading to overestimation of benefits and underestimation of harms). We used Trial Sequential Analysis to control risks of random errors (i.e. play of chance) and GRADE to assess the quality of the evidence and constructed 'Summary of findings' tables using GRADE software.
MAIN RESULTS
We identified 11 randomised clinical trials (of which one acetylcysteine trial was abandoned due to low numbers recruited), assessing several different interventions in 700 participants. The variety of interventions studied included decontamination, extracorporeal measures, and antidotes to detoxify paracetamol's toxic metabolite; which included methionine, cysteamine, dimercaprol, or acetylcysteine. There were no randomised clinical trials of agents that inhibit cytochrome P-450 to decrease the activation of the toxic metabolite N-acetyl-p-benzoquinone imine.Of the 11 trials, only two had two common outcomes, and hence, we could only meta-analyse two comparisons. Each of the remaining comparisons included outcome data from one trial only and hence their results are presented as described in the trials. All trial analyses lack power to access efficacy. Furthermore, all the trials were at high risk of bias. Accordingly, the quality of evidence was low or very low for all comparisons. Interventions that prevent absorption, such as gastric lavage, ipecacuanha, or activated charcoal were compared with placebo or no intervention and with each other in one four-armed randomised clinical trial involving 60 participants with an uncertain randomisation procedure and hence very low quality. The trial presented results on lowering plasma paracetamol levels. Activated charcoal seemed to reduce the absorption of paracetamol, but the clinical benefits were unclear. Activated charcoal seemed to have the best risk:benefit ratio among gastric lavage, ipecacuanha, or supportive treatment if given within four hours of ingestion. There seemed to be no difference between gastric lavage and ipecacuanha, but gastric lavage and ipecacuanha seemed more effective than no treatment (very low quality of evidence). Extracorporeal interventions included charcoal haemoperfusion compared with conventional treatment (supportive care including gastric lavage, intravenous fluids, and fresh frozen plasma) in one trial with 16 participants. The mean cumulative amount of paracetamol removed was 1.4 g. One participant from the haemoperfusion group who had ingested 135 g of paracetamol, died. There were no deaths in the conventional treatment group. Accordingly, we found no benefit of charcoal haemoperfusion (very low quality of evidence). Acetylcysteine appeared superior to placebo and had fewer adverse effects when compared with dimercaprol or cysteamine. Acetylcysteine superiority to methionine was unproven. One small trial (low quality evidence) found that acetylcysteine may reduce mortality in people with fulminant hepatic failure (Peto OR 0.29, 95% CI 0.09 to 0.94). The most recent randomised clinical trials studied different acetylcysteine regimens, with the primary outcome being adverse events. It was unclear which acetylcysteine treatment protocol offered the best efficacy, as most trials were underpowered to look at this outcome. One trial showed that a modified 12-hour acetylcysteine regimen with a two-hour acetylcysteine 100 mg/kg bodyweight loading dose was associated with significantly fewer adverse reactions compared with the traditional three-bag 20.25-hour regimen (low quality of evidence). All Trial Sequential Analyses showed lack of sufficient power. Children were not included in the majority of trials. Hence, the evidence pertains only to adults.
AUTHORS' CONCLUSIONS
These results highlight the paucity of randomised clinical trials comparing different interventions for paracetamol overdose and their routes of administration and the low or very low level quality of the evidence that is available. Evidence from a single trial found activated charcoal seemed the best choice to reduce absorption of paracetamol. Acetylcysteine should be given to people at risk of toxicity including people presenting with liver failure. Further randomised clinical trials with low risk of bias and adequate number of participants are required to determine which regimen results in the fewest adverse effects with the best efficacy. Current management of paracetamol poisoning worldwide involves the administration of intravenous or oral acetylcysteine which is based mainly on observational studies. Results from these observational studies indicate that treatment with acetylcysteine seems to result in a decrease in morbidity and mortality, However, further evidence from randomised clinical trials comparing different treatments are needed.
Topics: Acetaminophen; Acetylcysteine; Analgesics, Non-Narcotic; Antidotes; Charcoal; Cysteamine; Dimercaprol; Drug Overdose; Gastric Lavage; Humans; Intestinal Absorption; Liver Failure, Acute; Liver Transplantation; Methionine; Randomized Controlled Trials as Topic
PubMed: 29473717
DOI: 10.1002/14651858.CD003328.pub3 -
BMJ (Clinical Research Ed.) Jul 2022To assess the benefits and harms of different types and doses of anticoagulant drugs for the prevention of venous thromboembolism in patients who are acutely ill and... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the benefits and harms of different types and doses of anticoagulant drugs for the prevention of venous thromboembolism in patients who are acutely ill and admitted to hospital.
DESIGN
Systematic review and network meta-analysis.
