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JAMA Network Open May 2019The results from the recent International Duration Evaluation of Adjuvant Therapy (IDEA) collaboration have led some clinicians to adopt shorter durations of adjuvant... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The results from the recent International Duration Evaluation of Adjuvant Therapy (IDEA) collaboration have led some clinicians to adopt shorter durations of adjuvant chemotherapy for patients with stage III colon cancer. The extent to which these findings are supported by other data is unknown.
OBJECTIVE
To conduct a systematic review and meta-analysis of randomized and observational studies investigating the association between the duration of adjuvant chemotherapy and survival among individuals diagnosed as having stage II and III colon cancer (PROSPERO protocol CRD42018108711]).
DATA SOURCES
Abstracts published in English between 2003 and 2018 within the MEDLINE, Embase, CENTRAL, and CINAHL databases were reviewed by 2 authors. Also searched were conference proceedings and the indexes of high-impact oncology journals.
STUDY SELECTION
Studies were excluded if they did not present original data; focused on animal populations, on cancers in sites other than the colon, or on patients with stage 0, I, or IV disease; did not examine a 5-flourouracil-based monotherapy or combination therapy; or did not evaluate the association between treatment duration and survival. The search identified 2341 articles, from which 2 randomized trials and 20 observational studies were included in the meta-analysis.
DATA EXTRACTION AND SYNTHESIS
This study followed the PRISMA and MOOSE reporting guidelines. The risk of bias was assessed by 2 authors using the Cochrane and Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) tools. The results were synthesized using a random-effects model.
MAIN OUTCOMES AND MEASURES
The primary and secondary outcomes were overall survival and disease-free survival, respectively. It was hypothesized a priori that 3 months of chemotherapy would be as effective as 6 months of chemotherapy.
RESULTS
Twenty-two studies were included in the meta-analysis, representing 43 671 patients. The inclusion of patients with stage II disease or with rectal cancer was identified as a source of heterogeneity. After restricting the analysis to patients with stage III colon cancer, there was no association between the duration of chemotherapy and overall survival among studies involving FOLFOX (leucovorin calcium [folinic acid], fluorouracil, and oxaliplatin) or CAPOX (capecitabine plus oxaliplatin) regimens (hazard ratio [HR], 0.80; 95% CI, 0.58-1.09). Among studies focused exclusively on monotherapy, the standard 6-month regimen relative to a 3-month regimen was associated with improved survival (HR, 0.59; 95% CI, 0.52-0.68).
CONCLUSIONS AND RELEVANCE
Shortened durations of chemotherapy may reduce survival among patients with stage III colon cancer prescribed monotherapy but not a combination regimen.
Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemotherapy, Adjuvant; Colonic Neoplasms; Fluorouracil; Leucovorin; Neoplasm Staging; Observational Studies as Topic; Organoplatinum Compounds; Oxaliplatin; Progression-Free Survival; Randomized Controlled Trials as Topic; Time Factors
PubMed: 31099875
DOI: 10.1001/jamanetworkopen.2019.4154 -
The Cochrane Database of Systematic... May 2015It has been suggested that the severity of autism spectrum disorder (ASD) symptoms is positively correlated with the level of circulating or stored toxic metals, and... (Review)
Review
BACKGROUND
It has been suggested that the severity of autism spectrum disorder (ASD) symptoms is positively correlated with the level of circulating or stored toxic metals, and that excretion of these heavy metals, brought about by the use of pharmaceutical chelating agents, results in improved symptoms.
OBJECTIVES
To assess the potential benefits and adverse effects of pharmaceutical chelating agents (referred to as chelation therapy throughout this review) for autism spectrum disorder (ASD) symptoms.
SEARCH METHODS
We searched the following databases on 6 November 2014: CENTRAL, Ovid MEDLINE, Ovid MEDLINE In-Process, Embase,PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and 15 other databases, including three trials registers. In addition we checked references lists and contacted experts.
SELECTION CRITERIA
All randomised controlled trials of pharmaceutical chelating agents compared with placebo in individuals with ASD.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies, assessed them for risk of bias and extracted relevant data. We did not conduct a meta-analysis, as only one study was included.
