Abordaje de la enfermedad por reflujo gastroesofágico refractaria / Approach to refractory gastroesophageal reflux disease

RESUMEN Un adecuado abordaje de la enfermedad por reflujo gastroesofágico refractaria (rERGE) es imprescindible para lograr el éxito terapéutico. Desde la definición precisa de rERGE hasta la detallada caracterización de sus fenotipos, establecerá el camino hacia la personalización de la terapia óptima para cada paciente. En esta revisión narrativa de la literatura, se busca proporcionar una síntesis actualizada de la utilidad de las diversas herramientas diagnósticas y explorar el amplio espectro de opciones terapéuticas, tanto médicas como invasivas disponibles para esta condición.

ABSTRACT An adequate approach to refractory gastroesophageal reflux disease (rGERD) is essential for achieving therapeutic success. From the precise definition of rGERD to the detailed characterization of its phenotypes, it will pave the way for the customization of optimal therapy for each patient. In this narrative literature review, the aim is to provide an updated synthesis of the utility of various diagnostic tools and explore the wide range of therapeutic options, both medical and invasive, available for this condition.

Short-term efficacy of laparoscopic Nissen fundoplication for refractory gastroesophageal reflux disease / 中国医师进修杂志

Objective:To investigate the safety and short-term efficacy of laparoscopic Nissen fundoplication in the treatment of refractory gastroesophageal reflux disease (rGERD).Methods:The clinical data of 61 patients underwent laparoscopic Nissen fundoplication from March 2018 to March 2022 in Jiangyin People′s Hospital were retrospectively analyzed. Among them, 14 patients had significant symptom relief after using proton pump inhibitor (PPI) before operation (group A), 30 patients had partial symptom relief after using PPI (group B), and 17 patients had persistent symptoms despite regular treatment with double-dose PPI for more than 8 weeks (group C). The surgical outcomes and recovery were compared among the three groups.Results:For the 61 patients, the surgical time was (117.46 ± 28.50) min, the intraoperative blood loss was 23.00 (8.00, 34.00) ml, and the postoperative hospital stay was 3.00 (2.00, 5.00) d. There were no statistically significant differences in surgical time, intraoperative blood loss, postoperative hospital stay, concurrent hiatal hernia repair and mesh placement among the three groups ( P>0.05). No short-term severe complications such as abdominal bleeding, abdominal infection and gastrointestinal perforation occurred in any group. There were no statistical differences in satisfaction score, subjective relief of overall postoperative symptoms, reflux symptoms, PPI usage, dysphagia, abdominal distention, diarrhea or constipation among the three groups ( P<0.05). No upper abdominal pain, recurrence and reoperation occurred in the three groups. Conclusions:Laparoscopic Nissen fundoplication has a definite therapeutic effect on rGERD, with significant anti reflux effects. There are no serious complications after surgery, and there are no recurrence or reoperation.

Association of PPIs use with short-term and long-term mortality risk in patients with severe ischemic stroke:a retrospective cohort study based on the MIMIC-Ⅲ database / 药物流行病学杂志

Objective To investigate the association of proton pump inhibitors(PPIs)use with short-term and long-term mortality risk in patients with severe ischemic stroke.Methods This retrospective study based on the U.S.Medical Information Mark for Intensive Care Ⅲ(MIMIC-Ⅲ)database,ICU patients aged ≥18 years with the first ICU admission and a diagnosis of ischemic stroke were finally included in the study.All enrolled subjects were divided into PPIs group and non-PPIs group according to whether they had used PPIs(pantoprazole,lansoprazole and omeprazole)during hospitalization.Kaplan-Meier survival analyses and Cox regression models were used to analyze the association between the use of PPIs and the risk of ICU death,30 d risk of death,90 d risk of death in patients with severe ischemic stroke.Results A total of 1 015 patients were included,402 cases in the PPIs group and 613 in the non-PPIs group.The ICU-mortality,30 d and 90 d mortality were 15.37％,13.60％and 20.10％,respectively.Kaplan-Meier survival analyses illustrated that the PPIs group survived better than non-PPIs group in ICU mortality analysis(P=0.002).In Cox regression analysis,after adjustment for potential confounders,the hazard ratio(HR)for ICU mortality in the PPIs group relative to the non-PPIs group was 0.671 9(95％CI 0.478 8 to 0.942 8,P=0.021),but there was no significant difference between 30 d and 90 d mortality(P＞0.05).Conclusion In patients with severe ischemic stroke,the use of PPIs may be effective in reducing the risk of ICU death,but does not improve 30 d and 90 d risk of death in patients.

