Hot Topics – Hotlanta

1. Hot Topics – Hotlanta Justin A. Glass, MD Emory Family Medicine 4.24.08

2. What do you do after work? • Pick up your kids from daycare? • Come home to have your spouse hand you the kids and then disappear to meet his/her friends? • Make dinner? • Do the laundry? • Go for a run? • File for a tax extension? • Debate which job you are going to take? • Read a medical article every night?

3. Objectives • Review Selected Topics from Family Medicine Journals I found in my house on April 20th • American Family Physician 3/15/08 • The Journal of Family Practice April 2008 • Family Practice News 4/1/08 • Family Practice Management April 2008 My goal is to use case based examples to help illustrate the practice changing /reinforcing points in the articles that I identified.

4. Clinical scenario #1 • A 46 yr old male presents with L flank pain radiating toward the groin. In the ER he is noted to be in pain but is afebrile and not vomiting. Results of serum chemistries and urinalysis are only significant for hematuria. A non-contrast CT abdomen demonstrate a 5 mm stone in the distal L ureter.

5. Clinical Scenario #1 • In addition to narcotic medication, what additional treatment is likely to offer immediate benefit to this patient? • A. Potassium citrate • B. Ursodiol • C. Lisinopril • D. Tamsulosin • E. Atenolol

6. Clinical Scenario #1 • In addition to narcotic medication, what additional treatment is likely to offer immediate benefit to this patient? • A. Potassium citrate • B. Ursodiol • C. Lisinopril • D. Tamsulosin • E. Atenolol

7. Ureteral Stone Management • Kidney stone lifetime prevalence: 5.2% • Recurrence rate: 50% • Standard Treatment • Pain relief • Immediate intervention if high grade obstruction or infection. Otherwise delay intervention 1-2 mos. • Stones > 6 mm likely to not pass spontaneously (OR 10.7) • Can we help the stone pass?

8. Ureteral Stone Management • “Drugs Help Pass More Ureteral Stones”, The Journal of Family Practice, April 2008 • PURLs (Priority Updates from the Research Literature) Singh A, Alter, JH, Littlepage A. A systemic review of medical therapy to facilitate passage of ureteral calculi. Ann Emerg Med. 2007; 50:552-563.

9. URETERAL Stone Management • Meta-analysis of 16 studies of alpha antagonists and 9 studies of nifedipine published between 1980 – 2007. • Primary outcome: Percentage of patients who passed stone with medical expulsive therapy versus placebo • Secondary outcome: Time to stone passage with medical expulsive therapy versus placebo

10. Ureteral Stone management • Alpha blocker therapy • Tamsulosin (Flomax) was alpha blocker in 13 of 16 studies. Terazosin and Doxazosin in others. • 1235 patients with distal ureteral stones. • Stone size 4.3 to 7.8 mm. • Alpha antagonist therapy improved stone passage (RR 1.59, CI 1.44-1.75, NNT 3.3) • Mean time to expulsion <14 days • Stone expulsion was 2-6 days earlier than control. • Adverse effects in 4%. Mild.

11. Ureteral Stone management • Calcium Channel Blockers • Nifedipine studied in 9 trials • 686 patients • Stone size 3.9 – 12.8 mm • Some trials included stones in proximal ureter • Nifedipine improved stone passage (RR 1.5, CI 1.34-1.68, NNT 3.9) • Mean time to expulsion was <28 days • Time to stone passage was shorter in 7 of 9 studies. (1.4 days longer to 13 days shorter) • Adverse effects in 15%. Mild (Nausea, vomiting, asthenia, dyspepsia).

12. Ureteral Stone Management • Limitations? • All included studies were small (30-140 patients) • Unclear ratio of men:women. • Unclear what ethnic breakdown was present in the study.

13. URETERal Stone management • Are physicians using this information? • Clinic setting: • 7% of 1,345,000 patients in 2004-2005. • Hospital setting: • In 2003, 3% of patients with ureteral stone received tamsulosin. • In 2007, 34% of patients received the drug. • Similar with FM, IM, ER and Urology doctors. • Academic centers varied from 4 – 48% in use in 2007.

