CYD-TDV dengue vaccine: systematic review and meta-analysis of efficacy, immunogenicity and safety

Introduction: Dengue virus (DENV) is a serious global health problem. CYD-TDC (Dengvaxia®) was the first vaccine to gain regulatory approval to try and address this problem. Aim: Summarize all available evidence on the immunogenicity, efficacy and safety of the CYD-TDV dengue vaccine. Method: Meta-analysis and systematic review. Results: The best and worst immunogenicity results were for DENV4 and DENV1, respectively. Vaccine efficacy of 60% was derived from studies with participants aged 2–16 years old, with DENV4 and DENV2 presenting the best and worst results, respectively. Erythema and swelling were more frequent with CYD-TDV. No differences were detected for systemic adverse events. Conclusion: CYD-TDV showed moderate efficacy in children and adolescents. From the immunogenicity results in adults, we can expect satisfactory efficacy from vaccination in this population. </jats:p

Consumer willingness to pay for dengue vaccine (CYD-TDV, Dengvaxia®) in Brazil : implication for future pricing considerations

Introduction and objective: Dengue virus is a serious global health problem with an estimated 3.97 billion people at risk for infection worldwide. In December 2015, the first vaccine (CYD-TDV) for dengue prevention was approved in Brazil, developed by Sanofi Pasteur. However, given that the vaccine will potentially be paid via the public health system, information is need regarding consumers’ willingness to pay for the dengue vaccine in the country as well as discussions related to the possible inclusion of this vaccine into the public health system. This was the objective of this research. Methods: We conducted a cross-sectional study with residents of Greater Belo Horizonte, Minas Gerais, about their willingness to pay for the CYD-TDV vaccine. Results: 507 individuals were interviewed. These were mostly female (62.4%) had completed high school (62.17%), were working (74.4%), had private health insurance (64.5%) and did not have dengue (67.4%). The maximum median value of consumers’ willingness to pay for CYD-TDV vaccine is US$33.61 (120.00BRL) for the complete schedule and US$11.20 (40.00BRL) per dose. At the price determined by the Brazil's regulatory chamber of pharmaceutical products market (CMED) for the commercialization of Dengvaxia® for three doses, only 17% of the population expressed willingness to pay for this vaccine. Conclusion: Brazil is currently one of the largest markets for dengue vaccine and the price established is a key issue. We believe the manufacturer should asses the possibility of lower prices to reach a larger audience among the Brazilian population

Efficacy of Mobile Apps to Support the Care of Patients With Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background- Diabetes Mellitus (DM) is a chronic disease that is considered a global public health problem. Education and self-monitoring by diabetic patients help to optimize and make possible a satisfactory metabolic control enabling improved management and reduced morbidity and mortality. The global growth in the use of mobile phones makes them a powerful platform to help provide tailored health, delivered conveniently to patients through health applications (apps). Objective- Evaluate the efficacy of mobile apps through a systematic review and meta-analysis to assist diabetes mellitus patients in treatment. Methods- We conducted searches in the electronic databases MEDLINE (Pubmed), CENTRAL/ Cochrane Register of Controlled Trials and LILACS, manual search in references of publications included, systematic reviews, specialized journals and gray literature. We considered eligible randomized controlled trials (RCTs) conducted after 2008 with participants of all ages, diabetes mellitus patients and users of apps to help manage the disease. The meta-analysis of glycated hemoglobin (HbA1c) was performed in Review Manager Software 5.3. Results- The literature search identified 1236 publications. From these, 13 studies were included that evaluated 1263 patients. In six RCTs, there were a statistical significant reduction (P < 0.05) of HbA1c at the end of studies in the intervention group. The HbA1c data were evaluated by meta-analysis with the following results (MD = - .44; CI: - .59, - .29; P < .10; I² = 32%).The evaluation favored the treatment in patients who used apps without significant heterogeneity. Conclusions - The use of apps by diabetic patients could help improve the control of HbA1c. In addition, the apps seem to strengthen the perception of self-care contributing better information and health education to patients. Patients also become more self-confident to deal with their diabetes, mainly, by reducing fear of not knowing how to deal with potential hypoglycemic episodes that may occur

