top 10 innovations in primary care (in the past year) robert dachs, md, faafp assistant director,...

Top 10 innovations in Primary Care(in the past year)

Robert Dachs, MD, FAAFPAssistant Director, Dept of Emergency Medicine

Ellis Hospital, Schenectady, NYClinical Associate Professor

Ellis Family Medicine Residency ProgramAlbany Medical College

Mark Graber, MD, FACEPProfessor of Family and Emergency Medicine

University of Iowa Carver College of MedicineIowa City, Iowa

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Disclosure Statement• Drs. Dachs and Graber have no affiliations with any

product or pharmaceutical manufacturer. • We are clinicians so you are about to hear what we

think may be paradigm changers from this year’s literature.

• We will run through “bonus” topics at the end: things we don’t have time for but might tweak your interest.

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I. Atrial fibrillation Management

Dabigatran: Boon, Bust or Hype?

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Atrial fibrillation Management

• Who gets anticoagulation?

• Who is at risk for hemorrhages?

• And is dabigatran (Pradaxa) everything its cracked up to be?

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Atrial Fibrillation and StrokeWhy do we anticoagulate?

The older the patient with atrial fibrillation, the higher the risk of cardioembolic stroke.

Strokes due to Afib have higher mortality and morbidity. Warfarin decreases absolute annual risk from

4.5% --> 1.4% (NNT=30).

CVA rate(% per yr)

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Atrial Fibrillation: Who Gets Warfarin?

ACC/AHA 2011 Guideline

• No risk factors……………….• One moderate risk factor……• Any high-risk factor OR

> 2 moderate risk factors…….

Risk Category Recommended Therapy

ASA 81-325mg q dASA or warfarin

Warfarin (INR 2.0-3.0)

Moderate-risk factorsAge > 75yrs

HTNCHF

LV ejection fraction < 35%DM

High-risk factorsPrevious CVA,TIA,embolism

Mitral stenosisProsthetic heart valve

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Atrial fibrillation Management: 1) Who gets anticoagulation?

• Last year----- CHADS2

• This year--- CHA2DS2- Vasc

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Atrial Fibrillation: the CHADS2 Score

• CHF• HTN • Age >75 yrs• DM• Prior Stroke or TIA

CHADS2 Risk Criteria Score11112

Pts. (N=1733) CVA Rate (%/yr) (95%CI) CHADS2 Score 120 1.9 (1.2 - 3.0) 0 463 2.8 (2.0 - 3.8) 1 523 4.0 (3.1 - 5.1) 2 337 5.9 (4.6 - 7.3) 3

220 8.5 (6.3 - 11.1) 4 65 12.5 (8.2 - 17.5) 5 5 18.2 (10.5 -27.4) 6

Risk Category0: Low-risk (ASA)1: Moderate (ASA or warfarin)2+: High-risk (warfarin)

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CHADS2 vs. CHA2DS2-VASc?

• CHF• HTN • Age >75 yrs• DM• Prior Stroke or TIA

CHADS2 Score11112

Score11212111

CHA2DS2-VASc• CHF• HTN • Age >75 yrs• DM• Prior Stroke or TIA• Vascular disease• Age 65-74 yrs• Female sex

N=1733 vs. N= 1,084 ptswith afib, not on warfarin1 year in Euro Heart study Yip GB, et al. Chest 2010; 137:263-72Gage BF, et al JAMA 2001; 285:2864-70

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CHADS2 vs. CHA2DS2-VASc?

- Low risk = 0 points - Low risk = 0 points

- Intermediate = 1 pt - Intermediate = 1 pt

CHADS2 CVA Rate @ 1yr

1.67% vs. 0.78%

4.75% vs. 2.0%

CHA2DS2-VASc

N= 73,538 pts with afib, not on warfarin 10 year period in Denmark

Olesen, JB, et al. BMJ 2011; 342:d124

A large external validation study -

That’s what we like to see…

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Atrial Fibrillation: Anticoagulation Risks/Benefits

• Decreases CVA by approx 3%/yr

• Rate of ICH 0.1 - 0.6%– Increased with advanced age, HTN

• Major bleeding rates: 1.2%/yr

2. So which patients need to avoid anticoagulation???

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“But I Am Fearful of My Elderly Patient Falling (ie, Subdural)”• Using an analytic model …• A patient over age 65 with Afib must

sustain 295 falls in one year for the risk of subdural to outweigh benefit of stroke prevention

Man-Son-Hing, et al. Arch Intern Med. 1999;159(7):677-85.

