COW Week 17

61 yo patient with diabetes (HbA1c 7.2 on metformin) has been on Lipitor 80mg for over one year. His LDL is 146, HDL is 44, Tg are 118. How should you address his lipid profile?

a. add Zetia 10mg/day

b. change Lipitor to Crestor

c. add Niacin

d. add another statin

The first thing one should do is ensure the patient is taking the medication correctly and adhering to a strict diet and exercise regiment. The next step would be to try a more potent statin (Crestor).

Zetia has been show to decrease LDL by 14-17% when combined with a statin, however there is no evidence that addition of Zetia has any effect on mortality or cardiovascular outcomes.

The ENHANCE trial randomized patients to simvastatin 80mg with or without ezetimbide 10mg daily. Combination therapy provided a significant LDL decrease and HDL increase. However, there was no difference in primary outcome of carotid intima-media thickness or cardiovascular events.  The ARBITER 6-HALTs trial took patients with CHD or CHD equivalents who were already on statins and randomized them to niacin or ezetimibide. Addition of Niacin had better outcomes then addition of ezetimibide. We already know from the AIM-HIGH trial that niacin really provides no benefit in patients already on a statin. Thus, all this data seems to suggest that the addition of ezetimibe does not provide clinical benefit. Additionally, ezetimibe has some potential concerning side effects including a possible cancer link that was noted the SEAS trial.

In the absence of an indication other than prevention of CHD, do not treat patients with another lipid-lowering medication in combination with a statin even if the LDL-C is not at goal. There is a theory that the actual statin itself is more important than the LDL goal. Some advocate only adding on a second lipid lowering agent if the LDL is still greater then 160. 

The ATP 4 committee is actually discussing this issue right now and we asked our expert for insider information. Unfortunately, it is classified, so all we can advise is that it is a grade E recommendation (ie: expert opinion but little or no data to support it) to consider adding a second class of lipid lowering drugs in select patients. 

Statins are the only lipid lowering class of drugs to demonstrate clear improvements in overall mortality in primary and secondary prevention. It is reasonable to try a different statin as you may see better results and Crestor is more potent then lipitor.

COW week 16

40 yo F admitted for CAP, Has PCN allergy, no other PMHx. Febrile to 102.3, HR 105. BP 122/67. O2 is 96% on 2LNC. Patient is placed on levofloxacin. In addition to DVT Px, what other preventive measures should be considered?

Pepcid 20 mg po BID
Lactobacillus 1 cap Daily- Correct Answer
Protonix 40 mg daily
Pneumovax




Rationale:

This patient is healthy and has become ill with community acquired pneumonia.  Based on the question stub, there is no prior history of pneumonia or other recurrent infections. There is no data the pneumovax in indicated in patients presenting with CAP without other indications for Pneumovax

From the CDC  website- Adult indications 23-Valent Pneumococcal Polysaccharide Vaccine

• All adults 65 years of age and older.
• Anyone 2 through 64 years of age who has a long-term health problem such as: heart disease, lung disease, sickle cell disease, diabetes, alcoholism, cirrhosis, leaks of cerebrospinal fluid or cochlear implant.
• Anyone 2 through 64 years of age who has a disease or condition that lowers the body’s resistance to infection, such as: Hodgkin’s disease; lymphoma or leukemia; kidney failure; multiple myeloma; nephrotic syndrome; HIV infection or AIDS; damaged spleen, or no spleen; organ transplant.
• Anyone 2 through 64 years of age who is taking a drug or treatment that lowers the body’s resistance to infection, such as: long-term steroids, certain cancer drugs, radiation therapy.
• Any adult 19 through 64 years of age who is a smoker or has asthma.
• Residents of nursing homes or long-term care facilities.

