Potassium-competitive acid blockers, a new therapeutic class, and their role in acid-related diseases: a narrative review.

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.

Vonoprazan in the management of gastric/peptic ulcers: a systematic review of safety data.

Introduction: Although potassium-competitive acid blockers (P-CABs) prompted safety concerns when first developed, they ultimately proved to have a favourable safety profile. Aim: To assess the safety of vonoprazan in the management of gastroesophageal reflux disease (GERD), peptic ulcers, or gastroduodenal mucosal lesions induced by chronic use of aspirin or non-steroidal anti-inflammatory drugs (NSAIDs). Material and methods: From March to June 2021, a literature search was conducted using Medline via PubMed, Cochrane library, Lilacs, SciELO, and Centre for Reviews and Dissemination (CRD) electronic databases. After applying the eligibility criteria, 10 studies were included in this review. Of these 10 articles, vonoprazan was used as initial therapy in 6 and as maintenance therapy in 4. Adverse event rates were similar for vonoprazan and proton-pump inhibitors (PPIs). Conclusions: Our findings suggest that vonoprazan is a safe option for the management of erosive oesophagitis, gastric/peptic ulcers, or peptic ulcers induced by chronic use of aspirin or NSAIDs.

Vonoprazan in the management of erosive oesophagitis and peptic ulcer-induced medication: a systematic review.

Introduction: Vonoprazan has been found to promote a better antisecretory effect addressing acid-related diseases' unmet needs. Aim: To assess if vonoprazan effectively treats patients diagnosed with gastroesophageal reflux disease esophagitis or with peptic ulcers induced by chronic use of aspirin or non-steroidal anti-inflammatory drugs. Material and methods: A literature search was conducted (April/2021) using Medline via PubMed, Cochrane library, Lilacs, Scielo, and Centre for Reviews and Dissemination electronic databases. Results: We retrieved 55 titles. Of these, 13 met the eligibility criteria and were included in this review. Of these 13 articles, 4 were prospective cohort studies, 1 was a follow-up analysis of a preceding prospective study, 1 was a retrospective cohort study, and 6 were randomized clinical trials. Conclusions: Our findings suggest that vonoprazan was effective and non-inferior to proton pump inhibitors in healing and maintaining healed reflux oesophagitis, leading to faster symptom relief. Vonoprazan may also be considered for preventing aspirin- or non-steroidal anti-inflammatory drug-related peptic ulcer recurrence.

IMPACT OF HEARTBURN AND REGURGITATION ON INDIVIDUALS' WELL-BEING IN THE GENERAL POPULATION: A BRAZILIAN NATIONAL SURVEY.

BACKGROUND: Heartburn and acid regurgitation are typical symptoms usually associated with gastroesophageal reflux disease (GERD). GERD is one of the gastrointestinal diagnosis with higher prevalence worldwide, significantly impairing patients' quality of life. OBJECTIVE: The objective of this study was to analyze the impact of GERD-related symptoms in the Brazilian urban population. METHODS: National telephone survey with community-dwelling Brazilian individuals. Self-reported prevalence and frequency of symptoms (heartburn / regurgitation) were assessed. Individuals rated the impact of symptoms in their general well-being using a numeric scale from 1 to 10 (1 = no impact; 10 = very intense, preventing the person to eat and perform daily routine activities). Descriptive and bivariate statistical analyses were performed. RESULTS: The final sample was comprised of 1,773 subjects, 935 (52.7%) females, an average of 40 years old. The prevalence of heartburn and regurgitation in the past 6 months was 26.2% (n=466) and 11.0% (n=196), respectively. Women presented higher prevalence (heartburn n=266, 28.5% and regurgitation n=119, 12.7%) than men (n=200, 23.1% and n=78, 8.9%, respectively) (P<0.05). Heartburn in the past week was reported by 175 individuals (9.8%), while regurgitation episodes by 67 (3.8%). Absence of impact of the symptom in the overall well-being was observed for 82 subjects (17.6%) with heartburn and 18 individuals (9.2%) with regurgitation. Very intense impact was reported by 46 subjects (9.8%) with heartburn and 41 (20.9%) with regurgitation. Women's well-being was more affected than men's (mean score 5.45 vs 4.71, P<0.05). CONCLUSION: Heartburn and regurgitation were frequent symptoms, women with higher prevalence. These symptoms led to a substantial impact on individuals' well-being, women being more affected.

