Update in Primary Care 2009

1. Update in Primary Care 2009 • Joel C. Diamant, MD, FACP • Director, Internal Medicine Residency • Member Division of Internal Medicine • Scripps Clinic & Scripps Green Hospital • Scripps Translational Science Institute • October 2009

2. Format • Confined to Clinical Trials from 2008 • Sources: NEJM, Annals of IM, JAMA, ACP Journal Club • Many, many important trials not included

3. Gender Health

4. November 6, 2008

5. APHRODITE Background • Sexual Problems reported 9-43% of post-menopausal women • Decreased desire in #1 concern • Prior studies usually combined with estrogen and usually very short term

6. APHRODITE: Methods • Post menopausal > 1 yr, 40-70 yo, stable mamo, no estrogen • 65 centers, 814 women, intention to treat, randomized • 150 or 300 mcg testosterone patch • Efficacy measured thru 24 weeks, safety thru 52 wks • Measures: weekly Sexual Activity Log, Profile of Female Sexual Function, Personal Distress Scale

7. APHRODITE: Results • 71% completed 24 weeks, 57% elected to extend to 52 • At baseline 50% of sexual episodes were satisfying in all groups • Those receiving testosterone reported sig increases in sexual desire, # and percentage of encounters that were satisfying

11. APHRODITE: Conclusions • Moderately large, well designed trial • Sig effect on sexual satisfaction—not demod in several other trials • Effect occurs independent of estrogen • Trial not of sufficient duration to clearly assess safety nor durability of testosterone in women • Comparable product not currently available on market—but appears promising and possibly safe intervent

12. December 3, 2008

13. EtOH, Women & AF: Background • Modest EtOH: < CHD, CVA, CHF • Acute Intox/withdrawl: > MI, CVA, AF • Chronic Excess  CM • Studies in men show > 35d/w AF • Very little data on modest chronic consump in women

14. EtOH, Women & AF: Methods • Assessed effect of regular EtoH in 34,715 healthy women • Enrolled from WHS (ASA & Vit E primary target) • 1993— 2006 39,876 >45 yo, health prof • Questionnaires mailed annually,--EtOH queried at entry & every 4 years. AF queried yearly

15. EtOH, Women & AF: Results • Event rate • Non drinkers—294 events—1.9% • <1/d—284 events—1.8% • 1-2/d—35 events—1.6% • > 2/d—40 events—2.9%

16. EtOH, Women & AF: Results/Conclusions • HR = 1.58 ---58% more likely to develop AF if drink • > 2d/d  2.25 events/1000 pt years • Teetotalers 1.59 events/1000 pt years • Absolute risk increase is .66 events per 1000 person years • 10 years of drinking—NNH = 151 • Difficult to control for all con founders—tobacco, binging, other forms of excess • You decide—how hard should you push you women drinkers to stop based on rhythm concerns?

17. August 5, 2008

18. Prostate CA Screening USPSTF:Bkg • #1 Non skin CA in men; 1/6 men develop prostate CA over lifetime • #2 Cause of CA death in men,>27K deaths annually • 71% deaths in men are > 75 yo • Clinically heterogeneous—many never have symps • 2002 USPSTF stated insufficient ev to demo benefit to screening

19. Prostate Screen USPSTF: New Data • 2 poor metanalysis showed NO mort benefit • 1 RCT of 695 men with localized prostate CA found small death reduc with surg. • After 8.2 year 14.4% control & 8.6% surg were dead • In 372 men > 65 years—no dif in death at 10 years

20. Prostate CA Screen USPSTF: Rec • benefit of screening in men < 75 still unclear • Strong ev of no benefit in men > 75 • USPSTF rec against screeing men >75 • Perhaps better stated—men with life expect < 10 years—no indication for screening

21. March 26, 2009

22. PLCO Trial 3/26/09 • 76,693 men randomized • Annual PSA testing for 6 years • Median f/u is 11.5 years

23. ERSPC Trial 3/26/09 • 182,000 European men screened • Median F/U 9 years • 20% RRR for Prostate CA Death • Absolute reduc 7 CA deaths/10,000 men screened (NNS = 1429) • 17,000 had biopsies in screened group • Mort benefit not until > 10 years

24. Gastroenerology

26. CT Colography v. Oscopy: Bkg • #2 cause CA death; 154K new cases & 52K death/yr. • Great opportunity to save lives with early detection • Despite potential-- screening greatly underutilized • CT Colog advantages: no sedation, rapid imaging, relatively non-invasive, < comp risk

27. CT Colog v. Oscopy: Method • 2600 patients enrolled—97% with complete studies • Pts > 50 yo, sched to undergo routine screeing • CT first, colonoscopy 2nd—same day • Radiologists must have read >500 cases or gone to 1.5 day course and had > 90% detection on a test

