The Teaching Physician
for those who teach students and residents in family medicine
Volume 8, Issue 3
July 2009
Clinical Guidelines That Can Improve Your Care
A Guideline That Can Help Your Practice: Can We Prevent Prostate
Cancer With 5-a-Reductase Inhibitor Chemoprevention?
By Caryl Heaton, DO, UMDNJ-New Jersey Medical School
Unless you read the Journal of Clinical
Oncology, you might have missed this
guideline1 sponsored by the American
Urological Association and the American Society of Clinical Oncology. Curiously, they state that chemoprevention of cancer is “relevant to practicing
oncologists and urologists because its
application is well suited to the clinical setting in which shared decision
making takes place between health
professionals and individual patients.”
I would suggest that the primary care
medical home is a more appropriate
venue to discuss the prevention of
prostate cancer with our patients.
The purpose of the guideline was
to describe the impact of 5-ARIs
(5-alpha-Reductase Inhibitors) on
the risk of incident prostate cancer,
prostate cancer mortality, and overall
mortality. They also hoped to identify
any subgroups where 5-ARIs might
be especially beneficial and any risks
associated with 5-ARI treatment. They
used an “expert panel” that did not
include a primary care doctor. This is
also a guideline developed from very
few studies, ie, very little evidence.
So why do we bring it to your attention? Because this is a common cancer
that our patients care about, there
is unacceptable excess mortality in
(continued on page 2)
Teaching Points— A 2-minute Mini-lecture
Quality of Care
By Paul Paulman, University of Nebraska
Editor’s Note: The process of the
2-minute Mini-lecture is to get a commitment, probe for supporting evidence, reinforce what was right, correct any mistakes, and teach general
rules. In this scenario, Dr Paulman
(Dr P) works with a third-year medical
student (MS3) who has read an article
in a journal about the state of health
care quality in the United States.
Dr P: It’s the end of the day, and now
we have breathing room. Any thoughts
about what we did today?
MS3: Something you said got me
thinking—about that patient who was
seeing an endocrinologist, a cardiologist.
Dr P: Right. And a hematologist,
nephrologist. She even saw a rheumatologist and an orthopedist a couple of
years ago—we didn’t talk about that.
Anyway, you were saying?
MS3: Well, I’m not convinced that
her care was improved that greatly by
seeing all these doctors. I’m confused
about quality of health care. We have
so many resources, like this patient
who is able to see so many experts,
and yet, I read an article in an online
journal that stated that the quality of
health care in the US is very poor.
Dr P: I know what you mean about
the complexity of health care. And
it’s hard to manage that complexity.
I didn’t refer that patient to all those
subspecialists. The whole process got
out of my control a bit. Let’s pull that
article up on the Web. While we’re
on the subject: How would you define
quality?
(continued on page 4)
July 2009
Volume 8, Issue 3
FPIN HelpDesk Answers....................... 5
POEMs for the Teaching Physician...... 6
The Teaching Physician
2
(continued from page 1)
Can We Prevent Prostate
Cancer?
some communities, and it’s the best
synthesis we have. Here is what they
(we?) know so far:
It’s important to remember that
these trials followed men who had
regular PSA (prostate specific antigen)
tests and regular checks with their
doctors to discuss symptoms. The
guideline is designed to address men
who are asymptomatic but who are
followed over time to screen and diagnose “for-cause” prostate cancer. That
means men who are followed and biopsied if needed; if their PSA gets too
high or increases too quickly or who
get symptoms associated with lower
urinary tract obstruction. The actual
review of the evidence was done by
Wilt et al2 in a Cochrane review, so it
is fair to assume that the quality of the
research they included was high. The
largest study, the PCPT,3 was the only
study designed to answer the question
about cancer incidence in asymptomatic men. The mean age of enrollees
was 64.6 years, 91% were white, and
mean PSA was 2.1 ng/mL. The relative
risk of new for-cause prostate cancer
in men taking 5-ARIs was 0.74 (a 26%
relative reduction), but the absolute risk
reduction was only 1.4%, and this gives
a number needed to treat of 71 (71 men
must be given 5-ARI to prevent one additional prostate cancer that would not
have otherwise occurred) for 7 years.
