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:

COW Week 10

29yF presents with fever, sore throat, tonsillar exudate, anterior cervical LAD, no cough. Rapid strep negative. What is the next step? Pt has no allergies?

1) PCN V
2) Send Home
3) Send Throat Culture, start PCN
4) Augmentin

The correct answer is 2, Send Home. 

The IDSA just came out with new guidelines on September 9th 2012 for management of strep throat. GAS is the most common bacterial cause of acute pharyngitis, responsible for 5%–15% of sore throat visits in adults and 20%–30% in children. The main reason to treat strep throat is to decrease the chance of rheumatic fever and suppurative complications of strep throat. However, in adults, the chance of developing rheumatic fever is very small. We've all heard about the Centor criteria to diagnose strep throat. The 4 criteria are: Reported fever, anterior cervical LAD, lack of cough, tonsillar exudate. If the patient has 0 or 1 of these criteria this has pretty good negative predictive value and you can stop there. Generally, adults do not need to be tested for strep throat if they have a cough, runny nose, hoarseness and mouth sores, which are strong signs of a viral throat infection. However, strep and non strep symptoms have such overlap that even if a patient meets all 4 of the Centor criteria, there is a positive predictive value of only 35-55% leading to significant over treatment with abx that the IDSA says is unacceptable.  Because of this, treatment for strep throat should only be given with a positive diagnostic test, with rapid recommended over culture. If culture is chosen, you should wait until the culture is positive before giving abx even though it may delay treatment a couple days. Lastly, given the low frequency of strep complications in adults, a negative rapid strep test, even in the setting of 4 centor criteria, is enough to send the patient home without any further diagnostic studies. Cultures do not need to be sent to confirm the diagnosis.

The take home points are:
1) Rapid antigen/culture should be performed to diagnose and treat GAS pharygitis. Negative rapid should not be followed with a culture in adults.
2) Clinical Criteria has good negative predictive value, however, it is not specific enough to make a diagnosis alone.
3) PCN or Amoxicillin x 10 days is the treatment of choice for nonallergic patients
4) If PCN allergic, 10 day course of 1st generation cephalosporin, clindamycin, clarithromycin or 5 days of azithromycin can be used.

Click on the link below to see the new guidelines:
IDSA GAS Pharyngitis 2012 Guidelines

COW Week 9

37yo male complains of left leg painful swelling. Ultrasound confirms popliteal DVT. There was no antecedent trauma, surgery, hospitalizations, or trips. Family history is negative and thrombophilia workup is negative. After three months of warfarin therapy, what is the next step?

1. Continue Warfarin for 1 year
2. Stop Warfarin
3. Countinue Warfarin indefinitely
4. Stop Warfarin and start aspirin
5. Further diagnostic testing

After an idiopathic thrombotic event, the 10-year risk of recurrence is about 30 percent. The risk of major bleeding while on warfarin therapy is approximately 2 percent per year when warfarin is well managed. Therefore, it can be helpful to to further risk stratify patients which can be done with D-Dimer testing or lower extremity doppler ultrasound.

The Prolong Trial assessed using D-Dimer testing to determine the duration of anticoagulation. This was a prospective trial that evaluated 600 people with idiopathic DVT after 3 months of therapy with warfarin. Their D-Dimer was checked one month after stopping warfarin and if it was abnormal the patients were randomized to further anticoagulation or no therapy. The risk of venous thrombosis if you had a positive D-Dimer and you were left off of warfarin therapy was approximately 10 percent per year. A negative D-Dimer predicted a risk of recurrence of about 3 percent per year

The DACUS trial looked at 250 patients who had on warfarin for at least 3 months and then assessed residual thrombus by ultrasound. If there was residual thrombus, then they randomized patients either to resume warfarin or to stop warfarin; if there was no residual thrombus then they simply stopped warfarin therapy. Patient's without evidence of thrombosis had a low risk of DVT recurrence suggesting continued warfarin therapy was unnecessary in this group past the three month window.

The take-home points for unprovoked deep vein thrombosis are that the risk of recurrence is relatively high. The risk of major bleeding while on warfarin therapy is approximately 2 percent per year when warfarin is well managed. Using risk stratification tools such as D-Dimer and a duplex ultrasound for residual vein thrombosis can help guide your management.