Impacto da pirose e regurgitação no bem-estar de indivíduos da população geral: um inquérito nacional brasileiro / Impact of heartburn and regurgitation on individuals' well-being in the general population: a brazilian national survey

ABSTRACT BACKGROUND: Heartburn and acid regurgitation are typical symptoms usually associated with gastroesophageal reflux disease (GERD). GERD is one of the gastrointestinal diagnosis with higher prevalence worldwide, significantly impairing patients' quality of life. OBJECTIVE: The objective of this study was to analyze the impact of GERD-related symptoms in the Brazilian urban population. METHODS: National telephone survey with community-dwelling Brazilian individuals. Self-reported prevalence and frequency of symptoms (heartburn / regurgitation) were assessed. Individuals rated the impact of symptoms in their general well-being using a numeric scale from 1 to 10 (1 = no impact; 10 = very intense, preventing the person to eat and perform daily routine activities). Descriptive and bivariate statistical analyses were performed. RESULTS: The final sample was comprised of 1,773 subjects, 935 (52.7%) females, an average of 40 years old. The prevalence of heartburn and regurgitation in the past 6 months was 26.2% (n=466) and 11.0% (n=196), respectively. Women presented higher prevalence (heartburn n=266, 28.5% and regurgitation n=119, 12.7%) than men (n=200, 23.1% and n=78, 8.9%, respectively) (P<0.05). Heartburn in the past week was reported by 175 individuals (9.8%), while regurgitation episodes by 67 (3.8%). Absence of impact of the symptom in the overall well-being was observed for 82 subjects (17.6%) with heartburn and 18 individuals (9.2%) with regurgitation. Very intense impact was reported by 46 subjects (9.8%) with heartburn and 41 (20.9%) with regurgitation. Women's well-being was more affected than men's (mean score 5.45 vs 4.71, P<0.05). CONCLUSION: Heartburn and regurgitation were frequent symptoms, women with higher prevalence. These symptoms led to a substantial impact on individuals' well-being, women being more affected.

RESUMO CONTEXTO: Pirose e regurgitação ácida são sintomas típicos usualmente relacionados à doença do refluxo gastroesofágico (DRGE). A DRGE é um dos diagnósticos gastrointestinais com maior prevalência mundial, afetando significativamente a qualidade de vida dos pacientes. OBJETIVO: Analisar o impacto de sintomas relacionados à DRGE em uma amostra da população brasileira urbana. MÉTODOS: Inquérito nacional via telefone com indivíduos brasileiros em contexto comunitário. O inquérito foi conduzido entre 6 de agosto e 12 de setembro de 2018. A prevalência autorrelatada e a frequência dos sintomas foram avaliadas. Os respondentes classificaram o impacto dos sintomas no seu bem-estar geral utilizando uma escala numérica de 1 a 10 (1 = ausência de impacto; 10 = impacto muito grave, impedindo a pessoa de comer ou realizar atividades da vida diária). Análises estatísticas descritivas e bivariadas foram conduzidas. RESULTADOS: A amostra final foi constituída por 1.773 indivíduos, 935 (52,7%) mulheres, com idade média de 40 anos. A prevalência de pirose e regurgitação nos últimos 6 meses foi de 26,2% (n=466) e 11,0% (n=196), respectivamente. Sexo feminino (pirose n=266, 28,5% e regurgitação n=119, 12,7%) apresentou prevalência mais alta do que o masculino (n=200, 23,1% e n=78, 8,9%, respectivamente) (P<0,05). Pirose na última semana foi relatada por 175 indivíduos (9,8%), enquanto episódios de regurgitação por 67 (3,8%). Ausência de impacto dos sintomas no bem-estar geral dos indivíduos foi observada para 82 respondentes (17,6%) com pirose e 18 (9,2%) daqueles com regurgitação. Impacto muito grave foi reportado por 46 (9,8%) indivíduos com pirose e 41 (20,9%) com regurgitação. Sexo feminino foi mais afetado pelos sintomas do que o masculino. CONCLUSÃO: Pirose e regurgitação foram bastante frequentes sendo o sexo feminino mais afetado. Tais sintomas levaram a impacto no bem-estar dos indivíduos, com maior prejuízo para mulheres.

BRAZILIAN PHYSICIANS' PRACTICES ON THE MANAGEMENT OF SYMPTOMS SUGGESTING GASTROESOPHAGEAL REFLUX DISEASE: A MULTIDISCIPLINARY SURVEY.

BACKGROUND: Clinical guidelines are available to steer decisions regarding diagnosis, management and treatment of gastrointestinal disorders. Despite this, variations in physician's practices regarding gastroesophageal reflux disease (GERD) symptoms are well described in the literature. OBJECTIVE: To describe practices of physicians from different specialties on the management of patients with typical symptoms of GERD (heartburn and regurgitation) in a Brazilian sample. METHODS: National online survey enrolling a sample of general practitioners, gastroenterologists, cardiologists and otolaryngologists. The survey was conducted from August 6th to September 12th, 2018. Subjects answered a structured questionnaire addressing variables regarding physicians' profile (age, sex, specialty, practice setting, years in practice, type of medical expense reimbursement), their patients characteristics and prescribing behaviors. RESULTS: The final weighted sample was comprised of 400 physicians, 64% male, with an average of 15 years of experience. Physicians' estimates of gastroesophageal symptoms prevalence among their pool of patients was 37.6% for the total sample, reaching 70.3% among gastroenterologists. The medical specialty with lower average percentage of patients presenting gastroesophageal symptoms was otolaryngology (24.5%). Physicians reported that they request ancillary tests for 64.5% of patients with GERD typical symptoms. The most common diagnostic test was endoscopy (69.4%), followed by video nasolaryngoscopy (16.6%). The percentage of patient to whom endoscopy is performed was significantly higher among gastroenterologists and general practitioners as compared to otolaryngologists and cardiologists, while video nasolaryngoscopy is markedly more frequent among otolaryngologists. In terms of therapeutic options, the most frequently reported strategy was lifestyle modifications followed by proton pump inhibitors. CONCLUSION: Overall patients' profile and patterns of GERD diagnosis and management seem different between gastroenterologists, general practitioners, otolaryngologists, and cardiologists. Clinical guidelines should address this variability and include other medical specialties besides gastroenterologists in their scope.

