Top 10 Innovations in Primary Care (in the Past Year) (Text Version)

Slide presentation from the AHRQ 2011 conference.

On September 20, 2011, Robert Dachs and Mark Graber made this presentation at the 2011 Annual Conference. Select to access the PowerPoint® presentation (2.1 MB). .


Slide 1

Slide 1. Top 10 Innovations in Primary Care (in the past year)

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

Robert Dachs, MD, FAAFP
Assistant Director, Dept of Emergency Medicine
Ellis Hospital, Schenectady, NY
Clinical Associate Professor
Ellis Family Medicine Residency Program
Albany Medical College

Mark Graber, MD, FACEP
Professor of Family and Emergency Medicine
University of Iowa Carver College of Medicine
Iowa City, Iowa

Slide 2

Slide 2. Disclosure Statement

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.

Slide 3

Slide 3. Atrial Fibrillation Management

I. Atrial Fibrillation Management

  • Dabigatran: Boon, Bust or Hype?

Image: A graphic shows significant risk reduction of stroke (35%) using Pradaxa 150 MG twice daily versus warfarin.

Slide 4

Slide 4. Atrial Fibrillation Management

Atrial Fibrillation Management

  • Who gets anticoagulation?
  • Who is at risk for hemorrhages?
  • And is dabigatran (Pradaxa) everything its cracked up to be?

Slide 5

Atrial Fibrillation and Stroke
Why Do We Anticoagulate?

Image: Bar chart shows the following data:

  • <65 yrs: 4.9.
  • 65-75 yrs: 5.8.
  • >75 yrs: 8.

CVA rate (% per yr)

  • 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).

Slide 6

Slide 6. Atrial Fibrillation: Who Gets Warfarin? ACC/AHA 2011 Guideline

Atrial Fibrillation: Who Gets Warfarin?
ACC/AHA 2011 Guideline

Risk Category:

  • No risk factors.
  • One moderate risk factor.
  • Any high-risk factor OR.
  • ≥2 moderate risk factors.

Recommended Therapy:

  • ASA 81-325mg q d.
  • ASA or warfarin.
  • Warfarin (INR 2.0-3.0).

Moderate-risk factors:
Age ≥75yrs
HTN
CHF
LV ejection fraction <35%
DM

High-risk factors:
Previous CVA, TIA, embolism
Mitral stenosis
Prosthetic heart valve

Slide 7

Atrial Fibrillation Management:
1) Who Gets Anticoagulation?

  • Last year: CHADS2.
  • This year: CHA2DS2- Vasc.

Slide 8

Slide 8. Atrial Fibrillation: The CHADS2 Score

Atrial Fibrillation: The CHADS2 Score

CHADS2 Risk Criteria: Score:

  • CHF: 1.
  • HTN: 1.
  • Age >75 yrs: 1.
  • DM: 1.
  • Prior Stroke or TIA: 2.
Pts. (N=1733)CVA Rate (%/yr) (95%CI)CHADS2 Score
1201.9 (1.2–3.0)0
4632.8 (2.0v3.8)1
5234.0 (3.1–5.1)2
3375.9 (4.6–7.3)3
2208.5 (6.3–11.1)4
6512.5 (8.2–17.5)5
518.2 (10.5–27.4)6

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

Slide 9

CHADS2 vs. CHA2DS2-VASc?

CHADS2/Score/Score

  • CHF / 1 / 1.
  • HTN / 1 / 1.
  • Age >75 yrs / 1 / 2.
  • DM / 1 / 1.
  • Prior Stroke or TIA / 2 / 2.

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 pts with afib, not on warfarin.
1 year in Euro Heart study.

Yip GB, et al. Chest 2010; 137:263-72.
Gage BF, et al. JAMA 2001; 285:2864-70.

Slide 10

CHADS2 vs. CHA2DS2-VASc?

CHADS2 / CVA Rate @ 1yr / CHA2DS2-VASc

  • Low risk = 0 points - Low risk = 0 points 1.67% vs. 0.78%.
  • Intermediate = 1 pt - Intermediate = 1 pt 4.75% vs. 2.0%.

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…

Slide 11

Slide 11. Atrial Fibrillation: Anticoagulation Risks/Benefits

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???

Slide 12

Slide 12. "But I Am Fearful of My Elderly Patient Falling (i.e., Subdural)"

"But I Am Fearful of My Elderly Patient Falling (i.e., 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 subdural.
Note 2: Model uses assumptions—are they correct?

