{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T09:06:19Z","timestamp":1790240779433,"version":"4.1.0"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      Evidence on proton pump inhibitor (PPI) exposure and\n                      <jats:italic>Clostridioides difficile<\/jats:italic>\n                      infection (CDI) remains difficult to interpret because published estimates arise from heterogeneous target outcomes, risk sets, exposure contrasts, time structures, and ascertainment procedures. We evaluated whether a result-specific outcome-observability framework could make these differences explicit without using effect direction or statistical significance as classification criteria.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study design and setting<\/jats:title>\n                    <jats:p>We conducted a structured methodological audit of evidence sources evaluating PPI exposure and CDI-related outcomes. Original observational reports and observational or randomized trial-based meta-analytic reports were retained as distinct evidence types.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>For each eligible reported result, we extracted the target outcome and risk set, PPI exposure contrast, time zero and exposure\/outcome windows, outcome ascertainment, effect measure, event information, and data-source dependence. Four observability domains were coded as explicit\/target-aligned (E), partial\/proxy-based (P), unclear\/misaligned (U), or aggregate\/mixed (A). Codes were not summed, weighted, or dichotomized. Meta-analytic reports were described as aggregate evidence, and odds ratios, risk ratios, and hazard ratios were not treated as quantitatively interchangeable.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Eleven evidence sources contained an eligible PPI exposure contrast for a CDI-related outcome after one report was excluded during result-level reassessment. Eight addressed incident CDI, one addressed C. difficile detection without uniform confirmation of clinical CDI, one addressed severity among patients with established CDI, and one addressed mortality among patients with established CDI. Nine estimates were odds ratios, one was a risk ratio, and one was a hazard ratio. Temporal alignment and outcome ascertainment varied across original reports, while three meta-analytic reports combined heterogeneous component definitions. Two Swedish registry reports were treated as one overlapping data-source cluster.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The included estimates did not represent one common PPI-CDI estimand. A result-specific outcome-observability profile can identify methodological non-comparability, but it is not a score of study quality, causal validity, statistical power, or likelihood of a positive result. The framework should be interpreted as a descriptive methodological audit rather than evidence that observability conditions explain the direction of reported associations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1956355","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T08:36:33Z","timestamp":1790238993000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Outcome observability in evidence on proton pump inhibitor-associated clostridioides difficile outcomes: a result-specific methodological audit"],"prefix":"10.3389","volume":"13","author":[{"given":"Jiawang","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Pathophysiology, College of Basic Medical Science, Clinical Medical College of Anhui Medical University","place":["Hefei, 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