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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 -
Alimentary Pharmacology & Therapeutics Sep 2009No randomized controlled trial (RCT) has compared all European-licensed standard- and double-dose PPIs for the healing of severe erosive oesophagitis. (Comparative Study)
Comparative Study Review
Systematic review: standard- and double-dose proton pump inhibitors for the healing of severe erosive oesophagitis -- a mixed treatment comparison of randomized controlled trials.
BACKGROUND
No randomized controlled trial (RCT) has compared all European-licensed standard- and double-dose PPIs for the healing of severe erosive oesophagitis.
AIM
To compare the effectiveness of licensed doses of PPIs for healing severe erosive oesophagitis (i.e. esomeprazole 40 mg, lansoprazole 30 mg, omeprazole 20 mg and 40 mg, pantoprazole 40 mg and rabeprazole 20 mg).
METHODS
Systematic review of CENTRAL, EMBASE and MEDLINE for RCTs in patients with erosive oesophagitis (completed October 2008). Endoscopically verified healing rates at 4 and 8 weeks were extracted and re-calculated if not analysed by intention-to-treat. A mixed treatment comparison was used to combine direct treatment comparisons with indirect trial evidence while maintaining randomization. Odds ratios (OR) are reported compared to omeprazole 20 mg.
RESULTS
A total of 3021 papers were identified in the literature search; 12 were of sufficient quality to be included in the analysis. Insufficient data were available to included rabeprazole. Esomeprazole 40 mg was found to provide significantly higher healing rates at 4 weeks [OR 1.84, 95% Credible Interval (95% CrI): 1.50 to 2.22] and 8 weeks (OR 1.91, 95% CrI: 1.13 to 2.88). No other PPI investigated had significantly higher healing rates than omeprazole 20 mg.
CONCLUSION
Esomeprazole 40 mg consistently demonstrates higher healing rates compared with licensed standard- and double-dose PPIs.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Dose-Response Relationship, Drug; Esomeprazole; Esophagitis; Humans; Lansoprazole; Omeprazole; Proton Pump Inhibitors; Rabeprazole; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 19558609
DOI: 10.1111/j.1365-2036.2009.04077.x -
Drugs & Aging May 2018Residents of long-term care facilities (LTCFs) are at high risk of hospitalization. Medications are a potentially modifiable risk factor for hospitalizations. (Review)
Review
BACKGROUND
Residents of long-term care facilities (LTCFs) are at high risk of hospitalization. Medications are a potentially modifiable risk factor for hospitalizations.
OBJECTIVE
Our objective was to systematically review the association between medications or prescribing patterns and hospitalizations from LTCFs.
METHODS
We searched MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and International Pharmaceutical Abstracts (IPA) from inception to August 2017 for longitudinal studies reporting associations between medications or prescribing patterns and hospitalizations. Two independent investigators completed the study selection, data extraction and quality assessment using the Joanna Briggs Institute Critical Appraisal Tools.
RESULTS
Three randomized controlled trials (RCTs), 22 cohort studies, five case-control studies, one case-time-control study and one case-crossover study, investigating 13 different medication classes and two prescribing patterns were included. An RCT demonstrated that high-dose influenza vaccination reduced all-cause hospitalization compared with standard-dose vaccination (risk ratio [RR] 0.93; 95% confidence interval [CI] 0.88-0.98). Another RCT found no difference in hospitalization rates between oseltamivir as influenza treatment and oseltamivir as treatment plus prophylaxis (treatment = 4.7%, treatment and prophylaxis = 3.5%; p = 0.7). The third RCT found no difference between multivitamin/mineral supplementation and hospitalization (odds ratio [OR] 0.94; 95% CI 0.74-1.20) or emergency department visits (OR 1.05; 95% CI 0.76-1.47). Two cohort studies demonstrated influenza vaccination reduced hospitalization. Four studies suggested polypharmacy and potentially inappropriate medications (PIMs) increased all-cause hospitalization. However, associations between polypharmacy (two studies), PIMs (one study) and fall-related hospitalizations were inconsistent. Inconsistent associations were found between psychotropic medications with all-cause and cause-specific hospitalizations (11 studies). Warfarin, nonsteroidal anti-inflammatory drugs, pantoprazole and vinpocetine but not long-term acetylsalicylic acid (aspirin), statins, trimetazidine, digoxin or β-blockers were associated with all-cause or cause-specific hospitalizations in single studies of specific resident populations. Most cohort studies assessed prevalent rather than incident medication exposure, and no studies considered time-varying medication use.
CONCLUSION
High-quality evidence suggests influenza vaccination reduces hospitalization. Polypharmacy and PIMs are consistently associated with increased all-cause hospitalization.
