Abstract: Parabens are among the most widely used preservatives in cosmetic formulations. The aim of this study was to investigate the relationship between allergic contact dermatitis (ACD) and the use of parabens in cosmetics. A systematic review was performed with searches in PubMed, Scopus and Science Direct, in addition to a manual search. Interventional or observational studies that assessed the incidence of ACD in individuals using parabens were included. The quality of the articles was assessed and the data were extracted for a qualitative synthesis and single-arm meta-analysis. Fourteen studies (8 longitudinal, 3 cross-sectional, 1 quasi experimental and 2 case reports) were included in the systematic review and had their data extracted. Twelve studies reported ACD after the use of parabens and were included in the single-arm meta-analysis, resulting in an ACD incidence of 0.9%[95%CI: 0.4-2.0%], thus classified as a rare event. This result was related to already sensitized skin in most cases. In addition, the concentration of parabens in the contact test was above that recommended in cosmetics. The incidence of ACD due to parabens is rare, but further studies with control groups and at the usual concentrations of parabens are needed to better evaluate the results.

ABSTRACT Objective Diabetes mellitus (DM) is a chronic disease with great impact on patients’ quality of life (QoL). This variable can be measured using reliable, standardized, and validated instruments. The purpose of this study was to evaluate the application and reporting of the Diabetes Quality of Life Measure (DQOL) or the Diabetes Quality of Life for Youths Measure (DQOLY), an adapted version for young patients with DM. Materials and methods A systematic review of interventional and observational studies using the DQOL or DQOLY was performed. Searches were conducted in the electronic databases Medline, Scopus, Web of Science, Lilacs, and SciELO. Results After conducting the searches, 111 studies met the inclusion criteria and were included in the qualitative analysis. Of these, 32 studies were classified as interventional and 79 as observational, with 27,481 patients. The DQOL was applied in 82 studies, the DQOLY in another 27, and two studies used both instruments. DM was classified as type 1 DM in 69 studies and type 2 DM in 35 studies. Six studies included both patients. Improvement in patients’ QoL after an intervention was observed in 13 interventional studies. Most of the studies (90%) provide a detailed description of the instrument and 52% the previous validation. The interpretation of the scores obtained varies among the studies, probably due to the differences inherent in cultural validations, translations, and adaptations. Conclusion The application of the instruments in clinical practice must be rigorously standardized and requires an accurate understanding of psychometric and statistical concepts. Arch Endocrinol Metab. 2020;64(1):59-65

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.

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.

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.

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.

ABSTRACT 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.

Objective to know the financial impact of primary bloodstream infection for hospital organizations. Method integrative review carried out in the LILACS and EMBASE databases with MEDLINE, published between June 2005 and June 2015 with the descriptors: central venous catheters, catheter-related infections and costs and cost analyses. Results thirteen publications were included, and there was predominance of retrospective cohort studies conducted in Europe and the United States with critical patients. The cost for an episode of infection ranged from $ 24,090 to $ 34,544. European studies found values between €16,814 and €29,909. The infection increased the length of hospitalization between 1.5 and 26 days, and the mortality between 1.8% and 34%. Conclusion catheter-related infections incur a high cost for hospital organizations, and it is necessary to assess the cost in the case of each country because of discrepant values in different nations.

Objetivo conocer el impacto financiero de la infección primaria de corriente sanguínea para las organizaciones hospitalarias. Método revisión integradora desarrollada en las bases de datos LILACS y EMBASE con MEDLINE, publicadas entre jun/2005 y jun/2015 con los descriptores: catéteres venosos centrales, infecciones relacionadas a catéter y costos y análisis de costos. Resultados fueron listados 13 publicaciones y hubo predominio de estudios de cohorte retrospectiva, desarrollados en la Europa o Estados Unidos con pacientes críticos. El costo para un episodio de infección varió de $24.090 a $34.544. Estudios europeos encontraron valores entre €16.814 y €29.909. La infección aumentó los días de internación entre 1,5 y 26 días, y la mortalidad entre 1,8% y 34%. Conclusión las infecciones relacionadas al catéter representaron un costo elevado para las organizaciones hospitalarias y, debido a la discrepancia entre los valores en diferentes países, hay una necesidad de evaluar el costo en cada realidad.

