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PLoS Neglected Tropical Diseases Nov 2022Mucosal or mucocutaneous leishmaniasis is the most severe form of tegumentary leishmaniasis due to its destructive character and potential damage to respiratory and...
BACKGROUND
Mucosal or mucocutaneous leishmaniasis is the most severe form of tegumentary leishmaniasis due to its destructive character and potential damage to respiratory and digestive tracts. The current treatment recommendations are based on low or very low-quality evidence, and pentavalent antimonial derivatives remain strongly recommended. The aim of this review was to update the evidence and estimate the cure rate and safety profile of the therapeutic options available for mucosal leishmaniasis (ML) in the Americas.
METHODOLOGY
A systematic review was conducted in four different databases and by different reviewers, independently, to evaluate the therapeutic efficacy and toxicity associated with different treatments for ML. All original studies reporting cure rates in more than 10 patients from American regions were included, without restriction of design, language, or publication date. The risk of bias was assessed by two reviewers, using different tools according to the study design. The pooled cure rate based on the latest cure assessment reported in the original studies was calculated grouping all study arms addressing the same intervention. The protocol for this review was registered at the International Prospective Register of Systematic Reviews, PROSPERO: CRD42019130708.
PRINCIPAL FINDINGS
Twenty-seven original studies from four databases fulfilled the selection criteria. A total of 1,666 patients with ML were treated predominantly with pentavalent antimonials in Brazil. Other interventions, such as pentamidine, miltefosine, imidazoles, aminosidine sulfate, deoxycholate and lipidic formulations of amphotericin B (liposomal, lipid complex, colloidal dispersion), in addition to combinations with pentoxifylline, allopurinol or sulfa were also considered. In general, at least one domain with a high risk of bias was identified in the included studies, suggesting low methodological quality. The pooled cure rate based on the latest cure assessment reported in the original studies was calculated grouping all study arms addressing the same intervention. It was confirmed that antimony is still the most used treatment for ML, with only moderate efficacy (possibly increased by combining with pentoxifylline). There is already evidence for the use of miltefosine for ML, with a cure rate similar to antimony, as observed in the only direct meta-analysis including 57 patients (OR: 1.2; 0.43-3.49, I2 = 0). It was possible to gather all descriptions available about adverse events reported during ML treatment, and the toxicity reflected the pattern informed in the manufacturers' technical information.
CONCLUSIONS
This study provides an overview of the clinical experience in the Americas related to ML treatment and points out interventions and possible combinations that are eligible to be explored in future well-designed studies.
Topics: Humans; Antimony; Leishmaniasis, Mucocutaneous; Pentoxifylline
PubMed: 36395328
DOI: 10.1371/journal.pntd.0010931 -
Frontiers in Pharmacology 2022Gout is a common disease and is usually treated with uric acid-lowering drugs (the most commonly used of which are febuxostat and allopurinol). However, the...
Gout is a common disease and is usually treated with uric acid-lowering drugs (the most commonly used of which are febuxostat and allopurinol). However, the cardiovascular safety of febuxostat and allopurinol is still controversial. The purpose of our study is to evaluate the cardiovascular safety of the two drugs in patients with gout using one-stage and two-stage meta-analysis. PubMed, Embase, CBM, CNKI, WanFang, Central, and VIP were searched from inception to 30 January 2022. Randomized controlled trials which evaluated the cardiovascular safety of febuxostat or allopurinol for treating patients with gout were included. Based on the Kaplan-Meier curves of the two studies, individual patient data (IPD) were extracted and reconstructed. We used time-varying risk ratios (RRs) to summarize time-to-event outcomes, and the RRs of MACE incidence, cardiovascular mortality, and all-cause mortality were calculated by a multi-level flexible hazard regression model in 1-stage meta-analyses. values were calculated using a log-rank test. At the same time, using the reconstructed IPD, we performed 2-stage meta-analyses to inform the quantitative estimates of time-specific relative risks at the six time points (1 , 2, 3, 4, 5, and 6 years) based on a random-effects model. Two RCTs with 12,318 participants were included. In the incidence of major adverse cardiovascular events between the two regimens, there was no significant difference [RR = 0.99 (95% CI, 0.89-1.11), = 0.87]; at the same time, there was no significant difference in cardiovascular mortality [RR = 1.17 (95% CI, 0.98-1.40), = 0.08] or all-cause mortality [RR = 1.03 (95% CI, 0.91-1.17), = 0.62]. In terms of 2-stage meta-analyses, there was no significant difference in any outcomes at any time point (moderate-to low-certainty evidence). In patients without atherosclerotic disease, febuxostat likely has a similar cardiovascular profile to allopurinol. However, in patients with a history of cardiovascular disease, allopurinol treatment is associated with less cardiovascular mortality as compared with febuxostat. https://www.crd.york.ac.uk/prospero/#loginpage, identifier PROSPERO, CRD42022325656.