That's last year—this year

Slide 13

Slide 13. Previously…

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!!!!!!!

Risk Score = 0.49*Xage70+ + 0.32*Xfemale + 0.58*Xremote Bleed
+ 0.62*XRecent Bleed + 0.71*Xalcohol/Drug Abuse +
+ 0.86*Xanemia + 0.32*Xantiplatelet Agent

That's last year—this year

Slide 14

Slide 14. Two New Scoring Systems: HAS-BLED and ATRIA

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.

Slide 15

Slide 15. Who Needs to Avoid Anticoagulation?? HAS-BLED

Who Needs to Avoid Anticoagulation??
HAS-BLED

PointsDefinition
1HHypertensionSys BP >160
1 or 2
(1 pt each)
AAbnormal Renal and/or liver functionDialysis/transplant cirrhosis/T. Bili 2x or AST/ALT 3x normal
1SStroke 
1BBleedingPrevious bleed/predisposition
1LLabile INR<60% in therapeutic range
1EElderly (>65 yrs) 
1 or 2
(1 pt each)
DDrugs or alcohol excessAntiplatelet or NSAID's

A score of ≥3 is considered "high risk."
ESC recommends "caution" using warfarin1

1 ESC Guidelines for the management of atrial fibrillation, 2011.

Slide 16

Slide 16. HAS-BLED: Results

HAS-BLED: Results

Derivation CohortValidation Cohort
Scoren# of bleedsBleeds per 100 pt yrsn# of bleedsBleeds per 100 pt yrs
0151790.5979891.13
11589241.511286131.02
221973.20744141.88
341819.5118773.74
414321.434648.70
510-8112.50
6---200
7------
8------
9------

Major bleeds defined as any below:
1) Bleeding requiring hospitalization.
2) Require transfusion.
3) Drop in Hgb>2 g/L.
4) Hemorrhagic CVA.

Slide 17

Slide 17. ATRIA: Results

ATRIA: Results

Derived from 13,559 pts in Kaiser system
Derivation: Validation = 2:1 ratio

 Score
Anemia: Hgb <13 male, <12 female3
GFR <303
Age >75 yrs2
Any prior hemorrhage Dx1
HTN1

Risk category, pointsEvents/100 pt/yrs
DerivationValidation
Low risk (0-3)0.720.83
Intermediate (4)2.712.41
High (5-10)5.995.32

One of my favorite Web sites: mdcalc.com.

Slide 18

Slide 18. Atrial Fibrillation Management

Atrial Fibrillation Management

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

Image: A graphic shows significant risk reduction of stroke (35%) using Pradaxa 150 MG twice daily versus warfarin.

Slide 19

What About Dabigatran (Pradaxa)?

  • RE-LY trial: NEJM 2009; 361: 1139-51.
  • Methods: 18,113 pts with afib, randomized to:
    followed for 2 years: dabigatran, 110mg BID; dabigatran, 150mg BID; warfarin.
  • Results:
    OutcomeDabigatran, 110mg BIDDabigatran, 150mg BIDWarfarin
    CVA/embolism1.53%1.11%*1.69%
    Major bleeding/yr2.71%3.11%3.36%
    Mortality rate/yr3.75%3.64%4.13%

NNT=172

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

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

Slide 20

Slide 20. Pet Peeve.....

Pet Peeve.....

.......Benefits in: Relative Risk

Image: A graphic shows significant risk reduction of stroke (35%) using Pradaxa 150 MG twice daily versus warfarin.

......Harm in: Absolute numbers

Image: A graphic shows the lower total bleed rate for Pradaxa versus warfarin.

Slide 21

Slide 21. And there will be more to come.

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

Slide 22

Slide 22. Reservations.....

Reservations.....

  • Cost:
    • Even with INR monitoring, warfarin is cheaper.
            Shah SV, et al. Circulation 2011; 123: 2562-70.
  • 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.

Slide 23

Slide 23. II. Calcium Intake: Heart Disease and Bone Health

II. Calcium Intake: Heart Disease and Bone Health

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).

Slide 24

Slide 24. First Study

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.

Slide 25

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.

Slide 26

Slide 26. Second Study

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.

Slide 27

Slide 27. 24% of women had a fracture and 6% had a hip fracture

  • 24% of women had a fracture and 6% had a hip fracture.
  • Calcium intake of 750 mg-882 mg/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.