Costs in the Treatment of Schizophrenia in Adults Receiving Atypical Antipsychotics: An 11-Year Cohort in Brazil

Background: Schizophrenia is associated with significant economic burden. In Brazil, antipsychotics drugs, outpatient and hospital services are provided by the Brazilian National Health System for patients with schizophrenia. However, there are few studies that capture the cost of managing these patients within the Brazilian NHS. This is important to appraise different management approaches within universal healthcare systems. Objective: Describe the costs associated with the treatment of schizophrenia in adults receiving atypical antipsychotics in Brazil from 2000 to 2010 through real world data. Methods: We integrated three national databases for adult patients with schizophrenia receiving one or more atypical antipsychotics. Only direct medical costs were assessed as the perspective is a public payer. A multivariate log-linear regression model was performed to evaluate associations between costs and clinical and demographic variables. Results: 174,310 patients with schizophrenia were identified with mean (± SD) annual costs of USD 1,811.92 ± 284.39 per patient. Atypical antipsychotics accounted for 79.7% of the total cost, with a mean (± SD) annual cost per patient of USD 1,578.74 ± 240.40. Mean (± SD) annual costs per patient of psychiatric hospitalization were USD 2,482.90 ± 302.92 and outpatient psychiatric care was USD 862.96 ± 160.18. Olanzapine was used by 47.7% of patients and represented 62.8% of the total cost of atypical antipsychotics. Patients who used clozapine had the highest mean annual cost per patient regarding outpatient psychiatric care and psychiatric hospitalization. Conclusions: Atypical antipsychotics were responsible for the majority of the schizophrenia treatment cost, and psychiatric hospitalization costs were the highest mean annual cost per patient. As a result, authorities should ensure good quality of use of atypical antipsychotic and encourage outpatient psychiatric care over psychiatric hospitalization where possible

Ten-year kidney transplant survival of cyclosporine- or tacrolimus-treated patients in Brazil

Background: Cyclosporine and tacrolimus are well established immunosuppressants; however little know about long term survival rates. Aim: Compare 10-year graft survival and associated factors among kidney transplant patients within the Brazilian Public Health system (SUS) prescribed either medicine. Methods: Analyze a national cohort of kidney transplant recipients within SUS. Graft loss defined by death or dialysis for more than three months. Kaplan-Meier method used to estimate cumulative probabilities of survival. Cox proportional hazards model used to evaluate factors associated with progression to graft loss. Results: 13,811 patients were included, 5,887 used cyclosporine and 7,924 tacrolimus. A higher risk of graft loss was associated with tacrolimus, a deceased donor, additional years of age, median period of dialysis greater than 47 months, diagnosis of diabetes as the primary cause of chronic kidney disease and transplantation between 2005 and 2009. Conclusions: Among other factors, tacrolimus-based regimens were associated with worse graft survival

The Assessment for Disinvestment of Intramuscular Interferon Beta for Relapsing-Remitting Multiple Sclerosis in Brazil