Práticas de médicos brasileiros no manejo de sintomas sugestivos de doença do refluxo gastroesofágico: uma avaliação multidisciplinar / Brazilian physicians' practices on the management of symptoms suggesting gastroesophageal reflux disease: a multidisciplinary survey

ABSTRACT BACKGROUND: Clinical guidelines are available to steer decisions regarding diagnosis, management and treatment of gastrointestinal disorders. Despite this, variations in physician's practices regarding gastroesophageal reflux disease (GERD) symptoms are well described in the literature. OBJECTIVE: To describe practices of physicians from different specialties on the management of patients with typical symptoms of GERD (heartburn and regurgitation) in a Brazilian sample. METHODS: National online survey enrolling a sample of general practitioners, gastroenterologists, cardiologists and otolaryngologists. The survey was conducted from August 6th to September 12th, 2018. Subjects answered a structured questionnaire addressing variables regarding physicians' profile (age, sex, specialty, practice setting, years in practice, type of medical expense reimbursement), their patients characteristics and prescribing behaviors. RESULTS: The final weighted sample was comprised of 400 physicians, 64% male, with an average of 15 years of experience. Physicians' estimates of gastroesophageal symptoms prevalence among their pool of patients was 37.6% for the total sample, reaching 70.3% among gastroenterologists. The medical specialty with lower average percentage of patients presenting gastroesophageal symptoms was otolaryngology (24.5%). Physicians reported that they request ancillary tests for 64.5% of patients with GERD typical symptoms. The most common diagnostic test was endoscopy (69.4%), followed by video nasolaryngoscopy (16.6%). The percentage of patient to whom endoscopy is performed was significantly higher among gastroenterologists and general practitioners as compared to otolaryngologists and cardiologists, while video nasolaryngoscopy is markedly more frequent among otolaryngologists. In terms of therapeutic options, the most frequently reported strategy was lifestyle modifications followed by proton pump inhibitors. CONCLUSION: Overall patients' profile and patterns of GERD diagnosis and management seem different between gastroenterologists, general practitioners, otolaryngologists, and cardiologists. Clinical guidelines should address this variability and include other medical specialties besides gastroenterologists in their scope.

RESUMO CONTEXTO: Diretrizes clínicas estão disponíveis para orientar decisões sobre diagnóstico, manejo e tratamento de desordens gastrointestinais. Apesar disso, variações nas práticas relacionadas aos sintomas de doença do refluxo gastroesofágico (DRGE) são observadas na literatura. OBJETIVO: Descrever os conhecimentos e práticas relacionados ao manejo de pacientes com sintomas típicos de DRGE (pirose e regurgitação) em uma amostra brasileira de médicos de especialistas e não especialistas. MÉTODOS: Inquérito nacional online investigando a conduta frente ao diagnóstico de DRGE em uma amostra de médicos generalistas, gastroenterologistas, cardiologistas e otorrinolaringologistas. O inquérito foi conduzido entre 6 de agosto e 12 de setembro de 2018. Os sujeitos responderam a um questionário estruturado avaliando variáveis relacionadas ao perfil dos médicos (idade, sexo, especialidade, contexto de prática, anos de experiência, tipo de reembolso de despesas médicas), características dos pacientes e comportamentos de prescrição. RESULTADOS: A amostra final ponderada foi composta por 400 médicos, 64% homens, com um tempo médio de experiência de 15 anos. A estimativa dos médicos a respeito da prevalência de sintomas gastroesofágicos entre seus pacientes foi de 37,6% para a amostra total, alcançando 70,3% entre gastroenterologistas. A especialidade médica com menor percentual de pacientes apresentando sintomas gastroesofágicos foi otorrinola­ringologia (24,5%). Os médicos requisitaram exames complementares em 64,5% dos pacientes com sintomas típicos de DRGE. O exame diagnóstico mais frequente foi endoscopia (69,4%), seguida de nasolaringoscopia (16,6%). O percentual de pacientes nos quais uma endoscopia é realizada é significativamente maior entre gastroenterologistas e médicos generalistas, quando comparado a otorrinolaringologistas e cardiologistas, enquanto nasolaringoscopia é marcadamente mais frequente entre otorrinolaringologistas. Em termos de opções terapêuticas, a estratégia mais frequentemente reportada foi modificações no estilo de vida, seguida de inibidores da bomba de prótons. CONCLUSÃO: De modo geral, o perfil de pacientes e os padrões de diagnóstico e manejo de DRGE parecem diferir entre gastroenterologistas, médicos generalistas, otorrinolaringologistas e cardiologistas. Diretrizes clínicas devem abordar esta variabilidade e incluir outras especialidades médicas além de gastroenterologistas em seu escopo.