Objetivo conhecer o impacto financeiro da infecção primária de corrente sanguínea para as organizações hospitalares. Método revisão integrativa desenvolvida nas bases de dados LILACS e EMBASE com MEDLINE, publicadas entre jun/2005 e jun/2015 com os descritores: cateteres venosos centrais, infecções relacionadas a cateter e custos e análises de custos. Resultados foram elencadas 13 publicações e houve predomínio de estudos de coorte retrospectiva, desenvolvidos na Europa ou Estados Unidos com pacientes críticos. O custo para um episódio de infecção variou de $24.090 até $34.544. Estudos europeus encontraram valores entre €16.814 e €29.909. A infecção aumentou os dias de internação entre 1,5 e 26 dias, e a mortalidade entre 1,8% e 34%. Conclusão as infecções relacionadas ao cateter representaram um custo elevado para as organizações hospitalares e, devido à discrepância entre os valores em diferentes países, há necessidade de avaliar o custo em cada realidade.

ABSTRACT Glycemic control in patients with diabetes mellitus type 1 (DM1) reduces the risk of complications but requires a rigorous health care routine. Thus, diabetes education is central to increasing treatment compliance and self-care practices. This study aimed to evaluate the quality of life (QoL) and glycemic control of DM1 patients being treated with insulin analogs and receiving medication review with follow-up. This was a transversal study that included 110 patients registered at the 3rd Health Regional of Ponta Grossa-PR, aged ≥ 18 years, and receiving pharmaceutical care for at least 1 year. The Diabetes Quality of Life Measure (DQOL)-Brazil was used to evaluate QoL. The data were statistically analyzed using SPSS version 17.0 with 95% confidence levels. Of the 110 patients, 58.2% were women. The average age was 33.7 years (±10.5), and the average glycated hemoglobin (HbA1c) value was 8% (±1.4). The mean total DQOL-Brazil score was 2.11 (95% confidence interval, 2.02 - 2.21). All DQOL-Brazil scores were lower in patients with HbA1c ≤ 8%, indicating a better QoL. Good glycemic control, thus, appears to have a positive influence on the QoL, and pharmaceutical interventions are able to contribute to the achievement of therapeutic targets.

The aim of this study was to conduct a cost-utility study of adefovir, entecavir, interferon alpha, pegylated interferon alpha, lamivudine and tenofovir for chronic hepatitis B in the context of Brazilian Public Health Care System. A systematic review was carried out for efficacy and safety. Another review was performed to collect utility data and transition probabilities between health states. A Markov model was developed in a time horizon of 40 years with annual cycles for three groups of: HBeAg positive, HBeAg negative, and all patients. These strategies were compared to a fourth group that received no treatment. Discount rates of 5% were applied and sensitivity analyses were performed. Tenofovir offered the best cost-utility ratio for the three evaluated models: U$397, U$385 and U$384 (per QALY, respectively, for HBeAg positive, negative, and all patients). All other strategies were completely dominated because they showed higher costs and lower effectiveness than tenofovir. The sequence of cost-utility in the three models was: tenofovir, entecavir, lamivudine, adefovir, telbivudine, pegylated interferon alpha, and interferon alpha. In the sensitivity analysis, adefovir showed lower cost-utility than telbivudine in some situations. The study has some limitations, primarily related to the creation of scenarios and modeling. In this study, tenofovir presented the best cost-utility ratio. The results obtained in this study will be valuable in decision-making and in the review of the clinical protocol, mainly involving the allocation of available resources for health care.

IntroductionThe objetctive of this study was to evaluate the 2009 Pandemic Influenza A (H1N1) in the elderly and identify the clinical characteristics, mortality and prognostic factors of the infection in these patients.MethodsThis was an observational, retrospective study. Data were collected from the National Notifiable Diseases (SINAN), from the Brazilian Ministry of Health. Only patients 60 years old or more that had laboratory confirmed infections were included. The socio-demographic and clinical variables and outcomes were evaluated to compare mortality rates in the presence or absence of these factors.ResultsWe included 93 patients in the study, 16.1% of whom died. The symptoms of cough and dyspnea, the use of the antiviral oseltamivir, influenza vaccine and comorbidities influenced the outcomes of cure or death. Chest radiography can aid in diagnosis.ConclusionsAlthough relatively few elderly people were infected, this population presented high lethality that can be justified by the sum of clinical, physical and immunological factors in this population. Treatment with oseltamivir and vaccination against seasonal influenza have significantly reduced rates of hospitalization and mortality.

