-
Nutrients May 2017Much evidence suggests that the positive association between meat intake and colorectal adenoma (CRA) and cancer (CRC) risk is mediated by mutagenic compounds generated... (Meta-Analysis)
Meta-Analysis Review
Much evidence suggests that the positive association between meat intake and colorectal adenoma (CRA) and cancer (CRC) risk is mediated by mutagenic compounds generated during cooking at high temperature. A number of epidemiological studies have estimated the effect of meat-related mutagens intake on CRC/CRA risk with contradictory and sometimes inconsistent results. A literature search was carried out (PubMed, Web of Science and Scopus) to identify articles reporting the relationship between the intake of meat-related mutagens (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f] quinoxaline: DiMeIQx, benzo(a) pyrene (B(a)P) and "meat derived mutagenic activity" (MDM)) and CRC/CRA risk. A random-effect model was used to calculate the risk association. Thirty-nine studies were included in the systematic review and meta-analysis. Polled CRA risk (15229 cases) was significantly increased by intake of PhIP (OR = 1.20; 95% CI: 1.13,1.28; < 0.001), MeIQx (OR = 1.14; 95% CI: 1.05,1.23; = 0.001), DiMeIQx (OR = 1.13; 95% CI: 1.05,1.21; = 0.001), B(a)P (OR = 1.10; 95% CI: 1.02,1.19; = 0.017) and MDM (OR = 1.17; 95% CI: 1.07,1.28; = 0.001). A linear and curvilinear trend was observed in dose-response meta-analysis between CRA risk in association with PhIP, MDM, and MeIQx. CRC risk (21,344 cases) was increased by uptake of MeIQx (OR = 1.14; 95% CI: 1.04,1.25; = 0.004), DiMeIQx (OR = 1.12; 95% CI: 1.02,1.22; = 0.014) and MDM (OR = 1.12; 95% CI: 1.06,1.19; < 0.001). No publication bias could be detected, whereas heterogeneity was in some cases rather high. Mutagenic compounds formed during cooking of meat at high temperature may be responsible of its carcinogenicity.
Topics: Adenoma; Animals; Colorectal Neoplasms; Diet; Feeding Behavior; Humans; Meat; Risk Factors
PubMed: 28524104
DOI: 10.3390/nu9050514 -
Parasitology Nov 2022From a systematic review framework, we analysed the clinical evidence on the effectiveness and safety of monotherapy and combination chemotherapy for Chagas disease... (Review)
Review
From a systematic review framework, we analysed the clinical evidence on the effectiveness and safety of monotherapy and combination chemotherapy for Chagas disease (ChD) treatment. The research protocol was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and patient, intervention, comparison and outcome strategy. Only randomized controlled trials (RCT) were retrieved from Embase, Medline, Scopus and Web of Science databases. Diagnostic tools, treatment protocols, seroconversion rates and adverse events were investigated. Fifteen RCT mainly concentrated in endemic countries were identified. ChD diagnosis was mainly based on haemagglutination, immunofluorescence, enzyme-linked immunosorbent assay and polymerase chain reaction. Benznidazole (BNZ), nifurtimox, fosravuconazole, posaconazole, allopurinol and thioctic acid were the identified drugs. The best negative seroconversion results (100, 96, 94 and 91.3%) were, respectively, based on BNZ (5 mg kg day, 200 mg day, 150 mg day and 2.5 mg kg) administration for 60 days. Negative seroconversion was not achieved with allopurinol (300 mg day for 60 days). Adverse reactions ranged from 5 to 73% in patients receiving antiparasitic chemotherapy. Treatment discontinuation (1.5–57%) was mainly associated with gastrointestinal, cutaneous and neurological manifestations. Current RCT-based evidence indicates that BNZ is the most viable option for ChD treatment. However, new protocols need to be developed to mitigate side effects and increase patient adherence to antiparasitic chemotherapy. Therefore, shorter regimens, lower concentrations and treatments combining BNZ with posaconazole, fosravuconazole or ravuconazole may be viable to ensure comparable efficacy to BZN-based monotherapy, contributing to reduce dose- and time-dependent toxicity reactions.