The number is lower if you count all
prostate cancers, because they biopsied
everyone at the end of the study period.
That number needed to treat is 34, but
you would not discover the additional
cancers unless you biopsied everyone,
and discovering those extra cancers is
of highly questionable importance.
The recommendations from this
guideline are summarized in Table 1.
An ongoing large trial studying both
finasteride (Proscar®) and dutasteride
(Avodart ®), the REDUCE trial,4 in
the prevention of prostate cancer is
designed to give us better information
Table 1
Summary of Guideline Recommendations
• Should men routinely be offered a 5-ARI for the chemoprevention of prostate cancer?
Asymptomatic men with a PSA ≤ 3.0 who are regularly screened with PSA or are anticipating undergoing
annual PSA screening for early detection of prostate cancer may benefit from a discussion of the
benefits of 5-ARIs for 7 years for the prevention of prostate cancer and the potential risks (including
the possibility of high-grade prostate cancer) to be able to make a better-informed decision. Men who
are taking 5-ARIs for benign conditions such as LUTS would benefit from a similar discussion.
• What is the impact of 5-ARIs on the need for treatment for benign prostatic disease?
In the PCPT, the incidence of acute urinary retention was decreased by about one third in the finasteride
arm (RR_0.67; 95%CI, 0.59 to 0.76; absolute rates, 6.3% versus 4.2%).
• What is the impact of 5-ARIs on quality of life?
Finasteride decreased the risk of acute urinary retention in aymptomatic men, especially those with
larger prostates (PSA ≥ 4.0). The absolute risk difference was small, 2.3%, and the number needed
to harm was 43.
What is the treatment duration required for best outcome (period versus lifelong)?
No trial has directly compared different durations of 5-ARIs for the prevention of prostate cancer.
The largest trial’s duration was 7 years, and until other information becomes available, the duration
of treatment should be 7 years.
about the overall morbidity and mortality associated with 5-ARI treatments.
This guideline tells us nothing about
the prevention of death or significant
mortality from prostate cancer, and
that of course is what our patients really care about.
Another caveat for the reader: with
finasteride, the number of patients with
higher-grade lesions unexpectently
increased. It went from approximately
18/1,000 to 21/1,000 and was statistically significant. This is a pretty
low absolute number, but the finding
is troubling nonetheless. Our urology colleagues have not sorted this
through. There is a theory that because
the volume of the prostate is actually
smaller with 5-ARIs (approximately
25%–30% smaller), the cancer cells
take up more space and artificially
seem to show a higher grade. The
authors state, “Indeed, modeling incorporating prostate volume suggests that
the increase in high-grade cancers seen
in the PCPT may be nearly completely
explained by enhanced detection and
not tumor transformation or induction.” I think this theory needs some
work, but the calculation of number
July 2009
needed to harm comes out to 333 (333
men must take the 5-ARI to cause
the increase in Gleason grade (≥7) in
one man) for that higher grade tumor.
Another way of looking at this is that
there was a 14.8% higher number of
high-grade tumors in the finasteride
tumor group compared to the placebo
tumor group, so approximately one
out of seven have a higher grade than
they might have had if medication had
been taken.
There is more bad news on the side
effects. There is a small consistent
significant difference in the rate of
erectile dysfunction and gynecomastia
with 5-ARIs (2%–4% or a number
needed to harm of 25–50 persons).
The effect lessens over time, and the
total discontinuance rate in the studies
has consistently been similar in the
placebo and treatment arms (about
15%), but this should be part of the
decision.
So, the recommendation is to have
a discussion, it is really no stronger
than that. With this lack of evidence,
it would be easy to take a wait-andsee approach; no one could blame
you. But finasteride and its cousin
3
The Teaching Physician
References
(continued from page 2)
Can We Prevent Prostate
Cancer?
dutasteride will continue to be used for
the treatment of BPH (benign prostatic
hypertrophy) and male pattern baldness,
and patients will start (or continue) to
ask about their use in the prevention of
prostate cancer. A patient-centered decision made after a good best-evidence
discussion is what our job is really all
about.