O objetivo foi fornecer dados atualizados sobre eficácia clínica, segurança e tolerabilidade do uso de abatacepte para o tratamento da artrite reumatoide. Realizaram-se uma revisão sistemática (com dados até junho/2011) e metanálises. Somente estudos clínicos controlados randomizados comparando o abatacepte (10 mg/kg) com placebo, ambos com uso concomitante de metotrexato, foram incluídos; todos possuíam qualidade alta ou moderada. A eficácia foi avaliada baseando-se em mudanças no ACR, DAS e HAQ; a segurança foi avaliada pelos eventos adversos e infecções graves, malignidades e mortes e a tolerabilidade pelo abandono do tratamento devido a eventos adversos (graves ou não) e falta de eficácia. Todos esses parâmetros foram avaliados ao final de um ano de tratamento. Nove estudos se adequaram aos critérios de inclusão, envolvendo 4219 pacientes. Em todos os parâmetros avaliados, o grupo tratado com abatacepte obteve melhores resultados, exceto para a melhora (>0,3) no HAQ (sem diferença estatisticamente significativa). Nenhum critério de segurança ou tolerabilidade apresentou diferença significativa entre os grupos, com exceção dos abandonos devido à falta de eficácia (grupo abatacepte apresentou resultados favoráveis em relação ao controle). O abatacepte possui maior eficácia quando comparado com o placebo, sem diferença significativa entre os grupos em termos de segurança.

The objective is to provide an update on the clinical efficacy, safety and tolerability of the use of abatacept for treating rheumatoid arthritis. A systematic review (up to June 2011) followed by meta-analyses was performed. Randomized controlled clinical trials comparing abatacept at a dose of 10 mg/kg with a placebo, both with concomitant methotrexate, were used. Only high- or moderate-quality studies were included. The efficacy was evaluated based on changes in the ACR, DAS and HAQ; safety was assessed based on serious adverse events, serious infections, malignancies and deaths; tolerability was evaluated based on the withdrawals due to adverse events, serious adverse events and lack of efficacy. All these parameters were evaluated within one year of treatment. Nine studies met the inclusion criteria, comprising 4,219 patients. For all of the efficacy parameters, the abatacept group had better results than the placebo group, except in the case of HAQ improvement >0.3, which presented no statistically significant difference. None of the safety parameters presented a significant difference between the groups. The tolerability parameters were also similar between groups, with the exception of withdrawals due to lack of efficacy. For this criterion, the abatacept group presented favorably compared to the control group. Abatacept showed a higher efficacy compared to placebo without significant differences between the abatacept and control group in terms of safety.

Treatment for chronic hepatitis B in Brazil are funded by the Ministry of Health and by the state Departments of Health. Clinical protocol and therapeutic guidelines approve the use of adefovir, entecavir, interferon-a, lamivudine, and tenofovir for the treatment of chronic hepatitis B. The aim of this study was to establish the profile of users of these drugs in the state of Paraná. A cross-sectional study was conducted with patients under treatment in Paraná in August 2011. The following data were obtained: gender, hepatitis B used drug, International Classification of Diseases, and regional health unit. The monthly cost of these drugs for the public health system was also calculated. 1,093 patients registered were found, 70% male, and 2.6% co-infected with the delta agent. Tenofovir was the drug most commonly used (355 users). The highest prevalence was found in the regional health units of Pato Branco, Cascavel, Foz do Iguaçú, Francisco Beltrão, Toledo, Londrina, and Maringá. The annual cost for the public health system in Paraná was U$1,066,867. Through this study it was possible to investigate the distribution and profile of users of drugs for the treatment of chronic hepatitis B in Paraná in August 2011.

INTRODUÇÃO: O tratamento da artrite reumatoide (AR) no âmbito do Sistema Único de Saúde (SUS) tem financiamento do Ministério da Saúde e cofinanciamento das Secretarias Estaduais. O Protocolo Clínico e Diretrizes Terapêuticas (PCDT) para o tratamento da AR descreve o esquema terapêutico para a patologia, inclusive com as anticitocinas adalimumabe, etanercepte ou infliximabe. OBJETIVO: Traçar o perfil dos usuários de anticitocinas, medicamentos biológicos cadastrados no Sistema de Informação do Componente Especializado da Assistência Farmacêutica, gerenciado pelo Centro de Medicamentos do Paraná. MÉTODOS: Foi realizado um estudo transversal tomando como referência o mês de março de 2010. Com base em dados de dispensação, foram coletadas informações relativas a idade, gênero, regional de saúde (RS), Código Internacional de Doenças (CID) e medicamento dispensado. Calculou-se também o custo mensal com anticitocinas para o SUS. RESULTADOS: No estado do Paraná foram encontrados 923 pacientes recebendo anticitocinas, dos quais 40% recebiam adalimumabe, 44% etanercepte e 16% infliximabe, gerando um custo mensal de R$3.403.195,59. Com relação ao CID, 55% dos indivíduos apresentavam CID M05.8, 27% CID M06.0, 9% CID M6.8, 8% CID M5.0 e 1% dos indivíduos apresentava os outros CIDs relacionados com a doença. As RS do Paraná com o maior número de indivíduos em tratamento com anticitocinas foram as de Ponta Grossa, Cornélio Procópio, Londrina, Cianorte, Maringá, Irati e Campo Mourão. CONCLUSÃO: Por meio deste estudo foi possível verificar a distribuição e o perfil dos usuários de anticitocinas para o tratamento da AR no Paraná no âmbito do SUS no mês de março de 2010.

