Avaliação de tecnologias em saúde: evidência clí­nica, análise econômica e análise de decisão / Technology assessment in health care: clinical evidence, economic analysis and decision analysis

Considerando o constante avanço científico relacionado à área da saúde e a exigência de gerenciamento dos recursos alocados, é cada vez maior a necessidade de conhecimentos e de domínio da avaliação de tecnologias em saúde (ATS). Este livro é uma iniciativa pioneira, que contribui para o entendimento dos métodos envolvidos na ATS de maneira objetiva e didática.

Cost-effectiveness of entecavir versus lamivudine for the suppression of viral replication in chronic hepatitis B patients in Brazil

Hepatitis B virus infection is an important public-health issue. Chronic patients have a higher risk of death due to complications, which increases health-care expenses in. Cost-effectiveness analysis of entecavir (ETV) versus lamivudine (LVD) for treatment of chronic hepatitis B, in e antigen (AgHBe)-positive and negative patients, based on two phase 3, controlled and randomized studies. A decision analysis model was developed, using the following endpoints: cost per patient with undetectable viral load and cost per quality life year (QALY) gained. Risks for complications (compensated or decompensated cirrhosis and hepatocellular carcinoma) were based on the cohort study REVEAL, published in 2006. The REVEAL parameters were applied to the results of the viral load levels obtained from the clinical assay data. The complication costs were based on a study of the disease cost conducted in Brazil, in 2005. The cost data were obtained predominantly from Sistema Único de Saúde [SUS - Brazilian public health system] payment tables and drug price lists. The utility data were obtained from literature and life expectancy information was based on IBGE data. The analysis perspective was that of SUS. A discount rate of 3 percent per year was used. For the horizon of time of 10 years, the ETV had an incremental cost of approximately two million Brazilian Reais (R$) compared to LVD. Reducing the number of complications, ETV treatment reduced costs by around 3 million, reducing final costs by 1 million, for AgHBe-positive patients. ETV also reduced the incremental cost per QALY gained. ETV was found to be the most cost-effective alternative for AgHBe-positive and negative patients.

Cost-effectiveness of entecavir versus lamivudine for the suppression of viral replication in chronic hepatitis B patients in Brazil.

Hepatitis B virus infection is an important public-health issue. Chronic patients have a higher risk of death due to complications, which increases health-care expenses in. Cost-effectiveness analysis of entecavir (ETV) versus lamivudine (LVD) for treatment of chronic hepatitis B, in e antigen (AgHBe)-positive and negative patients, based on two phase 3, controlled and randomized studies. A decision analysis model was developed, using the following endpoints: cost per patient with undetectable viral load and cost per quality life year (QALY) gained. Risks for complications (compensated or decompensated cirrhosis and hepatocellular carcinoma) were based on the cohort study REVEAL, published in 2006. The REVEAL parameters were applied to the results of the viral load levels obtained from the clinical assay data. The complication costs were based on a study of the disease cost conducted in Brazil, in 2005. The cost data were obtained predominantly from Sistema Unico de Saúde [SUS - Brazilian public health system] payment tables and drug price lists. The utility data were obtained from literature and life expectancy information was based on IBGE data. The analysis perspective was that of SUS. A discount rate of 3% per year was used. For the horizon of time of 10 years, the ETV had an incremental cost of approximately two million Brazilian Reais (R$) compared to LVD. Reducing the number of complications, ETV treatment reduced costs by around 3 million, reducing final costs by 1 million, for AgHBe-positive patients. ETV also reduced the incremental cost per QALY gained. ETV was found to be the most cost-effective alternative for AgHBe-positive and negative patients.

Transtorno afetivo bipolar: carga da doença e custos relacionados / Bipolar disorder: burden of disease and related costs

CONTEXTO: O transtorno afetivo bipolar (TAB) é uma doença recorrente, crônica e grave. Comorbidades psiquiátricas e físicas, aumento do risco de suicídio, maior utilização de serviços de saúde e prejuízo na esfera social/profissional aumentam significativamente a carga e custos relacionados à doença. OBJETIVOS: Revisar aspectos clínicos, de carga da doença e conseqüentes desfechos financeiros do TAB. MÉTODOS: Pesquisa de base de dados MEDLINE/PubMed utilizando os termos bipolar disorder, epidemiology, burden of disease, comorbidity, cost of illness, outcomes e financial consequences, publicados entre 1980 e 2006. RESULTADOS: O TAB apresenta alta comorbidade com outros transtornos, o que agrava seu prognóstico e eleva os custos com os serviços de saúde. Os indivíduos com TAB apresentam mais fatores de risco cardiovascular e, conseqüentemente, maior risco de morte por evento cardíaco. O atraso e o erro diagnóstico no TAB elevam consideravelmente a carga e os custos da doença. CONCLUSÕES: As comorbidades, o risco de suicídio, o prejuízo social/profissional e a baixa adesão ao tratamento contribuem para a alta carga e os custos associados à doença. A pesquisa de comorbidades pode ajudar os médicos a ajustarem suas estratégias de tratamento, considerando cuidadosamente todos os fatores de risco e custos associados, fatores estes que devem ser levados em conta também pelos profissionais que trabalham com gestão de saúde, tanto no setor privado quanto público.

