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Centre for Evidence-
Based Medicine

Completed Harm Worksheet for Evidence-Based Gastroenterology and Hepatology


O'Keefe GE, Gentilello LM, and Maier RV. Incidence of infectious complications associated with the use of Histamine-2-receptor antagonists in critically ill trauma patients. Annals of Surgery 1998;227:120-125.

Are the results of this harm study valid?

  1. Were there clearly defined groups of patients, similar in all important ways other than exposure to the treatment or other cause?
    Subjects were participants in an RCT. Randomization should distribute all other exposures equally. The only significant difference between groups was duration of ITU stay (longer for ranitidine patients). After controlling for other factors only treatment with ranitidine was associated with longer stay.
  2. Were treatment exposures and clinical outcomes measured the same ways in both groups (e.g., was the assessment of outcomes either objective (e.g., death) or blinded to exposure)?

Do the results satisfy some "diagnostic tests for causation"?

  1. Is it clear that the exposure preceded the onset of the outcome?
    Not clear. Treatment was commenced on admission to ITU but some patients may have entered ITU with infections. However randomisation should distribute these cases equally in both groups.
  2. Is there a dose-response gradient?
  3. Is there positive evidence from a "dechallenge-rechallenge" study?
  4. Is the association consistent from study to study?
    Not known
  5. Does the association make biological sense?
    Probably, given the widespread effects of H2 antagonists
  6. Are the valid results from this harm study important?

    Adverse Outcome Totals
    Present (Case) Absent (Control)
    Exposed to the Treatment Ranitidine (Cohort)




    a + b

    Sucralfate (Cohort)




    c + d

    a + c

    b + d

    a + b + c + d

    In this study:

    Relative Risk (RR) = 75.5%/55.3%
    = 1.36
    p = 0.04

    NB this differs from the RR presented in the text!!

    Should these valid, potentially important results of a critical appraisal about a harmful treatment change the treatment of your patient?

    1. Can the study results be extrapolated to your patient?
    2. What are your patient's risks of the adverse outcome?
      To calculate the NNH (the Number of patients you Need to treat to Harm one of them) for any Odds Ratio (OR) and your Patient's Expected Event Rate for this adverse event if they were NOT exposed to this treatment (PEER):
      NNH = (PEER(OR-1)+1)/(PEER(OR-1)x(1-PEER))
      If we assume our patient is like the average individual in this, then her Absolute Risk Increase in infectious complications whilst in hospital is
      75.5% - 55.3%
      = 20.2%
      and 1/.202 gives an NNH of 5.
    3. What are your patient's preferences, concerns and expectations from this treatment?
      Need to be determined.
    4. What alternative treatments are available?
      Sucralfate is clearly one alternative. Proton pump inhibitors have not been investigated in this study.

    Additional Notes

    The evidence favours the use of sucralfate rather than ranitidine in this situation leading us to chose to use a drug that we would not normally prescribe for NSAID induced gastric erosions.

    Continue to CAT