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Introduction: A new therapeutic class, potassium-competitive acid blockers (P-CABs), has emerged in Brazil to promote a superior antisecretory effect addressing the unmet needs related to acid-related disease management. Vonoprazan fumarate showed a good safety profile and was approved by the Brazilian regulatory agency - ANVISA. Aim: This narrative review was conducted to review the general concepts regarding P-CABs, focussing on vonoprazan fumarate. Material and methods: A literature search was conducted through April-May 2021 using official databases with a combination of MeSH controlled vocabulary and text words. The authors selected articles that described pivotal and novel insights about P-CABs and vonoprazan fumarate. Results: Vonoprazan is a drug of the P-CABs class newly approved for the management of acid-related diseases in Brazil. P-CABs achieve rapid, potent, and prolonged acid suppression (including night-time) and promise to address some unmet clinical needs in GERD. Furthermore, considering the difficulties encountered in attaining effective symptomatic control - particularly at night - using currently available PPIs, this new drug class is promising. Conclusions: This review brings important information about vonoprazan, a new therapeutic option in Brazil, which may be considered as a valuable tool for managing acid-related diseases.
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BACKGROUND: The burden of dengue in Brazil is poorly documented and is based on data from the public health care setting. This study estimated the prevalence and costs of dengue management in the private health care system in Brazil from 2015 to 2020 using a large claims database from Orizon. METHODS: We selected claims with dengue ICD codes (ICD-10 A90 or A91) from January 2015 to December 2020. Prevalence was estimated based on the population enrolled in health insurance plans in the given year. Costs were adjusted for the inflation up to December 2021 and evaluated by measures of central tendency and dispersion. RESULTS: A total of 63,882 unique beneficiaries were included, with a total of 64,186 dengue cases. The year with the highest prevalence was 2015 (1.6% of patients who used health plans), and there was also an increase in cases in 2016 and 2019. The median cost per hospitalization in 2015 was US$486.17, and in 2020, it reached US$696.72. The median cost of a case seen at an emergency room ranged from US$ 97.78 in 2015 to US$ 118.16 in 2017. CONCLUSIONS: The estimated prevalence of dengue in this population of private health-insured patients followed the epidemiological trends of the general population in Brazil, with the highest rates in 2015, 2016, and 2019. The cost of dengue management has increased in the private health care setting over the years.
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Atenção à Saúde , Dengue , Humanos , Prevalência , Brasil/epidemiologia , Custos e Análise de Custo , Dengue/epidemiologia , Custos de Cuidados de SaúdeRESUMO
ABSTRACT Background: The burden of dengue in Brazil is poorly documented and is based on data from the public health care setting. This study estimated the prevalence and costs of dengue management in the private health care system in Brazil from 2015 to 2020 using a large claims database from Orizon. Methods: We selected claims with dengue ICD codes (ICD-10 A90 or A91) from January 2015 to December 2020. Prevalence was estimated based on the population enrolled in health insurance plans in the given year. Costs were adjusted for the inflation up to December 2021 and evaluated by measures of central tendency and dispersion. Results: A total of 63,882 unique beneficiaries were included, with a total of 64,186 dengue cases. The year with the highest prevalence was 2015 (1.6% of patients who used health plans), and there was also an increase in cases in 2016 and 2019. The median cost per hospitalization in 2015 was US$486.17, and in 2020, it reached US$696.72. The median cost of a case seen at an emergency room ranged from US$ 97.78 in 2015 to US$ 118.16 in 2017. Conclusions: The estimated prevalence of dengue in this population of private health-insured patients followed the epidemiological trends of the general population in Brazil, with the highest rates in 2015, 2016, and 2019. The cost of dengue management has increased in the private health care setting over the years.
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BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBDs) with a remission-relapsing presentation and symptomatic exacerbations that have detrimental impacts on patient quality of life and are associated with a high cost burden, especially in patients with moderate-to-severe disease. The Real-world Data of Moderate-to-Severe Inflammatory Bowel Disease in Brazil (RISE BR) study was a noninterventional study designed to evaluate disease control, treatment patterns, disease burden and health-related quality of life in patients with moderate-to-severe active IBD. We report findings from the prospective follow-up phase of the RISE BR study in patients with active UC or CD. AIM: To describe the 12-mo disease evolution and treatment patterns among patients with active moderate-to-severe IBD in Brazil. METHODS: This was a prospective, noninterventional study of adult patients with active Crohn's disease (CD: Harvey-Bradshaw Index ≥ 8, CD Activity Index ≥ 220), inadequate CD control (i.e., calprotectin > 200 µg/g or colonoscopy previous results), or active ulcerative colitis (UC: Partial Mayo score ≥ 5). Enrollment occurred in 14 centers from October 2016 to February 2017. The proportion of active IBD patients after 9-12 mo of follow-up, Kaplan-Meier estimates of the time to mild or no activity and a summary of treatment initiation, discontinuation and dose changes were examined. RESULTS: The study included 118 CD and 36 UC patients, with mean ± SD ages of 43.3 ± 12.6 and 44.9 ± 16.5 years, respectively. The most frequent drug classes at index were biologics for CD (62.7%) and 5-aminosalicylate derivates for UC patients (91.7%). During follow-up, 65.3% of CD and 86.1% of UC patients initiated a new treatment at least once. Discontinuations/dose changes occurred in 68.1% of CD patients [median 2.0 (IQR: 2-5)] and 94.3% of UC patients [median 4.0 (IQR: 3-7)]. On average, CD and UC patients had 4.4 ± 2.6 and 5.0 ± 3.3 outpatient visits, respectively. The median time to first mild or no activity was 319 (IQR: 239-358) d for CD and 320 (IQR: 288-358) d for UC patients. At 9-12 mo, 22.0% of CD and 20.0% of UC patients had active disease. CONCLUSION: Although a marked proportion of active IBD patients achieved disease control within one year, the considerable time to achieve this outcome represents an unmet medical need of the current standard of care in a Brazilian real-world setting.