Bastidores da prescrição de inibidores de bomba de prótons: uma pesquisa internacional sobre práticas e conhecimentos médicos / Behind the proton pump inhibitor prescription: an international survey on physician practices and knowledge

ABSTRACT Background: Proton pump inhibitors (PPIs) are widely prescribed worldwide, often resulting in their overuse. Consequently, it is essential to identify the likely causes of this overuse to facilitate their appropriate prescription. Objective: This study aims to assess physician prescribing patterns, their knowledge of PPIs, and factors affecting their knowledge. Methods: An online survey was conducted among Latin American and Spanish physicians, collecting the following data: professional information, patterns of PPI usage, familiarity with published evidence, and the management approach in three hypothetical case-scenarios. Participant knowledge was categorized as sufficient or insufficient based on the results of the case scenarios. Subsequently, subgroup analysis was performed based on physician training level, years in practice, specialty, and time since the last PPI literature review. Results: A total of 371 physicians participated in the survey. Thirty-eight percent frequently prescribe PPIs, primarily for prophylactic purposes (57.9%). Eighty percent were unfamiliar with PPI deprescribing strategies, and 54.4% rarely reviewed the ongoing indication of patients taking a PPI. Sixty-four percent demonstrated sufficient knowledge in the case-scenarios. A significant association was observed between specialty type (medical vs surgical: 69.4% vs 46.8%, P<0.001), the timing of the PPI indication literature review (<5 years vs >5 years: 71.4% vs 58.7%, P=0.010), and sufficient knowledge. Conclusion: While most participants prescribed PPIs regularly and for prophylaxis purposes, the majority were unfamiliar with deprescribing strategies and rarely reviewed ongoing indications. Sufficient knowledge is correlated with recent literature reviews and medical specialty affiliation.

RESUMO Contexto: Os inibidores da bomba de prótons (IBPs) são amplamente prescritos em todo o mundo, muitas vezes resultando em seu uso excessivo. Consequentemente, é essencial identificar as prováveis causas desse uso excessivo para facilitar sua prescrição adequada. Objetivo: Este estudo tem como objetivo avaliar o padrão de prescrição dos médicos, seu conhecimento sobre IBPs e fatores que afetam seu conhecimento. Métodos: Uma pesquisa on-line foi conduzida entre médicos latino-americanos e espanhóis, coletando os seguintes dados: informações profissionais, padrões de uso de IBP, familiaridade com evidências publicadas e abordagem de manejo em três casos-cenários hipotéticos. O conhecimento dos participantes foi categorizado em suficiente ou insuficiente com base nos resultados dos cenários de caso. Posteriormente, a análise de subgrupos foi realizada com base no nível de formação do médico, anos de prática, especialidade e tempo desde a última revisão da literatura dos IBPs. Resultados: Um total de 371 médicos participaram da pesquisa. Trinta e oito por cento prescrevem frequentemente IBP, principalmente para fins profiláticos (57,9%). Oitenta por cento não estavam familiarizados com as estratégias de prescrição de IBP, e 54,4% raramente revisaram a indicação contínua de pacientes em uso de IBP. Sessenta e quatro por cento demonstraram conhecimento suficiente nos cenários-caso. Observou-se associação significativa entre o tipo de especialidade (médica vs cirúrgica: 69,4% vs 46,8%, P<0,001), o momento da revisão da literatura de indicação do IBP (<5 anos vs >5 anos: 71,4% vs 58,7%, P=0,010) e conhecimento suficiente. Conclusão: Embora a maioria dos participantes prescrevesse IBPs regularmente e para fins de profilaxia, no entanto, não estava familiarizada com estratégias de prescrição e raramente revisava as indicações em andamento. O conhecimento suficiente está correlacionado com revisões recentes da literatura e afiliação à especialidade médica.

Is it Always Laryngopharyngeal Reflux? How Voice Disorders Can Manifest as LPR

Introduction: Laryngopharyngeal reflux (LPR) manifests with a constellation of common throat symptoms and inconclusive signs on laryngoscopic exam. It is a diagnosis, often made clinically, that can lead to prescriptions of proton pump inhibitors that are unnecessary and potentially harmful. Glottic insufficiency (GI) and the accompanying hyperfunctional laryngeal behaviors can also present with similar, common throat complaints that may or may not include a qualitative change to the voice. Methods: This is a reflection article. It is written to summarize, explain, and support with evidence the opinion of the author on the topic of how symptoms of voice disorders can easily be mistaken for symptoms of LPR. The offered reflection is based on his experience, research and the available literature. Reflection: This article intends to explore the similarities between GI and LPR, how to ultimately differentiate them and how to approach treatment with a broader differential diagnosis. Conclusion: LPR and GI can present with identical, vague throat, and voice symptoms. Empiric medication trials, behavioral interventions and objective laryngovideostroboscopy, impedance-based reflux, and esophageal motility testing may all be needed, sometimes in a trial and error fashion, to correctly diagnose and treat a patient's symptoms.

Introducción: El reflujo laríngeo-faríngeo (LPR, por sus siglas en inglés) se manifiesta con una serie de síntomas comunes en la garganta y signos no concluyentes en el examen larinoscópico. Es un diagnóstico que a menudo se realiza clínicamente y que puede llevar a la prescripción de inhibidores de la bomba de protones que son innecesarios y potencialmente perjudiciales. La insuficiencia glótica (IG) y los comportamientos laríngeos hiperfuncionales que la acompañan también pueden presentar síntomas de garganta comunes similares, que pueden o no incluir un cambio cualitativo en la voz. Métodos: Este es un artículo de reflexión. Está escrito para resumir, explicar y respaldar con evidencia la opinión del autor sobre cómo los síntomas de los trastornos de la voz pueden confundirse fácilmente con los síntomas del LPR. La reflexión ofrecida se basa en su experiencia, investigación y la literatura disponible. Reflexión: Este artículo tiene la intención de explorar las similitudes entre la IG y el LPR, cómo diferenciarlos finalmente y cómo abordar el tratamiento con un diagnóstico diferencial más amplio. Conclusión: El LPR y la IG pueden presentar síntomas idénticos y vagos en la garganta y la voz. Puede ser necesario realizar ensayos de medicación empírica, intervenciones conductuales y pruebas objetivas de laringovideostroboscopia, reflujo basado en impedancia y motilidad esofágica, a veces de manera experimental, para diagnosticar y tratar correctamente los síntomas de un paciente.