14. Ureteral Stone Management • Summary: • Consider tamsulosin 0.4 mg PO q day in patient with distal ureter stone. • The larger the stone over 6 mm, the more likely that urology intervention needed. • The smaller the stone under 6 mm, the more likely spontaneous passage occurs. • Alternate drug: Nifedipine ER 30 mg PO q day

16. Clinical Scenario #2 • 40 year old male presents for physical. Pertinent information is obtained: • No hx CAD / HTN / etc. • Fm Hx: Dad w/ MI @ age 60 • No medication • Physical exercise 1 day / week. • Non-smoker • Non-drinker • BMI 24 • BP 122/76 • Fasting glucose 87 • Lipids: Total chol 160 LDL 90 HDL 45

17. Clinical Scenario #2 • What else can you recommend to lower his risk of a heart attack? • A. Start drinking 1 daily serving of alcohol • B. Start taking vitamin E • C. Start taking folic acid • D. Increase physical activity to 5 days/week • E. Start ASA 81-162 mg PO q day

18. Clinical Scenario #2 • What else can you recommend to lower his risk of a heart attack? • A. Start drinking 1 daily serving of alcohol • B. Start taking vitamin E • C. Start taking folic acid • D. Increase physical activity to 5 days/week • E. Start ASA 81-162 mg PO q day

19. Heart Disease • Heart Disease accounted for 652,000 deaths in 2005 • Leading cause of death in United States overall

20. Heart Disease • Risk factors for CAD • Age • Sex M>F • Family History: Dad <55 Mom <65 • Smoking • Diabetes • Hypertension (>140/>90) • Total cholesterol >240

21. ASA and Primary Prevention of CAD • Why is ASA therapy not indicated?

22. ASA AND Primary Prevention of CAD • CHD Risk Calculator for this patient: • 10 yr risk of event: 3%

23. ASA ANd Primary Prevention of CAD • Primary Prevention of CAD with ASA • USPSTF -- Recommend ASA if 10 yr CAD risk exceeds 6% • AHA – Recommend ASA if 10 yr CAD risk exceeds 10% • Meta-analysis of 5 large trials shows ASA reduces risk of first CV event by 32%. Risk of hemorrhage is 2.3% at 28 months. • Arch Intern Med 2003 Sep 22;163(17):2006-10.

24. VITAMINS & CAD • Folic acid trials have not shown CAD benefit • Vitamin E trials have not shown CAD benefit

25. Exercise & CAD • Increased exercise can lead to reduction in risk of CAD • N Engl J Med 1999 Aug 26;341(9):650-8.

26. Clinical Scenario #2 • What else can you recommend to lower his risk of a heart attack? • A. Start drinking 1 daily serving of alcohol • B. Start taking vitamin E • C. Start taking folic acid • D. Increase physical activity to 5 days/week • E. Start ASA 81-162 mg PO q day

27. Moderate Drinking & CAD • “Moderate Drinking Cuts Heart Event Risks by 38%”, Family Practice News, April 1, 2008. • Summarizes the Atherosclerosis Risk In Communities (ARIC) Trial • American Journal Medicine. 2008; 121: 201-6.

28. Moderate Drinking & CAD • ARIC Trial: National Heart, Lung and Blood Institute prospective epidemiologic study of almost 15,792 people. • Middle age (45-64) • African American / Non African American • Men / Women • United States • At year six, survey identified 7,697 formerly non-drinking patients who began moderate alcohol intake.

29. Moderate Drinking & CAD • Endpoint: Combined rate of fatal and nonfatal cardiovascular events between years 6-10. • 6.9% among new moderate drinkers • 10.7% among continued non-drinkers • Adjustment for age, race, sex, diabetes, hypertension, hyperlipidemia and physical activity was made. New moderate drinkers had a 38% reduction in relative risk of endpoints. OR 0.62 (0.40 -0.95) • Mortality difference non-significant (29% less deaths in new moderate drinkers).

30. Moderate Drinking & CAD • Subgroups • Wine only: OR 0.32 (0.12-0.87) • Mixed intake: 0R 0.79 (0.49-1.26)

31. Moderate Drinking & CAD • What do other studies tell us: • Physician’s Health Study (Men) • Middle aged patients who initiated moderate drinking (1-6 drinks/week), lowered CV risk by 29% • Arch Intern Med. 2000;160:2605-2612. • Adult men who initiated moderate drinking lowered CV risk by 62% • Arch Intern Med. 2006;166(19):2145-2150.

32. Moderate Drinking & CAD • Should we be telling our non-drinking patients that adoption of moderate drinking behavior is associated with decreased CV mortality?