EVALUATION OF PSORIASIS TREATMENT WITH ESOMEPRAZOLE - A PILOT STUDY.

BACKGROUND: Psoriasis is an inflammatory skin disease that affects 1%-3% of Caucasian populations and may be persistent, disfiguring and stigmatising. Proton pump inhibitors (PPI) are potent blockers of gastric acid secretion. They are widely regarded as the agents of choice for the treatment of acid-peptic disorders. In addition to anti-secretory effects PPI have been found to have anti-oxidant properties and direct effects on neutrophils, monocytes, endothelial, and epithelial cells that might prevent inflammation. OBJECTIVE: This study evaluated the treatment of psoriasis with esomeprazole. METHODS: Ten patients were selected and psoriasis was evaluated according to Psoriasis Area and Severity Index (PASI). Exclusion criteria included concomitant use of any treatment for Psoriasis, organic diseases, use of other PPI than esomeprazole. Patients were medicated with esomeprazole 40 mg B.I.D. for 90 days. At the 90th day the patients were evaluated according PASI score. RESULTS: Statistically significant results were seen when compared PASI before and at 90th day of treatment (P=0.0002). CONCLUSION: The use of esomeprazole for psoriasis resulted in excellent clinical results with a significant reduction of PASI score.

Avaliação do tratamento da psoríase com esomeprazol - estudo piloto / Evaluation of psoriasis treatment with esomeprazole - a pilot study

ABSTRACT BACKGROUND: Psoriasis is an inflammatory skin disease that affects 1%-3% of Caucasian populations and may be persistent, disfiguring and stigmatising. Proton pump inhibitors (PPI) are potent blockers of gastric acid secretion. They are widely regarded as the agents of choice for the treatment of acid-peptic disorders. In addition to anti-secretory effects PPI have been found to have anti-oxidant properties and direct effects on neutrophils, monocytes, endothelial, and epithelial cells that might prevent inflammation. OBJECTIVE: This study evaluated the treatment of psoriasis with esomeprazole. METHODS: Ten patients were selected and psoriasis was evaluated according to Psoriasis Area and Severity Index (PASI). Exclusion criteria included concomitant use of any treatment for Psoriasis, organic diseases, use of other PPI than esomeprazole. Patients were medicated with esomeprazole 40 mg B.I.D. for 90 days. At the 90th day the patients were evaluated according PASI score. RESULTS: Statistically significant results were seen when compared PASI before and at 90th day of treatment (P=0.0002). CONCLUSION: The use of esomeprazole for psoriasis resulted in excellent clinical results with a significant reduction of PASI score.

RESUMO CONTEXTO: A psoríase é uma doença inflamatória da pele que afeta 1%-3% das populações caucasianas e pode ser persistente, desfigurante e estigmatizante. Inibidores da bomba de prótons (IBP) são potentes bloqueadores da secreção de ácido no estômago. Eles são considerados como os agentes de escolha para o tratamento de doenças ácido-pépticas. No entanto, além dos efeitos anti-secretores, IBP apresentam propriedades anti-oxidantes e efeitos diretos sobre os neutrófilos, monócitos, células epiteliais e endoteliais que podem impedir a inflamação. OBJETIVO: Avaliar o tratamento da psoríase com esomeprazol. MÉTODOS: Foram selecionados pacientes adultos (18 anos ou mais) com psoríase. Os critérios de exclusão foram o uso concomitante de qualquer tratamento para a psoríase, doenças orgânicas e uso de outro IBP. Foram selecionados 10 pacientes e a psoríase foi avaliada pelo índice de gravidade e área da psoríase (Psoriasis Area and Severity Index - PASI). Os pacientes foram medicados com esomeprazol 40 mg BID por 90 dias. No nonagésimo dia os pacientes foram novamente avaliados por meio do PASI. RESULTADOS: Dados estatisticamente significativos foram vistos quando comparado PASI antes do tratamento e no nonagésimo dia de tratamento, P=0,0002. CONCLUSÃO: O uso do esomeprazol para psoríase apresentou excelentes resultados clínicos com redução importante do PASI. Este estudo piloto é a primeira publicação na literatura inglesa sobre o tratamento da psoríase com esomeprazol.

