Mapping the characteristics, concepts and methodologies of matching-adjusted indirect comparison studies assessing pharmacological therapies in oncology: a scoping review protocol.

INTRODUCTION: Matching-adjusted indirect comparison (MAIC) studies are a subtype of indirect comparison, which uses propensity score weighting to enhance comparability. This method adjusts aggregated data based on covariables from individual patient data from studies to produce population-adjusted indirect comparisons. Some national Health Technology Assessment agencies have recently received submissions containing MAIC models. However, there can be a lack of confidence in its estimates when they are poorly reported and inconsistent with other techniques. The objective of this study is to map the characteristics, concepts and methodology of MAIC studies used for pharmacological therapies in the field of oncology. METHODS AND ANALYSIS: A scoping review methodology will be applied following the Joanna Briggs Institute framework and the results will be reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews. Studies that used MAIC to compare treatments in oncology conditions will be considered eligible. A systematic search will be conducted in PubMed, Embase and the Cochrane Library. No restriction of location or language will be applied. Study screening will be documented and presented in a Preferred Reporting Items for Systematic reviews and Meta-Analyses flow diagram. Data will be extracted and recorded on a predefined data form and will be presented in a tabular form accompanied by a descriptive summary. ETHICS AND DISSEMINATION: No ethical approval is required for this study. The results of this scoping review will be disseminated through peer-reviewed publications.

Pharmacovigilance: an evaluation on the practice of pharmacists acting in pharmacies and drugstores

Abstract Pharmacists acting in pharmacies and drugstores stores are some of the most accessible healthcare providers and the last to intervene before the patient takes their medicine. This puts the pharmacist in a position of authority that should be harnessed for the benefit of health. Thus, this professional is strategic for performing pharmacovigilance. Our objective of this study was to interrogate the practice of pharmacists in relation to pharmacovigilance activities, and to identify difficulties and possible stimuli for the improvement these activities in pharmacies and drugstores. The information was collected through an online questionnaire via Survey Monkey®. The data were analyzed statistically using SPSS software. Responses were received from 5174 pharmacists: mostly young women within five years of graduation and experience in pharmaceutical retail. 81% of them reported having identified suspected substandard medicines, but only 16% used the Brazilian notification system Notivisa. More than 85% of pharmacists agreed with the importance of pharmacovigilance and the recognition of reporting services as part of pharmacist duties and pharmaceutical care. The main barriers to making notifications were the lack of access and knowledge about Notivisa. Pharmacists agreed that simplifying the system would be a stimulus for notifications, and requested more feedback from notifications, as well as material and courses to understand the notification process. Pharmacists have important data to feed into pharmacovigilance systems, recognize their responsibilities and are willing to contribute, but still demonstrate low compliance. Simplification of the system and training on it are likely to increase notifications.

Sensitivity and specificity of multibacillary and paucibacillary leprosy laboratory tests: A systematic review and meta-analysis.

This systematic review (number register: CRD42018112736) was performed to compare the sensitivity and specificity of leprosy diagnostic methods. The search was conducted in 3 electronic databases in January 2021. Studies evaluating leprosy diagnostic tests were included according the eligibility criteria. Meta-analysis was performed to calculate the sensibility and specificity of the groups. We included 36 studies. The test sensitivity for paucibacillary patients was 0.31 (95%CI: 0.29-0.33) and the specificity was 0.92 (95%CI: 0.92-0.93). In multibacillary patients, the sensitivity was 0.78 (95%CI: 0.77-0.80) and specificity was 0.92 (95%CI: 0.92-0.93). Comparing the sensitivity and specificity of the different techniques included, it should be noted that polymerase chain reaction (PCR) test presented the highest sensitivity for paucibacillary patients, while the western blot technique showed the highest sensitivity for multibacillary patients. However, further studies are needed to optimise the diagnosis of leprosy, requiring research with a larger number of samples and more uniform protocols.

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.

