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A host of recently published observational studies receiving wide coverage in the lay press suggest weak associations between proton-pump inhibitor (PPI) use and a wide variety of disorders. The key question is: Do these associations infer causality?
To answer this question, investigators applied well-established epidemiologic (Hill) criteria for determining causation to studies showing associations between PPIs and various disorders. Factors that suggest that these associations are not causal include:
Weak magnitudes of association
Inconsistent results across different studies
Outcomes are not specific to PPI treatment, resulting in a high potential for confounding
Lack of dose or duration gradient of effect
Questionable or absent biologic expla…