ABSTRACT Objective: The aim of this study was to evaluate the frequency of hypoglycemia and the treatment satisfaction in patients with type 1 diabetes (T1D) using insulin analogues. Subjects and methods: This observational retrospective study included 516 adult patients with T1D from 38 cities in Southern Brazil. Demographics and clinical data were collected using a self-report questionnaire. Hypoglycemia was defined as an event based on either symptoms or self-monitored blood glucose < 70 mg/dL. Treatment satisfaction was evaluated using the Diabetes Treatment Satisfaction Questionnaire status version (DTSQs) and with a specific question with scores ranging from 0–10. Common mental disorders were assessed using the General Health Questionnaire (GHQ-12). Results: Overall, the mean age was 38 ± 14 years and 52% of the participants were women. The median diabetes duration was 18 years. The scores for insulin analogue treatment satisfaction were higher than those for previous treatments. DTSQ scores had a median value of 32 (interquartile range 29–35) and remained unchanged over time. The percentage of patients with hypoglycemia (including severe and nocturnal) was comparable across groups divided according to duration of use of insulin analogues. Most patients (n=395, 77%) screened positive for common mental disorders. Conclusions: Patient satisfaction with insulin analogue treatment was high and remained unchanged with time. Episodes of hypoglycemia also remained unchanged over time among patients using insulin analogues.

ABSTRACT This is a retrospective report of the frequency of severe hypoglycemia and the association between common mental disorders and type 1 diabetes mellitus treated with insulin analogues. Patients with severe hypoglycemia compared with those without this complication had a higher prevalence of positive screening for common mental disorders (88% vs.77%, respectively, p = 0.03).

Certain host single nucleotide polymorphisms (SNPs) affect the likelihood of a sustained virological response (SVR) to treatment in subjects infected with hepatitis C virus (HCV). SNPs in the promoters of interleukin (IL)-10 (-1082 A/G, rs1800896), myxovirus resistance protein 1 (-123 C/A, rs17000900 and -88 G/T, rs2071430) and tumour necrosis factor (TNF) (-308 G/A, rs1800629 and -238 G/A, rs361525) genes and the outcome of PEGylated α-interferon plus ribavirin therapy were investigated. This analysis was performed in 114 Brazilian, HCV genotype 1-infected patients who had a SVR and in 85 non-responders and 64 relapsers. A significantly increased risk of having a null virological response was observed in patients carrying at least one A allele at positions -308 [odds ratios (OR) = 2.58, 95% confidence intervals (CI) = 1.44-4.63, p = 0.001] or -238 (OR = 7.33, 95% CI = 3.59-14.93, p < 0.001) in the TNF promoter. The risk of relapsing was also elevated (-308: OR = 2.87, 95% CI = 1.51-5.44, p = 0.001; -238: OR = 4.20, 95% CI = 1.93-9.10, p < 0.001). Multiple logistic regression of TNF diplotypes showed that patients with at least two copies of the A allele had an even higher risk of having a null virological response (OR = 16.43, 95% CI = 5.70-47.34, p < 0.001) or relapsing (OR = 6.71, 95% CI = 2.18-20.66, p = 0.001). No statistically significant association was found between the other SNPs under study and anti-HCV therapy response.

A single-nucleotide polymorphism (SNP) upstream of interleukin (IL)28B was recently identified as an important predictor of the outcome of chronic hepatitis C patients treated with pegylated interferon plus ribavirin (PEG-IFN/RBV). The aim of this study was to investigate the association between the IL28B gene polymorphism (rs12979860) and virological response in chronic hepatitis C patients. Brazilian patients (n = 263) who were infected with hepatitis C virus (HCV) genotype 1 and were receiving PEG-IFN/RBV were genotyped. Early virological response (EVR) (12 weeks), end-of-treatment response (EOTR) (48 weeks), sustained virological response (SVR) (72 weeks) and relapse were evaluated using conventional and quantitative polymerase chain reaction (PCR) assays. The frequency of the C allele in the population was 39%. Overall, 43% of patients experienced SVR. The IL28B CC genotype was significantly associated with higher treatment response rates and a lower relapse rate compared to the other genotypes [84% vs. 58% EVR, 92% vs. 63% EOTR, 76% vs. 38% SVR and 17% vs. 40% relapse rate in CC vs. other genotypes (CT and TT), respectively]. Thus, the IL28B genotype appears to be a strong predictor of SVR following PEG-IFN/RBV therapy in treatment-naïve Brazilian patients infected with HCV genotype 1. This study, together with similar research examining other SNPs, should help to define adequate protocols for the treatment of patients infected with HCV genotype 1, especially those with a poor prognosis.

