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A. COHORT CONSTRUCTION AND EPISODE OVERLAP

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  eligible_operations                             : 2468

  distinct_patients                               : 2365

  patients_with_repeat_operations                 : 98

  first_operation_cohort                          : 2365

  first_operations_whose_window_overlaps_next     : 21



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B. CONCURRENT VERSUS NEWLY DETECTED AKI

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                               cohort  operations  patients  met_aki_criteria_ever  concurrent_at_landmark  concurrent_share_pct  at_risk_after_landmark  newly_detected_after_landmark

first operation per patient (primary)        2365      2365                    727                     531                  73.0                    1834                            196

all eligible operations (sensitivity)        2468      2365                    777                     570                  73.4                    1898                            207



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C. TIMING AND KDIGO LIMB OF NEWLY DETECTED AKI (primary cohort)

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                window  events  absolute_limb_involved  ratio_limb_only                                               note

 0-24 h after landmark     134                     131                3                 absolute-rise criterion still open

24-48 h after landmark      28                       0               28 absolute-rise criterion closed at 48 h from origin

  >48 h after landmark      34                       0               34 absolute-rise criterion closed at 48 h from origin



The absolute-rise criterion is only satisfiable up to 48 h from the time

origin, i.e. up to 24 h after the landmark. Beyond that point the composite

outcome can only be met by the ratio criterion, so the generating rule for

the outcome changes during follow-up.



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D. RENAL OBSERVATION PROCESS BY LACTATE STRATUM (primary cohort)

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lactate_stratum   n lactate_measurements_in_exposure_window post_landmark_creatinine_n hours_to_first_post_landmark_creatinine creatinine_per_day_of_followup

          <=1.9 714                           3.0 (1.0-7.0)              6.0 (5.0-8.0)                          8.2 (4.1-13.2)                  1.3 (1.1-1.6)

        2.1-3.0 476                           6.0 (3.0-9.0)              6.0 (4.0-8.0)                          9.1 (4.0-16.6)                  1.3 (1.0-1.7)

        3.8-5.9 541                          8.0 (6.0-10.0)             7.0 (4.0-10.0)                          6.9 (3.0-15.8)                  1.4 (1.1-2.0)

     8.6 capped 103                         10.0 (8.0-13.0)             7.0 (4.0-11.0)                          8.2 (1.9-16.8)                  1.4 (1.0-2.2)



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E. PRIMARY ASSOCIATION: CAUSE-SPECIFIC HAZARD OF NEWLY DETECTED AKI

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primary time-to-event set   : 1831 operations, 196 events, 7 competing deaths



                               cohort standard_errors    n  events              term   HR        ci      p

first operation per patient (primary)     model-based 1831     196       lac_2.1-3.0 1.16 0.79-1.69 0.4431

first operation per patient (primary)     model-based 1831     196       lac_3.8-5.9 1.48 1.04-2.10 0.0278

first operation per patient (primary)     model-based 1831     196    lac_8.6 capped 2.13 1.22-3.74 0.0080

first operation per patient (primary)     model-based 1831     196 per-stratum trend 1.25 1.08-1.45 0.0034

         all operations (sensitivity)  cluster-robust 1895     207       lac_2.1-3.0 1.16 0.80-1.68 0.4471

         all operations (sensitivity)  cluster-robust 1895     207       lac_3.8-5.9 1.54 1.09-2.17 0.0141

         all operations (sensitivity)  cluster-robust 1895     207    lac_8.6 capped 2.04 1.17-3.58 0.0124

         all operations (sensitivity)  cluster-robust 1895     207 per-stratum trend 1.26 1.08-1.46 0.0026