Given that this patient has 1 episode of CAP, she does not meet criteria for any of the above so should not have the testing.  Of note, the patient only has a 25% chance of having her CAP from Penumococcus to begin with:

Percentage of pathogens in CAP in inpatients NOT admitted to ICU:

S. pneumoniae 25% Respiratory viruses10% M. pneumoniae 6% H. influenzae 5% C. pneumoniae  3% Legionella species 3% Unknown 37%
	With regard to GI prophylaxis with PPI or H2 Blocker- the indications for Stess Ucler Prophylaxis are as follows: Coagulopathy (plts<50 inr="inr">1.5, ptt> 2x over control) Mechanical Ventilation > 48 hours Traumtic Brain or Spinal cord injury Severe Burns  2 or more of the following: Sepsis, ICU x7+days, GI bleed without a source >6 days, or equivalent prednisone dose 50 mg/day or more The patient meets none of these critera and has no hx of GERD or PUD so does not require acid suppression.  The addition of a PPI is associated with increased risk of C. Diff colitis The patient is on antibitiotics for her infection, and fluroquinolones are associated with risk of C. Diff Colitis.  A recent meta-analysis published online ahead of print in the Annals of Internal Medicine (www.annals.org) found that in 13 trials, patient on antibiotics who were given probiotics had a reduced the incidence of C. Diff associated diarrhea by 66% (pooled relative risk, 0.34 [95% CI, 0.24 to 0.49]).  Though there was variability of the type and dose of probiotic, the effect size was large.   Thus in this patient, probiotics (in this case lactobacillus caps) may be considered to reduced her risk of complications from her antibiotic therapy.

COW Week 15

39yM presents with left facial droop x 2days. No other neurologic symptoms. Given forehead muscle involvement, hyperacusis, you diagnose him with Bell's Palsy. What do you do now?

A) Valacyclovir x 7 days

B) Prednisone x 10 days

C) Prednsione and Valacyclovir

D) Observation  

 Answer: B (C is also acceptable)

Up to 30% of patients with Bell's Palsy fail to recover facial function completely. The disease is common, with an annual incidence of 20 per 100,000 leading to thousands of patients per year with facial weakness. In the updated guidelines from the American Academy of Neurology, oral steroids are recommended for new-onset Bell's palsy to improve recovery of facial function. In these guidelines, 9 studies were identified comparing steroids and antivirals to placebo for Bell's Palsy. Regarding oral steroids, 2 class 1 studies comparing oral prednisolone to placebo for 10 days showed a significant improvement in complete facial recovery translating to a Number Needed to Treat of 6-8 people to achieve one complete recovery.  Regarding antivirals, there was no evidence of any benefit however, the authors conclude that the statistical power was insufficient to exclude a small benefit or harm and some believe that antivirals carry an additional benefit when added to steroids. The academy says that antivirals may be offered in addition to steroids, but patients should be counseled that the benefit is unknown and likely modest at best. 

In Journal Watch Neurology, Robert T. Naismith comments: "The side-effect profile for oral glucocorticoids is relatively favorable, and a 10-day course can be recommended within 3 days after facial-weakness onset. If the patient is evaluated for treatment after 3 days, the benefit may be smaller, and treatment would be up to the judgment of the physician and patient."

Lastly, remember to consider other etiologies such as Lyme, VZV, HSV, rarely HIV, Sjorgren's, Sarcoid and others as some of these do require alternative treatments.

 American Academy of Neurology Updated Guidelines on Bell Palsy

COW Week 14

34 yo F presents for WH appt. Feels well, reports mild non-purulent vaginal discharge x2 months. Monogamous x4 years, no hx of STI. Speculum exam normal, wet mount/koh prep negative. Pap returns normal except rare trichomonas. What next?

1. Intravaginal metronidazole gel (0.75%) once daily for five days
2. Metronidazole 2g po xi
3. Metronidazole 500mg po BID x7d and treat partner
4. New specimen for Fungal and T. vaginalis Cultures -Correct Answer



This is a healthy patient with questionable symptoms (her discharge may also be physiologic).  She is not in a high risk group, and trichmononas, though a common disease, is an unlikely cause in this patient and is a surprising finding.  The most common vaginal discharges are BV, Trich and Candida.  Of the "bedside" tests, the Wet Mount has the best sensitivity (clue cells:sensitivity 98.2%, specificity 94.3%, positive predictive value 89.9%, negative predictive value 99.0%).  The Whiff Test is also relatively sensitive. BV is thus ruled out by the the findings.  Of note Intravaingal Metronidazole is a treatment only for BV, not TV.

