Mycosis fungoides and Sézary syndrome: focus on the current treatment scenario

Abstract Cutaneous T-cell lymphomas are a heterogeneous group of lymphoproliferative disorders, characterized by infiltration of the skin by mature malignant T cells. Mycosis fungoides is the most common form of cutaneous T-cell lymphoma, accounting for more than 60% of cases. Mycosis fungoides in the early-stage is generally an indolent disease, progressing slowly from some patches or plaques to more widespread skin involvement. However, 20% to 25% of patients progress to advanced stages, with the development of skin tumors, extracutaneous spread and poor prognosis. Treatment modalities can be divided into two groups: skin-directed therapies and systemic therapies. Therapies targeting the skin include topical agents, phototherapy and radiotherapy. Systemic therapies include biological response modifiers, immunotherapies and chemotherapeutic agents. For early-stage mycosis fungoides, skin-directed therapies are preferred, to control the disease, improve symptoms and quality of life. When refractory or in advanced-stage disease, systemic treatment is necessary. In this article, the authors present a compilation of current treatment options for mycosis fungoides and Sézary syndrome.

Mycosis fungoides and Sézary syndrome: focus on the current treatment scenario.

Cutaneous T-cell lymphomas are a heterogeneous group of lymphoproliferative disorders, characterized by infiltration of the skin by mature malignant T cells. Mycosis fungoides is the most common form of cutaneous T-cell lymphoma, accounting for more than 60% of cases. Mycosis fungoides in the early-stage is generally an indolent disease, progressing slowly from some patches or plaques to more widespread skin involvement. However, 20% to 25% of patients progress to advanced stages, with the development of skin tumors, extracutaneous spread and poor prognosis. Treatment modalities can be divided into two groups: skin-directed therapies and systemic therapies. Therapies targeting the skin include topical agents, phototherapy and radiotherapy. Systemic therapies include biological response modifiers, immunotherapies and chemotherapeutic agents. For early-stage mycosis fungoides, skin-directed therapies are preferred, to control the disease, improve symptoms and quality of life. When refractory or in advanced-stage disease, systemic treatment is necessary. In this article, the authors present a compilation of current treatment options for mycosis fungoides and Sézary syndrome.

Treatment of elderly patients with refractory/relapsed multiple myeloma: oral drugs adherence and the COVID-19 outbreak.

Once the treatment of refractory/relapsed multiple myeloma in the elderly is greatly influenced by the adherence of patients and family members, clinicians should be aware of patients' behavior and lifestyle, as it may influence the individual treatment plan for each patient. Furthermore, treatment with oral chemotherapy is of special value during the COVID-19 outbreak. Multidisciplinary healthcare involvement is crucial in the management of polypharmacy, adverse events and dose adjustment due to comorbidities and natural loss of renal function with age. Oral drugs simplify intake, reduce hospital visits, and improve autonomy and quality of life. However, although oral drugs have advantages, they also transfer control and responsibility from the healthcare professional to the patient, who must be able to understand and follow the directions given. Therefore, patient education and communication with healthcare professionals are critical for adherence.

Assessment of the prevalence of vertical hepatitis B transmission in two consecutive generations.

INTRODUCTION: Hepatitis B is an important public health problem in the world and one of the forms of contagion would be through vertical transmission. Precose diagnosis allows the adoption of prophylaxis measures, which results in prevention in more than 90% of cases. OBJECTIVE: To describe the prevalences of vertical transmission and compare two generations (mother/patient and patient/child). METHOD: This was a cross-sectional study, which included 101 patients. The interviews were performed through the application of the instrument of data collection and information of the physical file before the medical consultation. RESULTS: The mean ± SD of age was 50.9 ± 13.1 years, the male gender predominated, with 56.4% of the patients, and the predominance was white, with 43.6%. Vertical transmission between mother and patient occurred in 17.8% and between patient and child, in 7.9%. In all of the eight cases of vertical transmission, the diagnosis was after the birth of children infected with HBV, and in 3/8 (37.5%), there was more than one case of infection by this mechanism per patient, totaling 13 children with the disease. CONCLUSION: There was a reduction in vertical transmission, showing that preventive measures were effective.

