Update in Internal Medicine for the Outpatientalist: 2015

George D. Comerci, Jr., MD, FACPProfessor of Internal Medicine

Co Director Project ECHO Pain and Headache Clinic

Financial Disclosure

• I receive partial salary support from Project ECHO

Case: A Traveler with Fever

• JD is a 56 y/o geologist who recently returned from Nigeria where he was exploring potential shale-rich fields for possible test drilling. He traveled extensively on local buses and is worried that he may have come in contact with someone with Ebola virus. He is asymptomatic.

• How should he be managed?

Ebola: 2014

• Epidemiology• Clinical Presentation• Diagnosis• Treatment • Prevention of Spread

Structure of Ebolavirus.

Feldmann H. N Engl J Med 2014;371:1375-1378.

Outbreaks or Episodes of Filovirus Infections.

Feldmann H. N Engl J Med 2014;371:1375-1378.

Signs and Symptoms in Patients with Fatal and Nonfatal EVD.

Schieffelin JS et al. N Engl J Med 2014. DOI: 10.1056/NEJMoa1411680

Case Fatality Rates among Patients with Ebola Virus Disease (EVD) in Sierra Leone.

Schieffelin JS et al. N Engl J Med 2014. DOI: 10.1056/NEJMoa1411680

Structures of Ebola Vaccine Candidates rVSV (Panel A) and cAd3 (Panel B).

Kanapathipillai R et al. N Engl J Med 2014. DOI: 10.1056/NEJMp1412166

MSF Staff Members Lead a Young Patient with Suspected Ebola into the Case-Management Center.

Wolz A. N Engl J Med 2014;371:1081-1083.

Back to JD….

• Close observation by health authorities• Quarantine NOT required• Isolation and treatment if fever develops

Case: A Marathon Runner with abnormal lipids

• JJ is a 55 y/o attorney who exercises vigorously for 1.5 hours, six days per week and recently completed a marathon. His cardiovascular risk per the ACC/AHA calculator is 9%. He thinks that the “statin industry” is behind the “drive to treat health people with drugs” to enrich their stockholders and has heard that statins cause dementia.

• How would you approach his elevated CV risk?

2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults : A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. (J Am Coll Cardiol. 2014)

• NHLBI convened the ATP IV to update guidelines-first since 2001

• Task: to critically review the existing literature and develop evidence-based treatment guidelines

Pooled Cohort Risk Assessment Equationshttp://my.americanheart.org/professional/StatementsGuidelines/Prevention-Guidelines

(J Am Coll Cardiol. 2014, Muntner. Ann Int Med.2104)• ASCVD [MI, stroke]

Age Sex Race DM Treatment for HTN Total cholesterol HDL Systolic BP Smoking status

Recommendations: ATP IV

Statin therapy recommended for Patients with clinical ASCVD Patients with LDL >70 -189mg/dL Patients with DM (40-75 y/o) with LDL = 70-189

mg/dl Patients 40-75 y/o with 10 yr. risk of 7.5% or more (patients 40-75 y/o with 10 yr. risk of > 5%)

Percent of U.S. Adults Who Would Be Eligible for Statin Therapy for Primary Prevention, According to Set of Guidelines and Age Group.

Pencina MJ et al. N Engl J Med 2014;370:1422-1431.

Recommendations: ATP IV

• Engage in clinician-patient discussion before initiating statin therapy

• Initiate appropriate intensity of statin therapy• No need to follow cholesterol levels• Consider: FH, CRP, coronary calcium score

Back to JJ….

• Statins are associated with lower all cause mortality, major vascular events and revascularization [Taylor.JAMA.2013]

• Statins do not increase risk of dementia (Richardson. Ann I Med. 2013)

• Consider: FH, CAC, CRP to assist with treatment planning

Most Rxed. Drugs: [WebMD]

The top 10 drugs by sales are:

• Abilify, $7.2 billion• Humira, $6.3 billion• Nexium, $6.3 billion• Crestor, $5.6 billion• Enbrel, $5.0 billion• Advair Diskus, $5.0 billion• Sovaldi, $4.4 billion• Remicade, $4.3 billion• Lantus Solostar, $3.8 billion• Neulasta, $3.6 billion

The top 10 drugs by number of monthly prescriptions are:

• • Synthroid, 22.6 million• Crestor, 22.5 million• Nexium, 18.6 million• Ventolin HFA, 17.5 million• Advair Diskus, 15.0 million• Diovan, 11.4 million• Lantus Solostar, 10.1 million• Cymbalta, 10.0 million• Vyvanse, 10.0 million• Lyrica, 9.6 million

Case: A 48 year old man with Hypertension

• JG is a 48 y/o man who has chronic renal insufficiency from long standing hypertension. Until recently, his blood pressures have been maintained at or below 125/75 according to JNC 7 guidelines. His average home readings obtained after three months of monitoring are 134/82.