Note 1: Patients on warfarin, spontaneous ICH more common than subduralNote 2: Model uses assumptions - are they correct?

That’s last year - this year….

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Previously….• HEMORR2HAGES (2006)

– 1604 pts derived from NRAF database– 10 variables - not all easy to obtain (eg “Genetic factors

such as CYP 2C9 polymorphism)

• Shireman, et al. (2006)– 26,345 pts from NRAF database– 8 variables…but score too complicated!!!!!!!

That’s last year - this year….

Risk Score = 0.49*X age70+ + 0.32*Xfemale + 0.58*Xremote Bleed

+ 0.62*XRecent Bleed + 0.71*Xalcohol/Drug Abuse +

+ 0.86*Xanemia + 0.32*Xantiplatelet Agent

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Two new scoring systems:HAS-BLED and ATRIA

• A novel User-friendly Score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation. Pisters R, et al. Chest 2010; 138: 1093-1100.

• A new risk scheme to predict Warfarin-associated hemorrhage: The ATRIA study. Fang MC, et al. J AM Coll Card 2011; 58: 395-401

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Who needs to avoid anticoagulation?? HAS-BLED

1 H Hypertension Sys BP > 160

1 or2 A Abnormal Renal and/or dialysis/transplant(1pt each) liver function cirrhosis/T. Bili 2x or

AST/ALT 3x normal

1 S Stroke1 B Bleeding previous bleed/predisposition

1 L Labile INR < 60% in therapeutic range 1 E Elderly (> 65 yrs)1 or2 D Drugs or alcohol excess antiplatelet or NSAID’s(1pt each)

Points Definition

A score of > 3 is considered “high risk”ESC recommends “caution” using warfarin1

1ESC Guidelines for the management of atrial fibrillation, 2011

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HAS- BLED: Results

0 1517 9 0.59 798 9 1.131 1589 24 1.51 1286 13 1.022 219 7 3.20 744 14 1.88------------------------------------------------------------------------------------3 41 8 19.51 187 7 3.744 14 3 21.43 46 4 8.705 1 0 - 8 1 12.506 - - - 2 0 07 - - - - - -8 - - - - - -9 - - - - - -

Score

Derivation Cohort Validation Cohort

n # of bleeds

Bleeds per100 pt yrs

# of bleeds

Bleeds per100 pt yrsn

1) bleeding requiring hospitalization 2) require transfusion3) drop in Hgb > 2 g/L 4) Hemorrhagic CVA

Major bleeds defined as any below:

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ATRIA: Results Derived from 13,559 pts in Kaiser system

Derivation:Validation = 2 :1 ratio

• Low risk (0-3) 0.72 0.83• Intermediate (4) 2.71 2.41• High (5-10) 5.99 5.32

• Anemia: Hgb <13 male, <12 female• GFR < 30• Age >75 yrs• Any prior hemorrhage Dx• HTN

Score33211

Risk category, points Events/100 pt/yrsDerivation Validation

One of my favorite websites: mdcalc.com

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Atrial fibrillation Management

Dabigatran: Is it really 35% better?????

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What about dabigatran (Pradaxa)?• RE-LY trial: NEJM 2009; 361: 1139-51.• Methods: 18,113 pts with afib, randomized to:

dabigatran dabigatran warfarin110mg BID 150mg BID

• Results– CVA/embolism 1.53% 1.11%* 1.69%– Major bleeding/yr 2.71% 3.11% 3.36% – Mortality rate/yr 3.75% 3.64% 4.13%

followed for 2yrs

Cost: Pradexa = $230 per month, $2760 per year

Price accessed @ drugstore.com - 3/25/11

NNT=172

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Pet Peeve…..

…….Benefits in: Relative Risk

……Harm in: Absolute numbers

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And there will be more to come..

• Rivaroxaban (Xarelto)– ROCKET-AF trial, non-inferior to warfarin

Published online, NEJM Aug 10, 2011

NEJM Sept 8, 2011

• Apixaban (Eliquis)– ARISTOTLE trial, non-inferior to warfarin

Presented at European Society of Cardiology, Aug 2011

NEJM; Sept 15, 2011

Reservations…..• Cost

– Even with INR monitoring, warfarin is cheaperShah SV, et al. Circulation 2011; 123: 2562-

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• Efficacy vs. effectiveness (in the community)

• How about we do a better job with warfarin? Weekly home monitoring (vs. monthly outpt.) improves therapeutic range from 50-60% to

