27th Annual Family Medicine Review Updates/Pearls in Office-Based and Hospital-Based General Medicine Stephen Sibbitt, MD, FACP Chief Medical Officer, Scott & White Memorial Hospital Asst. System Chief Medical Officer, Scott & White Healthcare

A few disclaimers…

• • • ABIM style MCQs based upon New emerging concepts/trends • • I A level of evidence IB or best available. The final vote is still out on many of these.

Current (old) concepts • • New literature Re-emphasizing best practice

Special Thanks to Tresa McNeal, MD. Dept of Internal Medicine, Scott & White Healthcare

Question 1

      52 y.o male presents to the emergency room with 2-day history of melena, epigastric discomfort, and lightheadedness. No hematochezia, coffee-emesis, hematemesis.

Past history of 1-pack per day tobacco use (32 years), osteoarthritis of right knee, and etoh abuse.

Medications include ibuprofen 600-800mg bid On physical exam his BP = 110/70 supine, 90/50 sitting, HR is 115. Abdomen is soft, NABS, no rebound or masses, mild epigastric tenderness. Rectal reveals melena, no masses.

Labs reveal normal platelets, PT and aPTT. Hgb is 9.6 mg/dl Patient receives IV fluid resuscitation and undergoes EGD revealing shallow gastric ulcer, biopsy negative for H. Pylori.

Following endoscopic treatment for bleeding peptic ulcers, which of the following statements are true regarding high dose PPI therapy compared to non-high dose PPI therapy?

1.

2.

3.

4.

Decreased rate of re bleeding Decrease in mortality Decreased need for surgical intervention None of the above 25% 25% 25% 25% 1 2 3 4 10

Background



Endoscopy has reduced rates of re-bleeding, surgical intervention, and mortality.



10-20% re-bleed after endoscopic intervention 4% mortality rate.



Many studies showing PPI > H2 Blockers in gastric acid suppression and in controlling re-bleeding



Studies comparing high-dose PPIs to placebo have shown reduced re-bleeding rates.



A meta-analysis demonstrated that non-high-dose PPIs were also superior to placebo in terms of re-bleeding rates.

Literature search performed herein

Copyright restrictions may apply.

Wang, C. H. et al. Arch Intern Med 2010;170:751-758.

Study design

 Combined 7 trials – 1157 patients  High-dose PPI = 80 mg bolus of omeprazole (Prilosec) or pantoprazole (Protonix) followed by 8 mg/hour or higher for 72 hours  Non-high-dose = IV PPI once daily or PO PPI twice daily  LOE = 1a Systematic review (with homogeneity ) of randomized controlled trials

Effect of high-dose vs non-high-dose proton pump inhibitors (PPIs) on rebleeding Wang, C. H. et al. Arch Intern Med 2010;170:751-758.

Copyright restrictions may apply.

Effect of high-dose vs non-high-dose proton pump inhibitors (PPIs) on surgical intervention Wang, C. H. et al. Arch Intern Med 2010;170:751-758.

Copyright restrictions may apply.

Effect of high-dose vs non-high-dose proton pump inhibitors (PPIs) on mortality Wang, C. H. et al. Arch Intern Med 2010;170:751-758.

Copyright restrictions may apply.

Take home point

 For patients with bleeding ulcers who are treated endoscopically, high-dose proton pump inhibitors compared to non-high dose PPI therapy  do not decrease the rate of re-bleeding,  Do not affect mortality,  Do not reduce the need for surgical intervention  Use non-high dose PPI (IV PPI once daily or PO PPI twice daily)  LOE = 1a Systematic review (with homogeneity ) of randomized controlled trials

Question 2

• A 42-year-old male presents to the ED with syncope and hypotension. The patient has a history of polysubstance abuse including use of cocaine, etoh, marajuana, and has a dependence to opiates. Current medications are lorazepam, disulfiram, and methadone. • Initially he is found to be becoming progressively more agitated and having brief episodes of depressed conscious state, with improvement between. He is ‘jittery’ and on vitals, he is found to be afebrile with a fluctuating Glascow Coma Score, bradycardic, and to have a systolic blood pressure of 80mmHg, respirations of 12, and so he is taken to a resuscitation cubicle. • Initial ECG obtained and he experiences periodic arrythmias.

© 2010 ABIM

Which of the following medications is the most likely cause of this patient's arrhythmia?

10

A.

B.

C.

D.

E.

Alcohol Acetominophen Benzodiazepines Cannabis Methadone

20% 20% 20% 20% 20% A.

B.

C.

D.

E.

QT Prolongation

 Caused by:   Hypomagnesemia Hypokalemia       Hypocalcemia Na channel blocking drugs (IA antiarrythmic) Elevated intracranial pressure acute coronary syndrome Hypothermia hereditary causes  Management is Magnesium and in more severe cases of recurrent Torsades an implated defibrilator.

