Setting a tariff for IVF and ICSI treatment: a cost analysis.

In-vitro fertilisation (IVF) and intra-cytoplasmatic sperm injection (ICSI) are available in Scotland through the National Health Service (NHS) according to specific criteria. There is no standardised NHS tariff for these treatments in Scotland, and variation exists amongst different centres providing NHS services. The aim of this study was to calculate the mean cost of IVF and ICSI cycles for NHS-funded treatment in Scotland. A detailed cost analysis of fresh and frozen cycles was performed, and a breakdown of the various cost components was presented. A deterministic approach was applied using NHS-funded individual cycle data from 2015-2018 and aggregate data. All costs were calculated in UK pounds sterling (£- using 2018 prices). Resource use was assigned to individual cycles based on cycle-level data or expert-informed assumptions; whenever needed, average aggregate costs were assigned to cycles. A total of 9442 NHS-funded cycles were included in the analysis. The average cost of fresh IVF and ICSI cycles was £3247 [£1526-£4215] and £3473 [£1526-£4416], respectively. Frozen cycles averaged £938 [£272-£1085]. This data can be useful to decision-makers, especially where IVF/ICSI is publicly funded, as it delivers a detailed IVF/ICSI cost breakdown. It is an opportunity for other authorities to estimate IVF/ICSI costs, as the methods applied are clear and reproducible.

Cost of Illness in Patients With COVID-19 Admitted in Three Brazilian Public Hospitals.

OBJECTIVES: The severity and transmissibility of COVID-19 justifies the need to identify the factors associated with its cost of illness (CoI). This study aimed to identify CoI, cost predictors, and cost drivers in the management of patients with COVID-19 from hospital and Brazil's Public Health System (SUS) perspectives. METHODS: This is a multicenter study that evaluated the CoI in patients diagnosed of COVID-19 who reached hospital discharge or died before being discharged between March and September 2020. Sociodemographic, clinical, and hospitalization data were collected to characterize and identify predictors of costs per patients and cost drivers per admission. RESULTS: A total of 1084 patients were included in the study. For hospital perspective, being overweight or obese, being between 65 and 74 years old, or being male showed an increased cost of 58.4%, 42.9%, and 42.5%, respectively. From SUS perspective, the same predictors of cost per patient increase were identified. The median cost per admission was estimated at US$359.78 and US$1385.80 for the SUS and hospital perspectives, respectively. In addition, patients who stayed between 1 and 4 days in the intensive care unit (ICU) had 60.9% higher costs than non-ICU patients; these costs significantly increased with the length of stay (LoS). The main cost driver was the ICU-LoS and COVID-19 ICU daily for hospital and SUS perspectives, respectively. CONCLUSIONS: The predictors of increased cost per patient at admission identified were overweight or obesity, advanced age, and male sex, and the main cost driver identified was the ICU-LoS. Time-driven activity-based costing studies, considering outpatient, inpatient, and long COVID-19, are needed to optimize our understanding about cost of COVID-19.

Validation of the Brazilian version of the hepatitis B quality of life evaluation instrument - HBQOL, and its application to patients with chronic hepatitis B in Cascavel - PR

Abstract The objective of this study is to validate the specific questionnaire for Hepatitis B HBQOL (Hepatitis B Quality of Life Instrument, version 1.0) for the Brazilian version, in addition to testing its applicability in patients with hepatitis B under treatment and comparing the quality of life between patients using first-line drugs (tenofovir and entecavir). For the validation, the back-translation technique was used in a sample of 47 patients. Factor analysis was performed between the items in each domain of the questionnaire and the internal consistency was calculated using Cronbach's α coefficient. In assessing the applicability of the validated questionnaire, interviews were carried out with 124 patients. Sociodemographic and treatment data were collected to characterize the sample and perform correlation analyzes. The results demonstrate that the Brazilian version of the questionnaire was successfully validated. In the analysis carried out among the 124 patients, the domains psychological well-being and stigma obtained the highest scores in quality of life and the lowest level of education conferred better results in these two domains. The comparison between tenofovir and entecavir showed no significant difference in patients' quality of life. The use of this validated instrument can make therapeutic decisions more rational

A review of the application of hollow-fiber liquid-phase microextraction in bioanalytical methods - A systematic approach with focus on forensic toxicology.