Slide 28

Conclusion?

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

Slide 29

III. HIV Update: This Will Be in the New Guidelines…

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

and

The HIV-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.

Slide 30

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).

Slide 31

  • 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.

Slide 32

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.

Slide 33

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: 3 annual chest CT's vs. 1 Chest x-ray:
      • Enrolled 2002-04, followed to 12/31/09.

Slide 34

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

Results:Chest CTChest x-ray
Deaths per 100,000 Person/years247309
  • 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"

Slide 35

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

Results:Chest CTChest x-ray
Deaths per 100,000 Person/years247309
  • 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)

Slide 36

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

Results:Chest CT
N=26,722
Chest x-ray
N=26,732
Lung Ca Deaths356443
Lung cancer deaths1.33%1.65%
NNT312

Slide 37

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

Results:Chest CT
N=26,722
Chest x-ray
N=26,732
Deaths per 100,000 Person/years247309
Lung cancer deaths1.33%1.65%
NNT312
NNH
  • >1 in 3 false (+) CT scan.
  • 1 in 30 unnecessary surgery.
  • 1 in 161 with surgical complication.

One of my favorite Web sites: TheNNT.com

Slide 38

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....

Slide 39

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.

Slide 40

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

Slide 41

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.

Slide 42

Some Answers

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

Slide 43

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).

Slide 44

VI. The Potential PE Patient…

  • The problem: excessive CT utilization.
  • The answer: Risk stratification.

How to risk stratify?

  • Last year: Well's Criteria.
  • This year: PERC Rule.

Slide 45

CT Use in USA

  • 75 million in 2009.
  • 7% (5 million) in children.
  • 60% are women

Image: Line graph shows dramatic rise in use of CT scans from 1980 to 2005.

Slide 46

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.

Image: Line graph shows age of exposure decreasing for both colon and lung cancer per million patients exposed to radiation.

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

Slide 47

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.
  • Previous DVT or PE: 1.5.
  • Hemoptysis: 1.
  • Malignancy (actively treated in past 6 mos): 1.

High risk ≥6
78% PE

Moderate risk 2-6
27.8% PE

Low risk <2
3.4% PE

Wells PS, et al. Thromb Haemost 2000.

Slide 48

The PERC Rule

  • Low clinical gestalt (<15% chance) with:
    • Age <50—No hemoptysis.
    • Pulse <100—No estrogen use.
    • SaO2 ≥95%—No unilateral leg swelling.
    • No previous VTE—No surgery/trauma requiring hospitalization in past 4 weeks.

Derived from 3148 patients.

Kline JA, et al. Jour Thromb Haemostasis 2004.

Slide 49

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.

Slide 50

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.

Slide 51

VII. Antimicrobial Update

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.

Slide 52

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.

Slide 53

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.

Slide 54

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.

Slide 55

VIII. Decreasing Antibiotic Use and ClinicalTrials.gov

  • The antibiotic pipeline is drying up.
  • Strides (small) in decreasing antibiotic use are being made:
  • Antibiotics rarely useful in otitis media:
    • NNT = 16, NNH =24 (Cochrane Review, 2008).
    • Use of "delayed"/"Back-up" prescriptions.

Slide 56

This Article Takes a Step Backwards (And Why Its Wrong)

Treatment of Acute Otitis Media in Children under 2 Years of Age. Hoberman A, et al. NEJM 2011; 364:105-15.

  • Methods: 291 children, ages 6 mos-2 yrs:
    • With AOM (reasonable criteria).
    • Randomized, double-blind to: amoxicillin-clavulanate vs. Placebo (90 mg/kg).

Slide 57

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

Results:Amoxicillin-clavulanate
(n=144)
vs.Placebo
(n=147)
1. Resolution of symptoms
Day 235%vs.28%
Day 461%vs.74%
Day 780%vs.54%
P = 0.14
2. 2 successive days AOM-SOS score 0-1
Day 220%vs.14%
Day 441%vs.36%
Day 767%vs.53%
P=0.04, overall

Slide 58

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

Results:Amoxicillin-clavulanate
(n=144)
vs.Placebo
(n=147)
3. Severity of symptoms
AOM-SOS scores (14 pt scale) @10-12 day visit1.59vs.2.46
P=0.003, clinically insignificant
4. Clinical failure (otoscopy)
Day 4-54%vs.23%
Day 10-1216%vs.51%
P ≤0.001

Slide 59

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

  • Author's Conclusion:
    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."
  • Really???