Omeprazole-induced cardiac arrhythmia – A case report

Omeprazole, a Proton pump inhibitor, is widely prescribed in patients with chronic gastroesophageal reflux. Patients continue to use omeprazole for long period of time even without the supervision of the doctor. The authors report a 50-year-old male patient with a 5-year history of omeprazole use, who complained of chest discomfort. ECG on admission showed atrial fibrillation. Laboratory findings showed hypomagnesaemia, hypocalcaemia, and hypokalemia. The case report emphasizes the importance of patient education regarding the use and adverse drug reactions of the prescribed medications.

Systematic review of vonoprazan as Helicobacter pylori eradication therapy / 中国药房

OBJECTIVE To systematically evaluate the efficacy and safety of vonoprazan （VPZ） for Helicobacter pylori （Hp） eradication therapy. METHODS Retrieved from The Cochrane Library， Embase， PubMed， CNKI， VIP and Wanfang database， randomized controlled trials about VPZ for Hp eradication therapy （trial group） versus proton pump inhibitor （PPI） （control group） were collected during the inception to July 2022. After data extraction and quality evaluation with bias risk assessment tool recommended by Cochrane System Evaluation Manual 5.1.0， meta-analysis was performed by using RevMan5.3 software. RESULTS Nine studies with 2 134 patients were included. Compared with control group， the overall Hp eradication rate of trial group increased significantly in either the ITT analysis or PP analysis， being 87.5% vs. 76.2% [RR＝1.14， 95%CI （1.06，1.21）， P＜0.001] and 92.4% vs. 80.5% [RR＝1.11， 95%CI （1.03，1.21）， P＜0.01]， respectively. According to ITT and PP analysis of primary treatment subgroup， compared with control group， the overall Hp eradication rate of trial group increased significantly， being 88.4% vs. 76.5% [RR＝1.15， 95%CI （1.09，1.22）， P＜0.000 01] and 92.8% vs. 80.9% [RR＝1.12， 95%CI（1.03，1.23）， P＜ 0.05]； according to ITT and PP analysis of rescue therapy subgroup， there was no significant difference in the overall Hp eradication rate between control group and trial group （P＞0.05）. According to ITT and PP analysis of triple therapy subgroup， compared with control group， overall Hp eradication rate of trial group increased significantly， being 88.3% vs. 75.6% [RR＝1.16， 95%CI （1.08， 1.25）， P＜0.000 1] and 92.6% vs. 77.6% [RR=1.15， 95%CI （1.04， 1.28）， P＜0.01]； according to ITT and PP analysis of quadruple therapy subgroup， there was no significant difference in the overall Hp eradication rate between control group and trial group （P＞0.05）. Compared with control group， the incidence of adverse events in trial group decreased significantly， being 34.2% vs. 40.9% [RR＝0.84， 95%CI（0.70，0.99）， P＜ 0.05]. There was no statistical significance in the incidence of serious adverse events between 2 groups （P＞0.05）. CONCLUSIONS Compared with PPI therapy， the efficacy of VPZ-based triple therapy is better， particularly in primary treatment patients. However， VPZ has no significant advantage in rescue treatment and bismuth-containing quadruple regimen. And the safety and tolerance of VPZ for Hp eradication therapy are well， even better than PPI.

Timing of rivaroxaban re-administration after upper gastrointestinal bleeding in patients with lower extremity deep venous thrombosis / 中国基层医药

Objective:To investigate the timing of rivaroxaban re-administration after upper gastrointestinal bleeding in patients with lower extremity deep venous thrombosis.Methods:The clinical data of 176 patients who suffered from lower limb deep vein thrombosis due to trauma or surgery and upper gastrointestinal bleeding due to oral rivaroxaban and received treatment in the Third Hospital of Hebei Medical University from May 2018 to October 2021 were retrospectively analyzed. These patients were divided into an early group (≤ 7 days) ( n = 84 cases) and a late group (> 7 days) ( n = 92 cases) according to the timing of rivaroxaban re-administration. All patients were followed up for 2 months to record hemoglobin, D-dimer, and platelet values. The progression of deep venous thrombosis of the lower extremities was observed. The rebleeding rate, progression of lower extremity deep venous thrombosis, and mortality were analyzed. Results:There were no significant differences in hemoglobin and D-dimer levels between the two groups on admission (both P > 0.05). After admission, the D-dimer level in the late group was (4.1 ± 2.3) mg/L, which was significantly higher than (3.1 ± 1.9) mg/L in the early group ( t = 3.17, P < 0.05). After admission, hemoglobin level in each group was significantly decreased compared with that on admission (both P < 0.05). The lowest hemoglobin level in the late group was (78.7 ± 8.3) g/L, which was significantly higher than (75.6 ± 8.2) g/L in the early group ( t = 2.32, P < 0.05). There was no significant difference in rebleeding rate between early and late groups [5.95% (5/84) vs. 1.08% (1/92)] (log-rank 3.07, P > 0.05). Lower extremity deep venous thrombosis progressed more slowly in the early group compared with the late group [2.38% (2/84) vs. 10.86% (10/92)] (log-rank = 4.61, P < 0.05). Conclusion:Rivaroxaban should be re-administered as soon as possible after upper gastrointestinal bleeding in patients with lower extremity deep venous thrombosis.