 What caused QT prolongation in this patient   Methadone, effects potassium ion channels causes significant increases in the QT interval (Martell et al, Am J Cardiol 2005;95:915-918)

Question 9

Question 2

Question 2 – Take Home Point

 Chronic Methadone increases risk for malignant cardiac arrhythmias.

 Increase risk with higher doses (>40 mg/dl)  Pretreatment ECG to measure QTC interval  30-day follow up and annual ECG , after initiation of chronic therapy

Question 3

    62 y.o female recent move to your city; comes to see you to established care. History of DMII, High Cholesterol, HTN BP = 133/78 mmHg Meds include  ASA 325 mg daily   Glyburide 10 mg po qday Lisinopril 10mg po qd Labs    HgbA1C = 7.6, Creatinine is 0.8

T-chol = 172mg/dl, LDL = 100mg/dl, HDL= 38 mg/dl , TG= 174mg/dl,

You inform the patient that she requires treatment of her lipids. You advise her that in DMII patients, in comparison to statin treatment alone, the combination of a statin and a fibrate, has been shown to: 10 1.

Reduce the risk of fatal cardiovascular events 25% 25% 25% 25% 2.

3.

4.

Reduce the risk of non-fatal MI Reduce the risk of stroke None of the above 1 2 3 4

Background

 Increased atherosclerosis in DM patients  Statins are known to be efficacious in patients with diabetes but CV events remain elevated even with statins  VA-HIT ( 2001)trial showed decreased CV events with fenofibrate use  FIELD (2008) trial showed benefit in reduction of total cardiovascular events.

 In previous trials, patients were not on statins .

Action to Control Cardiovascular Risk in Diabetes

5518 diabetic patients 2765 Fenofibrate + simvastatin 2753 Placebo + simvastatin

Mean follow-up was 4.7 years

Primary outcome

major fatal or nonfatal cardiovascular events

Secondary outcomes

Revasc or hosp for CHF Major CAD event Nonfatal MI Stroke Death

Would type 2 DM patients benefit from combination statin and fibrate therapy?

Take home point

 In diabetics, compared to simvistatin alone, the combination of fenofibrate and simvastatin did not reduce the rate of fatal or non-fatal cardiovascular disease, non-fatal MI, or non-fatal stroke.

 In patients with markedly elevated TG or very low HDL, it is likely still worthwhile to initiate fenofibrate therapy.

Question 4

 A 64-year-old man is referred to you following evaluation by his orthopedist for total knee arthroplasty. He has a history of progressive osteoarthritis that is described as severe for multiple years, requiring use of a cane for ambulation. His orthopedist would like him ‘cleared for surgery’. Surgery is scheduled in two weeks.  Past Medical History pertinent for high cholesterol, hypertension, and coronary artery disease. Seven months ago, he underwent drug eluting stent placement for worsening angina, and he has been asymptomatic since the surgery.  Current medications are aspirin, clopidogrel, lisinopril, metoprolol, and simvastatin.

© 2010 ABIM

Following your evaluation which includes a normal ECG you advise the following with respect to the placement of his DES and anti platelet agents:

10 1.

25% 25% 25% 25% 2.

3.

4.

Proceed to surgery on aspirin alone. Proceed to surgery on Plavix alone.

Stop ASA and Plavix one week before surgery and resume immediately post-op.

Delay elective surgery for 5 more months. 1 2 3 4

Question 4

Question 4

Management of patients with previous percutaneous coronary intervention who require noncardiac surgery Previous PCI Balloon Angioplasty

Time since PCI

< 14 d > 14 d Bare-metal stent Drug eluting >30 – 45 d <30 – 45 d <365 d stent >365 d Delay for elective or nonurgent surgery Proceed to the operation room with aspirin Delay for elective or nonurgent surgery Proceed to the operation room with aspirin J Am Coll Cardiol 2007; 50:e159

Question 4...

Take Home Point

 The best available evidence:  elective surgery should be delayed at least 30 to 90 days following placement of a bare metal stent.  Elective surgery should be delayed at least one year after drug-eluting stent placement.

Question 5.

Is there any value in extending dual antiplatelet therapy (aspirin plus clopidogrel) beyond 12 months after DES implantation?

10 1.

33% 33% 33% 2.

3.

Yes, cardiovascular outcomes are improved.

No, mortality is increased.

Uncertain, further randomized controlled trials are required.

1 2 3

Background

 Drug-eluting stents significantly reduce restenosis.

 May be associated with increased late stent thrombosis, death, or MI.

 Stopping dual antiplatelet therapy early is a risk factor for late stent thrombosis in patients with drug-eluting stents.

