Frank J. Domino, M.D.
Professor
Dept. Family Medicine & Community Health
Un. Of Massachusetts Medical School
Worcester, MA
Frank.domino@umassmemorial.org
Disclosure
 Editor in Chief
5 Minute Clinical Consult
 Author and Editor for Up To Date
 Pri Med Curriculum Committee
 Author/Editor: Rxpalm, Inc.
 Author/Editor: www.Epocrates.com
 Editor: www.Familydoctor.org
By the end of this session, you will
 Review new data that will change your
practice about common medical problems
 Reconsider what you might assume is the
“standard of care”
 Remain skeptical of how the medical
literature influences the news, your
patients, and someone’s income
Which of the following is a result
of Chronic PPI Use?
1.
2.
3.
4.
↑ Hip Fracture
↑ Community Acquired Pneumonia
↑ Rates C. difficile
No Improvement in Asthma Control
5. ALL OF THE ABOVE
Omeprazole (Prilosec) OTC March 2008
PPIs & Hip Fracture
 PPI -> Hypochlorhydria -> ↓ Calcium Absorption
 Review of 1.8 Million Brits aged >/= 50 yrs
 13,556 Hip Fractures; After adjusting for cofounders
 Relative Risk of Hip Fracture among PPIs (> 12 months) =
1.6 [CI: 1.41-1.89]
 Risk Increased w/ duration of Tx & with ↑ doses
 Use of H2 RAs were analyzed; NO ↑ Risk
 JAMA 2006; 296: 2947-53, Yang, et al
PPI
&
Pneumonia
 Cohort Study Italy: Children on PPI for 4 months
increased risk of:
 Gastroenteritis OR=3.58 [1.87-6.86] & Comm. Ac.
Pneumonia OR=6.39 [1.38-29]
 Pediatrics 2006: 117: e817-20; Canani, R.
 Case Control Netherlands: Adults using Acid
Suppressing Rx
 Pneumonia OR 1.89 [1.36-2.62]
JAMA 2004; 292: 1955-60; Laheij, R.
PPI & C. difficile
 1,100+ Hospitalized Pts on PPI
 Adjusted for Antibiotic Exposure
 C. diff OR 2.1 [1.2 – 3.5] (not for H2RA)
AND, to decrease risk of confounding error, they
performed:
 Case Control of 94 Inpatients with C. diff
 OR = 2.6 [1.3 – 5.0]
 CMAJ 2004; 171: 33-8; Dial
Asthma & GERD

700 patients: inhaled corticosteroids treated with Nexium 40 mg
bid or placebo
 Divided into 3 Groups:
1. One group had nocturnal asthma and no GERD,
2. One had GERD and no nocturnal asthma,
3. and one had both GERD and nocturnal asthma.
***Nexium did NOT improve any clinically significant Sx: morning
PEF, use of rescue inhalers, or quality-of-life scores in any
subgroup
Am J Respir Crit Care Med 2006 May 15; 173:1091-7
Cochrane 2003 – No Benefit in GERD Tx on Asthma
PPI’s and Side Effects
 4 Articles in May 10, 2010 Archives Int Med: PPI’s
 Woman’s Health Initiative 130,000 women on PPI x
7.8 years  ↑ Fx Risk of Spine, Forearm/wrist and
total fractures
 100,000 Hospital Discharges x 5 years for risk of
developing nosocomial C. diff Infection
H2RA (1.52) vs PPI/d (1.74) vs > 1 PPI/day (2.36)
Arch Intern Med May 10, 2010
2. Sex and Drugs
CDC: 2009 National Youth Risk
Behavior Survey (YRBS)
 1 in 5 High School students say they have taken
a prescription drug without a Rx
 OxyContin, Percocet, Ritalin, Adderall, Xanax
 White Students:
23%
 Hispanic Students: 17%
 African American: 12%
 26% of 12th graders, 20% Male & Female
CDC: 2009 National Youth Risk
Behavior Survey (YRBS)







Alcohol:
Marijuana:
Prescription
Tobacco:
Cocaine:
Ecstasy:
Methamphetamine:
72%
36%
20%
19%
6.4%
6.7%
4.1%
 Passenger with Driver under Influence: 28%
 Sexually Active: 46%; 2/3 not used condom last IC
http://www.cdc.gov/healthyyouth/yrbs/index.htm
3. Drugs: Show of Hands
 “How many times in the past year have you
used an illegal drug or used a prescription drug
for non-medical reasons?”