HISTORICAL PERSPECTIVE OF GASTROESOPHAGEAL REFLUX DISEASE CLINICAL TREATMENT.

BACKGROUND: Gastroesophageal reflux disease (GERD) is one of the most prevalent gastrointestinal diseases. GERD generates significant impairment in patients' quality of life and it is associated to relevant medical resources utilization. A better understanding of GERD pathophysiology in the past five decades has favored the evolution of therapeutic strategies from non-drug interventions and antacids to more efficacious and safer alternatives. OBJECTIVE: To summarize data about the historical evolution of GERD management in Brazil, focusing on medical therapy and addressing evidence on efficacy and safety of drug classes currently recommended. METHODS: A narrative review was conducted by systematizing information about discoveries on GERD pathophysiology. We also addressed efficacy and safety of medications currently used to reduce symptoms and improve endoscopic healing of esophageal lesions. A structured search on Pubmed was performed to identify systematic reviews and meta-analysis investigating GERD outcomes positively impacted by proton pump inhibitors (PPIs), the first choice of pharmacotherapy for the disease. RESULTS: The chronological development of therapeutic measures for GERD in Brazil evolved from lifestyle interventions with relative poor effect on symptoms related to esophageal acid exposure, particularly heartburn, to effective and safe pharmacological interventions such as histamine H2-receptor antagonists and PPIs. In the present days, some drug classes play a minor role in disease management, namely prokinetics and antacids, due to their reduced efficacy and relevant safety concerns (particularly with prokinetics). The main challenge for prescribers and researchers seems to be finding long-acting acid suppressants strategies able to ameliorate patients' symptoms and quality of life, thereafter, reducing medical resource consumption. The dual delayed-release PPI dexlansoprazole seems to respond for some of the limitations other PPIs have. CONCLUSION: Recognizing the historical evolution of GERD management can help care providers to better understand therapeutic options for their patients, as well as focus on unmet needs that deserve further attention. PPIs are still the first choice therapy, with good evidence in favor of their efficacy, despite some safety concerns. However, as with any medical intervention, it is recommended to prescribe PPIs for patients with clear indication, using adequate dosing and monitoring for adverse events.

Perspectiva histórica do tratamento clínico da doença do refluxo gastroesofágico / Historical perspective of gastroesophageal reflux disease clinical treatment

ABSTRACT BACKGROUND: Gastroesophageal reflux disease (GERD) is one of the most prevalent gastrointestinal diseases. GERD generates significant impairment in patients' quality of life and it is associated to relevant medical resources utilization. A better understanding of GERD pathophysiology in the past five decades has favored the evolution of therapeutic strategies from non-drug interventions and antacids to more efficacious and safer alternatives. OBJECTIVE: To summarize data about the historical evolution of GERD management in Brazil, focusing on medical therapy and addressing evidence on efficacy and safety of drug classes currently recommended. METHODS: A narrative review was conducted by systematizing information about discoveries on GERD pathophysiology. We also addressed efficacy and safety of medications currently used to reduce symptoms and improve endoscopic healing of esophageal lesions. A structured search on Pubmed was performed to identify systematic reviews and meta-analysis investigating GERD outcomes positively impacted by proton pump inhibitors (PPIs), the first choice of pharmacotherapy for the disease. RESULTS: The chronological development of therapeutic measures for GERD in Brazil evolved from lifestyle interventions with relative poor effect on symptoms related to esophageal acid exposure, particularly heartburn, to effective and safe pharmacological interventions such as histamine H2-receptor antagonists and PPIs. In the present days, some drug classes play a minor role in disease management, namely prokinetics and antacids, due to their reduced efficacy and relevant safety concerns (particularly with prokinetics). The main challenge for prescribers and researchers seems to be finding long-acting acid suppressants strategies able to ameliorate patients' symptoms and quality of life, thereafter, reducing medical resource consumption. The dual delayed-release PPI dexlansoprazole seems to respond for some of the limitations other PPIs have. CONCLUSION: Recognizing the historical evolution of GERD management can help care providers to better understand therapeutic options for their patients, as well as focus on unmet needs that deserve further attention. PPIs are still the first choice therapy, with good evidence in favor of their efficacy, despite some safety concerns. However, as with any medical intervention, it is recommended to prescribe PPIs for patients with clear indication, using adequate dosing and monitoring for adverse events.