Effect of different interval training protocols on adiposity indicators in overweight-obese children and adolescents: a systematic review and meta-analysis / Efeito de diferentes protocolos de treinamento intervalado sobre indicadores de adiposidade em crianças e adolescentes com sobrepeso e obesidade: uma revisão sistemática e metanálise

ABSTRACT The present meta-analysis verified the impact of different protocols of high-intensity interval training (HIIT) on indicators of adiposity in overweight and obese children and adolescents. Searches were performed in the databases: PubMed, ScienceDirect, SPORTDiscus, LILACS and SciELO. Were included studies without caloric restriction that aimed to verify the effect of HIIT interventions on the adiposity indicators in overweight children and adolescents published until December 2018. The PEDro scale was used to assess the risk of bias. The meta-analysis was conducted in the Revman software using standardized mean difference (SMD) data and 95% confidence intervals (CI). Seventeen studies were selected, which involved 289 children and adolescents with overweight and obesity. HIIT interventions (mean=11.7±5.9 weeks) produced significant decreases in body fat percentage (SMD=-0.65; CI=-1.07, -0.23) and waist circumference (SMD=-0.34; CI=-0.49, -0.18). Also, major relative risk of decrease in body fat percentage were observed in favour to protocols with work/recovery interval ratios of 1:1 and 2:1. HIIT protocols with ratios (work/recovery intervals) 1:1 and 2:1 promote significant reductions in fat percentage and waist circumference in overweight and obese children, independently of the total work time.

RESUMO A presente meta-análise verificou o impacto de diferentes protocolos de treinamento intervalado de alta intensidade (HIIT) sobre indicadores de adiposidade em crianças e adolescentes com sobrepeso e obesidade. As buscas foram realizadas nas bases de dados: PubMed, ScienceDirect, SPORTDiscus, LILACS e SciELO. Foram incluídos estudos sem restrição calórica, que objetivaram verificar o efeito das intervenções do HIIT nos indicadores de adiposidade em crianças e adolescentes acima do peso publicados até dezembro de 2018. A escala PEDro foi utilizada para avaliar o risco de viés. A meta-análise foi conduzida no software Revman a partir dos dados de diferença média padronizada (SMD) e intervalos de confiança de 95% (IC). Foram selecionados 17 estudos, envolvendo 289 crianças e adolescentes com sobrepeso e obesidade. As intervenções de HIIT (duração=11,7±5,9 semanas) produziram reduções significativas no percentual de gordura corporal (SMD=-0,65; IC=-1,07,-0,23) e circunferência da cintura (SMD=-0,34; IC=-0,49-0.18). Também foi observado um risco relativo maior de diminuição do percentual de gordura corporal a favor de protocolos com proporção de intervalos de trabalho/recuperação de 1:1 e 2:1. Protocolos HIIT com proporções 1:1 e 2:1 promovem reduções significativas no percentual de gordura e circunferência da cintura em crianças com sobrepeso e obesidade, independentemente do tempo total de trabalho.

Quality of life of Brazilian chronic hepatitis C patients treated with interferon-free therapies.

Due to the severity of chronic hepatitis C, there are multiple factors that can negatively affect the quality of life of infected patients. The aim of this study was to evaluate changes in the health-related quality of life (HRQoL) in patients under second-generation direct-acting antiviral (DAA) (interferon-free) therapies and to assess treatment effectiveness. This was an observational study conducted in Curitiba (Brazil) using two instruments (a generic and a specific) for measuring the quality of life in patients with chronic hepatitis C, the Short Form-36 (SF-36) and the Chronic Liver Disease Questionnaire (CLDQ) for liver disease evaluation. The study included patients receiving any interferon-free therapy for hepatitis C treatment during 2016 and 2017. Data were collected before, during, and after treatment regarding the two questionnaires, effectiveness and safety. Fifty-six patients fulfilled all eligibility criteria and were included for analysis. Sustained virological response was obtained in 88% of the patients. They were mainly genotype 1, cirrhotic and treated with sofosbuvir combined with daclatasvir or sofosbuvir with simeprevir. Improvement in the quality of life was observed for several domains in both questionnaires (p < 0.05) in the comparison before and after treatment. Patients receiving sofosbuvir with daclatasvir had significantly lower scores compared to the group receiving sofosbuvir with simeprevir. Second-generation DAA therapies were effective and have considerably increased the HRQoL of patients with chronic hepatitis C virus.

Cost-effectiveness of amphotericin B formulations in the treatment of systemic fungal infections.

