A Cross-Sectional Study of Quality of Life Among Brazilian Adults With Type 1 Diabetes Treated With Insulin Glargine: Findings and Implications.

This article describes a cross-sectional study involving 401 adults with type 1 diabetes treated with insulin glargine in Minas Gerais, Brazil. Health-related quality of life was assessed, and worse scores were found to be associated with a low level of education, self-perceived health reported as poor/very poor, being bedridden and not physically exercised, having seen a doctor more than four times in the past year, and having reported comorbidities and episodes of hypoglycemia.

HEALTH TECHNOLOGY PERFORMANCE ASSESSMENT: REAL-WORLD EVIDENCE FOR PUBLIC HEALTHCARE SUSTAINABILITY.

OBJECTIVES: Health technology financing is often based on randomized controlled trials (RCTs), which are often the same ones used for licensing. Because they are designed to show the best possible results, typically Phase III studies are conducted under ideal and highly controlled conditions. Consequently, it is not surprising that technologies do not always perform in real life in the same way as controlled conditions. Because financing (and price paid) decisions can be made with overestimated results, health authorities need to ask whether health systems achieve the results they expect when they choose to pay for a technology. The optimal way to answer this question is to assess the performance of financed technologies in real-world settings. Health technology performance assessment (HTpA) refers to the systematic evaluation of the properties, effects, and/or impact of a health intervention or health technology in the real world to provide information for investment/disinvestment decisions and clinical guideline updates. The objective is to describe the development and principal aspects of the Guideline for HTpA commissioned by the Brazilian Ministry of Health. METHODS: Our methods used include extensive literature review, refinement with experts across countries, and public consultation. RESULTS: A comprehensive guideline was developed, which has been adopted by the Brazilian government. CONCLUSION: We believe the guideline, with its particular focus on disinvestment, along with the creation of a specific program for HTpA, will allow the institutionalization and continuous improvement of the scientific methods to use real-world evidence to optimize available resources not only in Brazil but across countries.

The pathogenesis-related protein PR-4b from Theobroma cacao presents RNase activity, Ca(2+) and Mg(2+) dependent-DNase activity and antifungal action on Moniliophthora perniciosa.

BACKGROUND: The production and accumulation of pathogenesis-related proteins (PR proteins) in plants in response to biotic or abiotic stresses is well known and is considered as a crucial mechanism for plant defense. A pathogenesis-related protein 4 cDNA was identified from a cacao-Moniliophthora perniciosa interaction cDNA library and named TcPR-4b. RESULTS: TcPR-4b presents a Barwin domain with six conserved cysteine residues, but lacks the chitin-binding site. Molecular modeling of TcPR-4b confirmed the importance of the cysteine residues to maintain the protein structure, and of several conserved amino acids for the catalytic activity. In the cacao genome, TcPR-4b belonged to a small multigene family organized mainly on chromosome 5. TcPR-4b RT-qPCR analysis in resistant and susceptible cacao plants infected by M. perniciosa showed an increase of expression at 48 hours after infection (hai) in both cacao genotypes. After the initial stage (24-72 hai), the TcPR-4b expression was observed at all times in the resistant genotypes, while in the susceptible one the expression was concentrated at the final stages of infection (45-90 days after infection). The recombinant TcPR-4b protein showed RNase, and bivalent ions dependent-DNase activity, but no chitinase activity. Moreover, TcPR-4b presented antifungal action against M. perniciosa, and the reduction of M. perniciosa survival was related to ROS production in fungal hyphae. CONCLUSION: To our knowledge, this is the first report of a PR-4 showing simultaneously RNase, DNase and antifungal properties, but no chitinase activity. Moreover, we showed that the antifungal activity of TcPR-4b is directly related to RNase function. In cacao, TcPR-4b nuclease activities may be related to the establishment and maintenance of resistance, and to the PCD mechanism, in resistant and susceptible cacao genotypes, respectively.

Treatment of psoriatic arthritis with anti-TNF agents: a systematic review and meta-analysis of efficacy, effectiveness and safety.