 ~400 patients
 Gold Standard: DAST-10 + Oral Fluid Testing
 Sensitivity: ~100%
 Specificity: ~75%
Arch Intern Med 2010: 170(13): 1155-60
Sources of Drugs: You & Me
 Diversion:
Unintended use of medication for unlawful purposes
 Using Pseudophedrine for Crystal Meth
 Using lawfully prescribed medications
(narcotics, anxiolytics, amphetamines)
for illegal purposes
 Diversion Perspective
 $8 Oxycontin sells for >$100.00 on street
Drug Fact
 Prescription Opioids cause more
drug overdose deaths than
cocaine and heroin combined.
 40% of teens and an almost equal
number of their parents think
abusing prescription painkillers is
safer than abusing "street" drugs
CDC/FDA 2008
30 Deaths/Day
Prevalence of STI’s: 14-19 Females
 838 females who completed a National Health &
Nutrition Examination Survey 2003-04
 Specimens (urine, self obtained vaginal swabs)
 GC, Chlamyida, Trichomonas, HS II, ↑ Risk HPV
 24% were + for at least 1
HPV: 18.3%
Trich: 2.5%
GC:
1.3%
Chlamydia: 3.9%
HSV:
1.9%
Pediat 2009; 124: 1505-12
4. Diabetes
Update on the ACCORD Trial
 Gluc: A1C-- lower is not better
 BP: 120 not better than 140 to prevent Endpoints:
Non-fatal MI, CVA or CHD Death
 Lipids: adding fibrate to statin did not decrease
end points and may, in women, increase adverse
outcomes
NEJM; 2010: 362(17): 1628
Landing on the U-Shaped Curve
Where is the Ideal A1C ???
 2 cohort studies, ~28,000 T2DM >/= 50 Yrs
 Compared Mean A1C and All Cause Mortality
A1C
Hazard Ratio for Death
 6.4%
 10.4%
 Insulin based vs. oral agents
Conclusion:
1.52
1.79
1.49
Ideal A1C Level was
7.5%
NEJM 2010: 362(17): 1563
Oral Agents Alone
Insulin Based Tx
Editorial: Glycemic Control in Type 2
Diabetes: “Time for an
Evidence-Based About Face”
“Tight glycemic control burdens patients with complex
treatment programs, hypoglycemia, weight gain, and
costs, and offers uncertain benefits in return.
“Glycemic control efforts should individualize A1C
targets so that those targets and the actions necessary
to achieve them reflect patients’ personal and
clinical context and their informed values and
preferences”
Montori; Ann of Intern Med 2009; 150: 803-808
American Diabetes Association
American College of Cardiology Foundation
American Heart Association
Joint Position Statement
 “intensive vs. standard glycemic control have not shown a
significant reduction of CVD outcomes”
 Tx Goals: “Blood pressure control, Lipid Lowering w/Statin,
ASA & Lifestyle modification”
AND:
 A1C < 7.0: “w/o Hx hypoglycemia, short duration of DM, long
life expectancy, no CVD”
 A1C > 7.0: “w/ Hx hypoglycemia, limited life expectancy,
advanced micro or macrovascular complications, extensive comorbidities, or long standing DM in whom the general goal is
difficult to attain…”
Diabetes Care 2009; 31(1): 187-192
Aspirin Recommendation for DM?
 AHA, ACC, ADA Position Statement on Primary
Prevention in Diabetes
 Meta Analysis of 9 RCTs of Aspirin
Low Dose ASA is “reasonable” for Pt with 10 Yr CVD
risk > 10% & no risk for bleeding
2. ASA should NOT be recommended for men < 50 or
women < 60 Yrs with no other CHD RF
3. ASA MIGHT be acceptable in the 5-10% risk
1.
Diabetes Care 2010; 33: 1395
http://hp2010.nhlbihin.net/atpIII/calculator.asp?usertype=prof
5. Gout
Low Dose Colchicine
 RCT of 1.8 mg in 1 hour (1.2 onset, 0.6 in 1 Hr) vs
4.8 mg in 6 Hr (1.2 onset, then 0.6-1.2 per hour)
 Outcome was >50% reduction pain @ 24 Hr and
Adverse Event
Low Dose
High Dose
Placebo
Pain
AE (D, SD, V)
31%
34%
50%
23%, 0%, 0%
77%, 19%, 17%
20%, 0%, 0%
Arthritis Rheum 2010; 62(4): 1060
Low Dose
High Dose
Placebo
Why did someone do a study of a Generic Medication?
