Evidence-Based Journal Club: An Overview

1. Evidence-Based Journal Club: An Overview Akbar Soltani MD. Tehran University of Medical Sciences (TUMS) Endocrine and Metabolism Research Center (EMRC) Evidence-Based Medicine Research Center (EBMRC) Shariati Hospital www.soltaniebm.com www.ebm.ir

2. Agenda • Introduction and problems • Conventional Vs Evidence-Based Journal club • What is CAT? • Examples • Goals for journal club • Limitations of CATs • Summary

3. The Problems • We need information to make decisions. • How often? From 5 times for every in-patient. To 2 times for every 3 out-patients. • We get less than a third of it. • To keep up to date it is estimated: I need to read 17 articles a day, 365 days a year. Covell DG, Uman GC, Manning PR: Information needs in office practice: Are they being met? Ann Intern Med 1985;103:596-9.

4. Sample scenario • In ICU patients, do you suggest tight blood glucose control? • Wrong format!

5. Traditional approach • Pathophysiologic approach • Recency bias (in a paper that i read last night or a case that i had ,… • Rarity bias (complications,…) • Personal habit bias • Territory bias • In my experience (selection bias , information bias,…)

6. Traditional journal club • Journal clubs are dying or dead in many clinical centers, especially when they rely on a rotating schedule by which members are asked to summarize the latest issues of pre-assigned journals. • Postman • Usefulness?

7. Information Sources for Use at the Point of Care Usefulness = Relevance x Validity Work POEM EBM

8. Evidence Based Medicine 1.Translate these needs into answerable questions 2. Trackdown the best evidence to answer them 3. Appraise that evidence for its validity (closeness to the truth) and applicability (usefulness in our clinical practices) 4.Integrate that evidence with our clinical expertise and apply it in practice (MDM) 5. Evaluate our performance

9. Evidence based journal club part 1 • Journal club members describe patientswho exemplify clinical situations which they are uncertain how best to diagnose or manage. • This discussion continues until there is consensus that a particular clinical problem, is worth the time and effort necessary to find its solution.

11. Pt Name: Mr, XY Learner : Resident Patient: Elderly, Stroke, HTN… Exposure, Intervention : Carotid Stenosis (+/- comparison): Outcome: Risk of (dying from) recurrent Stroke Date and Place to be filled: Discuss: Search strategy Search results Validity Importance of the valid results Can you apply this to your pt

12. PICO P: Among patients who are in ICU I: does the use of intensive insulin therapy to maintain tight blood glucose control C: standard therapy O:lead to improvements in ICU outcome?reduce their risk of dying? Right format

13. part 2 Evidence based journal club The results of the evidence search on the previous session’s problem are shared in the form of photocopies of the abstractsof four to six systematic reviews, original articles or other evidence.

14. Evidence based journal club part 3 The main part of the journal club session is spent in a critical appraisal of the evidence found in response to a clinical question posed two sessions ago and selected for detailed study last session.

15. Evidence Based Journal Club part 3 Making Your Presentation

16. Agenda • Introduction and problems • Conventional Vs Evidence-Based Journal club • What is CAT? • Examples • Goals for journal club • Limitations of CATs • Summary

17. Definition • A Critically Appraised Topic (CAT) is “a one- or two page ‘summary of a search and critical appraisal of the literature related to a focused clinical question, which should be kept in an easily accessible place so that it can be used to help make clinical decisions’” .

18. Six Necessary Elements of CATs • 1. Date of completion (of the CAT) • 2. Question • The person or problem being addressed • The intervention or exposure being considered • The comparison of the intervention or exposure, when relevant • The outcomes of interest. • 3. Clinical Bottom Line (CAT summary should include applicability of results to your client) • 4. Evidence (CAT summary should include a summary of evidence) • 5. Gold Standard (For Diagnosis or Screening - compare to best test out there; for Risk and Harm - compare to existing treatments. • 6. Notes (important issues, your reflections).

