Ribavirin dose management in HCV patients receiving ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin

Background & Aims: Some individuals with hepatitis C virus infection treated with direct-acting antivirals require ribavirin to maximize sustained virological response rates. We describe the clinical management of ribavirin dosing in hepatitis C virus-infected patients receiving ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin. Methods: We performed a post hoc analysis of patients receiving ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin for 12 or 24 weeks in six phase 3 trials. Multivariate stepwise logistic regression models assessed predictors associated with ribavirin dose adjustments and with developing anaemia. Results: Of 1548 patients, 100 (6.5%) modified ribavirin dose due to haemoglobin declines, of which 99% achieved sustained virological response at 12 weeks post-treatment. Median time to first ribavirin dose reduction was 37 days. Low baseline haemoglobin was significantly associated with an increased risk of requiring ribavirin dose modification (odds ratio: 0.618 [0.518, 0.738]; P < .001) and developing anaemia (odds ratio: 0.379 [0.243, 0.593]; P < .001). Conclusions: Ribavirin dose reductions were infrequent, occurred early in treatment, and did not impact sustained virological response at 12 weeks post-treatment. Patients with low baseline haemoglobin should be monitored for on-treatment anaemia

Striatal dopamine D2 receptor binding of risperidone in schizophrenic patients as assessed by 123I-iodobenzamide SPECT: a comparative study with olanzapine

The aim of this investigation was to compare the degree of striatal dopamine-(D2) receptor blockade by two atypical antipsychotic drugs, risperidone and olanzapine. The percentage of D2 receptor occupancy during treatment was calculated by comparing the results of 123I-iodobenzamide SPECT with those from healthy control subjects. Twenty inpatients suffering from schizophrenia or schizoaffective psychosis according to DSM IV/ICD-10 criteria were treated with clinically recommended doses of risperidone and compared with 13 inpatients treated with up to 20 mg olanzapine. Neuroleptic dose and D2 receptor blockade correlated strongly for both risperidone (Pearson r = –0.86, p = 0.0001) and olanzapine (Pearson r = –0.77, p = 0.002). There was no significant difference between the D2 receptor occupancy of the two substances when given in the clinically recommended dose range (unpaired t-test, t= –0.112, p=0.911)

Protective role of vitamin B6 (PLP) against DNA damage in Drosophila models of type 2 diabetes

Growing evidence shows that improper intake of vitamin B6 increases cancer risk and several studies indicate that diabetic patients have a higher risk of developing tumors. We previously demonstrated that in Drosophila the deficiency of Pyridoxal 5' phosphate (PLP), the active form of vitamin B6, causes chromosome aberrations (CABs), one of cancer prerequisites, and increases hemolymph glucose content. Starting from these data we asked if it was possible to provide a link between the aforementioned studies. Thus, we tested the effect of low PLP levels on DNA integrity in diabetic cells. To this aim we generated two Drosophila models of type 2 diabetes, the first by impairing insulin signaling and the second by rearing flies in high sugar diet. We showed that glucose treatment induced CABs in diabetic individuals but not in controls. More interestingly, PLP deficiency caused high frequencies of CABs in both diabetic models demonstrating that hyperglycemia, combined to reduced PLP level, impairs DNA integrity. PLP-depleted diabetic cells accumulated Advanced Glycation End products (AGEs) that largely contribute to CABs as α-lipoic acid, an AGE inhibitor, rescued not only AGEs but also CABs. These data, extrapolated to humans, indicate that low PLP levels, impacting on DNA integrity, may be considered one of the possible links between diabetes and cancer

Peginterferon alfa-2a (40KD) (PEGASYS®) plus ribavirin (COPEGUS®) in retreatment of chronic hepatitis C patients, nonresponders and relapsers to previous conventional interferon plus ribavirin therapy

Peginterferon alfa plus ribavirin is currently the treatment of choice for chronic hepatitis C. Peginterferon alfa-2a (40KD) plus ribavirin has given an overall sustained virological response of 18% in F3/F4 previous nonresponder US patients. We evaluated the effectiveness of peginterferon alfa-2a (40KD) plus ribavirin in Brazilian patients who were relapsers or nonresponders to previous interferon-based therapy. One-hundred-thirty-four patients with biopsy-proven chronic hepatitis C, HCV RNA positive, elevated ALT and who were either relapsers (n=37) or nonresponders (n=97) to at least 24 weeks of conventional interferon/ribavirin therapy were retreated with peginterferon alfa-2a (40KD) 180mg/qw and ribavirin 800mg bid for 48 weeks. Efficacy was assessed as virological response (defined as undetectable HCV RNA) at the end of treatment (EoT) and at the end of follow-up (SVR - Sustained Virological Response). Safety assessments consisted of clinical and laboratory evaluations. In the patient sample, 72% were genotype 1 and 34% were cirrhotic. In an intention-to-treat analysis, relapser patients showed 78% EoT response and 51% SVR. Nonresponders showed 57% EoT response and 26% SVR. Positive predictive factors of SVR were non-1 genotype and relapser state. Six percent of the patients interrupted treatment because of adverse events and 45% had dose reduction (mainly associated with leucopenia and anemia). Brazilian patient relapsers and nonresponders to conventional interferon and ribavirin treatment can achieve a sustained virological response when retreated with peginterferon alfa-2a (40KD) and ribavirin. The safety profile is similar to that of naive patients.Federal University of São PauloSanta Casa de Misericórdia Gastroenterology ServiceFederal University of ParáFederal University of Juiz de ForaSão Paulo University Medical School of Ribeirão PretoEmílio Ribas InstituteFederal University of Minas GeraisMedical School of São José do Rio PretoFederal University of AlagoasFederal University of Santa CatarinaFederal University of BahiaTropical Medicine FundationOswaldo Cruz HospitalFederal University of ParaíbaRocheUNIFESPSciEL