New Trends: Rx that Reinvent
 Colchicine:
Generic:
Colcrys
30 Pills
30 Pills
$25
$170
 Acetic Acid/Hydrocortisone Otic
Generic
15 ml
Brand Name 15 ml
$8
$210.00
 Doxepin (Sinequan)
Generic
Brand
Pill Cutter
10 mg
3, 6 mg
$19/90
$118/30
$ 2.00
6. Low Back Pain
What Predicts Chronic Low Back Pain
 SR of 20 studies (10,000+ Patients) to see what predicts
Chronic LBP at 1 Year





Non-Organic Signs
Mal-adapative Coping Behav.
Functional Impairment
Psychiatric Co-morbidities
Low Health Status
JAMA 2010; 303(13): 1295
Median LR
3.0
2.5
2.1
2.2
1.8
Opioid Use & Acute LBP
 Early opioid Rx & subsequent disability from back injuries
 “Receipt of opioids for >6 days doubled odds of disability”
Spine 2008:15;33(2):199-204.
 Relationship between early opioid prescribing for acute
occupational low back pain and disability duration
 8000+ Workers Comp Cohort
 Pts who received Opioids disabled 69 days longer than not.
 “CONCLUSION: Given the negative association between receipt
of early opioids for acute LBP and outcomes, it is suggested that
the use of opioids for the management of acute LBP may be
counterproductive to recovery.”
Spine 2007; 32(19):2127-32
7. Pain Relief
Running Hot or Cold
 RCT of 60 adults w/Acute Neck or Back pain
 400 mg Ibuprofen + Ice or Heat Pack x 30 Min
 “no difference in pain severity in Cold or Heat groups
before or after treatment” or in need for additional
medication
 80% would use same approach for next injury
Acad Emerg Med 2010; 17(5): 484
Osteoarthritis and the Knee
 RCT of ~225 patients with OA of Knee
 Usual Care (home exercise, NSAIDs, PT) vs
 Spa Therapy (18 days “hydrojet Tx, massage under
mineral water, mineral mud & mineral pool
exercises) + Usual Care
 At 6 months: 50% of Spa vs 36% of Usual Care had
“Minimal Clinically Important Improvement”
Ann Rheum Dis 2010; 69: 660
Migraine: Aspirin, really??
 SR of 13 studies; 4000+
 ASA (1000 mg + 10 metoclopramide) vs
others agents (Sumatriptan 50 or 100 mg)
 “Sumatriptan 50 mg did not differ from ASA
alone at 2 Hr Pain Free & HA relief”
 Sumatriptan 100 mg was better than
ASA+Meto At 2 hour Pain Free, BUT NOT
HEADACHE RELIEF & had > Side Effects
Cochrane DSR 2010
Acetaminophen & NSAIDs
Together, again
 SR 21 studies, 1900 patients for Pain Control
 Paracetamol vs. NSAID vs Para+NSAID
 “Combination of Para. And NSAID was more effective
than Para. Or NSAID alone in 85% and 64% of
relevant studies, respectively”
 “Current evidence suggests that a combination of Para.
And an NSAID may offer superior analgesia compared
to either drug alone.
 NO increase in adverse events from combination
Anesth Analges 2010; 110: 1170
Seabreeze
1 Part Vodka
3 Parts
Cranberry
Juice
3 Parts
Grapefruit
Juice
8. Food and Drugs
Grapefruit Juice & Statins
 Grapefruit Juice inhibits intestinal C P-450 3A4
 Can inhibit first pass metabolism and may result in ↑
serum concentrations of some drugs.
 Can reduce P-450 by ~45%
 Clinically: 1 case report of a 40 y/o woman on 80mg
Simvastatin, daily exercise, skydiving, and eating 1
grapefruit/day x 2 weeks
 Use Pravstatin or rosuvastatin
Nutrit Journal 2007; 6:33
Am Fam Phys 2006; 74:605
Why be on a Statin???
 Meta Analysis of 65,000 “intermediate to high risk
individuals without history of CVD” and Statin use
and All Cause Mortality
 “Use of statins in this high risk population was NOT
associated with a statistically significant reduction in
All Cause Mortality”
Arch Intern Med 2010: 170(12): 1024
Warfarin and Food
 High vitamin K intake can ↓effectiveness of warfarin
 Large amounts: ~14 oz of high Vit. K vegetables
 Typical servings (4 oz) have little impact on INR.
 2005 Dietary Guidelines for Americans recommends:
 3 cups/week of dark-green vegetables (contain ~100-570
microg/serving) of vitamin K1.
Nutr Rev. 2005 Mar;63(3):91-7.