Prolong Trial:
DACUS Trial:

COW Week 8

A 60 yo male is admitted  for his 3rd episode of diverticular lower GI bleeding. Surgery evaluates him for hemicolectomy. He has ETOH cirrhosis and his last drink was 1 week ago. His Child-Pugh class is C and MELD score is 23. He denies chest pain or DOE. Exercise tolerance is 8 Mets and his ECHO shows an EF of 65%. You are asked for a preoperative evaluation.

Which of the following is the best recommendation for his elective surgery?
a. Delay surgery 7-10 days
b. Delay surgery indefinitely until risk improves
c. Proceed with surgery without further risk stratification
d. Recommend against elective surgery

While this patient has no active cardiac conditions and a fair-moderate exercise tolerance, he is still a poor surgical candiate in terms of his liver disease and elective surgery should be avoided. Child-Turcotte-Pugh class A, B, anc C have a 10%, 30%, and 80% postoperative mortality respectively. Patients with MELD score greater then15 are also considered to be at greater risk for postoperative mortality. Other risk factors in cirrhotic patients include age greater then 70yrs, obstructive jaundice,and  portal hypertension. Therefore, elective surgeries are avoided in these patients.

Risk Factors for Mortality After Surgery in Patients With Cirrhosis: Gastroenterology. 2007; 132(4):1261-1269

COW Week 7

A 58 yo post-menopausal female presents for F/U. She is concerned about her risk for breast cancer and wants to know if there is preventative therapy. She is uptodate on mammogram screening with normal results. Her sister was diagnosed with breast cancer at age 65. She has no children and menarche was at age 11. What should you do?

a. half-yearly mammograms

b. reassurance

c. discuss tamoxifen  (correct answer)

d. prophylactic mastectomies

According to the Gail model or Breast Cancer Risk Assessment Tool (BCRAT),  this patient has a 3.1% risk of developing breast cancer in the next 5 years. The Gail model is a clinical tool to help physicians calculate a woman’s individual risk of developing breast cancer over the next five years based on current age, age of menarche, age of first live birth, first degree relatives with breast cancer, prior breast biopsies, and race. The tool was created based on the Care Trial (looking specifically at African Americans) and Breast Cancer Detection Demonstration Project. The tool is not intended for women with a history suggesting inherited breast cancer.

The SERMs tamoxifen and raloxifene reduce the risk for new breast cancer by as much as 50%. For premenopausal women, tamoxifen is the only Food and Drug Administration–approved SERM for breast cancer prevention. For postmenopausal women, both tamoxifen and raloxifene are Food and Drug Administration–approved therapies. Use of these agents is approved for women with Gail model scores of greater than 1.7% for the risk of breast cancer over the next 5 years. Side effect profiles dictate whether tamoxifen or raloxifene should be used. Both the American Society of Clinical Oncology and USPSTF recommend discussing the risks/benefts of breast cancer prevention with these high risk women and starting a SERM if benefits outweigh risks. There are many risks to these therapies which would warrant not starting medication including but not limited to uterine cancer. Models have been developed to estimate the risk/benefit ratio of raloxifene and tamoxifen for postmenopausal women based upon their risk factors and can assist in risk discussions

The American Breast Cancer Prevention Trial sponsored by the National Surgical Adjuvant Breast and Bowel Project (NSABP) first showed the benefits of tamoxifen for breast cancer prevention. Women were eligible for the NSABP trial if they were considered to be "at increased risk" for breast cancer (age;60yrs or age 35-59 with a Gail score of at least 1.66%) and randomized to receive tamoxifen 20mg/daily vs. placebo. The study was stopped early after a median follow-up of 48 months when an interim analysis found that the benefit of tamoxifen was already statistically significant showing a relative risk reduction of 43% (2.5% vs. 4.3%) of invasive breast cancer and 37% for non-invasive breast cancer. The reduction was entirely by a decrease in ER-positive tumors and thus there was no significant change in occurrence of ER-negative tumors. Older women were found to have derived the most benefit. However, there was no difference in overall or breast cancer specific-survival between those receiving tamoxifen versus those receiving placebo

COW week 6

35 yo F w/ SLE and HTN has 1 month of worsening dull substernal CP associated w/ nausea and SOB. Episodes lasts  less than 15 minutes She takes prednisone 10mg, ASA & lisinopril. Vitals & PE are normal. EKG: NSR, TWI leads V1- V3. the first troponin is less than 0.04. What do you do?