Effect of posaconazole combined with proton pump inhibitors on blood concentrations and invasive fungal infec-tion in patients with malignant hematological disorders / 中国药房

OBJECTIVE To explore the effects of posaconazole combined with proton pump inhibitors （PPI） on the blood concentration and the risk of invasive fungal disease （IFD） in patients with malignant hematological disorder. METHODS In accordance with the random number table method， 40 patients with malignant hematological disorders who were admitted to the hematology department of our hospital between December 2020 and December 2021 were chosen and divided into control group （20 cases） and observation group （20 cases）. The control group received Posaconazole oral suspension alone， while the observation group received Posaconazole oral suspension combined with PPI. The incidence of IFD， attainment rate of blood concentration， the time from the start of prophylaxis to IFD onset， the fatality associated with IFD， treatment of infected patients， and blood concentrations of posaconazole on 7th， 14th， 21st， and 28th day after posaconazole application were compared between 2 groups； the occurrence of adverse events during drug administration in the two groups was recorded. RESULTS The study was stopped because 2 patients in the observation group and 9 patients in the control group received hospital departures after taking posaconazole for fewer than 7 days. The incidence of IFD in the observation group was significantly higher than control group， and the attainment rate of blood concentration in the observation group was significantly lower than control group （P＜0.05）. There was no significant difference in the time from the start of prophylaxis to IFD onset， the fatality associated with IFD， treatment of infected patients and the incidence of adverse events （P＞ 0.05）. The blood concentration of posaconazole in the observation group was significantly lower than control group on 7th day of medication （P＜0.05）； there was no significant in blood concentration of posaconazole between 2 groups on the 14th day of medication （P＞0.05）. CONCLUSIONS Posaconazole combined with PPI can reduce the blood concentration of patients with malignant hematological disorders， increase the risk of IFD. Clinical practice should try to avoid the combination of the two or use them under the guidance of therapeutic drug monitoring.

Proton pump inhibitors and dementia: what association? / Inibidores da bomba de protões e demência: que associação?

ABSTRACT. Several recent studies have suggested an association between proton pump inhibitors and the development of cognitive changes. Objective: To assess the existence of this association. Methods: A comprehensive literature search was conducted including guidelines, meta-analyses, systematic reviews, observational and experimental studies published between February 2011 and February 2021. Results: The initial research identified 393 articles, 28 of which were included: 8 systematic reviews, 1 clinical trial, 15 observational studies, 3 case-control studies, and 1 cross-sectional observational study. Conclusions: Most studies classified with the highest level of evidence found no statistically significant association between the use of proton pump inhibitors and the development of cognitive impairment or dementia.

RESUMO. Nos últimos anos, têm sido publicados vários estudos que indicam uma associação entre o uso de inibidores da bomba de protões e o desenvolvimento de alterações cognitivas. Objetivo: Avaliar a existência desta associação. Métodos: Foi realizada uma pesquisa bibliográfica abrangente, incluindo diretrizes, meta-análises, revisões sistemáticas, estudos experimentais e observacionais publicados entre fevereiro de 2011 e de 2021. Resultados: A pesquisa inicial identificou 393 artigos, dos quais 28 foram incluídos: 8 revisões sistemáticas, 1 ensaio clínico, 15 estudos observacionais, 3 estudos de caso-controle e 1 estudo observacional transversal. Conclusões: A maioria dos estudos com o maior nível de evidência não encontrou uma associação estatisticamente significativa entre o uso de inibidores da bomba de protões e o desenvolvimento de défice cognitivo ou demência.

Eficácia e segurança do Esomeprazol e Lansoprazol comparados ao Omeprazol para o tratamento de doença do refluxo gastroesofágico em adultos: revisão rápida / Effectiveness and safety of esomeprazole and lansoprazole compared to omeprazole for the treatment of gastroesophageal reflux disease in adults: rapid review

Tecnologia: Esomeprazol e lansoprazol. Indicação: Tratamento de doença do refluxo gastroesofágico em adultos. Pergunta: Esomeprazol e lansoprazol são mais eficazes e toleráveis que o omeprazol já incorporado ao SUS para o tratamento de Doença do Refluxo Gastroesofágico (DRGE) em adultos? Métodos: Uma revisão rápida de evidências, uma revisão de revisões sistemáticas, com levantamento bibliográfico realizado na base de dados PUBMED, utilizando estratégia estruturada de busca. A qualidade metodológica das revisões sistemáticas foi avaliada com AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews). Resultados: Foram selecionadas três revisões sistemáticas com meta-análise, que atendiam aos critérios de inclusão. Conclusão: O esomeprazol era mais eficaz para cicatrização da lesão nos casos de esofagite erosiva, prevenção da mucosa do esôfago, maior controle de ácido no tratamento de curto prazo (4 e 8 semanas) de esomeprazol 40mg e tratamento de longo prazo (6 meses) de esomeprazol 20mg. A taxa de resposta no alívio dos sintomas, o esomeprazol 20mg e 40mg apresentou ser mais eficaz, especialmente, na azia e dor epigástrica. Quanto ao perfil de segurança, não houve diferença significativa entre as taxas de eventos adversos, todos medicamentos eram parecidos entre si