19. Agenda • Introduction and problems • Conventional Vs Evidence-Based Journal club • What is CAT? • Examples • Goals for journal club • Limitations of CATs • Summary

21. Bottom line read in seconds

22. For every 29 patients given intensive insulin therapy, to keep glucose 4.4-6.1 mmol.l-1, compared to standard therapy, one less patient dies in ICU (95% CI 17 to 101). Increased risk of biochemical, but not symptomatic, hypoglycaemia. Level 1+ evidence Get bottom line quickly (seconds) Tight blood glucose control improves ICU survival

23. For every 29 patients given intensive insulin therapy, to keep glucose 4.4-6.1 mmol.l-1, compared to standard therapy, one less patient dies in ICU (95% CI 17 to 101). Increased risk of biochemical, but not symptomatic, hypoglycaemia. Level 1+ evidence Get bottom line quickly (seconds) Declarative title Tight blood glucose control improves ICU survival

24. For every 29 patients given intensive insulin therapy, to keep glucose 4.4-6.1 mmol.l-1, compared to standard therapy, one less patient dies in ICU (95% CI 17 to 101). Increased risk of biochemical, but not symptomatic, hypoglycaemia. Level 1+ evidence Get bottom line quickly (seconds) Tight blood glucose control improves ICU survival Summary of treatment effect, and level of evidence

25. Citation details and search strategy, read in hours

26. Read the study (for hours) Citation/s:Intensive Insulin Therapy in Critically Ill Patients NEJM 2001; 345: 1359 - 67. Three-part Clinical Question: In ICU patients, does the use of intensive insulin therapy to maintain tight blood glucose control, compared to standard therapy, lead to improvements in ICU outcome?Search Terms: 1. exp sepsis/ or severe sep$.tw or sept$.tw or sepsi$.tw (50301), 2. exp critical care/ or critical ca$.tw or intensive ca$.tw (22553), 3. exp insulin or insuli$.tw (50202), 4. 1 and 2 and 3 (25), 5. therapy filter (652119), 6. 4 and 5 (17)

27. Read the study (for hours) Hyperlink to journal web site Citation/s:Intensive Insulin Therapy in Critically Ill Patients NEJM 2001; 345: 1359 - 67. Three-part Clinical Question: In ICU patients, does the use of intensive insulin therapy to maintain tight blood glucose control, compared to standard therapy, lead to improvements in ICU outcome?Search Terms: 1. exp sepsis/ or severe sep$.tw or sept$.tw or sepsi$.tw (50301), 2. exp critical care/ or critical ca$.tw or intensive ca$.tw (22553), 3. exp insulin or insuli$.tw (50202), 4. 1 and 2 and 3 (25), 5. therapy filter (652119), 6. 4 and 5 (17)

28. Read the study (for hours) Citation/s:Intensive Insulin Therapy in Critically Ill Patients NEJM 2001; 345: 1359 - 67. Three-part Clinical Question: In ICU patients, does the use of intensive insulin therapy to maintain tight blood glucose control, compared to standard therapy, lead to improvements in ICU outcome?Search Terms: 1. exp sepsis/ or severe sep$.tw or sept$.tw or sepsi$.tw (50301), 2. exp critical care/ or critical ca$.tw or intensive ca$.tw (22553), 3. exp insulin or insuli$.tw (50202), 4. 1 and 2 and 3 (25), 5. therapy filter (652119), 6. 4 and 5 (17) Search terms used, for reference, and to repeat in future

29. Trial details read in minutes

30. Read trial details (minutes) The Study: Single-blinded randomised controlled trial with intention-to-treat. The Study Patients: All patients admitted to a surgical ICU in Belgium (62% had cardiac surgery). Median APACHE 9 (IQ range 7-13). Median TISS 43. 13% had diabetes. Randomised at ICU admission. All patients given iv glucose on admission, next day: parenteral / enteral nutrition or enteral nutrition alone. Matched for blood glucose at admission. Control groupgroup (N = 783; 783 analysed): Insulin infusion (1 U.ml -1) started if glucose > 12 mmol.l-1, and titrated to range 10.0 - 11.1 mmol.l-1. Blood glucose checked 1 - 4 hourly, algorithm used and discussion with study clinician not involved in patient care. Experimental group (N = 765; 765 analysed): Insulin infusion (1 unit/ml) started if glucose > 6.1 mmol.l-1, and titrated to keep glucose in range 4.4 - 6.1 mmol.l-1. Blood glucose checked 1 - 4 hourly, algorithm used and discussion with study clinician not involved in patient care.