Answer:

B.  CCU: heparin/Diagnostic Cath

This young female has HTN but no other traditional or "Framingham " Risk factors for CAD, but has autoimmune inflammatory disease. The proposed mechanism for increased risk of premature CAD is endothelial injury.  CAD is a major cause of death in patients with SLE so they should be considered high risk. Given this history plus ASA use,  worsening Angina, and T wave inversions, this patient should be treated as a "High TIMI" equivelent Unstable Angina/NSTEMI and be triaged to early  coronary angiography (within 48-72 hours).  Heparin or LMWH can be considered along with NTG sublingual or gtt  and Beta-blocker for HR control.

One study found that  "after controlling for common risk factors at baseline, the increase in relative risk for these outcomes was 10.1 for nonfatal MI (95% CI 5.8-15.6), 17.0 for death due to CHD (95% CI 8.1-29.7), 7.5 for overall CHD (95% CI 5.1-10.4), and 7.9 for stroke (95% CI 4.0-13.6)."

Stress test is unlikely to be helpful as this patient is high risk rather than intermediate risk.  The patient's CV exam is normal, which is unlikely in pericarditis or pericardial effusion with tamponade (would be significant for friction rub, Elevated JVP and Pulsus Pardoxus) though this can happen in SLE. In addition low voltage and electrical alternans would likely be present on EKG, no TWI.

Observation Unit would not be appropriate as this patient is high risk. D/C home would not be appropriate.   The patient has SLE so her HSCRP would be unhelpful (likely high due to systemic disease.

See the references below:

Esdaile JM, Abrahamowicz M, Grodzicky T, etal Traditional Framingham risk factors fail to fully account for accelerated atherosclerosis in systemic lupus erythematosus. Arthritis Rheum. 2001 Oct;44(10):2331-7

Bessant R,  Hingorani A, Patel L, et al Risk of coronary heart disease and stroke in a large British cohort of patients with systemic lupus erythematosus Rheumatology (2004) 43 (7): 924-929.

COW Week 5 Answer

COW#5

You are a resident in the ICU. You admit a 57y/o male for a COPD exacerbation. When would prophylactic PPI not be indicated with the following additional history?

Answer D: The patient is started on solumedrol 40mg IV daily.

Data from large prospective observational studies have found that ICU patients who have coagulopathy or respiratory failure requiring mechanical ventilation have a substantially higher risk of clinically important bleeding.  A prospective multicenter cohort study evaluated potential risk factors for stress ulceration in patients admitted to ICUs (Cook et al, Risk Factors for gastrointestinal bleeding in critically ill patients, NEJM 1994). Of 2252 patients, 33 (1.5%) had clinically important bleeding. Two strong independent risk factors for bleeding were identified: respiratory failure requiring ventilation x 48 hours (odds ratio [OR] 15.6) and coagulopathy (OR 4.3) defined as Plt<50 inr="inr">1.5 or PTT>2x control. Of 847 patients who had one or both of these risk factors, 31(3.7%) had clinically important bleeding. Of 1405 patients without these risk factors, 2 (0.1%) had clinically important bleeding. Of note, some potential risk factors for bleeding have not been adequately studied and it is unclear if they are independent predictors of bleeding. A majority of investigations excluded patients with a history of ulcers or GI bleed as well as long term NSAID use. Additionally, it was found that as minor risk factors build up, there is a higher risk for GI bleed. In 1999, the American Society of Health-System Pharmaciests (ASHP) released guidelines for stress ulcer prophylaxis. The recommendations are as follows:

1) Prophylaxis is recommended in patients with coagulopathy or patients requiring mechanical ventilation for more than 48 hours. (Strength of evidence = C= Non randomized cohort studies)

2) Prophylaxis is also recommended in patients with a history of GI ulceration or bleeding within one year before admission(Strength of evidence = D = Expert Opinion)

3) Prophylaxis is also recommended in patients with at least TWO of the following risk factors: sepsis, ICU stay of more than one week, occult bleeding lasting six days or more, and use of high-dose corticosteroids (>250 mg per day of hydrocortisone or the equivalent). (Strength of evidence = D = Expert Opinion)

4) Many clinicians also recommend prophylaxis for patients with traumatic brain injury, traumatic spinal cord injury, or thermal injury (>35 percent of the body surface area), as these special populations are generally excluded from studies given their high risk of stress ulcers.

5) Lastly, it is recommended to continue a PPI for a patient already on a PPI as there is a risk for rebound gastric acid hypersecretion.

TAKE HOME POINT: The two biggest risk factors for GI bleeding in the ICU is coagulopathy and intubation! 

Click on the link below for a good summary

Stress Induced Ulcer PPX Summary 

Also below are the 1999 guidelines. Its pretty long but read the portion on stress ulcer ppx. They have nice summaries in italics after each section:

ASHP Therapeutic Guidelines on Stress Ulcer Prophylaxis. ASHP Commission on Therapeutics and approved by the ASHP Board of Directors on November 14, 1998 Am J Health Syst Pharm February 1, 1999 56:347-379

COW Week 4 Answer

This patient should have been started on argatroban 2 days ago when HIT was suspected and should stay in the hospital for minimum 2 weeks on an argatroban drip. Fonadaprinux can be used off-label for outpatient management but this is not FDA approved. Coumadin is not appropriate as HIT is a very hypercoagulable state requiring a “true” anticoagulant. Coumadin does not inhibit activated clotting factors and has also been associated with a purpura fulminans kind of syndrome in this setting. Up to 50% of patients with HIT develop thrombosis.

Words of Wisdom from Dr. Rosove:

This patient has heparin induced thrombocytopenia (HIT). HIT develops anywhere from day 4 to 14 of de novo therapy. It takes that long for IgG antibodies to the heparin-platelet factor 4 complex to develop. Thrombocytopenia can occur earlier than day 4, even immediately, upon exposure to unfractionated heparin (UFH) if there has been a recent exposure to any glycosaminoglycan anticoagulant, GAG, (UFH, LMWH, or fondaparinux) such that antibodies are already present. This patient was exposed to heparin recently which is why her platelets dropped so quickly.

HIT patients must be anticoagulated for a minimum of two weeks (3 months per Board Review), even if there is full recovery of the platelet count, no evident thrombosis, and no need for longer-term anticoagulation. By two weeks, nearly all of the acute risk has passed. If there is evidence of thrombosis then one must be anti-coagulated for 3-6months. The only FDA-approved anticoagulants for HIT are argatroban, bivalirudin, and lepirudin (the first two are on our formulary), but these are IV infusions, thus requiring inpatient care. Therefore fondaparinux SQ is often given off-label to allow outpatient management. Fondaprinux may perpetuate antibody formation but is virtually incapable of causing HIT. Rivaroxaban or dabigatran could also serve in the same capacity since they are not GAGs, but neither have been tested and thus should not be used at this time.

HIT is a preventable problem. By far it occurs more frequently with UFH than LMWH, and HIT due to fondaparinux is practically reportable. Therefore, whenever there is a reasonable choice of which anticoagulant to use, UFH is best avoided altogether. In the case of unstable angina and percutaneous coronary interventions, there are legitimate alternatives to UFH.

A positive HAPA, no matter how strongly positive, only permits a diagnosis of HIT, it does not make a diagnosis since the majority of patients who are antibody positive do not have HIT. However, the negative predictive value of HAPA is nearly perfect.

ACCP 2012 Guidelines: HIT 

HIT Clinical Review 

COW Week 3 Answer

Answer: 1 and 3

ALLHAT was a double blind RCT evaluating adults with HTN and at least one cardiac risk factor (prior MI, CVA, LVH, DM, Tob, low HDL, known atherosclerosis) and randomized them to 3 groups: Amlodipine vs Chlorthalidone vs Lisinopril. After 5 years, 68% of patients in the Chlorthalidone group achieved the blood pressure goal (less than140/90) vs 66% in the Amlodipine group and 61% in the Lisinopril group. There was no difference in all cause mortality or fatal coronary heart disease and nonfatal MIs. However, the Chlorthalidone group did have a significant decrease in Heart failure and stroke when compared to Lisinopril. Based on ALLHAT, a thiazide diuretic, chlorthalidone, is at least as effective if not better than several other medications as first line therapy in high risk patients with hypertension and it is definitely cheaper. For this reason, the JNC 7 recommends thiazides as first line agents for hypertension in most patients.

In this vignette, the patient has diabetic nephropathy due to his proteinuria. In such patients, JNC 7 recommends an ACE/ARB as first line treatment rather than a thiazide. However, the patient has stage II hypertension for which JNC recommends 2 medications as initial therapy. Thus, this patient should be started on both a Thiazide and ACE/ARB.

Lastly, the ACCOMPLISH trial compared HCTZ and Benazepril vs Amlodipine and Benazepril in patients with HTN and high cardiovascular risk and showed Amlodipine to be superior by decreasing cardiovascular events. Some experts believe this is due to HCTZ being a less potent Thiazide than Chlorthalidone. Stay tuned to the upcoming JNC 8 to see if the recommendations change!! Click on the link below to see the articles.

 ALLHAT
ACCOMPLISH

COW Week 2 Answer

The AIM-HIGH Study (N Engl J Med 2011; 365:2255-2267) looked at patients with established cardiovascular disease already on appropriate statin therapy who had low LDL and low HDL. They were randomized to statin alone or statin plus niacin. There was no incremental clinical benefit from the addition of niacin to statin therapy during a 36-month follow-up period, despite significant improvements in HDL cholesterol and triglyceride levels.

The ACCORD Trial (N Engl J Med 2010; 362:1563-1574) looked at combination lipid therapy in type 2 diabetes and found no difference in cardiovascular outcomes between statin alone and statin plus fenofibrate. However, a subgroup analysis of patients with low HDL and triglycerides above 200 did show improved outcomes. Based on this subgroup, a new clinical trial is currently underway to study whether addition of fibrates to patients on optimal statin therapy (ie: LDL less than 70) with low HDL and high triglycerides reduces cardiovascular mortality. 

So niacin is out, but the the utility of fibrates is yet to be determined.

Remember: just because the numbers look good doesn't mean it has any clinical significance!

NEJM Article: AIM-HIGH

NEJM Article: ACCORD

Choosing Wisely

Choosing Wisely:  ABIM asked professional societies how best to eliminate high-cost/low value care.  Consumer Reports got on board and the result was this.  See the link to the lists from each society with the rationale for each.   Below is the full list.

Choosing Wisely

1. Don’t perform unproven diagnostic tests, such as immunoglobulin G (IgG) testing or an indiscriminate battery of immunoglobulin E (IgE) tests, in the evaluation of allergy.

2. Don’t order sinus computed tomography (CT) or indiscriminately prescribe antibiotics for uncomplicated acute rhinosinusitis.

3. Don’t routinely do diagnostic testing in patients with chronic urticaria.

4. Don’t recommend replacement immunoglobulin therapy for recurrent infections unless impaired antibody responses to vaccinesare demonstrated.

5. Don’t diagnose or manage asthma without spirometry.

6. Don’t do imaging for low back pain within the first six weeks, unless red flags are present.

7. Don’t routinely prescribe antibiotics for acute mild-to-moderate sinusitis unless symptoms last for seven or more days, or symptoms worsen after initial clinical improvement.

8. Don’t use dual-energy x-ray absorptiometry (DEXA) screening for osteoporosis in women younger than 65 or men younger than 70 with no risk factors.

9. Don’t order annual electrocardiograms (EKGs) or any other cardiac screening for low-risk patients without symptoms.

10. Don’t perform Pap smears on women younger than 21 or who have had a hysterectomy for non-cancer disease.

11. Don’t perform stress cardiac imaging or advanced non-invasive imaging in the initial evaluation of patients without cardiac symptoms unless high-risk markers are present.

12. Don’t perform annual stress cardiac imaging or advanced non-invasive imaging as part of routine follow-up in asymptomatic patients.

13. Don’t perform stress cardiac imaging or advanced non-invasive imaging as a pre-operative assessment in patients scheduled to undergo low-risk non-cardiac surgery.

14. Don’t perform echocardiography as routine follow-up for mild, asymptomatic native valve disease in adult patients with no change in signs or symptoms.