Assessment of the prevalence of vertical hepatitis B transmission in two consecutive generations / Avaliação da prevalência de transmissão vertical de hepatite B em duas gerações consecutivas

Summary Introduction: Hepatitis B is an important public health problem in the world and one of the forms of contagion would be through vertical transmission. Precose diagnosis allows the adoption of prophylaxis measures, which results in prevention in more than 90% of cases. Objective: To describe the prevalences of vertical transmission and compare two generations (mother/patient and patient/child). Method: This was a cross-sectional study, which included 101 patients. The interviews were performed through the application of the instrument of data collection and information of the physical file before the medical consultation. Results: The mean ± SD of age was 50.9 ± 13.1 years, the male gender predominated, with 56.4% of the patients, and the predominance was white, with 43.6%. Vertical transmission between mother and patient occurred in 17.8% and between patient and child, in 7.9%. In all of the eight cases of vertical transmission, the diagnosis was after the birth of children infected with HBV, and in 3/8 (37.5%), there was more than one case of infection by this mechanism per patient, totaling 13 children with the disease. Conclusion: There was a reduction in vertical transmission, showing that preventive measures were effective.

Resumo Introdução: A hepatite B é um importante problema de saúde pública no mundo e uma das formas de contágio seria através da transmissão vertical. O diagnóstico precoce possibilita a adoção de medidas de profilaxia, o que resulta na prevenção em mais de 90% dos casos. Objetivo: Descrever as prevalências de transmissão vertical e comparar duas gerações (mãe/paciente e paciente/filho). Método: Trata-se de um estudo transversal, que incluiu 101 pacientes. As entrevistas foram realizadas por meio da aplicação do instrumento de coleta de dados e informações do prontuário físico antes da consulta médica. Resultados: A média ± DP de idade foi de 50,9 ± 13,1 anos, houve predomínio do gênero masculino, com 56,4% dos pacientes, e predominou a cor branca, com 43,6%. A transmissão vertical entre mãe do paciente/paciente ocorreu em 17,8% e entre paciente/filho, em 7,9%. Em todos os oito casos de transmissão vertical, o diagnóstico foi posterior ao nascimento dos filhos infectados por HBV; em 3/8 (37,5%), houve mais de um caso de infecção por esse mecanismo por paciente, totalizando 13 filhos com a doença. Conclusão: Houve uma redução na transmissão vertical, mostrando que as medidas preventivas foram efetivas.

Clinical Features of Refractory Ascites in Outpatients.

OBJECTIVES:: To present the clinical features and outcomes of outpatients who suffer from refractory ascites. METHODS:: This prospective observational study consecutively enrolled patients with cirrhotic ascites who submitted to a clinical evaluation, a sodium restriction diet, biochemical blood tests, 24 hour urine tests and an ascitic fluid analysis. All patients received a multidisciplinary evaluation and diuretic treatment. Patients who did not respond to the diuretic treatment were controlled by therapeutic serial paracentesis, and a transjugular intrahepatic portosystemic shunt was indicated for patients who required therapeutic serial paracentesis up to twice a month. RESULTS:: The most common etiology of cirrhosis in both groups was alcoholism [49 refractory (R) and 11 non-refractory ascites (NR)]. The majority of patients in the refractory group had Child-Pugh class B cirrhosis (p=0.034). The nutritional assessment showed protein-energy malnutrition in 81.6% of the patients in the R group and 35.5% of the patients in the NR group, while hepatic encephalopathy, hernia, spontaneous bacterial peritonitis, upper digestive hemorrhage and type 2 hepatorenal syndrome were present in 51%, 44.9%, 38.8%, 38.8% and 26.5% of the patients in the R group and 9.1%, 18.2%, 0%, 0% and 0% of the patients in the NR group, respectively (p=0.016, p=0.173, p=0.012, p=0.012, and p=0.100, respectively). Mortality occurred in 28.6% of the patients in the R group and in 9.1% of the patients in the NR group (p=0.262). CONCLUSION:: Patients with refractory ascites were malnourished, suffered from hernias, had a high prevalence of complications and had a high postoperative death frequency, which was mostly due to infectious processes.