CONTEXTO: Estudos de farmacovigilância têm por objeto a detecção, avaliação, compreensão e prevenção dos riscos dos efeitos adversos dos medicamentos ou qualquer outro possível problema relacionado com medicamento. A alfainterferona (IFN) está sendo produzida por Bio-Manguinhos/Fiocruz e utilizada no tratamento da hepatite C crônica no âmbito do Sistema Único de Saúde (SUS). OBJETIVO: Conhecer o perfil de segurança e efetividade deste IFN em uma amostra de pacientes brasileiros com hepatite crônica pelo vírus C genótipos 2 e 3, em Porto Alegre, RS, Brasil. MÉTODO: Trata-se de uma coorte de pacientes com hepatite crônica pelo vírus C genótipos 2 e 3 tratados com IFN e ribavirina e acompanhados em um serviço ambulatorial especializado no sul do Brasil. Os eventos adversos foram coletados e classificados de acordo com a gravidade em entrevistas mensais estruturadas. Para medida de eficácia foi avaliada a carga viral do HCV antes, ao final e 24 semanas após o término do tratamento. RESULTADOS: Foram acompanhados 141 pacientes no período do estudo, sendo 52,5% do sexo feminino com média de idade de 52 anos. Os eventos adversos mais frequentes foram fadiga (84%), cefaleia (79%) e mialgia (75%). Ocorreram 13 interrupções de tratamento por eventos adversos, sendo nove destes considerados eventos adversos graves. A resposta virológica ao final do tratamento foi de 54,6% e 24 semanas após de 39,7%, considerando todos os pacientes que iniciaram o tratamento. CONCLUSÃO: O produto produzido por Bio-Manguinhos possui eficácia e um perfil de eventos adversos e de resposta virológica sustentada comparáveis aos encontrados na literatura. Este é o primeiro estudo de farmacovigilância realizado com o produto brasileiro. Estes dados serão úteis para planejamento e gestão do tratamento desta doença no Brasil.

CONTEXT: Pharmacovigilance studies aim to detect, assess, understand and prevent risks of adverse effects of medications or any other possible drug related problem. Alpha interferon is being produced by Bio-Manguinhos/Fiocruz, Rio de Janeiro, RJ, Brazil and used in the treatment of chronic hepatitis C at Brazilian National Health System. OBJECTIVE: To study the safety profile and effectiveness of alpha interferon in a sample of Brazilian patients with chronic hepatitis C genotypes 2 and 3, in Porto Alegre, RS, Brazil. METHOD: We followed a cohort of chronic hepatitis C genotypes 2 and 3 patients treated with alpha interferon plus ribavirin in a specialized outpatient clinic in southern Brazil. Adverse events were collected and classified according to severity in monthly structured interviews. To measure effectiveness, hepatitis C viral load was evaluated before, at the end and 24 weeks after the treatment. RESULTS: We followed 141 patients during the study period, of which 52.5% were female with mean age of 52 years. The most frequent adverse events were fatigue (84%), headache (79%) and myalgia (75%). There were 13 treatment interruptions due to adverse events, 9 of those considered serious adverse events. Virological response at end of treatment was 54.6% and after 24 weeks 39.7%, considering all patients who started treatment. CONCLUSION: The product produced by Bio-Manguinhos has similar efficacy and adverse event and sustained virological response profiles comparable to those found in the literature. This is the first study of pharmacovigilance performed with the Brazilian product. These data will be useful for planning and management of this disease in Brazil.