BACKGROUND: Bipolar disorder (BD) is a recurrent, chronic and severe disease. Mental and physical comorbidities, risk of suicide, health services use and impairment of social and professional domains significantly worsen the burden and increase the costs of illness. OBJECTIVES: Review clinical aspects, burden of disease, and consequent financial outcomes of BD. METHODS: MEDLINE/PubMed database search using the terms bipolar disorder, epidemiology, burden of disease, comorbidity, cost of illness, outcomes e financial consequences, published in MEDLINE from 1980 to 2006. RESULTS: BD has a high rate of comorbidities, which worsen the prognosis and increase costs with health services. Subjects with BD have more cardiovascular risk factors than the general population, and therefore a higher risk of death by cardiovascular event. Delay of diagnosis and misdiagnosis increase the costs of illness. DISCUSSION: Comorbidities, risk of suicide, social and professional impairment and low adherence to treatment increase the cost of illness. The search of comorbidities may help clinicians to adjust treatment strategies, taking into account all associated risk factors and costs, which may be considered also by professionals involved in health care management, either private or public.

A naturalistic, 9-month follow-up, comparing olanzapine and conventional antipsychotics on sexual function and hormonal profile for males with schizophrenia.

Second generation antipsychotics have less influence on prolactin levels than conventional antipsychotics (CA), which are commonly associated with sexual dysfunction and hyperprolactinaemia. However, only a few studies have been conducted assessing these newer antipsychotics and sexual function/dysfunction. The aim of this study is to evaluate the sexual function and hormonal profile of male schizophrenic patients taking olanzapine or CA. Sixty-three inpatients with acute episodes of schizophrenia were randomly assigned to take either olanzapine, or go on conventional antipsychotic treatment. The Dickson-Glazer sexual functioning questionnaire was used to assess sexual functioning where serum prolactin, luteinizing hormone, follicle-stimulating hormone, total testosterone, free testosterone, and sex hormone-binding globulin concentrations were measured. All measurements were taken on discharge from the inpatient unit (baseline), and again at 3 and 9 months after discharge. Prolactin levels in the olanzapine group decreased more rapidly and were significantly lower than in the CA group after 3 months (12.1+/-6.3 microg/l, p=0.01; 18.1+/-11.2 microg/l, p=0.564, respectively). After nine months, there was a tendency toward normal levels in both groups, and the frequency of sexual complaints did not differ between the groups. This study showed no difference between olanzapine and conventional antipsychotics regarding sexual complaints in the treatment of schizophrenia, but did show a difference in the hormone level normalization rate.

A systematic review on clinical management of antipsychotic-induced sexual dysfunction in schizophrenia

INTRODUCTION: Sexual dysfunction frequently occurs in patients with schizophrenia under antipsychotic therapy, and the presence of sexual side effects may affect compliance. The aim of this study was to review and describe clinical findings relating to the appropriate management of such dysfunctions. MATERIAL AND METHODS: The research was carried out through Medline (from 1966 to March 2005), PsycInfo (from 1974 to March 2005), and Cochrane Library (from 1965 to March 2005) and included any kind of study, from case reports to randomized trials. RESULTS: The most common sexual dysfunctions found in the literature were libido decrease, difficulties in achieving and maintaining erection, ejaculatory dysfunction, orgasmic dysfunction, and menstrual irregularities. Thirteen papers were found: eight of them were open-label studies, four were descriptions of cases, and only one was a randomized clinical trial. All of them were short-term and had small sample sizes. The agents used were: bromocriptine, cabergoline, cyproheptadine, amantadine, shakuyaku-kanzo-to, sildenafil and selegiline. DISCUSSION: There was no evidence that those agents had proper efficacy in treating the antipsychotic-induced sexual dysfunction. An algorithm for managing sexual dysfunction induced by antipsychotics is suggested as a support for clinical decisions. Since the outcome from schizophrenia treatment is strongly related to compliance with the antipsychotics, prevention of sexual dysfunction is better than its treatment, since there is a scarcity of data available regarding the efficacy of intervention to deal with these problems.