28. CT Colog v. Oscopy: Results • CT Colog with 90% sensitivity for lesion> 10 mm • CT Colog with 65% sens for lesions > 5mm • 30 lesions seen on CT but not on colonoscopy—5 confirmed on repeat CT3.9% miss on colonoscopy • CT with extra-colonic findings in 66%!!! (16% deemed to require f/u) • Virtual Optical Colonoscopy in 17% of patients b/c of polyp

29. CT Colog v. Oscopy: Conclusions • CT Colography has 90% sensitivity for large lesions • Colonoscopy has 96% sensitivity for large lesions • CT colog has sensitivity of 65% for lesions if cut off is 5mm instead of 10 • Pop of 1000 patients with 20% risk • 200 patients will have adenoma • CT will miss 70 of the total adenomas • CT will miss 20 large ones • CT will ID 160 with extracolonic CT findings needing f/u • CT Colog is legit alt to colonoscopy—recognizing much lower sensitivity and a large amount of additional data of unclear utility • Radiation risk with CT every 5 years x 25-30 years unknown • Impact on mortality entirely unknown

30. May 29,2008

31. Methylnaltrexone for Opiod Constipation: Background • Constipation distressing SE of opiates • Laxatives frequently ineffective & limit opiate dosing • Opiate constipation mediated via μ receptor in gut • Methylnaltrexone is peripheral μ blocker with little cross of BBB

32. Melthylnaltrexone & Constipation: Methods • 2 week 2x-blind, randomized, placebo controlled with open label extension • All patients in SNF &/or Hospice • > 18 yo, advanced disease, life expectancy > 1 mo, on stable opiates & laxatives for > 3d • < 3 BM/wk & 0 BM x 24° b-4 entry • 1:1 study v placebo; 133 patients • 0.15 mg/kg SQ qod x 2 weeks, continue usual laxatives • Outcome: Frequency and ease of defecation

34. Methylnaltrexone: Conclusions • SQ Methylnaltrexone may be effectively used for opiate induced constipation • No impact upon analgesia, no dif in SEs • May be used in single does or ongoing fashion • Onset is rapid, most responding w/i 2 hours • Probably can be safely delivered at home—not tested there • Not known if it will help non-opiate induced constip

35. August 27, 2008

36. Nuts & Tics: Background • By age 60 1/3 have tics, by 85 2/3 have tics • 10-35%  diverticulitis or sig bleed • $2.4 Billion direct HC costs per annum • Luminal trauma from roughage postulated as cause • Nuts, corn, & popcorn deemed most evil • 47% colorec surgeons feel nuts/corn should be avoided

37. Nuts & Tics: Methods • HPS began 1986 51,529 male HP 40-75 yo • Health & Lifestyle questionnaire biennially • 84% response to GI questions for > 18 years • Questionnaire included 131 food items • Excluded if colonic disease at entry • Remainder 47,228 men • 1⁰ endpoint: Diverticulitis or Tic bleed

40. Nuts & Tics: Conclusions • Very large survey suggests nuts/corn/popcorn have no pathogenic role in comps of diverticular disease • Nuts & popcorn may actually reduce risk of diverticulitis • Self reported survey may be limited by respondent fatigue and inaccuracies • Extrapolation to women is speculative • Bottom line: little indication to rec against nuts and seeds in patients with tics.

41. Cardiovascular

43. JUPITER: Background • ½ of all MI/CVA occur in otherwise healthy with low LDL • CRP independently predicts future vascular events • Statins lower CRP • Using CRP as indication for statin might have desirable result

44. JUPITER: Methods • Randomized, 2x blind, placebo controlled, intention to rx analysis • 1315 sites, 16 countries • Men > 50, women >60, o CVD, LDL <130; CRP > 2 mg/l • Rosuvastatin 20 vs. Placebo; 1:1 • 1⁰ outcome: 1st CV event, non-fatal MI, non-fatal stroke, hosp for USA, revasc procedure, CV death • 2⁰ outcome: any 1⁰ + any death • Terminated 3/29/08 by data safety board

45. JUPITER: Results • 89,890 screened; 17,802 eligible • Median age 66, 38% women, 71% white, 16% smokers • Mean CRP 4.2, LDL = 108, HDL = 49, TG= 118 • At study end: Rosuv Placebo LDL 55 109 CRP 1.8 3.3

49. JUPITER: Conclusions • NNT for 2 years = 95, NNT for 4 yrs = 31—touted by authors—fuzzy math. Recalc suggests NNT = 83 for 4 years (Also, note only 1/16th of patients followed for 4 years) • Rosuv costs $3.45/pill = $1259/yr (cost $417,988 per event prevented) • Rosuvastatin reduces CV events in patients with norm LDL, and patients with elev CRP (don’t know anything about patients with norm CRP) • This was a statin trial—not really a CRP trial—does not answer—should I treat the CRP??