A Systematic Review and Meta-analyses of Longitudinal Studies on Drug Treatments for Gaucher Disease.

OBJECTIVE: Gaucher disease (GD) is a rare disorder linked to the absence/deficiency of glucocerebrosidase. GD can be treated by enzyme replacement therapy (ERT) and substrate reduction therapy (SRT). The aim of this systematic review (SR) is to assess the effectiveness of drugs used for GD treatment. DATA SOURCES: Searches were conducted in PubMed and Scopus, in April 2021. The search strategies encompassed the name of the disease and of the drug treatments. Manual search was also conducted. STUDY SELECTION AND DATA EXTRACTION: Observational and interventional longitudinal studies evaluating ERT and SRT for GD were included. Single mean meta-analyses were conducted for each drug using R. DATA SYNTHESIS: The initial search retrieved 2246 articles after duplicates were removed. Following screening and eligibility assessment, 68 reports were included. The studies evaluated imiglucerase, velaglucerase alfa, taliglucerase alfa, miglustat, and eliglustat. The results showed that ERT is effective as a treatment in both naïve and experienced patients. Miglustat did not significantly improve blood outcomes in naïve patients and resulted in a decrease in the platelet levels of experienced patients. Eliglustat was mainly assessed for experienced patients and resulted in stable outcome values. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This extensive SR confirms the effectiveness of GD treatments in short- and long-term follow-ups. CONCLUSIONS: The results were favorable for all ERTs and for eliglustat. Based on the assessed evidence, miglustat did not achieved expressive results. However, all evidence should be interpreted considering its limitations and does not replace well-conducted randomized trials.

Cost-utility analysis of interferon-free treatments for patients with early-stage genotype 1 hepatitis C virus in Brazil.

INTRODUCTION: We conducted a cost-utility analysis of available interferon-free treatments for patients with early-stage genotype 1 chronic hepatitis C based on a Brazilian public health system perspective. METHODS: A Markov model was derived using a cohort of stage F0-F2 patients treated as recommended by the Brazilian national guidelines. RESULTS: Glecaprevir plus pibrentasvir was superior to all other treatments, followed by sofosbuvir plus velpatasvir. Sofosbuvir plus daclatasvir was identified as the least cost-effective option. CONCLUSIONS: The above findings were confirmed via probabilistic sensitivity analysis and the tested scenarios.

Cost-utility analysis of interferon-free treatments for patients with early-stage genotype 1 hepatitis C virus in Brazil

Abstract INTRODUCTION We conducted a cost-utility analysis of available interferon-free treatments for patients with early-stage genotype 1 chronic hepatitis C based on a Brazilian public health system perspective. METHODS A Markov model was derived using a cohort of stage F0-F2 patients treated as recommended by the Brazilian national guidelines. RESULTS: Glecaprevir plus pibrentasvir was superior to all other treatments, followed by sofosbuvir plus velpatasvir. Sofosbuvir plus daclatasvir was identified as the least cost-effective option. CONCLUSIONS: The above findings were confirmed via probabilistic sensitivity analysis and the tested scenarios.

Doença de Chagas: do surgimento ao tratamento - revisão da literatura / Chagas Disease: from emergence to treatment - a literature review

Embora a doença de Chagas seja endêmica em certas regiões da América Latina, os fluxos migratórios recentes permitiram sua expansão para áreas onde antes era desconhecida. Mais de 8 milhões de pessoas estão infectadas pelo Trypanosoma cruzi, o que resulta em aproximadamente 10.000 mortes por ano. Esta revisão tem como objetivo fornecer uma compilação sobre os tópicos mais importantes da doença de Chagas em um único trabalho: a descoberta por Carlos Chagas (1909), sua ocorrência, epidemiologia, vetores, via de transmissão, patologia, sinais e sintomas, diagnóstico, e tratamentos, ainda limitado a duas drogas utilizadas há mais de 40 anos: nifurtimox e benzonidazol

Although Chagas disease is endemic in certain regions of Latin America, recent migratory flows have allowed it to expand into areas where it was previously unknown. More than 8 million people are infected with Trypanosoma cruzi, causing around 10,000 deaths a year. This review aims to provide a compilation on the most important topics about the Chagas disease in a single place: its discovery by Carlos Chagas (1909), its occurrence, epidemiology, vectors, transmission route, pathology, signs and symptoms, diagnosis, and current treatments, which is still limited to two drugs for more than 40 years: nifurtimox and benzonidazole

Sustained Virological Response in Special Populations with Chronic Hepatitis C Using Interferon-Free Treatments: A Systematic Review and Meta-analysis of Observational Cohort Studies.