Topics: Humans; Trypanosoma cruzi; Trypanocidal Agents; Allopurinol; Randomized Controlled Trials as Topic; Chagas Disease; Nitroimidazoles; Drug Therapy, Combination; Treatment Outcome
PubMed: 35957576
DOI: 10.1017/S0031182022001081 -
The Cochrane Database of Systematic... Aug 2014Paraquat is an effective and widely used herbicide but is also a lethal poison. In many developing countries paraquat is widely available and inexpensive, making... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Paraquat is an effective and widely used herbicide but is also a lethal poison. In many developing countries paraquat is widely available and inexpensive, making poisoning prevention difficult. However most of the people who become poisoned from paraquat have taken it as a means of suicide.Standard treatment for paraquat poisoning both prevents further absorption and reduces the load of paraquat in the blood through haemoperfusion or haemodialysis. The effectiveness of standard treatments is extremely limited.The immune system plays an important role in exacerbating paraquat-induced lung fibrosis. Immunosuppressive treatment using glucocorticoid and cyclophosphamide in combination is being developed and studied.
OBJECTIVES
To assess the effects of glucocorticoid with cyclophosphamide on mortality in patients with paraquat-induced lung fibrosis.
SEARCH METHODS
The most recent search was run on the 15th April 2014. We searched the Cochrane Injuries Group's Specialised Register, The Cochrane Library, Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), Embase Classic+Embase (Ovid), ISI WOS (SCI-EXPANDED, SSCI, CPCI-S & CPSI-SSH), trials registries, Chinese databases (, , ) and reference lists.
SELECTION CRITERIA
RCTs were included in this review. All patients were to receive standard care, plus the intervention or control. The intervention was glucocorticoid with cyclophosphamide in combination versus a control of a placebo, standard care alone or any other therapy in addition to standard care.
DATA COLLECTION AND ANALYSIS
The mortality risk ratio (RR) and 95% confidence interval (CI) was calculated for each study on an intention-to-treat basis. Data for all-cause mortality at final follow-up were summarised in a meta-analysis using a fixed-effect model.
MAIN RESULTS
This systematic review includes three trials with a combined total of 164 participants who had moderate to severe paraquat poisoning. Patients who received glucocorticoid with cyclophosphamide in addition to standard care had a lower risk of death at final follow-up than those receiving standard care only (RR 0.72; 95% CI 0.59 to 0.89).
AUTHORS' CONCLUSIONS
Based on the findings of three small RCTs of moderate to severely poisoned patients, glucocorticoid with cyclophosphamide in addition to standard care may be a beneficial treatment for patients with paraquat-induced lung fibrosis. To enable further study of the effects of glucocorticoid with cyclophosphamide for patients with moderate to severe paraquat poisoning, hospitals may provide this treatment as part of an RCT with allocation concealment.
Topics: Cause of Death; Cyclophosphamide; Drug Therapy, Combination; Glucocorticoids; Herbicides; Humans; Immunosuppressive Agents; Paraquat; Poisoning; Pulmonary Fibrosis; Randomized Controlled Trials as Topic
PubMed: 25099931
DOI: 10.1002/14651858.CD008084.pub4 -
BMC Endocrine Disorders Jan 2024To evaluate the efficacy and safety of combined glucocorticoids (GCs) and cyclophosphamide (CYC) treatment in Graves' ophthalmopathy (GO). (Meta-Analysis)
Meta-Analysis
PURPOSE
To evaluate the efficacy and safety of combined glucocorticoids (GCs) and cyclophosphamide (CYC) treatment in Graves' ophthalmopathy (GO).