RESUMO CONTEXTO: A doença do refluxo gastroesofágico (DRGE) é uma das doenças gastrointestinais mais prevalentes, resultando em limitações significativas na qualidade de vida dos pacientes e, também, relevante utilização de recursos médicos. Um melhor entendimento da fisiopatologia da doença nas últimas cinco décadas tem favorecido a evolução das estratégias de tratamento, desde intervenções não farmacológicas e antiácidos, a alternativas mais eficazes e seguras. OBJETIVO: Resumir os dados sobre a evolução histórica do manejo da DRGE no Brasil, focando na terapia medicamentosa e abordando evidências sobre a eficácia e segurança de classes medicamentosas atualmente recomendadas. MÉTODOS: Uma revisão narrativa foi conduzida para sistematizar informações sobre descobertas na fisiopatologia da DRGE e, também, sobre a eficácia e segurança de medicamentos utilizados atualmente para reduzir os sintomas e melhorar a cicatrização endoscópica de lesões esofágicas. Uma busca estruturada na base de dados Pubmed foi realizada para identificar revisões sistemáticas e metanálises que investigassem desfechos da doença impactados positivamente pelos inibidores da bomba de prótons (IBPs), a primeira escolha farmacológica para a doença. RESULTADOS: O desenvolvimento cronológico das medidas terapêuticas para a DRGE no Brasil evoluiu de modificações no estilo de vida que demonstraram relativamente pouco efeito sobre os sintomas relacionados à exposição esofágico ao ácido, particularmente a azia, a intervenções farmacológicas eficazes e seguras como os anti-histamínicos H2 e os IBPs. Atualmente, algumas classes de medicamentos exercem um papel menor no manejo da doença, procinéticos e antiácidos por exemplo, devido à sua eficácia reduzida e a preocupações relevantes quanto a segurança (particularmente com os procinéticos). O principal desafio para os prescritores e pesquisadores parece ser encontrar estratégias supressoras de ácidos de longa duração capazes de melhorar os sintomas e a qualidade de vida dos pacientes, reduzindo assim o consumo de recursos médicos. O dexlansoprazol, um IBP de liberação retardada dupla, parece responder a algumas limitações que outros IBPs têm. CONCLUSÃO: O reconhecimento da evolução histórica do manejo da DRGE pode auxiliar aos profissionais assistentes a melhor entender as opções terapêuticas para seus pacientes, assim como focar em necessidades não atendidas que necessitem de maior atenção. IBPs ainda são a terapia de escolha inicial, com boas evidências a favor de sua eficácia, apesar algumas questões acerca da segurança de seu uso. No entanto, assim como para qualquer intervenção medicamentosa, é recomendada a prescrição dos IBPs para pacientes com indicação clara, utilizando doses adequadas e monitorando a ocorrência de eventos adversos.

IVTH BRAZILIAN CONSENSUS CONFERENCE ON HELICOBACTER PYLORI INFECTION.

Significant progress has been obtained since the III Brazilian Consensus Conference on H. pylori infection held in 2012, in Bento Gonçalves, Brazil, and justify a fourth meeting to establish updated guidelines on the current management of H. pylori infection. Therefore, the Núcleo Brasileiro para Estudo do Helicobacter pylori e Microbiota (NBEHPM), association linked to Brazilian Federation of Gastroenterology (FBG) held its fourth meeting again in Bento Gonçalves, RS, Brazil, on August 25-27, 2017. Twenty-six delegates, including gastroenterologists, endoscopists, and pathologists from the five regions of Brazil as well as one international guest from the United States, participated in the meeting. The participants were invited based on their knowledge and contribution to the study of H. pylori infection. The meeting sought to review different aspects of treatment for infection; establish a correlation between infection, dyspepsia, intestinal microbiota changes, and other disorders with a special emphasis on gastric cancer; and reassess the epidemiological and diagnostic aspects of H. pylori infection. Participants were allocated into four groups as follows: 1) Epidemiology and Diagnosis, 2) Dyspepsia, intestinal microbiota and other afections, 3) Gastric Cancer, and, 4) Treatment. Before the consensus meeting, participants received a topic to be discussed and prepared a document containing a recent literature review and statements that should be discussed and eventually modified during the face-to-face meeting. All statements were evaluated in two rounds of voting. Initially, each participant discussed the document and statements with his group for possible modifications and voting. Subsequently, during a second voting in a plenary session in the presence of all participants, the statements were voted upon and eventually modified. The participants could vote using five alternatives: 1) strongly agree; 2) partially agree; 3) undecided; 4) disagree; and 5) strongly disagree. The adopted consensus index was that 80% of the participants responded that they strongly or partially agreed with each statement. The recommendations reported are intended to provide the most current and relevant evidences to management of H. pylori infection in adult population in Brazil.

3rd Brazilian Consensus on Helicobacter pylori.

Signicant progress has been obtained since the Second Brazilian Consensus Conference on Helicobacter pylori Infection held in 2004, in São Paulo, SP, Brazil, and justify a third meeting to establish updated guidelines on the current management of H. pylori infection. The Third Brazilian Consensus Conference on H pylori Infection was organized by the Brazilian Nucleus for the Study of Helicobacter, a Department of the Brazilian Federation of Gastroenterology and took place on April 12-15, 2011, in Bento Gonçalves, RS, Brazil. Thirty-one delegates coming from the five Brazilian regions and one international guest, including gastroenterologists, pathologists, epidemiologists, and pediatricians undertook the meeting. The participants were allocated in one of the five main topics of the meeting: H pylori, functional dyspepsia and diagnosis; H pylori and gastric cancer; H pylori and other associated disorders; H pylori treatment and retreatment; and, epidemiology of H pylori infection in Brazil. The results of each subgroup were submitted to a final consensus voting to all participants. Relevant data were presented, and the quality of evidence, strength of recommendation, and level of consensus were graded. Seventy per cent and more votes were considered as acceptance for the final statement. This article presents the main recommendations and conclusions to guide Brazilian doctors involved in the management of H pylori infection.