INTRODUCTION: The Brazilian Unified Health Care System (SUS) offers treatment for patients with RA through federal funding (Ministry of Health) and state co-financing. The Clinical Protocol and Therapeutic Guidelines for the treatment of rheumatoid arthritis describe the therapeutic regimen for the disease, including the anticytokines adalimumab, etanercept or infliximab. OBJECTIVES: The aim of this study was to evaluate the profile of registered users of those anticytokines, biologics registered in the Information System of the Pharmaceutical Assistance Specialized Division, managed by the Paraná State Drug Center. METHODS: A cross-sectional study regarding data from March 2010 was conducted. Based on dispensation data, information regarding the following variables were collected: age; gender; regional health care centers; International Classification of Diseases (ICD); and drug dispensed. In addition, the monthly cost with anticytokines for the SUS was calculated. RESULTS: In the state of Paraná, 923 patients on anticytokines were identified, 40%, 44% and 16% of whom receiving adalimumab, etanercept and infliximab, respectively. This generated a monthly cost of R$3,403,195.59. Regarding the ICD, the distribution of patients was as follows: 55% had ICD M05.8; 27%, ICD M06.0; 9%, ICD M6.8; 8%, ICD M5.0; and 1% had other ICDs related to the disease. The regional health care centers of the state of Paraná with the largest number of patients on anticytokines were in the following municipalities: Ponta Grossa; Cornélio Procópio; Londrina; Cianorte; Maringá; Irati; and Campo Mourão. CONCLUSION: This study assessed the distribution and profile of users of anticytokines for the rheumatoid arthritis treatment covered by the SUS in the state of Paraná, in March 2010.

OBJECTIVE: The pandemic of new influenza A (H1N1) has spread rapidly throughout the world, characterized by high transmissibility, but low pathogenicity and virulence. The aim of this study was to understand the pandemic event and available technologies for disease surveillance, prevention, control and management. METHODS: In this retrospective study, we used data from patients in the State of Paraná who had been diagnosed with the disease during the 2009 pandemic. Data were collected from the disease notification form and the study only included patients with confirmed laboratory diagnosis by RT-PCR. RESULTS: We present the epidemiological profile of 4,740 patients that met the inclusion criteria. The variables age, level of schooling and gestational age were shown to be associated with mortality due to the infection. Gender and race/ethnicity were not associated with the outcome of the infection. CONCLUSION: These results underscore the importance of knowing the variables associated with unfavorable outcomes of pandemic influenza infection in order to minimize the health related consequences. Attention should be given to its forms of transmission and to the frailty of certain age groups that have no cross-immunity.

BACKGROUND AND AIM: Chronic hepatitis B is a highly prevalent disease worldwide, leading to serious consequences if not properly treated. Six treatment options for chronic hepatitis B are currently provided by the Brazilian public health system. Telbivudine is a nucleoside analogue that is neither included in the Brazilian clinical protocol nor in the therapeutic guidelines for chronic hepatitis B. OBJECTIVE: The aim of this study was to evaluate the cost-effectiveness of telbivudine for the viewpoint of the Brazilian public system, comparing it to lamivudine. METHODS: A Markov model was used to project lifetime complications and costs of treatment with lamivudine or telbivudine for chronic hepatitis B in both HBeAg-positive and HBeAg-negative patients. To evaluate disease progression, probabilities and utilities of virologic response, virologic resistance, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, treatment, interruption of treatment, death and seroconversion were collected in systematic reviews. Costs were collected in DATASUS, ABC da Saúde and scientific literature. RESULTS: Higher rate of virologic response and seroconversion was obtained with telbivudine, and also higher values of quality adjusted life years. However lamivudine is associated with lower costs and also lower cost-effectiveness values. The incremental cost-effectiveness ratios for telbivudine, when compared with lamivudine, were US$ 30,575 and US$ 40,457, respectively for HBeAg-positive and HBeAg-negative patients. CONCLUSION: In chronic hepatitis B lamivudine is a more cost-effective or even cost-saving strategy when compared with telbivudine.