Hot Topics in Internal Medicine

1. Hot Topics in Internal Medicine Molly Cooke MD Chair-elect, Board of Governors

2. Questions • Does intensive glucose control improve outcomes in Type 2 diabetes? • What is the optimal prophylaxis to prevent contrast-induced acute kidney injury? • Do inhaled medications increase morbidity and/or mortality in patients with COPD?

3. Questions • Does intensive glucose control improve outcomes in Type 2 diabetes? • What is the optimal prophylaxis to prevent contrast-induced acute kidney injury? • Do inhaled medications increase morbidity and/or mortality in patients with COPD?

4. Does intensive glucose control improve outcomes in Type 2 diabetes? • ACCORD Effects of intensive glucose lowering in Type 2 diabetes N Engl J Med 2008; 358: 2545-59 • The ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with Type 2 diabetes. N Engl J Med 2008; 358:2560-72 • Duckworth W et al. Glucose control and vascular complications in veterans with Type 2 diabetes. N Engl J Med 2009; 360:129-39.

5. Background

6. ACCORD 2008 • RCT 10,251 patients • Intensive therapy HgbA1c 6.4% vs. standard therapy HgbA1c 7.5% • Terminated early after 3.5 years

7. ADVANCE 2008 RCT 11,140 patients Median follow up 5 years Intensive control HgbA1c 6.5% Standard control HgbA1c 7.3%

8. ADVANCE 2008

9. Glucose control and vascular complications (Duckworth) 2008 • RCT 1791 veterans, median follow up 5.6 years • Intensive therapy HgbA1c 6.9% vs. standard therapy HgbA1c 8.4% • Adverse effects, particularly hypoglycemia, 17.6% in standard therapy vs. 24.1% in intensive therapy

10. Questions • Does intensive glucose control improve outcomes in Type 2 diabetes? • What is the optimal prophylaxis to prevent contrast-induced acute kidney injury? • Do inhaled medications increase morbidity and/or mortality in patients with COPD?

11. Risk of death associated with medications for recently diagnosed COPD Lee 2008

12. Inhaled corticosteroids in patients with stable COPD Drummond Ann Intern Med 2008

13. Long-term daily erythromycin and COPD exacerbations Seemungal Am J Resp Crit Care Med 2008

14. Questions • Does intensive glucose control improve outcomes in Type 2 diabetes? • What is the optimal prophylaxis to prevent contrast-induced acute kidney injury? • Do inhaled medications increase morbidity and/or mortality in patients with COPD?

15. Summary • Does intensive glucose control improve outcomes in Type 2 diabetes? • No, and it is associated with excess morbidity and mortality • What is the optimal prophylaxis to prevent contrast-induced acute kidney injury? • Discontinuation of NSAID’s, pre-procedure hydration, possibly possibly sodium bicarbonate > sodium chloride, probably N-acetylcysteine • Do inhaled medications increase morbidity and/or mortality in patients with COPD? • Inhaled steroids are associated with increased pneumonia • Ipatropium may be associated with increased mortality • Daily macrolide prophylaxis appears to decrease exacerbations

16. Acute Kidney Injury • Sensitivity and specificity of a single emergency department measurement of urinary neutrophil gelatinase-associated lipocalin for diagnosing acute kidney injury Nickolas T, et al. Ann Intern Med 2008; 148(11):810-819

17. Neutrophil Gelatinase-Associate Lipocalin (NGAL) • Small protein belonging to the lipocalin family of proteins • Expressed by neutrophils and various epithelia, including the renal proximal tubules • Functions are not completely understood • Upregulated in cells under “stress” • Released from secondary granules of activated neutrophils • Initially proposed as a marker for infections and certain adenocarcinomas • NGAL has an early and dramatic rise in urine after renal injury

19. Print Nikolas et al Ann Intern Med 2008

20. A single measurement of urinary NGAL helps to distinguish acute injury from normal renal function, prerenal azotemia, and CKI • This may help patient disposition from the ED to home, observation unit for hydration, versus full admission

21. Acute kidney injury with iodinated contrast McCullough PA. Crit Care Med 2008; 36(4Suppl):S204-211

22. Acute Kidney Injury

23. Meta-analysis - Nephrotoxicity of high- and low- osmolality iodinated contrast medium Barrett 1993, as presented in McCullough 2008

24. Acute Kidney Injury Prevention, incidence, and outcomes of contrast-induced acute kidney injury Weisbord SD, et al. Arch Intern Med 2008; 168(12):1325-32

25. Use of preventive therapy is variable Weisbord SD, et al. Arch Intern Med 2008; 168(12):1325-32

28. Acute Kidney Injury (AKI) Meta-analysis: effectiveness of drugs for preventing contrast-induced nephropathy Kelly AM, et al. Ann Intern Med 2008; 148(4):284-294.

29. Dopamine Fenoldopam Furosemide N-Acetylcysteine 0.62 (0.44-0.88) Theophylline

30. Acute Kidney Injury (AKI) • Bottomline • CIAKI is associated with poor outcomes • Need to standardize contrast induced acute kidney injury (CIAKI) prophylaxis • Patients with risk factors for CIAKI (chronic kidney disease and diabetes) should receive non-ionic contrast • NAC is more effective in preventing CIAKI injury than hydration alone

31. Summary • Does intensive glucose control improve outcomes in Type 2 diabetes? • What is the optimal prophylaxis to prevent contrast-induced acute kidney injury? • Do inhaled medications increase morbidity and/or mortality in patients with COPD?

32. Systematic abstracting of papers from > 130 journals • Ratings of each article for quality and newsworthiness • Customizable email alerts • Cumulative searchable database of alerts from 2003 https://plus.mcmaster.ca/acpjc/Registration.aspx