85%Decreases VTE events, mortality and

hemorrhages!!Heneghan C, et al. Lancet 2006; 367:404-11 Cochrane review, April 2010

Bolland MJ et al. Calcium supplements with or without vitamin D and risk of cardiovascular events: Reanalysis of the Women's Health Initiative limited access dataset

and meta-analysis. BMJ 2011 Apr 19; 342:d2040. (

http://dx.doi.org/10.1136/bmj.d2040) and

Warensjo E et al. Dietary calcium intake and risk of fracture and osteoporosis prospective longitudinal cohort study

BMJ 2011; 342:d1473 doi: 10.1136/bmj.d1473 (Published 24 May 2011)

II. Calcium intake: heart disease and bone health

http://dx.doi.org/10.1136/bmj.d2040

First Study

• Reanalysis of Women’s Health Initiative• Randomized 36, 282 to placebo or calcium• 1000mg/d and 400 IU daily of Vit. D.• Primary endpoint was fracture.• This is a second analysis of the randomized

data looking for cardiac outcomes.• Original study included serial EKGs

What did they find?

• Hazard ratio for cardiovascular event (MI, CVA, Revascularization: 1.13-1.22 (significant p value) only in those not taking supplements already.

• In those taking supplements at randomization, overall mortality was less.

• NNH: 178, NNT: 302

Second study

• Cohort study of 61,433 women born 1914-1948. • Randomized study started 1987 and was of fracture

risk.• Based on the Swedish Mammography Cohort• 5022 in the sub-cohort that looked at Dexa scans. • Followed for 19 years.• Calcium intake as reported by patients.

• 24% of women had a fracture and 6% had a hip fracture.

• Calcium intake of 750mg-882mg/day (second quintile) was as good at preventing fractures and osteoporosis as were higher levels of calcium intake.

• In fact, highest quintile had Hazard ratio = 1.19 (95%CI 1.06-1.32) for hip Fx.

Conclusion?

• Cardiac disease: who knows?• But, shoot for lower dose calcium

supplementation.

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http://www.nih.gov/news/health/may2011/niaid-12.htm(In press….)

andThe H IV-CAUSAL Collaboration. When to initiate

combined antiretroviral therapy to reduce mortality and AIDS-defining illness in HIV-infected persons in developed countries: An observational study. Ann

Intern Med 2011 Apr 19; 154:509.

III. HIV Update: This will be in the new guidelines…

http://www.nih.gov/news/health/may2011/niaid-12.htm

We know early treatment helps the patient

• Kitahata MM et al. Effect of early versus deferred antiretroviral therapy for HIV on survival. N Engl J Med 2009 Apr 1; [e-pub ahead of print]. (http://dx.doi.org/doi:10.1056/NEJMoa0807252)

• Sax PE and Baden LR. When to start antiretroviral therapy — Ready when you are? N Engl J Med 2009 Apr 1; [e-pub ahead of print]. (http://dx.doi.org/10.1056/NEJMe0902713)

http://dx.doi.org/doi:10.1056/NEJMoa0807252

http://dx.doi.org/10.1056/NEJMe0902713

• 1,763 couples. 97% heterosexual.• One HIV+ partner• Randomized to HAART immediately or after

CD4<250 cells/mm3

• Total cases: 39• 28 cases from partner to partner transmission

based on genetics.• 27 in the late HAART group.• Early treatment prevents transmission

Second study

• 8392 patients• Observational study• If started HAART at 350/mm3 instead of at

500/mm3 40% increase in AIDS-defining illness + death.

• NNT 48

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IV. Cancer screening:One step up,____ step back?

The National Lung Screening Trial. NEJM 2011; 365: 395-409.

• Methods: 53,454 adults, age 55-74 yrs– 30+ pack yr smokers– Randomized to:

– enrolled 2002 - 04, followed to 12/31/09

3 annual chest CT’s vs. 1 Chest x-ray

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• Results: Chest CT Chest x-ray

Deaths per 100,000 247 309Person/years

• Author’s Conclusion “…representing a relative risk reduction in mortality from lung cancer with low-dose CT screening of 20.0% (95%CI, 6.8 -26.7)

p=0.004”

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• Author’s Conclusion “…representing a relative risk reduction in mortality from lung cancer with low-dose CT screening of 20.0% (95%CI, 6.8 -26.7)

P=0.004”When will we stop allowing RRR?