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Colite Ulcerativa , Doenças Inflamatórias Intestinais , Adulto , Brasil/epidemiologia , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/epidemiologia , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de VidaRESUMO
BACKGROUND: Understanding the treatment landscape of inflammatory bowel diseases (IBD) is essential for improving disease management and patient outcomes. Brazil is the largest Latin American country, and it presents socioeconomic and health care differences across its geographical regions. This country has the highest increase in IBD incidence and prevalence in Latin America, but information about the clinical and treatment characteristics of IBD is scarce. AIM: To describe the sociodemographic, clinical, and treatment characteristics of IBD outpatients in Brazil overall and in the Southeast, South and Northeast/Midwest regions. METHODS: Multicenter, cross-sectional study with a 3-year retrospective chart review component. Patients with moderate-to-severe Crohn's disease (CD) or ulcerative colitis (UC) were consecutively enrolled between October 2016 and February 2017. Active CD at enrollment was defined as a Harvey Bradshaw Index ≥ 8 or a CD Activity Index ≥ 220 or a calprotectin level > 200 µg/g or an active result based on colonoscopy suggestive of inadequate control during the previous year; active UC was defined as a partial Mayo score ≥ 5. Descriptive statistics were used to analyze all variables. RESULTS: In a total of 407 included patients, CD was more frequent than UC, both overall (264 CD/143 UC patients) and by region (CD:UC ratios of 2.1 in the Southeast, 1.6 in the South and 1.2 in the Northeast/Midwest). The majority of patients were female (54.2% of CD; 56.6% of UC), and the mean ages were 45.9 ± 13.8 years (CD) and 42.9 ± 13.0 years (UC). The median disease duration was 10.0 (range: 0.5-45) years for both IBD types. At enrollment, 44.7% [95% confidence interval (CI): 38.7-50.7] of CD patients and 25.2% (95%CI: 18.1-32.3) of UC patients presented with active disease. More than 95% of IBD patients were receiving treatment at enrollment; CD patients were commonly treated with biologics (71.6%) and immunosuppressors (67.4%), and UC patients were commonly treated with mesalazine [5-Aminosalicylic acid (5-ASA)] derivates (69.9%) and immunosuppressors (44.1%). More than 50% of the CD patients had ileocolonic disease, and 41.7% presented with stricturing disease. One-quarter of CD patients had undergone CD-related surgery in the past 3 years, and this proportion was lower in the Northeast/Midwest region (2.9%). CONCLUSION: In Brazil, there are regional variations in IBD management. CD outweighs UC in both frequency and disease activity. However, one-quarter of UC patients have active disease, and most are receiving 5-ASA treatment.