Technology: Esomeprazole and Lansoprazole. Indication: Treatment of gastroesophageal reflux disease in adults. Question: Are Esomeprazole and Lansoprazole more effective and tolerable than omeprazole already incorporated into SUS for the treatment of Gastroesophageal Reflux Disease (GERD) in adults? Methods: A rapid review of evidence, an overview of systematic reviews, with bibliographic survey carried out in the PUBMED database, using a structured search strategy. The methodological quality of systematic reviews was assessed using AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews). Results: Three systematic reviews with meta-analysis were selected, which met the inclusion criteria. Conclusion: Esomeprazole was more effective in achieving wound healing in cases of erosive esophagitis, prevention of esophageal mucosa, greater acid control in short-term treatment (4 and 8 weeks) of esomeprazole 40mg and long-term treatment (6 months) of esomeprazole 20mg. the response rate in symptom relief, esomeprazole 20mg and 40mg proved to be more effective, especially in heartburn and epigastric pain. As for the safety profile, there was no significant difference between the rates of adverse events, all drugs were similar to each other

Assessment of gastric-acid suppressants prescribing at an internal medicine service of a tertiary hospital in Latin America: A retrospective record review study

Gastric-acid suppressants are one of the most frequently used classes of drugs worldwide. Several studies about their overprescribing have been carried out in recent years. The aim of the study was to assess the appropriateness of these drugs at an internal medicine service of a tertiary hospital in Venezuela. A retrospective record review of patients admitted to the internal medicine service from January 2020 to February 2021 was performed. Data about indications for gastric-acid suppressants, the type used, and their continuation at discharge were collected. The prescribing was grouped into two categories, appropriate or inappropriate, according to current clinical guidelines. Of the 1203 patients who were newly prescribed gastric-acid suppressants in hospital during the study period, 993 (82.5%) had an inappropriate prescription. Prophylaxis of peptic ulcers in low-risk patients was the most frequent no evidence-based indication (20.24%). Seven hundred sixty-two patients were discharged on gastric-acid suppressants. Of these, 74.7% did not have an acceptable indication to continue this treatment on an outpatient basis. Many hospitalized patients in a Venezuelan academic tertiary healthcare center were given gastric acid suppressants not in accordance with the current clinical practice guidelines.

Los supresores del ácido gástrico son uno de los grupos farmacológicos más frecuentemente prescritos en todo el mundo. En los últimos años se han realizado varios estudios sobre su prescripción inadecuada. El objetivo del estudio fue evaluar la idoneidad de estos medicamentos en un servicio de medicina interna de un hospital de tercer nivel en Venezuela. Se realizó una revisión retrospectiva de historias medicas de pacientes ingresados en el servicio de medicina interna desde enero de 2020 hasta febrero de 2021. Se recogieron datos sobre indicaciones de supresores de ácido gástrico, tipo utilizado y su continuación al alta. La prescripción se agrupó en dos categorías, adecuada o inadecuada, según las guías clínicas vigentes. Entre los 1203 pacientes a los que se les prescribió recientemente supresores de ácido gástrico en el hospital durante el período de estudio, 993 (82,5%) tenían una prescripción inapropiada. La profilaxis de úlceras pépticas en pacientes de bajo riesgo fue la indicación no basada en evidencia más frecuente (20,24%). Setecientos sesenta y dos pacientes fueron dados de alta con supresores de ácido gástrico. De estos, el 74,7% no tenía una indicación apropiada para continuar este tratamiento de forma ambulatoria. Un alto número de pacientes hospitalizados en un centro asistencial de nivel terciario en Venezuela fueron prescritos con supresores de ácido gástrico que no se ajustaban a las guías de práctica clínica vigentes.

Segurança dos inibidores de bomba de prótons utilizados a longo prazo: fatos e fantasias / Safety of long-term proton pump inhibitors: facts and myths

ABSTRACT Background: Proton pump inhibitors (PPIs) are one of the most prescribed drugs in the world. Frequent use and long-term maintenance of these drugs drew the attention of researchers for sporadic adverse effects reports. Objective: The purpose of this narrative review is to discuss appropriate data and causality related to these adverse events and PPIs. Methods: A narrative review was conducted by systematizing information about safety and adverse events on PPIs from 2015 to 2020. A structured search on Pubmed was performed to identify systematic reviews and meta-analysis investigating the following situations: a) gastric cancer; b) micronutrients deficiency; c) acid rebound; d) infections; e) fractures; f) dementia; g) kidney disease; and h) sudden death and cardiovascular changes. Results: Recent studies have potentially associated PPIs with some adverse events as osteoporosis-related fractures. There are also reports of intestinal infections, including Clostridium difficile, besides poor vitamins absorption and minerals such as vitamin B12, magnesium, and iron. Furthermore, there are some dementia, pneumonia, kidney disease, myocardial infarction, and stroke reports. For kidney diseases, studies consistently suggest that the use of PPI may be associated with an increased risk of adverse kidney events, especially in the elderly, with long-term PPI use and pre-existing kidney disease. Another additional question is whether chronic PPI use would also lead to the onset of gastric cancer. The abrupt discontinuation of PPIs is also related to increased gastric acid production above pre-PPI treatment levels; this phenomenon is called acid rebound. Conclusion: The key to mitigate adverse effects is the rational use of PPIs at the lowest effective dose and in the shortest possible duration. Although these adverse effects have a potential clinical impact, their causal association is still subject to validation.