Clinical Features of Refractory Ascites in Outpatients

OBJECTIVES: To present the clinical features and outcomes of outpatients who suffer from refractory ascites. METHODS: This prospective observational study consecutively enrolled patients with cirrhotic ascites who submitted to a clinical evaluation, a sodium restriction diet, biochemical blood tests, 24 hour urine tests and an ascitic fluid analysis. All patients received a multidisciplinary evaluation and diuretic treatment. Patients who did not respond to the diuretic treatment were controlled by therapeutic serial paracentesis, and a transjugular intrahepatic portosystemic shunt was indicated for patients who required therapeutic serial paracentesis up to twice a month. RESULTS: The most common etiology of cirrhosis in both groups was alcoholism [49 refractory (R) and 11 non-refractory ascites (NR)]. The majority of patients in the refractory group had Child-Pugh class B cirrhosis (p=0.034). The nutritional assessment showed protein-energy malnutrition in 81.6% of the patients in the R group and 35.5% of the patients in the NR group, while hepatic encephalopathy, hernia, spontaneous bacterial peritonitis, upper digestive hemorrhage and type 2 hepatorenal syndrome were present in 51%, 44.9%, 38.8%, 38.8% and 26.5% of the patients in the R group and 9.1%, 18.2%, 0%, 0% and 0% of the patients in the NR group, respectively (p=0.016, p=0.173, p=0.012, p=0.012, and p=0.100, respectively). Mortality occurred in 28.6% of the patients in the R group and in 9.1% of the patients in the NR group (p=0.262). CONCLUSION: Patients with refractory ascites were malnourished, suffered from hernias, had a high prevalence of complications and had a high postoperative death frequency, which was mostly due to infectious processes.

UGT1A1*28 relationship with abnormal total bilirubin levels in chronic hepatitis C patients: Outcomes from a case-control study.

Gilbert syndrome (GS) is a frequent benign clinical condition, marked by intermittent unconjugated hyperbilirubinemia, mostly due to the polymorphism uridine diphosphate-glucuronosyltransferase 1A1*28 (UGT1A1*28). Hyperbilirubinemia has been reported in a GS patient undergoing hepatitis C treatment, and other UGT isoforms polymorphisms have been linked to worse outcomes in viral hepatitis. Yet, little is known to GS contributions' to the liver disease scenario. Our aim was to assess UGT1A1 genotypes' frequency in chronic hepatitis C (CHC) patients and correlate with total bilirubin (TB). This is a case-control study in a large tertiary medical center. Cases were CHC patients confirmed by hepatitis C virus (HCV)-polymerase chain reaction. Exclusion criteria were hepatitis B virus or human immunodeficiency virus (HIV) coinfection. Control were healthy blood donors. UGT1A1 promoter region gene genotyping was performed, and bilirubin serum levels were available for HCV patients. Genotypes and alleles frequencies were similar in case (n = 585; P = 0.101) and control groups (n = 313; P = 0.795). Total bilirubin increase was noticed according to thymine-adenine repeats in genotypes (P < 0.001), and the TB greater than 1 mg/dL group had more UGT1A1*28 subjects than in the group with TB values <1 mg/dL (18.3 vs 5.3; P < 0.001). Bilirubin levels are linked to the studied polymorphisms, and this is the first time that these findings are reported in a chronic liver disease sample. Among patients with increased TB levels, the frequency of UGT1A1*28 is higher than those with normal TB. Personalized care should be considered to GS, regarding either abnormal bilirubin levels or drug metabolism.

Cost-effectiveness analysis of paricalcitol versus calcitriol for the treatment of SHPT in dialytic patients from the SUS perspective.

Introduction: Secondary hyperparathyroidism (SHPT) is a consequence of chronic kidney disease. The treatment at the Brazilian Unified Heath System (SUS) is performed with calcitriol, a drug which favors hypercalcemia and/or hyperphosphatemia, hindering the control of SHPT. Another option is paricalcitol, which causes parathormone (PTH) suppression faster than calcitriol, with minor changes in calcium-phosphorus product and calcium and phosphorus serum levels. Objective: This study aims to develop a cost-effectiveness analysis of paricalcitol versus calcitriol for patients in dialytic treatment with SHPT, from the SUS perspective. Methods: A Markov decision model was developed for patients ≥ 50 years old with end stage renal disease in dialytic treatment and SHPT. Quarterly cycles and a lifetime time horizon were considered. Life years (LY) gained were assessed as clinical outcome. Clinical and economic inputs were obtained from systematic literature review and official databases. Costs are presented in Brazilian real (BRL), for the year 2014. Results: In the base case: paricalcitol generated a clinical benefit of 16.28 LY gained versus 14.11 LY gained with calcitriol, total costs of BRL 131,064 and BRL 114,262, respectively, determining an incremental cost-effectiveness ratio of BRL 7,740 per LY gained. The data robustness was confirmed by the sensitivity analysis. Conclusions: According to cost-effectiveness threshold recommended by the World Health Organization for 2013, the treatment of SHPT in patients on dialysis with paricalcitol is cost-effective when compared to calcitriol, from the public healthcare system perspective, in Brazil.