Topics: Age Factors; Aged; Aged, 80 and over; Case-Control Studies; Cohort Studies; Cross-Over Studies; Drug Prescriptions; Emergency Service, Hospital; Hospitalization; Humans; Inappropriate Prescribing; Long-Term Care; Nursing Homes; Polypharmacy
PubMed: 29582403
DOI: 10.1007/s40266-018-0537-3 -
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 -
Gut Pathogens Mar 2021Spontaneous bacterial peritonitis (SBP) is one of the most common infectious diseases in patients with cirrhosis and is associated with serious prognosis. A prevailing...
BACKGROUND
Spontaneous bacterial peritonitis (SBP) is one of the most common infectious diseases in patients with cirrhosis and is associated with serious prognosis. A prevailing dogma posits that SBP is exacerbated by the frequent use of proton pump inhibitors (PPIs).
AIMS
To re-assess the association between PPIs use and SBP incidence with larger and better-quality data.
METHOD
The studies were identified by searching Proquest, Medline, and Embase for English language articles published between January 2008 and March 2020 using the following keywords alone or in combination: anti-ulcer agent, antacid, proton pump inhibitor, proton pumps, PPI, omeprazole, rabeprazole, lansoprazole, pantoprazole, esomeprazole, peritonitis, spontaneous bacterial peritonitis, SBP, ascites, cirrhosis, ascitic and cirrhotic. Three authors critically reviewed all of the studies retrieved and selected those judged to be the most relevant. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was followed. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Sub-group analyses were done to decrease the heterogeneity.
RESULTS
A total of twenty-three studies: seven case-control, and sixteen cohorts, involving 10,386 patients were analyzed. The overall results showed a statistically significant association between SBP and PPIs use (pooled odds ratio (OR): 1.80, 95% CI of 1.41 to 2.31). Substantial heterogeneity was observed. On subgroup analysis involving cohort studies, the association was weaker (OR: 1.55 with 95% CI of 1.16 to 2.06 p < 0.00001) but still statistically significant and with high heterogeneity (Chip = 57.68; I = 74%). For case-control studies, the OR was 2.62 with a 95% CI of 1.94 to 3.54. The funnel plot was asymmetric and Egger's test confirmed asymmetry suggesting publication bias (intercept = - 0.05, SE = 0.27, P = 0.850 two-tailed).
CONCLUSION
This meta-analysis sheds light on the conflicting results raised by previous studies regarding the association of SBP with PPIs use. Our meta-analysis showed that there is a weak association, although statistically significant, between SBP and PPIs use. However, the magnitude of the possible association diminished when analysis focused on higher quality data that were more robust. Thus, this updated meta-analysis suggests judicious use of PPIs among cirrhotic patients with ascites.
PubMed: 33741033
DOI: 10.1186/s13099-021-00414-8 -
Archives of Medical Research Apr 2012Conclusions from clinical studies and previous meta-analyses were inconsistent regarding the cardiovascular effects of concomitant use of proton pump inhibitors (PPIs)... (Meta-Analysis)
Meta-Analysis Review
Adverse cardiovascular effects of concomitant use of proton pump inhibitors and clopidogrel in patients with coronary artery disease: a systematic review and meta-analysis.
BACKGROUND AND AIMS
Conclusions from clinical studies and previous meta-analyses were inconsistent regarding the cardiovascular effects of concomitant use of proton pump inhibitors (PPIs) and clopidogrel. As new studies are constantly emerging, we performed this meta-analysis to further assess the cardiovascular effects of concomitant use of PPIs and clopidogrel with a focus on individual PPIs.
METHODS
A systematic electronic literature search was conducted in EMBASE, MEDLINE, PubMed and Chinese Biomedical Literature Database (CBM) to identify the studies reporting on the association of concomitant use of PPIs and clopidogrel with adverse cardiovascular outcomes. A hand search of reference lists was performed to identify further studies. Only studies published in English or Chinese were included in this review.
RESULTS
Twenty seven full-text articles and five abstracts with 159,998 patients were included in meta-analysis. Concomitant use of PPIs and clopidogrel is associated with an increased risk of major cardiovascular events (MACE) (HR 1.40, 95% CI 1.19-1.64; OR 1.27, 95% CI 1.13-1.42) and acute coronary syndrome (HR 1.42, 95% CI 1.14-1.77; OR 1.42, 95% CI 1.08-1.87) but not with all-cause mortality (HR 1.30, 95% CI 0.91-1.86; OR 0.92, 95% CI 0.82-1.04), cardiovascular death (HR 1.21, 95% CI 0.60-2.43) and stent thrombosis (HR 1.52, 95% CI 0.87-2.65). In the analyses of individual PPIs, none of the PPIs is associated with an increased MACE risk except for pantoprazole (HR 1.52, 95% CI 1.18-1.94).
