Una visión integral del manejo de la hepatitis C y el objetivo de erradicarla / A comprehensive view of hepatitis C management and the goal of eradication

La hepatitis C es una enfermedad viral causada por el virus de la hepatitis C (VHC), que fue identificada por primera vez en 1989 por un equipo de científicos liderado por Michael Houghton en Chiron Corporation. Esta forma de hepatitis era conocida como "hepatitis no-A no-B", ya que no se podía identificar el agente infeccioso responsable. Puede afectar a personas de diferentes géneros y orientaciones sexuales, incluidos los hombres que tienen sexo con hombres (HSH); y su transmisión ocurre a través de situaciones en las que hay un intercambio de sangre, como el uso compartido de agujas o equipo para la inyección de drogas, o durante prácticas sexuales que pueden causar microlesiones en la mucosa anal. Es importante destacar que la hepatitis C también puede transmitirse a través de otras vías, como la transfusión de sangre no segura, la exposición a instrumentos médicos contaminados, o el compartir objetos personales que puedan tener sangre infectada.

Hepatitis C is a viral disease caused by the hepatitis C virus (HCV), which was first identified in 1989 by a team of scientists led by Michael Houghton at Chiron Corporation. This form of hepatitis was known as "non-A non-B hepatitis" as the infectious agent responsible couldn't be identified. It can affect individuals of different genders and sexual orientations, including men who have sex with men (MSM); transmission occurs through situations involving blood exchange, such as needle sharing or equipment for drug injection, or during sexual practices that may cause microlesions in the anal mucosa. It's important to note that hepatitis C can also be transmitted through other routes, such as unsafe blood transfusion, exposure to contaminated medical instruments, or sharing personal items that may have infected blood.

Effect of Direct-acting Antivirals Treatment on Renal Function Among HCV-infected Patients / 中山大学学报(医学科学版)

； ObjectiveTo explore the effect of direct-acting antiviral treatment on renal function in patients with chronic hepatitis C. MethodsA total of 123 HCV-infected patients receiving DAAs treatment at the Third Affiliated Hospital of Sun Yat-sen University from January 2017 to December 2021 were included in this study. To explore the renal function in patients with chronic hepatitis C treated with direct-acting antivirals， serum creatinine values were collected before， during and after the treatment， which were used to estimate the eGFR by the MDRD equation to assess the changes in renal function. ResultsOf the 123 patients enrolled， 67.5%（n=83）were male， and the mean age of participants was （50±11） years old. The mean follow-up period was 24 weeks . Comorbidities included cirrhosis in 26.8%， and diabetes in 10.6%. Meanwhile， 11.4% of the cohort had eGFR < 60 mL/（min ·1.73 m2）， 33.3% of the cohort had eGFR 60 to 90 mL/（min ·1.73 m2）， and 55.3% had eGFR≥90 mL/（min ·1.73 m2）. No decrease in renal function was seen among all the HCV-infected patients at the end of treatment or the follow-up period after treatment. However， compared with the eGFR at the baseline， eGFR in CKD2 patients in the follow-up period was improved 【（88.65±15.52） mL/（min ·1.73 m2）vs （78.12 ±7.60） mL/（min ·1.73 m2）， P< 0.001】. And 14.6% （n=18） of patients experienced progressive deterioration of renal function. Logistic regression analysis showed that diabetes could predict the deterioration of renal function （OR=4.663， P=0.016）. ConclusionsOur study shows renal function is not impair among HCV-infected patients following DAAs treatment， and renal function in CKD2 patients have improvements. However， HCV-infected patients with diabetes mellitus are at a high risk of renal impairment and closely monitoring of renal function is still needed.

Effect of treatment with direct-acting antiviral agents on the prognosis of extrahepatic diseases in patients with hepatitis C / 临床肝胆病杂志

The prognosis of patients with hepatitis C virus infection depends not only on liver lesions， but also on extrahepatic sequelae. Direct-acting antiviral agents （DAAs）， as the first-line drugs in the treatment of hepatitis C， have helped more and more patients achieve sustained virologic response and clinical cure， but its effect on the prognosis of extrahepatic diseases remains unclear. This article reviews the effect of DAAs treatment on the prognosis of extrahepatic diseases in patients with hepatitis C and points out that long-term follow-up monitoring is still required for patients with hepatitis C after cure.

Evidence of intrauterine device insertion by nurses in Primary Health Care: an integrative review / Evidencias de inserción de dispositivos intrauterinos por parte de enfermeros en Atención Primaria de Salud: revisión integradora / Evidências da inserção de dispositivo intrauterino por enfermeiros na Atenção Primária à Saúde: revisão integrativa

ABSTRACT Objectives: to synthesize and analyze evidence on intrauterine device insertion by nurses in Primary Health Care. Methods: an integrative review, carried out in the BDENF, CINAHL, LILACS, SciELO, Scopus, PubMed and Web of Science databases in June 2022, delimiting the period from 1960 to 2022. Results: 141 articles were identified in the initial search, and 10 studies made up the final sample. Four (40%) were developed in the United States and one (10%) in Brazil, with publications from 1979 to 2021. The findings were grouped into three categories: Nurse training to insert an intrauterine device; Nurses' competency to insert an intrauterine device; and Women's access to intrauterine devices. Conclusions: nurse theoretical and practical training is a prominent element, consolidated in the favorable outcomes of insertions performed by nurses and satisfaction among women, a practice that has expanded access to the contraceptive method in Primary Health Care.