BACKGROUND AND OBJECTIVES: Hepatitis C treatment has changed considerably in recent years, and many interferon (IFN)-free therapies are now available. Considering the high rates of sustained virological response (SVR) presented by clinical trials for these treatments, high rates of effectiveness are also expected in real-world clinical practice. Hence, this study aimed to conduct a systematic review and meta-analysis of observational cohort studies to evaluate the clinical effectiveness and safety of IFN-free therapies for hepatitis C. METHODS: The search was performed in four electronic databases and included cohort studies that evaluated IFN-free schemes and provided data on SVR at 12 weeks after the end of treatment (SVR12) as the primary outcome. Overall and subgroup meta-analyses of patients' clinical conditions (e.g. co-infection with human immunodeficiency virus (HIV), cirrhosis, liver transplant, specific genotypes, and other conditions) were performed. RESULTS: Sixty-eight studies encompassing a total of 24,151 patients were included for quantitative and qualitative analyses, evaluating six treatments: sofosbuvir with ledipasvir, daclatasvir, or simeprevir; daclatasvir with asunaprevir; paritaprevir/ritonavir in combination with ombitasvir and dasabuvir; and sofosbuvir with ribavirin. The overall analysis showed SVR rates of 88-96% for all treatments except sofosbuvir combined with ribavirin, which had SVR rates of approximately 80%. The results of subgroup analyses showed that the genotype 3 virus appears to be the most difficult to treat. CONCLUSION: In order to choose the best treatment option, it is necessary to consider the patients' conditions and characteristics. In conclusion, the use of IFN-free therapies meets the high expectations created by clinical trials, including patients in special clinical conditions.

Treatment interruption of biological drugs and tofacitinib in rheumatoid arthritis: A systematic review of case reports

The aim of this study was to evaluate interruption of treatment with biological drugs and tofacitinib due to adverse events in patients with rheumatoid arthritis. A systematic review was performed in the electronic databases MEDLINE, Cochrane, Scopus, CRD, IPA, Lilacs and Scielo. Case reports addressing interruption of treatment due to any adverse event related to abatacept (ABA), adalimumab (ADA), anakinra (ANA), certolizumab pegol (CER), etanercept (ETA), golimumab (GOL), infliximab (IFX), rituximab (RTX), secukinumab (SEC), tocilizumab (TCZ), tofacitinib (TOF) or ustekinumab (UST) in rheumatoid arthritis patients were evaluated. Baseline data, patient profile, previous and current treatments, cause of discontinuation and information on reintroduction of treatment were extracted from the case reports. One hundred and fifty-four studies (154 patients) reported 162 discontinuations of rheumatoid arthritis treatment due to adverse events (ETA = 57; IFX = 46; ADA = 32; TCZ = 13; RTX = 5; ANA = 3; GOL = 2; ABA = 2; TOF = 1; CER = 1; SEC = 0 and UST = 0). The mean age of patients was 56 (± 12.1) years and 82% were female. Seventy-four adverse events were confirmed (related to used drug), and 138 were observed in patients using anti-TNF. The most common adverse events were infections (21%), skin disease (15%), autoimmune disease (13%) and hematological disorders (9%). Case reports are important in the detection of rare adverse events and should be considered in the choice of appropriate therapy for patients.

New Metabolites of Coumarin Detected in Human Urine Using Ultra Performance Liquid Chromatography/Quadrupole-Time-of-Flight Tandem Mass Spectrometry.

Coumarin (1,2-benzopyrone) is a natural compound whose metabolism in humans was established in the 1970s. However, a new metabolite was recently identified in human plasma, indicating that the metabolism of coumarin has not been completely elucidated. To complement the knowledge of its metabolism, a rapid and sensitive method using UPLC-QTOF-MS was developed. A total of 12 metabolites was identified using MetaboLynxTM software, including eight metabolites not previously reported in human urine. The identified biotransformation included hydroxylation, glucuronidation, sulfation, methylation, and conjugation with N-acetylcysteine. The present work demonstrates that the metabolism study of coumarin was incomplete, possibly due to limitations of old techniques. The identification of eight inedited metabolites of such a simple molecule suggests that the information regarding the metabolism of other drugs may also be incomplete, and therefore, new investigations are necessary.