 Current guidelines recommend clopidogrel 75 mg daily for at least 12 months.

The Question

 Optimal duration of dual antiplatelet therapy and the risk-benefit ratio for long-term antiplatelet therapy are uncertain in the setting of drug eluting stents.

The Study Design

 Data merged from 2 similarly designed trials in Korea (REAL-LATE & ZEST-LATE)  Enrolled people (2701) who had drug eluting stent placed at least 12 months ago and who were still on dual antiplatelet therapy  Randomly assigned to clopidogrel plus aspirin vs. aspirin alone.

 Primary endpoint of MI or death from cardiac causes

Factors to consider in interpreting results

 Not blinded  Inadequate sample size  Interval between stent placement and study enrollment differed; unable to determine optimal duration  New generation of stents may have different performance.

Question 5… Take home point

 ACC and AHA recommend dual antiplatelet rx in pts with DES.

 Continuing dual antiplatelet therapy beyond 12 months is not currently recommended for patients who have a drug-eluting stent. Continued use did not improve outcomes and may worsen them.

 Larger clinical trials will be needed.

 Dual Antiplately Therapy Trail (DAPT) ongoing   DES and BMS 12 vs 30 months of dual therapy

Question 6

 67 y.o. male with chronic atrial fibrillation is seen in your office for routine follow up. He reports his home heart rate monitor shows his HR runs approximatetly 100 beats/min. He has no complaints of chest pain, palpitations, lightheadedness, or dyspnea. He reports he feels fine and continues to walk 3 miles per day without difficulty. He is concerned that his HR should be lower.

 He has been compliant with his medications consisting of Coumadin 5mg daily, and metoprolol 25mg twice daily.

 Vitals and physical exam normal with noted irregular rhythm with a rate of 98 beats/min. ECG reveals atrial fibrillation and is otherwise unchanged from previous.

Question 6: You advise the patient that strict rate control (HR <80 beats per minute) as compared to lenient rate control (HR < 110 beats/min) is associated with which of the following?

10

1.

25% 25% 25% 25%

2.

3.

4.

Reduced risk of life threatening arrythmic events.

Reduced risk of stroke.

No difference in risk of cardiovascular death.

Reduced rate of hospitalizations for heart failure.

1 2 3 4

Background

 Complications similar between rate and rhythm control for atrial fibrillation.

 Degree of rate control not previously studied.

 AHA Guidelines recommend strict rate control with target resting HR of 60-80 ranging up to 90-115 with exercise.

RACE II – Rate Control Efficacy in Permanent Atrial Fibrillation

RACE II

 Prospective, multicenter, randomized, open label  The Netherlands  Patients assigned to strict (resting HR <80)or lenient ( resting HR <110) HR control using  Beta blocker or   Ca channel blocker or digoxin

RACE-II

 Followed every 2 weeks to titrate meds.

 At the end of the dose adjustment phase, almost all pts in the lenient group were at goal HR. Only 2/3 of pts in the strict group.

 Office visits  75 for lenient  684 for strict

RACE II – Primary Outcome

 Composite of death from the following causes:  CHF  CVA  Systemic embolism, major bleeding, arrhythmic events, sustained VT, arrest, life threatening adverse events, placement of PM or AICD

RACE II

 At 3 years, the cumulative incidence of the primary outcome between the 2 groups did not differ significantly  12.9% lenient group  14.9% strict group Frequency of symptoms and hospitalizations were similar in the 2 groups.

Question 6 …Take home point

 AFFIRM trial, rate control is equivalent to rhythm control in terms of survival.  In patients with permanent atrial fibrillation, lenient rate control with a target resting HR<110 is as effective as strict rate control in reducing adverse outcomes without increasing symptoms or number of hospitalizations.

 This can be achieved with less meds and less clinic visits in general.

Question 7

 A 32-year-old male presents to the emergency department with 6 hour complaint of substernal chest pain. Patient admits to habit of crack-cocaine use. Denies any other illicit drug use. No other past medical history and denies family history of coronary disease.

 Physical exam reveals blood pressure of 148/88 mmhg, heart rate of 88 beats/min , and respiratory rate of 14 breaths/min.  Cardiac enzymes (creatine kinase and troponin) are normal. ECG is normal without evidence of ischemia.

© 2010 ABIM

Which of the following is the best treatment option for this patient?

A.

B.

C.

Treat with aspirin and a benzodiazepine and observe until chest pain resolves Treat with aspirin and a beta adrenergic blocking agent, order complete cardiac enzyme studies, then discharge after pain resolves.

Treat with aspirin alone and order complete cardiac enzyme studies, then order a stress test before discharge

33% 33% 33% 10 A.

B.

C.