 Cranberry Juice: Ancedotal reports of interaction
 “Moderate consumption does not affect anticoagulation”
Am J Med 2010 123(5): 384
9. AHRQ: Update on Prevention
Grade
A. Folic Acid for Pregnancy: 0.4-0.8 mg/day
B. Mammography (50-74) Biennial
B. Obesity: start Age 6 Years
B. Screen Adolescents for Depression
C. Mammography < 50 years
I. Screening for Hyperbilirubinemia for infants
www.ahrq.gov
CA: 59 (4): 215 - 275
Summing the data
 Man screened is 48 times more likely to be
harmed than saved at 9 years after diagnosis;
 Harms: Impotence, Incontinence, mental
anguish, and “even death”
 Screening doubles risk of Dx but does not
significantly decrease risk of dying
 1985: 8.7% risk of Dx; 2.5% risk of death
 2005: 17% risk of Dx; 3% risk of death
 Is it really worth it?
Boyle & Brawley Conclusion
 “Testing has been based on blind faith in early
detection as opposed to being based on evidence of a
decrease mortality”
 “Prostate Cancer screening and treatment of early
disease is also a profitable industry”
 “If we are to stem the spiraling costs of health care,
we must move toward the use of evidence based,
rather than faith based or profit based practice of
medicine.”
 “The collective data clearly cannot justify mass
screening and indeed appear to justify support for a
recommendation against mass screening.”
 “Shared decision making.. should include discussion
of the quantified risks and benefits.”
CA: 59 (4): 215 - 275
Colonoscopy Safety
Post Colonoscopy surveillance 21,000 adults
-GI Bleeding
1.59/1000 exams
(Risk ↑ w/Warfarin, but not ASA/NSAIDs
-Perforations
0.19/1000 exams
-Diverticulitis
0.23/1000 exams
-Postpolypectomy Synd 0.09/1000 exams
Overall Incidence of SE 2.01/1000 exams
Clin Gastroent Hepat 2010; 8(2): 166
10. All the other stuff
How long is your average day?
 6000 British civil servants lifestyle; x=7.5 Hr/d
 60% male, 40% female; 39-61 Yrs x 11 years
 Outcomes: Fatal MI, Non-Fatal MI, Angina
 Adjusted for CHD Risk Factors
 Conclusions:
3-4 hours of overtime
(beyond 7.5 Hr) 
60% ↑in risk of Outcomes
European Heart Journal 2010
Life Expectancy of Men in US
White
Black
 Physician
73.0
68.7
 Lawyers
72.3
62.0
 All Professionals
70.9
65.3
 All Men
70.3
63.6
Am J Prev Med. 2000 Oct;19(3):155-9.
Vitamin D
 Vitamin D’s job is to regulate
serum Ca
 Annual High Dose Vitamin D & Fractures
 RCT of 500,000 IU D3 x 3-5 Years
 ↑ Risk of Falls (83/100 Person Yrs vs 72/100 PY)
 ↑ Risk of Fractures (4.9/100 PY vs 3.9/100 PY)
JAMA 2010; 303(18): 1815-22; Editorial 1861
Calcium Supplementation
 Meta Analysis of 15 Trials, ~12,000
 Evaluated trials of calcium Supp. And CHD
 Calcium Supp of > 500 mg/day (Without
Vitamin D Supplementation)
 Hazard Ratio MI = 1.31
 Non-Signif. Increase in risk of CVA, Death,
& composite Endpoint of MI, CVA or Death
BMJ. 2010 Jul 29;341:
First BB for CHF, now COPD???
 Retrospective analysis 2230 patients w/COPD
 Death:
 COPD Exacerb
Beta Block
27.2%
42.7%
Non BB
32.3%
49.3%
 Mortality benefit in seen in cardioselective BB
(Atenolol, Metoprolol)
Arch Intern Med 2010; 170(10): 880
Summary
1. Use PPI’s for < 1 Yr, then Step Down
2. Screen for Rx drug use, limit their use
3. Screen teens for STI’s
4. Diabetes: A1C goal of 7.5 unless no
comorbidities, ASA only for risk > 10%
5. Gout: Colchicine 1.2, then 0.6 @ 1 Hr
Summary
6. Acute Low Back Pain: no Narcotics
7. Pain Relief:
1. NSAID + Hot or Cold, Spa Tx
2. Migraine: ASA 1000mg + 10 Metoclopramide
3. NSAID + Acetaminophen Safe & Effective
8. Statins, Warfarin and diet
9. Screening: ∆ Breast & Prostate Ca; Colon-safe
10. Keep the work to < 10 hours per day
Frank .domino@umassmemorial.org
Frank J. Domino, M.D.
Frank.domino@umassmemorial.org