Articles from the past year or so that may change your practice

1. Articles from the past year or so that may change your practice Mark Graber, MD FACEP Professor Christopher Hogrefe, MD Assistant Professor Departments of Family and Emergency Medicine University of Iowa Carver College of Medicine

2. Sacred Cows

4. Quassem et al. Appropriate Use of Screening and Diagnostic Tests to FosterHigh-Value, Cost-Conscious Care. Ann Intern Med. 2012;156:147-149. How can we reduce health care costs by using only high value screening and diagnostic tests?

5. Delphi technique in which “experts” come to a consensus on each item.

6. BOGSAT

7. GOBSAT

8. What did they decide are money wasters? 37 tests…. • Cath in patients with stable angina. • “Routine” EKG. • PAP smear for those >65 years of age or those who have had a hysterectomy for benign disease. • Colon cancer screening in those >75 years of age. • Almost any routine pre-operative testing. • Sinus imaging. • D-dimer in those who are not low risk. • Imaging in those with syncope and normal neuro exam. • Imaging studies in those with non-specific low back pain.

9. And, in fact • Back Pain: http://archive.ahrq.gov/research/jan03/0103RA9.htm • Cath in stable angina: Arch Intern Med. 2012;172(4):312-319 • D-dimer:Newman, D.H., et al, Ann Emerg Med 57(6):622, June 2011

10. Schjerning Olsen A-M et al. Duration of treatment with nonsteroidal anti-inflammatory drugs and impact on risk of death and recurrent myocardial infarction in patients with prior myocardial infarction: A nationwide cohort study. Circulation 2011 May 24; 123:2226. C

11. Even short term NSAIDS lead in increased Cardiovascular Risk • >83,000 Danish Registry • Mean age 68, 63% men • Looked at hospitalization after FIRST MI in relationship to NSAIDS • So…these patients had known CAD • 42% received an NSAID • 42% of the whole cohort had death or recurrent MI

12. Hazard Ratio for MI in 1st week of NSAID use: 1.45 (45% increase) • Hazard Ratio going forward >90 days: 1.55 (55% increase) • All NSAIDS except Naproxen (statistical fluke??)Naproxen does seem to be the drug of choice, though.

13. Bangalore S et al. Angiotensin receptor blockers and risk of myocardial infarction: Meta-analyses and trial sequential analyses of 147 020 patients from randomised trials. BMJ 2011 Apr 26; 342:d2234. (http://dx.doi.org/10.1136/bmj.d2234)

15. We know not all BP lowering is equal. ALLHAT, Beta-blockers, alpha-blockers

16. What we know • ARBS don’t decrease mortality in those with diabetic nephropathy. BMJ 2004 Oct 9; 329:828-31 • Some hint ARBS worsen cardiovascular outcomes. • „The ARBS-MI Paradox“

17. This Study • Well done meta-analysis of 37 trials (with 39 arms) of ARBs vs Placebo or active drug for HTN • 147,000 patients total. 3.3 year follow-up • Sensitivity analysis: highest bias and and lowest bias studies came to same conclusion. • Good homogeneity of studies

18. What did they find? • Lower risk of stroke (RR reduction 10%) • Lower heart failure (RR reduction 13%) • Lower risk of diabetes (RR reduction 15%) • But wait for it….

22. But wait for it…. • BMJ editors say, based on the data: • “Despite lower blood pressure with angiotensin receptor blockers when compared with placebo, there also was no detectable beneficial effect for the outcome of myocardial infarction or cardiovascular mortality.” • No benefit in overall mortality. • QED. Use something else.

23. Well done meta-analysis • Did not get unpublished data but this would likely have supported their conclusion (un-spinablestudies critical of ARBs likely would not see the light of day). • Good homogeneity

24. Do nothing which is of no use. • Miyamoto Musashi

25. Howard R, et al. Donepezil and Memantine for Moderate-to-Severe Alzheimer's Disease. N Engl J Med 2012;366:893. Does memantine add anything to donepezil for moderate to severe Alzheimer’s disease?

26. Previous Literature • NNT 12 • No important positive outcomes (time to nursing home, ability to do ADLs, etc.) • Donepezil not effective in minimal cognitive impairment • Cholinesterase inhibitors for patients with Alzheimer’s disease: systematic review of randomized trials, BMJ 2005;331;321-327 • Doody RS et al. Donepezil treatment of patients with MCI: A 48-week randomized, placebo-controlled trial. Neurology 2009 May 5; 72:1555.