METHODS
We searched PubMed, Embase, Cochrane Library, and four Chinese databases (Chinese National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), WanFang, and SinoMed) for any published randomized controlled trials (RCTs) produced from inception to December 1, 2023. Articles obtained using appropriate keywords were selected independently by two reviewers according to the established inclusion and exclusion criteria.
FINDINGS
We retrieved 1120 records which were eventually reduced to 13 RCTs which were then included in this evaluation. Pooled results indicated that the experimental group (CYC/GCs) showed a higher response rate than control group (GCs or negative control) (RR 1.27; 95% confidence interval 1.19 to 1.37). The subgroup analysis showed that the difference in response rates among treatment protocols (CYC/P, CYC/MPS, CYC/DEX) was not statistically significant (p = 0.23).
IMPLICATIONS
The combination of GCs and CYC could be recommended as a therapeutic option for GO, especially in patients who experience recurrence after a withdrawal GCs, have a poor response to GCs, or cannot obtain monoclonal antibody agents for various reasons.
Topics: Humans; Glucocorticoids; Graves Ophthalmopathy; Cyclophosphamide; China
PubMed: 38273269
DOI: 10.1186/s12902-024-01545-0 -
Regulatory Toxicology and Pharmacology... Oct 2023Propylene dichloride (PDC) is a chlorinated substance used primarily as an intermediate in basic organic chemical manufacturing. The United States Environmental... (Review)
Review
Propylene dichloride (PDC) is a chlorinated substance used primarily as an intermediate in basic organic chemical manufacturing. The United States Environmental Protection Agency (EPA) is currently evaluating PDC as a high-priority substance under the Toxic Substances Control Act (TSCA). We conducted a systematic review of the non-cancer and cancer hazards of PDC using the EPA TSCA and Integrated Risk Information System (IRIS) frameworks. We identified 12 epidemiological, 16 toxicokinetic, 34 experimental animal, and 49 mechanistic studies. Point-of-contact respiratory effects are the most sensitive non-cancer effects after inhalation exposure, and PDC is neither a reproductive nor a developmental toxicant. PDC is not mutagenic in vivo, and while in vitro evidence is mixed, DNA strand breaks consistently occur. Nasal tumors in rats and lung tumors in mice occurred after lifetime high-level inhalation exposure. Cholangiocarcinoma (CCA) was observed in Japanese print workers exposed to high concentrations of PDC. However, co-exposures, as well as liver parasites, hepatitis, and other risk factors, may also have contributed. The cancer mode of action (MOA) analysis revealed that PDC may act through multiple biological pathways occurring sequentially and/or simultaneously, although chronic tissue damage and inflammation likely dominate. Critically, health benchmarks protective of non-cancer effects are expected to protect against cancer in humans.
PubMed: 37562533
DOI: 10.1016/j.yrtph.2023.105468 -
Supportive Care in Cancer : Official... Dec 2023This systematic review updates the MASCC/ESMO recommendations for high-emetic-risk chemotherapy (HEC) published in 2016-2017. HEC still includes cisplatin, carmustine,...
PURPOSE
This systematic review updates the MASCC/ESMO recommendations for high-emetic-risk chemotherapy (HEC) published in 2016-2017. HEC still includes cisplatin, carmustine, dacarbazine, mechlorethamine, streptozocin, and cyclophosphamide in doses of > 1500 mg/m and the combination of cyclophosphamide and an anthracycline (AC) in women with breast cancer.
METHODS
A systematic review report following the PRISMA guidelines of the literature from January 1, 2015, until February 1, 2023, was performed. PubMed (Ovid), Scopus (Google), and the Cochrane Database of Systematic Reviews were searched. The literature search was limited to randomized controlled trials, systematic reviews, and meta-analyses.
RESULTS
Forty-six new references were determined to be relevant. The main topics identified were (1) steroid-sparing regimens, (2) olanzapine-containing regimens, and (3) other issues such as comparisons of antiemetics of the same drug class, intravenous NK receptor antagonists, and potentially new antiemetics. Five updated recommendations are presented.
CONCLUSION
There is no need to prescribe steroids (dexamethasone) beyond day 1 after AC HEC, whereas a 4-day regimen is recommended in non-AC HEC. Olanzapine is now recommended as a fixed part of a four-drug prophylactic antiemetic regimen in both non-AC and AC HEC. No major differences between 5-HT receptor antagonists or between NK receptor antagonists were identified. No new antiemetic agents qualified for inclusion in the updated recommendations.
Topics: Female; Humans; Emetics; Antiemetics; Consensus; Olanzapine; Nausea; Vomiting; Antineoplastic Agents; Cyclophosphamide; Anthracyclines
PubMed: 38127246
DOI: 10.1007/s00520-023-08221-4 -
The Cochrane Database of Systematic... May 2015Neuroblastoma is a rare malignant disease and mainly affects infants and very young children. The tumors mainly develop in the adrenal medullary tissue and an abdominal... (Review)
Review
BACKGROUND
Neuroblastoma is a rare malignant disease and mainly affects infants and very young children. The tumors mainly develop in the adrenal medullary tissue and an abdominal mass is the most common presentation. The high-risk group is characterized by metastasis and other characteristics that increase the risk for an adverse outcome. In the rapid COJEC induction schedule, higher single doses of selected drugs than standard induction schedules are administered over a substantially shorter treatment period, with shorter intervals between cycles. Shorter intervals and higher doses increase the dose intensity of chemotherapy and might improve survival.
OBJECTIVES
The aim of this study was to evaluate the efficacy and adverse events of the rapid COJEC induction schedule as compared to standard induction schedules in patients with high-risk neuroblastoma (as defined by the International Neuroblastoma Risk Group (INRG) classification system). Outcomes of interest were complete response, early toxicity and treatment-related mortality as primary endpoints and overall survival, progression- and event-free survival, late non-hematological toxicity, and health-related quality of life as secondary endpoints.
SEARCH METHODS
We searched the electronic databases CENTRAL (2014, Issue 11), MEDLINE (PubMed), and EMBASE (Ovid) for articles from inception to 11 November 2014. Further searches included trial registries, conference proceedings, and reference lists of recent reviews and relevant articles. We did not apply limits on publication year or languages.
SELECTION CRITERIA
Randomized controlled trials evaluating the rapid COJEC induction schedule for high-risk neuroblastoma patients compared to standard induction schedules.
DATA COLLECTION AND ANALYSIS
Two review authors performed study selection, abstracted data on study and patient characteristics, and assessed risk of bias independently. We resolved differences by discussion or by appeal to a third review author. We performed analyses according to the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions. We used the five GRADE considerations, study limitations, consistency of effect, imprecision, indirectness, and publication bias, to judge the quality of the evidence. We downgraded for risk of bias and imprecision
MAIN RESULTS
We identified one randomized controlled trial (CCLG-ENSG-5) that included 262 patients with high-risk neuroblastoma who were randomized to receive either rapid COJEC (N = 130) or standard OPEC/COJEC (N = 132) induction chemotherapy. We graded the evidence as low quality; we downgraded for risk of bias and imprecision.There was no clear evidence of a difference between the treatment groups in complete response (risk ratio (RR) 0.99, 95% confidence interval (CI) 0.71 to 1.38), treatment-related mortality (RR 1.21, 95% CI 0.33 to 4.39), overall survival (hazard ratio (HR) 0.83, 95% CI 0.63 to 1.10), and event-free survival (HR 0.86, 95% CI 0.65 to 1.13). We calculated the HRs using the complete follow-up period of the trial.Febrile neutropenia (two or more episodes), proven fungal infections, septicemia (one or more episodes), gastrointestinal toxicity (grade 3 or 4), renal toxicity (glomerular filtration rate < 80 ml/min per body surface area of 1.73 m(2)), neurological toxicity (grade 3 or 4), and ototoxicity (Brock grade 2 to 4) were addressed as early toxicities (during pre-operative chemotherapy). For febrile neutropenia, septicemia, and renal toxicity, a statistically significant difference in favor of the standard treatment arm was identified; for all other early toxicities no clear evidence of a difference between treatment groups was identified. With regard to late non-hematological toxicities (median follow-up 12.7 years; range 6.9 to 16.5 years), the study provided data on any complication, renal toxicity (glomerular filtration rate < 80 ml/min per body surface area of 1.73m(2)), ototoxicity (Brock grade 1 to 4), endocrine complications, neurocognitive complications (i.e. behavioral, speech, or learning difficulties), and second malignancies. For endocrine complications and neurocognitive complications, a statistically significant difference in favor of the rapid COJEC arm was found; for all other late non-hematological toxicities no clear evidence of a difference between treatment groups was identified.Data on progression-free survival and health-related quality of life were not reported.
AUTHORS' CONCLUSIONS
We identified one randomized controlled trial that evaluated rapid COJEC versus standard induction therapy in patients with high-risk neuroblastoma. No clear evidence of a difference in complete response, treatment-related mortality, overall survival, and event-free survival between the treatment alternatives was found. This could be the result of low power or too short a follow-up period. Results of both early and late toxicities were ambiguous. Information on progression-free survival and health-related quality of life were not available. This trial was performed in the 1990s. Since then, many changes in, for example, treatment and risk classification have occurred. Therefore, based on the currently available evidence, we are uncertain about the effects of rapid COJEC and standard induction therapy in patients with high-risk neuroblastoma. More research is needed for a definitive conclusion.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Child; Child, Preschool; Cisplatin; Cyclophosphamide; Drug Administration Schedule; Etoposide; Humans; Induction Chemotherapy; Infant; Neuroblastoma; Randomized Controlled Trials as Topic; Vincristine
PubMed: 25989478
DOI: 10.1002/14651858.CD010774.pub2 -
Medicine Apr 2020Rituximab (RTX) is considered to be a promising drug for curing membranous nephropathy. However, the efficacy and safety of RTX in treating membranous nephropathy remain... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND AND OBJECTIVES
Rituximab (RTX) is considered to be a promising drug for curing membranous nephropathy. However, the efficacy and safety of RTX in treating membranous nephropathy remain uncertain. This meta-analysis aimed to investigate the efficacy and safety of RTX in patients with membranous nephropathy.
METHODS
A literature search was performed using Pubmed, Embase, OVID, and Cochrane Library and randomized controlled trials (RCTs) case-controls and cohort studies published till 30 July 2019 were assessed. The studies assessing the efficacy and safety of RTX in patients with membranous nephropathy were included.
RESULTS
Eight relevant trials involving 542 patients were included in the meta-analysis. It was found that RTX did not significantly improve serum albumin levels and e-GFR when compared with the control group (including cyclosporine and cyclophosphamide, chlorambucil, prednisone, non-immunosuppressive anti-proteinuria treatment), serum albumin levels (OR = 0.31, 95%CI-0.12-0.74, P = .15), e-GFR (OR = -1.49, 95%CI-17.14-14.17, P = .85). However, RTX did reduce the serum creatinine (OR = -0.01, 95%CI-0.36-0.34, P = .95) and urinary protein (OR = -2.39, 95%CI -7.30 -2.53, P = .34) levels. Also, in comparison to the control group, RTX did improve the total remission rate (OR = 1.63, 95%CI 0.48-5.54, P = .43), achieve a higher rate of complete remission (OR = 2.54, 95%CI 1.65-3.90, P < .01) and also reduced the amount of M-type phospholipase A2 receptor-Antibody depletion in patients (OR = 5.59, 95%CI 1.81-17.2, P = .003). RTX-related adverse events were mostly mild (most infusion-related reactions) in nature and serious adverse events were rare.