RESUMEN Objetivos: sintetizar y analizar la evidencia sobre la inserción de dispositivos intrauterinos por parte de enfermeras en la Atención Primaria de Salud. Métodos: revisión integrativa, realizada en las bases de datos BDENF, CINAHL, LILACS, SciELO, Scopus, PubMed y Web of Science en junio de 2022, delimitando el período de 1960 a 2022. Resultados: se identificaron 141 artículos en la búsqueda inicial y 10 publicaciones conformaron la muestra final. Cuatro (40%) fueron desarrollados en Estados Unidos y uno (10%) en Brasil, con publicaciones de 1979 a 2021. Los hallazgos se agruparon en tres categorías: Capacitación de enfermeras para insertar un dispositivo intrauterino; Competencia de las enfermeras para insertar un dispositivo intrauterino; y Acceso de las mujeres a los dispositivos intrauterinos. Conclusiones: la formación teórica y práctica de los enfermeros es un elemento destacado, consolidado en los resultados favorables de las inserciones realizadas por los enfermeros y la satisfacción de las mujeres, práctica que ha ampliado el acceso al método anticonceptivo en la Atención Primaria de Salud.

RESUMO Objetivos: sintetizar e analisar as evidências da inserção de dispositivo intrauterino por enfermeiros na Atenção Primária à Saúde. Métodos: revisão integrativa, realizada nas bases de dados BDENF, CINAHL, LILACS, SciELO, Scopus, PubMed e Web of Science em junho de 2022, delimitando-se o período de 1960 a 2022. Resultados: identificaram-se 141 artigos na busca inicial, e 10 publicações compuseram a amostra final. Quatro (40%) foram desenvolvidos nos Estados Unidos e um (10%) no Brasil, sendo publicações de 1979 a 2021. Os achados foram agrupados em três categorias: Treinamento dos enfermeiros para inserção de dispositivo intrauterino; Competência dos enfermeiros para inserção de dispositivo intrauterino; e Acesso das mulheres aos dispositivos intrauterinos. Conclusões: o treinamento teórico e prático dos enfermeiros é um elemento de destaque, consolidado nos desfechos favoráveis das inserções realizadas por enfermeiros e satisfação entre as mulheres, prática que tem ampliado o acesso ao método contraceptivo na Atenção Primária à Saúde.

Sofosbuvir más glecaprevir/pibrentasvir como terapia de rescate postrasplante hepático en pacientes con exposición previa a inhibidores de NS5A. Serie de casos / Sofosbuvir plus glecaprevir/pibrentasvir as salvage therapy after liver transplantation in NS5A inhibitor-experienced patients. A case series

Resumen Antecedentes: El tratamiento de la infección crónica por el virus de la hepatitis C (VHC) con antivirales de acción directa logra tasas de respuesta virológica sostenida superiores a 95 %. Sin embargo, el manejo del fracaso virológico sigue siendo un desafío clínico y la evidencia sobre el retratamiento es limitada, especialmente en poblaciones como los receptores de trasplante hepático (TH). Objetivo: Este estudio evaluó el régimen de sofosbuvir más glecaprevir/pibrentasvir (GLE/PIB) en receptores de TH en quienes falló el régimen basado en inhibidores de la proteína no estructural 5A (NS5A). Material y métodos: Estudio retrospectivo de 111 pacientes trasplantados entre enero de 2018 y diciembre de 2020; 18 pacientes presentaron infección recurrente por VHC posterior al TH, tres de ellos tuvieron antecedentes de al menos un régimen basado en inhibidores de NS5A. Se inició terapia de rescate con sofosbuvir más GLE/PIB durante 12 semanas posterior al TH; se registraron las características basales de los pacientes y sus desenlaces. Resultados: En los tres pacientes se logró obtener una carga viral indetectable de VHC a las 12 semanas de finalizar el tratamiento. No se observaron eventos adversos graves. Conclusión: En nuestra serie, sofosbuvir más GLE/PIB durante 12 semanas demostró ser una terapia de rescate efectiva y segura posterior al TH en pacientes previamente tratados con inhibidores de NS5A.

Abstract Background: Treatment of chronic hepatitis C virus (HCV) infection with direct-acting antivirals achieves a sustained virologic response rates higher than 95%. However, virologic failure remains a clinical challenge, and data on retreatment are limited, especially in special populations such as liver transplant (LT) recipients. Objective: This study evaluated the sofosbuvir plus glecaprevir-pibrentasvir (GLE/PIB) regimen in LT recipients who had failed to a nonstructural protein 5A (NS5A) inhibitor-based regimen. Material and methods: Retrospective study of 111 liver transplant recipients between January 2018 and December 2020; 18 patients presented with HCV recurrent infection after LT, out of whom three had a history of at least one NS5A inhibitor-based regimen. Salvage therapy with sofosbuvir plus GLE/PIB was started for 12 weeks; baseline characteristics and outcomes were recorded. Results: All three patients (100%) achieved an undetectable HCV viral load 12 weeks after treatment completion. No serious adverse events were observed. Conclusion: In our series, sofosbuvir plus GLE/PIB for 12 weeks is an effective and safe salvage therapy after LT in patients previously treated with NS5A inhibitors.