RESUMO: Contexto: Os inibidores da bomba de prótons (IBPs) são um dos medicamentos mais prescritos no mundo. O uso frequente e a manutenção a longo prazo dessas drogas chamaram a atenção dos pesquisadores devido aos relatos esporádicos de efeitos adversos. Objetivo: Esta revisão narrativa tem o objetivo de discutir os dados e a causalidade relacionada a esses eventos adversos e o uso de IBPs. Métodos: Uma revisão narrativa foi conduzida através da sistematização das informações sobre segurança e eventos adversos de IBPs de 2015 a 2020. Uma busca estruturada na base de dados PubMed foi realizada visando identificar revisões sistemáticas e meta-análises investigando as situações a seguir: a) câncer gástrico; b) deficiência de microelementos; c) acidez de rebote; d) infecções; e) fraturas; f) demência; g) doença renal; e h) morte súbita e alterações cardiovasculares. Resultados: Estudos recentes têm potencialmente associado IBPs a alguns eventos adversos, como fraturas relacionadas à osteoporose. Também há relatos de infecções intestinais, incluindo Clostridium difficile, além de má absorção de vitaminas e minerais como vitamina B12, magnésio e ferro. Além disso, há alguns relatos de demência, pneumonia, doença renal, infarto do miocárdio e acidente vascular cerebral. Na doença renal, os estudos sugerem consistentemente que o uso de IBPs pode estar associado a um risco aumentado de eventos renais adversos, especialmente em idosos, com o uso de IBPs a longo prazo e doença renal preexistente. Outra questão adicional é se o uso crônico de IBPs também levaria ao aparecimento de câncer gástrico. A descontinuação abrupta de IBPs também está relacionada ao aumento da produção de ácido gástrico acima dos níveis de tratamento pré-IBPs; este fenômeno é conhecido como rebote ácido. Conclusão: A chave para mitigar esses efeitos adversos é o uso racional de IBPs na menor dose efetiva e com a menor duração possível. Embora esses efeitos adversos tenham um impacto clínico potencial, sua associação causal ainda está pendente de uma validação.

Déficit de Vitamina B12 en consumo de Metformina e Inhibidores de Bomba de Protones / Vitamin B12 Deficiency in consumption of Metformin and Proton Pump Inhibitors

Resumen El espectro de enfermedades asociadas con la deficiencia de la vitamina B 12 es amplio y abarca desde la ausencia de síntomas hasta el síndrome de malabsorción, insuficiencia medular, o síntomas neurológicos acompañados de parestesias, mielopatía o neuropatía. Existe evidencia sugestiva que indica que el empleo de inhibidores de bomba de protones (IBP) a largo plazo puede disminuir los niveles séricos de vitamina B12. Igualmente, estudios previos han asociado el déficit de vitamina B 12 a consumo en dosis altas de metformina, sin embargo, el mecanismo por el cual se genera la descompensación no está claro. Se ha llegado a describir una asociación aditiva de la administración de inhibidores bomba de protones/ Antagonistas receptor Histamina - 2 y metformina, sugiriendo que promueven la malabsorción de Vitamina B 12. Ambas categorías de medicamentos son ampliamente utilizadas, y en muchos casos sin prescripción médica, y su uso no debería ser pasado por alto. Cuando están clínicamente indicados, su uso debería ser monitorizado debido a la posibilidad de malabsorción de vitamina B 12 y sus consecuencias. Por tanto, en este artículo se revisan aspectos generales sobre la vitamina B12 y el estado del arte sobre la deficiencia de vitamina B12 en pacientes con consumo de metformina o uso de inhibidor de bomba de protones.

Abstract The spectrum of diseases associated with vitamin B12 deficiency is broad, ranging from no symptoms to malabsorption syndrome, spinal cord injury, neurological symptoms accompanied by paresthesia, myelopathy, or neuropathy. There is suggestive evidence that long-term use of proton pump inhibitors (PPIs) can lower serum levels of vitamin B12. Additionally, previous studies have associated vitamin B12 deficiency with high doses consumption of metformin; however, the mechanism in which this occurs is not clear. An additive association between the administration of proton pump inhibitors / Histamine H2 receptor antagonists, and metformin has been described, which suggest that these promote vitamin B12 malabsorption. Both categories of drugs are widely used, in many cases without a prescription, and its use should not be overlooked. When clinically indicated, their use should be monitored in view of the possibility of vitamin B12 malabsorption and its consequences. This article aims to review general aspects of vitamin B12 and delve into the state of the art regarding vitamin B12 deficiency in patients with metformin and / or proton pump inhibitor consumption.