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Colite Ulcerativa , Doenças Inflamatórias Intestinais , Adulto , Brasil/epidemiologia , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Inflammatory bowel diseases (IBD) have been associated with a low quality of life (QoL) and a negative impact on work productivity compared to the general population. Information about disease control, patient-reported outcomes (PROs), treatment patterns and use of healthcare resources is relevant to optimizing IBD management. AIM: To describe QoL and work productivity and activity impairment (WPAI), treatment patterns and use of healthcare resources among IBD patients in Brazil. METHODS: A multicenter cross-sectional study included adult outpatients who were previously diagnosed with moderate to severe Crohn's disease (CD) or ulcerative colitis (UC). At enrolment, active CD and UC were defined as having a Harvey Bradshaw Index ≥ 8 or a CD Activity Index ≥ 220 or calprotectin > 200 µg/g or previous colonoscopy results suggestive of inadequate control (per investigator criteria) and a 9-point partial Mayo score ≥ 5, respectively. The PRO assessment included the QoL questionnaires SF-36 and EQ-5D-5L, the Inflammatory Bowel Disease Questionnaire (IBDQ), and the WPAI questionnaire. Information about healthcare resources and treatment during the previous 3 years was collected from medical records. Chi-square, Fisher's exact and Student's t-/Mann-Whitney U tests were used to compare PROs, treatment patterns and the use of healthcare resources by disease activity (α = 0.05). RESULTS: Of the 407 patients in this study (CD/UC: 64.9%/35.1%, mean age 42.9/45.9 years, 54.2%/56.6% female, 38.3%/37.1% employed), 44.7%/25.2% presented moderate-to-severe CD/UC activity, respectively, at baseline. Expressed in median values for CD/UC, respectively, the SF-36 physical component was 46.6/44.7 and the mental component was 45.2/44.2, the EQ-visual analog scale score was 80.0/70.0, and the IBDQ overall score was 164.0/165.0. Moderate to severe activity, female gender, being unemployed, a lower educational level and lower income were associated with lower QoL (P < 0.05). Median work productivity impairment was 20% and 5% for CD and UC patients, respectively, and activity impairment was 30%, the latter being higher among patients with moderate to severe disease activity compared to patients with mild or no disease activity (75.0% vs 10.0%, P < 0.001). For CD/UC patients, respectively, 25.4%/2.8% had at least one surgery, 38.3%/19.6% were hospitalized, and 70.7%/77.6% changed IBD treatment at least once during the last 3 years. The most common treatments at baseline were biologics (75.3%) and immunosuppressants (70.9%) for CD patients and 5-ASA compounds (77.5%) for UC patients. CONCLUSION: Moderate to severe IBD activity, especially among CD patients, is associated with a substantial impact on QoL, work productivity impairment and an increased number of IBD surgeries and hospitalizations in Brazil.
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Colite Ulcerativa/epidemiologia , Doença de Crohn/epidemiologia , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Adulto , Brasil/epidemiologia , Colite Ulcerativa/complicações , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/cirurgia , Doença de Crohn/complicações , Doença de Crohn/diagnóstico , Doença de Crohn/cirurgia , Estudos Transversais , Emprego/estatística & dados numéricos , Utilização de Instalações e Serviços/estatística & dados numéricos , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Estudos Prospectivos , Índice de Gravidade de DoençaRESUMO
In experimental Chagas' disease, lymphocytes from mice infected with Trypanosoma cruzi show increased apoptosis in vivo and in vitro. Treatment with a pan-caspase blocker peptide inhibited expression of the active form of effector caspase-3 in vitro and rescued both B and T cells from cell death. Injection of the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethyl ketone, but not a control peptide, reduced parasitemia and lymphocyte apoptosis in T. cruzi-infected mice. Moreover, treatment with caspase inhibitor throughout acute infection increased the absolute numbers of B and T cells in the spleen and lymph nodes, without affecting cell infiltrates in the heart. Following treatment, we found increased accumulation of memory/activated CD4 and CD8 T cells, and secretion of IFN-gamma by splenocytes stimulated with T. cruzi antigens. Caspase inhibition in the course of infection reduced the intracellular load of parasites in peritoneal macrophages, and increased the production of TNF-alpha and nitric oxide upon activation in vitro. Our results indicate that inhibition of caspases with a pan-caspase blocker peptide improves protective type-1 immune responses to T. cruzi infection. We suggest that mechanisms of apoptosis are potential therapeutic targets in Chagas' disease.
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Apoptose/imunologia , Inibidores de Caspase , Doença de Chagas/imunologia , Doença de Chagas/patologia , Linfócitos/enzimologia , Trypanosoma cruzi/imunologia , Clorometilcetonas de Aminoácidos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Doença de Chagas/tratamento farmacológico , Doença de Chagas/enzimologia , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB CRESUMO
Chagas' disease, caused by Trypanosoma cruzi infection, is one of the main causes of death due to heart failure in Latin American countries. Benznidazole, the chemotherapeutic agent most often used for the treatment of chagasic patients, is highly toxic and has limited efficacy, especially in the chronic phase of the disease. In the present study we used a mouse model of chronic Chagas' disease to investigate the effects of benznidazole treatment during the chronic phase on disease progression. The hearts of benznidazole-treated mice had decreased parasitism and myocarditis compared to the hearts of untreated chagasic mice. Both groups of Trypanosoma cruzi-infected mice had significant alterations in their electrocardiograms compared to those of the healthy mice. However, untreated mice had significantly higher cardiac conduction disturbances than benznidazole-treated mice, including intraventricular conduction disturbances, atrioventricular blocks, and extrasystoles. The levels of antibodies against T. cruzi antigens (epimastigote extract, P2beta, and trans-sialidase) as well as antibodies against peptides of the second extracellular loops of beta1-adrenergic and M2-muscarinic cardiac receptors were also lower in the sera from benznidazole-treated mice than in the sera from untreated mice. These results demonstrate that treatment with benznidazole in the chronic phase of infection prevents the development of severe chronic cardiomyopathy, despite the lack of complete parasite eradication. In addition, our data highlight the role of parasite persistence in the development of chronic Chagas' disease and reinforce the importance of T. cruzi elimination in order to decrease or prevent the development of severe chagasic cardiomyopathy.