In Brazil, inclusion and exclusion of health technologies within the Unified Health System (SUS) is the responsibility of the National Committee for Health Technology Incorporation (CONITEC). A recent Cochrane systematic review demonstrated that intramuscular interferon beta 1a (IFN-beta-1a-IM) was inferior to the other beta interferons (IFN-beta s) for multiple sclerosis (MS). As a result, CONITEC commissioned an analysis to review possible disinvestment within SUS. The objective of this paper is to describe the disinvestment process for IFN-beta-1a-IM in Brazil. The first assessment comprised a literature review and mixed treatment comparison meta-analysis. The outcome of interest was the proportion of relapse-free patients in 2 years. This analysis confirmed the inferiority of IFN-beta-1a-IM. Following this, CONITEC recommended disinvestment, with the decision sent for public consultation. More than 3000 contributions were made on CONITEC's webpage, most of them against the preliminary decision. As a result, CONITEC commissioned a study to assess the effectiveness of IFN-beta-1a-IM among Brazilian patients in routine clinical care. The second assessment involved an 11-year follow-up of a non-concurrent cohort of 12,154 MS patients developed by deterministic-probabilistic linkage of SUS administrative databases. The real-world assessment further demonstrated that IFN-beta-1a-IM users had a statistically higher risk of treatment failure, defined as treatment switching or relapse treatment or death, with the assessment showing that IFN-beta-1a-IM was inferior to the other IFN-beta s and to glatiramer acetate in both direct and indirect analysis. In the drug ranking with 40,000 simulations, IFN-beta-1a-IM was the worst option, with a success rate of only 152/40,000. Following this, CONITEC decided to exclude the intramuscular presentation of IFN-beta from the current MS treatment guidelines, giving patients who are currently on this treatment the option of continuing until treatment failure. In conclusion, we believe this is the first example of this new disinvestment process in action, providing an exemplar for other treatments in Brazil as well as other countries.Ministry of Health of BrazilUniv Fed Minas Gerais, Fac Farm, SUS Collaborating Ctr Technol Assessment & Excell, Sala 1042,Ave Presidente Antonio Carlos 6627, BR-31270901 Belo Horizonte, MG, BrazilUniv Fed Minas Gerais, Fac Med, Programa Posgrad Saude Publ, Sala 533,Ave Porf Alfredo Balena 190,Campus Saude, BR-30130100 Belo Horizonte, MG, BrazilUniv Fed Minas Gerais, Fac Farm, Programa Posgrad Medicamentos & Assistencia Farma, Sala 1023,Ave Presidente Antonio Carlos 6627, BR-31270901 Belo Horizonte, MG, BrazilInst Nacl Cardiol, Nucleo Avaliacao Tecnol Saude, R Laranjeiras 374, BR-22240006 Rio De Janeiro, RJ, BrazilMinist Saude, Dept Gestao & Inc Tecnol Saude, Secretaria Ciencia Tecnol & Insumos Estrateg, Esplanada Minist Bloco G, BR-70058900 Brasilia, DF, BrazilUniv Fed Sao Paulo, Programa Posgrad Saude Baseada Evidencias, Rua Botucatu 740,3 Andar, BR-04023900 Sao Paulo, SP, BrazilKarolinska Inst, Karolinska Univ Hosp Huddinge, Div Clin Pharmacol, S-14186 Stockholm, SwedenUniv Strathclyde, Strathclyde Inst Pharm & Biomed Sci, 161 Cathedral St, Glasgow G4 0RE, Lanark, ScotlandUniv Liverpool, Sch Management, Ctr Hlth Econ, Liverpool, Merseyside, EnglandUniv Fed Sao Paulo, Programa Posgrad Saude Baseada Evidencias, Rua Botucatu 740,3 Andar, BR-04023900 Sao Paulo, SP, BrazilMinistry of Health of Brazil: TED 78/2015, BR/LOA 1500033.001Web of Scienc

Initiatives across countries to reduce antibiotic utilization and resistance patterns : impact and implications

Greater accessibility to antibiotics has resulted in their excessive use, leading to increasing antimicrobial resistance (AMR) and strains on healthcare systems, with only a limited number of patients in ambulatory care treated according to guidelines. High rates of AMR are now seen across countries and continents, resulting in AMR becoming one of the most critical issues facing healthcare systems. It is estimated that AMR could potentially cause over 10 million deaths per year by 2050 unless addressed, resulting in appreciable economic consequences. There are also concerns with under-treatment especially if patients are forced to fund more expensive antibiotics as a result of AMR to first line antibiotics and do not have available funds. Over-prescribing of antibiotics is not helped by patient pressure even when physicians are aware of the issues. There is also extensive dispensing of antibiotics without a prescription; although this is now being addressed in some countries. Review interventions that have been instigated across continents and countries to reduce inappropriate antibiotic prescribing and dispensing, and associated AMR, to provide future guidance. Narrative case history approach. A number of successful activities have been instigated to reduce inappropriate prescribing and dispensing of antibiotics across sectors. These include the instigation of quality indicators, suggested activities of pharmacists as well as single and multiple interventions among all key stakeholder groups. Multiple inter-linking strategies are typically needed to enhance appropriate antibiotic prescribing and dispensing. The impact of ongoing activities need to be continually analysed to provide future direction if AMR rates, and their impact on subsequent morbidity, mortality and costs, are to be reduced