PubMed: 36249825
DOI: 10.3389/fphar.2022.998441 -
Hormones (Athens, Greece) Dec 2022Cardiovascular disease (CVD) remains the main cause of death in patients with type 2 diabetes (T2D). Although hyperuricemia has been associated with multiple CV... (Review)
Review
BACKGROUND
Cardiovascular disease (CVD) remains the main cause of death in patients with type 2 diabetes (T2D). Although hyperuricemia has been associated with multiple CV complications, it is not officially recognized as a target parameter for CVD risk reduction.
AIM
To systematically review the literature in order to determine whether treating hyperuricemia with allopurinol in patients with T2D reduces CVD risk.
METHODS
A thorough literature search in the PubMed, CENTRAL, and EMBASE databases from inception to August 2022 was performed. After application of selection criteria, 6 appropriate studies were identified.
RESULTS
Detailed analysis of the data derived indicated that there is an association between allopurinol treatment and CV benefits, resulting in a reduced risk of CVD events and mortality rates. This association can be attributed mainly to the reduction of inflammation and oxidative burden, as well as to the improvement of glycemic and lipid profiles.
CONCLUSIONS
This systematic review provides evidence that allopurinol may reduce CVD risk in patients with T2D. Randomized, placebo-controlled trials should be performed in order to confirm these findings and identify specific subgroups of patients who will benefit most.
Topics: Humans; Allopurinol; Diabetes Mellitus, Type 2; Hyperuricemia; Cardiovascular Diseases; Blood Glucose
PubMed: 36197637
DOI: 10.1007/s42000-022-00403-9 -
Archives of Medical Sciences.... 2021Contrast-induced nephropathy (CIN) is the third most common cause of iatrogenic acute renal failure and is triggered by administration of radiopaque contrast media.... (Review)
Review
Protective effect of allopurinol in preventing contrast-induced nephropathy among patients undergoing percutaneous coronary intervention: a systematic review and meta-analysis.
INTRODUCTION
Contrast-induced nephropathy (CIN) is the third most common cause of iatrogenic acute renal failure and is triggered by administration of radiopaque contrast media. Periprocedural hydration is imperative in prevention of CIN, and uric acid has been recognized to have an integral role in development of renal disease. The aim of our study is to understand the efficacy of allopurinol in preventing CIN among patients undergoing percutaneous coronary intervention.
MATERIAL AND METHODS
A literature search was performed on PubMed (Medline), Science Direct and Cochrane Library using a combination of Mesh terms. We limited our search to randomized controlled trials (RCTs) and articles published in the English language. The PRISMA protocol was utilized to conduct this meta-analysis.
RESULTS
Six studies were included in the final analysis. All included studies were clinical trials conducted between 2013 and 2019. A total of 853 patients were included. There was a significant reduction in the risk of CIN among patients who were pretreated with adequate hydration plus allopurinol (100 to 600 mg) compared to hydration only before undergoing percutaneous coronary angiography (RR = 0.39, 95% CI: 0.21-0.73). A sensitivity analysis of studies using 300 mg of allopurinol only reported a significant reduction in CI-AKI compared to hydration alone (RR = 0.26, 95% CI: 0.11-0.57).
CONCLUSIONS
Our study demonstrates that Allopurinol is effective in preventing contrast-induced nephropathy in patients undergoing percutaneous coronary intervention. Larger clinical trials are warranted to better understand this effect.
PubMed: 36161220
DOI: 10.5114/amsad.2021.112226 -
Clinical Pharmacology and Therapeutics Dec 2022The objective of this study was to evaluate the evidence on cost-effectiveness of pharmacogenetic (PGx)-guided treatment for drugs with Clinical Pharmacogenetics...
The objective of this study was to evaluate the evidence on cost-effectiveness of pharmacogenetic (PGx)-guided treatment for drugs with Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. A systematic review was conducted using multiple biomedical literature databases from inception to June 2021. Full articles comparing PGx-guided with nonguided treatment were included for data extraction. Quality of Health Economic Studies (QHES) was used to assess robustness of each study (0-100). Data are reported using descriptive statistics. Of 108 studies evaluating 39 drugs, 77 (71%) showed PGx testing was cost-effective (CE) (N = 48) or cost-saving (CS) (N = 29); 21 (20%) were not CE; 10 (9%) were uncertain. Clopidogrel had the most articles (N = 23), of which 22 demonstrated CE or CS, followed by warfarin (N = 16), of which 7 demonstrated CE or CS. Of 26 studies evaluating human leukocyte antigen (HLA) testing for abacavir (N = 8), allopurinol (N = 10), or carbamazepine/phenytoin (N = 8), 15 demonstrated CE or CS. Nine of 11 antidepressant articles demonstrated CE or CS. The median QHES score reflected high-quality studies (91; range 48-100). Most studies evaluating cost-effectiveness favored PGx testing. Limited data exist on cost-effectiveness of preemptive and multigene testing across disease states.