DIREITOS HUMANOS DE GÊNERO FEMININO E A GLOBALIZAÇÃO DE UMA NECESSIDADE LATENTE

Os Direitos Humanos de Gênero Feminino e globalização de uma necessidade latente objetiva traduzir sob a ótica do masculino ativo e do feminino passivo ao longo da história a localização da existência ou perda dos direitos humanos de gênero feminino, dentro do ordenamento jurídico globalizado. Os momentos em os movimentos de luta social voltaram-se para as mulheres absorvendo as críticas feministas e a criação de conceitos. A análise da sujeição passiva das mulheres e o reflexo nos crimes de gênero motivados pela desigualdade social e dependência financeira. A noção de direitos humanos condicionada a diversos elementos como o sistema político e econômico, e a cultura de cada país, bem como a moral e às regras sociais vigentes em determinada sociedade. Entre outros questionamentos que foram respondidos com estatísticas realizadas em trabalhos de campo por equipes multidisciplinares que compilaram uma série de dados específicos motivadores de modificações de leis que versam sobre direitos humanos de gênero feminino, precisamente a Lei 14.188/21 altera o art. 12-C da Lei 11.340/06 quepassa elencar a possibilidade do risco atual ou iminente à integridade psicológica. Diante de toda pesquisa realizada observou-se que a base para a construção dos direitos humanos de gênero feminino, encontra-se na possibilidade de resgate do valor da pessoa humana – mulher que apesar de formalmente garantido por cartas constitucionais ou pelo direito internacional ainda sofre com a insuficiência de mecanismos para garanti-los. A presente pesquisa envolve o tema: direitos humanos de gênero feminino, dentro do ordenamento jurídico globalizado, a busca por respostas relativas à existência e perda destes direitos, se chegou a existir em algum momento, quando deixou de fazer parte do sistema social, quando os direitos humanos passaram proteger objetivamente mulheres? Busca que utiliza procedimentos constituídos pelo método qualitativo, proporcionando a construção e/ou revisão de novas abordagens, sobre o tema direitos humanos de gênero feminino. Palavras-chave: Direitos Humanos de Gênero Feminino. Feminismo. Direito Internacional. Direito Humanitário. Movimentos de luta social. Novos Direitos

Incidência de cárie após tratamento profissional com fluoretos : uma revisão sistemática

Aim:The purpose of this studywas to assess whether individuals with active caries lesions treated with professional topical application of fluoride at high concentrations show a lower incidence of caries than individuals who have not received professional treatment with fluoridated products. Literature review:Randomized clinical trials in which patients were followed up for at least 6 months were included. Studieswere identified with MEDLINE, Embase, LILACS, SCOPUS, and Cochrane Database of Systematic Reviews. Pairs of reviewers independently conducted study selection, data extraction, and risk-of-bias assessments. Eight trials, which included 5018 children and adolescents, were eligible. Results were evaluated by calculating the preventive fraction to standardize the outcomes.Results:Fluoride varnish yielded a better preventive fraction (90.18% to 14.6%) in both primary and permanent dentitions in comparison with methods using gel (22.3% to 6%) and foam (24%) after a mean follow-up period of 20.6 months. Regardless of the product used, increased frequency of application yielded greater benefit. Discussion:Theseresults do not agree with previous findings that, in 8 weeks periods, did not observe an additional effect of the professional use of fluorides over the control treatments(biofilm control). The presentreview indicatesthe need for long-term monitoring of the effect of treatment, whereby the effects of high fluoride concentrations may appear. Conclusion:Professional fluoride treatment proved to be effective in preventing new long-term injuries in both primary and permanent dentition, irrespective of the vehicle used (varnish, gel, or foam). (PROSPERO Register number CRD42021210740).Objetivo: Avaliar se indivíduos com lesões ativas de cárie tratadas com aplicação tópica profissional de fluoretos em altas concentrações apresentam menor incidência de cárie do que indivíduos que não receberam este tratamento. Revisão da literatura: Ensaios clínicos randomizados, com acompanhamento de pelo menos 6 meses foram incluídos. Os estudos foram identificados nas bases de dados MEDLINE, Embase, LILACS, SCOPUS e Cochrane Database of Systematic Reviews. Pares de revisores conduziram de forma independente a seleção de estudos, extração de dados e avaliações de risco de viés. Oito estudos, que incluíram 5.018 crianças e adolescentes, foram elegíveis. Os resultados foram avaliados por meio do cálculo da fração preventiva. Resultados:O verniz fluoretado apresentou melhor fração preventiva (90,18% a 14,6%), tanto na dentição decídua quanto na permanente, em comparação com os métodos com gel (22,3% a 6%) e espuma (24%) após um período médio de seguimento de 20,6 meses. Independentemente do produto utilizado, o aumento da frequência de aplicação apresentou maior benefício. Discussão:Estes resultados diferem de achados anteriores em que, em períodos de 8 semanas, não houve efeito adicional do uso profissional de fluoretos em relação ao tratamento controle. A presente revisão indicou a necessidade de monitoramento a longo prazo do efeito do tratamento, quando os efeitos do fluoreto de alta concentração podem aparecer. Conclusão: O tratamento profissional com flúor mostrou-se eficaz na prevenção de novas lesões a longo prazo, tanto na dentição decídua quanto na permanente, independente do veículo utilizado (verniz, gel ou espuma). (Número de registro PROSPERO CRD42021210740)