KOH prep is not particularly sensitive 60% for vulvovaginal candidasisis (a more likely Dx than Trich in this patient).  If symptoms persist, it may be reasonable to send for gram stain/fungal culture in this patient to clarify the diagnosis. Also fungal culture is indicated if patient has failed Rx for candida to look for non-abicans species.

Wet mount is not particularly sensitive for T. vaginalis (40–70%), especially if there is time lag in sample transport.  Trich is likely under diagnosed as a result, and further investigation is warranted, especially in patients treated for Candida or BV (without partner treatment-as males are almost always asymptomatic). The wet mount does have good specificity for Trich.  Patients with history of STIs should be investigated for T. vaginalis (along with CT/GC) if they have any symptoms of discharge. Any patient that is diagnosed with T. Vaginalis should have partner treatment as well to reduce risk of re-infection, and barrier methods should be used until treatment is complete.

However, in this case we have the opposite situation. We doubt the diagnosis of TV as it did not show up on bedside tests and the patient is not high risk.  The specificity of cytology for trich is such that in an endemic area or high risk population, treatment can be based upon a positive result, but not in low risk/low endemic area. In this case, it's reasonable for us to use a more sensitive and specific test for trichomonas: either culture or PCR to confirm diagnosis. In addition, fungal culture would help rule out candidaisis. 

 Sherrard J, Donders G, White D, Jensen JS; European IUSTI. European (IUSTI/WHO) guideline on the management of vaginal discharge, 2011. Int J STD AIDS. 2011 Aug;22(8):421-9.

COW Week 13

A 58 yo American female presents to establish care. She has a history of exercise induced asthma and HTN but is otherwise healthy without bad habits. What test should be part of your health maintenance screening?


a. DEXA
b. Hep C- Correct Answer
c. Zoster Vaccine
d. TSH

The Centers for Disease Control and Prevention (CDC) now recommends screening for all persons in the United States born between 1945 and 1965. This is a new recommendation as of 2012. This was based on a mathematical model that showed theapproach of 1-time screening for hepatitis C in this birth cohort followed by treatment was cost-effective. 

Annals of Internal Medicine February 2012

Dexa scan is recommended in females >65: The USPSTF recommends screening for osteoporosis in women aged 65 years or older and in younger women whose fracture risk is equal to or greater than that of a 65-year-old white woman who has no additional risk factors. The patient has no additional risk factors so should NOT be screened

USPSTF- Osteoporosis Screening

Zoster Vaccine in recommended by the CDC in patients without contraindications. This patient does not meet criteria based on age.

Shingles

There is insufficient evidence for thyroid screening in asymptomatic adults

USPSTF- TSH

COW Week 12

64 yo M presents to establish care. Has CAD, HTN, DM-II.  He feels well, had recent negative stress test with his cardiologist, has good exercise tolerance.  Meds are metofromin/glipizide, metoprolol, ASA, lisinopril, fish oil and atorvastatin. Labs: Cr 1.1, A1c 7.1, HDL 30, LDL 68, U protein/CR Ratio 450mg/day.  Echo shows EF 40%.

What should you do:

Add Niacin

Change MTP to Coreg

Add Losartan- Correct Answer

Change glipizide to insulin basal/bolus

This patient's CAD is well controlled and though he has a low EF he does not have clinical evidence of CHF. The patient's EF does not necessitate a change to carvedilol .  The landmark Comet Trial compared long-acting Metoprolol (Toprol XL) to Carvedilol (Coreg) in NYHA Class II-V CHF with EF 35% or less. The results showed improvement in these patients with Carvedilol.   This patient does not have symptomatic CHF and his EF is 40% so he does not meet inclusion criteria for this trial and thus does not have in indication for a change in Beta Blocker Therapy.
 
 The patient's LDL is a at goal, and he is on fish oil, however he has low HDL.  Currently there are limited effective therapy to raise HDL other than statins and fish oil.  Niacin is controversial.

The patient's A1c is at/near goal, there is no indication to change his hypoglycemics to insulin at this time.  However, the patient has evidence of nephropathy, and his proteinuria is not controlled by his ACE-I.  Thus he requires dual RAAS inhibition, which will confer now additional anti-hypertensive benefit but will decrease his proteiuria,.

