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Effects of Proton Pump Inhibitors on Glycemic Control and Incident Diabetes: A Systematic Review and Meta-analysis.
Peng, CC, Tu, YK, Lee, GY, Chang, RH, Huang, Y, Bukhari, K, Tsai, YC, Fu, Y, Huang, HK, Munir, KM
The Journal of clinical endocrinology and metabolism. 2021;(11):3354-3366
Abstract
CONTEXT Whether proton pump inhibitors (PPI) can improve glycemic control among individuals with diabetes or decrease the risk of incident diabetes in the general population is unclear. OBJECTIVE To evaluate the impact of PPI therapy on glycemic control among individuals with diabetes and the risk of diabetes among those without diabetes. RESULTS PubMed, Embase, Scopus, and ClinicalTrials.gov were searched from inception to November 21, 2020. We included studies comparing glycosylated hemoglobin (HbA1c) or fasting blood glucose (FBG) among individuals with diabetes treated with and without PPI therapy as an add-on to standard therapy. Studies evaluating the risk of incident diabetes among individuals taking PPI were assessed. We performed dual independent review, data extraction, and quality assessment. Weighted mean differences between groups or relative risks were imputed using random-effects models. RESULTS Seven studies (n = 342) for glycemic control and 5 studies (n = 244 439) for risk of incident diabetes were included. Compared with standard therapy, add-on PPI was associated with a significant decrease in HbA1c (WMD, -0.36 %; 95% CI, -0.68 to -0.05; P = 0.025) and FBG (WMD, -10.0 mg/dL; 95% CI, -19.4 to -0.6; P = 0.037). PPI use did not reduce the risk of incident diabetes (pooled RR, 1.10; 95% CI, 0.89 to 1.34; P = 0.385). CONCLUSION Add-on PPI improved glycemic indices among individuals with diabetes but did not alter the risk of incident diabetes. The effects of PPI on glycemic control should be considered when prescribing antacids to patients with diabetes.
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Reassessing the Use of Proton Pump Inhibitors and Histamine-2 Antagonists in Critically Ill Children: A Systematic Review and Meta-Analysis.
Yao, DWJ, Ong, C, Eales, NM, Sultana, R, Wong, JJ, Lee, JH
The Journal of pediatrics. 2021;:164-176.e7
Abstract
OBJECTIVE To determine the associations of stress ulcer prophylaxis with gastrointestinal (GI) bleeding, nosocomial pneumonia (NP), mortality, and length of stay in the pediatric intensive care unit (PICU). STUDY DESIGN We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies in the English language assessing the effects of proton pump inhibitors and histamine-2 receptor antagonists on patients in the PICU published before October 2018 from the PubMed, Embase, CINAHL, and Cochrane Central Register of Controlled Trials databases. A random-effects Mantel-Haenszel risk difference (MHRD) model was used to pool all the selected studies for meta-analysis. Primary outcomes were the incidences of GI bleeding and NP. Secondary outcomes included mortality and length of PICU stay. RESULTS Seventeen studies (4 RCTs and 13 observational studies) with a total of 340 763 patients were included. The overall incidence of GI bleeding was 15.2%. There was no difference in the risk of GI bleeding based on stress ulcer prophylaxis status (MHRD, 5.0%; 95% CI, -1.0% to 11.0%; I2 = 62%). There was an increased risk of NP in patients who received stress ulcer prophylaxis compared with those who did not (MHRD, 5.3%; 95% CI, 3.5%-7.0%; I2 = 0%). An increased risk of mortality was seen in patients receiving stress ulcer prophylaxis (MHRD, 2.1%; 95% CI, 2.0%-2.2%; I2 = 0%), although this association was no longer found when 1 large study was removed in a sensitivity analysis. There was no statistically significant difference in length of PICU stay between the groups (standardized mean difference, 0.42 days; 95% CI, -0.16 to 1.01 days; I2 = 89.8%). CONCLUSIONS Stress ulcer prophylaxis does not show a clear benefit in reducing GI bleeding or length of PICU stay. Observational studies suggest an increased risk of NP and mortality with stress ulcer prophylaxis, which remains to be validated in clinical trials.
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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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The efficacy of vonoprazan for management of post-endoscopic submucosal dissection ulcers compared with proton pump inhibitors: A meta-analysis.
