Evidence Based Journal Club: An Overview Akbar Soltani. MD, MS, Endocrinologist 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

Agenda Introduction: (problems, traditional approach) Traditional Vs Evidence Based Journal club What is CAT? Examples Goals for journal club Limitations of CATs Summary

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.

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

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,…)

Agenda Introduction: (problems, traditional approach) Traditional Vs Evidence Based Journal club What is CAT? Examples Goals for journal club Limitations of CATs Summary

Usefulness? Traditional journal club Postman 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?

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

Evidence Based Medicine 1.Translate these needs into answerable questions 2. Track down 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 5. Evaluate our performance

Evidence based journal club part 1 Journal club members describe patients who 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.

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

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

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.

Making Your Presentation Evidence Based Journal Club part 3 Making Your Presentation

Agenda Introduction: (problems, traditional approach) Traditional Vs Evidence Based Journal club What is CAT? Examples Goals for journal club Limitations of CATs Summary

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’” .

Agenda Introduction: (problems, traditional approach) Traditional Vs Evidence Based Journal club What is CAT? Examples Goals for journal club Limitations of CATs Summary

Bottom line read in seconds

Get bottom line quickly (seconds) Tight blood glucose control improves ICU survival 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 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 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 Summary of treatment effect, and level of evidence

Citation details and search strategy, read in hours

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)

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)

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

Trial details read in minutes

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 group group (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.

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 group group (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.

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 group group (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)

95% Confidence Intervals Read trial details (minutes) Outcome Time to outcome CER EER RRR ARR NNT Mortality ICU 63/783 0.08 35/765 0.046 43% 0.034 29 95% Confidence Intervals 0.01 to 0.058 17 to 101 Hypoglycaemia (biochemical) 6/783 0.008 39/765 0.059 -61% -0.043 -23 -0.06 to -0.026 -38 to -17

95% Confidence Intervals Read trial details (minutes) Outcome Time to outcome CER EER RRR ARR NNT Mortality ICU 63/783 0.08 35/765 0.046 43% 0.034 29 95% Confidence Intervals 0.01 to 0.058 17 to 101 Hypoglycaemia (biochemical) 6/783 0.008 39/765 0.059 -61% -0.043 -23 -0.06 to -0.026 -38 to -17 Outcome (s) of interest

95% Confidence Intervals Read trial details (minutes) Control group event rate Outcome Time to outcome CER EER RRR ARR NNT Mortality ICU 63/783 0.08 35/765 0.046 43% 0.034 29 95% Confidence Intervals 0.01 to 0.058 17 to 101 Hypoglycaemia (biochemical) 6/783 0.008 39/765 0.059 -61% -0.043 -23 -0.06 to -0.026 -38 to -17

95% Confidence Intervals Read trial details (minutes) Control group event rate Experimental group event rate Outcome Time to outcome CER EER RRR ARR NNT Mortality ICU 63/783 0.08 35/765 0.046 43% 0.034 29 95% Confidence Intervals 0.01 to 0.058 17 to 101 Hypoglycaemia (biochemical) 6/783 0.008 39/765 0.059 -61% -0.043 -23 -0.06 to -0.026 -38 to -17

95% Confidence Intervals Read trial details (minutes) Relative risk reduction Outcome Time to outcome CER EER RRR ARR NNT Mortality ICU 63/783 0.08 35/765 0.046 43% 0.034 29 95% Confidence Intervals 0.01 to 0.058 17 to 101 Hypoglycaemia (biochemical) 6/783 0.008 39/765 0.059 -61% -0.043 -23 -0.06 to -0.026 -38 to -17

95% Confidence Intervals Read trial details (minutes) Relative risk reduction Absolute risk reduction Outcome Time to outcome CER EER RRR ARR NNT Mortality ICU 63/783 0.08 35/765 0.046 43% 0.034 29 95% Confidence Intervals 0.01 to 0.058 17 to 101 Hypoglycaemia (biochemical) 6/783 0.008 39/765 0.059 -61% -0.043 -23 -0.06 to -0.026 -38 to -17

95% Confidence Intervals Read trial details (minutes) Relative risk reduction Absolute risk reduction Outcome Time to outcome CER EER RRR ARR NNT Mortality ICU 63/783 0.08 35/765 0.046 43% 0.034 29 95% Confidence Intervals 0.01 to 0.058 17 to 101 Hypoglycaemia (biochemical) 6/783 0.008 39/765 0.059 -61% -0.043 -23 -0.06 to -0.026 -38 to -17 Negative risk reduction = an increase !

95% Confidence Intervals Read trial details (minutes) Number needed to treat to benefit Outcome Time to outcome CER EER RRR ARR NNT Mortality ICU 63/783 0.08 35/765 0.046 43% 0.034 29 95% Confidence Intervals 0.01 to 0.058 17 to 101 Hypoglycaemia (biochemical) 6/783 0.008 39/765 0.059 -61% -0.043 -23 -0.06 to -0.026 -38 to -17

95% Confidence Intervals Read trial details (minutes) Number needed to treat to benefit Outcome Time to outcome CER EER RRR ARR NNT Mortality ICU 63/783 0.08 35/765 0.046 43% 0.034 29 95% Confidence Intervals 0.01 to 0.058 17 to 101 Hypoglycaemia (biochemical) 6/783 0.008 39/765 0.059 -61% -0.043 -23 -0.06 to -0.026 -38 to -17 Number needed to treat to harm

Particularised for your own practice, integrate with your expertise

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.

Critically Appraised Topic (CAT) A one page summary: Declarative title Bottom line Question Name of paper Search terms Design Setting Patients Intervention Outcome Measures Results Table Commentary and Conclusion

Making Your Presentation The clinical question.  How it was formed. (5 min) HOW you found what you found. (2 min) WHAT you found. (3 min) The VALIDITY & APPLICABILITY of what you found. (7 min) How what you found will ALTER your MANAGEMENT of the patient. (8 min)

Agenda Introduction: (problems, traditional approach) Traditional Vs Evidence Based Journal club What is CAT? Examples Goals for journal club Limitations of CATs Summary

Goals for Journal Club Be able to develop a well-built (PICO) question from a clinical scenario  Understand key search terms and use them to identify relevant literature Critically appraise an article in the style outlined by Sackett et al.  Apply the results of the EBM process to the care of a patient (clinical reasoning)

Goals for Journal Club Present journal club in an educational fashion, giving equal emphasis to both the clinical content and the EBM process  Highlight one aspect of study design or statistics during the journal club, making it relevant and useful to those in attendance. Contribute a well-done Critically-Appraised Topic (CAT) to the files 

Agenda Introduction: (problems, traditional approach) Traditional Vs Evidence Based Journal club What is CAT? Examples Goals for journal club Limitations of CATs Summary

Limitations 􀁺First is the limited applicability of individual CAT. –Created in busy practice –It is a single piece of evidence summarized –Incomplete, non-representative of the entire body of evidence 􀁺Individual CATs can be wrong –First appear as drafts, without peer review. –May contain inferior evidence, or errors of fact, calculation, or interpretation. 􀁺They have a short “half life” –be obsolete as new evidence becomes available.

Agenda Introduction: (problems, traditional approach) Traditional Vs Evidence Based Journal club What is CAT? Examples Goals for journal club Limitations of CATs Summary

Bottom Line! 1. The new challenge in medicine is information mastery. (Vs content expert) 2. In order to survive in the information age every clinician needs tools, based on the information mastery equation: Usefulness = (Relevance x Validity)/ Work 3. CATs have evolved to be highly useful !

Thank you