Examples include:. Proton pump inhibitors are generally very safe and effective in adult men and women. While there are some adverse effects and warnings for this class of medications, using the lowest necessary dose and not exceeding the recommended length of therapy usually results in low rates of serious effects.
Proton pump inhibitors are approved for use in children over 1-year of age and are dosed based on weight. Use of PPIs in children may result in an increased risk of infections like pneumonia and a stomach infection caused by the organism C.
Proton pump inhibitors may also increase the risk of fractures in children. Therefore, these medications are not generally given to children unless first consulting with a healthcare provider. However, because use of a proton pump inhibitor in infants is not approved by the U. Food and Drug Administration FDA , it is up to the discretion of your healthcare provider to decide the need. Because long-term use of PPIs can increase the risk of C.
In fact, the Beers List of potentially inappropriate medications for older adults recommends no more than eight weeks of continued use in adults over the age of Auromedics Pharma LLC: Voluntary recall of pantoprazole 40mg for Injection due to presence of glass particles in the vial , December Do not take proton pump inhibitors if you have a history of a hypersensitivity reaction to any proton pump inhibitor.
Except for esomeprazole , proton pump inhibitors should be avoided in patients who are also taking products containing rilpivirine. Because small amounts of these drugs can pass into breast milk, nursing mothers should talk to their healthcare providers before using a proton pump inhibitor. Proton pump inhibitors are generally well-tolerated.
Talk with your doctor before taking them for longer than two weeks. Be sure you have a good reason to take the PPI, and take it for the shortest time possible.
PPIs interact with some common prescription drugs. This can increase the risk of heart attack and even death. If you take Plavix, talk to your doctor about whether you should take a PPI. Both the prescription and over-the-counter versions of PPIs are usually more expensive than antacids and H2 blockers. If you are worried about cost, talk to your doctor. In terms of tolerance, the comparison results among active drugs did not reach statistical significance; however, the tolerance was better than the placebo Fig.
Effects of active drugs with different recommended doses and the overall effects from PPI and H 2 RA families compared with placebo for healing. Effects of active drugs with different recommended doses and the overall effects from PPI and H 2 RA families compared with placebo for the relief of symptoms.
Effects of active drugs with different recommended doses and the overall effects from PPI and H 2 RA families compared with placebo for tolerance. Post hoc comparison results from the sensitivity analysis are presented Supplementary Table S8. The one inconsistency node did not cause substantive changes to the results, and it further confirmed the reliability of our results. All ranks did not significantly change. The placebo was the worst for all outcomes. All rankings exhibited strong stability in the sensitivity analyses.
All drug treatments were ranked according to their surface under the cumulative ranking SUCRA values. In ranking order for healing rates, from best to worst, the higher SUCRA scores demonstrate better effects. The red line indicates healing. In a similar manner, the green line indicates the relief of symptoms, and the blue line indicates tolerance. For the main outcome, the quality of estimates substantially varied across comparisons within the network. All quality ratings of pair-wise comparisons from the network results, which were derived from quality ratings of direct comparisons and included 9 high, 16 moderate, 18 low, and 13 very low, had 10 high, 40 moderate, 91 low, and 91 very low Supplementary Table S9.
Moreover, 14 quality ratings of the network results had changed. Thus, the quality rating of the network meta-analysis was clearly defined as low. In our network meta-analysis, we performed a series of adjusted hierarchical multi-regressions to investigate the effectiveness and tolerability of PPIs and H 2 RAs in the treatment of GERD for adults, thereby overcoming the major limitation of conventional pairwise meta-analysis 23 , 24 , with the ultimate aim to obtain current, reliable and high-quality evidence to influence the latest guideline development 8.
Moreover, we have provided rankings of all included drug interventions with various recommended doses from the guidelines, which may serve as a decision-making tool for clinicians To better grasp the true nature of the drugs, we discussed relevant baseline and potential confounding factors that may influence the size of the treatment effect. First, our study indicated that most factors did not influence the size of the treatment effect in our main outcome, whereas the results for relevant coefficient factors indicated that there was a specific relationship between baseline and treatment effects.
For example, a higher percentage of females was associated with a worse healing efficacy of endoscopy For the relief of symptom outcome, the inconsistency will be further discussed later.