• What course of action should you follow in view of the new JNC 8 Guidelines?

JNC 8Questions Guiding Evidence Review

• Does anti- HTNive pharmacologic therapy at specific BP thresholds improve outcomes?

• Does anti- HTNive pharmacologic therapy to a specified goal improve outcomes?

• Do anti- HTNive drugs differ with respect to health outcomes?

Recommendations:BP Thresholds and Goals

Age Comorbidity Systolic BP Diastolic BP Evidence

> or = 60 years None 150 (<150) 90 (<90) A

< 60 years None 140 (<140) 90 (<90) A

> or = 18 years CKD 140 (<140) 90 (<90) E

> Or = 18 years DM 140 (<140) 90 (<90) E

Recommendations:Drugs

Demographic Comorbidity Drug (initial) Evidence

General (not AA) None or DM Thiazide, CCB, ACE or ARB

B

General (AA ) None or DM Thiazide or CCB B

General (all) CKD ACE or ARB B

Controversies !

• Some panel members continue to recommend a treatment target of 140/90 in those > 60 y/o

• CKD: JNC 7 (125/75) vs. JNC 8 (<140/90)• DM: JNC 7: start with ACE I vs. JNC 8: start with thiazide, ACE, ARB,CCB

(Wright J, et. al. 2014, Mancia G. 2014)

Back to JG….

• Make sure that his regimen contains an ACE or an ARB (not both)

• No need to alter therapy

A Man with a TIA

RJ is a 59 y/o man with HTN and hyperlipidemia who was recently admitted to the hospital with right sided weakness and dysphasia for 6 hours. During his hospitalization, he had a continuous EKG monitoring for 48 hours, an echocardiogram and carotid dopplers, all of which were unremarkable. An MRI of the brain was normal. How should he be treated at this point?

Atrial Fibrillation in Patients with Cryptogenic Stroke (Gladstone, et. al. NEJM.2014)

• Stroke: leading cause of death and disability 12 million annually!

• 1 in 6 strokes due to Afib• 20-40% of strokes and 1 of 2 TIAs are

“cryptogenic”• Standard workup

Echo, 24 hour Holter and brain imaging

Atrial Fibrillation in Patients with Cryptogenic Stroke

• Gladstone and colleagues 16 stroke centers @ Canadian Stroke Consortium

• Hypothesis: 30 days of electrocardiographic monitoring vs. standard monitoring would improve diagnosis and treatment of Afib

• Primary Outcome: ECG documented Afib lasting > 30 seconds

Atrial Fibrillation in Patients with Cryptogenic Stroke

• Study Population: 55 or older with stroke or TIA within last 6 mos. Stroke was classified as “cryptogenic” after: 24

hour Holter, Echo and neurovascular imaging 572 patient randomized to 30 day event triggered

loop monitor vs. 24 hour Holter All patient followed up at 90 days

Detection of Atrial Fibrillation in the Two Monitoring Groups.

Gladstone DJ et al. N Engl J Med 2014;370:2467-2477.

Incremental Yield of Prolonged ECG Monitoring for the Detection of Atrial Fibrillation in Patients with Cryptogenic Stroke or TIA.

Gladstone DJ et al. N Engl J Med 2014;370:2467-2477.

Cryptogenic stroke and underlying atrial fibrillation CRYSTAL AF.

(Sanna, et. Al. NEJM 2014)

• Sanna and colleagues enrolled patients at 55 centers in Europe, Canada and the US

• Hypothesis: long term follow-up of stroke/ TIA patients with an implantable cardiac monitor (ICM) is superior to conventional follow-up for detection of Afib

• Primary Outcome: first detection of Afib at 6 months of follow-up

Cryptogenic stroke and underlying atrial fibrillation CRYSTAL AF.

(Sanna, et. Al. NEJM 2014)

• Study Population: 40 years or older with recent diagnosis of stroke or TIA with the last 90 days

• Stroke was classified as “cryptogenic” after evaluation with: 24 hour Holter, TEE, screening for thrombophilic states and MRA, CTA or catheter angiography of carotids

• Industry sponsored: Medtronics

Time to First Detection of Atrial Fibrillation.

Sanna T et al. N Engl J Med 2014;370:2478-2486.