Liu, C, Feng, BC, Zhang, Y, Li, LX, Zuo, XL, Li, YQ
Journal of digestive diseases. 2019;(10):503-511
Abstract
OBJECTIVE Artificial ulcers after endoscopic submucosal dissection (ESD) are usually treated by proton pump inhibitors (PPIs) in clinical setting. Vonoprazan, a newly developed potassium-competitive acid blocker, has recently been used to treat post-ESD ulcers. We aimed to evaluate the efficacy and safety of vonoprazan on the healing of post-ESD artificial ulcers compared with those of proton pump inhibitors (PPIs) using a meta-analysis. METHODS EMBASE, MEDLINE, Scopus and Cochrane Library databases were searched for all studies comparing the efficacy and safety of vonoprazan with those of PPIs in the treatment of post-ESD ulcers. RESULTS Fourteen articles with 1328 patients were included in this meta-analysis. When comparing ulcer shrinkage rate, vonoprazan showed a better efficacy than PPIs (mean difference 0.56, 95% confidence interval [CI] 0.18-0.93). Vonoprazan also led to a higher scar formation rate (odds ratio [OR] 1.58, 95% CI 1.00-2.47) and showed a potential superiority on reducing the risk of post-ESD bleeding compared with PPIs, with a pooled OR of 0.69, although there was no statistically significant difference. CONCLUSIONS Compared with PPIs, vonoprazan showed a better efficacy in ulcer shrinkage rate and achieved more complete healing in the treatment of post-ESD ulcers. Vonoprazan did not induce any incremental risk of post-ESD bleeding as well. It may be an appropriate choice in the management of artificial ulcers after ESD.
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Proton pump inhibitors and hypomagnesemia: A meta-analysis of observational studies.
Srinutta, T, Chewcharat, A, Takkavatakarn, K, Praditpornsilpa, K, Eiam-Ong, S, Jaber, BL, Susantitaphong, P
Medicine. 2019;(44):e17788
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Abstract
BACKGROUND Previous meta-analyses have suggested that there might be an association between the use of proton pump inhibitors (PPIs) and the development of hypomagnesemia, although the conclusions were no definitive. METHODS To provide an update on this topic, we performed a meta-analysis of all observational studies that examined the association between the use of PPIs and the development of hypomagnesemia. A literature search was conducted in MEDLINE, Scopus and Cochrane Central Register of Controlled Trials (January 1970 to June 2018) to identify observational studies that examined the association between the use of PPIs and the incidence and prevalence of hypomagnesemia. STUDY ELIGIBILITY CRITERIA In the absence of randomized controlled trials, we focused primarily on observational studies, including cross-sectional, case-control, retrospective, and prospective cohort studies. There was no limitation on sample size or study duration. Random-effect models meta-analyses were used to compute pooled unadjusted and adjusted odds ratios (ORs) for binary variables. RESULTS Sixteen observational studies were identified, including 13 cross-sectional studies, 2 case-control studies, and 1 cohort study, with a total of 131,507 patients. The pooled percentage of PPI users was 43.6% (95% confidence interval [CI] 25.0%, 64.0%). Among PPI users, 19.4% (95% CI 13.8%, 26.5%) had hypomagnesemia compared to 13.5% (95% CI 7.9%, 22.2%) among nonusers. By meta-analysis, PPI use was significantly associated with hypomagnesemia, with a pooled unadjusted OR of 1.83 (95% CI 1.26, 2.67; P = .002) and a pooled adjusted OR of 1.71 (95% CI 1.33, 2.19; P < .001). In subgroup analyses, high-dose PPI use was associated with higher odds for hypomagnesemia relative to low-dose PPI use (pooled adjusted OR 2.13; 95% CI 1.26, 3.59; P = .005). CONCLUSION Our findings are in support of the results of the previous meta-analyses. Furthermore, we found a dose-response between the PPI use and development of hypomagnesemia.
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Saccharomyces boulardii as an adjuvant therapy for Helicobacter pylori eradication: A systematic review and meta-analysis with trial sequential analysis.