MAIN RESULTS
We excluded nine studies because they were non-randomised trials or were withdrawn before enrolment.We included one study, which was conducted in two phases. During the first phase of the study, 77 children with ASD were randomly assigned to receive seven days of glutathione lotion or placebo lotion, followed by three days of oral dimercaptosuccinic acid (DMSA). Forty-nine children who were found to be high excreters of heavy metals during phase one continued on to phase two to receive three days of oral DMSA or placebo followed by 11 days off, with the cycle repeated up to six times. The second phase thus assessed the effectiveness of multiple doses of oral DMSA compared with placebo in children who were high excreters of heavy metals and who received a three-day course of oral DMSA. Overall, no evidence suggests that multiple rounds of oral DMSA had an effect on ASD symptoms.
AUTHORS' CONCLUSIONS
This review included data from only one study, which had methodological limitations. As such, no clinical trial evidence was found to suggest that pharmaceutical chelation is an effective intervention for ASD. Given prior reports of serious adverse events, such as hypocalcaemia, renal impairment and reported death, the risks of using chelation for ASD currently outweigh proven benefits. Before further trials are conducted, evidence that supports a causal link between heavy metals and autism and methods that ensure the safety of participants are needed.
Topics: Administration, Oral; Chelating Agents; Chelation Therapy; Child; Child Development Disorders, Pervasive; Child, Preschool; Female; Glutathione; Humans; Male; Metals, Heavy; Randomized Controlled Trials as Topic; Skin Cream; Succimer
PubMed: 26106752
DOI: 10.1002/14651858.CD010766 -
Critical Reviews in Oncology/hematology Oct 2017Uncertainty exists regarding the comparative effectiveness of triplet chemotherapy (FOLFOXIRI) as backbone first-line chemotherapy for metastatic colorectal cancer... (Comparative Study)
Comparative Study Meta-Analysis Review
Triplet (FOLFOXIRI) versus doublet (FOLFOX or FOLFIRI) backbone chemotherapy as first-line treatment of metastatic colorectal cancer: A systematic review and meta-analysis.
Uncertainty exists regarding the comparative effectiveness of triplet chemotherapy (FOLFOXIRI) as backbone first-line chemotherapy for metastatic colorectal cancer (mCRC). We conducted a systematic review and meta-analysis of randomized-controlled trials (RCTs) comparing triplet versus doublet chemotherapy (FOLFOX or FOLFIRI) as first-line therapy in mCRC. Methods and reporting followed PRISMA and SAMPL guidelines. Eight RCTs were included, comprising 1732 patients. In pooled analysis, FOLFOXIRI was associated with improvements in efficacy outcomes, notably with a 25% survival increase (95%CI: 10-37%). FOLFOXIRI was also associated with increased toxicity, with a non-significant 25% increase in the risk of patients experiencing grade ≥3 adverse events (95% CI: -3 to 61%) and with a 1.83 (95% CI: 1.62-2.07) increase in the rate ratio of grade ≥3 adverse events. Moderate quality evidence suggests that first-line FOLFOXIRI provides clinically meaningful efficacy benefits in this setting, at the expense of increased toxicity. Further research is warranted to better characterize safety and to evaluate the most beneficial combination with targeted agents.
Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Neoplasm Metastasis; Organoplatinum Compounds
PubMed: 28917269
DOI: 10.1016/j.critrevonc.2017.08.006 -
Environmental Monitoring and Assessment Jul 2023Heavy metals contaminated soils are posing severe threats to food safety worldwide. Heavy metals absorbed by plant roots from contaminated soils lead to severe plant...
Heavy metals contaminated soils are posing severe threats to food safety worldwide. Heavy metals absorbed by plant roots from contaminated soils lead to severe plant development issues and a reduction in crop yield and growth. The global population is growing, and the demand for food is increasing. Therefore, it is critical to identify soil remediation strategies that are efficient, economical, and environment friendly. The use of biochar and slag as passivators represents a promising approach among various physicochemical and biological strategies due to their efficiency, cost-effectiveness, and low environmental impact. These passivators employ diverse mechanisms to reduce the bioavailability of metals in contaminated soils, thereby improving crop growth and productivity. Although studies have shown the effectiveness of different passivators, further research is needed globally as this field is still in its early stages. This review sheds light on the innovative utilization of biochar and slag as sustainable strategies for heavy metal remediation, emphasizing their novelty and potential for practical applications. Based on the findings, research gaps have been identified and future research directions proposed to enable the full potential of passivators to be utilized effectively and efficiently under controlled and field conditions.