Over the past three decades, many studies employing hollow-fiber liquid-phase microextraction (HF-LPME) bioanalytical methods have been published. The basic mechanism of extraction relies on the migration of the analytes through a liquid membrane sustained in the pores of the walls of a porous hollow fiber, and from there into an acceptor phase present in the lumen of the fiber. The mass transfer occurs by passive diffusion and it can be enhanced by using a carrier or applying an electrical potential across the phases. This type of extraction method presents many advantages over classical techniques, such as high preconcentration factor, clean extracts, and a green chemistry approach. Due to its advantages, and considering that no study systematically compiled the characteristics of the published methods in one single accessible source of information, the aim of this systematic review is to assess the data regarding bioanalytical methods, compile, and analyse the studies published until up to October of 2017. The data source used for the systematic review were Pubmed, Web of Science, and Science Direct, and 171 studies were included in the final review by two independent reviewers, resulting in a reliable and accessible source of information about bioanalytical methods employing HF-LPME.

Safety of Biologics Approved for the Treatment of Rheumatoid Arthritis and Other Autoimmune Diseases: A Disproportionality Analysis from the FDA Adverse Event Reporting System (FAERS).

INTRODUCTION: The molecular and pharmacological complexity of biologic disease-modifying antirheumatic drugs used for the management of rheumatoid arthritis (RA) favors the occurrence of adverse drug reactions (ADRs), which should be constantly monitored in post-marketing safety studies. OBJECTIVE: The aim of this study was to identify signals of disproportionate reporting (SDR) of clinical relevance related to the use of biologic drugs approved for RA and other autoimmune diseases. METHODS: All suspected ADRs registered in the FDA Adverse Event Reporting System between January 2003 and June 2016 were collected. The reporting odds ratio was used as a measure of disproportionality to identify possible SDRs related to biologics. Those involving important medical events and designated medical events (DME) were prioritized. RESULTS: In total, 2602 SDRs were prioritized. The most commonly reported were 'Infections and infestations' (32.2%) and 'Neoplasms benign, malignant, and unspecified' (20.4%), and were mainly related to use of infliximab (25.3%, p < 0.001, and 28.8%, p = 0.002, respectively). Sixty-three signals involving DMEs were identified, most of which were related to rituximab (n = 27), and were mainly due to 'blood disorders'. Amongst the DMEs detected for more than one biologic, 'intestinal perforation' and 'pulmonary fibrosis' were related to most of them. CONCLUSIONS: The results of this study highlight possible safety issues associated with biologics, whose relationship should be more thoroughly investigated. Our results contribute to future research on the identification of clinically relevant risks associated with these drugs, and may help contribute to their rational and safe use.

Application of a Urine and Hair Validated LC-MS-MS Method to Determine the Effect of Hair Color on the Incorporation of 25B-NBOMe, 25C-NBOMe and 25I-NBOMe into Hair in the Rat.

NBOMes are a group of new psychoactive substances derived from phenethylamines. Recreational abuse is thought to have begun in 2010 and they are commonly associated with the "club drug" scene. They are administered in liquid form or as blotters due to their high potency. An LC-MS-MS method was validated using Scientific Working Group for Forensic Toxicology parameters for the detection of 25B-, 25C- and 4-iodo-2,5-dimethoxy-N-[(2-methoxyphenyl)methyl]-benzeneethanamine (25I-NBOMe) using 4-bromo-2,5-dimethoxy-N-[(2-methoxyphenyl)methyl]-benzeneethanamine (25B-NBOMe)-D3 as internal standard for urine and hair. Calibration graphs with R2 values >0.99 were observed for urine and hair for concentrations ranging from 0.1 to 100 ng/mL and 0.025 to 2.5 ng/mg, respectively. Urine LODs ranged from 5 to 25 pg/mL and had an LOQ of 50 pg/mL. Hair LOD and LOQs ranged from 3 to 5 pg/mg and 6.25 to 12.5 pg/mg, respectively. Intra- and inter-day precision was <20% and accuracy was within ±20% for both matrices. The method was shown to be selective for both exogenous and endogenous compounds. No matrix effects were observed for either matrix. LLE recovery ranged from 90 to 103% for urine samples and solid phase extraction recovery ranged from 80 to 107% for hair samples. Long-Evans rats (n = 55) were administered 25B-, 25C- or 25I-NBOMe at doses ranging from 30 to 300 µg/kg over a period of 10 days. Rats were shaved prior to their first dose and re-shaved after the 10-day period. Hair was separated by color (black: n = 55 and white: n = 55) and analyzed using the validated LC-MS-MS method to assess the impact hair color has on the incorporation of these drugs. All drugs were successfully detected in black hair. 25B-NBOMe from rats receiving the highest dose and 25C-NBOMe from rats receiving the medium and high doses were quantified in white hair. 25I-NBOMe was detected but fell below the limit of quantification. A dose-dependent concentration increase was observed in the black hair. All pooled urine samples tested positive for their expected NBOMes.