Safety of the 2D/3D direct-acting antiviral regimen in HCV-induced Child-Pugh A cirrhosis – A pooled analysis

AbstractBackground & aimsChronic hepatitis C virus (HCV)-infected patients with cirrhosis are a high-priority population for treatment. To help inform the benefit–risk profile of the all-oral direct-acting antiviral (DAA) combination regimen of ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir (OBV/PTV/r ± DSV) in patients with Child-Pugh A cirrhosis, we undertook a comprehensive review of AbbVie-sponsored clinical trials enrolling patients with Child-Pugh A cirrhosis.MethodsTwelve phase II or III clinical trials of the 2-DAA regimen of OBV/PTV/r ± ribavirin (RBV) or the 3-DAA regimen of OBV/PTV/r + DSV ± RBV that included patients with Child-Pugh A cirrhosis were reviewed; patients who completed treatment by November 16, 2015 were included in a pooled, post hoc safety assessment. The number and percentage of patients with treatment-emergent adverse events (TEAEs), serious TEAEs, and TEAEs consistent with hepatic decompensation were reported.ResultsIn 1066 patients with Child-Pugh A cirrhosis, rates of serious TEAEs and TEAEs leading to study drug discontinuation were 5.3% (95% CI: 4.1–6.8) and 2.2% (95% CI: 1.4–3.2), respectively. Thirteen patients (1.2%; 95% CI: 0.7–2.1) had a TEAE that was consistent with hepatic decompensation. The most frequent TEAEs consistent with hepatic decompensation were ascites (n=8), esophageal variceal hemorrhage (n=4), and hepatic encephalopathy (n=2).ConclusionsThis pooled analysis in 1066 HCV-infected patients with Child-Pugh A cirrhosis confirms the safety of OBV/PTV/r ± DSV ± RBV in this population. These results support the use of OBV/PTV/r ± DSV ± RBV in this high-priority population.Lay summaryThis pooled safety analysis in 1066 HCV-infected patients with compensated cirrhosis, receiving treatment with ombitasvir, paritaprevir, and ritonavir with or without dasabuvir, with or without ribavirin, shows that the rate of hepatic decompensation events was comparable to rates from historical reports for untreated patients

Evaluation of sustainable solutions for water supply and sewage treatment in small municipalities using gradients of urban density

Com o crescimento urbano, torna-se necessário definir as formas de atendimento à necessidade humana por água, em qualidade e quantidade adequadas. O presente artigo busca identificar como os gradientes de densidades populacionais podem contribuir na definição de soluções sustentáveis para o suprimento de água e tratamento de esgoto em pequenas municipalidades. Partiu-se da definição das áreas estratégicas, em termos de sustentabilidade, buscando-se determinar, com base em dados gratuitos e publicamente disponíveis, a densidade urbana do município de Feliz/RS, bem como a distribuição do abastecimento de água e destinação dos efluentes domésticos. A partir desse diagnóstico, que considera as particularidades do município, foram propostas soluções alternativas e descentralizadas para as áreas avaliadas. Os resultados mostram que a avaliação integrada e espacial pode conduzir a soluções mais sustentáveis, que envolvam e empoderem a comunidade local quanto ao uso e cuidado com a água e como potencial de suporte à tomada de decisão.As cities grow, it becomes necessary to define ways of meeting the human need for water in adequate quality and quantity. In this article, it was identified how population densities gradients can contribute to the definition of sustainable solutions for water supply and sewage treatment in small municipalities. Strategic areas were defined in terms of sustainability, seeking to determine, based on free and public data, the urban density of the municipality of Feliz/RS and the distribution of water supply and solutions for domestic effluents. Based on this diagnosis, which considers the particularities of the municipality, alternative and decentralized solutions were proposed for the assessed areas. The results show that the integrated and spatial assessment can lead to more sustainable solutions, which involve and empower the local community regarding the use and care of water and with the potential to support decision makin