OBJETIVO: Esse estudo avalia resultados em pacientes submetidos à cirurgia para troca valvar aórtica utilizando substituto biológico ou mecânico, com poder de relevância na seleção do tipo da prótese. MÉTODOS: Foram selecionados, randomicamente, 301 pacientes submetidos à cirurgia para troca valvar aórtica entre 1990 e 2005, com seguimento máximo de 20 anos. RESULTADOS: Sobrevivência em 5, 10 e 15 anos após cirurgia utilizando substituto mecânico foi de 83,9%, 75,4% e 60,2% e, para substituto biológico, foi de 89,3%, 70,4% e 58,4%, respectivamente (P=0,939). Fatores associados com óbito foram: idade, obesidade, doença pulmonar, arritmias, eventos hemorrágicos e insuficiência valvar aórtica. Probabilidade livre de reoperação desses pacientes em 5, 10 e 15 anos após cirurgia utilizando substituto mecânico foi de 97,9%, 95,8% e 95,8% e, para bioprótese, foi de 94,6%, 91,0% e 83,3%, respectivamente (P=0,057). Fatores associados com reoperação foram: insuficiência renal, endocardite de prótese e idade. Probabilidade livre de eventos hemorrágicos em 5, 10 e 15 anos após cirurgia utilizando substituto mecânico foi de 94,5%, 91,7% e 91,7% e, para bioprótese, foi de 98,6%, 97,8% e 97,8%, respectivamente (P=0,047). Fatores associados com eventos hemorrágicos foram: insuficiência renal e prótese mecânica. CONCLUSÕES: Os autores concluíram que: 1) mortalidade foi estatisticamente semelhante entre os grupos; 2) características basais dos pacientes foram os maiores determinantes de mortalidade tardia após a cirurgia; 3) houve tendência à reoperação para o grupo com bioprótese; 4) pacientes com prótese mecânica tiveram mais eventos hemorrágicos ao longo do tempo; 5) dados encontrados no presente estudo são concordantes com a literatura atual

OBJECTIVE: This paper evaluates outcomes in patients subjected to surgery for replacement of the aortic valve using biological or mechanical substitutes, where selection of the type of prosthesis is relevant. METHODS: Three hundred and one patients, randomly selected, who had been subjected to aortic valve replacement surgery between 1990 and 2005, with a maximum follow-up period of 20 years. RESULTS: Survival at 5, 10 and 15 years after surgery using mechanical substitute was 83.9%, 75.4% and 60.2% and, for biological substitute, was 89.3%, 70.4% and 58.4%, respectively (P=0.939). Factors associated with death were: age, obesity, pulmonary disease, arrhythmia, bleeding and aortic valve failure. Probability free of reoperation for these patients at 5, 10 and 15 years after surgery using mechanical substitute was 97.9%, 95.8% and 95.8% and, for those using bioprostheses, was 94.6%, 91.0% and 83.3%, respectively (P=0.057). Factors associated with reoperation were: renal failure, prosthesis endocarditis and age. Probability free of bleeding events at 5, 10 and 15 years after surgery using mechanical substitute was 94.5%, 91.7% and 91.7% and, for bioprostheses, was 98.6%, 97.8% and 97.8%, respectively (P=0.047). Factors associated with bleeding events were: renal failure and mechanical prostheses. CONCLUSIONS: The authors have concluded that: 1) mortality was statistically similar in the groups; 2) patient characteristics at baseline were a major determinant of late mortality after surgery; 3) there was a tendency toward reoperation in the bioprostheses group; 4) patients using mechanical prosthesis had more bleeding events as time passed; 5) data presented in this paper is in accordance with current literature

Resumo Avaliar a associação entre obesidade, comprometimento cognitivo e sintomas depressivos em pacientes de alto risco cardiovascular. Métodos: Foi selecionada uma amostra de 93 pacientes com 50 anos ou mais em acompanhamento no Centro de Dislipidemia e Alto Risco Cardiovascular do Hospital de Clínicas de Porto Alegre (HCPA). Pacientes com história de acidente vascular cerebral (AVC) foram excluídos. Para a avaliação cognitiva, foi utilizado o MEEM (Mini Exame do Estado Mental). Escores de 24 ou menos foram considerados como comprometimento cognitivo, para pacientes com 4 ou menos anos de escolaridade, o ponto de corte usado foi de 17 pontos. A escala GDS-15 (Geriatric Depression Scale) também foi utilizada, sendo adotado o ponto de corte 6 para a presença de sintomas depressivos. Resultados: Pacientes obesos apresentaram valores menores na média dos escores do MEEM quando comparados a pacientes não-obesos (p=0,0012). Além disso, para cada ponto de acréscimo no IMC acima de 30, houve um aumento de 27% na chance do paciente ter comprometimento cognitivo. Os pacientes obesos apresentaram 31% de chance de ter comprometimento cognitivo quando comparados com pacientes com sobrepeso. Conclusões: Os achados do presente estudo corroboram a associação entre obesidade e comprometimento cognitivo em pacientes de alto risco cardiovascular. Entretanto, esta associação não foi observada ao se analisar os sintomas depressivos.