Economic evaluation of treatments for chronic hepatitis B

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.

Economic evaluation of treatments for chronic hepatitis B.

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.

Comparative efficacy of oral nucleoside or nucleotide analog monotherapy used in chronic hepatitis B: a mixed-treatment comparison meta-analysis.

STUDY OBJECTIVE: To compare the efficacy of nucleoside or nucleotide analog monotherapy for the treatment of chronic hepatitis virus B (HBV) with adefovir dipivoxil, entecavir, lamivudine, telbivudine, and tenofovir disoproxil fumarate. DESIGN: Mixed-treatment comparison meta-analysis of nine randomized controlled clinical trials. PATIENTS: A total of 3972 adults with a diagnosis of chronic hepatitis B. MEASUREMENTS AND MAIN RESULTS: A systematic review was conducted to search for randomized clinical trials that evaluated the efficacy of nucleoside or nucleotide analogs used as monotherapy. The evaluated outcomes were reduction of HBV DNA levels, normalization of alanine aminotransferase levels, and seroconversion of hepatitis B e antigen (HBeAg). A mixed-treatment comparison was conducted to compare the odds ratios among the treatments and to rank the therapies to determine the optimal treatment option. Tenofovir had the best results among the nucleoside or nucleotide analogs for the three evaluated efficacy outcomes in both HBeAg-positive and -negative patients. CONCLUSION: Tenofovir has the highest probability of reducing HBV DNA, normalizing alanine aminotransferase levels and inducing HBeAg seroconversion after 1 year of treatment. An efficacy comparison of therapies is an important tool to guide clinicians in selecting the optimal treatment option.

Insulin analogues versus human insulin in type 1 diabetes: direct and indirect meta-analyses of efficacy and safety

All patients with Diabetes Mellitus (DM) receive insulin therapy. In this study, we evaluated the efficacy, safety and tolerability of human insulin and insulin analogues. We performed a systematic review of the literature and a meta-analysis according to the Cochrane Collaboration methodology. In the absence of clinical studies comparing insulins, we performed a mixed treatment comparison to establish the differences between the active treatments. We included studies published from 1995 to 2010. HbA1c results, episodes of hypoglycemia and nocturnal hypoglycemia data were extracted and analyzed. Thirty-five randomized clinical trials were selected after examining the abstract and a full text review. These studies included 4,206 patients who received long-acting insulin analogues and 5,733 patients who received short-acting insulin analogues. Pooled data regarding efficacy indicated no significant differences in HbA1c values between glargine or detemir (once daily) and NPH insulin. However, a twice-daily dose of detemir produced differences in HbA1c values that favored detemir (-0.14% [95% CI: -0.21 to -0.08]; p<0.0001; I²=0%). Direct and indirect comparisons are consistent and show that there were no significant differences between human insulin and insulin analogues in efficacy or safety. Our results indicate that long- and short-acting insulin analogues offer few clinical advantages over conventional human insulin.