Impacto psicológico de la hiperhidrosis primaria / Psychological impact of primary hyperhidrosis / Impacto psicológico da hiperidrose primária

La hiperhidrosis primaria es una patología frecuente que representa un motivo de consulta dermatológica común, se caracterizada por una sudoración excesiva en regiones axilares, plantares, palmares o craneofaciales que aparece generalmente en la pubertad o en la adolescencia, sus portadores con frecuencia desarrollan discapacidad psicológica como síntomas de depresión, ansiedad y auto aislamiento social. Objetivo. Identificar el impacto la hiperhidrosis primaria produce en la calidad de vida de los pacientes, mediante el análisis de la efectividad de tratamientos disponibles para la mejora de síntomas generados antes su padecimiento. Metodología. En la revisión sistemática se recopiló información científica en Pubmed, Scopus y Taylor & Francis, la información obtenida fue de artículos originales y metaanálisis comprendido entre enero de 2011 a diciembre de 2022, la ecuación de búsqueda "hiperhidrosis", "psicología", "salud mental" y "calidad de vida. Resultados. Se obtuvo 127 fuentes entre PubMed, Scopus, Taylor & Francis, se revisó y eliminó los duplicados y los artículos carentes de información de interés, seleccionando 41 artículos, y posteriormente se aplicó a los artículos restantes los criterios de inclusión y exclusión, obteniéndose finalmente 8 artículos para el análisis. Conclusión. El principal impacto psicológico de la hiperhidrosis primaria es la ansiedad y la depresión, las cuales se pueden evidenciar con mayor prevalencia en pacientes de sexo femenino y la repercusión principal en la vida diaria es el aislamiento social, donde el apoyo de sus familiares juega un papel importante en las recuperaciones del paciente, además se desconoce la causa directa de la enfermedad, siendo su causa multifactorial.

Primary hyperhidrosis is a common pathology that represents a common reason for dermatologic consultation, characterized by excessive sweating in axillary, plantar, palmar or craniofacial regions that usually appears at puberty or adolescence, its carriers often develop psychological disability such as symptoms of depression, anxiety and social self-isolation. Objective. To identify the impact of primary hyperhidrosis on the quality of life of patients, by analyzing the effectiveness of available treatments for the improvement of symptoms generated before the condition. Methodology. In the systematic review, scientific information was collected in Pubmed, Scopus and Taylor & Francis, the information obtained was from original articles and meta-analysis from January 2011 to December 2022, the search equation "hyperhidrosis", "psychology", "mental health" and "quality of life". Results. We obtained 127 sources among PubMed, Scopus, Taylor & Francis, reviewed and eliminated duplicates and articles lacking information of interest, selecting 41 articles, and then applied the inclusion and exclusion criteria to the remaining articles, finally obtaining 8 articles for analysis. Conclusion. The main psychological impact of primary hyperhidrosis is anxiety and depression, which are more prevalent in female patients, and the main repercussion in daily life is social isolation, where the support of family members plays an important role in the patient's recovery, and the direct cause of the disease is unknown, being its cause multifactorial.

A hiperidrose primária é uma patologia comum que representa um motivo frequente de consulta dermatológica, caracterizada por sudorese excessiva nas regiões axilar, plantar, palmar ou craniofacial, que geralmente aparece na puberdade ou na adolescência, e seus portadores frequentemente desenvolvem deficiência psicológica, como sintomas de depressão, ansiedade e autoisolamento social. Objetivo. Identificar o impacto da hiperidrose primária na qualidade de vida dos pacientes, analisando a eficácia dos tratamentos disponíveis para a melhora dos sintomas gerados antes da doença. Metodologia. Na revisão sistemática, foram coletadas informações científicas no Pubmed, Scopus e Taylor & Francis, as informações obtidas foram de artigos originais e meta-análises entre janeiro de 2011 e dezembro de 2022, a equação de busca "hyperhidrosis", "psychology", "mental health" e "quality of life". Resultados. Obtivemos 127 fontes do PubMed, Scopus, Taylor & Francis, revisamos e eliminamos duplicatas e artigos sem informações de interesse, selecionando 41 artigos e, em seguida, aplicamos os critérios de inclusão e exclusão aos artigos restantes, obtendo finalmente 8 artigos para análise. Conclusão. O principal impacto psicológico da hiperidrose primária é a ansiedade e a depressão, que são mais prevalentes em pacientes do sexo feminino, e a principal repercussão na vida diária é o isolamento social, em que o apoio dos familiares desempenha um papel importante na recuperação do paciente. Além disso, a causa direta da doença é desconhecida, pois é multifatorial.

Impact of hepatitis C virus eradication with direct-acting antivirals on glycidic metabolism