3rd Brazilian consensus on Helicobacter pylori / 3º Consenso Brasileiro para Estudo do Helicobacter pylori

Significant progress has been obtained since the Second Brazilian Consensus Conference on Helicobacter pylori Infection held in 2004, in São Paulo, SP, Brazil, and justify a third meeting to establish updated guidelines on the current management of H. pylori infection. The Third Brazilian Consensus Conference on H pylori Infection was organized by the Brazilian Nucleus for the Study of Helicobacter, a Department of the Brazilian Federation of Gastroenterology and took place on April 12-15, 2011, in Bento Gonçalves, RS, Brazil. Thirty-one delegates coming from the five Brazilian regions and one international guest, including gastroenterologists, pathologists, epidemiologists, and pediatricians undertook the meeting. The participants were allocated in one of the five main topics of the meeting: H pylori, functional dyspepsia and diagnosis; H pylori and gastric cancer; H pylori and other associated disorders; H pylori treatment and retreatment; and, epidemiology of H pylori infection in Brazil. The results of each subgroup were submitted to a final consensus voting to all participants. Relevant data were presented, and the quality of evidence, strength of recommendation, and level of consensus were graded. Seventy per cent and more votes were considered as acceptance for the final statement. This article presents the main recommendations and conclusions to guide Brazilian doctors involved in the management of H pylori infection.

Os avanços significativos ocorridos desde o Segundo Consenso Brasileiro sobre H. pylori realizado em 2004, em São Paulo, justificam este terceiro consenso. O evento foi organizado pelo Núcleo Brasileiro para Estudo do Helicobacter, departamento da Federação Brasileira de Gastroenterologia, tendo sido realizado em Bento Gonçalves, RS, nos dias 12 a 15 de abril de 2011. Contou com a participação de 30 delegados provenientes das cinco regiões brasileiras e um convidado internacional, incluindo gastroenterologistas, patologistas, epidemiologistas e pediatras. Os participantes foram alocados em um dos cinco subgrupos do evento, a saber: Helicobacter pylori, dispepsia funcional e diagnóstico; Helicobacter pylori e câncer gástrico; Helicobacter pylori e afecções não-gastroduodenais; Helicobacter pylori, tratamento e retratamento, e, epidemiologia da infecção por Helicobacter pylori no Brasil. Após extensa discussão, todas as recomendações e conclusões emanadas tinham definidas a força da recomendações e seu grau de evidência científica. As conclusões de cada subgrupo foram referendadas em votação final com todos os participantes. Foi adotado como consensual as decisões que atingissem 70% ou mais de concordância entre os participantes. Este artigo apresenta as principais recomendações e conclusões para orientação aos profissionais brasileiros envolvidos com a infecção por H. pylori.

Clarithromycin-based triple therapy for Helicobacter pylori treatment in peptic ulcer patients.

INTRODUCTION: The scheme proton pump inhibitor/amoxicillin/clarithromycin (PPI/AC) is still the first-line treatment for Helicobacter pylori (H. pylori) infections despite evidence suggesting its failure in up to 20% to 30% of patients. METHODOLOGY: This study involved 493 patients who were prescribed omeprazole (20 mg twice a day) or another proton pump inhibitor in equivalent dosage, amoxicillin (1 g twice a day), and clarithromycin (500 mg twice a day) for seven days. Efficacy was determined by negative urease test and absence of H. pylori on gastric biopsy samples twelve weeks after the end of treatment. Safety was defined according to the adverse effects reported. Mean age of the patients was (± SD) 48.96 ± 13, and demographic and clinical data were recorded for correlation with treatment outcomes. RESULTS: Out of 493 patients, 316 (64.1%) presented duodenal ulcer, 111 (22.5%) gastric ulcer, and 66 (14.4%) simultaneous gastric and duodenal ulcers. Additionally, 267 (54.2%) patients had at least one risk factor for peptic ulcer disease, smoking being the most common (99 [36.5%]). Successful eradication was achieved in 408 patients. The eradication rates per protocol, and according to the intention to treat, were 88.8% and 82.7%, respectively.  Of 164 (35.5%) patients who presented adverse effects, 100 (61%) reported them as mild and only six (3.7%) patients had to discontinue treatment. Previous use of tobacco and non-steroid anti-inflammatory drugs was the only risk factor for treatment failure (P = 0.00). CONCLUSION: PPI/AC is still a valuable and remarkably tolerable option for first-line H. pylori eradication in Brazil.

