Umbrella review of 42 systematic reviews with meta‐analyses: the safety of proton pump inhibitors
Bibliographic record
Abstract
BACKGROUND: Proton pump inhibitors (PPIs) are widely used to treat and prevent acid-related disorders. Despite high efficacy, PPI safety has been increasingly scrutinised. However, no comprehensive review summarising investigations of various adverse events is available. AIMS: To perform an umbrella review to comprehensively assess associations between adverse events and PPI use. METHODS: In accordance with PRISMA, an umbrella review of systematic reviews with meta-analyses was conducted. PubMed and EMBASE were searched from 2015 to July 2019. AMSTAR 2 and GRADE were used to assess quality and certainty of evidence. Author-reported quality assessments were also reviewed. RESULTS: Forty-two systematic reviews with meta-analyses, supported predominantly by observational evidence, were included. The most comprehensive studies reported statistically significant associations with PPI use for several outcomes, including: fractures (eg, hip; RR = 1.20; 95% CI = 1.14-1.28; n = 2 103 800), kidney disease (eg, acute kidney injury; RR = 1.61; 95% CI = 1.16-2.22; n = 2 396 640), infections (eg, Clostridioides difficile; OR = 1.99; 95% CI = 1.73-2.30; n = 356 683), gastric cancer (OR = 2.50; 95% CI = 1.74-3.85; n = 943 070) and gastrointestinal events (eg, fundic gland polyps; OR = 2.46; 95% CI = 1.42-4.27; n = 40 218). No associations with non-gastric cancers, or neurological disease were concluded, with conflicting evidence for cardiovascular outcomes. Certainty based on GRADE was very low for most outcomes. CONCLUSIONS: This review identified several published associations between PPIs and adverse outcomes, however, further investigation is needed to understand their clinical significance and the likelihood of causal relationship. If higher quality evidence is generated substantiating the potential risks, it may be necessary for clinicians to consider alternative treatment strategies, especially when PPI efficacy is suboptimal.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.049 | 0.141 |
| Meta-epidemiology (narrow) | 0.005 | 0.003 |
| Meta-epidemiology (broad) | 0.024 | 0.034 |
| Bibliometrics | 0.028 | 0.021 |
| Science and technology studies | 0.002 | 0.002 |
| Scholarly communication | 0.006 | 0.004 |
| Open science | 0.004 | 0.005 |
| Research integrity | 0.004 | 0.002 |
| Insufficient payload (model declined to judge) | 0.014 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".