(and insist on absolute risk reduction and NNT)

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N=26,722 N=26,732

Lung Ca Deaths 356 443

Lung cancer deaths 1.33% 1.65% NNT 312

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Lung cancer deaths 1.33% 1.65% NNT 312

NNH >1 in 3 false (+) CT scan

1 in 30 unnecessary surgery

1 in 161 with surgical complication

One of my favorite websites: TheNNT.com

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Putting those risks into perspective….

• Chest CT group: 26,722– Any (+) test 10,448

(39.1%)– Lung CA confirmed 649 (3.6%)

False (+) rate = 96.5%

More CT’s, bronchoscopy, needle biopsy, ect….

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What happens when you go after those “nodules” with needle transthoracic (CT) needle biopsy?

• Methods: 15,865 pts with CT needle biopsy– From 2006 State Ambulatory Surgery

Databases in California, NY, Michigan, FL• Results:

– Pneumothorax 15.0%• Needing chest tube 6.6% of all

procedures NNH = 6.6 and 15

– Hemorrhage 1.0%• Needing transfusion 17% of

“hemorrhages” Weiner RS, et al. Ann of Intern Med 2011; 155: 137-144

Not another infectious disease guideline!

Urinary Tract Infection: Clinical Practice Guideline for the Diagnosis and Management of the Initial UTI in Febrile Infants and Children 2 to 24 Months SUBCOMMITTEE ON QUALITY IMPROVEMENT AND STEERING MANAGEMENT SUBCOMMITTEE ON URINARY TRACT INFECTION and STEERING

Pediatrics; originally published online August 28, 2011;DOI: 10.1542/peds.2011-1330

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What we know?

• Treatment and diagnosis is all over the place.

• Workup after 1st episode?• Workup after 2nd episode?• And what workup should be done.

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Some answers

• Analysis of medical literature.• UTI defined as pyuria and at least 50,000

cfu

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What do they recommend?

• US for all children after first febrile UTI (Level of evidence: C).

• NO VCUG unless US shows scarring of kidneys, hydronephrosis, etc. (Level of evidence: B)

• Modelling: Only 1:100 will have grade V• NO prophylactic antibiotics if grade I-IV reflux

(Level of evidence: ??? But RCT)

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VI. The potential PE patient…

•The problem: excessive CT utilization

•The answer: Risk stratification

• Last year: Well’s Criteria• This year: PERC Rule

How to risk stratify?

– 75 million in 2009

–- 7% (5 million) in children

–-60% are women

CT use in USA

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CT scan and radiation risks• Children/young adults: greater Cancer risk

– tissues are more radiosensitive– more years of life to develop radiation induced cancer

• Est. lifetime risk of cancer from one 64 slice Chest CT – 20 y/o female = 1 in 142– 40 y/o female = 1 in 284– 60 y/o female = 1 in 466– 80 y/o female = 1 in 1338

Einstein AJ, et al. JAMA 2007; 298: 317-23.

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Wells Clinical Prediction Rules for: PE

• Clinical Symptoms of DVT 3• Other diagnosis less likely that PE 3• Pulse > 100 1.5• Immobilization or surgery within 4 weeks 1.5 1• Previous DVT or PE 1.5• Hemoptysis 1• Malignancy (actively treated in past 6 mos) 1

Points

High risk >6 Moderate risk 2-6 Low risk <2 78% PE 27.8% PE 3.4% PE

Wells PS, et al. Thromb Haemost 2000

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The PERC rule

• low clinical gestalt (<15% chance) with

– Age <50– Pulse <100– SaO2 > 95%– No previous VTE

- No hemoptysis- No estrogen use- No unilateral leg swelling- No surgery/trauma requiring hospitalization in past 4 weeks

Derived from 3148 patients

Kline JA, et al. Jour Thromb Haemostasis, 2004

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PERC Rule:Validation Study

• Methods: 13 ED’s, 8183 patients– 85% with CC of chest pain or dyspnea– Enrolled if study for PE was ordered– Measures: PE or death within 45 days

• Results: 1666 pts. very low risk: PERC (-)neg– 15 with PE, 1 death = 1.0% (95%CI; 0.6 -

1.6%)Kline JA, et al. J Thromb Haemost May 2008; 6: 772-80.

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How about a community hospital?or “Why I believe in PERC..”

• Methods: 308 pts with chest CT– 7/1/08 - 10/31/08, @ Ellis Hospital ED– 213 (69%) to “R/O PE”– 2 reviewers applied PERC rule

• Results: 48 (of the 213) met PERC rule• All 48 were negative for PE (100% sensitive)!

