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Proton pump inhibitors and dysbiosis: Current knowledge and aspects to be clarified.
Bruno, G, Zaccari, P, Rocco, G, Scalese, G, Panetta, C, Porowska, B, Pontone, S, Severi, C
World journal of gastroenterology. 2019;(22):2706-2719
Abstract
Proton pump inhibitors (PPIs) are common medications within the practice of gastroenterology. These drugs, which act through the irreversible inhibition of the hydrogen/potassium pump (H+/K+-ATPase pump) in the gastric parietal cells, are used in the treatment of several acid-related disorders. PPIs are generally well tolerated but, through the long-term reduction of gastric acid secretion, can increase the risk of an imbalance in gut microbiota composition (i.e., dysbiosis). The gut microbiota is a complex ecosystem in which microbes coexist and interact with the human host. Indeed, the resident gut bacteria are needed for multiple vital functions, such as nutrient and drug metabolism, the production of energy, defense against pathogens, the modulation of the immune system and support of the integrity of the gut mucosal barrier. The bacteria are collected in communities that vary in density and composition within each segment of the gastrointestinal (GI) tract. Therefore, every change in the gut ecosystem has been connected to an increased susceptibility or exacerbation of various GI disorders. The aim of this review is to summarize the recently available data on PPI-related microbiota alterations in each segment of the GI tract and to analyze the possible involvement of PPIs in the pathogenesis of several specific GI diseases.
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Stress ulcer prophylaxis with proton pump inhibitors or histamine 2 receptor antagonists in critically ill adults - a meta-analysis of randomized controlled trials with trial sequential analysis.
Zhou, X, Fang, H, Xu, J, Chen, P, Hu, X, Chen, B, Wang, H, Hu, C, Xu, Z
BMC gastroenterology. 2019;(1):193
Abstract
BACKGROUND Proton pump inhibitors (PPI) and histamine 2 receptor antagonists (H2RA) have been widely used as stress ulcer prophylaxis (SUP) in critically ill patients, however, its efficacy and safety remain unclear. This study aimed to assess the effect of SUP on clinical outcomes in critically ill adults. METHODS Literature search was conducted in PubMed, EMBASE, Web of Science, and the Cochrane database of clinical trials for randomized controlled trials (RCTs) that investigated SUP, with PPI or H2RA, versus placebo or no prophylaxis in critically ill patients from database inception through 1 June 2019. Study selection, data extraction and quality assessment were performed in duplicate. The primary outcomes were clinically important gastrointestinal (GI) bleeding and overt GI bleeding. Conventional meta-analysis with random-effects model and trial sequential analysis (TSA) were performed. RESULTS Twenty-nine RCTs were identified, of which four RCTs were judged as low risk of bias. Overall, SUP could reduce the incident of clinically important GI bleeding [relative risk (RR) = 0.58; 95% confidence intervals (CI): 0.42-0.81] and overt GI bleeding (RR = 0.48; 95% CI: 0.36-0.63), these results were confirmed by the sub-analysis of trials with low risk of bias, TSA indicated a firm evidence on its beneficial effects on the overt GI bleeding (TSA-adjusted CI: 0.31-0.75), but lack of sufficient evidence on the clinically important GI bleeding (TSA-adjusted CI: 0.23-1.51). Among patients who received enteral nutrition (EN), SUP was associated with a decreased risk of clinically important GI bleeding (RR = 0.61; 95% CI: 0.44-0.85; TSA-adjusted CI: 0.16-2.38) and overt GI bleeding (RR = 0.64; 95% CI: 0.42-0.96; TSA-adjusted CI: 0.12-3.35), but these benefits disappeared after adjustment with TSA. Among patients who did not receive EN, SUP had only benefits in reducing the risk of overt GI bleeding (RR = 0.37; 95% CI: 0.25-0.55; TSA-adjusted CI: 0.22-0.63), but not the clinically important GI bleeding (RR = 0.27; 95% CI: 0.04-2.09). CONCLUSIONS SUP has benefits on the overt GI bleeding in critically ill patients who did not receive EN, however, its benefits on clinically important GI bleeding still needs more evidence to confirm.
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3.
Enteral nutrition better than proton pump inhibitors?