Efficacy of a 7-day course of furazolidone, levofloxacin, and lansoprazole after failed Helicobacter pylori eradication.

BACKGROUND: Increasing resistance to clarithromycin and nitroimidazole is the main cause of failure in the Helicobacter pylori eradication. The ideal retreatment regimen remains unclear, especially in developing countries, where the infection presents high prevalence and resistance to antibiotics. The study aimed at determining the efficacy, compliance and adverse effects of a regimen that included furazolidone, levofloxacin and lansoprazole in patients with persistent Helicobacter pylori infection, who had failed to respond to at least one prior eradication treatment regimen. METHODS: This study included 48 patients with peptic ulcer disease. Helicobacter pylori infection was confirmed by a rapid urease test and histological examination of samples obtained from the antrum and corpus during endoscopy. The eradication therapy consisted of a 7-day twice daily oral administration of lansoprazole 30 mg, furazolidone 200 mg and levofloxacin 250 mg. Therapeutic success was confirmed by a negative rapid urease test, histological examination and 14C- urea breath test, performed 12 weeks after treatment completion. The Chi-square method was used for comparisons among eradication rates, previous treatments and previous furazolidone use. RESULTS: Only one of the 48 patients failed to take all medications, which was due to adverse effects (vomiting). Per-protocol and intention-to-treat eradication rates were 89% (95% CI- 89%-99%) and 88% (88-92%), respectively. Mild and moderate adverse effects were reported by 41 patients (85%). For patients with one previous treatment failure, the eradication rate was 100%. Compared to furazolidone-naïve patients, eradication rates were lower in those who had failed prior furazolidone-containing regimen(s) (74% vs. 100%, p = 0.002). CONCLUSION: An empiric salvage-regimen including levofloxacin, furazolidone and lansoprazole is very effective in the eradication of Helicobacter pylori, particularly in patients that have failed one prior eradication therapy.

Quadruple therapy with furazolidone for retreatment in patients with peptic ulcer disease.

AIM: To establish the efficacy and safety of a 7-d therapeutic regimen using omeprazole, bismuth subcitrate, furazolidone and amoxicillin in patients with peptic ulcer disease who had been previously treated with other therapeutic regimens without success. METHODS: Open cohort study which included patients with peptic ulcer who had previously been treated unsuccessfully with one or more eradication regimens. The therapeutic regimen consisted of 20 mg omeprazole, 240 mg colloidal bismuth subcitrate, 1000 mg amoxicillin, and 200 mg furazolidone, taken twice a day for 7 d. Patients were considered as eradicated when samples taken from the gastric antrum and corpus 12 wk after the end of treatment were negative for Helicobacter pylori (H pylori) (rapid urease test and histology). Safety was determined by the presence of adverse effects. RESULTS: Fifty-one patients were enrolled. The eradication rate was 68.8% (31/45). Adverse effects were reported by 31.4% of the patients, and these were usually considered to be slight or moderate in the majority of the cases. Three patients had to withdraw from the treatment due to the presence of severe adverse effects. CONCLUSION: The association of bismuth, furazolidone, amoxicillin and a proton-pump inhibitor is a valuable alternative for patients who failed to respond to other eradication regimens. It is an effective, cheap and safe option for salvage therapy of positive patients.

Factors related to Helicobacter pylori prevalence in an adult population in Brazil.

BACKGROUND: The prevalence of Helicobacter pylori is higher in developing countries. Sanitary facilities, crowding and ethnic group are some of the factors related to H. pylori infection. The aim of this study was to investigate in blood donors, free of dyspeptic symptoms, the prevalence and factors influencing H. pylori infection. MATERIALS AND METHODS: This study was conducted in São Paulo, a city known to have a mixed population coming from all over the country. A total of 1008 blood donors were initially included in the study. After a final revision of all the questionnaires, 993 were included in the final analysis (746 males). H. pylori status was checked by an ELISA test. The following associations to infection were analyzed: sex, age, ethnic group, previous upper gastrointestinal (GI) endoscopy, smoking, alcoholism, drug addiction, type of drinking water, crowding, sanitary facilities, and family income. RESULTS: Infection was observed in 496 of 746 male (66.5%) and in 156 of 247 female (63.2%) blood donors. Infection prevalence increased according to age group, regardless of sex. Prevalence was lower in White population than in non-White. No relationship was observed between infection and smoking, drug addiction, and alcohol. A positive relation was observed between infection and previous upper GI endoscopy, and type of drinking water, regardless if currently or during childhood. Crowding and lack of toilet in the house during childhood resulted in a higher infection rate. Lower familial income and educational level showed a positive association to infection. CONCLUSIONS: Prevalence of H. pylori is higher in non-White population, independent of gender. A positive association was observed in aging, previous upper GI endoscopy, crowding, type of drinking water, lack of toilet during childhood, lower family income, and lower educational level.