Amphotericin formulations, indicated for invasive fungal infections (IFIs), vary in effectiveness, safety and costs. In Brazil, only the conventional formulation is provided by the Public Health System. The aim of this study was to perform a cost-effectiveness analysis comparing conventional amphotericin B (CAB), liposomal amphotericin B (LAB) and amphotericin B lipid complex (ABLC). Therefore, a decision tree was developed. The model began with high-risking patients on suspicion or confirmation of IFI. The analysis was conducted under the perspective of the Brazilian Public Health System. Model health states were defined according to medication use and clinical evolution. Clinical efficacy (cure) and transition probabilities were derived from the literature. Resource use was estimated from Brazilian data. Time horizon followed the maximum treatment time determined in the patient information leaflets (3 or 6 weeks). One-way and probabilistic-sensitivity analyses were conducted. The conventional formulation was the most cost-effective. No dominance was observed; however, high incremental cost-effectiveness ratios were obtained for LAB (USD 313 130) and ABLC (USD 1 711 280). Sensitivity analyses demonstrated the robustness of the results. CAB is the most cost-effective treatment, followed by LAB and ABLC. Although CAB presents critical safety aspects, the high acquisition costs of the other formulations prevent their large-scale use in Brazil.

Effectiveness and tolerability of direct-acting antivirals for chronic hepatitis C patients in a Southern state of Brazil

ABSTRACT Background This study aimed to evaluate the clinical effectiveness in terms of sustained virological response and tolerability of available second generation direct-acting antivirals in Brazilian patients. Methods This was a retrospective observational study conducted in six centers in Southern Brazil. The sample comprised adult patients who were chronically infected with hepatitis C virus, regardless of virus genotype, fibrosis stage, or prior treatment. Statistical analysis was performed to compare the effectiveness among the treatments, and also to uncover the factors influencing the achievement of sustained virological response. Results A total of 296 patients were included in the study, with the majority receiving sofosbuvir with daclatasvir (59%) or sofosbuvir with simeprevir (26%). Overall sustained virological response rates were approximately 91.6%. For genotype 1, sofosbuvir with daclatasvir had an sustained virological response rate of approximately 95%, while the sustained virological response rate of sofosbuvir with simeprevir was 92%; this difference was statistically significant only for subtype 1b. The only treatment used for genotype 3 patients was sofosbuvir with daclatasvir, and lower rates of sustained virological response were observed for this group, compared to genotype 1 (84% versus 95%, p < 0.05). Apart from this difference between genotypes, and a difference between patients who achieved rapid virologic response compared with those who did not, there were no other statistically significant factors associated with sustained virological response. Conclusions The results point to the effectiveness of second-generation direct-acting antivirals in hepatitis C virus Brazilian patients, especially those with genotype 1. Furthermore, that patients with genotype 3 need more attention and adjustments in available treatment options.

Effectiveness and tolerability of direct-acting antivirals for chronic hepatitis C patients in a Southern state of Brazil.

BACKGROUND: This study aimed to evaluate the clinical effectiveness in terms of sustained virological response and tolerability of available second generation direct-acting antivirals in Brazilian patients. METHODS: This was a retrospective observational study conducted in six centers in Southern Brazil. The sample comprised adult patients who were chronically infected with hepatitis C virus, regardless of virus genotype, fibrosis stage, or prior treatment. Statistical analysis was performed to compare the effectiveness among the treatments, and also to uncover the factors influencing the achievement of sustained virological response. RESULTS: A total of 296 patients were included in the study, with the majority receiving sofosbuvir with daclatasvir (59%) or sofosbuvir with simeprevir (26%). Overall sustained virological response rates were approximately 91.6%. For genotype 1, sofosbuvir with daclatasvir had an sustained virological response rate of approximately 95%, while the sustained virological response rate of sofosbuvir with simeprevir was 92%; this difference was statistically significant only for subtype 1b. The only treatment used for genotype 3 patients was sofosbuvir with daclatasvir, and lower rates of sustained virological response were observed for this group, compared to genotype 1 (84% versus 95%, p<0.05). Apart from this difference between genotypes, and a difference between patients who achieved rapid virologic response compared with those who did not, there were no other statistically significant factors associated with sustained virological response. CONCLUSIONS: The results point to the effectiveness of second-generation direct-acting antivirals in hepatitis C virus Brazilian patients, especially those with genotype 1. Furthermore, that patients with genotype 3 need more attention and adjustments in available treatment options.

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.

Quality of life in Brazilian patients with treated or untreated chronic hepatitis C.