Ongoing strategies to improve the management of upper respiratory tract infections and reduce inappropriate antibiotic use particularly among lower and middle-income countries: findings and implications for the future

Introduction: Antibiotics are indispensable to maintaining human health; however, their overuse has resulted in resistant organisms, increasing morbidity, mortality and costs. Increasing antimicrobial resistance (AMR) is a major public health threat, resulting in multiple campaigns across countries to improve appropriate antimicrobial use. This includes addressing the overuse of antimicrobials for self-limiting infections, such as upper respiratory tract infections (URTIs), particularly in lower- and middle-income countries (LMICs) where there is the greatest inappropriate use and where antibiotic utilization has increased the most in recent years. Consequently, there is a need to document current practices and successful initiatives in LMICs to improve future antimicrobial use. Methodology: Documentation of current epidemiology and management of URTIs, particularly in LMICs, as well as campaigns to improve future antimicrobial use and their influence where known. Results: Much concern remains regarding the prescribing and dispensing of antibiotics for URTIs among LMICs. This includes considerable self-purchasing, up to 100% of pharmacies in some LMICs. However, multiple activities are now ongoing to improve future use. These incorporate educational initiatives among all key stakeholder groups, as well as legislation and other activities to reduce self-purchasing as part of National Action Plans (NAPs). Further activities are still needed however. These include increased physician and pharmacist education, starting in medical and pharmacy schools; greater monitoring of prescribing and dispensing practices, including the development of pertinent quality indicators; and targeted patient information and health education campaigns. It is recognized that such activities are more challenging in LMICs given more limited resources and a lack of healthcare professionals. Conclusion: Initiatives will grow across LMICs to reduce inappropriate prescribing and dispensing of antimicrobials for URTIs as part of NAPs and other activities, and these will be monitored

Eficácia dos medicamentos biológicos e gastos no tratamento de Psoríase e Artrite Psoriásica no Sistema Único de Saúde em Minas Gerais: 2010 - 2013