1. Use of 5-α-reductase inhibitors for prostate
cancer chemoprevention: American Society
of Clinical Oncology/American Urological
Association 2008 Clinical Practice Guideline Use of Journal of Clinical Oncology
2009;27(9):1502-16.
2. Wilt T, MacDonald R, Hagerty K, et al.
5-α-reductase inhibitors for prostate cancer
prevention. Cochrane Database Syst Rev
2008, issue 2.
3. Thompson IM, Goodman PJ, Tangen CM,
et al. The influence of finasteride on the development of prostate cancer. N Engl J Med
2003;349:215-24.
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4. Gomella LG. Chemoprevention using dutasteride: the REDUCE trial. Curr Opin Urol
2005;15(1):29-32.
Caryl Heaton, DO, UMDNJ-New
Jersey Medical School, Editor
Diana Heiman, MD, University of
Connecticut, Co-Editor
Clinical Guidelines That Can Improve Your Care
Caryl Heaton, DO, editor—heaton@umdnj.edu
Diana Heiman, MD, coeditor—dheiman@stfranciscare.org
Family Physicians Inquiries Network (FPIN)
HelpDesk
Jon Neher, MD, editor—ebpeditor@fpin.org
For the Office-based Teacher of Family Medicine
John Delzell Jr, MD, MSPH, editor—jdelzell@kumc.edu
Information Technology and Teaching
in the Office
Richard Usatine, MD, editor—usatine@uthscsa.edu
Thomas Agresta, MD, coeditor—Agresta@nso1.uchc.edu
POEMs for the Teaching Family Physician
Mark Ebell, MD, MS, editor—ebell@msu.edu
Teaching Points—A 2-minute Mini-lecture
Alec Chessman, MD, editor—chessmaw@musc.edu
Betty Gatipon, PhD, coeditor—bgatip@lsuhsc.edu
Copyright 2009 by the Society of Teachers of Family Medicine
July 2009
The Teaching Physician
4
(continued from page 1)
Dr P: Excellent. Can you think of any
patient we saw today where that issue
of transitions came up?
MS3: I’m not sure. Standards of care
are met?
MS3: We saw that one person who was
following up after a hospital admission.
There was no note in the chart. We had
to call the team who cared for him in the
hospital to find out what they had done.
I’m not happy to be training in a country
that performs so poorly compared to
other countries. So, the US doesn’t do
much of anything right when it comes
to health care quality, right?
Quality of Care
Dr P: I like that, as long as you throw in
something about delivery, too. So, I use
this definition: “delivery of treatments,
technologies, and medical services
known to be effective, to patients who
need them.”
MS3: Makes sense.
MS3: For lots of patients with common
chronic diseases, like hypertension,
diabetes, and asthma, the US health care
system delivers about 50% of effective
treatments to patients who need them.1
Dr P: Well, hang on. It’s not that bad. In
most states, more than 90% of eligible
children have received part or all of the
required immunizations. Vaccination
rates have been a bright spot in US
health care quality. Also, partly because
of national campaigns aimed at blood
pressure and cholesterol control, the US
cardiac death rate has declined in the
past several years. So there are some
programs that have improved quality.
Dr P: 50%, only. Interesting. How does
our system compare to the systems in
other industrialized countries?
MS3: I still don’t get it, though. If the
US is such an advanced country, why do
we have such low health care quality?
MS3: According to the article, the US
ranks very low, almost last among industrialized countries in many areas of
health care quality.
Dr P: I think there are different factors
that contribute. The US lacks a uniform,
standardized health care information
system. Lack of information about a
patient can lead to expensive duplication of medical services or failure to
provide needed services. Some authorities feel that the decline in the number
of primary care physicians, compared
to the number of subspecialists, has led
to increasing health care costs and decreasing health care quality in the US.
Some physicians resist programs that
seek to improve care, because they fear
that a system of care threatens their
professional autonomy. We also know,
in general, that innovations and new
knowledge take a long time to get incorporated into regular use. New medical
technologies take about 17 years from
discovery to application for patients.
Some authorities cite “defensive
medicine” as a cause for some of our
health care quality problems. Add this
information to the fact that more than
Dr P: So how well does the US health
care system do in delivering effective
health care services to patients who
need them?