Slide 60

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

Problems with this study....

  • You can't report out multiple (4) "primary outcomes":
    • The more outcomes you look at, by chance alone one will be positive.

Slide 61

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

Problems with this study....

  • You can't have 4 primary outcomes....
  • Who cares what the TM looks like????
4. Clinical failure (otoscopy)Amoxicillin- clavulanatePlacebo
Day 4-54%23%
Day 10-1216%51%
P ≤0.001

This is a "DOE" not a "POEM".

Slide 62

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

Problems with this study....

  • 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.

Slide 63

Images: Three line graphs show the first, second, and third recording of AOM-SOS Scores of 0 or 1 for children with continuing symptoms over a period of 7 days. Next to the first graph is a caption, "The "predefined" primary outcomes." Next to the second graph is a caption, "No clinical differences."

Note: Figure 2. Resolution of Children's Symptoms during the First 7 Days of Follow-up. During the first 3 days, the Acute Otitis Media Severity of Symptoms (AOM-SOS) scale11,12 was administered twice daily; thereafter, it was administered once daily. Panels A and B show the proportion of children in whom symptoms had not resolved. Resolution of symptoms is defined in Panel A as the first recording of an AOM-SOS score of 0 or 1 and in Panel B as the second of two successive recordings of a score of 0 or 1. Panel C shows the mean scores on the AOM-SOS scale over the course of the first 7 days of the study treatment. Since multiple assessments were made on the first 3 study days, numbers on the x axis in all three panels indicate the end of a study day.

Slide 64

This Is the Primary Endpoint

Images: A graph shows the first recording of AOM-SOS Scores of 0 or 1 for children with continuing symptoms over a period of 7 days.

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

Slide 65

Why I Am Thankful For ClinicalTrials.gov

"The primary objective of this study will be to compare time to resolution of symptoms in children receiving amoxicillin/clavulanate and children receiving placebo".

  • 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.

Slide 66

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

Other secondary outcomes—not reported

Results:Amoxicillin-clavulanate
(n=143)
vs.Placebo
(n=146)
Mean # of times analgesia0.37vs.0.43
P=0.35
Mean # of visits to office0.15vs.0.23
P=0.20
Mean # of ED visits0.07vs.0.07
# of cases of family member missing work33vs.33

Slide 67

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

Other secondary outcomes—not reported

Results:Amoxicillin-clavulanate
(n=143)
vs.Placebo
(n=146)
Day 54.19vs.4.13
P=0.71
Day 114.40vs.4.12
P=0.04

Parental satisfaction:

  • 1 - Very dissatisfied.
  • 5 - Very satisfied.

Slide 68

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

Results:Amoxicillin-clavulanate
(n=144)
vs.Placebo
(n=147)
Clinical failure (otoscopy)
Day 4-54%vs.23%
Day 10-1216%vs.51%
P≤0.001
Side effects
Diarrhea24%vs.7%
C. difficile6 casesvs.1
Diaper dermatitis47%vs.16%

Slide 69

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

  • Author's Conclusion:
     

    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."

  • Really???
     

    Antibiotics "…provide no clinical benefit and increase the rate of diarrhea illness with potential harm." R. Dachs.

Slide 70

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).

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

Slide 71

Skin Infections in 2000 = 13th Place
Skin Infections in 2009 = 7th Place

Image: A graph compares rate of discharges per 10,000 population for the most frequent conditions by body system for 2000-2009.

Slide 72

IX. Are the Millions of Dollars Spent on Alzheimer Meds and Antidepressants in Demented Elderly Worthwhile?

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 ).

Slide 73

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.

Slide 74

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.

Slide 75

  • ADAS-cog.
  • CIBIC-plus.
  • ADCS-ADL scale.
  • Neuropsychiatric Inventory.

Images: Four graphs compare Favors Memantine vs. Favors Placebo.

Slide 76

Conclusion: Memantine Doesn't Work For Mild Alzheimer's.

Slide 77

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.

Slide 78

This Study

  • 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").

Slide 79

  • 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 (??).

Slide 80

  • 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.

Slide 81

  • 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.

Slide 82

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.

Slide 83

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.