Topics: Humans; Pharmacogenomic Testing; Pharmacogenetics; Cost-Benefit Analysis; Warfarin; Carbamazepine
PubMed: 36149409
DOI: 10.1002/cpt.2754 -
European Journal of Human Genetics :... Feb 2024The Dutch Pharmacogenetics Working Group (DPWG) aims to facilitate PGx implementation by developing evidence-based pharmacogenetics guidelines to optimize...
The Dutch Pharmacogenetics Working Group (DPWG) aims to facilitate PGx implementation by developing evidence-based pharmacogenetics guidelines to optimize pharmacotherapy. This guideline describes the gene-drug interaction of ABCG2 with allopurinol, HLA-B with allopurinol, MTHFR with folic acid, and MTHFR with methotrexate, relevant for the treatment of gout, cancer, and rheumatoid arthritis. A systematic review was performed based on which pharmacotherapeutic recommendations were developed. Allopurinol is less effective in patients with the ABCG2 p.(Gln141Lys) variant. In HLA-B*58:01 carriers, the risk of severe cutaneous adverse events associated with allopurinol is strongly increased. The DPWG recommends using a higher allopurinol dose in patients with the ABCG2 p.(Gln141Lys) variant. For HLA-B*58:01 positive patients the DPWG recommends choosing an alternative (for instance febuxostat). The DPWG indicates that another option would be to precede treatment with allopurinol tolerance induction. Genotyping of ABCG2 in patients starting on allopurinol was judged to be 'potentially beneficial' for drug effectiveness, meaning genotyping can be considered on an individual patient basis. Genotyping for HLA-B*58:01 in patients starting on allopurinol was judged to be 'beneficial' for drug safety, meaning it is advised to consider genotyping the patient before (or directly after) drug therapy has been initiated. For MTHFR-folic acid there is evidence for a gene-drug interaction, but there is insufficient evidence for a clinical effect that makes therapy adjustment useful. Finally, for MTHFR-methotrexate there is insufficient evidence for a gene-drug interaction.
Topics: Humans; Allopurinol; ATP Binding Cassette Transporter, Subfamily G, Member 2; Drug Interactions; Folic Acid; Gout Suppressants; HLA-B Antigens; Methotrexate; Methylenetetrahydrofolate Reductase (NADPH2); Neoplasm Proteins; Pharmacogenetics
PubMed: 36056234
DOI: 10.1038/s41431-022-01180-0 -
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 -
Renal Failure Dec 2022Diabetes mellitus is a common "non-gout" disease with high incidence. Several studies have shown that serum uric acid level in patients with diabetes is higher than that... (Meta-Analysis)
Meta-Analysis
BACKGROUND/OBJECTIVE
Diabetes mellitus is a common "non-gout" disease with high incidence. Several studies have shown that serum uric acid level in patients with diabetes is higher than that in healthy individuals, and is accompanied by severe albuminuria and high serum creatinine (Scr). Recent clinical studies have found that uric acid-lowering therapy (such as allopurinol) could reduce urinary albumin excretion rates (UAER) and Scr, increase eGFR, and thus reduce kidney damage in patients with diabetes. Therefore, this meta-analysis [PROSPERO CRD42021274465] intended to evaluate the efficacy and safety of allopurinol in patients with diabetes mellitus.
METHODS
We thoroughly searched five electronic resource databases for randomized controlled trials (RCTs) that compared the efficacy and safety of allopurinol versus conventional treatment or placebo for the treatment of patients with diabetes mellitus. Predetermined outcomes were considered continuous variables, mean difference (MD) was used for the determination of effect size (standardized mean difference [SMD] was used to determine the effect size when there were different evaluation criteria in different articles), and the corresponding 95% confidence interval (CI) was calculated. All outcome measures were analyzed using a random-effects model for data analysis.
RESULTS
Ten eligible trials with a total of 866 participants were included in the meta-analysis. Allopurinol was more effective in decreasing serum uric acid (SUA) levels compared with conventional treatment ( = 0.0001) or placebo ( < 0.00001). Moreover, the levels of 24-hour urine protein were significantly lower in the allopurinol group ( < 0.00001). The subgroup analysis of Scr showed that the Scr of patients with an allopurinol treatment duration of fewer than six months was significantly lower than that of the control group ( = 0.03). No significant difference in adverse events (AEs) was identified between the treatment and control groups.
CONCLUSIONS
Our meta-analysis of RCTs showed that oral administration of allopurinol effectively reduced SUA levels in patients with diabetes, and patients' renal function was protected. More RCTs with larger sample sizes and higher quality are needed to clarify the role of allopurinol use in decreasing blood pressure, maintaining blood glucose levels, and improving renal function in patients with diabetes.
Topics: Allopurinol; Diabetes Mellitus; Gout; Gout Suppressants; Humans; Hyperuricemia; Kidney; Uric Acid
PubMed: 35856157
DOI: 10.1080/0886022X.2022.2068443 -
BMC Nephrology Jun 2022Asymptomatic hyperuricemia was found to be associated with increased cardiovascular disease risk but the potential benefits of urate-lowering therapy (ULT) remain... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Asymptomatic hyperuricemia was found to be associated with increased cardiovascular disease risk but the potential benefits of urate-lowering therapy (ULT) remain controversial. We conducted a systematic review and network meta-analysis (NMA) with frequentist model to estimate the efficacy and safety of ULT in asymptomatic hyperuricemia.
METHODS
MEDLINE, Embase, and Scopus were searched without language restrictions. Randomized controlled trials (RCT) of adults with asymptomatic hyperuricemia were eligible if they compared any pair of ULTs (i.e., allopurinol, febuxostat, probenecid, benzbromarone, sulfinpyrazone, rasburicase, lesinurad, and topiroxostat) and placebo or no ULT, and had outcomes of interest, including composite renal events, major adverse cardiovascular events, serum urate levels, estimated glomerular filtration rate (eGFR), systolic blood pressure, and adverse events.
RESULTS
NMA with frequentist approach was applied to estimate relative treatment effects, i.e., risk ratio (RR) and mean difference (MD). A total of 23 RCTs were eligible. NMA identified beneficial effects of ULT on composite renal events and eGFR but not for other outcomes. Allopurinol and febuxostat had significantly lower composite renal events than placebo (RR 0.39, 95% confidence interval [CI] 0.23 to 0.66, and RR 0.68, 95% CI 0.46 to 0.99, respectively). Both treatments also resulted in significantly higher eGFR than placebo (MD 3.69 ml/min/1.73 m, 95% CI 1.31 to 6.08, and MD 2.89 ml/min/1.73 m, 95% CI 0.69 to 5.09, respectively). No evidence of inconsistency was identified.
CONCLUSIONS
Evidence suggests that allopurinol and febuxostat are the ULTs of choice in reducing composite renal events and improving renal function.
TRIAL REGISTRATION
This study was registered with PROSPERO: CRD42019145908. The date of the first registration was 12 November 2019.
Topics: Adult; Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Network Meta-Analysis; Randomized Controlled Trials as Topic; Uric Acid
PubMed: 35739495
DOI: 10.1186/s12882-022-02850-3 -
Journal of Current Ophthalmology 2022To systematically review the role of antioxidants in management of patients with thyroid eye disease (TED). (Review)
Review
PURPOSE
To systematically review the role of antioxidants in management of patients with thyroid eye disease (TED).
METHODS
A literature search of the electronic databases was performed without restrictions on the date of publication till the end of March 2021, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Clinical trials, case-control studies, cohorts, case series, case reports, and experimental (including ) studies in the English language were included. The primary outcome in human studies was improvement in severity, activity scores, and/or quality of life scores. There was a decrease in the level of HO-dependent oxidative stress, Hyaluronic acid release, reactive oxygen species, cell proliferation, or antifibrotic/antiproliferative actions in the studies.
RESULTS
Out of 374 initially screened articles, 157 studies were selected, the full texts of 82 were reviewed, and 14 papers were finally included. There were 4 clinical and 10 studies from 1993 to 2018. While β-carotene, retinol, Vitamin E, Vitamin C, melatonin, resveratrol, N-acetyl-l-cysteine, and quercetin showed some efficacy in studies; allopurinol, nicotinamide, pentoxifylline, and selenium (Se) were effective in both clinical and experimental reports. Se was the only recommended antioxidant based on one high-level randomized controlled trial.
CONCLUSION
While different antioxidants could potentially be effective in the management of TED, no strong recommendation for any or combination of antioxidants could be made to be implemented in the daily practice.
PubMed: 35620378
DOI: 10.4103/joco.joco_266_21