34. Clinical Scenario #3 • A 26 yr old female presents to your clinic with concern about sleep issues. On further questioning, she answers positive to most of your depression screening tool. After discussing depression, she wants to both see your on-site behavioral medicine provider and start medication. • What medication do you start?

35. Treatment of Depression • Incidence 10-14% in primary care clinics • Antidepressant use doubled between 1995 and 2002.

36. Treatment of Depression • Review article: “Pharmacologic Management of Adult Depression” Am Fam Physician. 2008; 77(6): 785-792.

37. Treatment of Depression • Classes • Selective Serotonin Reuptake Inhibitors (SSRI’s) • Serotonin Norepinephrine Reuptake Inhibitors (SSNI’s) • Tricyclic Antidepressants • Norepinephrine reuptake inhibitor • Also affect acetylcholine, histamine, adrenergic receptors • Aminoketone Antidepressant (Buproprion) • Inhibit reuptake of norepinephrine and dopamine • Serotonin Modulators (Trazodone / Nefazodone) • Selectively inhibit the 5-HT2A and 5-HT2C serotonin receptors • Tetracyclic Antidepressant (Mirtazapine)

38. TREATment of Depression • SSRI’s: Fluoxetine (Prozac) / Paroxetine (Paxil) / Sertraline (Zoloft) / Citalopram (Celexa) / Escitalopram (Lexapro) / Fluvoxamine • First line agents • SE’s: Agitation / Insomnia / Nausea / Diarrhea / Sexual dysfunction / GI hemorrhage • Metabolism: P450 system in liver. Fluoxetine and paroxetine can inhibit metabolism of other drugs (TCA levels increase)

39. TREATMent of Depression • SSNI’s: Venlafaxine (Effexor) and Duloxetine (Cymbalta) • First line agents (more expensive than SSRI’s) • SE’s: Nausea / HA / Insomnia / Somnolence / Sexual dysfunction • Metabolism: P450 system. Can inhibit metabolism of other drugs (TCA levels increase)

40. TREATment of Depression • TCA’s: Amitriptyline / Nortriptyline / Desipramine / Imipramine • SE’s: Weight gain / sedation / constipation / dry mouth / orthostatic hypotension / reflex tachycardia (less w/ nortriptyline and desipramine) • Metabolism: P450 system. Wide variety in drug levels due to polymorphism in P450 systems. • Overdose lethality is high: Resp depression / cardiac arrhythmias / hypothermia / seizures / hallucination / hypertension

41. Treatment of Depression • Buproprion (Wellbutrin) • Advantages: Less sexual dysfunction, Weight loss, smoking cessation • Disadvantages: Increased insomnia / HA’s

42. Treatment of Depression • Serotonin Modulators: • Trazodone • Usually used as insomnia treatment • Nefazodone • Can be associated with fulminant hepatic failure (Black box warning) • Mirtazapine (Remeron) • Used to induce weight gain

43. Treatment of Depression • General Guidelines • Antidepressants improve depression symptoms in adults compared to placebo. (A rating) • Efficacy is similar among different classes of antidepressants (A rating) • Consider a change in therapy if there is no effect after 4-12 weeks of treatment (B rating) • The change in therapy can be to a different medication in the same class, to a new class or augmentation with a second agent (B rating)

44. Treatment of Depression • Serotonin Discontinuation Syndrome • Can happen on abrupt discontinuation of SSRI or SNRI. • Symptoms: Anxiety / Irritability / Insomnia / Headache / Fatigue / Dizziness / Ataxia / Tremor / Parasthesias or electric shock sensations / Visual disturbances / Vomiting / Diarrhea

45. TREATMEnt of DepRession • Oh…. And don’t forget…. Combination of psychotherapy and medication is more efficacious than medication alone. J Affect Disord. 1998; 49(1): 59-72.

47. Clinical Scenario #4 • You are driving to work at 7:30 AM when you witness an oncoming truck strike a bicyclist on the median of the highway. The bicyclist is thrown into the outside lane of traffic. • You pull a U-turn and park on the median.

49. Clinical Scenario #4 • Medical emergency “in the field” • Notify 911 • Secure scene safety before assisting patient • Provide emergency medical care while awaiting additional assistance

50. Good Samaritan Laws • Review Article: “What You Need to Know When Called Upon to Be a Good Samaritan” Fam Prac Management. April 2008; 15(4): 37-43.