Zhou, BG, Chen, LX, Li, B, Wan, LY, Ai, YW
Helicobacter. 2019;(5):e12651
Abstract
BACKGROUND AND AIMS Whether Saccharomyces boulardii (S boulardii) as an adjuvant therapy are beneficial to H pylori eradication remains controversial. The aim of the study was to update and determine the effects of S boulardii as an adjuvant therapy on H pylori eradication rates and adverse effects. METHODS We searched PubMed, Embase, CENTRAL, and Web of Science to collect all randomized controlled trials assessing the effects of S boulardii as an adjuvant therapy for H pylori eradication from inception to February 2019. Quality of evidence was appraised using Grading of Recommendations, Assessment, Development and Evaluation system. Trial sequential analysis was performed to control the risk of type I and type II errors. RESULTS Eighteen trials with 3592 patients were eligible for meta-analysis. Compared with standard eradication regimen, the S boulardii supplementation could significantly improve eradication rates [risk ratio (RR) = 1.09, 95% confidence interval (CI):1.05-1.13; moderate quality evidence] and reduce the incidence of total side effects (RR = 0.47, 95%CI:0.36-0.61; low quality evidence), as well as some gastrointestinal adverse effects, especially diarrhea (RR = 0.33, 95%CI:0.23-0.47; low quality evidence) and constipation (RR = 0.37, 95%CI:0.23-0.57; moderate quality evidence). In addition, the need for discontinuation rate in S boulardii supplementation group was significantly lower than in the control group (RR = 0.33, 95%CI:0.16-0.69, P = .003; moderate quality evidence). The TSA results for overall eradication rates and total side effects indicated that the effects were conclusive. CONCLUSIONS Our meta-analysis shows that S boulardii supplementation on standard eradication therapy significantly increased H pylori eradication rates and reduced the incidence of total side effects and some gastrointestinal adverse effects during eradication therapy.
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Clinical outcomes of laryngopharyngeal reflux treatment: A systematic review and meta-analysis.
Lechien, JR, Saussez, S, Schindler, A, Karkos, PD, Hamdan, AL, Harmegnies, B, De Marrez, LG, Finck, C, Journe, F, Paesmans, M, et al
The Laryngoscope. 2019;(5):1174-1187
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Abstract
OBJECTIVES To investigate the therapeutic benefit of proton pump inhibitors (PPIs) over placebo in patients with laryngopharyngeal reflux (LPR) and to analyze the epidemiological factors of heterogeneity in the literature. METHODS An electronic literature search was conducted to identify articles published between 1990 and 2018 about clinical trials describing the efficiency of medical treatment(s) on LPR. First, a meta-analysis of placebo randomized controlled trials (RCTs) comparing PPIs versus placebo was conducted according to diet. The heterogeneity, response to PPIs, and evolution of clinical scores were analyzed for aggregate results. Second, a systematic review of diagnosis methods, clinical outcome of treatment, and therapeutic regimens was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. RESULTS The search identified 1,140 relevant publications, of which 72 studies met the inclusion criteria for a total of 5,781 patients. Ten RCTs were included in the meta-analysis. The combined relative risk was 1.31 in favor of PPIs and increased to 1.42 when patients did not receive diet recommendations. Randomized controlled trials were characterized by a significant heterogeneity due to discrepancies in clinical therapeutic outcomes, diagnosis methods (lack of gold standard diagnostic tools), and therapeutic scheme. The epidemiological analysis of all articles supports the existence of these discrepancies in the entire literature. In particular, many symptoms and signs commonly encountered in LPR are not assessed in the treatment effectiveness. The lack of diagnosis precision and variability of inclusion criteria particularly create bias in all reported and included articles. CONCLUSION This meta-analysis supports a mild superiority of PPIs over placebo and the importance of diet as additional treatment but demonstrates the heterogeneity between studies, limiting the elaboration of clear conclusions. International recommendations are proposed for the development of future trials. Laryngoscope, 129:1174-1187, 2019.
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Comparison of the Use of Vonoprazan and Proton Pump Inhibitors for the Treatment of Peptic Ulcers Resulting from Endoscopic Submucosal Dissection: A Systematic Review and Meta-Analysis.