ABSTRACT Objective: To compare the glucose metabolism of patients with chronic hepatitis C virus infection treated with direct-acting antivirals (DAAs) in pretreatment and sustained viral response (SVR) periods. Materials and methods: This was an intervention pre-post study of 273 patients with chronic hepatitis C virus infection treated with DAAs from March 2018 to December 2019. Glycidic metabolism was evaluated through homeostasis model assessment (HOMA) - insulin resistance (IR) and HOMA-β indices and assessments of insulinemia and HbA1c levels. These parameters were analyzed with a T test by paired comparison of the means of the variables and Wilcoxon's test paired for the median; in the variables with an abnormal distribution, the Z score was generated for the mean in both the pretreatment and SVR periods. Statistical significance was considered at p ≤ 0.05. Results: Among 273 participants, 125 (45.8%) had prediabetes, and 50 (18.3%) had diabetes. In SVR, there was a significant increase in platelets, albumin, alkaline phosphatase, cholesterol and triglycerides and a significant decrease in aspartate aminotransferase, alanine aminotransferase, gamma GT and bilirubin. The HOMA-IR and HOMA-β indices increased in SVR from 1.95 to 2.29 (p = 0.087) and 71.20 to 82.60 (p = 0.001), respectively. Insulinemia increased from 7.60 μU/mL to 8.90 μU/mL (p = 0.011). HbA1c decreased from 5.6 to 5.4 (p < 0.001). Among patients with prediabetes and those with diabetes, the reduction in HbA1c values was significant (p = 0.006 and p = 0.026, respectively). Conclusion: SVR significantly impacts and leads to improvement in glucose metabolism in patients with chronic liver disease induced by hepatitis C virus.

Management of Hepatitis C in Children – A New Paradigm

Introduction: With the advent of direct-acting antivirals (DAAs), the past decade has seen a paradigm shift in the management of hepatitis C (HCV) infection in children. In this review, we summarize the various treatment options for pediatric HCV infection, highlighting the recent changes in the management. Methods: A literature search was performed using the PubMed database with the relevant keywords. Filters included were human, ages 0-18 years, and the English language. Results: Initial phase of HCV treatment using conventional or pegylated interferon and ribavirin combination regimens yielded poor outcomes in children, especially in genotypes 1 and 4, with an overall sustained virologic response of 58%. Also, treatment with interferon and ribavirin combination was associated with significant side effects in up to 52% of those treated. Presently, various combinations of direct-acting antivirals (DAAs) have been approved in children above three years of age with documented evidence of high efficacy (SVR12 of 92% to 100%) and excellent safety, and the current standard of care. Conclusion: With various DAA regimens now being approved for children above three years of age, the treatment of active HCV infection (HCV-RNA positive) in children has become simple. Besides the effectiveness of DAA therapy, public awareness about HCV transmission, better screening, and making the DAAs available at a subsidized price in the public sectors are necessary to eliminate HCV infection in India.

Cost-effectiveness analysis of long-acting versus short-acting recombinant human granulocyte stimulating factor in the treatment of III° and IV° bone marrow suppression after chemotherapy / 中国基层医药

Objective:To investigate the cost-effectiveness of long-acting versus short-acting recombinant human granulocyte stimulating factor in the treatment of III° and IV° bone marrow suppression after chemotherapy. Methods:The data of patients who presented with III and IV° bone marrow suppression after chemotherapy and received treatment with recombinant human granulocyte stimulating factor from January 2018 to December 2019 were collected. These patients were divided into the short-acting recombinant human granulocyte stimulating factor group (rhG-CSF group) and the long-acting recombinant human granulocyte stimulating factor group (PEG-rhG-CSF group) group. Clinical efficacy, the incidence of adverse reactions, and cost-effectiveness were compared between the two groups.Results:There were 88 patients, aged (63.97 ± 11.64) years, in the rhG-CSF group. There were 80 patients, aged (63.26 ± 9.09) years in the PEG-rhG-CSF group. There was no significant difference in baseline data between the two groups ( P > 0.05). Total response rate was 72.72% (64/88) in the rhG-CSF group and 78.75% (63/80) in the PEG-rhG-CSF group ( χ2 = 0.82, P = 0.360). The incidence of related adverse reactions was 7.95% (7/88) and 7.5% (6/80) in the rhG-CSF and PEG-rhG-CSF groups respectively ( χ2 = 0.01, P = 0.910). The average cost was (124.88 ± 113.07) yuan and (3 159.04 ± 505.05) yuan in the rhG-CSF and PEG-rhG-CSF groups respectively ( t = 51.68, P < 0.01). The cost-effectiveness ratio was 1.55 and 40.11 in the rhG-CSF and PEG-rhG-CSF groups respectively. Taking the rhG-CSF group as a reference, the incremental cost-effectiveness ratio in the PEG-rhG-CSF group was 505.13. Conclusion:Long-acting and short-acting recombinant human granulocyte stimulating factors have similar curative effects and related adverse reactions in the treatment of III° and IV°bone marrow suppression after chemotherapy. The cost-effectiveness ratio of the rhG-CSF group is lower than that of the PEG-rhG-CSF group. Appropriate treatment schemes for increasing white blood cell levels should be selected based on the individual situation of the patient.

Research on expression of Toll-like receptors and IFN-α in HCV infected patients with different clinical outcomes / 中国热带医学

