Illustrative Cohort Flowcharts and Analysis in Acid Suppression Therapy Studies

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Detailed flowcharts of primary and secondary cohorts in studies related to acid suppression therapy, along with figures estimating the impact of various factors on outcomes like risk of death. The visuals depict the cohort selection process, exposure durations, confounding factors, and external adjustments made for accurate analysis.


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  1. Supplemental Figure 1: Flowchart of primary cohort Date of first acid suppression therapy prescription T0 With first H2 blockers or PPI prescriptions between October, 2006 and September, 2008 PPI With at least 1 outpatient serum creatinine before T0 H2 Blockers

  2. Supplemental Figure 2a: Flowchart of secondary cohort PPI vs no PPI October 01, 2006 T0 Change to PPI group at the time received PPI prescription PPI With no PPI prescription before October 2006 With at least 1 outpatient serum creatinine before T0 No PPI

  3. Supplemental Figure 2b: Flowchart of secondary cohort PPI vs no PPI no H2 blockers October 01, 2006 T0 Change to PPI group at the time received PPI prescription PPI With no PPI prescription before October 2006 No acid suppression therapy With at least 1 outpatient serum creatinine before T0 Excluded from cohort if received H2 blockers prescription

  4. Supplemental Figure 3: Duration of PPI exposure and risk of death among new PPI users in an older (less contemporary) sensitivity cohort (n=101,109)

  5. Supplemental Figure 4: Estimation of the impact of uncontrolled confounder using the rule-out approach 10.00 AHR=1.25 8.00 OR for confounder and PPI 6.00 4.00 2.00 0.00 0.00 2.00 4.00 6.00 8.00 10.00 HR for confounder and death

  6. Supplemental Figure 5: External adjustment to estimate the impact of 3 unmeasured confounders 30 External adjustment 25 Obese 20 Bias of HR for PPI to death in % 15 Smoking Assuming HR=1.30 Bias=3.96% 10 Assuming HR=2.80, Bias=4.23 % anticoagulants, antiplatelet agents, and non-streroidal anti-inflammatory drugs 5 0 Assuming HR=1.30, Bias=1.47 % -5 1 1.5 2 2.5 3 3.5 4 4.5 HR for confounder to death

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