Exportado OPUSMade available in DSpace on 2019-08-11T23:35:08Z (GMT). No. of bitstreams: 1 disserta__o.pdf: 8671514 bytes, checksum: 35952c8790d6ea52b5e87b334fd41852 (MD5) Previous issue date: 23A psoríase é uma doença com manifestações predominantemente cutâneas, sendo provavelmente a mais prevalente doença de pele imunomediada em adultos. Seu tratamento sistêmico consiste na fototerapia e no uso de medicamentos sintéticos e biológicos. A artrite psoriásica (AP) é uma espondiloartropatia soronegativa associada à psoríase. Seu tratamento envolve o uso de medicamentos modificadores do curso da doença (MMCD) sintéticos e biológicos. Ambas as doenças estão relacionadas a um decréscimosignificativo da qualidade de vida. Desde 2002 são fornecidas a acitretina e a ciclosporina para psoríase por meio do Componente Especializado da Assistência Farmacêutica (CEAF). Em 2010, o metotrexato injetável passou a ser fornecido, e a AP foi contemplada, com o fornecimento de MMCD sintéticos e biológicos (adalimumabe, etanercepte e infliximabe). Considerando que os gastos com medicamentos do CEAF têm sido crescentes faz-se necessárioavaliar os efeitos dos agentes biológicos e caracterizar o perfil dos pacientes e os gastos do CEAF com psoríase e AP. Para a avaliação da eficácia, efetividade e segurança de adalimumabe, etanercepte, golimumabe e infliximabe no tratamento de AP em adultos, foi conduzida uma revisão sistemática de ensaios clínicos controlados e randomizados (ECR) e de estudos observacionais (coortes ou estudos de registro). Foram avaliados desfechos clínicos, progressão radiográfica, qualidade de vida, eventos adversos e persistência. Foram incluídos nove ECR e seis estudos observacionais, bem como dois estudos observacionais em andamento sobre o golimumabe. As respostas ACR20, ACR50, PsARC e PASI75 foram alcançadas por mais pacientes que utilizaram anti-TNF em comparação com o grupo controle após 24 semanas de acompanhamento. Mais participantes queutilizaram etanercepte e infliximabe alcançaram ACR70. Após todos ospacientes originalmente randomizados para anti-TNF ou placebo teremutilizado anti-TNF por pelo menos 24 semanas, foram observadas diferenças entre os grupos apenas com relação a ACR70. Desfechos radiográficos foram alcançados por mais pacientes que utilizaram anti-TNF, e esses resultados parecem ser tempo-dependentes quanto mais tempo o paciente utilizou anti-TNF, melhor o resultado. Etanercepte e infliximabe apresentaram os piores resultados com relação à reação à aplicação, mas em geral os anti-TNF, nos regimes estudados, foram tão seguros quanto placebo/controle. Não foram observadas diferenças em relação à eficácia e à efetividade entre os anti-TNF, mas estudos de superioridade com comparação anti-TNF vs. anti-TNF aindasão necessários. Para a análise do perfil dos pacientes e do gasto do CEAF em Minas Gerais com psoríase e AP, foi construída uma coorte histórica a partir do pareamento determinístico-probabilístico da base de dados de Autorização de Procedimentos de Alta Complexidade/Custo (APAC) do Sistema de Informação Ambulatorial (SIA) do SUS no período de março de 2010 a fevereiro de 2013. Foram atendidos 1.623 pacientes com psoríase e 218 pacientes com AP. O gasto total foi de R$3.438.798,00 e R$7.013,663,00, respectivamente. A distribuição entre sexos para ambas as doenças aproximou-se de 1:1. Parapsoríase a idade foi superior à observada na literatura. Guias de tratamento de ambas as doenças recomendam o uso de metotrexato como primeira linha, apesar disso os medicamentos sintéticos mais utilizados foram acitretina, para psoríase, e leflunomida, para AP. Diferentemente do observado pelo Registro Brasileiro de Biológicos, o biológico mais utilizado foi o etanercepte. O gasto médio per capita foi crescente, sendo maior para os pacientes com AP que iniciaram o tratamento com MMCD sintéticos, que para os pacientes compsoríase. Para adalimumabe e etanercepte o gasto médio foi decrescente. Considerando os resultados dos dois trabalhos, tem-se que adalimumabe, etanercepte e infliximabe são eficazes, efetivos e seguros. O golimumabe parece ser eficaz e seguro, a partir dos resultados de apenas um ECR. Entretanto esses resultados necessitarão ser confirmados por outros estudos, como os dois estudos observacionais em andamento incluídos na revisão sistemática. As diferenças encontradas entre a população da coorte e aliteratura com relação aos medicamentos mais utilizados parecem estarrelacionadas com o baixo custo do metotrexato, podendo ter sido custeado pelos próprios pacientes, e pela possibilidade de os pacientes portadores de AP terem buscado infliximabe como pacientes diagnosticados com artrite reumatoide. Esse último caso e o crescente gasto com medicamentos biológicos indica que mecanismos mais rígidos devam ser adotados para o fornecimento de medicamentos pelo CEAF. Para ampliar o acesso aos tratamentos e conter gastos, medidas podem ser adotadas pelo SUS, dentre elas, a revisão periódica de decisões sobre incorporação e