(95% CI; 83.4 - 100%)

• Of the remaining 165 pts, 18 had (+) PE– Negative Predictive value = 100%(95% CI,93.8-

100%)Dachs R, Kulkani D, Higgins,G.

published ahead of print, Am J Emerg Med 2010

Kullar R et al. Impact of vancomycin exposure on outcomes in patients with methicillin-resistant Staphylococcus aureus bacteremia: Support for consensus guidelines suggested

targets. Clin Infect Dis 2011 Apr 15; 52:975.

VII. Antimicrobial Update

Previous Literature

• Vancomycin vs. Traditional anti-Staph drug for MSSA (Beta-Lactam)

• Mortality: (37% vs. 11%; P=0.006).

• Kim S-H et al. Outcome of vancomycin treatment in patients with methicillin-susceptible Staphylococcus aureus bacteremia. Antimicrob Agents Chemother 2008 Jan; 52:192.

This study

• Vanco has poor tissue penetration, slow bacteriocidal activity

• Retrospective look at 320 patients treated with vancomycin for MRSA (2005-2010)

• 52% failed using standard clinical criteria• Predictors:

– Endocarditis– Hospital acquired MRSA– Trough level <15 micrograms/ml– Value of area under curve vs. MIC <421

Conclusion:

• Increase trough levels to 15-20 micrograms/ml• Area under curve of >400.• Linezolid• Tigecycline • Change from Vanco if you have sensitivities of

MSSA• But…companion piece points out that if MIC >2,

high risk of renal injury if reach goals

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VIII. Decreasing antibiotic use and ClinicalTrials.gov

• The antibiotic pipeline is drying up• Strides (small) in decreasing antibiotic use are

being made– Weiss K, et al. CID, published online 7/25/11– http://www.cdc.gov/nchs/ahcd.htm

• Antibiotics rarely useful in otitis media– NNT = 16, NNH =24 (Cochrane Review, 2008)– Use of “delayed”/“Back-up” prescriptions

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This article takes a step backwards (and why its wrong)

• Methods: 291 children, ages 6 mos - 2 yrs– With AOM (reasonable criteria)– Randomized, double-blind to:

Treatment of Acute Otitis Media in Children under 2 years of age. Hoberman A, et al.

NEJM 2011; 364:105-15.

amoxicillin-clavulanate vs. Placebo (90mg/kg)

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• Results: amoxicillin-clavulanate vs. Placebo

(n=144) (n=147)

1. Resolution of symptoms- Day 2 35%

28%- Day 4 61%

54%- Day 7 80%

74%

P = 0.142. 2 successive days AOM-SOS score 0-1

- Day 2 20% 14%

- Day 4 41% 36%

- Day 7 67% 53%

P=0.04, overall

Antibiotics and AOM. Hoberman A, et al. NEJM 2011; 364:105-15.

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(n=144) (n=147)

3. Severity of symptomsAOM-SOS scores (14 pt scale) 1.59

2.46@10-12 day visit P=0.003, clinically insignificant

4. Clinical failure (otoscopy)- Day 4-5 4%

23%- Day 10-12 16%

51% P = < 0.001


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• Author’s Conclusion:

• Really???


Antibiotics “…tended to reduce time to resolution of symptoms and reduced overall symptom burden and rate of persistent signs of acute infection on

otoscopic examination.”

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• You can’t report out multiple (4) “primary outcomes”– The more outcomes you look at, by chance

alone one will be positive


Problems with this study….

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• You can’t have 4 primary outcomes….• Who cares what the TM looks like????

4. Clinical failure (otoscopy) amox-clavulanateplacebo- Day 4-5 4%

23%- Day 10-12 16%

51% P = < 0.001



This is a “DOE” not a “POEM”

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• You can’t have 4 primary outcomes….• Who cares what the TM looks like????• You can’t convert a secondary outcome

into a primary outcome(just to create a positive study)



Enter…ClinicalTrials.gov

The “predefined” primary outcomes

No clinical differences

Hoberman A et al. N Engl J Med 2011;364:105-115.

This is the primary endpoint

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• You can’t report a secondary outcome as a primary outcome!!!– Otoscopy findings were predefined as a

secondary outcome!!! – It only allows for hypothesis generation– Especially when there are 21 secondary

outcomes

“The primary objective of this study will be to compare time to resolution of symptoms in children receiving

amoxicillin/clavulanate and children receiving placebo”.

Why I am thankful for ClinicalTrials.gov

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(n=143) (n=146)

Mean # of times analgesia 0.37 0.43

P=0.35Mean # of visits to office 0.15

0.23

P=0.20Mean # of ED visits 0.07

0.07

# of cases of family membermissing work 33 33


Other secondary outcomes - not reported

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(n=143) (n=146)

Parental satisfaction1 = very dissatified5 - Very satisfied

Day 5 4.19 4.13

P=0.71 Day 11 4.40 4.12

P=0.04


Other secondary outcomes - not reported

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(n=144) (n=147)

Clinical failure (otoscopy)- Day 4-5 4%

23%- Day 10-12 16%

51% P = < 0.001

Side effects: diarrhea 24% 7%C.difficile 6 cases 1

Diaper dermatitis 47% 16%


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• Author’s Conclusion:

• Really???


Antibiotics “…tended to reduce time to resolution of symptoms and reduced overall symptom burden and rate of persistent signs of acute infection on

otoscopic examination.”

Antibiotics “…provide NO clinical benefit and increase the rate of

diarrhea illness with potential harm” R. Dachs

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And antibiotics in children….

• Increasing rates of C. difficile infection in hospitalized children in US1.– 3565 cases in 1997--> 7779 cases in 2006

• Antibiotic use increases risk of CA-MRSA in children2 (and adults3)

1Nylund CM et al. Arch Pediatr Adolesc Med 2011; published online Jan 3, 20112Schneider-Lindner, et al. Arch Pediatr Adolesc Med 2011; published online Aug 1, 2011 3Schneider-Lindner, et al. Emerg Infect Dis 2007; 13: 994-1000

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Skin infections in 2000 = 13th placeSkin infections in 2009 = 7th place

Schneider LS et al. Lack of evidence for the efficacy of memantine in mild Alzheimer disease. Arch Neurol

2011 Apr 11; [e-pub ahead of print]. (http://dx.doi.org/10.1001/archneurol.2011.69)

IX. Are the millions of dollars spenton Alzheimer meds and antidepressants

in demented elderly worthwhile?

http://dx.doi.org/10.1001/archneurol.2011.69

Previous Literature

• NNT 12

• No important positive outcomes (time to nursing home, ability to do ADLs, etc.)

• Donepezil not effective in minimal cognitive impairment

• Cholinesterase inhibitors for patients with Alzheimer’s disease: systematic review of randomized trials, BMJ 2005;331;321-327

• Doody RS et al. Donepezil treatment of patients with MCI: A 48-week randomized, placebo-controlled trial. Neurology 2009 May 5; 72:1555.

This study

Why is this study important?•Meta-analysis of 3 studies of patients with “mild” Alzheimer’s disease.•3 trials including 431 with mild disease (MMSE 20-23)•Did not find any benefit in cognitive function, global functioning, ADL or behaviour.•No difference in any scale between memantine and placebo.

• ADAS-cog,

• CIBIC-plus,

• ADCS-ADL scale,

• Neuropsychiatric Inventory

Conclusion: Memantine doesn’t work for mild Alzheimer's.

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Sube B. et. Al. Sertraline or mirtazapine for depression in dementia (HTA-SADD): a randomised, multicentre, double-blind,

placebo-controlled trial Lancet 2011; 378: 403–11

• Double blind, placebo controlled trial of those with “possible or probable” Alzheimers who were attending a geriatric psychiatry clinic (not shut-ins). Cornell score of depression of >8, had a care giver, not suicidal. (only 8 patient’s were “possible”)

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• Randomized to placebo, sertraline (Zoloft) (150mg), or mirtazapine (Remeron) (45mg)

• Outcome was 13 and 39 week Cornell Score

• Used linear regression to control for which center patients were from (??), baseline Cornell scale of depression in dementia, time of participation (??)

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• 111 controls• 107 patients randomized to sertraline or

mirtazapine

• No differences between placebo and treatment arms. No difference between mirtazapine and sertraline arms.

• Side effects worse in treatment arms.80

• They changed power calculation from 507 to 339 once initial data was collected (?)

• Does not apply to shut-ins (but likely the same).

• Participation in a trial (someone caring about you, active interactions) works as well as drugs

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X. Guidelines run amok….

• Definition and Evaluation of Transient Ischemic Attack: A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association Stroke Council; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; and the Interdisciplinary Council on Peripheral Vascular Disease. Easton JD, et al. Stroke 2009; 40: 2276-2293.

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AHA/ASA Definition and Evaluation of Transient Ischemic Attack: #1

• Now a “tissue-based” diagnosis• MRI needed within 24 hours of arrival

– Class I, Level of Evidence B

Their explanation: You pick up more strokes

Response: And this improves outcomes???

“For a guideline to be sound it should be linked on the basis of scientific evidence to the very health outcome that the guideline is designed to promote”. Jt Comm J Qual Improv. 1993 Jul;19(7):248-63.

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AHA/ASA Definition and Evaluation of

Transient Ischemic Attack: #2

“It is reasonable to hospitalize patients with TIA if they present within 72 hours of the event and any of the following criteria are present:

a. ABCD2 score of > 3

b. ABCD2 score of 0-2 and uncertainty that diagnostic workup can be completed within 2 days as an outpatient

c. ABCD2 score of 0-2 and other evidence that indicates the patient’s event was caused by focal ischemia”

All Class IIa “reasonable”, Level of evidence: C

“GOBSAT”

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ABCD2 score: BackgroundCalifornia Score:

1 pt for each

• Age > 60• DM• Duration > 10min• Motor weakness• Speech impairment

Johnson SC, et al. JAMA 2000

ABCD Score:

1 pt for each, except*

• Age > 60• BP > 140/90• Unilateral weakness: 2pt

–Speech only: 1pt• Duration: >10min

–> 60min: 2pt

Rothwell PM, et al. Lancet 2005

ABCD2 score\ /

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ABCD2 Score• Age: greater than or equal to 60 (1pt)• Blood pressure: SBP>=140 or DBP>=90 (1 pt)• Clinical Features:

– focal weakness (2pt) or – speech impairment without focal weakness (1pt)

• Duration of symptoms: – >=60minutes (2pt) or– <=59 minutes (1pt)

• Diabetes (1pt) Risk of CVA at 2 days 0-3 points = 1% risk 4-5 points = 4.1% risk 6-7 points = 8.1% risk

Johnson SC, et al. Lancet 2007;369:283-92.

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Problems with ABCD2 recommendation…Lack of validation

• Recommendation was made without any study examining the external validity of the score

• You essentially admit everyone (> 2 score)– Original Kaiser study: 92%– Sensitivity of 95%, but very poor specificity (12.5%)

Perry JJ, et al. CMAJ 2011 Jul 12; 183(10):1137-45.

• Insurers now utilize (corrupted) these recommendations

Shah KH, et al. Ann Emerg Med 2009; 53: 662-73

….the cart before the horse…

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Problems with ABCD2 recommendation…and it probably does not work!!!

• Methods: 637 pts. prospectively eval with TIA– At Mayo Clinic, 2001-2006

• Results: 15 ischemic strokes at 90 days

ABCD2 score CVA @7 days CVA @90 daysLow (0-3) 2/187 (1.06%) 4/185 (2.12%)

Intermediate (4-5) 1/335 (0.30%) 7/329 (2.08%)

High (6-7) 3/109 (2.68%) 4/108 (3.57%)

Stead LG, et al. Ann Emerg Med 2011; 57 (1): 46

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Kudos to AHRQ…National Guideline Clearinghouse

• The bad news: 2573 guidelines (as of 7/31/11)

• The Good news: You are aware of some of these issues…

Promoting Transparent and Actionable Clinical Practice Guidelines: Viewpoint from the National Guideline

Clearinghouse/National Quality Measures Clearinghouse (NGC/NQMC) Editorial Board released Dec 20, 2010

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Promoting Transparent and Actionable Clinical Practice Guidelines: 2 needs

#1 “…encourages CPG developers to describe their conflict of interest policies, to disclose potential conflicts of interest, and to describe all funding sources for the development of their CPGs”

#2 “…encourages CPG developers to formulate recommendation statements that are "actionable" and that employ active voice rather than passive voice

A.Establishing “trustworthiness” of CPGB. Promoting actionable CPG’s to be used in CDS

My plea: get rid of “consider”

recommendation

But who decides who sits at the table??

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Promoting Transparent and Actionable Clinical Practice Guidelines: 2 needs

#3 “avoiding vague or ambiguous recommendation statements (such as "Physicians may offer.." or "When possible..")

#4 “…encourages guideline developers to distinguish explicitly between factual statements and recommendations.

A.Establishing “trustworthiness” of CPGB. Promoting actionable CPG’s to be used in CDS

Agree - but how about a step further…give the data NNT/NNH in the

recommendation

Yes, and give clear drug/dosing recommendations

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Kudos to USPSTF (AHRQ)….They got the “guideline thing” right

• An excellent read….