In the tolerance comparison, esomeprazole did not demonstrate a strong advantage among active interventions. Year is a comprehensive indicator, including the development of new drugs, improved efficacy and safety of drugs, as well as high-quality study design Thus, the course of treatment may be reduced following professional evaluation by a clinical physician. Bias refers to systematic error, which suggests that multiple replications of the same trial would not reach the same conclusion 29 , In general, randomized research designs are not subject to many biases that affect the weaker forms of evidence obtained from non-randomized studies; however, important deficits in the design, conduct, analysis, and reporting may lead to bias in randomized controlled trials According to the results from the pre-set selective design bias 31 , we determined that the results obtained from adjusting four selective design bias models were similar to the results obtained from the non-adjusted model for all outcomes.
In the relief of symptom category, the PPI favored bias was significant, and the variance of the coefficient from the fixed coefficients model 1.
Despite its lower global heterogeneity results, PPI favored bias exhibited specific advantages compared with the other design biases, as well as the non-adjusted bias model, and the models failed to adequately explain the sources of the inconsistencies.
When the supplementary merger favored models were simultaneously used, the results demonstrated a substantial change. This finding suggested that an interaction effect between PPI favored bias and sponsored favored bias may exist 32 because some studies exhibited antagonistic sponsored favored biases that weakened the efficacy of the PPI favored bias Compared with the other outcomes, the main and tolerance outcomes demonstrated that all design bias models had sufficient advantages compared with the non-adjusted model.
Consistency has been described as the relationship between direct and indirect sources of evidence for a single comparison in a network meta-analysis When inconsistency is identified in a statistical analysis, it may indicate a lack of transitivity. The results for the relief of symptom outcome were negative; however, inconsistency comprised several nodes.
However, the results obtained from the adjustment of confounding factors and design bias suggest that pharmaceutical industry sponsorship did not affect the results in terms of the scale of statistical significance. This finding suggested that the nature of the inconsistency was consistent with the boundary, which was falsely associated with pharmaceutical industry sponsorship on the surface, and inconsistency as part of the heterogeneity was widespread and difficult to identify among all comparisons The two main reasons for exaggerated clinical heterogeneity were that the relief of symptoms was evaluated using the standard of excessive subjective judgments from specialist physicians or patients and too many types of symptoms were mixed chaotic, such as heartburn, regurgitation, and other related symptoms 36 , We simultaneously considered that the number of esomeprazole was one important factor that led to the result deviation from clinical significance.
Based on the cost of the guideline of NICE 8 , it was determined that the cost of esomeprazole was more expensive than omeprazole. Considering these factors, the result of the relief of symptoms may require caution by clinicians. However, the ranking results following the addition of the inconsistency factors were not affected based on the hierarchical modeling approach that incorporated dose-related and PPI favored constraints. Network meta-analyses may be used to analyze studies with multiple intervention groups, synthesize studies that make different comparisons of interventions and provide rankings for all interventions Rankings based on a network meta-analysis may provide important evidence for making clinical decisions However, the guidelines indicated that this result was based on one small trial; thus, it was subject to substantial uncertainty.
Considering that more samples and more reliable methodologies were used in our study, we maintained that our results were more reliable in terms of healing for GERD in adults based on 4—8 weeks of short-term therapy. Direct-comparison methodology remains the most widely used research technique. However, when multiple interventions are investigated in one clinical question, a network meta-analysis may provide answers In this study, we used a Bayesian approach 40 and pooled direct and indirect comparison data from 98 randomized studies that investigated the effects of numerous pharmacological interventions, specifically PPIs and H 2 RAs, for the treatment of GERD; moreover, we obtained a hierarchical ranking of their efficacy and tolerability profiles.
Furthermore, the corresponding covariates and biases were adjusted and analyzed via the multiple meta-analysis method. From a clinical perspective, our analysis reinforces the existing evidence and both updates and supplements the evidence limited by potential confounding factors, such as the level of disease from endoscopy and symptoms.
Considering the clinical significance, a hierarchical modeling approach that incorporated dose-related and PPI favored constraints was used to fully determine the potential advantages of both the PPI family and high-dose interventions.
