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Table 2 Quality of evidence and risks of adverse effects associated with long-term proton pump inhibitors (PPIs)

From: When is proton pump inhibitor use appropriate?

  Potential adverse effect Nature of evidence Risk estimate
Causality established, idiosyncratic, rare Acute interstitial nephritis Observational, case–control OR 5.16 (2.21–12.05)
Causality proven but of minimal significance Fundic gland polyps Observational OR 2.2 (1.3–3.8) [6]
  B12 deficiency Observational, case–control OR 1.65 (1.58–1.73) [7]
Weak association, causality probable Small intestinal bacterial overgrowth Meta-analysis OR 2.28 (1.23–4.21) [8]
  Spontaneous bacterial peritonitis in cirrhotic patients Systematic review/meta-analysis OR 2.17 (1.46–3.23) [9]
Hepatic encephalopathy in cirrhotic patients Observational, case–control Dose dependent response, up to OR 3.01 (1.78–5.10) [10]
Clostridium difficile infection Observational cohort study OR 2.10 (1.20–3.50)
Iron deficiency Observational, case control OR 2.49 (2.35–2.64) [11]
Hypomagnesemia Observational, population-based cohort OR 2.00 (1.36–2.93)a [12]
Weak association, unproven causality Bone fracture Observational, case–control OR 2.65 (1.80–3.90)
Chronic kidney disease Observational, population-based cohort HR 1.50 (1.14–1.96) [13]
Dementia Prospective observational cohort HR 1.44 (1.36–1.52)
Myocardial infarction Observational, data mining HR 1.16 (1.09–1.24)b
Community-acquired pneumonia Systematic review/meta-analysis OR 1.49 (1.16–1.92)b
  1. Table adapted from Kia et al. [14]
  2. aThe risk of hypomagnesemia increases to OR 7.22 (1.69–30.83) in patients on concurrent loop diuretics
  3. bRisk ratio based on observational study; no association found in RCTs
  4. HR hazard ratio, OR odds ratio