INTRODUCTION: Multiple factors negatively affect the quality of life of patients infected with hepatitis C virus. This study aims to evaluate the effect of pharmacological treatment on the quality of life of these individuals. METHODS: This is a cross-sectional study conducted in two Southern Brazilian centers that used two instruments (a generic and a specific one) for measuring the quality of life in patients with chronic hepatitis C: the Short Form-36 (SF-36); and the Chronic Liver Disease Questionnaire (CLDQ) for liver disease. We included patients from two centers without any treatment (control group), or receiving medication (peginterferon + ribavirin ± telaprevir or boceprevir, i.e., respectively, dual, and triple therapies). RESULTS: One hundred and forty-seven patients were included. Patients under treatment (n = 86) had a lower score in 7 of the 8 SF-36 domains, with statistical significance (p<0.05) only for the emotional function domain. Patients who were not treated (n = 58) had higher scores in 4 of the 6 (p<0.05) CLDQ domains. A comparison of patients, receiving dual or triple therapies for both questionnaires, was only significant in the Vitality domain from CLDQ. CONCLUSIONS: Treatment can affect the subjective perception of patients regarding quality of life. Due to the complexity of the disease, each patient must be evaluated in multiple dimensions. Thus, the results may be useful for understanding the patient's perceptions during treatment, and it can also serve as a reference for care instructions.

Revisão sistemática da eficácia e da segurança das terapias livres de interferon para hepatite C crônica em pacientes coinfectados com o Vírus da Imunodeficiência Humana / Systematic review of the efficacy and safety of interferon-free therapies for chronic hepatitis C in patients coinfected with the Human Immunodeficiency Virus

RESUMO O objetivo deste estudo foi realizar uma revisão sistemática para avaliar a eficácia e a segurança de terapias livres de interferon para hepatite C em pacientes coinfectados com o Vírus da Imunodeficiência Humana. Ao todo, 10 ensaios clínicos foram incluídos em um total de 1.626 pacientes coinfectados com o Vírus da Hepatite C/Vírus da Imunodeficiência Humana, em sua maioria, portadores do genótipo 1, e tratados principalmente por 12 ou 24 semanas. Os pacientes apresentaram taxas de aproximadamente 91% para desfechos de eficácia, enquanto descontinuações por eventos adversos foram inferiores a 3%. Desta forma, as terapias livres de interferon aparecem como uma boa opção para tratamento da hepatite C crônica no grupo de pacientes coinfectados com o Vírus da Imunodeficiência Humana.

ABSTRACT The aim of this study was to conduct a systematic review to evaluate the efficacy and safety of interferon-free therapies for hepatitis C in patients coinfected with the Human Immunodeficiency Virus. In all, 10 clinical trials were included in a total of 1.626 patients coinfected with Hepatitis C Virus/Human Immunodeficiency Virus, mostly, carriers of genotype 1, and treated mainly for 12 or 24 weeks. Patients presented rates of approximately 91% for efficacy outcomes, while discontinuations due to adverse events were less than 3%. In this way, interferon-free therapies appear as a good option for the treatment of chronic hepatitis C in the group of patients coinfected with Human Immunodeficiency Virus.

Condições microbiológicas e higienicossanitárias do caldo de cana comercializado no município de Curitiba- PR / Microbiological and hygienic sanitary conditions of saccharum juice marketed in the city of Curitiba, PR

O caldo de cana é uma bebida popular e amplamente comercializada por ambulantes em diversas cidades brasileiras. Esse tipo de comércio deve cumprir as boas práticas determinadas pela legislação, uma vez que pode propiciar as Doenças Transmitidas por Alimentos (DTA) pela venda de bebidas contaminadas. O objetivo deste trabalho foi avaliar as condições higienicossanitárias e microbiológicas da produção de caldo de cana no município de Curitiba em 10 pontos de venda. O estudo foi dividido em duas etapas: avaliação de cinco parâmetros relativos às condições estruturais e dos manipuladores, por meio de um roteiro de inspeção; e avaliação da qualidade microbiológica do caldo de cana, por meio da coleta de duas amostras em cada ponto de venda. Foi observado que 60% dos comerciantes manipulavam dinheiro simultaneamente ao preparo do caldo e não utilizavam luvas. Além disso, em 40% havia a presença de insetos, 30% apresentavam estrutura precária e 10% dos manipuladores não usavam cabelos presos. Dos locais avaliados, 60% tiveram amostras classificadas como impróprias para o consumo, sendo observados valores superiores a 2 Log.NMP/mL de coliformes termotolerantes, em que todas estavam contaminadas por E. coli. Por fim, a melhoria no cumprimento das boas práticas relaciona-se com a qualidade microbiológica. De acordo com os resultados obtidos no presente estudo, foi visto que se faz necessária a implementação de medidas para a capacitação deste grupo de comerciantes sobre as boas práticas e constante atuação de vigilância de seu cumprimento, preservando a saúde da população no sentido de prevenir as DTA.(AU)

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.