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