@#Abstract: Objective To investigate the changes in expression of Toll-like receptor 3 (TLR3) and interferon-α (IFN-α) in patients with different clinical outcomes of hepatitis C virus (HCV) infection treated with direct-acting antiviral agents (DAAs), and to explore the relationship between the expression of TLR3 and IFN-α with the clinical outcomes of HCV infection. Methods A total of 149 HCV infected patients who received initial treatment were selected from Hainan General Hospital between September 2020 and August 2022. The patients were divided into two groups: chronic hepatitis C (CHC) group (n=129) and liver cirrhosis (LC) group (n=20). Additionally, 28 volunteers were selected as the control group during the same period. All patients with HCV infection were first treated with Sofosbuvir/Vipatavir tablets for 12 weeks. Blood samples were collected at 0, 4, 12, 24 and 48 weeks after treatment. Liver function indicators were detected by enzyme-linked immunosorbent assay (ELISA), while TLR3 mRNA were detected by real-time fluorescence quantitative polymerase chain reaction (qRCR), IFN-α was detected by Luminex multiplex cytokine assays. Measurement data subject to normal distribution were represented by x±s, and t test was used between groups. Compare differences between groups. Results TLR3 mRNA in CHC group was higher than that in LC group and control group at baseline (P<0.05). After 4 weeks of DAAs treatment, TLR3 mRNA in CHC and LC groups was significantly up-regulated (P<0.05). TLR3 mRNA in the CHC group was gradually down-regulated to the level of the control group at 12, 24, and 48 weeks. In addition, IFN-α expression gradually increased with prolonged treatment, while it decreased in the LC group. The liver inflammation indicators in both the CHC and LC groups partially recovered after treatment with DAAs. Conclusions TLR3 is involved in viral clearance and chronic inflammatory response. The expression difference of TLR3 in patients with different clinical outcomes of HCV infection after DAAs treatment may be related to the severity of the disease.

The Ubiquitin Ligase SMURF1 Catalyzes the Polyubiquitination of ADAR1 / 中国生物化学与分子生物学报

It is known that SMAD specific E3 ubiquitin protein ligase 1 (SMURF1) mediates autophagy through its E3 ubiquitin ligase activity, but the ubiquitinated substrates of SMURF1 need to be further explored. In this paper, the interacting proteins of SMURF1 in THP-1 cells were captured and identified by co-immunoprecipitation (Co-IP) combined with mass spectrometry. It was found that SMURF1 could physically bind to 222 proteins in THP-1 cells, and Adenosine deaminase acting on RNA 1 (ADAR1) had a higher peptide binding score. SMURF1 overexpression vectors were constructed and transfected into HEK-293T cells, then Co-IP and Western blotting assays verified the interaction between exogenous SMURF1 and endogenous ADAR1. qRT-PCR and Western blotting assays were carried out after transfecting SMURF1 overexpression vectors in HEK-293T cells, which identified that overexpression of SMURF1 attenuated the protein levels of ADAR1 (P<0. 05). However, there was no significant difference in the mRNA level of ADAR1. HEK-293T cells with normal and overexpressing SMURF1 were treated with cycloheximide (CHX), respectively, and Western blotting assays showed a shortened half-life of ADAR1 after overexpression of SMURF1 (P < 0. 05). Furthermore, overexpression of SMURF1 increased the polyubiquitination level of ADAR1 as detected by Co-IP and Western blot (P<0. 05). After the proteasome inhibitor (MG132) treatment, the Western blotting assay was performed to demonstrate that the negative regulatory effect of SMURF1 on ADAR1 was weakened after the proteasome degradation pathway was attenuated (P<0. 05). This study shows that SMURF1 interacts with ADAR1, catalyzes the polyubiquitination of ADAR1 and mediates its degradation through the proteasome pathway, which provides a theoretical basis for exploring the various biological functions of SMURF1 by affecting the stability of ADAR1.

Progress in clinical research on remazolam / 中国临床药理学与治疗学

Benzodiazepines are among the most commonly used drugs in the field of anesthesia. Remazolam is a newly developed ultra-short-acting benzodiazepine, which has the characteristics of rapid onset, rapid recovery, high safety, and less side effects such as hypotension and respiratory depression. The aim of this review is to summarize the progress of pharmacokinetics, clinical pharmacology mechanism of action and clinical application of remazolam.

Key points in hepatitis C guidance 2023 update： American Association for the Study of Liver Diseases-Infectious Diseases Society of America recommendations for testing， managing， and treating hepatitis C virus infection / 临床肝胆病杂志

The Infectious Diseases Society of America and the American Association for the Study of Liver Diseases have collaboratively developed evidence-based guidance regarding the diagnosis， management， and treatment of hepatitis C virus （HCV） infection since 2013. A panel of clinicians and investigators with extensive expertise in infectious diseases or hepatology specific to HCV infection periodically reviews related evidence and update existing recommendations or introduce new recommendations based on such evidence. This update focuses on the changes to the guidance since the update in 2020， including recommendations for extensive universal screening， simplified treatment and testing regimens， treatment of poor compliance， and management of unique and key populations such as children aged <3 years and patients undergoing transplantation.

Effects of ADRB2 gene regulatory region polymorphism on the efficacy of SABA in the treatment of acute asthma attack in children / 中国药房