The Anatomy of a US Preventive Services TaskForce Recommendation: Lipid Screening for

Children and Adolescents. Grossman DC, et al. Arch Pediatric Adolesc Med 2011; 165 (3): 205-10

Thank you for time and consideration!!!

R. Dachs - Contact info: [email protected]. Graber - Contact info: [email protected]

mailto:[email protected]

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#1 Bonus topic: EHR/CPOE and is being “electronic” really helping my patients?

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Bonus topic: EHR/CPOE

• Case #1: Electronic prescribing

• Methods: 3,898 computer-generated Rx’s– obtained from outpt. Pharmacies, in 3

states• Results: 452 errors (11.6%) Range 5-

37%– 275 (60.8%) were omissions (no big deal)– 163 (35%) were potential ADE’s (a big

deal)

and is being “electronic” really helping my patients?

Errors associated with outpatient computerized prescribing systems. Nanji KC,et al. .J Am Med Inform Assoc. 2011 Jun 29. [Epub ahead of print]

No difference in rates of ADE’s in hand-written vs. computerized Rx’s Gandhi TK, et al. NEJM 2003; 348: 1556-64.

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• Methods: NAMCS and NHAMCS 2005-07– 255,402 ambulatory visits– Analyzed 20 previously developed quality

measures

• Results: EHR used in 30% of 1.1 billion visits– Clinical Decision Support (CDS) in 57% of

theseOnly 1 of 20 indicators was greater in EHR

with CDS visits (lack of routine EKG in low-risk pts)

Electronic Health Records and Clinical Decision Support Systems. Romano MJ, et al. Arch Intern Med 2011 171: 897-903.

EHR: Case #2: Quality indicators:outpatient

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• Methods: Compared 2086 US hospitals, – No EHR vs. Basic EHR vs. advanced EHR– On 17 performance measures (AMI, CHF,

CAP)– 2003-2006

• Results: No clear relationship between the use of EHR and improvement in quality measures

Electronic Health Record adoption and quality improvement in US Hospitals. Jones SS, et al. Am J Man Care 2010; 16: SP64

EHR: Case #3: Quality indicators:inpatient

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• Methods: Retrospective analysis 46 primary care sites in Cleveland area – Reviewed (4) diabetes care and (5)

outcomes– 24,547 EHR pts. vs. 2,660 paper-based

practices– 7/07 - 6/10

• Results: EHR had greater adherence to DM care measures and improved outcomes– Note: the “outcomes” were intermediate (DOE’s)

endpoints, not firm clinical ones (POEM’s)

Electronic Health Records and Quality of Diabetes Care. Cebul RD, et al. NEJM Sept 1, 2011; 365:825-33.

EHR: Case #4: All is not lost……

Vasu TS et al. Norepinephrine or dopamine for septic shock: A systematic review of randomized clinical trials. J Intensive Care Med 2011 Mar 24; [e-pub

ahead of print]. (http://dx.doi.org/10.1177/0885066610396312)

#2: Bonus Topic: Sepsis Care

http://dx.doi.org/10.1177/0885066610396312

Previous Literature

• Not the best done study but norepinephrine was as good as dopamine overall and better in cardiogenic shock.

• De Backer D et al. Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med 2010 Mar 4; 362:779.

This study

• Meta-analysis of 6 studies that compared norepinephrine with dopamine

• 995 randomized to norepinephrine• 1048 randomized to dopamine• Endpoint: 28 day mortality• Mortality: 48% vs. 53%• Relative risk of arrhythmias 0.43

http://www.nih.gov/news/health/may2011/nhlbi-26.htm

• In Press. NIH press release

#3 Bonus Topic: The Niacin Issue

• 3414 patients with hx CAD taking a drug to reduce LDL.

• Randomized to niacin or no niacin (1,718, 1696) up to 2000mg/day

• Trial stopped early. No difference in outcomes and increased incidence of stroke (??!)

• One problem is that 515 patients were on Zetia (ezetimibe) for HDL lowering

www.cdc.gov/nchhstp/Newsroom/docs/PREVENT-TB-Factsheet.pdf

• (In Press…CDC release)

Bonus Topic #4: TB Update

Prior Literature

• 6-9 months of Isoniazid

This study

• 8,053 patients mostly from US and Canada (low prevalence area)

• Randomized to: – INH self administered daily (69% finished)– Rifampin + INH administered weekly by physician

(82% finished)– 10 year follow-up

• Results: 7 vs 15 cases (favoring rifampin + INH)• But..low prevalence, observed, no HIV+

top 10 innovations in primary care (in the past year) robert dachs, md, faafp assistant director,...

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