The GRADE system was applied in our main outcome to evaluate the quality of treatment effect and provide advice for clinicians. Thus, our findings are more applicable in the formulation of clinical practice guidelines. Our study has several limitations. First, our meta-regression analyses used a single covariate to obtain adjusting results; future efforts that introduce multiple covariates to establish a high-quality and accurate model for further analyses are warranted Second, missing data present a threat to the validity of a randomized trial because the individuals with observed outcomes may not be representative of all individuals in the trial, and our study lacked corresponding evidence to demonstrate its impact on the overall results Third, additional samples and high quality randomized controlled trials are critical components in the production of high quality sources of evidence We look forward to additional research and superior methodology to update and perfect the current body of evidence.
These findings may be applicable for the development of the latest clinical practice guidelines and should serve as a useful decision-making reference for clinicians. We also screened the reference lists of relevant published systematic reviews for additional studies and searched the US Food and Drug Administration FDA website for information regarding approvals.
We included randomized, parallel-group clinical trials that investigated the efficacy and tolerability of PPIs, H 2 RAs and placebos. Our primary outcome was healing, measured via endoscopy. The secondary outcomes included the relief of symptoms and tolerance. Tolerance was defined as any reason that caused discontinuation during the entire treatment duration.
Studies that reported at least one of the three outcomes were eligible for inclusion. Based on the principles gained from the similarity of overall research 36 and clinical applicability 9 , we designated the treatment periods for all outcomes as short-term therapy 4—8 weeks.
If there were multiple nodes of data within 4—8 weeks, we selected the final time node as the outcome data. If the data were not in this range, the nodes could be no less than 1 week and no more than 12 weeks, and data from the closest setting time were extracted.
The language of all included studies was limited to English. Duplicate published research and sample study arms of less than 30 were excluded. Based on the potential differences in molecular structures and drug efficacies of dexlansoprazole and lansoprazole, our study does not include dexlansoprazole For missing data, particularly study design or outcomes, we contacted the original study authors for clarification.
Intention-to-treat ITT data were used for all outcomes when possible; otherwise, per-protocol PP data were used The percentages of levels C and D from the Los Angeles grade LA or the Savary-Miller criteria SM: 3—4 or the Hetzel-Dent scale HD: 3—4 standard were defined to describe the covariation of the level of severe erosive esophagitis obtained via endoscopy. We gathered all doses per day as a unit, according to the recommended standards based on guidelines 8.
We assessed the following domains: i random sequence generation; ii allocation concealment; iii blinding of participants and personnel; iv blinding of outcome assessors; v incomplete outcome data; vi selective reporting; and vii other sources of bias.
Disagreements were resolved by discussion between the two authors or consultation with a third author Joey S. For each methodological attribute included, we assigned the studies a rating of high, uncertain, or low quality. Using this information, we evaluated the distribution of the methodological qualities of different comparisons across the evidence network. We subsequently extracted information regarding the funding sources of the included trials.
Two potential funding sources were industry and non-industry such as government, academic institutions, and other not-for-profit research organizations. The industry sources included private, for-profit pharmaceutical companies involved in research and development, manufacturing, or marketing sources. Most of the included trial publications contained a statement that delineated the funding sources; in cases in which the sponsorship information was not clearly documented, we checked the author affiliations and categorized the studies with industry affiliated authors as industry sponsored.
To investigate the presence of related potential bias 44 , we compared four categories of selective design bias for the existence of small-study effects: new favored bias, sponsored favored bias, high-dose favored bias, and PPI favored bias 8 , 24 , New favored bias was defined by considering the date of licensing for each treatment or from the date of publication of the first trial that evaluated a treatment for the investigated condition.
Sponsored favored bias was defined by considering the profit relationship between drugs and industry sponsors. High-dose bias was defined by only considering a potentially favored high-dose intervention relation to a low-dose intervention in different doses from identity intervention.
Based on the related clinical evidence 31 , 32 that the PPI family was more effective as an anti-reflux agent than the H 2 RA family for patients with persistent symptoms who are treated empirically for GERD, we included another design bias, which was referred to as the PPI favored bias. Finally, we considered a supplementary merger favored bias, which is related to two types of probable design bias, to further investigate the cumulative effects and interrelations of design bias. Network meta-analyses provide reliable evidence for direct and indirect multiple-intervention comparisons You can help normalize your overactive bladder naturally by avoiding artificial sweeteners, caffeine, and alcohol, losing weight, and performing….
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