Dr P: I agree with you—it is a paradox.
Such wealth and richness to our system,
and yet we score poorly in quality compared to the systems in other nations.
We have trouble delivering helpful care
to everyone who needs it. And we make
mistakes in delivering the care. More
than 40,000 patients die in the US annually due to medical errors. So why do
we have trouble delivering care?
MS3: Miscommunication can contribute to errors. Sometimes information
gets dropped or garbled during transitions, like when a patient goes from
one care setting to another, from the
nursing home to the hospital or back.
Or the order is not understood. That’s
why we aren’t supposed to use certain
abbreviations in the chart.
July 2009
40 million people in the US lack health
care access due to inadequate or no
health insurance and you can see why
the US health care system has trouble
with quality.
MS3: Now you are depressing me.
Dr P: (smiles) I’m sorry. You can do
something about it, though.
MS3: Like what?
Dr P: Exactly what you are doing right
here, right now, is the best first step.
Get informed.
One of the best, most current information sites in this area is the Institute
of Medicine’s Web site, www.iom.edu.
Keep questioning what you are doing,
and keep looking to improve the systems of care around you—for example,
improve the system for coordinating
care among a set of subspecialists—
so, we now have an electronic health
record that contains the notes from all
these consulting physicians, and that
has improved my understanding of that
patient’s care greatly. And we’ll look
into what happened to the usual hospital
discharge system for that other patient.
Why didn’t the discharge summary get
into his chart?
MS3: I do need to learn more about this
topic. When I start my residency training, I will look for a training program
that emphasizes systems of care and
practice improvement.
Dr P: You should consider the residency
program at Brigadoon, Nebraska. They
will help you learn how to set up a
system to look continuously at practice outcomes, as well as work with
your hospital’s quality improvement
programs.
Reference
1. McGlynn EA, Asch SM, Adams J, et al.
The quality of health care delivered to
adults in the United States. N Engl J Med
2003;348(26):2635-45.
Alec Chessman, MD, Medical University of South Carolina, Editor
5
The Teaching Physician
From the “Evidence-Based Practice” HelpDesk Answers
Published by Family Physicians Inquiries Network (FPIN)
Does Stretching Before or After Exercise
Prevent Muscle Soreness?
By Kevin O’Donnell, DO, and Deepak Patel, MD,
The Toledo Hospital Primary Care Sports Medicine Fellowship, Toledo, Ohio
Evidence-based Answer
Although frequently recommended,
stretching before or after exercise does
not prevent delayed-onset mus­cle soreness. (SOR B, based on meta-analyses
of pri­marily low-quality studies.)
Evidence Summary
Muscle pain experienced approximately 12 to 48 hours after exercise
is known as delayed-onset muscle
soreness (DOMS). A 2007 Cochrane
meta-analysis identified randomized
or quasi-randomized studies of preor post-exercise stretching to prevent
DOMS.1 Ten studies with a total of 130
patients were included; three studies
examined the effects of stretching before exercise, and seven measured the
effects of stretching after exercise. Nine
of the 10 studies were performed in a
laboratory setting.
Day-after soreness with pre-exercise
stretch­ing was reduced, although the
difference was not significant (0.5-point
improvement on a 100-point scale; 95%
confidence interval [CI], –11.3 to 10.3).
Post-exercise stretching was also associated with reduced day-after soreness;
again, the differ­ence was not significant
(1.0-point improvement on a 100-point
scale; 95% CI, –6.9 to 4.8).
These results reinforce the conclusion of an ear­lier systematic review that
identified five randomized controlled
trials (RCTs) or quasi-RCTs also exam­
ining the effects of stretching immediately before or after exercise on DOMS.2
Only studies published in English were
included. Two trials evaluated stretch­
ing before exercise, and three looked at
stretching after exercise. Data from 77
subjects were pooled using a 100-mm
visual analog scale (with negative num­
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July 2009
bers favoring stretching). Pooled mean
effects on muscle soreness 24, 48, and
72 hours after exercise were –0.9 mm
(95% CI, –4.4 to 2.6 mm; P=.70; n=77),
0.3 mm (95% CI, –4.0 to 4.5 mm;
P=.45; n=77), and –1.6 (95% CI, –5.9
to 2.6 mm; P=.77; n=67), respectively.