An observational study on adverse drug reaction profile in patients on long-term treatment with proton pump inhibitors

Background: Proton pump inhibitors (PPI) are most commonly prescribed medications in the world which are highly effective drugs in treatment of upper gastrointestinal disorders, but there are concerns regarding its long term use. Aim and Objective: To assess the pattern of reported adverse drug reactions (ADR) in patients with long term use of PPI and to estimate the frequency of adverse drug effects. Materials and Methods: A study conducted as an observational study among 100 consecutive patients who attended the medical-gastro inpatient and outpatient department on treatment with PPI for more than 4 months, according to inclusion and exclusion criteria. After attaining the written informed consent, data regarding patient’s demographic details, occupational status, addictions, co-morbidities, and lab investigations were recorded in pre-prepared proforma after interviewing the patient and referring the case sheet. Details including PPI used and per day dose of the drug with any ADR developed were noted. Data collected were analyzed using appropriate statistical method. Categorical variables are expressed as frequency (percentage) and continuous variables as mean (standard deviation). Chi-square test was used to find out the association between PPI and ADR. Results: Out of 100 study participants, 57% case reported ADR which included 19 cases (33.3%) of hypomagnesemia, 8 cases (14%) each of hypocalcemia, and hyperkalemia, 7 cases (12.3%) of anemia, and 5 cases (8.9%) of acute kidney injury. Out of the 57 reported adverse events, 29 (50.9%) were caused by Rabeprazole followed by 18 (31.6%) by Pantoprazole, then Esomeprazole: 8 (14%), and least by Omeprazole (3.5%). Conclusion: Long-term use of PPI can lead to various ADR which requires the withdrawal of drug. Since PPIs are easily available without prescriptions, self-medication with PPIs are increasing alarmingly. With every antibiotic one PPI is always prescribed, as a result, there is irrational use of PPIs which is of concern and requires attention. These adverse events could be reduced by preventing self-medication of long duration and reducing the irrational prescribing of PPIs. Doctors should be sensitized about the ADRs. The patient should be educated about the long-term adverse effects of PPIs.

Uso práctico de inhibidores de bomba de protones / Practical use of proton pump inhibitors / Uso prático de inibidores da bomba de prótons

Los inhibidores de la bomba de protones (IBP) se encuentran entre los medicamentos más utilizados en el mundo por su bajo costo, extensa prescripción y efectividad. Sin embargo, su uso a largo plazo no es inocuo y aún hay vacíos en el conocimiento del empleo adecuado de estos medicamentos. Por lo tanto, en esta revisión se expone, además de sus propiedades generales, sus verdaderas indicaciones, el uso recomendado a largo plazo y las estrategias para lograr la deprescripción, con el fin de evitar el uso indiscriminado.

Proton pump inhibitors (PPIs) are among the most widely used drugs in the world, due to their low cost, extensive prescription and effectiveness. However, its long-term use is not safe and there are still certain gaps in the knowledge of the proper use of these drugs. Therefore, this review aims to expose their general properties as well as their true indications, the appropriate long-term use and strategies to achieve adequate deprescription of these drugs, seeking to avoid indiscriminate use.

Os inibidores da bomba de prótons (IBP) se encontram entre os medicamentos mais utilizados no mundo pelo seu baixo custo, extensa prescrição e efetividade. Embora, seu uso a longo prazo não é inócuo e ainda há vazios no conhecimento do uso adequado destes medicamentos. Por tanto, nesta revisão se expõe, além das suas propriedades gerais, suas verdadeiras indicações, o uso recomendado ao longo prazo e as estratégias para conseguir a deprescrição, com o fim de evitar o uso indiscriminado.

Hemorragia del tracto digestivo superior, enfoque para el médico general / Upper digestive tract bleeding, approach for the general Practitioner / Hemorragia do trato digestivo superior, enfoque para o médico geral

La hemorragia del tracto digestivo superior (HTDS) es el sangrado originado por encima del ángulo de Treitz. A pesar del aumento en las estrategias de prevención, del incremento en los tratamientos con Inhibidor de bomba de protones (IBP) y de la intervención endoscópica temprana, esta patología sigue siendo una causa frecuente de consulta a urgencias, con una morbimortalidad no despreciable y alta carga para el sistema de salud. Esta revisión se enfoca en la HTDS de causa diferente a las varices. La principal causante de esta entidad es la enfermedad ácido-péptica, que es consecuencia del gran consumo de antiinflamatorios no esteroideos (AINES) y de la infección por Helicobacter Pylori. Otras causas son el síndrome de Mallory Weiss, la esofagitis erosiva, las malformaciones arteriovenosas y la malignidad.

Upper gastrointestinal bleeding (UGIB) refers to any bleeding originating above the angle of Treitz. Despite an increase in prevention strategies, proton pump inhibitor (PPI) therapy and early endoscopic intervention, this pathology continues to be an important cause of admission to the emergency department for gastrointestinal causes, having a pretty high morbidity and mortality in addition to a high burden on the health system. This review focuses on non-variceal UGIB. The main cause of this entity being peptic acid disease, due to great consumption of NSAIDs and Helicobacter Pylori infection. Other causes are Mallory Weiss syndrome, erosive esophagitis, arteriovenous malformations, and malignancy.

A hemorragia do trato digestivo superior (HTDS) é o sangrado originado acima do ângulo de Treitz. Apesar do aumento nas estratégias de prevenção, do incremento nos tratamentos com Inibidor da bomba de prótons (IBP) e da intervenção endoscópica precoce, esta patologia segue sendo uma causa frequente de consulta a urgências, com uma morbimortalidade não depreciável e alta carga para o sistema de saúde. Esta revisão se enfoca na HTDS de causa diferente às varizes. A principal causante desta entidade é a doença ácido-péptica, que é consequência do grande consumo de anti-inflamatórios não esteróideos (AINES) e da infecção por HelicobacterPylori. Outras causas são a síndrome de Mallory Weiss, a esofagites erosiva, as malformações arteriovenosas e a malignidade. Palavras-chave: hemorragia gastrointestinal; úlcera péptica; endoscopia gastrointestinal; inibidores da bomba de prótons; medicina geral.