INTRODUÇÃO: Disfunção sexual freqüentemente ocorre em pacientes com esquizofrenia em terapia com antipsicóticos e a presença de efeitos adversos sexuais pode afetar a adesão ao tratamento. O objetivo do estudo é rever e descrever achados clínicos relacionados ao manejo apropriado de tais disfunções. MATERIAIS E MÉTODOS: A pesquisa foi feita pelo Medline (de 1966 a março de 2005), PsycInfo (de 1974 a março de 2005) e Biblioteca Cochrane (de 1965 a março de 2005) e incluiu qualquer tipo de desenho de estudo de relato de caso a estudos clínicos randomizados. RESULTADOS: As disfunções sexuais mais comuns encontradas na literatura foram diminuição da libido, dificuldades em alcançar e manter ereção, disfunção ejaculatória, orgásmica e irregularidades menstruais. Treze artigos foram encontrados: oito deles eram estudos abertos, quatro descrições de casos e somente um estudo clínico randomizado. Todos eram de curta duração e com tamanho de amostra pequeno. Os agentes usados foram: bromocriptina, cabergolina, ciproheptadina, amantadina, shakuyaku-kanzo-to, sildenafil e selegilina. DISCUSSÃO: Não há evidências de eficácia apropriada destes agentes no tratamento da disfunção sexual induzida por antipsicóticos. Um algoritmo foi sugerido para manejo da disfunção sexual induzida por antipsicóticos, suportando decisões clínicas. Como o desfecho da esquizofrenia é fortemente relacionado a adesão ao tratamento com antipsicóticos, a prevenção da disfunção sexual é melhor que seu tratamento, visto que muito poucos dados estão disponíveis sobre a eficácia de intervenções destes problemas.

A systematic review on clinical management of antipsychotic-induced sexual dysfunction in schizophrenia.

INTRODUCTION: Sexual dysfunction frequently occurs in patients with schizophrenia under antipsychotic therapy, and the presence of sexual side effects may affect compliance. The aim of this study was to review and describe clinical findings relating to the appropriate management of such dysfunctions. MATERIAL AND METHODS: The research was carried out through Medline (from 1966 to March 2005), PsycInfo (from 1974 to March 2005), and Cochrane Library (from 1965 to March 2005) and included any kind of study, from case reports to randomized trials. RESULTS: The most common sexual dysfunctions found in the literature were libido decrease, difficulties in achieving and maintaining erection, ejaculatory dysfunction, orgasmic dysfunction, and menstrual irregularities. Thirteen papers were found: eight of them were open-label studies, four were descriptions of cases, and only one was a randomized clinical trial. All of them were short-term and had small sample sizes. The agents used were: bromocriptine, cabergoline, cyproheptadine, amantadine, shakuyaku-kanzo-to, sildenafil and selegiline. DISCUSSION: There was no evidence that those agents had proper efficacy in treating the antipsychotic-induced sexual dysfunction. An algorithm for managing sexual dysfunction induced by antipsychotics is suggested as a support for clinical decisions. Since the outcome from schizophrenia treatment is strongly related to compliance with the antipsychotics, prevention of sexual dysfunction is better than its treatment, since there is a scarcity of data available regarding the efficacy of intervention to deal with these problems.

Hormone profile in acute psychotic disorders: A cross-sectional comparison of serum hormone concentrations in treated and untreated male patients with schizophrenia.

