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Neurogastroenterology and Motility Jan 2023The comparative efficacy and safety of medical therapies for gastro-esophageal reflux symptoms in endoscopy-negative reflux disease is unclear. We conducted a network... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The comparative efficacy and safety of medical therapies for gastro-esophageal reflux symptoms in endoscopy-negative reflux disease is unclear. We conducted a network meta-analysis to evaluate efficacy and safety of proton pump inhibitors (PPIs), histamine-2-receptor antagonists, potassium-competitive acid blockers (PCABs), and alginates in patients with endoscopy-negative reflux disease.
METHODS
We searched MEDLINE, EMBASE, EMBASE Classic, and the Cochrane central register of controlled trials from inception to February 1, 2022. We included randomized controlled trials (RCTs) comparing efficacy of all drugs versus each other, or versus a placebo, in adults with endoscopy-negative reflux disease. Results were reported as pooled relative risks with 95% confidence intervals to summarize effect of each comparison tested, with treatments ranked according to P-score.
KEY RESULTS
We identified 23 RCTs containing 10,735 subjects with endoscopy-negative reflux disease. Based on failure to achieve complete relief of symptoms between ≥2 and <4 weeks, omeprazole 20 mg o.d. (P-score 0.94) ranked first, with esomeprazole 20 mg o.d. or 40 mg o.d. ranked second and third. In achieving adequate relief, only rabeprazole 10 mg o.d. was significantly more efficacious than placebo. For failure to achieve complete relief at ≥4 weeks, dexlansoprazole 30 mg o.d. (P-score 0.95) ranked first, with 30 ml alginate q.i.d. combined with omeprazole 20 mg o.d., and 30 ml alginate t.i.d. second and third. In terms of failure to achieve adequate relief at ≥4 weeks, dexlansoprazole 60 mg o.d. ranked first (P-score 0.90), with dexlansoprazole 30 mg o.d. and rabeprazole 20 mg o.d. second and third. All drugs were safe and well-tolerated.
CONCLUSIONS & INFERENCES
Our results confirm superiority of PPIs compared with most other drugs in treating endoscopy-negative reflux disease. Future RCTs should aim to better classify patients with endoscopy-negative reflux disease, and to establish the role of alginates and PCABs in achieving symptom relief in both the short- and long-term.
Topics: Adult; Humans; Gastrointestinal Agents; Rabeprazole; Dexlansoprazole; Heartburn; Network Meta-Analysis; Gastroesophageal Reflux; Proton Pump Inhibitors; Omeprazole; Endoscopy, Gastrointestinal; Alginates; Treatment Outcome
PubMed: 36153790
DOI: 10.1111/nmo.14469 -
Medicine Nov 2022Proton-pump inhibitors (PPIs) and vonoprazan are recommended as first-line therapies for erosive esophagitis (EE). However, it is uncertain how the magnitude of efficacy... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Proton-pump inhibitors (PPIs) and vonoprazan are recommended as first-line therapies for erosive esophagitis (EE). However, it is uncertain how the magnitude of efficacy and safety of first-line therapy, the choice of individual PPIs or vonoprazan in the treatment of EE remains controversial. This study aimed to evaluate the efficacy and safety of vonoprazan and PPIs in healing esophageal mucosal injury in patients with EE.
METHODS
Relevant databases were searched to collect randomized controlled trials of proton pump inhibitors and vonoprazan in the treatment of reflux esophagitis up to December 2021. Studies on standard-dose PPIs or vonoprazan that were published in Chinese or English and assessed healing effects in EE were included in the analysis. Stata16.0 was used to conduct a network Meta-analysis to evaluate the efficacy and safety of the treatment.
RESULTS
A total of 41 literatures were included with 11,592 enrolled patients. For the endoscopic cure rate, all the PPIs and vonoprazan significantly improve compared to Placebo; Based on the surface under the cumulative ranking curve, Ilaprazole ranked first, followed by esomeprazole, vonoprazan, pantoprazole, lansoprazole, omeprazole, rabeprazole and placebo therapy ranked the last. For the rate of adverse events, there was no significant difference among all the PPIs, vonoprazan, and placebo.
CONCLUSIONS
Ilaprazole, esomeprazole and vonoprazan have more advantages in mucosal erosion healing, there was no significant difference in the comparative safety among all interventions.