Adding an ARB is currently not recommended in patients with CHF on an ACEi + BB but still symptomatic. A Cochrane review of outcomes of ARB plus ACE inhibitor therapy to ACE inhibitor therapy alone in patients with HF was dominated by the Val-HeFT and CHARM-Added results [3,12,13]. There were no statistically significant differences in total mortality (RR 0.98, 0.90-1.06), cardiovascular mortality, or non-cardiovascular mortality between combined ARB plus ACE inhibitor and ACE inhibitor monotherapy. Combination therapy reduced hospitalization for HF compared to ACE inhibitor therapy (RR 0.81, 95% CI .074, 0.89) but did not reduce total hospitalizations. Withdrawals due to adverse effects were more frequent with combination therapy

Poole-Wilson  PA  et al Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomised controlled trial.
Lancet. 2003 Jul 5;362(9377):7-13.

Cohen DL, and Townsend RR Is There Added Value to Adding ARB to ACE Inhibitors in the Management of CKD?JASN August 1, 2009 vol. 20 no. 8 1666-1668

COW Week 11

Your 60yo male patient has COPD (FEV1 50%, FEV1/FVC 60%). He is compliant with his Advair and prn Combivent (with good technique) and stopped smoking 2 years ago. He is enrolled in pulmonary rehab and has a normal resting and ambulatory oxygen saturation. He has had 4 exacerbations in the past year. His other medications include lisinopril and atorvastatin and he has no cardiac history. What should be your next step?

a. Azithromycin 250mg MWF
b. EKG
c. Lung Reduction Surgery
d. Oxygen

Acute exacerbations of COPD portend to further morbidity. Each exacerbation increases the rate of FEV1 decline by an additional 2ml or 7ml per year in non-smokers and smoker respectively. The cost to society is also high. Treatment of COPD includes smoking cessation, pulmonary rehab, anti-cholinergics, beta-agonists, and glucocorticoids. Some patients, despite maximal therapy, may still have uncontrolled disease. Macrolides have anti-inflammatory and immune-modultating effects and may decrease the production of cytokines in the lungs (Role of Macrolide therapy in COPD. Int J Chron Obstruc Pulmon Dis 2008;3:331-50). Thus, these have been studied in COPD.

NEJM published a study in 2011 showing daily use of azithromycin 250mg reduced the frequency of acute exacerbations of COPD (NEJM Article). The median time to the first acute exacerbation was increased by 92 days compared to the placebo group (266 days compared to 174 days). Quality of life was also improved per the St. George's Respiratory Questionnaire. There was no statistically significant difference in mortality. Similar results were found in a trial using erythromycin (Am J Respir Crit Care Med 2008; 178:1139-47).

Long-term use of azithromycin comes with many concerns including prolonged QT (greater than 450), ototoxicity, drug interactions, and possible antibiotic resistance. The risk of torsades is of great concern. It is because of these side-effecs that the GOLD report guidelines stated that despite it's proven efficacy azithromycin is "not recommended because of an unfavorable balance between benefits and side effects" (GOLD Report).

Many expert believe it is still safe and reasonable to add azithromycin if proper baseline screening is done.  Important baseline tests include heart-rate, QTc, audiography,  LFTs, and medicationreview. If the patient is taking a QTc prolonging agent, has a baseline QTc greater than 450, or has a significant cardiac history (CHF, hx of stroke) then azithromycin is not recommended. Additionally it is not recommended if the patient has an abnormal audiogram or LFTs greater then 3x the ULN. If these tests are normal then it is reasonable to start a trial of azithromycin, but only in those patients who continue to have frequent COPD exacerbations despite being on maximal therapy (~ 2 or more a year). Expert opinion favors three times a week dosing, despite the trials using a daily dose based on pharmacokinietics of the drug. This may also minimize the side effects. (NEMJ Clinical Therueptucis article). They also recommend repeating EKG, audiography, and labs every three months to monitor for side effects. Some experts suggest obtaining a baseline sputum culture to asses for nontuberculous mycobactermia as well.

Therefore, for this patient the answer is to obtain a baseline EKG and hearing test. If normal, it is reasonable to start azithromycin three times a week with monitoring of side effects.

This case is based on the following article: NEJM Clinical Therapeutics of COPD: