A

A RE E MERGENCY C ARE S YSTEMS F LATLINING ?
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Family Practice News
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T he Leading Inde p endent Ne wspaper for the Family Physician—Since 1971
Febuxostat Stamps
Out Gout Flares at
Four-Year Follow-Up
M IKE S TACK /S AINT J OSEPH R EGIONAL M EDICAL C ENTER
INSIDE
Low urate levels may eliminate tophi.
No Pain,
Plenty Gain
A
new proposal from the
Centers for Medicare and
Medicaid Services could
result in a better bottom line next
year for physicians who spend a
lot of time on evaluation and
management services.
CMS officials are seeking to
increase the work component for
relative value units (RVUs) for a
number of evaluation and management service codes. For example, Medicare is proposing to
increase the work RVUs for the
commonly used established office visit codes 99213 and 99214.
The proposed changes, which are
the result of a mandatory 5-year
review by the CMS, would take
effect in January 2007.
The proposed rule, issued on
June 29, also calls for changes in
the practice expense methodology that would involve the use of
practice expense survey data
from eight specialties—including
cardiology, dermatology, and gastroenterology—to better calculate the costs incurred by physicians. These changes would
begin in January but would be
phased in over 4 years.
To pay for the proposed increases in reimbursement, the
CMS is required to impose
across-the-board cuts in work
PAGE 23
It’s Official
ACIP endorses vaccinating
girls and women against
HPV; AAFP to follow suit.
PAGE 8
Calming Force
A yoga program boosted
quality of life in women
undergoing radiation.
BY MIRIAM E. TUCKER
Senior Writer
PAGE 40
VITAL SIGNS
West Nile Virus
After Seven Summers, What’s in Store for 2006?
CASES
DEATHS
1999
62
7
2000
21
2
2001
66
9
2002
4,156
284
2003
9,862
264
2004
2,539
100
2005
3,000
119
Source: Centers for Disease Control and Prevention
maceutical Products Inc. that
febuxostat represents such an advance over standard therapies in
terms of safety, efficacy, and ease
of use that internists and family
physicians will take on a more active primary role in gout management, he said.
Nearly two-thirds of the 26
study patients who had palpable
tophi at baseline had no detectable
tophus after 4 years, in the longest
trial involving the novel nonpurine selective xanthine oxidase
inhibitor, he reported.
“Maintaining serum urate at
that level of less than 6 mg/dL
looks like it’s going to be able to
resorb tophi,” observed Dr. Schumacher, professor of medicine at
See Gout page 52
Hypertension Risk Soars
In Type 2 Diabetic Child
CDC
Ne w York Bureau
RVUs. This could mean payment
cuts for physicians who provide
fewer evaluation and management services.
Moreover, the expected increase for primary care physicians
could be offset by the end of the
year if physicians are unable to get
a temporary fix to the sustainable
growth rate formula, which is expected to cut physician payments
under Medicare by nearly 5%.
“The CMS proposal reinforces
the urgent need for Congress to
act to stop the Medicare physician payment cuts and ensure
that payments keep up to pracSee E&M Pay page 56
A M S T E R D A M — The investigational gout medication febuxostat consistently maintained
serum urate levels below 6
mg/dL while markedly reducing
gout flares in a 4-year study, Dr.
H. Ralph Schumacher Jr. said at
the annual European Congress of
Rheumatology.
Dr. Schumacher reported on
116 patients with chronic gout
who participated in the ongoing
Febuxostat Open-Label Clinical
Trial of Urate-Lowering Efficacy
and Safety (FOCUS). The study
was conducted predominantly by
primary care physicians, reflecting the expectation of TAP Phar-
COURTESY
SCHNEIDER
Denver Bureau
E LSEVIER G LOBAL M EDICAL N EWS /P HOTO
B Y M A RY E L L E N
BY BRUCE JANCIN
Corneal confocal microscopy
noninvasively diagnoses
neuropathy.
The two main codes used by FPs—99213 and 99214—are set to
increase by about 10% in 2007, said Dr. Thomas Felger.
CMS Proposes
Hike in E&M Pay
J U LY 1 5 , 2 0 0 6
W A S H I N G T O N — People of
all ages with type 2 diabetes are
at increased risk for essential hypertension, but the relationship is
exceptionally strong among children and adolescents, Dr. Scott J.
Jacober and his associates reported in a poster at the annual
scientific sessions of the American Diabetes Association.
In children younger than 12,
essential hypertension may be
present in more than a quarter of
patients.
Essential hypertension and
type 2 diabetes often coexist, but
this retrospective review of a nationwide electronic medical
records database is believed to
be the first to examine the prevalence of essential hypertension
by age group among individuals
with and without diabetes, said
Dr. Jacober, who was with Lilly
Research Laboratories, Indianapolis, at the time of the study.
The database contained more
than 4 million patients, and the
study population, from 49 states
during 1996-2005, comprised
231,492 individuals with a physician’s diagnosis of type 2 diabetes
See Hypertension page 15
Clinical Rounds
F A M I LY P R A C T I C E N E W S • J u l y 1 5 , 2 0 0 6
BRIEF SUMMARY
For Intravenous Infusion Only
DESCRIPTION
Adenosine is an endogenous nucleoside occurring in all cells of the body. It is chemically 6-amino-9-beta-D-ribofuranosyl-9-H-purine.
Adenosine is a white crystalline powder. It is soluble in water and practically insoluble in alcohol. Solubility increases by warming and lowering the pH of
the solution.
Each Adenoscan vial contains a sterile, non-pyrogenic solution of adenosine 3 mg/mL and sodium chloride 9 mg/mL in Water for Injection, q.s. The pH of
the solution is between 4.5 and 7.5.
INDICATIONS AND USAGE:
Intravenous Adenoscan is indicated as an adjunct to thallium-201 myocardial perfusion scintigraphy in patients unable to exercise adequately.
(See WARNINGS).
CONTRAINDICATIONS:
Intravenous Adenoscan should not be administered to individuals with:
1. Second- or third-degree AV block (except in patients with a functioning artificial pacemaker).
2. Sinus node disease, such as sick sinus syndrome or symptomatic bradycardia (except in patients
with a functioning artificial pacemaker).
3. Known or suspected bronchoconstrictive or bronchospastic lung disease (e.g., asthma).
4. Known hypersensitivity to adenosine.
WARNINGS:
Fatal Cardiac Arrest, Life Threatening Ventricular Arrhythmias, and Myocardial Infarction.
Fatal cardiac arrest, sustained ventricular tachycardia (requiring resuscitation), and nonfatal myocardial infarction have been reported coincident with
Adenoscan infusion. Patients with unstable angina may be at greater risk. Appropriate resuscitative measures should be available.
Sinoatrial and Atrioventricular Nodal Block
Adenoscan exerts a direct depressant effect on the SA and AV nodes and has the potential to cause first-, second- or third-degree AV block, or sinus
bradycardia. Approximately 6.3% of patients develop AV block with Adenoscan, including first-degree (2.9%), second-degree (2.6%) and third-degree
(0.8%) heart block. All episodes of AV block have been asymptomatic, transient, and did not require intervention. Adenoscan can cause sinus
bradycardia. Adenoscan should be used with caution in patients with pre-existing first-degree AV block or bundle branch block and should be avoided
in patients with high-grade AV block or sinus node dysfunction (except in patients with a functioning artificial pacemaker). Adenoscan should be
discontinued in any patient who develops persistent or symptomatic high-grade AV block. Sinus pause has been rarely observed with adenosine infusions.
Hypotension
Adenoscan is a potent peripheral vasodilator and can cause significant hypotension. Patients with an intact baroreceptor reflux mechanism are able to
maintain blood pressure and tissue perfusion in response to Adenoscan by increasing heart rate and cardiac output. However, Adenoscan should be used
with caution in patients with autonomic dysfunction, stenotic valvular heart disease, pericarditis or pericardial effusions, stenotic carotid artery disease with
cerebrovascular insufficiency, or uncorrected hypovolemia, due to the risk of hypotensive complications in these patients. Adenoscan should be discontinued
in any patient who develops persistent or symptomatic hypotension.
Hypertension
Increases in systolic and diastolic pressure have been observed (as great as 140 mm Hg systolic in one case) concomitant with Adenoscan infusion; most
increases resolved spontaneously within several minutes, but in some cases, hypertension lasted for several hours.
Bronchoconstriction
Adenoscan is a respiratory stimulant (probably through activation of carotid body chemoreceptors) and intravenous administration in man has
been shown to increase minute ventilation (Ve) and reduce arterial PCO 2 causing respiratory alkalosis. Approximately 28% of patients experience breathlessness (dyspnea) or an urge to breathe deeply with Adenoscan. These respiratory complaints are transient and only rarely require
intervention.
Adenosine administered by inhalation has been reported to cause bronchoconstriction in asthmatic patients, presumably due to mast cell degranulation
and histamine release. These effects have not been observed in normal subjects. Adenoscan has been administered to a limited number of patients
with asthma and mild to moderate exacerbation of their symptoms has been reported. Respiratory compromise has occurred during adenosine infusion in patients
with obstructive pulmonary disease. Adenoscan should be used with caution in patients with obstructive lung disease not associated with bronchoconstriction
(e.g., emphysema, bronchitis, etc.) and should be avoided in patients with bronchoconstriction or bronchospasm (e.g., asthma). Adenoscan should be
discontinued in any patient who develops severe respiratory difficulties.