Cocaine and the heart

  Increase myocardial oxygen demand  Increase HR  Increase BP (peripheral vasoconstriction)  Increase contractility Acute Thrombosis  Increase platelet activation  Increase platelet aggregation  Early atherosclerosis  Seen on autopsy of young cocaine users

β-Blockers for Chest Pain Associated With Recent Cocaine Use

Carlos Rangel; Richard G. Shu, MD; Lawrence D. Lazar, MD; Eric Vittinghoff, PhD; Priscilla Y. Hsue, MD, MAS; Gregory M. Marcus, MD, MAS Arch Intern Med. 2010;170(10):874-879.

Background:

Recommendations against this use of β-blockers are based on animal studies, small human experiments, and anecdote.

Methods

Retrospective cohort study of consecutive patients admitted to the San Francisco General Hospital, San Francisco, California, with chest pain and urine toxicologic test results positive for cocaine. Mortality data were collected from the National Death Index.

Results

Of 331 patients with chest pain in the setting of recent cocaine use, 151 (46%) received a β-blocker in the emergency department. There were no meaningful differences in electrocardiographic changes, troponin levels, ventricular tachycardia or ventricular fibrillation, or death between those who did and did not receive a β-blocker.

Conclusion

β-Blockers do not appear to be associated with adverse events in patients with chest pain with recent cocaine use

Treatment algorithm for patients with cocaine-associated chest pain Schwartz, B. G. et al. Circulation 2010;122:2558-2569

Copyright ©2010 American Heart Association

Question 7 …Take Home Point

 Cocaine-induced chest pain without ECG changes or elevated biomarkers can be managed conservatively with aspirin, nitrates, and benzodiazepines.

 Beta-adrenergic blocking agents continue to be contraindicated because they can cause unopposed alpha stimulation that can worsen ischemia. However recent uncontrolled study cast some doubt on this.

 Stress tests have a high false-positive rate in the setting of recent cocaine use and should be delayed or avoided.

Question 8

A correlation exists between the use of proton pump inhibitors and which of the following?

A) B) C) D)

Clostridium difficile colitis

No Yes No Yes

Hospital-acquired pneumonia

No Yes Yes Yes

Osteoporosis related fracture

No No Yes Yes

© 2010 ABIM

A.

B.

C.

D.

A correlation exists between the use of proton pump inhibitors and which of the following?

25% 25% 25% 25% 10

A B C D

A.

B.

C.

D.

Question 8

Question 17

Question 17

Question 8 …Take Home Point

 Several studies now show a correlation between PPI use and each of the conditions mentioned in the table.  PPIs overuse is widely reported, and clinicians should be aware of potential complications.

Question 9

 A 58-year-old woman was diagnosed with Clostridium difficile colitis following a course of antibiotics for pyelonephritis. Symptoms resolved entirely after treatment with a 14-day course of metronidazole.  Ten days after completing the antibiotic course, the patient reports a two-day history of abdominal pain and diarrhea. She has not had fever or blood in her stools, but reports seven bowel movements during the past 24 hours.

Question 9

 Temperature is 37.1 C (98.7 F), pulse rate is 85 per minute, respirations are 14 per minute, and blood pressure is 105/62 mm Hg. The abdomen is soft, and examination reveals mild diffuse tenderness; bowel sounds are decreased. No peritoneal signs are detected. Leukocyte count is 13,600/μL, serum albumin is 3.2 g/dL, and stool assay for Clostridium difficile toxin is positive.

Which of the following oral agents should you prescribe next?

10 25% 25% 25% 25%

A.

B.

C.

D.

Cholestyramine Metronidazole Rifampin Vancomycin

A.

B.

C.

D.

Question 9

Question 9… Take Home Point

 Relapse rate of Clostridium difficile colitis is 10-25%  Relapse typically occurs one to two weeks after antibiotics are discontinued, but can occur months later. 

Initial relapse with non-severe disease should be treated with a second course of metronidazole; has been shown to be noninferior to vancomycin

. 

Patients with a second relapse or with severe disease should be treated with oral vancomycin.

 Severe disease defined as age > 60, T > 38.3 C (100.9 F), WBC > 20,000/microliter, albumin < 2.5 g/dL, and more than ten bowel movements daily)

Question 10. Supplementation with which of the following vitamins has been shown to lower the risk of prostate cancer?

25% 25% 25% 25%

A.

B.

C.

D.

Vitamin E

Yes Yes No No

Vitamin C Selenium

No Yes No No Yes No Yes No

A.

B.

C.

D.

:10

Question 16

Question 10… Take Home Point

 Previous studies (observational) suggested certain vitamin supplements may be effective for primary prevention of prostate cancer,  Recent randomized, controlled trials failed to show any benefit of vitamin E, vitamin C, or selenium in reducing the risk of prostate cancer or all-cause mortality.