Cumulative incidence (Aalen-Johansen, death competing), primary cohort:

lactate_stratum  horizon_days  at_risk  cif_pct         ci

          <=1.9           1.0      663     5.64  3.94-7.34

          <=1.9           2.0      620     7.23  5.32-9.15

          <=1.9           3.0      594     7.84  5.85-9.84

          <=1.9           5.0      365     8.96 6.80-11.13

        2.1-3.0           1.0      435     6.55  4.32-8.78

        2.1-3.0           2.0      408     8.07 5.61-10.53

        2.1-3.0           3.0      377     8.99 6.39-11.59

        2.1-3.0           5.0      245     9.87 7.12-12.63

        3.8-5.9           1.0      476     9.11 6.68-11.54

        3.8-5.9           2.0      442    10.65 8.04-13.27

        3.8-5.9           3.0      410    11.06 8.40-13.73

        3.8-5.9           5.0      259    12.54 9.67-15.41

     8.6 capped           1.0       88    13.61 6.98-20.24

     8.6 capped           2.0       83    15.58 8.56-22.59

     8.6 capped           3.0       78    15.58 8.56-22.59

     8.6 capped           5.0       54    15.58 8.56-22.59



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F. SECONDARY: BINARY OUTCOME AMONG OPERATIONS WITH ASCERTAINABLE STATUS

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primary cohort   : n=1109, events=196

all operations   : n=1155, events=207



                              population standard_errors    n  events           term   OR        ci      p

ascertainable, first operation (primary)     model-based 1109     196    lac_2.1-3.0 1.15 0.76-1.74 0.5131

ascertainable, first operation (primary)     model-based 1109     196    lac_3.8-5.9 1.57 1.06-2.31 0.0235

ascertainable, first operation (primary)     model-based 1109     196 lac_8.6 capped 1.77 0.93-3.37 0.0822

           ascertainable, all operations  cluster-robust 1155     207    lac_2.1-3.0 1.14 0.75-1.73 0.5340

           ascertainable, all operations  cluster-robust 1155     207    lac_3.8-5.9 1.62 1.11-2.38 0.0130

           ascertainable, all operations  cluster-robust 1155     207 lac_8.6 capped 1.67 0.89-3.10 0.1079



Absolute risk among operations with ascertainable status (primary cohort):

lactate_stratum   n  events  risk_pct    exact_ci

          <=1.9 426      62     14.55 11.34-18.27

        2.1-3.0 290      49     16.90 12.77-21.72

        3.8-5.9 323      69     21.36 17.02-26.24

     8.6 capped  70      16     22.86 13.67-34.45



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G. EXPOSURE DEFINITIONS WITH DIFFERING MEASUREMENT OPPORTUNITY

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                              exposure_definition    n  events  top_stratum_OR         ci      p

                       peak within 24 h (primary) 1834     196            2.18  1.16-4.07 0.0150

                                 peak within 12 h 1834     196            2.43  1.25-4.69 0.0085

                                  peak within 6 h 1833     196            1.98  0.77-5.07 0.1555

                first value after the time origin 1834     196            2.22 0.43-11.54 0.3423

peak within 24 h, restricted to 4-9 lactate draws  869      71            6.98 2.00-24.33 0.0023



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H. 90-DAY MORTALITY ON THE CORRECTED COHORT

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                               cohort lactate_stratum   n  deaths  risk_pct   exact_ci

first operation per patient (primary)           <=1.9 815      11      1.35  0.68-2.40

first operation per patient (primary)         2.1-3.0 570      17      2.98  1.75-4.73

first operation per patient (primary)         3.8-5.9 765      40      5.23  3.76-7.05

first operation per patient (primary)      8.6 capped 215      22     10.23 6.52-15.08

all eligible operations (sensitivity)           <=1.9 835      11      1.32  0.66-2.34

all eligible operations (sensitivity)         2.1-3.0 584      18      3.08  1.84-4.83

all eligible operations (sensitivity)         3.8-5.9 813      46      5.66  4.17-7.48

all eligible operations (sensitivity)      8.6 capped 236      30     12.71 8.74-17.65



                               cohort           term  firth_OR profile_ci    n  events

first operation per patient (primary)    lac_2.1-3.0      2.27  1.06-5.03 2365      90

first operation per patient (primary)    lac_3.8-5.9      3.64  1.89-7.59 2365      90

first operation per patient (primary) lac_8.6 capped      9.48 4.45-21.23 2365      90

all eligible operations (sensitivity)    lac_2.1-3.0      2.38  1.13-5.23 2468     105

all eligible operations (sensitivity)    lac_3.8-5.9      3.94  2.08-8.10 2468     105

all eligible operations (sensitivity) lac_8.6 capped     11.12 5.46-24.11 2468     105



Outputs: <local path>\analysis\results\gate7