DATA SOURCES
Cochrane CENTRAL, PubMed/Medline, Embase, Web of Science, clinical trial registries, and national health authority databases. The search was last updated on 16 November 2021.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Published and unpublished randomised controlled trials that evaluated low or intermediate dose low-molecular-weight heparin, low or intermediate dose unfractionated heparin, direct oral anticoagulants, pentasaccharides, placebo, or no intervention for the prevention of venous thromboembolism in acutely ill adult patients in hospital.
MAIN OUTCOME MEASURES
Random effects, bayesian network meta-analyses used four co-primary outcomes: all cause mortality, symptomatic venous thromboembolism, major bleeding, and serious adverse events at or closest timing to 90 days. Risk of bias was also assessed using the Cochrane risk-of-bias 2.0 tool. The quality of evidence was graded using the Confidence in Network Meta-Analysis framework.
RESULTS
44 randomised controlled trials that randomly assigned 90 095 participants were included in the main analysis. Evidence of low to moderate quality suggested none of the interventions reduced all cause mortality compared with placebo. Pentasaccharides (odds ratio 0.32, 95% credible interval 0.08 to 1.07), intermediate dose low-molecular-weight heparin (0.66, 0.46 to 0.93), direct oral anticoagulants (0.68, 0.33 to 1.34), and intermediate dose unfractionated heparin (0.71, 0.43 to 1.19) were most likely to reduce symptomatic venous thromboembolism (very low to low quality evidence). Intermediate dose unfractionated heparin (2.63, 1.00 to 6.21) and direct oral anticoagulants (2.31, 0.82 to 6.47) were most likely to increase major bleeding (low to moderate quality evidence). No conclusive differences were noted between interventions regarding serious adverse events (very low to low quality evidence). When compared with no intervention instead of placebo, all active interventions did more favourably with regard to risk of venous thromboembolism and mortality, and less favourably with regard to risk of major bleeding. The results were robust in prespecified sensitivity and subgroup analyses.
CONCLUSIONS
Low-molecular-weight heparin in an intermediate dose appears to confer the best balance of benefits and harms for prevention of venous thromboembolism. Unfractionated heparin, in particular the intermediate dose, and direct oral anticoagulants had the least favourable profile. A systematic discrepancy was noted in intervention effects that depended on whether placebo or no intervention was the reference treatment. Main limitations of this study include the quality of the evidence, which was generally low to moderate due to imprecision and within-study bias, and statistical inconsistency, which was addressed post hoc.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42020173088.
Topics: Anticoagulants; Bayes Theorem; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Hospitals; Humans; Network Meta-Analysis; Randomized Controlled Trials as Topic; Thrombosis; Venous Thromboembolism
PubMed: 35788047
DOI: 10.1136/bmj-2022-070022 -
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 -
JAMA Network Open Apr 2023Calciphylaxis is a rare disease with high mortality mainly involving patients with chronic kidney disease (CKD). Sodium thiosulphate (STS) has been used as an off-label... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Calciphylaxis is a rare disease with high mortality mainly involving patients with chronic kidney disease (CKD). Sodium thiosulphate (STS) has been used as an off-label therapeutic in calciphylaxis, but there is a lack of clinical trials and studies that demonstrate its effect compared with those without STS treatment.
OBJECTIVE
To perform a meta-analysis of the cohort studies that provided data comparing outcomes among patients with calciphylaxis treated with and without intravenous STS.
DATA SOURCES
PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov were searched using relevant terms and synonyms including sodium thiosulphate and calci* without language restriction.
STUDY SELECTION
The initial search was for cohort studies published before August 31, 2021, that included adult patients diagnosed with CKD experiencing calciphylaxis and could provide a comparison between patients treated with and without intravenous STS. Studies were excluded if they reported outcomes only from nonintravenous administration of STS or if the outcomes for CKD patients were not provided.
DATA EXTRACTION AND SYNTHESIS
Random-effects models were performed. The Egger test was used to measure publication bias. Heterogeneity was assessed using the I2 test.
MAIN OUTCOMES AND MEASURES
Skin lesion improvement and survival, synthesized as ratio data by a random-effects empirical Bayes model.
RESULTS
Among the 5601 publications retrieved from the targeted databases, 19 retrospective cohort studies including 422 patients (mean age, 57 years; 37.3% male) met the eligibility criteria. No difference was observed in skin lesion improvement (12 studies with 110 patients; risk ratio, 1.23; 95% CI, 0.85-1.78) between the STS and the comparator groups. No difference was noted for the risk of death (15 studies with 158 patients; risk ratio, 0.88; 95% CI, 0.70-1.10) and overall survival using time-to-event data (3 studies with 269 participants; hazard ratio, 0.82; 95% CI, 0.57-1.18). In meta-regression, lesion improvement associated with STS negatively correlated with publication year, implying that recent studies are more likely to report a null association compared with past studies (coefficient = -0.14; P = .008).