Conclusions

• Subclinical Afib is detected in a significant number of patients with prolonged monitoring

• Failure to diagnose Afib in the setting of stroke or TIA represent suboptimal care

• Current standard of care should change to prolonged monitoring

• Outcome studies need to be performed.

Back to RJ…

• Strongly consider prolonged monitoring with event monitor

• Initiate warfarin or oral anticoagulant if Afib found

Prevention and Screening

• High dose influenza vaccine for patients > 65 y/o

• PCV 13 for patients > 65 y/o• Diabetes and the Mediterranean diet• Screening for AAA• Screening for heritable breast cancer

Efficacy of High-Dose versus Standard Dose Influenza Vaccine in Older Adults

(DiazGranados, CA, et. al. NEJM 2014)

• Multicenter (126) study sites• 31,989 participants• Randomized to receive IIV3-HD or IIV3-SD• 228 (1.4%) vs 301 (1.9%) developed laboratory

confirmed influenza• Overall relative efficacy was 24.2%

Use of 13-Valent Pneumococcal Conjugate Vaccine and 23-Valent Pneumococcal Polysaccharide Vaccine Among Adults Aged ≥65 Years: Recommendations of the Advisory Committee on Immunization Practices (ACIP)

Date of download: 11/1/2014

From: Prevention of Diabetes With Mediterranean Diets: A Subgroup Analysis of a Randomized Trial

Ann Intern Med. 2014;160(1):1-10. doi:10.7326/M13-1725

Cumulative incidence of diabetes (or either diabetes or death).Nelson-Aalen curves are shown with the outcome of new-onset diabetes (top) or either diabetes or death (bottom), by exposure to each MedDiet intervention vs. the control diet. EVOO = extra-virgin olive oil; HR = hazard ratio; MedDiet = Mediterranean diet.

Figure Legend:

Copyright © American College of Physicians. All rights reserved.

Screening for Abdominal Aortic Aneurysm:(USPSTF Ann Intern Med. 2014:)

• AAA U/S for ALL men, 65-75 y/o who have ever

smoked [B] U/S selectively for men 65-75 who have never

smoked [C] Evidence insufficient for women

Risk Assessment of BRCA-related Cancer in WomenUSPSTF Ann Intern Med.2104

• Screening for women who have family members with breast, ovarian, tubal, or peritoneal cancer to identify a family history that may be associated with an increased risk for potentially harmful mutations in breast cancer susceptibility genes (BRCA1 or BRCA2).

Date of download: 10/13/2014

From: Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer in Women: U.S. Preventive Services Task Force Recommendation Statement

Ann Intern Med. 2014;160(4):271-281. doi:10.7326/M13-2747

Copyright © American College of Physicians. All rights reserved.

New drugs, New uses for Old Drugs

• Neprilysin and CHF• Oral Zinc for the common cold• Paroxetine for menopausal hot flashes• PPIs/H2 blockers and B12 deficiency

•

Angiotensin- neprilysin inhibition versus enalapril in heart failure.

McMurry J. NEJM. 2014

• Neprilysin is a neutral endopeptidase that degrades endogenous vasoactive peptides (natiruretic peptides, bradykinin and adrenomedullin)

• Neprilysin + ARB was superior to enalapril in patients with CHF and reduced EF

Kaplan–Meier Curves for Key Study Outcomes, According to Study Group.

McMurray JJ et al. N Engl J Med 2014;371:993-1004.

Oral Zinc for the Common ColdDas R, Singh M. JAMA. 2014

• Zinc blocks ICAM-1 receptor which is what the receptor where the rhinovirus attaches to nasal mucosa

• Initiation of therapy with Zn within 24-48 hours of symptoms reduces cold duration by one day but does not reduce symptoms

• High dose lozenges (> 75 mg/d) better)

Paroxetine controlled release in the treatment of menopausal hot flashes: a randomized controlled

trial.(Stearns V. JAMA.2014)

• Paroxetine 7.5 mg nightly reduces hot flushes from a median of 10-12 per day to 5-6/day.

Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency.

(Lam R. JAMA. 2014

.

• PPIs and H2 Blockers used for greater than 2 years significantly increased the risk of B12 deficiency

Summary• Ebola virus• New cholesterol guidelines• New HTN guidelines• Occult Afib in TIA and stroke• Prevention:

– Screening women for FH BRCA cancers– Ultrasound for all med > 65 y/0

• Screening

Flu and PCV 13 vaccines in 65 year olds

Mediterranean diet and DM reduction

THANK YOU!!