CONCLUSIONS
Concomitant use of PPIs and clopidogrel in patients with coronary artery disease is associated with an increased risk of MACE or acute coronary syndrome, but there is insufficient evidence to conclude that there is an interaction between individual PPIs and clopidogrel.
Topics: Clopidogrel; Coronary Artery Disease; Drug Interactions; Drug Therapy, Combination; Humans; Proton Pump Inhibitors; Ticlopidine; Treatment Outcome
PubMed: 22564422
DOI: 10.1016/j.arcmed.2012.04.004 -
Expert Review of Clinical Pharmacology Dec 2018Chronic idiopathic nausea (CIN) and functional dyspepsia (FD) cause considerable strain on many children's lives and their families. Areas covered: This study aims to... (Comparative Study)
Comparative Study Review
INTRODUCTION
Chronic idiopathic nausea (CIN) and functional dyspepsia (FD) cause considerable strain on many children's lives and their families. Areas covered: This study aims to systematically assess the evidence on efficacy and safety of pharmacological treatments for CIN or FD in children. CENTRAL, EMBASE, and Medline were searched for Randomized Controlled Trials (RCTs) investigating pharmacological treatments of CIN and FD in children (4-18 years). Cochrane risk of bias tool was used to assess methodological quality of the included articles. Expert commentary: Three RCTs (256 children with FD, 2-16 years) were included. No studies were found for CIN. All studies showed considerable risk of bias, therefore results should be interpreted with caution. Compared with baseline, successful relief of dyspeptic symptoms was found for omeprazole (53.8%), famotidine (44.4%), ranitidine (43.2%) and cimetidine (21.6%) (p = 0.024). Compared with placebo, famotidine showed benefit in global symptom improvement (OR 11.0; 95% CI 1.6-75.5; p = 0.02). Compared with baseline, mosapride versus pantoprazole reduced global symptoms (p = 0.011; p = 0.009). One study reported no occurrence of adverse events. This systematic review found no evidence to support the use of pharmacological drugs to treat CIN or FD in children. More high-quality clinical trials are needed.
ABBREVIATIONS
AP-FGID: Abdominal Pain Related Functional Gastrointestinal Disorders; BART: Biofeedback-Assisted Relaxation Training; CIN: Chronic Idiopathic Nausea; COS: Core Outcomes Sets; EPS: Epigastric Pain Syndrome; ESPGHAN: European Society for Pediatric Gastroenterology Hepatology and Nutrition; FAP: Functional Abdominal Pain; FD: Functional Dyspepsia; GERD: Gastroesophageal Reflux Disease; GES: Gastric Electrical Stimulation; HRAs: H2 Receptor Antagonists; IBS: irritable bowel syndrome; NASPGHAN: North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition; PDS: Postprandial Distress Syndrome; PPIs: Proton Pump Inhibitor; PROMs: Patient Reported Outcome Measures; RCTs: Randomized Controlled Trials; SSRIs: selective serotonin reuptake inhibitors; TCAs: tricyclic antidepressants.
Topics: Adolescent; Child; Child, Preschool; Chronic Disease; Dyspepsia; Gastrointestinal Agents; Humans; Nausea; Randomized Controlled Trials as Topic
PubMed: 30360666
DOI: 10.1080/17512433.2018.1540298 -
Canadian Journal of Diabetes Aug 2017Proton-pump inhibitors (PPIs) have shown antihyperglycemic effects by stimulating insulin secretion. The aim of this study was to analyze the effect of PPIs on glucose... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Proton-pump inhibitors (PPIs) have shown antihyperglycemic effects by stimulating insulin secretion. The aim of this study was to analyze the effect of PPIs on glucose metabolism in general and any potential antidiabetes effects in patients with type 2 diabetes.
METHODS
A systematic search was conducted in MEDLINE, Embase, Cochrane and PubMed. Studies using PPIs as interventions and reporting glucose levels, glycated hemoglobin (A1C) levels and insulin levels were selected. Weighted-mean differences (WMDs) were calculated for all outcomes. A random-effects model was used for moderate and high heterogeneity and a fixed-effects model for low heterogeneity data.
RESULTS
The research included 9 studies have involving 320 patients in total. Among patients with type 2 diabetes, those exposed to PPIs did not see significant reductions in A1C levels; WMD -0.36, 95% confidence interval (CI) -0.87, 0.15; p=0.17. Pantoprazole resulted in a statistically significant reduction in A1C levels in patients with type 2 diabetes when compared to control interventions; WMD -0.93, 95% CI -1.49, -0.37; p=0.001. There was no statistically significant difference in other outcomes (p≥0.05).