Jalil, BA, El-Kersh, K
Current opinion in critical care. 2019;(4):334-339
Abstract
PURPOSE OF REVIEW Stress ulcer prophylaxis in critically-ill patients has been a subject of extensive research, with multiple clinical trials attempting to study the best method of stress ulcer prophylaxis with the least adverse effects. Until recently, pharmacologic prophylaxis has prevailed as the primary choice for the prevention of stress ulcers but recent clinical studies have attempted to evaluate the role of enteral nutrition in stress ulcer prophylaxis. RECENT FINDINGS The incidence of stress ulcers that result in clinically important gastrointestinal bleeding (CIGIB) has drastically decreased over the last two decades. Furthermore, in the current era CIGB in the ICU does not seem to be associated with an increased mortality. Multiple recent clinical studies aimed to evaluate the role of proton pump inhibitors (PPIs) in patients who tolerate enteral nutrition in the ICU. SUMMARY The results of multiple recent clinical studies call for re-evaluation of the routine use of PPIs in critically ill patients who tolerates enteral nutrition in the ICU. Despite the promising preliminary results, definitive recommendations need larger clinical trials that are powered to evaluate any added benefits of using PPI in critically ill patients who tolerate enteral nutrition given the low incidence of CIGB in the current era.
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4.
Diagnosis and Treatment of Peptic Ulcer Disease.
Kavitt, RT, Lipowska, AM, Anyane-Yeboa, A, Gralnek, IM
The American journal of medicine. 2019;(4):447-456
Abstract
Peptic ulcer disease continues to be a source of significant morbidity and mortality worldwide. Approximately two-thirds of patients found to have peptic ulcer disease are asymptomatic. In symptomatic patients, the most common presenting symptom of peptic ulcer disease is epigastric pain, which may be associated with dyspepsia, bloating, abdominal fullness, nausea, or early satiety. Most cases of peptic ulcer disease are associated with Helicobacter pylori infection or the use of nonsteroidal anti-inflammatory drugs (NSAIDs), or both. In this review, we discuss the role of proton pump inhibitors in the management of peptic ulcer disease, highlight the latest guidelines about the diagnosis and management of H. pylori, and discuss the latest evidence in the management of complications related to peptic ulcer disease, including endoscopic intervention for peptic ulcer-related bleeding. Timely diagnosis and treatment of peptic ulcer disease and its sequelae are crucial in order to minimize associated morbidity and mortality, as is prevention of peptic ulcer disease among patients at high risk, including those infected with H. pylori and users of NSAIDs.
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PEPTIC ULCER DISEASE.
Dunlap, JJ, Patterson, S
Gastroenterology nursing : the official journal of the Society of Gastroenterology Nurses and Associates. 2019;(5):451-454
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Proton pump inhibitor-induced hypomagnesemia complicated with serious cardiac arrhythmias.
Chrysant, SG
Expert review of cardiovascular therapy. 2019;(5):345-351
Abstract
Introduction: Magnesium is the third most common intracellular ion after potassium and calcium and is an important element in the functions of the body, since it participates in more than 300 enzyme systems. It also, plays a significant role in the transport of calcium and potassium across the cell membranes and protects against cardiac arrhythmias and is useful for their treatment due to hypomagnesemia induced from the proton pump inhibitors (PPIs). Areas covered: PPIs are used for the treatment of peptic ulcer disease (PUD) and gastroesophageal reflux disease (GERD), but have been associated with hypomagnesemia with serious cardiac arrhythmias including torsades de pointes (TdP). To better understand the magnitude of this problem, a Medline search of the English language literature was conducted from 2010 to 2018 and 35 papers with pertinent information were selected. Expert commentary: The review of these papers suggests that PPIs cause hypomagnesemia, which could be associated with serious cardiac arrhythmias including TdP. However, its incidence is not very common considering the millions of people taking PPIs, but the FDA has advised the physicians to be watchful about this serious adverse effect of PPIs and check the magnesium levels before initiation of PPI treatment.
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The Proton Pump Inhibitor Nonresponder: a Behavioral Approach to Improvement and Wellness.
Riehl, ME, Chen, JW
Current gastroenterology reports. 2018;(7):34
Abstract
PURPOSE OF REVIEW Gastroesophageal reflux disease (GERD) is a difficult to treat medical condition, where nearly 40% of patients are refractory to standard medical intervention, which typically begins with a proton pump inhibitor (PPI). These PPI nonresponders represent a population of patients, where treatment planning must be individualized; multidisciplinary and psychiatric comorbidities should be considered. This review highlights treatment options that include neuromodulators, lifestyle, and psychological interventions for the PPI nonresponder. RECENT FINDINGS Mental health specialists in the field of psychogastroenterology can aid in the management of esophageal hypersensitivity, which can drive the symptom experience of a PPI nonresponder. Considerations for comorbid anxiety and depression in this population require careful assessment and treatment. Physicians are encouraged to create realistic expectations for symptom management and offer multidisciplinary options for treatment early in care. Patients will frequently benefit from working with a GI psychologist and find value in behavioral interventions.
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Proton Pump Inhibitors, H2-Receptor Antagonists, Metformin, and Vitamin B-12 Deficiency: Clinical Implications.
Miller, JW
Advances in nutrition (Bethesda, Md.). 2018;(4):511S-518S
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Abstract
There is clear evidence that proton-pump inhibitors (PPIs), H2-receptor antagonists (H2RAs), and metformin can reduce serum vitamin B-12 concentrations by inhibiting the absorption of the vitamin. However, it is unclear if the effects of these drugs on serum vitamin B-12 are associated with increased risk of biochemical or functional deficiency (as is indicated by elevated blood concentrations of homocysteine and methylmalonic acid) or clinical deficiency (including megaloblastic anemia and neurologic disorders such as peripheral neuropathy and cognitive dysfunction). This review provides an overview of vitamin B-12 absorption and biochemistry and the mechanisms by which PPIs, H2RAs, and metformin affect these functions. It also summarizes the literature relating the use of these drugs to the risk of vitamin B-12 deficiency. Also discussed is that strategies for assessing vitamin B-12 status and diagnosing vitamin B-12 deficiency have evolved in recent years beyond solely measuring serum total vitamin B-12. Multiple analyte testing, a strategy in which ≥2 of 4 biomarkers of vitamin B-12 status-serum total vitamin B-12, holotranscobalamin, homocysteine, and methylmalonic acid-are measured, increases sensitivity and specificity for diagnosing vitamin B-12 deficiency. It is concluded that randomized controlled trials are now needed that use the strategy of multiple analyte testing to determine if PPIs, H2RAs, and metformin do indeed increase the risk of vitamin B-12 deficiency. Until these studies are conducted, a reasonable recommendation for physicians and their patients who are taking these drugs is to monitor vitamin B-12 status and to provide vitamin B-12 supplements if altered blood biomarkers or clinical signs consistent with low or deficient vitamin B-12 status develop.
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Toxicity of long-term use of proton pump inhibitors in children.
De Bruyne, P, Ito, S
Archives of disease in childhood. 2018;(1):78-82
Abstract
Proton pump inhibitor (PPI) use is becoming increasingly common. Although the toxicity profiles of PPIs are not well understood particularly in children, PPIs have been associated with increased risks of gastrointestinal and respiratory tract infection, vitamin B12 deficiency, hypomagnesaemia, bone fractures, and rebound hyperacidity after discontinuation. Prescribers should take into account that PPI uses pose toxicity risks, which remain to be fully characterised in infants and children.
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Pharmacologic Treatment of Eosinophilic Esophagitis: An Update.
Schoepfer, AM, Straumann, A, Safroneeva, E
Gastrointestinal endoscopy clinics of North America. 2018;(1):77-88
Abstract
Eosinophilic esophagitis (EoE) is defined as a chronic, immune-medicated or antigen-mediated, esophageal disease, characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation. Food allergens are identified in most patients. Treatment strategies include elimination diets, drugs, and esophageal dilation. This article focuses on pharmacologic treatment. Currently, there is no pharmacologic treatment that has been approved by regulatory authorities. Established pharmacologic options to treat EoE include proton pump inhibitors and swallowed topical steroids. Several biologic therapies are currently under evaluation and some of them have shown promising results in improving biologic endpoints and patient-reported outcomes.