BACKGROUND: Antipsychotic drugs for the treatment of schizophrenia provide effective treatment of psychotic symptoms but might lead to neuroendocrine abnormalities. OBJECTIVE: The aim of this study was to assess hypothalamic-pituitary-gonadal (HPG) axis function by comparing serum hormone profiles of newly admitted patients with psychotic disorders who were receiving antipsychotic drugs with those who were antipsychotic-drug-free during the preceding 6 months. METHODS: Adult male patients admitted during a 1-year period (December 1999 to December 2000) to 1 of 2 Brazilian public psychiatric inpatient units that provide care for severely ill patients were eligible for this cross-sectional study if they had a diagnosis of schizophrenia based on the criteria given in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and a score >24 on the Brief Psychiatric Rating Scale. On the morning after admission, serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone-binding globulin (SHBG), prolactin, free testosterone (FT), and total testosterone (TT) were determined. A commercial laboratory provided the normal serum hormone concentrations of healthy Brazilian men in the same age range as that of the study patients. RESULTS: Sixty-three adult male patients, aged 18 to 55, were included in the study. Forty-eight (76.2%) patients (mean [SD] age, 30.6 [8.9] years) were receiving antipsychotic drugs (treated). Fifteen (23.8%) patients (mean [SD] age, 36.5 [9.8] years) were antipsychotic-drug-free for 6 months before admission (untreated). The only significant between-group difference was for disease duration (treated, 7.6 [8.1] years vs untreated, 12.3 [9.7] years; P = 0.044). Treated patients were more likely to have higher dispersed serum hormone concentrations than the untreated patients. Serum concentration of FSH was numerically higher in the treated patients than in the untreated patients, although the difference was not statistically significant. Compared with the control group (1436 men and women for prolactin; 226 men for LH; 207 for FSH; 128 for TT; 128 for FT; and 128 for SHBG), patients in the treated group had significantly different mean [SD] serum concentrations of all hormones (treated vs control: prolactin, 24.3 [23.7] µg/L vs 6.8 [0.12] µg/L, P < 0.001; LH, 4.9 [3.4] U/L vs 3.3 [0.13] U/L, P = 0.001; FSH, 4.4 [3.9] U/L vs 3.0 [0.06] U/L, P = 0.025; TT, 17.5 [7.8] nmol/L vs 20.1 [1.64] nmol/L, P = 0.004; FT, 0.056 [0.08] nmol/L vs 0.06 [0.003] nmol/L, P < 0.001; and SHBG, 33.3 [18.9] nmol/L vs 48.4 [1.45] nmol/L, P= 0.002). Compared with the control group, patients in the untreated group had significantly different mean (SD) serum concentrations of all hormones except FSH and TT (untreated vs control: prolactin, 19.9 [12.8] µg/L vs 6.8 [0.12] µg/L, P = 0.001; LH, 6.0 [1.9] U/L vs 3.3 [0.13] U/L, P = 0.002; FT, 0.08 [0.04] nmol/L vs 0.06 [0.003] nmol/L, P= 0.001; and SHBG, 26.6 [11.6] nmol/L vs 48.4 [1.45] nmol/L, P < 0.001). No differences were found between the TT distribution curve of the control group and that of the untreated patients. CONCLUSION: This study supports further investigation of a potential difference in the HPG axis among treated and untreated patients with schizophrenia and those who do not have that condition.

Aripiprazol: omais novo antipsicótico de nova geração / Aripiprazol: the newest antipsychotic of the second generation

Estima-se que um por cento da população tenha esquizofrenia, a qual atinge indivíduos jovens e coloca crescente sobrecarga econômica à sociedade. É importante o tratamento precoce e com uma medicaçaõ eficaz,bem tolerável e segura, para maximizar a adesão ao tratamento o prognóstico a longo prazo. O fato de al-guns antipsicóticos de primeira e segunda geração estarem associados a um aumento significante do peso e outros eventos adversos pode piorar a já precária adesão ao tratamento e favorecer a recaída. Diferente dos demais antipsicóticos ( antagonistas puros de dopamina), os agonistas parciais de dopamina são drogas co afinidade total de ligação ao receptor dopaminérgico e certa atividade intrínseca no mesmo, o que possibilita um perfil superior de segurança e tolerabilidade; o aripiprazol é a mais recente adição desta nova classe de antipsicóticos, com comprovada eficácia na eaquizofrenia. Os dados sobre seu mecanismo de ação, eficácia e segurança são apresentados, e sugerem ser o aripiprazol uma importante adição ao arsenal terapêutica da esquizofrênia.

Ganho de peso e medicações antipsicóticas / Weight gain and antipsycotics

Desde sua introdução no mercado, os antipsicóticos têm sido relacionados a aumento de peso. O advento dos antipsicóticos de nova geração trouxe avanços significativos no tratamento dos quadros esquizofrênicos tanto em relação à sintomatologia negativa, depressiva e cognitiva quanto em relação à segurança e tolerabilidade. No entanto, o ganho de peso ainda se mantém como um evento adverso frequente nesta classe. As autoras apresentam um breve resumo da literatura sobre o ganho de peso associado à terapia antipsicótica e seus possíveis mecanismo de ação. Descrevem ainda estratégias cognitivo-comportamentais e farmacológicas para o manejo do ganho de peso para os pacientes em uso de medicações antipsicóticas.