Todos os pacientes com Diabetes Mellitus (DM) tipo 1 recebem insulina. Neste estudo, avaliaram-se eficácia, segurança e tolerabilidade de insulinas humanas e análogas. Realizou-se uma revisão sistemática e meta-análise, de acordo com o preconizado pela Colaboração Cochrane. Na ausência de estudos clínicos comparando insulinas entre si, realizaram-se meta-análises de comparações indiretas a fim de estabelecer diferenças entre tratamentos ativos. Incluíram-se estudos de 1995 a 2010. Resultados de HbA1c, episódios de hipoglicemia e hipoglicemia noturna foram extraídos e analisados. Após leitura de resumos e, posteriormente, de artigos na íntegra, selecionaram-se 35 ensaios clínicos randomizados, totalizando 4206 pacientes utilizando insulina análoga de longa duração e 5733 pacientes insulina análoga de curta duração. Os resultados não demonstraram diferença estatisticamente significativa para redução de HbA1c entre glargina e detemir (uma vez ao dia) comparados a NPH. No entanto, insulina detemir utilizada duas vezes ao dia reduz a HbA1c (-0.14% [95% CI: -0.21 to -0.08]; p<0.0001; I²=0%). Comparações diretas e indiretas indicam que não existem diferenças significativas na médica de redução de HbA1c, independente da posologia de detemir, sendo estes resultados de eficácia e segurança consistentes. Os resultados indicam que insulinas análogas de longa ou curta duração apresentam pequenas vantagens, quando comparadas às insulinas tradicionais. Ademais, não existem diferenças entre eficácia e segurança quando comparamos insulinas análogas entre si.

Perfil dos usuários de anticitocinas disponibilizadas pelo Sistema Único de Saúde no estado do Paraná para o tratamento da artrite reumatoide / Profile of users of anticytokines off ered by the health care system in the state of Paraná for the treatment of rheumatoid arthritis

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 por cento recebiam adalimumabe, 44 por cento etanercepte e 16 por cento infliximabe, gerando um custo mensal de R$3.403.195,59. Com relação ao CID, 55 por cento dos indivíduos apresentavam CID M05.8, 27 por cento CID M06.0, 9 por cento CID M6.8, 8 por cento CID M5.0 e 1 por cento 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 percent, 44 percent and 16 percent 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 percent had ICD M05.8; 27 percent, ICD M06.0; 9 percent, ICD M6.8; 8 percent, ICD M5.0; and 1 percent 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.

Profile of users of anticytokines offered by the health care system in the state of Paraná for the treatment of rheumatoid arthritis.

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.

An analysis of quality of systematic reviews on pharmacist health interventions.

BACKGROUND: In the past 20 years, many studies have evaluated the impact of pharmaceutical practices on clinical, humanistic and economic outcomes. However, few studies have critically analysed the primary studies and published reviews regarding pharmaceutical practices. AIM OF THE REVIEW: The aim of this review is to assess the quality of systematic reviews and meta-analysis on pharmacist health interventions published from 1990 to 2009. METHOD: The data sources used were MEDLINE, Cochrane Library, International Pharmaceutical Abstracts, Latin American and Caribbean Health Sciences, Scientific Electronic Library Online, and Scopus. Studies in which interventions were done by a pharmacist or in which the pharmacist was a health team member were included. There were no restrictions based on the type of intervention, country or languages. The data extracted by two independent reviewers were the following: publication journal, language, publication year, search strategy, study design, quality assessment of the included studies, disease, study settings, intervention description, and outcome measures. The methodological quality of systematic reviews was accessed with AMSTAR. RESULTS: A total of 151 articles were found from which 31 were included. An increase in the number of publications occurred after 2005. Nineteen reviews evaluated the quality of primary studies, and 6 of these reviews performed meta-analyses. The methodological quality of reviews was considered to be moderate (52.8 ± 22.3% for reviewer #1 and 54.8 ± 16.5% for reviewer #2); of the 31 included reviews, 7, 18 and 6 reviews had high, moderate and poor quality, respectively. CONCLUSION: The quality of published reviews varies from moderate to poor. Improvements in the study design can be achieved by following specific recommendations, such as clearly describing the methods, performing the data extraction in duplicate, researching at least two databases, listing the included and excluded studies, employing tables with the main studies data and evaluating and reporting the scientific quality of the included articles.