CONCLUSIONS AND RELEVANCE
Intravenous STS was not associated with skin lesion improvement or survival benefit in patients with CKD experiencing calciphylaxis. Future investigations are warranted to examine the efficacy and safety of therapies for patients with calciphylaxis.
Topics: Adult; Humans; Male; Middle Aged; Female; Calciphylaxis; Retrospective Studies; Bayes Theorem; Renal Insufficiency, Chronic
PubMed: 37099293
DOI: 10.1001/jamanetworkopen.2023.10068 -
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 -
Clinical Toxicology (Philadelphia, Pa.) Oct 2020Beta-adrenoreceptor antagonist (beta-blocker) poisoning is a common overdose which can lead to significant morbidity and mortality. To evaluate the effects of...
Beta-adrenoreceptor antagonist (beta-blocker) poisoning is a common overdose which can lead to significant morbidity and mortality. To evaluate the effects of treatments for beta-adrenoreceptor antagonist poisoning. Searches were conducted across MEDLINE (1946-26 November 2019, Ovid); Embase (1974-26 November 2019, Ovid); and the Cochrane Central Register of Controlled Trials (CENTRAL, to 26 November 2019) utilising a combination of subject headings and free text. The search strategy identified 15, 553 citations. Two reviewers screened titles and abstracts prior to selecting 141 articles (Kappa on articles included = 0.982, 95% CI 0.980-0.985). Primary outcomes included mortality and improvement in haemodynamic parameters (e.g., heart rate, blood pressure or a composite measure able to quantitate a haemodynamic response). The risk of bias was high for all interventions. Fifteen case reports described the administration of activated charcoal and five detailed the use of gastric lavage. As there was concurrent utilisation of multiple interventions, it was difficult to draw definitive conclusions regarding the relative contribution of these interventions to mortality or survival. The use of catecholamines in treating beta-blocker toxicity was reported in 16 case reports, 3 case series and 2 animal studies. These agents most likely provided a survival benefit and improved haemodynamics. Multiple intravenous boluses of atropine were associated with improvement in heart rate and blood pressure in one case report. Intravenous calcium was associated with an improvement in haemodynamics in three out of six case reports but in association with multiple other therapies as well as in two animal studies. The use of this therapy was associated with mortality benefit in 10 case series. Two case reports showed clear haemodynamic improvement in a timeframe consistent with insulin administration (bolus then continuous infusion). Maintenance dosing ranged from 1 to 10 units/kg/h of insulin. However, it is unclear whether high-dose insulin euglycaemic therapy improved haemodynamic response above catecholamines and other inotropic agents in humans. Hypoglycaemia and hypokalemia were commonly observed adverse effects. Glucagon was associated with minor improvements in haemodynamics through an increase in heart rate in two cases series, nine case reports and five animal studies. Four case reports reported an association with improvement in haemodynamics following administration of methylene blue but in the setting of co-ingestion with amlodipine. There was variable response to intravenous lipid emulsion therapy reported in 10 case series, 5 animal studies and 21 case reports. There were four case reports showing variable response to lignocaine in arrhythmias secondary to beta-blocker toxicity. Fructose diphosphate, levosimendan and amrinone did not provide a mortality or significant haemodynamic benefit in three animal studies and nine case reports. . Veno-arterial extracorporeal membrane oxygenation was associated with improved survival in patients with severe cardiogenic shock or cardiac arrest in an observational study and four cases series. The evidence of four case reports suggest haemodialysis may assist in the management of massive overdose of specific water-soluble beta-blockers (e.g., atenolol) by improving elimination; however, a survival or haemodynamic benefit was not established. One case series and a single case report showed the utility of temporary overdrive cardiac pacing to prevent arrhythmias in sotalol toxicity. Catecholamines, vasopressors, high-dose insulin euglycaemic therapy and veno-arterial extracorporeal membrane oxygenation were associated with reduced mortality. However, it must be acknowledged that multiple treatments were often given simultaneously. Haemodynamic improvements in blood pressure and cardiac output were seen with the use of catecholamines, vasopressin and high-dose insulin euglycaemic therapy. Evidence for treatment recommendations is almost entirely drawn from very low- to low-quality studies and subject to bias. However, it is reasonable to have a graduated response to cardiovascular instability beginning with intravenous fluids, commencement of a single or a combination of catecholamine inotropes and vasopressors depending upon the type of haemodynamic compromise (bradycardia, left ventricular dysfunction, vasodilation). High-dose insulin euglycaemic therapy can be introduced as an adjunctive inotrope and lastly, more invasive methods such as veno-arterial extracorporeal membrane oxygenation should be considered in cases unresponsive to other therapies.
Topics: Adrenergic beta-Antagonists; Animals; Atropine; Catecholamines; Drug Overdose; Extracorporeal Membrane Oxygenation; Fat Emulsions, Intravenous; Hemodynamics; Humans; Insulin; Practice Guidelines as Topic
PubMed: 32310006
DOI: 10.1080/15563650.2020.1752918