A Systematic Review of the Adverse Effects of Long-Term Proton Pump Inhibitor Use on the Gastrointestinal System in the Adult Population
Bibliographic record
Abstract
Proton pump inhibitors (PPIs) have been the first-line drug of choice for acid-peptic diseases for a long time. While literature is abundant on the efficacy of the drug, the adverse effects of this drug, especially in the gastrointestinal (GI) system, have been a topic of ongoing research interest. The long-term safety profile remains controversial. PPIs have been found to cause polyps, malignancies, and pre-cancerous conditions such as intestinal metaplasia, enteric infections such as Clostridium difficile, and microscopic colitis. Furthermore, long-term use is seen to be associated with decreased iron absorption and disruption in gut microbiota. This systematic review aims to perform a qualitative synthesis of the literature on the long-term adverse effects of PPIs on the GI system. This review utilized the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) 2020 guidelines. PubMed, PubMed Central (PMC), MEDLINE (Medical Literature Analysis and Retrieval System Online), MDPI (Multidisciplinary Digital Publishing Institute), and EBSCO (Elton B. Stephens Company) Library databases were searched for data published in the past 15 years, between 2010 and 2024, using Medical Subject Headings (MeSH) and keywords, and a total of 260 articles were identified. The PubMed search, which included articles from MEDLINE and PMC, yielded 216 results; the MeSH search included 11 articles. EBSCO and MDPI searches retrieved nine and 24 articles, respectively. After applying the eligibility criteria and performing qualitative synthesis, 50 articles were shortlisted. Quality assessment tools, such as the Assessment of Multiple Systematic Review (AMSTAR) for systematic reviews, the Cochrane bias assessment tool for randomized control trials, the scale for the assessment of narrative review articles (SANRA) checklist for narrative reviews, and the Newcastle-Ottawa Scale (NOS) for observational studies, and JBI critical appraisal checklist for case reports, were used. This review will help clinicians evaluate the risk-benefit factors of PPI use on a case-by-case basis, help mitigate unnecessary long-term prescription of PPI, and reduce the incidence of unwanted adverse events.
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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 | 0.010 | 0.037 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.008 | 0.009 |
| Bibliometrics | 0.009 | 0.012 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
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".