PRECAUTIONS:
Drug Interactions
Intravenous Adenoscan has been given with other cardioactive drugs (such as beta adrenergic blocking agents, cardiac glycosides, and calcium
channel blockers) without apparent adverse interactions, but its effectiveness with these agents has not been systematically evaluated. Because
of the potential for additive or synergistic depressant effects on the SA and AV nodes, however, Adenoscan should be used with caution in the
presence of these agents. The vasoactive effects of Adenoscan are inhibited by adenosine receptor antagonists, such as methylxanthines (e.g.,
caffeine and theophylline). The safety and efficacy of Adenoscan in the presence of these agents has not been systematically evaluated. The
vasoactive effects of Adenoscan are potentiated by nucleoside transport inhibitors, such as dipyridamole. The safety and efficacy of Adenoscan
in the presence of dipyridamole has not been systematically evaluated. Whenever possible, drugs that might inhibit or augment the effects of
adenosine should be withheld for at least five half-lives prior to the use of Adenoscan.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Studies in animals have not been performed to evaluate the carcinogenic potential of Adenoscan. Adenosine was negative for genotoxic potential in the
Salmonella (Ames Test) and Mammalian Microsome Assay.
Adenosine, however, like other nucleosides at millimolar concentrations present for several doubling times of cells in culture, is known to produce a variety
of chromosomal alterations. Fertility studies in animals have not been conducted with adenosine.
Pregnancy Category C
Animal reproduction studies have not been conducted with adenosine; nor have studies been performed in pregnant women. Because it is not known whether
Adenoscan can cause fetal harm when administered to pregnant women, Adenoscan should be used during pregnancy only if clearly needed.
Pediatric Use
The safety and effectiveness of Adenoscan in patients less than 18 years of age have not been established.
Geriatric Use
Clinical studies of Adenoscan did not include sufficient numbers of subjects aged younger than 65 years to determine whether they respond
differently. Other reported experience has not revealed clinically relevant differences of the response of elderly in comparison to younger patients. Greater
sensitivity of some older individuals, however, cannot be ruled out.
ADVERSE REACTIONS:
The following reactions with an incidence of at least 1% were reported with intravenous Adenoscan among 1421 patients enrolled in controlled and uncontrolled
U.S. clinical trials. Despite the short half-life of adenosine, 10.6% of the side effects occurred not with the infusion of Adenoscan but several hours after the
infusion terminated. Also, 8.4% of the side effects that began coincident with the infusion persisted for up to 24 hours after the infusion was complete. In
many cases, it is not possible to know whether these late adverse events are the result of Adenoscan infusion.
Flushing
44%
Lightheadedness/dizziness
12%
Hypotension
Chest discomfort
40%
Upper extremity discomfort
4%
Nervousness
Dyspnea or urge to breathe deeply
28%
ST segment depression
3%
Arrhythmias
Headache
18%
First-degree AV block
3%
Throat, neck or jaw discomfort
15%
Second-degree AV block
3%
Gastrointestinal discomfort
13%
Paresthesia
2%
Adverse experiences of any severity reported in less than 1% of patients include:
Body as a Whole: back discomfort; lower extremity discomfort; weakness.
Cardiovascular System: nonfatal myocardial infarction; life-threatening ventricular arrhythmia; third-degree AV block; bradycardia;
palpitation; sinus exit block; sinus pause; sweating; T-wave changes, hypertension (systolic blood pressure > 200 mm Hg).
Central Nervous System: drowsiness; emotional instability; tremors.
Genital/Urinary System: vaginal pressure; urgency.
Respiratory System: cough.
Special Senses: blurred vision; dry mouth; ear discomfort; metallic taste; nasal congestion; scotomas; tongue discomfort.
2%
2%
1%
Urate Below 6 mg/dL Common
Gout from page 1
the University of Pennsylvania and director of rheumatology at the Veterans Affairs Medical Center, Philadelphia.
Food and Drug Administration approval
of febuxostat is expected imminently. The
drug should be on pharmacy shelves later this year, according to Dr. Schumacher.
If so, it would be the first new drug approved for gout in 40 years.
Participants in FOCUS started on oncedaily febuxostat at 80 mg. During weeks
4-24 they were allowed to titrate to 40 or
120 mg/day in an effort to maintain serum
urate levels in the
target range or to
address adverse reactions. Patients remained on their
week-28 dose for
the remainder of
the 4 years.
The majority of
patients reduced
their serum urate
level to below 6 mg/dL—the generally accepted saturation point, and a level at
which crystals would be expected to dissolve—within 7 days. The proportion of
patients with a serum urate level below 6
mg/dL climbed from 78% at year 1 to 90%
at year 4. Even among the handful of patients on 40 mg/day, which isn’t expected
to be a recommended dose, 86% had a
serum urate below 6 mg/dL.