Topics: Soil Pollutants; Environmental Restoration and Remediation; Charcoal; Metals, Heavy; Industrial Waste; Soil
PubMed: 37454303
DOI: 10.1007/s10661-023-11561-7 -
Giornale Italiano Di Nefrologia :... 2012Calcific uremic arteriopathy (CUA), also known as calciphylaxis, is a rare condition occurring in patients with moderate to severe chronic kidney disease. It is a... (Review)
Review
Calcific uremic arteriopathy (CUA), also known as calciphylaxis, is a rare condition occurring in patients with moderate to severe chronic kidney disease. It is a serious, debilitating and potentially fatal clinical disorder affecting 1-4% of the dialysis population and is associated with a high mortality rate (60-80%). The clinical picture is characterized by painful skin lesions tending to necrotic or gangrenous ulceration ultimately necessitating amputation. Severe infectious complications leading to sepsis and death are frequent. The pathogenesis of CUA is still unknown and several pathogenetic hypotheses have been put forward; this makes its treatment difficult and often empirical. The current paper presents a systematic review of recent findings on the pathogenesis, diagnosis and treatment of CUA.
Topics: Arterioles; Calciphylaxis; Chelating Agents; Diagnosis, Differential; Humans; Hyperbaric Oxygenation; Italy; Kidney Failure, Chronic; Prevalence; Renal Dialysis; Risk Factors; Skin; Survival Rate; Thiosulfates
PubMed: 23229665
DOI: No ID Found -
European Review For Medical and... Nov 2017Dry mouth (xerostomia), is a fairly common, well-researched condition, which is an indirect cause of oral malodour. This systematic literature review looked into another... (Review)
Review
Dry mouth (xerostomia), is a fairly common, well-researched condition, which is an indirect cause of oral malodour. This systematic literature review looked into another cause of bad breath: adverse drug reactions in the orofacial region causing halitosis. The study focused on extraoral halitosis, and its subdivisions, particularly blood borne halitosis in which malodourous compounds in the blood stream are carried to the lungs, passively diffused across the pulmonary alveolar membrane to enter the breath. An electronic search was conducted in various databases. Inclusion criteria were: editorials, case control studies, retrospective studies and randomized double-blind studies published in English between 1983 and March 2017. The search identified a total of 23 articles. According to these, drug-related halitosis may be caused by nine medications. Dimethyl sulfoxide, cysteamine and suplatast tosilate are metabolised to dimethyl sulfide, a malodourous compound that is stable in blood and is transported into the breath. Disulfiram is reduced to carbon disulfide, also a stable compound in blood. Nitric oxide reacts with foul-smelling volatile organosulfur compounds. The degradation of penicillamine raises the pH level, favouring the growth of gram-negative bacteria in the oral cavity producing halitosis. Chloral hydrate, phenothiazine, and paraldehyde could not be related to halitosis. The analysis showed that halitosis can be caused by medication but does not correlate to any specific disease or specific form of drug therapy. The pharmacological compounds identified as causes of halitosis are administered to treat a broad spectrum of diseases, or in therapeutic regimes.
Topics: Gram-Negative Bacteria; Halitosis; Humans; Hydrogen Sulfide; Penicillamine; Smell; Sulfhydryl Compounds; Sulfides
PubMed: 29164566
DOI: No ID Found -
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 -
Current Medicinal Chemistry 2011Among potential radiological, nuclear, biological and chemical weapons, cholinergic nerve agents from chemical weapons remain a realistic terrorist threat due to its... (Comparative Study)
Comparative Study Review
Among potential radiological, nuclear, biological and chemical weapons, cholinergic nerve agents from chemical weapons remain a realistic terrorist threat due to its combination of high lethality, demonstrated use and relative abundance of un-destroyed stockpiles in various militaries around the world. While current fielded antidotes are able to mitigate acute poisoning, effective neuroprotection in the field remains a challenge amongst subjects with established status epilepticus following nerve agent intoxication. Due to ethical, safety and surety issues, extensive preclinical and clinical research on cholinergic nerve agents is not possible. This may have been a contributory factor for the slow progress in uncovering new neuroprotectants for nerve agent casualties with established status epilepticus. To overcome this challenge, comparative research with surrogate chemicals that produce similar hypercholinergic toxicity but with less security concerns would be a useful approach forward. In this paper, we will systemically compare the mechanism of seizure generation, propagation and the subsequent clinical, hematologic, and metabolic, biochemical, neuroinflammatory changes and current therapeutic approaches reported in pilocarpine, soman, and sarin models of seizures. This review will be an important first step in closing this knowledge gap among different closely related models of seizures and neurotoxicity. Hopefully, it will spur further efforts in using surrogate cholinergic models by the wider scientific community to expedite the development of a new generation of antidotes that are better able to protect against delayed neurological effects inflicted by nerve agents.