Slide 84

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:

  1. ABCD2 score of ≥3.
  2. ABCD2 score of 0-2 and uncertainty that diagnostic workup can be completed within 2 days as an outpatient.
  3. 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"

Slide 85

ABCD2 Score: Background

California Score:1 pt for each

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

Johnson SC, et al. JAMA 2000. ABCD2 score.

ABCD Score: 1 pt for each, except*

  • Age >60.
  • BP >140/90.
  • Unilateral weakness: 2 pt:
    • Speech only: 1 pt.
  • Duration: >10min:
    • →60 min: 2 pt.

Rothwell PM, et al. Lancet 2005. ABCD2 score.

Slide 86

ABCD2 Score

  • Age: greater than or equal to 60 (1 pt).
  • Blood pressure: SBP≥140 or DBP≥90 (1 pt).
  • Clinical Features:
    • Focal weakness (2 pt) or
    • Speech impairment without focal weakness (1 pt).
  • Duration of symptoms:
    • ≥60minutes (2 pt) or
    • ≤59 minutes (1 pt).
  • Diabetes (1 pt).

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.

Slide 87

Problems With ABCD2 Recommendation…
Lack of Validation

  • Recommendation was made without any study examining the external validity of the score. Shah KH, et al. Ann Emerg Med 2009; 53: 662-73.
  • 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.

....the cart before the horse...

Slide 88

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 scoreCVA @7 daysCVA @90 days
    Low (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

Slide 89

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.

Slide 90

Promoting Transparent and Actionable Clinical Practice Guidelines: 2 Needs

A. Establishing "trustworthiness" of CPG.
B. Promoting actionable CPG's to be used in CDS.

  • #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".

    But who decides who sits at the table??

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

    My plea: get rid of "consider" recommendation.

Slide 91

Promoting Transparent and Actionable Clinical Practice Guidelines: 2 Needs

A. Establishing "trustworthiness" of CPG.
B. Promoting actionable CPG's to be used in CDS.

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

    Yes, and give clear drug/dosing recommendations.

  • #4 "...encourages guideline developers to distinguish explicitly between factual statements and recommendations.

    Agree—but how about a step further... give the data NNT/NNH in the recommendation.

Slide 92

Kudos to U.S. Preventive Services Task Force (USPSTF) (AHRQ).... They Got the "Guideline Thing" Right

  • An excellent read....

The Anatomy of a US Preventive Services Task Force Recommendation: Lipid Screening for Children and Adolescents. Grossman DC, et al. Arch Pediatric Adolesc Med 2011; 165 (3): 205-10.

Slide 93

Thank You for Time and Consideration!!!

R. Dachs— Contact info: dachsmd@aol.com
M. Graber—Contact info: markgraber@gmail.com

Slide 94

#1 Bonus Topic: Electronic Health Records (EHR)/Computerized Physician Order Entry (CPOE)

And is being "electronic" really helping my patients?

Image: A poster lauds Computerized Physician Order Entry (CPOE) as "Quality Care."

Slide 95

Bonus Topic: EHR/CPOE

And is being "electronic" really helping my patients?

  • 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).

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.

Slide 96

EHR: Case #2: Quality Indicators: Outpatient

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

  • 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 these:
      • Only 1 of 20 indicators was greater in EHR with CDS visits (lack of routine EKG in low-risk pts).

Slide 97

EHR: Case #3: Quality Indicators: Inpatient

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

  • 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.

Slide 98

EHR: Case #4: All Is Not Lost......

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

  • 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).

Slide 99

#2: Bonus Topic: Sepsis Care

#2: Bonus Topic: Sepsis Care

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).

Slide 100

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.

Slide 101

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.

Slide 102

Slide 2. Disclosure Statement

#3 Bonus Topic: The Niacin Issue

  • In Press. NIH press release.

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

Slide 103

  • 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.

Slide 104

Bonus Topic #4: TB Update

  • (In Press…CDC release).

http://www.cdc.gov/nchhstp/Newsroom/docs/PREVENT-TB-Factsheet.pdf Plugin Software Help

Slide 105

Prior Literature

  • 6-9 months of Isoniazid.

Slide 106

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+
Page last reviewed March 2012
Internet Citation: Top 10 Innovations in Primary Care (in the Past Year) (Text Version). March 2012. Agency for Healthcare Research and Quality, Rockville, MD. http://www.ahrq.gov/news/events/conference/2011/dachs-graber/index.html