CONCLUSION
RTX proved to be efficient, well-tolerated and a safe drug in the treatment of membranous nephropathy. Most patients reach complete remission during the follow-up period, and relapse is rare. RTX may turn out to be promising in membranous nephropathy patients.
Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Immunological; Case-Control Studies; Chlorambucil; Cyclophosphamide; Cyclosporine; Female; Glomerular Filtration Rate; Glomerulonephritis, Membranous; Humans; Immunosuppressive Agents; Male; Middle Aged; Prednisone; Proteinuria; Randomized Controlled Trials as Topic; Receptors, Phospholipase A2; Remission Induction; Rituximab; Safety; Serum Albumin; Treatment Outcome
PubMed: 32311997
DOI: 10.1097/MD.0000000000019804 -
International Journal of Fertility &... 2015Dioxin-related compounds are associated with teratogenic and mutagenic risks in laboratory animals, and result in adverse pregnancy outcomes. However, there were... (Review)
Review
Dioxin-related compounds are associated with teratogenic and mutagenic risks in laboratory animals, and result in adverse pregnancy outcomes. However, there were inconsistent results in epidemiology studies. In view of this difference, we conducted a systematic review and meta-analysis to examine this association and to assess the heterogeneity among studies. Comprehensive literature searches were performed to search for relevant articles published in English up to 15 May 2012. In total, we identified 15 studies which included 9 cohort and 6 case control studies. The Cochrane Q test and index of heterogeneity (I(2)) were used to evaluate heterogeneity. In either cohort studies (I(2)=0.89, p<0.0001) or case control studies (I(2)=0.69, p=0.02), significant heterogeneity of risk estimates were observed. Subgroup analyses found no significant increased risk of adverse pregnancy outcome with air dioxin-related compounds exposure (RR=0.99, 95% CI:0.85-1.16), no significant increased risk of spontaneous abortion (SAB) with exposure to food dioxin-related compounds (RR=1.05, 95% CI:0.80-1.37), higher significant risks of low birth weight (LBW) with exposure to food dioxin-related compounds (RR=1.55, 95% CI:1.24-1.94), and higher significant risks of birth defects with maternal solid contaminants dioxin exposure (OR=1.24, 95% CI:1.19-1.29). In conclusion, more evidences are needed to confirm the association between environmental dioxin-related compounds exposure and pregnancy outcome.
PubMed: 25780516
DOI: 10.22074/ijfs.2015.4174 -
Journal of Oral Science Jun 2020A systematic review was conducted to identify the biological responses, allergic reaction, hypersensitivity, toxicity, and ion release profile associated with pediatric...
A systematic review was conducted to identify the biological responses, allergic reaction, hypersensitivity, toxicity, and ion release profile associated with pediatric stainless steel crowns (SSCs) in the existing literature. A systematic search was undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The inclusion criteria consisted of patients younger than 20 years of age with SSC placement on primary or permanent teeth and in vivo and in vitro exposure to SSCs. Outcomes measures included adverse oral/mucosal effects; removal/failure/replacement of the SSC; type of allergic reaction; nickel (Ni) or other ion levels in bodily fluids, cellular, genotoxic, cytotoxic, mutagenic or carcinogenic effects related to the SSC. After an initial search of 764 studies in the database, 17 articles were included in the analysis. Evidence of allergic reactions to SSCs in children is limited and obtained from mostly low-quality research. Some studies showed that the amount of Ni detected was less than the amount ingested in the daily diet. In contrast, other studies reported a significantly higher release of Ni occurred into the saliva in acidic environments. There is some concern about the leaching of metal ions such as Ni from SSCs in children at high risk for caries. Further long-term studies are required to investigate this phenomenon.
Topics: Adult; Child; Crowns; Dental Caries; Dentition, Permanent; Humans; Nickel; Stainless Steel; Tooth, Deciduous; Young Adult
PubMed: 32522913
DOI: 10.2334/josnusd.20-0083