Topics: Animals; Brain; Chemical Warfare Agents; Humans; Pilocarpine; Sarin; Soman; Status Epilepticus
PubMed: 21182477
DOI: 10.2174/092986711794927720 -
The Cochrane Database of Systematic... Mar 2012Phosphorus burns are rarely encountered in usual clinical practice and occur mostly in military and industrial settings. However, these burns can be fatal, even with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Phosphorus burns are rarely encountered in usual clinical practice and occur mostly in military and industrial settings. However, these burns can be fatal, even with minimal burn area, and are often associated with prolonged hospitalisation.
OBJECTIVES
To summarise the evidence of effects (beneficial and harmful) of all interventions for treating people with phosphorus burns.
SEARCH METHODS
We searched the Cochrane Wounds Group Specialised Register (searched 30 September 2011); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 3); Ovid OLDMEDLINE (1947 to 1965); Ovid MEDLINE (1950 to September Week 3 2011); Ovid MEDLINE (In-Process & Other Non-Indexed Citations 29 September 2011); Ovid EMBASE (1980 to 2011 Week 38); EBSCO CINAHL (1982 to 23 September 2011) and Conference Proceedings Citation Index - Science (CPCI-S) (1990 to 30 September 2011).
SELECTION CRITERIA
Any comparisons of different ways of managing phosphorus burns including, but not restricted, to randomised trials.
DATA COLLECTION AND ANALYSIS
We found two non-randomised comparative studies, both comparing patients treated with and without copper sulphate.
MAIN RESULTS
These two comparative studies provide no evidence to support the use of copper sulphate in managing phosphorus burns. Indeed the small amount of available evidence suggests that it may be harmful.
AUTHORS' CONCLUSIONS
First aid for phosphorus burns involves the common sense measures of acting promptly to remove the patient's clothes, irrigating the wound(s) with water or saline continuously, and removing phosphorus particles. There is no evidence that using copper sulphate to assist visualisation of phosphorus particles for removal is associated with better outcome, and some evidence that systemic absorption of copper sulphate may be harmful. We have so far been unable to identify any other comparisons relevant to informing other aspects of the care of patients with phosphorus burns. Future versions of this review will take account of information in articles published in languages other than English, which may contain additional evidence based on treatment comparisons.
Topics: Burns, Chemical; Copper Sulfate; Humans; Length of Stay; Military Personnel; Phosphorus; Retrospective Studies; United States
PubMed: 22419338
DOI: 10.1002/14651858.CD008805.pub2 -
Lakartidningen Sep 2015Lipid rescue is increasingly used as treatment of various types of poisoning despite weak scientific evidence. Some experimental studies have confirmed a positive... (Review)
Review
Lipid rescue is increasingly used as treatment of various types of poisoning despite weak scientific evidence. Some experimental studies have confirmed a positive effect, but others have failed. Clinical studies are lacking, wherefore we decided to do a systematic review of all published human cases. Case reports were searched for in PubMed and Web of Science and thereafter examined by two experts according to an assessment form grading the probability for a causal connection between lipid rescue and improved symptoms. A total of 114 case reports were identified. No correlation was found between the ratings of the cases and the fat solubility of the respective toxins. The findings do not support the predication that lipid rescue is an effective antidote, not even in cases involving local anaesthetics. In view of the potentially negative effects of lipid rescue, it seems reasonable to strictly limit its indication to life-threatening situations where conventional therapies have failed.
Topics: Acute Disease; Antidotes; Fat Emulsions, Intravenous; Humans; Poisoning; Treatment Outcome
PubMed: 26418936
DOI: No ID Found