Efficacy, safety and tolerability of using abatacept for the treatment of rheumatoid arthritis

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.

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.

Revisiting the efficacy of long-acting insulin analogues on adults with type 1 diabetes using mixed-treatment comparisons.

AIM: To perform a network meta-analysis between long-acting insulin analogues (glargine and detemir) and Neutral Protamine Hagedorn (NPH) insulin on adults with type 1 diabetes. METHODS: A systematic review of the literature was conducted according to the Cochrane Collaboration guidelines. The search for randomized controlled trials was performed in process databases, conferences and "gray literature" by 1995. RESULTS: We found 1051 citations comparing glargine or detemir with human insulin and 187 comparing long-acting insulin analogues. Data on Glycated Hemoglobin (HbA1c), hypoglycemia episodes, nocturnal hypoglycemia and withdrawal were meta-analyzed. After review, 8 studies comparing glargine and 9 comparing detemir with NPH and 2 comparing glargine with detemir were considered relevant. Were included 1508 patients that received glargine, 2698 detemir and 2654 NPH insulin. Efficacy data showed no significant differences in HbA1c change between glargine or detemir (once daily) and NPH insulin. Twice-daily regimen of detemir caused a difference in HbA1c that favored detemir (-0.14% [95% CI -0.21 to -0.08]). Direct comparisons showed no significant differences between glargine and detemir in safety or HbA1c mean change. CONCLUSION: The long-acting insulin analogues offer little to no clinical advantages over NPH insulin, and there is no significant difference in the efficacy and safety.

Cost-effectiveness of telbivudine versus lamivudine for chronic hepatitis B.

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.

Cost-effectiveness of telbivudine versus lamivudine for chronic hepatitis B

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.

Avaliação econômica das anticitocinas adalimumabe, etanercepte e infliximabe no tratamento da artrite reumatoide no Estado do Paraná / Economic evaluation of anticitokines adalimumab, etanercept and infliximab for treatment of rheumatoid arthritis in Paraná State, Brazil

Este estudo objetivou realizar uma avaliação econômica das anticitocinas adalimumabe (ADA), etanercepte (ETA) e infliximabe (IFX) para o tratamento da artrite reumatoide no Estado do Paraná, sob a perspectiva do SUS. Os dados de eficácia e segurança dos tratamentos foram buscados na literatura, e os custos foram calculados com valores gastos pelo SUS para cada um dos tratamentos. Foi elaborado o modelo de Markov para obter a relação custo-efetividade de cada tratamento. A relação custo-efetividade incremental (ICER) comparado ao tratamento padrão também foi calculada para cada anticitocina. Análises de sensibilidade e taxas de desconto foram aplicadas. Na avaliação custo-efetividade, encontraram-se custos por QALY de R$ 511.633,00, R$ 437.486,00 e R$ 657.593,00 para ADA, ETA e IFX, respectivamente. O ICER por QALY foi R$ 628.124,00, R$ 509.974,00 e R$ 965.927,00 para ADA, ETA e IFX, respectivamente. Nas análises de sensibilidade, o ETA e o ADA apresentaram valores próximos. Cabe aos gestores públicos e aos médicos prescritores a escolha adequada para cada paciente, entre os tratamentos disponibilizados.

This study aimed to perform an economic evaluation of anticytokines adalimumab (ADA), etanercept (ETA) and infliximab (IFX) for the treatment of rheumatoid arthritis in the State of Parana, in Brazil, in the perspective of the Brazilian Unified Health System. Data on efficacy and safety of treatment were collected in literature, and costs were calculated on the amounts spent by the Government for each treatment. A Markov model was performed to get the cost-effectiveness of each treatment. The incremental cost-effectiveness relationship (ICER) compared to a standard treatment was also calculated for each anticytokine. Sensitivity analysis and discount rates were applied. In assessing cost-effectiveness we found the following values (cost at R$ per QALY): 511,633.00, 437,486.00 and 657,593.00 (respectively for ADA, ETA and IFX). The ICER (R$ per QALY) was 628,124.00, 509,974.00 and 965,927.00 (for ADA, ETA and IFX). In the sensitivity analysis, ETA and ADA showed similar values. It is for public managers and physicians the choice for each patient, among the treatments available.