However, nobody on 40 mg/day got
their serum urate level to less than 4
mg/dL, a range in which tophi dissolve
more rapidly. In contrast, 30% of patients
on 80 or 120 mg of febuxostat once daily
had serum urate levels consistently falling
below 4 mg/dL.
The mean number of gout flares per
year declined sharply over time: an average of 2.22 in year 1, 0.44 in year 2, 0.26
in year 3, and 0.18 in year 4.
Prophylaxis against gout flares was provided by concomitant colchicine at 6
mg/day for the first 4 weeks of FOCUS.
Upon discontinuation of the drug, however, the flare rate temporarily went up. This
suggests that maintaining prophylaxis for
longer than 4 weeks is warranted in clinical practice, Dr.
Schumacher said.
Allopurinol, the
Approval is
only FDA-approved
expected
serum urate–lowerimminently, and it
ing drug, is a probshould be on
lematic agent with
pharmacy shelves
numerous side eflater this year.
fects, particularly in
patients with renal
DR. SCHUMACHER
insufficiency.
Fifty-five patients dropped out of FOCUS. Dr. Schumacher, however, emphasized that the majority of dropouts occurred in the first year and were due to
patient disenchantment with trial logistics
rather than safety or efficacy issues.
No serious adverse events were attributed to febuxostat. The most common reported adverse event was transient, mild
to moderate elevation of liver function
test results. This occurred in 14 patients;
however, 3 were alcohol abusers and 9 others were on concomitant medications having hepatotoxic effects, including acetaminophen, colchicin, and NSAIDs.
■
Monitor Bone Health in a
Rheumatic Disease Setting
OVERDOSAGE:
The half-life of adenosine is less than 10 seconds and side effects of Adenoscan (when they occur) usually resolve quickly when the infusion is
discontinued, although delayed or persistent effects have been observed. Methylxanthines, such as caffeine and theophylline, are competitive
adenosine receptor antagonists and theophylline has been used to effectively terminate persistent side effects. In controlled U.S. clinical trials,
theophylline (50-125 mg slow intravenous injection) was needed to abort Adenoscan side effects in less than 2% of patients.
DOSAGE AND ADMINISTRATION:
For intravenous infusion only.
Adenoscan should be given as a continuous peripheral intravenous infusion.
The recommended intravenous dose for adults is 140 mcg/kg/min infused for six minutes (total dose of 0.84 mg/kg).
The required dose of thallium-201 should be injected at the midpoint of the Adenoscan infusion (i.e., after the first three minutes of Adenoscan).
Thallium-201 is physically compatible with Adenoscan and may be injected directly into the Adenoscan infusion set.
The injection should be as close to the venous access as possible to prevent an inadvertent increase in the dose of Adenoscan (the contents
of the IV tubing) being administered.There are no data on the safety or efficacy of alternative Adenoscan infusion protocols.
The safety and efficacy of Adenoscan administered by the intracoronary route have not been established.
Note: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.
Rx only
Marketed by Astellas Pharma US, Inc.
Deerfield, IL 60015
Manufactured by Hospira Inc.
47101/Revised: April 2005
Lake Forest, IL 60045 USA
D E S T I N , F L A . — Patients with
rheumatic disease and osteoporosis or
low-impact fracture might benefit from
early sequential therapy with anabolic and
antiresorptive drugs to build and maintain
bone, Dr. Nancy Lane reported at a
rheumatology meeting sponsored by Virginia Commonwealth University.
“You could use parathyroid hormone for
a year or two to change the bone architecture in a positive way and then maintain
those gains with an antiresorptive agent—
either a bisphosphonate or a selective estrogen receptor modulator,” Dr. Lane said.
Continuous inflammation appears to
adversely affect bone health by increasing
bone resorption and decreasing formation, said Dr. Lane, director, the Center for
Healthy Aging at the University of California, Davis.
In a study of vertebral fractures in 70 patients with systemic lupus erythematosus
who were compared with 22 matched
healthy controls, no bone mineral density differences were found between the
two groups. However, 21% of the lupus
group had at least one thoracic or lumbar
spine fracture, compared with no subjects
in the control group. The study included
premenopausal women with a mean age
C OURTESY D R . N ANCY L ANE
52
MRI of an L4 vertebrae fracture in a 40year-old woman taking glucocorticoids.
of 31.5 years (Lupus 2005;14:529-33).
The first step is to address the problem
of systemic inflammation. But it’s also critical to be aggressive in identifying and treating those who are at risk for fracture.
Rheumatic disease patients often have additional risk factors, including vitamin D deficiency, sedentary lifestyle, and concomitant endocrine dysfunction. Glucocorticoid
therapy can also induce osteoporotic
changes, Dr. Lane said at the meeting, also
sponsored by the International Society for
Clinical Densitometry and the Alabama
Chapter of the Arthritis Foundation.
—Michele G. Sullivan
`