OBJECTIVE To explore the effects of ADRB2 gene regulatory region polymorphism on the efficacy of short-acting beta 2 receptor agonists （SABA） in the treatment of acute asthma attack in children. METHODS A total of 127 children with acute mild to moderate bronchial asthma who received SABA treatment for 7 days in the General Hospital of Northern Theater Command from October 2016 to October 2020 were selected to detect their genotype distribution and compare the improvement of pulmonary functional indicators and curative effect among different genotypes. The effect of the high-order interaction of gene polymorphism on therapeutic effect was investigated. RESULTS Among 127 children， there were 80， 44 and 3 cases of TT， TA and AA types at locus rs2895795， 93， 32 and 2 cases of CC， CG and GG types at locus rs11168070， and 41， 64 and 22 cases of GG， GA and AA types at locus rs12654778， respectively， in accordance with Hardy-Weinberg equilibrium （P＞0.05）. After treatment， the improvement rate of the peak expiratory flow in percent predicted value （PEF%pred） and the improvement rate of the forced expiratory flow at 75% vital capacity in percent predicted value （FEF75%pred） in children with TA type were significantly lower than that of TT type at locus rs2895795 （P＜0.05）； the improvement rates of PEF%pred and FEF75%pred in children with CG type were significantly lower than that of CC type at locus rs11168070 （P＜0.05）； the improvement rates of PEF%pred in children with GA and AA type were significantly lower than that of GG type at locus rs12654778 （P＜0.05）. The differences in fractional exhaled nitric oxide before and after treatment were not statistically significant among different genotypes at each locus （P＞0.05）. The proportion of remarkable improvement of children with TT type at locus rs2895795 was 2.358 times that of children with TA+ AA type （P＜0.05）， and there was no significant effect of higher-order interaction of ADRB2 polymorphism on the efficacy in children with asthma （P＞0.05）. CONCLUSIONS Polymorphisms in the regulatory region of the ADRB2 gene in children with bronchial asthma are associated with the efficacy of SABA in the treatment of acute asthma attack in children. At locus rs2895795， rs11168070 and rs12654778， the improvement of lung function of children with wild-type is more obvious， and the efficacy of SABA treatment on children with TT type is better at locus rs2895795.

Effect evaluation of medical insurance policy for hepatitis C DAA drugs based on patient survey / 中国药房

OBJECTIVE To provide reference for the prevention and treatment of hepatitis C and the formulation and improvement of medical insurance payment policy for direct-acting antiviral （DAA） drugs. METHODS An questionnaire survey was conducted among the patients who received hepatitis C treatment in a third-grade class-A hospital in Sichuan province from 2019 to 2020 and enjoyed Chengdu medical insurance policy. The patients’ hepatitis C treatment and satisfaction with the medical insurance policy for DAA drugs were compared before and after DAA drugs were included in the medical insurance list. RESULTS A total of 203 patients effectively responded among 644 investigated patients. In terms of treatment plans， although there were significant differences in the treatment plan between patients who saw a doctor in 2019 and 2020 （P＜0.05）， the vast majority of patients were cured within the course of treatment （200 cases， 98.52%）， and there were no obvious adverse reactions （193 cases， 95.07%）. In terms of economic burden， the out-of-pocket costs and economic burden of patients treated with DAA drugs in 2020 were significantly lower than those treated with DAA drugs in 2019 （P＜0.05）； in terms of patient services， 78.82% of patients received expert consultation services from designated medical institutions， but 9.85% of patients still did not receive any patient services provided by the hospital. In terms of satisfaction with outpatient reimbursement policy， the overall satisfaction of patients who saw a doctor in 2020 （95.37%） was significantly higher than those who saw a doctor in 2019 （81.05%）（P＜0.05）. CONCLUSIONS The surveyed patients with hepatitis C obtain good efficacy after DAA drugs treatment， and are satisfied with the medical insurance policy of DAA drugs， but the standardized management of patient services in designated medical institutions is insufficient.

Actively separated microneedle patch for sustained-release of growth hormone to treat growth hormone deficiency

Growth hormone deficiency (GHD) has become a serious healthcare burden, and presents a huge impact on the physical and mental health of patients. Here, we developed an actively separated microneedle patch (PAA/NaHCO3-Silk MN) based on silk protein for sustained release of recombinant human growth hormone (rhGH). Silk protein, as a friendly carrier material for proteins, could be constructed in mild full-water conditions and ensure the activity of rhGH. After manually pressing PAA/NaHCO3-Silk MN patch to skin for 1 min, active separation is achieved by absorbing the interstitial fluid (ISF) to trigger HCO3 ‒ in the active backing layer to produce carbon dioxide gas (CO2). In rats, the MN patch could maintain the sustained release of rhGH for more than 7 days, and produce similar effects as daily subcutaneous (S.C.) injections of rhGH in promoting height and weight with well tolerated. Moreover, the PAA/NaHCO3-Silk MN patch with the potential of painless self-administration, does not require cold chain transportation and storage possess great economic benefits. Overall, the PAA/NaHCO3-Silk MN patch can significantly improve patient compliance and increase the availability of drugs, meet current unmet clinical needs, improve clinical treatment effects of GHD patients.

Terapia antiviral de acción directa para infección del virus de hepatitis C en pacientes en hemodiálisis

Introducción: La infección por el virus C de la hepatitis resulta común en pacientes en hemodiálisis y se considera endémica en estas unidades. El tratamiento utilizado lo componían el interferón pegilado y la ribavirina, combinación que presentaba niveles de toxicidad y baja respuesta. Las drogas actuales aportan mejores resultados. Objetivos: Determinar la eficacia y seguridad de la terapia antiviral de acción directa para la infección del virus de la hepatitis C en pacientes con insuficiencia renal crónica en hemodiálisis. Métodos: Estudio descriptivo prospectivo en 19 pacientes en régimen de hemodiálisis y con infección por virus C, pertenecientes al Hospital General Docente "Dr. Mario Muñoz Monroy", desde diciembre de 2020 hasta septiembre de 2021," A todos se les prescribió durante 12 semanas Sofosbuvir® 400 mg más Daclatasvir® 60 mg diarios. Se caracterizaron las variables edad, sexo, fibrosis hepática por el índice aspartato-aminotransferasa/plaquetas, reacciones adversas y respuesta viral 12 semanas después del tratamiento. Resultados: La infección predominó en el grupo de 51 a 60 años (36,84 %). La mayoría de los pacientes mostró un índice aspartato-aminotransferasa/plaquetas ≤ 0,5, lo que correspondió con ausencia de fibrosis hepática significativa (14 pacientes). Una minoría de pacientes registró reacciones adversas. No se demostró toxicidad cardiovascular ni hepática. La totalidad de los pacientes manifestaron carga viral no detectable 12 semanas después del tratamiento. Conclusiones: La combinación de Sofosbuvir® con Daclatasvir® para el tratamiento de la infección por virus de la hepatitis C en pacientes con insuficiencia renal crónica en tratamiento de hemodiálisis resultó eficaz, bien tolerada y segura.