He, HS, Li, BY, Chen, QT, Song, CY, Shi, J, Shi, B
Medical science monitor : international medical journal of experimental and clinical research. 2019;:1169-1176
Abstract
BACKGROUND Currently, proton pump inhibitors (PPIs) are the first-line treatment for ulcers resulting from endoscopic submucosal dissection (ESD). Vonoprazan is a new oral potassium-competitive acid blocker (P-CAB). The aim of this systematic review and meta-analysis was to compare the efficacy, safety, and tolerance of vonoprazan with PPIs in the treatment of peptic ulcers resulting from ESD. MATERIAL AND METHODS Published results of randomized clinical trials (RCTs) comparing vonoprazan with PPIs in the treatment of ulcers resulting from ESD were identified up to March 2018. The main clinical endpoints evaluated were healing rate and adverse events. The meta-analysis included quality assessment of the studies, statistical analysis of endpoints, and sensitivity analysis using Revman version 5.3 meta-analysis software. RESULTS Systematic literature review identified seven published studies that included 548 patients. Five studies were published as full-text manuscripts, and two studies were published as abstracts. Meta-analysis of the vonoprazan treatment, compared with PPI treatment, for ESD showed that the pooled relative risk (RR) of healing rate was 0.64 (95% CI, 0.33-1.22) for the 4-week study group and 0.98 (95% CI, 0.84-1.15) for the 8-week study group. The RR for adverse events was 0.65 (95% CI, 0.31-1.38) (P>0.05). No statistical evidence of publication bias was found. CONCLUSIONS The findings of the systematic review and meta-analysis showed that the efficacy of vonoprazan was comparable with PPIs for the treatment of peptic ulcers following ESD. Further studies are required to support the safety and efficacy of vonoprazan compared with different types of PPIs.
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Proton pump inhibitors' use and risk of hip fracture: a systematic review and meta-analysis.
Hussain, S, Siddiqui, AN, Habib, A, Hussain, MS, Najmi, AK
Rheumatology international. 2018;(11):1999-2014
Abstract
In the last decade, epidemiological studies presented inconsistent findings concerning the proton pump inhibitors (PPI) use and the risk of hip fracture. So, this systematic review and meta-analysis were performed with the aim to quantify the risk of hip fracture associated with PPI use. PubMed® and Cochrane Central databases were searched from inception to January 2018. The quality of included studies in meta-analysis was assessed using Newcastle-Ottawa scale. Primary outcome of this study was to assess the risk of hip fracture among PPI user. Secondary outcomes include subgroup analysis based on study design, study quality, duration of PPI use, calcium intake, and geographical region. Sensitivity analysis was also performed. Review Manager (RevMan) was used to perform statistical analysis. This meta-analysis was based on seventeen studies. Pooled risk ratio showed a statistically significant association between PPI use and hip fracture risk (RR 1.26 [95% CI 1.17-1.35], p < 0.00001). Subgroup analysis, based on the study design, showed a highly significant association between PPI use and risk of hip fracture (p < 0.0001). The risk of hip fracture persisted even when stratified by calcium adjustment and the duration of PPI use (p < 0.0001). This meta-analysis suggests that PPI user have a 26% increased risk of hip fracture as compared to non-PPI user. Physicians should take caution in prescribing PPI to patients who are at increased risk of hip fracture.
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Effects of Helicobacter pylori eradication on insulin resistance and metabolic parameters: a systematic review and meta-analysis.
Upala, S, Sanguankeo, A, Saleem, SA, Jaruvongvanich, V
European journal of gastroenterology & hepatology. 2017;(2):153-159
Abstract
INTRODUCTION Previous studies have shown a close relationship between Helicobacter pylori (H. pylori), insulin resistance, and altered metabolic parameters. However, the effects of H. pylori eradication on these conditions remain controversial. We carried out a systematic review and meta-analysis to evaluate the effects of H. pylori eradication on insulin resistance and metabolic parameters. METHODS We searched CENTRAL, MEDLINE, and EMBASE databases from their inception to July 2016. Insulin resistance (HOMA-IR), body weight (BW), BMI, waist circumference, triglycerides (TG), high-density and low-density lipoprotein-cholesterol (HDL-C and LDL-C), and fasting blood glucose (FBG) were compared between patients with and without H. pylori eradication using a random-effects model. We reported pooled mean differences (MD) and 95% confidence intervals (CI) for the change in outcomes. RESULTS Data from five studies showed no difference in HOMA-IR after H. pylori eradication (pooled MD=-0.52, 95% CI: -1.47 to 0.42). Eradication significantly increased BMI (MD=0.36, 95% CI: 0.11-0.60) and BW (MD=1.1, 95% CI: 0.8-1.5), but had no significant effects on TG, LDL-C, HDL-C, or FBG. CONCLUSION H. pylori eradication does not improve insulin resistance, TG, HDL-C, LDL-C, or FBG, but may increase BW and BMI. Further studies are needed to clarify the effect of H. pylori eradication on metabolism.