Introdução: O hiperparatireoidismo secundário (HPTS) é uma consequência da doença renal crônica. O tratamento no SUS é realizado com calcitriol, que favorece a hipercalcemia e/ou hiperfosfatemia, dificultando o controle do HPTS. Uma opção clinicamente relevante é o paricalcitol, que ocasiona a supressão do paratormônio (PTH) de forma mais rápida que o calcitriol e com menores alterações nas taxas séricas de cálcio, fósforo e do produto cálcio-fósforo. Objetivo: Este trabalho tem como objetivo desenvolver uma análise de custo-efetividade de paricalcitol versus calcitriol para pacientes em diálise com HPTS, perspectiva do SUS. Métodos: Foi desenvolvido um modelo de decisão de Markov para a população ≥ 50 anos, com DRC em diálise e HPTS. Foram considerados ciclos trimestrais e um horizonte temporal lifetime. O desfecho clínico avaliado foram os anos de vida ganhos. Dados foram obtidos a partir de revisão sistemática da literatura e bases de dados oficiais. Custos em reais (R$), ano de 2014. Resultados: No caso base: paricalcitol gerou benefício clínico de 16,28 anos de vida ganhos versus 14,11 anos de vida ganhos com calcitriol, custos totais de R$ 131.064 e R$ 114.262, respectivamente. A razão de custo-efetividade incremental de R$ 7.740 por ano de vida salvo. Dados robustos confirmados pela análise de sensibilidade. Conclusão: De acordo com o limiar de custo-efetividade recomendado pela Organização Mundial de Saúde para o ano de 2013, o tratamento de pacientes com HPTS em diálise com paricalcitol é custo-efetivo, comparado ao calcitriol, perspectiva SUS.

Cost-effectiveness analysis of paricalcitol versus calcitriol for the treatment of SHPT in dialytic patients from the SUS perspective / Análise de custo-efetividade de paricalcitol versus calcitriol no tratamento do HPTS em pacientes do SUS dialíticos, da perspectiva

Abstract Introduction: Secondary hyperparathyroidism (SHPT) is a consequence of chronic kidney disease. The treatment at the Brazilian Unified Heath System (SUS) is performed with calcitriol, a drug which favors hypercalcemia and/or hyperphosphatemia, hindering the control of SHPT. Another option is paricalcitol, which causes parathormone (PTH) suppression faster than calcitriol, with minor changes in calcium-phosphorus product and calcium and phosphorus serum levels. Objective: This study aims to develop a cost-effectiveness analysis of paricalcitol versus calcitriol for patients in dialytic treatment with SHPT, from the SUS perspective. Methods: A Markov decision model was developed for patients ≥ 50 years old with end stage renal disease in dialytic treatment and SHPT. Quarterly cycles and a lifetime time horizon were considered. Life years (LY) gained were assessed as clinical outcome. Clinical and economic inputs were obtained from systematic literature review and official databases. Costs are presented in Brazilian real (BRL), for the year 2014. Results: In the base case: paricalcitol generated a clinical benefit of 16.28 LY gained versus 14.11 LY gained with calcitriol, total costs of BRL 131,064 and BRL 114,262, respectively, determining an incremental cost-effectiveness ratio of BRL 7,740 per LY gained. The data robustness was confirmed by the sensitivity analysis. Conclusions: According to cost-effectiveness threshold recommended by the World Health Organization for 2013, the treatment of SHPT in patients on dialysis with paricalcitol is cost-effective when compared to calcitriol, from the public healthcare system perspective, in Brazil.

Resumo Introdução: O hiperparatireoidismo secundário (HPTS) é uma consequência da doença renal crônica. O tratamento no SUS é realizado com calcitriol, que favorece a hipercalcemia e/ou hiperfosfatemia, dificultando o controle do HPTS. Uma opção clinicamente relevante é o paricalcitol, que ocasiona a supressão do paratormônio (PTH) de forma mais rápida que o calcitriol e com menores alterações nas taxas séricas de cálcio, fósforo e do produto cálcio-fósforo. Objetivo: Este trabalho tem como objetivo desenvolver uma análise de custo-efetividade de paricalcitol versus calcitriol para pacientes em diálise com HPTS, perspectiva do SUS. Métodos: Foi desenvolvido um modelo de decisão de Markov para a população ≥ 50 anos, com DRC em diálise e HPTS. Foram considerados ciclos trimestrais e um horizonte temporal lifetime. O desfecho clínico avaliado foram os anos de vida ganhos. Dados foram obtidos a partir de revisão sistemática da literatura e bases de dados oficiais. Custos em reais (R$), ano de 2014. Resultados: No caso base: paricalcitol gerou benefício clínico de 16,28 anos de vida ganhos versus 14,11 anos de vida ganhos com calcitriol, custos totais de R$ 131.064 e R$ 114.262, respectivamente. A razão de custo-efetividade incremental de R$ 7.740 por ano de vida salvo. Dados robustos confirmados pela análise de sensibilidade. Conclusão: De acordo com o limiar de custo-efetividade recomendado pela Organização Mundial de Saúde para o ano de 2013, o tratamento de pacientes com HPTS em diálise com paricalcitol é custo-efetivo, comparado ao calcitriol, perspectiva SUS.

Assessment of Adherence to Prescribed Therapy in Patients with Chronic Hepatitis B.

INTRODUCTION: Evidence shows that treatment for hepatitis B virus (HBV) can suppress viral load. Among the factors directly linked to therapeutic success is adherence to the treatment. Several instruments to assess adherence are available, but they are not validated for use in chronic hepatitis B. The purpose of this paper was to adapt and validate the "Assessment of Adherence to Antiretroviral Therapy Questionnaire-HIV" (CEAT-VIH) for patients with chronic hepatitis B (referred to herein as CEAT-HBV). METHODS: The validity of the adapted questionnaire evidence was established through concurrent, criterion, and construct validities. RESULTS: We found negative and significant correlation between the domain "degree of compliance to antiviral therapy" assessed by CEAT-HBV and the Morisky test (r = -0.62, P < 0.001) and between the domain "barriers to adherence" and HBV viral load (r = -0.42, P < 0.001). In terms of the construct's discriminative capacity, scores greater than or equal to 80 detected antiviral therapy success, which are necessary for the prediction of an undetectable HBV viral load. Thus, a cutoff value of 80.5 was set with a value of 81% for sensitivity and 67% for specificity. CONCLUSION: The CEAT-HBV identified 43% (n = 79) non-adherent patients and was shown to be a useful tool in clinical practice.

Overview of hemodialysis treatment funded by the Brazilian Unified Health System--An economic perspective.

INTRODUCTION: End-stage renal disease (ESRD) is a public health problem and, in Brazil, lacks of data on one of the main treatments, hemodialysis, are still identified. OBJECTIVE: To determine, through description of resources used in ESRD treatment and its complications, the cost associated to hemodialysis and supplementary medical therapy in patients attended by Brazilian Public Health (SUS). METHODS: Methods of cross-sectional and prospective cohort observational analysis were conducted using public data, where information about inpatient and outpatient resource use and patients' characteristics were collected. From described resource use, costs were calculated. In cross-sectional analysis subjects who underwent hemodialysis between January/2008 and November/2012 were considered and in prospective cohort, started in 2009. Descriptive analyses were performed. RESULTS: 91,475 and 118,847 hemodialysis procedures were performed in 2008 and 2012, respectively, and 24.8% of increase was estimated until 2017. Analysis by federation unit showed that São Paulo, Minas Gerais and Rio de Janeiro states represented almost half of the procedures observed, with mean cost per patient of US$ 7,932.52 in 2008 and US$ 9,112.75 in 2011. In the cohort, composed by 96,600 subjects, the most used drug was alfaepoetin and 8% of the sample used calcitriol 1.0 mcg. The occurrence of complications was observed in 28.2% of patients. CONCLUSION: After data analysis, different aspects of hemodialysis use were demonstrated, with an increase in amount of procedures and, also, in disease related expenses.

Panorama do tratamento hemodialítico financiado pelo Sistema Único de Saúde - Uma perspectiva econômica / Overview of hemodialysis treatment funded by the Brazilian Unified Health System - An economic perspective

ResumoIntrodução:A doença renal crônica (DRC) é um problema de saúde pública e, no Brasil, ainda são identificadas carências de dados sobre características de um dos principais tratamentos, a hemodiálise.Objetivo:Determinar, por meio da descrição do consumo de recursos para o tratamento e suas complicações, o custo associado à hemodiálise e às terapias medicamentosas suplementares em pacientes financiados pelo SUS.Métodos:Métodos de análise observacional transversal e coorte prospectiva foram utilizados considerando dados públicos, dos quais foram coletadas informações referentes a procedimentos hospitalares e ambulatoriais, além de características dos pacientes. Os custos foram calculados a partir dos recursos descritos. Na análise transversal foram considerados indivíduos que realizaram hemodiálise entre janeiro de 2008 e novembro de 2012 e na coorte prospectiva, iniciada em 2009. Análises descritivas foram conduzidas.Resultados:Um total de 91.475 e 118.847 procedimentos de hemodiálise foram realizados em 2008 e 2012, respectivamente, e, para o ano 2017, foi estimado um aumento de 24,8%. A análise por unidade federativa mostrou que São Paulo, Minas Gerais e Rio de Janeiro representam quase metade dos procedimentos, com média de custo, por paciente, de US$ 7.932,52 em 2008, e de US$ 9.112,75 em 2011. Na coorte, composta por 96.600 indivíduos, o medicamento mais utilizado foi a alfapoetina, além de 8% da amostra utilizar calcitriol 1,0 mcg. Foi observada a ocorrência de complicações em 28,2% dos pacientes.Conclusão:Após análise dos dados, diferentes aspectos da utilização da hemodiálise foram demonstrados, sendo observado um aumento na quantidade de procedimentos e, também, nos gastos decorrentes do procedimento.

AbstractIntroduction:End-stage renal disease (ESRD) is a public health problem and, in Brazil, lacks of data on one of the main treatments, hemodialysis, are still identified.Objective:To determine, through description of resources used in ESRD treatment and its complications, the cost associated to hemodialysis and supplementary medical therapy in patients attended by Brazilian Public Health (SUS).Methods:Methods of cross-sectional and prospective cohort observational analysis were conducted using public data, where information about inpatient and outpatient resource use and patients' characteristics were collected. From described resource use, costs were calculated. In cross-sectional analysis subjects who underwent hemodialysis between January/2008 and November/2012 were considered and in prospective cohort, started in 2009. Descriptive analyses were performed.Results:91,475 and 118,847 hemodialysis procedures were performed in 2008 and 2012, respectively, and 24.8% of increase was estimated until 2017. Analysis by federation unit showed that São Paulo, Minas Gerais and Rio de Janeiro states represented almost half of the procedures observed, with mean cost per patient of US$ 7,932.52 in 2008 and US$ 9,112.75 in 2011. In the cohort, composed by 96,600 subjects, the most used drug was alfaepoetin and 8% of the sample used calcitriol 1.0 mcg. The occurrence of complications was observed in 28.2% of patients.Conclusion:After data analysis, different aspects of hemodialysis use were demonstrated, with an increase in amount of procedures and, also, in disease related expenses.

A fast and cost-effective method for identifying a polymorphism of interleukin 28B related to hepatitis C.

Approximately 170 million people are chronic carriers of hepatitis C virus (HCV). Patients with chronic hepatitis C are currently treated with pegylated interferon and ribavirin (PEG-IFN/RBV). A genome-wide association with PEG-IFN/RBV treatment response and a single nucleotide polymorphism (rs12979860) has been identified near the interleukin 28B gene that encodes interferon-λ-3. In this paper, we describe an innovative, fast, and low-cost multiplex polymerase chain reaction with confronting two-pair primers that detects the rs12979860 polymorphism. The assay is internally controlled and does not require the use of restriction endonucleases or special equipment. Moreover, the assay decreases costs, being about 40% cheaper than direct sequencing methods.