Introduction: Hepatitis C virus infection is common in hemodialysis patients and is considered endemic in these units. The treatment used consisted of pegylated interferon and ribavirin, a combination that presented levels of toxicity and low response. Current drugs bring better results. Objectives: To determine the efficacy and safety of direct-acting antiviral therapy for hepatitis C virus infection in patients with chronic renal failure on hemodialysis. Methods: Prospective descriptive study in 19 patients on hemodialysis and with virus C infection, belonging to "Dr. Mario Muñoz Monroy" Teaching General Hospital, from December 2020 to September 2021. All were prescribed for 12 weeks with Sofosbuvir® 400 mg plus Daclatasvir® 60 mg daily. The variables age, sex, liver fibrosis were characterized by the aspartate aminotransferase/platelet index, adverse reactions and viral response 12 weeks after treatment. Results: Infection predominated in the group of 51 to 60 years (36.84%). Most patients showed an aspartate aminotransferase/platelet ratio ≤ 0.5, corresponding to the absence of significant liver fibrosis (14 patients). A minority of patients reported adverse reactions. No cardiovascular or hepatic toxicity was demonstrated. All patients had an undetectable viral load 12 weeks after treatment. Conclusions: The combination of Sofosbuvir® with Daclatasvir® for the treatment of hepatitis C virus infection in patients with chronic renal failure undergoing hemodialysis was effective, well tolerated and safe.

Recurrence of hepatitis C virus after treatment with pegylated interferon and direct acting antivirals in Punjab Pakistan / Recorrência do vírus da hepatite C após tratamento com interferon peguilado e antivirais de ação direta em Punjab, Paquistão

Although increased response rates concomitant in hepatitis C virus but relapse after treatment is threatened. Therefore, it is terrible requirement to evaluate the response of Pegylated interferon and direct acting antivirals in Punjab Pakistan. The study was conducted to find the rate of recurrence of HCV infection after treatment with Pegylated Interferon and Direct Acting Antivirals in Punjab Pakistan. This study was conducted at Department of Pathology, Nawaz Sharif Medical College Gujrat, while treatment effects monitored in different Government and Private Hospitals of Punjab, Pakistan. Total 973 patients who administered the recommended dose and divided in two groups (i) Interferon based therapy (ii) direct acting antivirals (DAAs).Other parameters like ALT and viral load studied. The rate of recurrence was higher in female infected with genotype 2b and in male with mixed genotype 3a/2b after six month of antiviral therapy. Genotype 3a showed significant response to therapy after three month. 32 among 374 (8.5%) were positive after 24 weeks of treatment with interferon, 29 (7.7%) patients have same genotype while 3 patients were re-infected with different HCV strains. With DAAs, only 27 (4.8%) patients were positive among 558 after 2 weeks and one patient re-infected with different genotype. Early and sustained virological response noted in DAAs. ALT and viral load decreased faster with DAAs that not achieved after 4 weeks with pegylated interferon. Sustained virological response appears in DAAs and recurrence rate is high in interferon therapy compared to DAAs. Therefore, reinfection has implications for correct treatment efficiency and to select strategies for retreatment cases.

Embora aumentem as taxas de resposta concomitantes no vírus da hepatite C (HCV), há risco de recidiva após o tratamento. Portanto, é um requisito terrível avaliar a resposta do interferon peguilado e antivirais de ação direta em Punjab, Paquistão. O estudo foi conduzido para encontrar a taxa de recorrência da infecção por HCV após o tratamento com interferon peguilado e antivirais de ação direta em Punjab, Paquistão. Este estudo foi conduzido no Departamento de Patologia Nawaz Sharif Medical College Gujrat, enquanto os efeitos do tratamento foram monitorados em diferentes hospitais públicos e privados de Punjab, Paquistão. Total de 973 pacientes que administraram a dose recomendada foram divididos em dois grupos: (i) Terapia baseada em interferon, (ii) antivirais de ação direta (DAAs). Outros parâmetros como ALT e carga viral foram estudados. A taxa de recorrência foi maior em mulheres infectadas com o genótipo 2b e em homens com genótipo misto 3a / 2b após seis meses de terapia antiviral. O genótipo 3a mostrou resposta significativa à terapia após três meses. 32 entre 374 (8,5%) foram positivos após 24 semanas de tratamento com interferon, 29 (7,7%) pacientes têm o mesmo genótipo, enquanto 3 pacientes foram reinfectados com diferentes cepas de HCV. Com DAAs, apenas 27 (4,8%) pacientes foram positivos entre 558 após duas semanas e um paciente reinfectado com genótipo diferente. Resposta virológica precoce e sustentada observada em DAAs. ALT e carga viral diminuíram mais rapidamente com DAAs, que não alcançou após 4 semanas com interferon peguilado. A resposta virológica sustentada aparece em DAAs, e a taxa de recorrência é alta na terapia com interferon em comparação com DAAs. Portanto, a reinfecção tem implicações para a eficiência do tratamento correto e para selecionar estratégias para casos de retratamento.