Meta-analysis of the efficacy and safety of adalimumab, etanercept, and infliximab for the treatment of rheumatoid arthritis.

STUDY OBJECTIVE: To evaluate the efficacy and safety of using the anti-tumor necrosis factor-alpha (anti-TNF-alpha) drugs adalimumab, etanercept, and infliximab for the treatment of rheumatoid arthritis. DESIGN: Systematic review and meta-analysis of 21 randomized, placebo-controlled trials (eight adalimumab, seven infliximab, six etanercept). PATIENTS: Adults with rheumatoid arthritis who received adalimumab (1524 patients), infliximab (1116 patients), etanercept (1029 patients), or placebo (2834 patients) with or without concomitant methotrexate in all groups. MEASUREMENTS AND MAIN RESULTS: A literature search of several databases from January 1995-December 2008 was performed. There were no restrictions based on language or date of publication, and low-quality studies (based on Jadad score) were excluded. American College of Rheumatology (ACR) 20% improvement criteria (ACR20), 50% improvement criteria (ACR50), and 70% improvement criteria (ACR70) were used to compare treatment efficacy. Safety was compared based on frequency of serious adverse events, serious infections, malignancy, and death. Withdrawals due to adverse events and lack of efficacy were also evaluated. With short-term treatment (12-30 wks), etanercept demonstrated the highest risk ratios (RRs) for reaching ACR20 and ACR50: 2.94 (95% confidence interval [CI] 2.27-3.81) and 5.28 (95% CI 3.12-8.92), respectively. Adalimumab demonstrated the highest RR for achieving ACR70 (5.36, 95% CI 3.76- 7.64). Over a long-term treatment course (1-3 yrs), adalimumab demonstrated the highest RRs (95% CIs) for these parameters: 1.85 (1.07-3.19), 2.80 (1.16-6.77), and 3.23 (1.37-7.61) for ACR20, ACR50, and ACR70, respectively. No statistically significant differences were noted in the safety of any of the three drugs compared with placebo. Infliximab had the highest RRs for withdrawing from the study due to lack of efficacy (2.05, 95% CI 1.33-3.16) and adverse events (0.41, 95% CI 0.18-0.95). CONCLUSION: With short-term treatment, etanercept and adalimumab had higher efficacy results; with long-term treatment, adalimumab appeared to be the most effective. Clinicians should be aware that each of the three drugs has different rates of efficacy and different safety considerations that must be taken into account when selecting the best treatment for an individual with rheumatoid arthritis.

A systematic review and meta-analysis of the efficacy and safety of adalimumab for treating rheumatoid arthritis.

Adalimumab (ADA) is a monoclonal antibody. Published studies indicate that its use in patients with rheumatoid arthritis can be efficient in providing long-term benefits. The aim of this study is to evaluate the efficacy and safety of ADA for treating rheumatoid arthritis. A systematic review was performed to search for randomized clinical trials that compare subcutaneous doses of ADA 20 mg weekly or 40 mg every other week with placebo, with or without concomitant methotrexate. Only studies of moderate or high quality were included. A meta-analysis was conducted to assess the efficacy (based in changes of American College of Rheumatology ACR criteria) and the safety (based in serious adverse events, serious infections, malignancy and deaths) of ADA use. Withdrawals due to adverse events or lack of efficacy were also evaluated. Eight studies met the inclusion criteria, comprising 2,692 patients. In the efficacy meta-analysis, a greater number of ADA-treated patients relative to those in placebo group achieved ACR20, ACR50 and ACR70 values from 6 months to 2 years of treatment. For safety results, there were no statistically significant differences between the groups. Withdrawals due to adverse events were higher in ADA group relative to the placebo group, and withdrawals due to the lack of efficacy were higher in placebo group relative to the ADA-treated group. This meta-analysis shows a higher efficacy of ADA relative to placebo, but clinicians should be careful regarding adverse events in ADA-treated patients.