Stretching provided nonsignifi­cant improvement in muscle soreness.
References
1. Herbert RD, de Noronha M. Stretching to
prevent or reduce muscle soreness after
exercise. Cochrane Database Syst Rev 2007;
(4):CD004577. [LOE1a]
2. Herbert RD, Gabriel M. Effects of stretching
before and after exercising on muscle soreness
and risk of injury: systematic review. BMJ
2002;325:468. [LOE1a]
SOR—strength of recommendation
LOE—level of evidence
Jon O. Neher, MD, University of
Washington, Editor
HelpDesk Answers are provided
by Evidence-Based Practice,
a monthly publication of the
Family Practice Inquiries Network
(www.fpin.org)
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The Teaching Physician
6
POEMs for the Teaching Physician
Three-drug Approach More Effective Than Nicotine Replacement
Alone
Clinical Question: Is the combination
of nicotine patch, nicotine inhaler, and
bupropion more effective than nicotine
patch alone in providing sustained
smoking cessation?
Setting: Outpatient (primary care)
Study Design: Randomized controlled
trial (nonblinded)
Funding: Foundation
Allocation: Concealed
Synopsis: To test their hypothesis,
the researchers conducting this study
enrolled 127 adult smokers recruited
from the community who also had
at least one chronic medical illness,
such as cardiovascular or pulmonary
disease, but not unstable angina, recent
myocardial infarction, or severe arrhythymia. The patients were randomized,
using concealed allocation, to receive
single-drug or triple-drug therapy.
Single-drug therapy consisted of a nicotine patch, starting at 21 mg per day
and tapering, over 10 weeks, ending
with 7 mg per day. Triple-drug therapy
patients received the nicotine patch at
the same starting dose, with tapering
beginning after 2 weeks without notable symptoms or cravings for tobacco,
decreasing every 2 weeks after that if
symptom free. They also were given a
nicotine inhaler to use as needed and
bupropion 150 mg per day, continued
for 2 weeks following discontinuation
of the nicotine patch. Using intentionto-treat analysis, quit rates at 6 months
were 35% in the triple-drug group and
19% in the patch-only group (P=.040).
One additional person quit smoking
for every 5.4 people receiving triple
therapy instead of the single therapy
(number needed to treat=5.4; 95% CI,
2.5–131). Insomnia and anxiety were
reported more frequently with the
combination treatment, but drop-outs
due to side effects were similar in both
groups. This was a small study, and
we will know better what to expect
when it is repeated in another group
of patients.
Bottom Line: In this small study, the
combination of a nicotine patch, nicotine inhaler, and bupropion (Zyban)
was shown to be more effective than
nicotine patch alone, with 35% of users abstinent at 26 weeks compared
with 19% of patients in the patch-only
group (number needed to treat=5.4).
In the triple-therapy group, the patch
strength was tapered down according to symptoms instead on a fixed
schedule, the inhaler was used as
needed for symptom control, and the
bupropion was continued until 2 weeks
following discontinuation of the patch.
(LOE=1b-)
Source article: Steinberg MB, Greenhaus S,
Schmelzer AC, et al. Triple-combination pharmacotherapy for medically ill smokers. A randomized trial. Ann Intern Med 2009;150:447-54.
Single Intra-articular Hyaluronic
Acid=Placebo in Hip DJD
Clinical Question: Is a single intraarticular injection of hyaluronic acid
effective in reducing pain or improving
function in patients with symptomatic
degenerative joint disease of the hip?
Setting: Outpatient (specialty)
Study Design: Randomized controlled
trial (double-blinded)
Funding: Industry
Allocation: Concealed
Synopsis: To be eligible for this study,
patients had to be between 30 years and
July 2009
80 years of age; have radiographically
confirmed, moderately severe degenerative joint disease involving the hip;
have had daily pain for at least 1 month
with a severity of at least 40 mm on a
100-mm visual analog scale (VAS) in
spite of treatment with acetaminophen
or nonsteroidal antiinf lammatory
drugs (NSAIDs). These patients were
randomly assigned (concealed allocation) to receive a single fluoroscopically guided intra-articular injection of
hyaluronic acid or a placebo. After the
injections, patients could use NSAIDs
or stronger analgesics only if the pain
did not respond to optimal doses of
acetaminophen (4 g/day). The main
outcomes—change in pain ratings
and some measures of function—
were analyzed by intention to treat.
The researchers estimated they would
need 122 patients to find a difference
in pain response of 20 mm on the
VAS. This is the minimal clinically
important difference for pain scores.
They only studied 85 patients because
recruitment was slow and their supply
of medication had expired. At the end
of 12 weeks, the patients who received
active therapy saw their pain scores
decrease by the same amount as those
who received placebo (average=8 mm
compared with 9 mm). Additionally,
approximately one third of the patients in each group were categorized
as responders (not defined by the
researchers).
Bottom Line: A single intra-articular
injection of hyaluronic acid to the hip
of patients with symptomatic degenerative joint disease was no better than
placebo in decreasing pain or improving function. (LOE=2b)
Source Article: Richette P, Ravaud P, Conrozier
T, et al. Effect of hyaluronic acid in symptomatic hip osteoarthritis: a multicenter, randomized, placebo-controlled trial. Arthritis Rheum
2009;60(3):824-30.
7
The Teaching Physician
Vitamin D, at High Doses, Prevents
Fractures
Clinical Question: Can vitamin D
prevent important fractures related to
osteoporosis?
Setting: Various (meta-analysis)
Study Design: Meta-analysis (randomized controlled trials)
Funding: Foundation
Synopsis: This meta-analysis, now the
fourth on this topic in the past 5 years,
went further than the other ones and
looked at the relationship of dose and
effectiveness of vitamin D in preventing nonvertebral fractures, especially
hip fracture. To identify articles, the
authors searched three databases,
including the Cochrane Controlled
Trials Register, and searched meeting
abstracts and reference lists of identified
articles and contacted experts in the
field. They identified 12 double-blind
randomized controlled trials (enrolling a total of 42,279 patients with an
average age of 78 years) that included
data on how the fractures happened
and data regarding adherence so they
could calculate the received dosage of
vitamin D. Data from the studies were
independently abstracted by three researchers, then compared. Combining
all trials, vitamin D supplementation
produced a small decrease in nonvertebral fractures (relative risk=.86;
95% CI, .77–.96). However, the results
across studies were heterogeneous until
they stratified study results by dosage.
Dosages of 400 IU per day or less did
not reduce nonvertebral fracture risk.
Dosages of greater than 400 IU per
day significantly reduced nonvertebral
fractures, with one fracture prevented
for every 93 patients treated with vitamin D instead of placebo for 12 months
to 84 months (number needed to treat
[NNT]=93; 66–160). The effect was
more pronounced with cholecalciferol
(vitamin D3) than with erogocalciferol
(vitamin D2). Similarly, hip fractures
were also prevented by higher dosages
of vitamin D (NNT=202; 114–823). The
addition of calcium supplementation did
not improve results.
Bottom Line: Vitamin D at dosages
greater than 400 IU per day is effective
in decreasing nonvertebral fractures, in-
July 2009
cluding hip fractures. The effect is dose
dependent; dosages less than 400 IU per
day are ineffective. A practical way to
implement this low-cost approach is
to suggest nonprescription vitamin D
supplements at dosages of 800 IU per
day; that way, missed doses will still
keep the average daily dose in the range
of effectiveness. (LOE=1a)
Source Article: Bischoff-Ferrari HA, Willett
WC, Wong JB, et al. Prevention of nonvertebral
fractures with oral vitamin D dose dependency.
A meta-analysis of randomized controlled trials.
Arch Intern Med 2009;169(6):551-61.
LOE—level of evidence. This is on a scale of 1a
(best) to 5 (worst). 1b for an article about treatmen
is a well-designed randomized controlled trial
with a narrow confidence interval.
Mark Ebell, MD, MS, Michigan State
University, Editor
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Copyright 2009