We did a systematic review and meta-analysis on the efficacy and safety of the anti-TNF drugs adalimumab, etanercept, golimumab and infliximab used in psoriatic arthritis (PsA) adult treatment. Additionally, we present results of anti-TNF use in real life settings. We searched Embase, Medline, Cochrane Central and LILACS, from inception to 11/08/2013, for studies comparing anti-TNFs with each other or with controls. We included nine randomized controlled trials and six observational studies. ACR20, ACR50, PsARC and PASI75 responses were achieved by more users of anti-TNF than control after up to 24 weeks of treatment. More participants who used etanercept and infliximab achieved ACR70. After all patients originally randomized to anti-TNF or 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 drug the better the results. Etanercept and infliximab had 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-head studies are still needed. Meanwhile, other factors should be taken into account in the choice of medication, such as costs and patient convenience.

Racial disparities in breast cancer survival after treatment initiation in Brazil: a nationwide cohort study.

BACKGROUND: Breast cancer is a public health priority in Brazil and ensuring equity in health care is one of the cancer control plan goals. Our aim was to present the first assessment on the influence of race or skin colour on breast cancer survival at the national level. METHODS: In this nationwide cohort study, data on women who initiated treatment for breast cancer in the public health-care system (Sistema Unico de Saúde), Brazil, were assembled through record linkage of administrative and mortality information systems. The administrative information systems were the Outpatient Information System (data from high complexity procedure authorisations) and the Hospital Information System (data from hospitalisation authorisations). We included women aged 19 years or older who started treatment between Jan 1, 2008, and Nov 30, 2010; self-identified as having White, Black, or Brown race or skin colour; had tumour stage I-IV; and were treated with chemotherapy or radiotherapy, or both. Patients were followed up until Dec 31, 2015. Patients with only hormone therapy records or who underwent only surgery were excluded. The Kaplan-Meier method was used to estimate crude overall survival for race or skin colour by time since treatment initiation, and Cox regression to estimate all-cause mortality hazard ratios (HRs) before and after adjustment for other covariates. FINDINGS: We identified 59 811 women treated for stage I-IV breast cancer. 37 318 (62·4%) women identified themselves as White, 18 779 (31·4%) as Brown, and 3714 (6·2%) as Black. 5-year overall survival probability was higher for White women (74% [95% CI 73-74]) than Black women (64% [62-65]; p<0·0001). In adjusted regression models stratified by the absence of hormone therapy, Black women had a 24% (HR 1·24 [95% CI 1·16-1·34]; p<0·0001) higher risk of all-cause death than White women, and in the presence of hormone therapy Black women had a 25% (1·25 [1·14-1·38]; p<0·0001) higher risk of all-cause death than White women. INTERPRETATION: Black skin colour was identified as a statistically significant risk marker for lower 5-year survival probability and higher risk of all-cause death among women treated for breast cancer by the Sistema Unico de Saúde. Actions to understand and mitigate this unfair difference in health results are urgently needed. FUNDING: Conselho Nacional de Desenvolvimento Científico e Tecnológico and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior and Pró-Reitoria de Pesquisa da Universidade Federal de Minas Gerais.

Computed tomography and magnetic resonance imaging in Brazil: an epidemiological study on the distribution of equipment and frequency of examinations, with comparisons between the public and private sectors.

Objective: To compare information on highly complex radiological procedures-computed tomography (CT) and magnetic resonance imaging (MRI)-between the public and private health care systems, across the five regions of Brazil, in terms of the numbers of radiological devices and examinations performed, between 2015 and 2021. Materials and Methods: This was a descriptive time series analysis of secondary data in the public domain, available from the Information Technology Department of the Brazilian Unified Health Care System, an entity of the Brazilian National Ministry of Health (NMH) that is responsible for collecting and storing health-related information in Brazil. The analysis included the numbers of CT and MRI scanners; the volumes and types of examinations; the type of institution (public or private); the regions of the country; and the years (2015 to 2021). Results: Progressive increases in the numbers of CT and MRI devices, as well as in the volumes of examinations, were observed over the years in all regions of the country. The private sector showed higher rates of equipment acquisition and of growth in the number of examinations. However, the public health care system did not reach the equipment targets set by the NMH, whereas the private health care system surpassed those targets. A greater number of examinations were performed in the private sector than in the public sector. Conclusion: During the period evaluated, the public health care system did not meet the equipment or examination targets recommended by the NMH, in any of the regions of the country, unlike the private health care system, which exceeded both in all of the regions.