Bioanalytical methods for the detection of antidiabetic drugs: a review.

Type 2 diabetes mellitus, a disease which prevalence has been progressively increasing worldwide, is characterized by chronic hyperglycemia resulting from the combination of inappropriate insulin secretion and/or resistance to insulin action. If left uncontrolled, diabetes is associated with complications such as dysfunction and failure of various organs, and even premature death. Along with lifestyle-modification strategies, several classes of oral antidiabetic agents can be employed for glycemic control. Thus, therapeutic drug monitoring of these drugs is essential to maintain appropriate treatment. This review discusses the most frequently employed analytical techniques and sample preparation systems to obtain a reliable and trustworthy method to quantify antidiabetic drugs in biological matrices. An adequate choice of internal standard, ideal chromatography conditions and most suitable analytical detector are reported.

A systematic and critical review on bioanalytical method validation using the example of simultaneous quantitation of antidiabetic agents in blood.

A systematic and critical review was conducted on bioanalytical methods validated to quantify combinations of antidiabetic agents in human blood. The aim of this article was to verify how the validation process of bioanalytical methods is performed and the quality of the published records. The validation assays were evaluated according to international guidelines. The main problems in the validation process are pointed out and discussed to help researchers to choose methods that are truly reliable and can be successfully applied for their intended use. The combination of oral antidiabetic agents was chosen as these are some of the most studied drugs and several methods are present in the literature. Moreover, this article may be applied to the validation process of all bioanalytical.

Fluconazole Doses Used for Prophylaxis of Invasive Fungal Infection in Neonatal Intensive Care Units: A Network Meta-Analysis.

OBJECTIVES: To evaluate the safety and efficacy of different doses of fluconazole used for invasive prophylaxis of fungal infection in neonates. STUDY DESIGN: A systematic search was conducted with PubMed, Scopus, and Web of Science. A manual search was performed as well. Only randomized controlled trials of neonates in a neonatal intensive care unit (NICU) who received fluconazole prophylaxis for invasive fungal infection, regardless of the dose or therapeutic regimen, were included in this review. Data on baseline characteristics, outcomes incidence of proven invasive Candida infection, overall mortality, and invasive Candida infection-related mortality were extracted. RESULTS: Eleven studies were included in the review, with fluconazole doses of 3, 4, or 6?mg/kg. When the incidence of invasive Candida and invasive Candida-related mortality were considered as outcomes, the 3 and 6?mg/kg fluconazole doses were found to be statistically superior to placebo (OR, 5.48 [95% credible interval, 1.81-18.94] and 2.63 [1.18-7.02], respectively, and 15.32 [1.54-54.31] and 9.14 [1.26-142.7], respectively), but data for the 3 doses were not statistically significantly different. CONCLUSIONS: Use of the lowest fluconazole dose (3?mg/kg) should be recommended for Candida prophylaxis in neonates, given that increasing the fluconazole dose is not associated with higher efficacy and has greater potential for toxicity and increased cost.

Simultaneous Quantification of Antidiabetic Agents in Human Plasma by a UPLC-QToF-MS Method.

An ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry method for the simultaneous quantification of chlorpropamide, glibenclamide, gliclazide, glimepiride, metformin, nateglinide, pioglitazone, rosiglitazone, and vildagliptin in human plasma was developed and validated, using isoniazid and sulfaquinoxaline as internal standards. Following plasma protein precipitation using acetonitrile with 1% formic acid, chromatographic separation was performed on a cyano column using gradient elution with water and acetonitrile, both containing 0.1% formic acid. Detection was performed in a quadrupole time-of-flight analyzer, using electrospray ionization operated in the positive mode. Data from validation studies demonstrated that the new method is highly sensitive, selective, precise (RSD < 10%), accurate (RE < 12%), linear (r > 0.99), free of matrix and has no residual effects. The developed method was successfully applied to volunteers' plasma samples. Hence, this method was demonstrated to be appropriate for clinical monitoring of antidiabetic agents.