The effect of CYP2C19 genetic polymorphism on proton pump inhibitors and the efficacy of Hp eradication in children / 国际儿科学杂志

The polymorphism of CYP2C19 gene constitutes the basis for the difference in enzyme activity and affects the metabolism of many drugs including proton pump inhibitors.The distribution of CYP2C19 gene varies by region and race.The study on the relationship between CYP2C19 genotype and proton pump inhibitors is of great significance for the individualized treatment of Helicobacter pylori (Hp) in children.This paper reviews the effects of CYP2C19 gene polymorphism on proton pump inhibitors and the efficacy of Hp eradication in children.

Effects of proton pump inhibitors on outcomes for advanced solid tumor patients treated with immune checkpoint inhibitors / 国际肿瘤学杂志

Objective:To evaluate the effects of proton pump inhibitors (PPIs) on the clinical outcomes for advanced solid tumor patients treated with immune checkpoint inhibitors (ICIs).Methods:A total of 204 patients with advanced solid tumors who received ICIs in the Affiliated Hospital of Yangzhou University from November 2016 to December 2020 were retrospectively analyzed. The patients were divided into PPIs group ( n=73) and Non-PPIs group ( n=131) according to whether they received PPIs within 1 month before or after the initiation of ICIs treatment. The correlations between the uses of PPIs and the clinical characteristics of patients were explored, and the clinical efficacy of the two groups was evaluated. Kaplan-Meier survival curve was applied to analyze the effects of PPIs uses on overall survival (OS) and progression-free survival (PFS) of patients. The Cox proportional hazards model was used to clarify whether PPIs was an independent indicator of patients′ prognosis. Results:During ICIs treatment of advanced solid tumors, the use of PPIs was not correlated with the patients′ gender, age, tumor type, the score of the United States Eastern Collaborative Group, types of immunotherapy drugs and treatment strategy (all P>0.05). The objective response rate of the Non-PPIs group was better than that of the PPIs group (45.0% vs. 24.7%, χ2=8.286, P=0.004). The disease control rate of the Non-PPIs group was better than that of the PPIs group (75.6% vs. 52.0%, χ2=11.755, P=0.001). In patients with advanced solid tumors, the median OS (3.4 months vs. 6.1 months) and median PFS (2.8 months vs. 4.0 months) in the PPIs group were shorter than those in the Non-PPIs group ( χ2=9.563, P=0.002; χ2=5.761, P=0.016). Univariate analysis showed that among patients with advanced solid tumors treated with ICIs, PPIs uses was significantly correlated with OS ( HR=1.85, 95% CI: 1.24-2.76, P=0.003); PPIs uses( HR=1.65, 95% CI: 1.09-2.51, P=0.019) and age ( HR=1.56, 95% CI: 1.05-2.32, P=0.029) were significantly correlated with PFS. Multivariate analysis showed that PPIs uses was an independent prognostic factor affecting OS ( HR=1.90, 95% CI: 1.27-2.85, P=0.002) and PFS ( HR=1.73, 95% CI: 1.12-2.65, P=0.013). Meanwhile, subgroup analysis discovered that in the course of ICIs treatment of lung cancer patients, the median OS (3.2 months vs. 6.2 months) and median PFS (2.2 months vs. 3.8 months) in the PPIs group ( n=64) were shorter than those in the Non-PPIs group ( n=34) ( χ2=16.187, P<0.001; χ2=5.106, P=0.020). Univariate analysis showed that PPIs uses was associated with OS ( HR=2.97, 95% CI: 1.70-5.22, P<0.001) and PFS ( HR=1.97, 95% CI: 1.09-3.55, P=0.025) in lung cancer patients treated with ICIs. Multivariate analysis showed that PPIs uses was an independent prognostic factor for OS ( HR=3.38, 95% CI: 1.87-6.11, P<0.001) and PFS ( HR=2.31, 95% CI: 1.22-4.38, P=0.010) in lung cancer patients treated with ICIs. Conclusion:The use of PPIs reduces the effect of ICIs in the treatment of advanced solid tumor, especially in lung cancer. PPIs should be used cautiously in patients with advanced solid tumors treated with ICIs.

Case report of pleural ectopic gastric mucosa / 中华实用儿科临床杂志

The clinical data of a child with congenital ectopic gastric mucosa and infections admitted to Wuhan Children′s Hospital, Tongji Medical College, Huazhong University of Science and Technology in May 2020 were analyzed retrospectively.The child was a female who presented to the doctor with " phlegm in the throat with mild cough for more than 1 month" at the age of 1 month and 27 days.The pleural biopsy showed that the gastrointestinal mucosa tissue submitted for examination resembled the gastric mucosa under the microscope.The patient was diagnosed with pleural ectopic gastric mucosa.The child was discharged after her conditions improved.Twenty four days after the discharge, she returned to the hospital due to hemoptysis once.Closed thoracic drainage, partial lobectomy, thoracoscopic resection of mediastinal lesions and thoracoscopic conversion were then performed.In chest exploration, gastric mucosa-like tissue was seen on the top of the left pleura.The first case of pediatric pleural ectopic gastric mucosa in China was analyzed in this study.The results suggested that chest exploration should be performed on children with cough and hemoptysis if necessary to confirm the diagnosis as soon as possible.