Abstract To evaluate the relationship of obesity, cognitive impairment and depressive symptoms in patients with high cardiovascular risk. Methods: A sample of 93 patients aged 50 years or older was selected from the Center of Dyslipidemia and High Cardiovascular Risk from Hospital de Clínicas de Porto Alegre (HCPA). Patients with stroke were excluded. For cognitive evaluation, the MMSE (Mini Mental State Examination) was used. A score of 24 or less was considered as cognitive impairment, and for those who had 4 years or less of education, the cutoff point was 17. The GDS-15 (Geriatric Depression Scale) was also used, with the cutoff of 6 for presence of depressive symptoms. Results: Obese patients showed lower mean MMSE scores compared to non-obese patients (p=0.0012). Additionally, for every one point increase in BMI above 30 there was a 27% increase in the chances of the patient having cognitive impairment. The obese patients presented 31% chance of having cognitive impairment compared with overweight subjects. Conclusions: Our findings corroborated the association between obesity and cognitive impairment in high cardiovascular risk patients. This association however, was not observed for depressive symptoms.

Este artigo aborda, de forma crítica, aspectos das políticas públicas brasileiras para medicamentos, com ênfase nos de alto custo dirigidos às doenças raras. As doenças lisossômicas foram utilizadas como exemplo pela sua raridade e pela tendência mundial para o desenvolvimento de novos fármacos para seu tratamento. Três doenças foram abordadas: doença de Gaucher, doença de Fabry e mucopolissacaridose tipo I. Embora todas tenham medicamentos registrados no Brasil, a doença de Gaucher é a única com protocolo clínico e diretrizes de tratamento balizadas pelo Ministério da Saúde. Os autores almejam, com este artigo, fomentar a discussão sobre o papel da avaliação de tecnologias em saúde para o tratamento das doenças raras no Brasil, enfatizando a necessidade de políticas legitimadas dirigidas especialmente a elas. A despeito das dificuldades de se estabelecer uma política de saúde específica para cada doença rara, é possível o estabelecimento de modelos racionais para lidar com esse crescente desafio.

This paper approaches in a critical way aspects of Brazilian public policies for drugs, emphasizing those classified as high cost and for rare diseases. The lysosomal storage diseases was taken as an example because of their rarity and the international trend for the development of new drugs for their treatment, all at high costs. Three lysosomal storage diseases were approached: Gaucher disease, Fabry disease and mucopolysaccharidosis type I. Gaucher disease has its treatment drug licensed in Brazil and guidelines for its use are established through a clinical protocol by the Ministry of Health. The others have their drug treatments registered in Brazil; however, no treatment guidelines for them have been developed by the government. The objective of the paper was to foster the discussion on the role of health technology assessment for high-cost drugs for rare diseases in Brazil, emphasizing the need for establishing health policies with legitimacy towards these diseases. Despite the difficulties in establishing a health policy for each rare disease, it is possible to create rational models to deal with this growing challenge.

Este artigo aborda, de forma crítica, aspectos das políticas públicas brasileiras para medicamentos, com ênfase nos de alto custo dirigidos às doenças raras. As doenças lisossômicas foram utilizadas como exemplo pela sua raridade e pela tendência mundial para o desenvolvimento de novos fármacos para seu tratamento. Três doenças foram abordadas: doença de Gaucher, doença de Fabry e mucopolissacaridose tipo I. Embora todas tenham medicamentos registrados no Brasil, a doença de Gaucher é a única com protocolo clínico e diretrizes de tratamento balizadas pelo Ministério da Saúde. Os autores almejam, com este artigo, fomentar a discussão sobre o papel da avaliação de tecnologias em saúde para o tratamento das doenças raras no Brasil, enfatizando a necessidade de políticas legitimadas dirigidas especialmente a elas. A despeito das dificuldades de se estabelecer uma política de saúde específica para cada doença rara, é possível o estabelecimento de modelos racionais para lidar com esse crescente desafio.