Topics: Humans; Proton Pump Inhibitors; Esomeprazole; Network Meta-Analysis; Peptic Ulcer; Rabeprazole; Esophagitis, Peptic; Abdominal Injuries
PubMed: 36451489
DOI: 10.1097/MD.0000000000031807 -
Arquivos de Gastroenterologia Dec 2017Proton pump inhibitors and histamine H2 receptor antagonists are two of the most commonly prescribed drug classes for pediatric gastroesophageal reflux disease, but... (Review)
Review
BACKGROUND
Proton pump inhibitors and histamine H2 receptor antagonists are two of the most commonly prescribed drug classes for pediatric gastroesophageal reflux disease, but their efficacy is controversial. Many patients are treated with these drugs for atypical manifestations attributed to gastroesophageal reflux, even that causal relation is not proven.
OBJECTIVE
To evaluate the use of proton pump inhibitors and histamine H2 receptor antagonists in pediatric gastroesophageal reflux disease through a systematic review.
METHODS
A systematic review was performed, using MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials databases. The search was limited to studies published in English, Portuguese or Spanish. There was no limitation regarding date of publication. Studies were considered eligible if they were randomized-controlled trials, evaluating proton pump inhibitors and/or histamine H2 receptor antagonists for the treatment of pediatric gastroesophageal reflux disease. Studies published only as abstracts, studies evaluating only non-clinical outcomes and studies exclusively comparing different doses of the same drug were excluded. Data extraction was performed by independent investigators. The study protocol was registered at PROSPERO platform (CRD42016040156).
RESULTS
After analyzing 735 retrieved references, 23 studies (1598 randomized patients) were included in the systematic review. Eight studies demonstrated that both proton pump inhibitors and histamine H2 receptor antagonists were effective against typical manifestations of gastroesophageal reflux disease, and that there was no evidence of benefit in combining the latter to the former or in routinely prescribing long-term maintenance treatments. Three studies evaluated the effect of treatments on children with asthma, and neither proton pump inhibitors nor histamine H2 receptor antagonists proved to be significantly better than placebo. One study compared different combinations of omeprazole, bethanechol and placebo for the treatment of children with cough, and there is no clear definition on the best strategy. Another study demonstrated that omeprazole performed better than ranitidine for the treatment of extraesophageal reflux manifestations. Ten studies failed to demonstrate significant benefits of proton pump inhibitors or histamine H2 receptor antagonists for the treatment of unspecific manifestations attributed to gastroesophageal reflux in infants.
CONCLUSION
Proton pump inhibitors or histamine H2 receptor antagonists may be used to treat children with gastroesophageal reflux disease, but not to treat asthma or unspecific symptoms.
Topics: Child; Child, Preschool; Gastroesophageal Reflux; Histamine H2 Antagonists; Humans; Infant; Proton Pump Inhibitors; Randomized Controlled Trials as Topic
PubMed: 28954042
DOI: 10.1590/S0004-2803.201700000-42 -
Antibiotics (Basel, Switzerland) Sep 2023Cephalexin is a first-generation β-lactam antibiotic used in adults and pediatrics to treat various streptococcal and staphylococcal infections. This review aims to... (Review)
Review
Cephalexin is a first-generation β-lactam antibiotic used in adults and pediatrics to treat various streptococcal and staphylococcal infections. This review aims to summarize and evaluate all the pharmacokinetic (PK) data on cephalexin by screening out all pertinent studies in human beings following the per oral (PO) route. By employing different online search engines such as Google Scholar, PubMed, Cochrane Central, and Science Direct, 23 studies were retrieved, among which nine were in healthy subjects, five in diseased ones, and the remaining were drug-drug, drug-food, and bioequivalence-related. These studies were included only based on the presence of plasma concentration-time profiles or PK parameters, i.e., maximum plasma concentration (C), half-life (t) area under the curve from time 0-infinity (AUC and clearance (CL/F). A dose-proportional increase in AUC and C can be portrayed in different studies conducted in the healthy population. In comparison to cefaclor, C was recorded to be 0.5 folds higher for cephalexin in the case of renal impairment. An increase in AUC was seen in cephalexin on administration with probenecid, i.e., 117 µg.h/mL vs. 68.1 µg.h/mL. Moreover, drug-drug interactions with omeprazole, ranitidine, zinc sulfate, and drug-food interactions for cephalexin and other cephalosporins have also been depicted in different studies with significant changes in all PK parameters. This current review has reported all accessible studies containing PK variables in healthy and diseased populations (renal, dental, and osteoarticular infections, continuous ambulatory peritoneal dialysis) that may be favorable for health practitioners in optimizing doses among the latter.
PubMed: 37760698
DOI: 10.3390/antibiotics12091402 -
PloS One 2014Although many case reports have described patients with proton pump inhibitor (PPI)-induced hypomagnesemia, the impact of PPI use on hypomagnesemia has not been fully... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Although many case reports have described patients with proton pump inhibitor (PPI)-induced hypomagnesemia, the impact of PPI use on hypomagnesemia has not been fully clarified through comparative studies. We aimed to evaluate the association between the use of PPI and the risk of developing hypomagnesemia by conducting a systematic review with meta-analysis.
METHODS
We conducted a systematic search of MEDLINE, EMBASE, and the Cochrane Library using the primary keywords "proton pump," "dexlansoprazole," "esomeprazole," "ilaprazole," "lansoprazole," "omeprazole," "pantoprazole," "rabeprazole," "hypomagnesemia," "hypomagnesaemia," and "magnesium." Studies were included if they evaluated the association between PPI use and hypomagnesemia and reported relative risks or odds ratios or provided data for their estimation. Pooled odds ratios with 95% confidence intervals were calculated using the random effects model. Statistical heterogeneity was assessed with Cochran's Q test and I2 statistics.
RESULTS
Nine studies including 115,455 patients were analyzed. The median Newcastle-Ottawa quality score for the included studies was seven (range, 6-9). Among patients taking PPIs, the median proportion of patients with hypomagnesemia was 27.1% (range, 11.3-55.2%) across all included studies. Among patients not taking PPIs, the median proportion of patients with hypomagnesemia was 18.4% (range, 4.3-52.7%). On meta-analysis, pooled odds ratio for PPI use was found to be 1.775 (95% confidence interval 1.077-2.924). Significant heterogeneity was identified using Cochran's Q test (df = 7, P<0.001, I2 = 98.0%).
CONCLUSIONS
PPI use may increase the risk of hypomagnesemia. However, significant heterogeneity among the included studies prevented us from reaching a definitive conclusion.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Dexlansoprazole; Esomeprazole; Humans; Lansoprazole; Magnesium; Odds Ratio; Omeprazole; Pantoprazole; Proton Pump Inhibitors; Rabeprazole; Risk Factors; Treatment Outcome
PubMed: 25394217
DOI: 10.1371/journal.pone.0112558 -
Cureus Mar 2024As the global incidence of idiopathic pulmonary fibrosis (IPF) is on the rise, there is a need for better diagnostic criteria, better treatment options, early and... (Review)
Review
As the global incidence of idiopathic pulmonary fibrosis (IPF) is on the rise, there is a need for better diagnostic criteria, better treatment options, early and appropriate diagnosis, adequate care, and a multidisciplinary approach to the management of patients. This systematic review explores the role of proton pump inhibitors (PPIs) in IPF and answers the question, "Does proton pump inhibitor improve only the prognosis of gastroesophageal associated idiopathic pulmonary fibrosis or for other types of idiopathic pulmonary fibrosis too?" We used PubMed (PMC) and Google Scholar for data collection for this systematic review and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for conducting this review. After in-depth literature screening and quality appraisal, 12 articles were selected for this systematic review. On the one hand, the efficacy of PPI therapy is supported by research such as the CAPACITY and ASCEND trials, a pilot randomized control trial (RCT) investigating the role of omeprazole in IPF and a bidirectional two-sample Mendelian randomization (MR) study, respectively. On the other hand, a systematic review and meta-analysis on antacid and antireflux surgery in IPF negate these results and show no statistical significance. Questions regarding the efficacy of PPI therapy must be dealt with in an adequately powered multicenter and double-blinded randomized control trial. The anti-inflammatory properties of antacids can serve as the cornerstone for future trials. In the following systematic review, antacid, antireflux therapy, omeprazole, and proton pump therapy are synonymous with stomach acid suppression therapy.
PubMed: 38606271
DOI: 10.7759/cureus.55980 -
World Journal of Gastroenterology Nov 2021The use of proton pump inhibitors (PPI) is common worldwide, with reports suggesting that they may be overused. Several studies have found that PPI may affect colorectal...
BACKGROUND
The use of proton pump inhibitors (PPI) is common worldwide, with reports suggesting that they may be overused. Several studies have found that PPI may affect colorectal cancer (CRC) risk.
AIM
To summarize current knowledge on the relationship between PPI and CRC from basic research, epidemiological and clinical studies.
METHODS
This systematic review was based on the patients, interventions, comparisons, outcome models and performed according to PRISMA guidelines. MEDLINE, EMBASE, Scopus, and Web of Science databases were searched from inception until May 17, 2021. The initial search returned 2591 articles, of which, 28 studies met the inclusion criteria for this review. The studies were categorized as basic research studies ( = 12), epidemiological studies ( = 11), and CRC treatment studies ( = 5). The quality of the included studies was assessed using the Newcastle-Ottawa Scale or Cochrane Risk of Bias 2.0 tool depending on the study design.
RESULTS
Data from basic research indicates that PPI do not stimulate CRC development the trophic effect of gastrin but instead may paradoxically inhibit it. These studies also suggest that PPI may have properties beneficial for CRC treatment. PPI appear to have anti-tumor properties (omeprazole, pantoprazole), and are potential T lymphokine-activated killer cell-originated protein kinase inhibitors (pantoprazole, ilaprazole), and chemosensitizing agents (pantoprazole). However, these mechanisms have not been confirmed in human trials. Current epidemiological studies suggest that there is no causal association between PPI use and increased CRC risk. Treatment studies show that concomitant PPI and capecitabine use may reduce the efficacy of chemotherapy resulting in poorer oncological outcomes, while also suggesting that pantoprazole may have a chemosensitizing effect with the fluorouracil, leucovorin, oxaliplatin (FOLFOX) regimen.
CONCLUSION
An unexpected inhibitory effect of PPI on CRC carcinogenesis by way of several potential mechanisms is noted. This review identifies that different PPI agents may have differential effects on CRC treatment, with practical implications. Prospective studies are warranted to delineate this relationship and assess the role of individual PPI agents.
Topics: Capecitabine; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Proton Pump Inhibitors
PubMed: 34908809
DOI: 10.3748/wjg.v27.i44.7716 -
International Journal of General... 2021Aspirin appeared as a medicine to deal with aches and inflammation, but due to its antiplatelet properties, it has evolved into a drug mainly used to avert... (Review)
Review
INTRODUCTION
Aspirin appeared as a medicine to deal with aches and inflammation, but due to its antiplatelet properties, it has evolved into a drug mainly used to avert cardiovascular disease. Regardless of its therapeutic uses, the limiting aspect for aspirin use has been its affiliation with gastrointestinal (GI) toxicity, classifying from acute mucosal damage to GI problems and death.
OBJECTIVE
The aim of this systematic review is to address the question regarding the ECA effect on the gastric mucosa.
METHODS
A systematic search of the literature was conducted in the PubMed electronic databases from April 10th to April 23rd, 2020. Eligibility has been set, and based on those criteria, initially a total of 637 results were obtained, from these 58 of them were not written in English. Then, 168 articles which were free from duplication were screened and all the included articles were RCTs published after 2000. Based on these, final number of articles included on this review was 6.
RESULTS
Data were obtained from 6 published articles which reported on 15,621 participants. The reports were from 3 different countries. Most of the studies revealed that enteric-coated aspirin (ECA) treatment was not an effective mechanism against GI protection. ECA administration with omeprazole can hugely reduce the incidence of endoscopic GI damage compared to the impact of ECA used alone. Even short-term administration of a low dose of ECA was significantly associated with an apparent small bowel injury.
CONCLUSION
ECA treatment is not an effective mechanism against GI protection, and it is highly associated with small bowel injury. So the coating does not reduce risk of GI complications.
PubMed: 34466020
DOI: 10.2147/IJGM.S326929 -
Canadian Journal of Gastroenterology =... Sep 2008Proton pump inhibitors (PPIs) have become the mainstay of treatment for and prevention of many serious gastrointestinal diseases. Laboratory and clinical evidence... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Proton pump inhibitors (PPIs) have become the mainstay of treatment for and prevention of many serious gastrointestinal diseases. Laboratory and clinical evidence suggests that the increase in gastric pH caused by PPIs may be linked to increased bacterial colonization of the stomach and may predispose patients to an increased risk for respiratory infections.
OBJECTIVE
To examine the association between PPI treatment and respiratory infections.
METHODS
A literature search was conducted using PubMed, MEDLINE and Cochrane databases of randomized, placebo-controlled trials evaluating the efficacy of PPIs. Studies that listed and quantified the specific adverse events of 'respiratory infection' or 'upper respiratory infection' (or equivalent), and compared their rates between PPIs and placebo were included. The chi(2) analysis was used to calculate the significance of association in individual studies and a meta-analysis of the selected studies was performed.
RESULTS
Of 7457 studies initially identified and 70 relevant randomized, controlled trials (RCTs) selected, seven studies met the inclusion criteria. A total of 16 comparisons for chi(2) analysis were possible given the multiple dosage arms used in several studies. PPIs included in the studies were esomeprazole, rabeprazole, pantoprazole and omeprazole. More than one-half of the studies showed a trend toward an association between PPI use and respiratory infections, although the majority of the studies failed to show a significant correlation. A single study using high-dose esomeprazole (40 mg) showed a significant association -4.3% rate of respiratory infections in the active group compared with 0% in the placebo group (P<0.05). Meta-analysis showed a trend toward an association between PPIs and respiratory infections, although it failed to reach significance (OR 1.42, 95% CI 0.86 to 2.35; P=0.17).
CONCLUSION
Although a trend was evident in both a chi(2) analysis of individual studies and a meta-analysis, the present review and meta-analysis failed to show a conclusive association between PPIs and respiratory infections. Very few RCTs actively sought out respiratory infections, which excluded the majority of RCTs identified. A well-structured, placebo-controlled prospective study would be needed to determine whether a true association between PPIs and respiratory infections exists.
Topics: Clinical Trials as Topic; Community-Acquired Infections; Humans; Proton Pump Inhibitors; Respiratory Tract Infections
PubMed: 18818790
DOI: 10.1155/2008/821385 -
Clinical and Experimental Dental... Oct 2022Proton pump inhibitors, such as omeprazole and pantoprazole, are frequently prescribed for the treatment of acid reflux. However, those medications have been shown to... (Review)
Review
OBJECTIVES
Proton pump inhibitors, such as omeprazole and pantoprazole, are frequently prescribed for the treatment of acid reflux. However, those medications have been shown to affect a variety of physiologic processes, including bone homeostasis and the gastrointestinal microbiome. The objective of this study was to assess the relationship between proton pump inhibitors and attachment levels around teeth and dental implants. A scoping review was performed to assess the extent and quality of the relevant literature.
MATERIALS AND METHODS
We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) and searched four relevant biomedical literature databases in addition to the grey literature. Keywords in the title and abstract fields, and subject headings for proton pump inhibitors, teeth, and dental implants were included as search terms.
RESULTS
Overall search results identified 791 publications which, after applying the inclusion and exclusion criteria, yielded 27 publications that were further analyzed for relevance and quality of scientific evidence. The majority of eligible publications were retrospective cohort studies. Following critical analysis, 13 publications, including six abstracts, were used to assess the effect of proton pump inhibitors on tissue attachment around teeth and dental implants.
CONCLUSIONS
There are few high-quality studies describing the effect of proton pump inhibitors on tissue attachment around teeth and dental implants. Nevertheless, among the included papers with the fewest confounding factors, there was a positive relationship between proton pump inhibitors and soft tissue attachment levels around teeth, and a predominantly negative but variable effect of proton pump inhibitors on the bone level around dental implants. Additional well-controlled prospective studies are required to fully elucidate those relationships.
Topics: Dental Implants; Humans; Omeprazole; Pantoprazole; Proton Pump Inhibitors; Retrospective Studies
PubMed: 35799099
DOI: 10.1002/cre2.616