31. Read trial details (minutes) Key design validity features The Study: Single-blinded randomised controlled trial with intention-to-treat. The Study Patients: All patients admitted to a surgical ICU in Belgium (62% had cardiac surgery). Median APACHE 9 (IQ range 7-13). Median TISS 43. 13% had diabetes. Randomised at ICU admission. All patients given iv glucose on admission, next day: parenteral / enteral nutrition or enteral nutrition alone. Matched for blood glucose at admission. Control groupgroup (N = 783; 783 analysed): Insulin infusion (1 U.ml -1) started if glucose > 12 mmol.l-1, and titrated to range 10.0 - 11.1 mmol.l-1. Blood glucose checked 1 - 4 hourly, algorithm used and discussion with study clinician not involved in patient care. Experimental group (N = 765; 765 analysed): Insulin infusion (1 unit/ml) started if glucose > 6.1 mmol.l-1, and titrated to keep glucose in range 4.4 - 6.1 mmol.l-1. Blood glucose checked 1 - 4 hourly, algorithm used and discussion with study clinician not involved in patient care.

32. Read trial details (minutes) The Study: Single-blinded randomised controlled trial with intention-to-treat. The Study Patients: All patients admitted to a surgical ICU in Belgium (62% had cardiac surgery). Median APACHE 9 (IQ range 7-13). Median TISS 43. 13% had diabetes. Randomised at ICU admission. All patients given iv glucose on admission, next day: parenteral / enteral nutrition or enteral nutrition alone. Matched for blood glucose at admission. Control groupgroup (N = 783; 783 analysed): Insulin infusion (1 U.ml -1) started if glucose > 12 mmol.l-1, and titrated to range 10.0 - 11.1 mmol.l-1. Blood glucose checked 1 - 4 hourly, algorithm used and discussion with study clinician not involved in patient care. Experimental group (N = 765; 765 analysed): Insulin infusion (1 unit/ml) started if glucose > 6.1 mmol.l-1, and titrated to keep glucose in range 4.4 - 6.1 mmol.l-1. Blood glucose checked 1 - 4 hourly, algorithm used and discussion with study clinician not involved in patient care. Intervention (s)

33. Read trial details (minutes)

34. Read trial details (minutes) Outcome (s) of interest

35. Read trial details (minutes) Control group event rate

36. Read trial details (minutes) Control group event rate Experimental group event rate

37. Read trial details (minutes) Relative risk reduction

38. Read trial details (minutes) Relative risk reduction Absolute risk reduction

39. Read trial details (minutes) Relative risk reduction Absolute risk reduction Negative risk reduction = an increase !

40. Read trial details (minutes) Number needed to treat to benefit

41. Read trial details (minutes) Number needed to treat to benefit Number needed to treat to harm

42. Particularised for your own practice, integrate with your expertise

43. Remember to particularise for your patient • Predominantly cardiac surgery patients (59% had CABG) could this group be more like the DIAGMI group of patients? • No, main effect was reduction in deaths due to multiple organ failure due a proven septic focus. • No details provided of algorithm in article – aimed for normoglycaemia. Now available via NEJM website. • Reduction in sepsis and critical illness neuropathy, but are EMG recordings are a surrogate end-point. • Insulin is an inexpensive drug, especially compared to activated protein C, and may be more widely applicable. • Only single episodes of hypoglycaemia reported with no physical complications. • We have a higher MR, death (and death due to sepsis) is more common per 100 patients, we need to treat fewer patients to save a life = NNT / f = 29 / 3 = 10. Note this is a rough estimate.

44. Antioxidant vitamins did not reduce death, vascular events, or cancer in high risk patientspresenter: endocrine fellowsEMRC

45. Q • Inpatients with a high risk of death ,does antioxidant supplementation reduce death,vascular events,and cancer?

46. Design • RCT • Blinded • F/U 5 y • Setting: 69 UK hospitals

47. Patients • 20536 patients who were 40-80y(28%were >70y ,75%men) • Total cholestrol >3.5mmol/l • 5y risk of death because history of CHD ,oclusive disease of noncoronary arteies,DM,or treated HTN

48. Exclusion Criteria • Indication of statin therapy • Abnormal LFT or RFT • Severe heart failure • COPD • Cancer • Indication Of high dose vitamin E f/u :99.7%

49. Intervention • Patients : Synthetic vitamin E 600 mg/d plus vitaminC 250 mg/d ,B-caroten20mg/d (n=10269) • Placebo(10267)

50. Outcome • All cause,vascular or non vascular mortality • Secondary outcome;coronary(non fatal MI or death from CHD) stroke ; revascularisation cancer