This paper approaches in a critical way aspects of Brazilian public policies for drugs, emphasizing those classified as high cost and for rare diseases. The lysosomal storage diseases was taken as an example because of their rarity and the international trend for the development of new drugs for their treatment, all at high costs. Three lysosomal storage diseases were approached: Gaucher disease, Fabry disease and mucopolysaccharidosis type I. Gaucher disease has its treatment drug licensed in Brazil and guidelines for its use are established through a clinical protocol by the Ministry of Health. The others have their drug treatments registered in Brazil; however, no treatment guidelines for them have been developed by the government. The objective of the paper was to foster the discussion on the role of health technology assessment for high-cost drugs for rare diseases in Brazil, emphasizing the need for establishing health policies with legitimacy towards these diseases. Despite the difficulties in establishing a health policy for each rare disease, it is possible to create rational models to deal with this growing challenge.

OBJETIVO: desenvolvimento da versão em português brasileiro do Endometriosis Health Profile Questionnaire (EHP-30), adaptação transcultural ao Brasil e avaliação das medidas psicométricas do EHP-30 Português em amostra brasileira. MÉTODOS: o instrumento original em inglês foi vertido para o português, seguindo diretrizes internacionais, passando por todas as etapas de tradução, retrotradução e comparação das versões para adaptação transcultural, validade de face e de conteúdo. O EHP-30 Português foi aplicado a uma amostra de 54 pacientes com diagnóstico de endometriose para análise de consistência interna, usando o alfa de Cronbach. A fidedignidade teste-reteste foi avaliada pelo coeficiente de correlação intraclasse (ICC). Para a avaliação de validade de construto convergente foi testada correlação entre o EHP-30 Português, WHOQOL-Bref e o Inventário de Depressão de Beck (BDI). RESULTADOS: a avaliação da consistência interna apresentou valores de α=0,8 a 0,9, sugerindo homogeneidade entre as questões. A fidedignidade teste-reteste apresentou ICC de 0,8 a 0,9, demonstrando estabilidade do instrumento. Na validação de construto, demonstraram-se fortes correlações da escala de auto-imagem do EHP-30 com os domínios físico (-0,6) e psicológico (-0,6) do WHOQOL-Bref e da escala de suporte social com o BDI (0,5), evidenciando-se, assim, boa correlação com outros instrumentos de avaliação de qualidade de vida. CONCLUSÕES: o EHP-30 Português mostrou ser um instrumento de fácil e rápida aplicação e bem aceito pelas pacientes, apresentando bom desempenho psicométrico, com medidas de fidedignidade adequadas (consistência interna e fidedignidade teste-reteste) e validade de construto. Estes resultados demonstram que o EHP-30 Português é um instrumento adequado para avaliação de qualidade de vida em mulheres brasileiras com endometriose em ambiente clínico e de pesquisa.

PURPOSE: the objective of the present study was the development of the Brazilian Portuguese version of Endometriosis Health Profile Questionnaire (EHP-30), the cross-cultural adaptation to Brazil and the evaluation of EHP-30 Portuguese psychometric measures in a Brazilian sample. METHODS: the original instrument in English was translated into Portuguese following international guidelines, going through all stages of translation, back-translation and comparison of the versions for cross-cultural adaptation, face and content validity. A sample of 54 patients with endometriosis was used for internal consistency analyses using the Cronbach alpha. Test-retest reliability was evaluated through the intraclass correlation coefficient (ICC). In order to evaluate the convergent construct validity, the correlation between EHP-30 Portuguese and WHOQOL-Bref and Beck Depression Inventory (BDI) was tested. RESULTS: internal consistency presented alpha values of 0.8 to 0.9 suggesting homogeneity between questions. The test-retest reliability presented ICC of 0.8 to 0.9 showing instrument stability. In the construct validation, strong correlations were demonstrated of the EHP-30 Portuguese self-image scale with physical (-0.6) and psychological domains (-0.6) of WHOQOL-Bref, and EHP-30 Portuguese social support scale with BDI (0.5), confirming good correlation with other quality of life evaluation instruments. CONCLUSIONS: the EHP-30 Portuguese was found to be an easy, quickly applied instrument, and well-accepted by the patients. It presented good psychometric properties with appropriate reliability measures (internal consistency and test-retest reliability) and construct validity. These results show that EHP-30 Portuguese is an adequate instrument for quality of life evaluation in Brazilian women with endometriosis, both in clinical and research setting.