Recurrence of hepatitis C virus after treatment with pegylated interferon and direct acting antivirals in Punjab Pakistan

Abstract Although increased response rates concomitant in hepatitis C virus but relapse after treatment is threatened. Therefore, it is terrible requirement to evaluate the response of Pegylated interferon and direct acting antivirals in Punjab Pakistan. The study was conducted to find the rate of recurrence of HCV infection after treatment with Pegylated Interferon and Direct Acting Antivirals in Punjab Pakistan. This study was conducted at Department of Pathology, Nawaz Sharif Medical College Gujrat, while treatment effects monitored in different Government and Private Hospitals of Punjab, Pakistan. Total 973 patients who administered the recommended dose and divided in two groups (i) Interferon based therapy (ii) direct acting antivirals (DAAs).Other parameters like ALT and viral load studied. The rate of recurrence was higher in female infected with genotype 2b and in male with mixed genotype 3a/2b after six month of antiviral therapy. Genotype 3a showed significant response to therapy after three month. 32 among 374 (8.5%) were positive after 24 weeks of treatment with interferon, 29 (7.7%) patients have same genotype while 3 patients were re-infected with different HCV strains. With DAAs, only 27 (4.8%) patients were positive among 558 after 2 weeks and one patient re-infected with different genotype. Early and sustained virological response noted in DAAs. ALT and viral load decreased faster with DAAs that not achieved after 4 weeks with pegylated interferon. Sustained virological response appears in DAAs and recurrence rate is high in interferon therapy compared to DAAs. Therefore, reinfection has implications for correct treatment efficiency and to select strategies for retreatment cases.

RESUMO Embora aumentem as taxas de resposta concomitantes no vírus da hepatite C (HCV), há risco de recidiva após o tratamento. Portanto, é um requisito terrível avaliar a resposta do interferon peguilado e antivirais de ação direta em Punjab, Paquistão. O estudo foi conduzido para encontrar a taxa de recorrência da infecção por HCV após o tratamento com interferon peguilado e antivirais de ação direta em Punjab, Paquistão. Este estudo foi conduzido no Departamento de Patologia Nawaz Sharif Medical College Gujrat, enquanto os efeitos do tratamento foram monitorados em diferentes hospitais públicos e privados de Punjab, Paquistão. Total de 973 pacientes que administraram a dose recomendada foram divididos em dois grupos: (i) Terapia baseada em interferon, (ii) antivirais de ação direta (DAAs). Outros parâmetros como ALT e carga viral foram estudados. A taxa de recorrência foi maior em mulheres infectadas com o genótipo 2b e em homens com genótipo misto 3a / 2b após seis meses de terapia antiviral. O genótipo 3a mostrou resposta significativa à terapia após três meses. 32 entre 374 (8,5%) foram positivos após 24 semanas de tratamento com interferon, 29 (7,7%) pacientes têm o mesmo genótipo, enquanto 3 pacientes foram reinfectados com diferentes cepas de HCV. Com DAAs, apenas 27 (4,8%) pacientes foram positivos entre 558 após duas semanas e um paciente reinfectado com genótipo diferente. Resposta virológica precoce e sustentada observada em DAAs. ALT e carga viral diminuíram mais rapidamente com DAAs, que não alcançou após 4 semanas com interferon peguilado. A resposta virológica sustentada aparece em DAAs, e a taxa de recorrência é alta na terapia com interferon em comparação com DAAs. Portanto, a reinfecção tem implicações para a eficiência do tratamento correto e para selecionar estratégias para casos de retratamento.

Real-world effectiveness and safety of direct-acting antivirals for the treatment of hepatitis C virus in kidney and liver transplant recipients: experience of a large transplant center in Brazil

ABSTRACT Direct-acting antivirals are the gold-standard treatment for chronic HCV infections, but few studies have investigated their use on kidney and liver transplant recipients. We conducted a real-world study to evaluate the rates of sustained virological response with direct-acting antivirals in kidney and liver transplant recipients. Moreover, it also aimed to evaluate direct-acting antivirals (DAAs) interference with immunosuppressant levels and to describe the frequency of adverse events. As part of this retrospective observational cohort, we included adult patients that had undergone a kidney transplant (KT) or liver transplant (LT) at our center, had a chronic HCV infection, and were treated with DAAs from June 2016 to December 2021. A total of 165 patients were included in the analysis, divided in 108 KT and 57 LT recipients. HCV genotype 1 was more frequent in KT (58.4%), and genotype 3 was more prevalent in LT (57.9%) patients. Sustained virological response was achieved in 89.6% of patients. Adverse effects were reported by 36% of patients. There were significant interactions with immunosuppressants requiring dose adjustments. A total of three episodes of rejection were reported in KT recipients. In conclusion, DAA treatment resulted in high rates of SVR and was well tolerated in both kidney and liver transplant patients. Adverse events were frequent but not severe in most patients, with low treatment drop-out rates. Interactions with immunosuppressants need monitoring since dose adjustments may be required. Reporting real-life experiences is important to help build evidence for patient management in non-controlled environments.