desinvestimento, negociações com as indústrias, o estabelecimento de critérios mais rigorosos para o fornecimento de medicamentos, o monitoramento das prescrições e adisseminação das evidências por meio do detalhamento acadêmico.Psoriasis is a disease with predominantly cutaneous manifestations, being the most prevalent immune-mediated skin disease in adults. Its systemic treatment consists of phototherapy and the use of synthetic and biological medicines. Psoriatic arthritis (PsA) is a seronegative spondyloarthropathy associated with psoriasis. Its treatment comprises the use of synthetic and biological diseasemodifying antirheumatic drugs (DMARDs). Both diseases are associated with a significant decrease in quality of life. Since 2002 acitretin and cyclosporin are provided by the Unified Health System (SUS Sistema Único de Saúde) through the Specialized Medicines Component of Pharmaceutical Assistance(from now on referred as Component). In 2010 methotrexate was included and PsA was covered, with the provision of synthetic and biological (adalimumab, etanercept and infliximab) DMARDs. Considering that the expenditures with the Components medicines is increasing, it is timely to conduct studies to evaluate the effects of biological DMARDs and to chraracterize the profile of patients andthe spending of the Component with psoriasis and PsA. To evaluate efficacy, effectiveness and safety of adalimumab, etanercept, golimumab e infliximab for the treatment of active adult PsA, we conducted a systematic review of randomized controlled clinical trials (RCT) and observational studies (registries and cohort studies). We assessed clinical outcomes, radiographic progression, quality of life, adverse events and persistence. Nine RCT and six observational studies were included. Two observational ongoing studies on golimumab werealso included. ACR20, ACR50, PsARC and PASI75 responses were achieved by more anti-TNF users than control after up to 24 weeks of treatment. More participants who used etanercept and infliximab achieved ACR70. After all patients originally randomized to placebo had used anti-TNF for at least 24 weeks, we observed difference only with regard to ACR70 response. Radiographic end points were achieved by more patients in anti-TNF group, and they seem to be time dependent the longer patients use the medicine the better the results. Etanercept and infliximab presented the worse results on application site reactions, but in general anti-TNF drugs, in the regimens studied, were as safe as control/placebo. There seems to be no difference in efficacy and effectiveness among anti-TNFs, but superiority head-to-headstudies are still needed. To characterize the patients profile and the expeditures of Minas Gerais State with psoriasis and PsA we developed a cohort of patients attended by the Component from March 2010 to February 2013, using deterministic-probabilistic linkage of the Outpatient Information System (Sistema de Informação Ambulatorial do SUS) databases. 1,623 psoriasis patients and 218 patients with AP were attended by the Component. The total expenditure was R$3.438.798,00 and R$7.013,663,00, respectively. Sex distribution was approximately 1:1 for both diseases. Psoriasis patients were older than expected. Guidelines of both diseases recommend the use of methotrexate as first-line therapy. In our study the most used synthetic medicines were acitretin for psoriasis ans leflunomide for PsA. Unlike what wasobserved by the Brazilian Registry of Bilogicals, the most widely used biological was etanercept. The average per capita expenditure increased over time and was higher for patients with PsA who started treatment with synthetic drugs than for patients with psoriasis. The average expenditure for adalimumab and etanercept groups decreased over time. Considering the results of the two works, we can conclude that adalimumab, etanercept and infliximab are effective both in RCTs and in the real world studies. Golimumab presented favourable results of efficacy and safety, but these results need to be confirmed by the results of the included ongoing observational studies. The differences between the cohorts population and the literature with respect to the use of medicines seem to have to do with the low cost of methotrexate whencompared to acitretin and leflunomide, so that it could have been payed by the patients themselves, and with the likelihood of patients with PsA having required infliximab as patients with rheumatoid arthritis. This and the increasing expenditure with biologicals indicate that stricter mechanisms should be adopted for the provision of medicines of the Component. To broaden access to treatment and contain costs, measures can be adopted by SUS, among them the periodis revision of investiment and disinvestment decisions, egotiation wiith the pharmaceutical industry, the establishment of stricter criteria for theprovision of medicines, the monitoring of prescriptions and dissemination of evidence through academic detailing