15. Don’t perform stenting of non-culprit lesions during percutaneous coronary intervention (PCI) for uncomplicated hemodynamically stable ST-segment elevation myocardial infarction (STEMI).

16. Don’t obtain screening exercise electrocardiogram testing in individuals who are asymptomatic and at low risk for coronary heart disease.

17. Don’t obtain imaging studies in patients with non-specific low back pain.

18. In the evaluation of simple syncope and a normal neurological examination, don’t obtain brain imaging studies (CT or MRI).

19. In patients with low pretest probability of venous thromboembo­lism (VTE), obtain a high-sensitive D-dimer measurement as the initial diagnostic test; don’t obtain imaging studies as the initial diagnostic test.

20. Don’t obtain preoperative chest radiography in the absence of a clinical suspicion for intrathoracic pathology.

21. Don’t do imaging for uncomplicated headache.

22. Don’t image for suspected pulmonary embolism (PE) without moderate or high pre-test probability.

23. Avoid admission or preoperative chest x-rays for ambulatory patients with unremarkable history and physical exam.

24. Don’t do computed tomography (CT) for the evaluation of suspected appendicitis in children until after ultrasound has been considered as an option.

25. Don’t recommend follow-up imaging for clinically inconsequential adnexal cysts.

26. For pharmacological treatment of patients with gastroesophageal reflux disease (GERD), long-term acid suppression therapy (proton pump inhibitors or histamine2 receptor antagonists) should be titrated to the lowest effective dose needed to achieve therapeutic goals.

27. Do not repeat colorectal cancer screening (by any method) for 10 years after a high-quality colonoscopy is negative in average-risk individuals.

28. Do not repeat colonoscopy for at least five years for patients who have one or two small (< 1 cm) adenomatous polyps, without high-grade dysplasia, completely removed via a high-quality colonoscopy.

29. For a patient who is diagnosed with Barrett’s esophagus, who has undergone a second endoscopy that confirms the absence of dysplasia on biopsy, a follow-up surveillance examination should not be performed in less than three years as per published guidelines.

30. For a patient with functional abdominal pain syndrome (as per ROME III criteria) computed tomography (CT) scans should not be repeated unless there is a major change in clinical findings or symptoms.

31. Don’t use cancer-directed therapy for solid tumor patients with the following characteristics: low performance status (3 or 4), no benefit from prior evidence-based interventions, not eligible for a clinical trial, and no strong evidence supporting the clinical value of further anti-cancer treatment.

32. Don’t perform PET, CT, and radionuclide bone scans in the staging of early prostate cancer at low risk for metastasis.

33. Don’t perform PET, CT, and radionuclide bone scans in the staging of early breast cancer at low risk for metastasis.

34. Don’t perform surveillance testing (biomarkers) or imaging (PET, CT, and radionuclide bone scans) for asymptomatic individuals who have been treated for breast cancer with curative intent.

35. Don’t use white cell stimulating factors for primary prevention of febrile neutropenia for patients with less than 20 percent risk for this complication.

36. Don’t perform routine cancer screening for dialysis patients with limited life expectancies without signs or symptoms.

37. Don’t administer erythropoiesis-stimulating agents (ESAs) to chronic kidney disease (CKD) patients with hemoglobin levels greater than or equal to 10 g/dL without symptoms of anemia.

38. Avoid nonsteroidal anti-inflammatory drugs (NSAIDS) in individuals with hypertension or heart failure or CKD of all causes, including diabetes.

39. Don’t place peripherally inserted central catheters (PICC) in stage III–V CKD patients without consulting nephrology.

40. Don’t initiate chronic dialysis without ensuring a shared decision-making process between patients, their families, and their physicians.

41. Don’t perform stress cardiac imaging or coronary angiography in patients without cardiac symptoms unless high-risk markersare present.

42. Don’t perform cardiac imaging for patients who are at low risk.

43. Don’t perform radionuclide imaging as part of routine follow-up in asymptomatic patients.

44. Don’t perform cardiac imaging as a pre-operative assessment in patients scheduled to undergo low- or intermediate-risknon-cardiac surgery.

45. Use methods to reduce radiation exposure in cardiac imaging, whenever possible, including not performing such tests when limited benefits are likely.