Objetivo: Comparar informações sobre procedimentos radiológicos de alta complexidade ­ tomografia computadorizada (TC) e ressonância magnética (RM) ­, considerando o número de aparelhos e o quantitativo de exames nas esferas pública e privada nas cinco regiões brasileiras entre 2015 e 2021. Materiais e Métodos: Trata-se de um estudo descritivo de série temporal que utilizou dados secundários do Departamento de Informática do Sistema Único de Saúde, órgão do Ministério da Saúde (MS) responsável pela coleta e armazenamento das informações relacionadas à saúde no Brasil. Analisamos os números de aparelhos e de exames de TC e RM, considerando os tipos de aparelhos e exames, instituição (pública ou privada), região brasileira e ano (2015 a 2021). Resultados: Houve aumento de aparelhos e exames de TC e RM em todas as regiões ao longo dos anos. A esfera privada apresentou maior aquisição desses aparelhos e crescimento no número de exames. O sistema público não atingiu o número de aparelhos preconizado pelo MS, enquanto o sistema privado superou a recomendação. Observou-se maior número de exames na esfera privada quando comparada à pública. Conclusão: O sistema público não atendeu aos números de aparelhos e exames realizados preconizados pelo MS, diferentemente da esfera privada, em todas as regiões no período estudado.

Cost-effectiveness of continuous glucose monitoring with FreeStyle Libre® in Brazilian insulin-treated patients with types 1 and 2 diabetes mellitus.

BACKGROUND: Hypoglycemia is a barrier to optimal glucose control in the treatment of both type 1 (T1DM) and type 2 diabetes mellitus (T2DM). Blood glucose monitoring is essential in diabetes management. Inappropriate glucose management is associated with high mortality and morbidity. FreeStyle Libre® (FSL) is a continuous glucose monitoring (CGM) system that provides effective, safe, and convenient glucose monitoring, without routine finger pricking. This study aims to estimate the incremental cost-effectiveness ratio (ICER) of the FSL system in comparison to conventional Self-monitoring of blood glucose (SMBG) in T1DM and T2DM patients that require intensive insulin therapy. METHODS: A decision-tree model was developed to compare the cost-effectiveness ratio between FSL and conventional SMBG from the perspective of the Brazilian Public Healthcare System (SUS). The model captures the cumulative rates of acute complications such as severe hypoglicemia and diabetic ketoacidosis, per-event costs, and quality-adjusted life-years (QALYs) gained over a 1-year time horizon in adult and pediatric patients (≥ 4 years old) with T1DM or T2DM. Inputs from the Brazilian health databases, clinical trials, and real-world data were used in the study. RESULTS: The results demonstrated that, regarding solely severe hypoglicemia and diabetic ketoacidosis events, T1DM have a QALY difference of 0.276, a cost difference of R$ 7.255, and an ICER of R$ 26,267.69 per QALY gained for CGM with FSL, when compared to conventional SMBG. T2DM results demonstrated equally a QALY difference of 0.184, a cost difference of R$ 7290, and an ICER of R$ 39,692.67 per QALY gained, in favour of CGM with FSL. CONCLUSION: Our findings demonstrated that FSL is cost-effective in T1DM and T2DM for acute diabetic complications, from a SUS perspective. CGM with FSL can promote safe, convenient, and cost-effective glucose monitoring, therefore contributing to the improvement of the incidence of complications and quality of life.

Inflammation in Coronary Atherosclerosis: Insights into Pathogenesis and Therapeutic Potential of Anti-Inflammatory Drugs.

Atherosclerosis is a lipid-driven immune-inflammatory disease that affects the arteries, leading to multifocal plaque development. The inflammatory process involves the activation of immune cells and various inflammatory pathways. Anti-inflammatory drugs have been shown to be effective in reducing cardiovascular events in individuals with coronary disease. However, their use is still limited due to concerns about long-term follow-up, cost-effectiveness, adverse effects, and the identification of the ideal patient profile to obtain maximum benefits. This review aims to improve the understanding of inflammation in coronary atherosclerosis and explore potential therapeutic interventions, encompassing both traditional and non-traditional anti-inflammatory approaches. By addressing these concepts, we seek to contribute to the advancement of knowledge about this type of treatment for coronary artery disease.

The population genetics of Quechuas, the largest native South American group: autosomal sequences, SNPs, and microsatellites evidence high level of diversity.

Elucidating the pattern of genetic diversity for non-European populations is necessary to make the benefits of human genetics research available to individuals from these groups. In the era of large human genomic initiatives, Native American populations have been neglected, in particular, the Quechua, the largest South Amerindian group settled along the Andes. We characterized the genetic diversity of a Quechua population in a global setting, using autosomal noncoding sequences (nine unlinked loci for a total of 16 kb), 351 unlinked SNPs and 678 microsatellites and tested predictions of the model of the evolution of Native Americans proposed by (Tarazona-Santos et al.: Am J Hum Genet 68 (2001) 1485-1496). European admixture is <5% and African ancestry is barely detectable in the studied population. The largest genetic distances were between African versus Quechua or Melanesian populations, which is concordant with the African origin of modern humans and the fact that South America was the last part of the world to be peopled. The diversity in the Quechua population is comparable with that of Eurasian populations, and the allele frequency spectrum based on resequencing data does not reflect a reduction in the proportion of rare alleles. Thus, the Quechua population is a large reservoir of common and rare genetic variants of South Amerindians. These results are consistent with and complement our evolutionary model of South Amerindians (Tarazona-Santos et al.: Am J Hum Genet 68 (2001) 1485-1496), proposed based on Y-chromosome data, which predicts high genomic diversity due to the high level of gene flow between Andean populations and their long-term effective population size.

Effectiveness of first-line treatment for relapsing-remitting multiple sclerosis in Brazil: A 16-year non-concurrent cohort study.

BACKGROUND: Relapsing-remitting multiple sclerosis (RRMM) is a chronic, progressive, inflammatory and immune-mediated disease that affects the central nervous system and is characterized by episodes of neurological dysfunction followed by a period of remission. The pharmacological strategy aims to delay the progression of the disease and prevent relapse. Interferon beta and glatiramer are commonly used in the Brazilian public health system and are available to patients who meet the guideline criteria. The scenario of multiple treatments available and in development brings the need for discussion and evaluation of the technologies already available before the incorporation of new drugs. This study analyses the effectiveness of first-line treatment of RRMS measured by real-world evidence data, from the Brazilian National Health System (SUS). METHODS AND FINDINGS: We conducted a non-concurrent national cohort between 2000 and 2015. The study population consisted of 22,722 patients with RRMS using one of the following first-line drugs of interest: glatiramer or one of three presentations of interferon beta. Kaplan-Meier analysis was used to estimate the time to treatment failure. A univariate and multivariate Cox proportional hazard model was used to evaluate factors associated with treatment failure. In addition, patients were propensity score-matched (1:1) in six groups of comparative first-line treatments to evaluate the effectiveness among them. The analysis indicated a higher risk of treatment failure in female patients (HR = 1.08; P = 0,01), those with comorbidities at baseline (HR = 1.20; P<0,0001), in patients who developed comorbidities after starting treatment (i.e., rheumatoid arthritis-HR = 1.65; P<0,0001), those exclusive SUS patients (HR = 1.31; P<0,0001) and among patients using intramuscular interferon beta (IM ßINF-1a) (28% to 60% compared to the other three treatments; P<0,0001). Lower risk of treatment failure was found among patients treated with glatiramer. CONCLUSIONS: This retrospective cohort suggests that glatiramer is associated with greater effectiveness compared to the three presentations of interferon beta. When evaluating beta interferons, the results suggest that the intramuscular presentation is not effective in the treatment of multiple sclerosis.

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.

Stage at diagnosis and stage-specific survival of breast cancer in Latin America and the Caribbean: A systematic review and meta-analysis.

BACKGROUND: Female breast cancer is the most common cancer in Latin American and Caribbean (LAC) countries and is the leading cause of cancer deaths. The high mortality-to-incidence ratio in the regions is associated with mainly the high proportion of advanced stage diagnosis, and also to inadequate access to health care. In this study we aimed to systematically review the proportion of advanced stage (III-IV) at diagnosis (pas) and the five-year stage-specific survival estimates of breast cancer in LAC countries. METHODS: We searched MEDLINE, Embase, and LILACS (Latin American and Caribbean Health Science Literature) to identify studies, in any language, indexed before Nov 5, 2018. We also conducted manual search by reviewing citations of papers found. pas was summarized by random effects model meta-analysis, and meta-regression analysis to identify sources of variation. Stage-specific survival probabilities were described as provided by study authors, as it was not possible to conduct meta-analysis. PROSPERO CRD42017052493. RESULTS: For pas we included 63 studies, 13 of which population-based, from 22 countries comprising 221,255 women diagnosed from 1966 to 2017. The distribution of patients by stage varied greatly in LAC (pas 40.8%, 95%CI 37.0% to 44.6%; I2 = 99%; p<0.0001). The heterogeneity was not explained by any variable included in the meta-regression. There was no difference in pas among the Caribbean (pas 43.0%, 95%CI 33.1% to 53.6%), Central America (pas 47.0%, 95%CI 40.4% to 53.8%) and South America (pas 37.7%, 95%CI 33.1% to 42.5%) regions. For 5-year stage-specific survival we included 37 studies, comprising 28,988 women from ten countries. Seven of these studies were included also for pas. Since we were unable to adjust for age, comparability between countries and regions was hampered, and as expected, the results varied widely from study to study. CONCLUSIONS: LAC countries should look to address concerns with early detection and diagnosis of breast cancer, and wherever viable implement screening programs and to provide timely treatment.

Computed tomography and magnetic resonance imaging in Brazil: an epidemiological study on the distribution of equipment and frequency of examinations, with comparisons between the public and private sectors / Tomografia computadorizada e ressonância magnética no Brasil: estudo epidemiológico sobre distribuição dos equipamentos, frequência de realização dos exames e comparação entre setores público e privado

Abstract Objective: To compare information on highly complex radiological procedures—computed tomography (CT) and magnetic resonance imaging (MRI)—between the public and private health care systems, across the five regions of Brazil, in terms of the numbers of radiological devices and examinations performed, between 2015 and 2021. Materials and Methods: This was a descriptive time series analysis of secondary data in the public domain, available from the Information Technology Department of the Brazilian Unified Health Care System, an entity of the Brazilian National Ministry of Health (NMH) that is responsible for collecting and storing health-related information in Brazil. The analysis included the numbers of CT and MRI scanners; the volumes and types of examinations; the type of institution (public or private); the regions of the country; and the years (2015 to 2021). Results: Progressive increases in the numbers of CT and MRI devices, as well as in the volumes of examinations, were observed over the years in all regions of the country. The private sector showed higher rates of equipment acquisition and of growth in the number of examinations. However, the public health care system did not reach the equipment targets set by the NMH, whereas the private health care system surpassed those targets. A greater number of examinations were performed in the private sector than in the public sector. Conclusion: During the period evaluated, the public health care system did not meet the equipment or examination targets recommended by the NMH, in any of the regions of the country, unlike the private health care system, which exceeded both in all of the regions.

Resumo Objetivo: Comparar informações sobre procedimentos radiológicos de alta complexidade - tomografia computadorizada (TC) e ressonância magnética (RM) -, considerando o número de aparelhos e o quantitativo de exames nas esferas pública e privada nas cinco regiões brasileiras entre 2015 e 2021. Materiais e Métodos: Trata-se de um estudo descritivo de série temporal que utilizou dados secundários do Departamento de Informática do Sistema Único de Saúde, órgão do Ministério da Saúde (MS) responsável pela coleta e armazenamento das informações relacionadas à saúde no Brasil. Analisamos os números de aparelhos e de exames de TC e RM, considerando os tipos de aparelhos e exames, instituição (pública ou privada), região brasileira e ano (2015 a 2021). Resultados: Houve aumento de aparelhos e exames de TC e RM em todas as regiões ao longo dos anos. A esfera privada apresentou maior aquisição desses aparelhos e crescimento no número de exames. O sistema público não atingiu o número de aparelhos preconizado pelo MS, enquanto o sistema privado superou a recomendação. Observou-se maior número de exames na esfera privada quando comparada à pública. Conclusão: O sistema público não atendeu aos números de aparelhos e exames realizados preconizados pelo MS, diferentemente da esfera privada, em todas as regiões no período estudado.

The long-term costs for treating multiple sclerosis in a 16-year retrospective cohort study in Brazil.

BACKGROUND: Multiple Sclerosis (MS) is a disease that appreciably impacts on the quality of life of patients and is associated with high expenditure. MS is a chronic multifactorial disease, characterized by inflammation, demyelination and axonal loss. The Brazilian public health system provides pharmacological treatment as well as hospital and outpatient care for patients with relapsing-remitting and secondary progressive multiple sclerosis. However, we are not aware of any previous publications assessing total direct medical costs in patients with a long follow-up within the Brazilian healthcare system. Consequently, the objective is to analyze public spending on patients with MS to guide stakeholders in future investment and disinvestment decisions. METHODS AND FINDINGS: We retrospectively analyzed public Brazilian spending on patients with MS between 2000 and 2015 using the patient-centered registry of all patients in the public health system (SUS) obtained through deterministic-probabilistic record linkage of the Outpatient Information System, Hospital Information System and Mortality Information Systems in Brazil. Descriptive data analysis and a multiple linear regression model was performed to evaluate the associations between the mean annual cost per patient and the clinical and demographic variables. The suitability of the model was verified from a residue analysis and the level of significance adopted was 5%. RESULTS: 28,401 patients were identified and subsequently 23,082 patients were analyzed. The majority of the patients were female (73.3%), lived in the southeast region (58.9%), had a mean age of 36.8 (± 12.2) years and started treatment using one of the interferons beta (78.9%). The total direct medical cost spending in the sixteen years of the follow-up was US $ 2,308,393,465.60, and the mean annual expenditure per patient was US $ 13,544.40 (± 4,607.05). In the best fit model (p <0.001), approximately 40% of the variability of the mean annual cost per patient was explained by the region of residence; medication used (intention to treat); if the patient was a non-exclusive user of medicines, i.e., used SUS for other procedures other than high-cost medicines; year of treatment start; and presence of events (death; Relapse; change of treatment and/or comorbidity). CONCLUSIONS: In the public health system of Brazil, disease modifying therapies currently represent almost all of the total direct costs of multiple sclerosis treatment. Around the world, new and emerging health technologies to treat of MS impose a challenge to health budgets, highlighting the need for cost-effectiveness studies comparing these technologies to those already available. Our regression model may help in this process, and calls attention to the need to access the real world performance of new therapies available in SUS, with the potential for disinvestment and/ or price reductions if needed.

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, antipsychotic drugs and outpatient and hospital services are provided by the Brazilian National Health System (SUS) for patients with schizophrenia. However, few studies capture the cost of managing these patients within the Brazilian NHS. This is important to appraise different management approaches within universal healthcare systems. OBJECTIVE: Our objective was to use real-world data to describe the costs associated with the treatment of schizophrenia in adults receiving atypical antipsychotics in Brazil from 2000 to 2010. METHODS: We integrated three national databases for adult patients with schizophrenia receiving one or more atypical antipsychotics. We assessed only direct medical costs and the study was conducted from a public-payer perspective. A multivariate log-linear regression model was performed to evaluate associations between costs and clinical and demographic variables. RESULTS: We identified 174,310 patients with schizophrenia, with mean ± standard deviation (SD) annual costs of $US1811.92 ± 284.39 per patient. Atypical antipsychotics accounted for 79.7% of total costs, with a mean annual cost per patient of $US1578.74 ± 240.40. Mean annual costs per patient were $US2482.90 ± 302.92 for psychiatric hospitalization and $US862.96 ± 160.18 for outpatient psychiatric care. Olanzapine was used by 47.7% of patients and represented 62.8% of the total costs of atypical antipsychotics. Patients who used clozapine had the highest mean annual cost per patient for outpatient psychiatric care and psychiatric hospitalization. CONCLUSIONS: Atypical antipsychotics were responsible for the majority of the schizophrenia treatment costs, and psychiatric hospitalization costs were the highest mean annual cost per patient. Authorities should ensure efficient use of atypical antipsychotics and encourage outpatient psychiatric care over psychiatric hospitalization where possible.

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-ß-1a-IM) was inferior to the other beta interferons (IFN-ßs) 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-ß-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-ß-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-ß-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-ß-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-ß-1a-IM was inferior to the other IFN-ßs and to glatiramer acetate in both direct and indirect analysis. In the drug ranking with 40,000 simulations, IFN-ß-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-ß 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.

Consumer Willingness to Pay for Dengue Vaccine (CYD-TDV, Dengvaxia®) in Brazil; Implications 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 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.

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.

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 apps. OBJECTIVE: The aim of our study was to evaluate the efficacy of mobile apps through a systematic review and meta-analysis to assist DM patients in treatment. METHODS: We conducted searches in the electronic databases MEDLINE (Pubmed), Cochrane Register of Controlled Trials (CENTRAL), and LILACS (Latin American and Caribbean Health Sciences Literature), including manual search in references of publications that included systematic reviews, specialized journals, and gray literature. We considered eligible randomized controlled trials (RCTs) conducted after 2008 with participants of all ages, patients with DM, and users of apps to help manage the disease. The meta-analysis of glycated hemoglobin (HbA1c) was performed in Review Manager software version 5.3. RESULTS: The literature search identified 1236 publications. Of these, 13 studies were included that evaluated 1263 patients. In 6 RCTs, there were a statistical significant reduction (P<.05) of HbA1c at the end of studies in the intervention group. The HbA1c data were evaluated by meta-analysis with the following results (mean difference, MD -0.44; CI: -0.59 to -0.29; P<.001; 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 by contributing better information and health education to patients. Patients also become more self-confident to deal with their diabetes, mainly by reducing their fear of not knowing how to deal with potential hypoglycemic episodes that may occur.

Genome size, cytogenetic data and transferability of EST-SSRs markers in wild and cultivated species of the genus Theobroma L. (Byttnerioideae, Malvaceae).

The genus Theobroma comprises several trees species native to the Amazon. Theobroma cacao L. plays a key economic role mainly in the chocolate industry. Both cultivated and wild forms are described within the genus. Variations in genome size and chromosome number have been used for prediction purposes including the frequency of interspecific hybridization or inference about evolutionary relationships. In this study, the nuclear DNA content, karyotype and genetic diversity using functional microsatellites (EST-SSR) of seven Theobroma species were characterized. The nuclear content of DNA for all analyzed Theobroma species was 1C = ~ 0.46 pg. These species presented 2n = 20 with small chromosomes and only one pair of terminal heterochromatic bands positively stained (CMA+/DAPI- bands). The small size of Theobroma ssp. genomes was equivalent to other Byttnerioideae species, suggesting that the basal lineage of Malvaceae have smaller genomes and that there was an expansion of 2C values in the more specialized family clades. A set of 20 EST-SSR primers were characterized for related species of Theobroma, in which 12 loci were polymorphic. The polymorphism information content (PIC) ranged from 0.23 to 0.65, indicating a high level of information per locus. Combined results of flow cytometry, cytogenetic data and EST-SSRs markers will contribute to better describe the species and infer about the evolutionary relationships among Theobroma species. In addition, the importance of a core collection for conservation purposes is highlighted.