CONCLUSIONS
This meta-analysis demonstrates that PPIs, in general, do not decrease A1C levels in patients with type 2 diabetes. However, pantoprazole produced significant reductions in A1C levels in patients with type 2 diabetes. Given the limitations and the presence of bias in the primary studies, larger and better-quality studies are warranted.
Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glycemic Index; Humans; Hypoglycemic Agents; Proton Pump Inhibitors
PubMed: 28373033
DOI: 10.1016/j.jcjd.2016.11.004 -
Journal of the American Heart... Oct 2015Observational studies evaluating the possible interaction between proton pump inhibitors (PPIs) and clopidogrel have shown mixed results. We conducted a systematic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Observational studies evaluating the possible interaction between proton pump inhibitors (PPIs) and clopidogrel have shown mixed results. We conducted a systematic review comparing the safety of individual PPIs in patients with coronary artery disease taking clopidogrel.
METHODS AND RESULTS
Studies performed from January 1995 to December 2013 were screened for inclusion. Data were extracted, and study quality was graded for 34 potential studies. For those studies in which follow-up period, outcomes, and multivariable adjustment were comparable, meta-analysis was performed.The adjusted odds or hazard ratios for the composite of cardiovascular or all-cause death, myocardial infarction, and stroke at 1 year were reported in 6 observational studies with data on individual PPIs. Random-effects meta-analyses of the 6 studies revealed an increased risk for adverse cardiovascular events for those taking pantoprazole (hazard ratio 1.38; 95% CI 1.12-1.70), lansoprazole (hazard ratio 1.29; 95% CI 1.09-1.52), or esomeprazole (hazard ratio 1.27; 95% CI 1.02-1.58) compared with patients on no PPI. This association was not significant for omeprazole (hazard ratio 1.16; 95% CI 0.93-1.44). Sensitivity analyses for the coronary artery disease population (acute coronary syndrome versus mixed) and exclusion of a single study due to heterogeneity of reported results did not have significant influence on the effect estimates for any PPIs.
CONCLUSIONS
Several frequently used PPIs previously thought to be safe for concomitant use with clopidogrel were associated with greater risk of adverse cardiovascular events. Although the data are observational, they highlight the need for randomized controlled trials to evaluate the safety of concomitant PPI and clopidogrel use in patients with coronary artery disease.
Topics: Clopidogrel; Coronary Artery Disease; Drug Interactions; Drug Therapy, Combination; Humans; Observational Studies as Topic; Odds Ratio; Patient Safety; Platelet Aggregation Inhibitors; Proton Pump Inhibitors; Risk Assessment; Risk Factors; Ticlopidine; Treatment Outcome
PubMed: 26514161
DOI: 10.1161/JAHA.115.002245 -
Clinical Therapeutics Feb 2017We performed a systematic review of patient-centered outcomes after the concomitant use of proton pump inhibitors (PPIs) and other drugs. (Review)
Review
PURPOSE
We performed a systematic review of patient-centered outcomes after the concomitant use of proton pump inhibitors (PPIs) and other drugs.
METHODS
We searched 4 databases in July 2016 to find studies that reported mortality and morbidity after the concomitant use of PPIs and other drugs. We conducted direct meta-analyses using a random-effects model and graded the quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation working group approach.
FINDINGS
We included data from 17 systematic reviews and meta-analyses, 16 randomized controlled trials, and 16 observational studies that examined the concomitant use of PPIs with medications from 10 drug classes. Low-quality evidence suggests that the use of PPIs is associated with greater morbidity when administered with antiplatelet drugs, bisphosphonates, antibiotics, anticoagulants, metformin, mycophenolate mofetil, or nelfinavir. Concomitant PPIs reduce drug-induced gastrointestinal bleeding and are associated with greater docetaxel and cisplatin response rates in patients with metastatic breast cancer. For demonstrated statistically significant relative risks and benefits from concomitant PPIs, the magnitudes of the effects are small, with <100 attributable events per 1000 patients treated, and the effects are inconsistent among specific drugs. Among individual PPIs, the concomitant use of pantoprazole or esomeprazole, but not omeprazole or lansoprazole, is associated with an increased risk for all-cause mortality, nonfatal myocardial infarction, or stroke. Clopidogrel is associated with a greater risk for myocardial infarction compared with prasugrel. Conflicting results between randomized controlled trials and observational studies and high risk for bias in the body of evidence lessened our confidence in the results.
IMPLICATIONS
Available evidence suggests a greater risk for adverse patient outcomes after the concomitant use of PPIs and medications from 9 drug classes and warns against inappropriate drug combinations.
Topics: Drug Interactions; Gastrointestinal Hemorrhage; Humans; Myocardial Infarction; Proton Pump Inhibitors; Randomized Controlled Trials as Topic; Risk; Stroke
PubMed: 28189362
DOI: 10.1016/j.clinthera.2017.01.011