27. 285 Patients randomized • Double-blind, randomized, 2x2 factorial design study of donepezil +/- memantine vs placebo for moderate-to-severe community-dwelling patients with probable Alzheimer dementia. • Outcome: Mini mental status exam: 0-30 • Bristol ADL Scale: 0-60

28. Outcome • MMSE: Memantine+ donezapil vs. placebo + donezapil: 1.2 • BALDS: Memantine + donezapilvs. placebo + donepazil: 1.5 points • MMSE: donepazil vs. placebo: 1.9 points • BALDS: donepazil vs placebo: 3.0 points

29. Their conclusions: • Memantine adds nothing to donepazil- I’ll buy that • Donepazil has “significant functional benefit” over placebo- Not so fast

30. Hmmm… • They decided arbitrarily that clinically “significant” was 1.4 on the MMSE and 3.5 points on BALDS based on • …..0.4 SD from baseline…. • …the response seen from 127 patients. • Nowhere does this say anything about clinically detectable differences.

31. Bristol Activity of Daily Living Scale: BADLS: 0-60

32. No difference between donepazil + memantine vs. donepazil alone. • What do we take from this? • The combination of donepezil and memantine for moderate-to-severe AD is not beneficial. • The discontinuation rates of dementia medications are high. • The “clinically significant” benefit is marginal. • If you start donepezil (or another AChE inhibitor) for dementia, it’s reasonable to continue it through the course of the disease (or not…you could argue either point with this article).

33. Zeiger RS et al. Daily or intermittent budesonide in preschool children with recurrent wheezing. N Engl J Med 2011 Nov 24; 365:1990 c

34. What we know… • Oral steroids for acute exacerbations often cause behavioural problems in children. • 1mg/kg/d is as good as 2mg/kg/d • Chest 2002;122;624-628 DOI 10.1378/chest.122.2.624 • Treating those that wheeze with URIs at the start of the URI is helpful

35. This article.. • Compared 278 children age 12-53 months randomized to: • Low dose budesonide daily (0.5mg BID) • High dose budesonide 1mg BID for 7 days at onset of wheezing or URI symptoms • These were all children who had required oral glucocorticoid therapy, ED visit (??), hospitalization

36. Outcome • No difference in need for oral glucocorticoids • No difference in time to first exacerbation • No difference in growth, etc. • No difference in treatment failure • 104mg less budesonide in intermittent group

37. So what do I take from this? • Am I ready to stop controlled meds on my asthma patients? NO. • But for those who we only burst with steroids for a URI this is an acceptable option.

38. Calcium and Bisphosphonates are killing me…..

39. Park-Wyllie LY et al. Bisphosphonate use and the risk of subtrochanteric or femoral shaft fractures in older women. JAMA 2011 Feb 23; 305:783 And Schilcher J et al. Bisphosphonate use and atypical fractures of the femoral shaft. N Engl J Med 2011 May 5; 364:1728

40. What we know… • Bisphosphonates reduce bone remodeling

41. First study • Population based, nested, case control study • 716 women over age 68 who were taking a bisphosphonate and had an atypical hip fracture over 7 years. • 3580 controls on bisphosphonates but with no fracture

42. “Long term” versus transient bisphosphonate use associated with “atypical” hip fracture OR of 2.74 for fracture. • 2 of 1000 women so absolute risk is low. • Still reduced “typical” hip fractures that were much more common

43. Next study • Sweden. Looked all all hip fractures in 2008 • Total of 1271 fractures • Of these, 59 were “atypical” • Relative Risk for atypical fracture with bisphosphonate use was 47.3 • But…still only 5 more per 10,000 patient-years

44. 78% of “atypical” fractures had used bisphosphonates • 10% of controls had used bisphosphonates • Likelihood went up with duration of bisphosphonate use

45. Should we have a drug holiday at 5 years? In whom should we continue the drug?

46. Finally some guide: opinion only, though. N Engl J Med 2012; 366:2048-2051May 31, 2012 N Engl J Med 2012; 366:2051-2053May 31, 2012 • Patients with low bone-mineral density at the femoral neck (T score below -2.5) following 3 to 5 years' of treatment have the highest risk for vertebral fracture and seem to benefit most from treatment continuation.

47. Those with existing vertebral fractures who have T scores below -2.0 may also benefit. • Those with femoral neck T scores above -2.0 have low vertebral fracture risk and are not likely to benefit.

48. OK. We solved that problem. What about calcium?

49. Li K, Kaaks R, et al. Associations of dietary calcium intake and calcium supplementation with myocardial infarction and stroke risk and overall cardiovascular mortality in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition study (EPIC-Heidelberg) . Heart 2012;98:920-925 So what about this calcium and heart attack thing anyway?

50. 25,540 local residents, who were then aged 35-64 years • Free of CVD at baseline • excluded participants with: MI, stroke, or transient ischaemic attack (but not angina, etc.) • Used a validated food frequency questionnaire.