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the osteopathic physician.

The treatment
approach involves therapeutic lifestyle
changes with diet, exercise, and weight
loss. It requires regular, careful moni-
toring of serum cholesterol levels. The The National Cholesterol Education
new ATP III guidelines expand greatly Program Adult Treatment Panel III
the total number of patients who are eli- guidelines
gible for treatment of hypercholes-
terolemia. Definite goals for LDL-C are
defined for patients with coronary heart Michael B. Clearfield, DO
disease and patients at risk for subse-
quent clinical events. Many, if not most
of these patients, will not be able to
achieve their target LDL-C level without
pharmacologic therapy.
The ATP III evidence-based guide- Coronary heart disease (CHD) remains the leading cause of death in the United
lines have defined the standard. It is our States with more than 40% of all deaths each year directly attributed to the
responsibility and unique opportunity disease. Current evidence suggests that early identification and aggressive
to fulfill these expectations through modification of risk factors offer the most promising approach to reducing
thoughtful clinical practice. We might the burden of CHD. Dyslipidemia has been identified as the primary risk
consider this supplement to represent a factor leading to the development of CHD. It is estimated that nearly 65 mil-
tool to help us accomplish this task. lion Americans require some form of lipid-modification therapy.
The National Cholesterol Education Program Adult Treatment Panel III
References (NCEP ATP III) set of guidelines released in May 2001 provides physicians with
1. Expert Panel on the Detection, Evaluation, and evidence-based recommendations on the classification, diagnosis, and treatment
Treatment of High Blood Cholesterol in Adults.
Executive Summary of the Third Report of the of lipid disorders. New features of the guidelines include a scoring system
National Cholesterol Education Program (NCEP) for calculating CHD risk, as well as the identification of CHD risk equiva-
Expert Panel on Detection, Evaluation and Treat- lents, lower treatment target goals, and an emphasis on conditions conferring
ment of High Blood Cholesterol in Adults (Adult
Treatment Panel III). JAMA. 2001;285:2486-2497. a higher risk for CHD, such as the metabolic syndrome. The ATP III emphasis
on risk assessment substantially increases the number of patients considered
2. The American Heart Association 2002 Heart at risk for CHD and will expand the number eligible for lifestyle and drug inter-
and Stroke Statistical Update. Dallas, Tex: American
Heart Association; 2001; pp 4-23. ventions.
This article highlights the new recommendations and reviews the impact
3. Pearson TA, Laurora I, Chu H, Kafonek S. The
Lipid Treatment Assessment Project (L-TAP): A
of ATP III on osteopathic physicians.
multicenter survey to evaluate the percentages (Key words: atherosclerosis, cholesterol, coronary heart disease, dyslipi-
of dyslipidemic patients receiving lipid-lowering demia, low-density lipoprotein cholesterol [LDL-C])
therapy and achieving low-density lipoprotein
cholesterol goals. Arch Intern Med. 2000;160:459-
467.

4. Stafford RS, Blumenthal D, Pasternak RC. Vari-


C oronary heart disease (CHD) has
persisted as the single leading cause
of death among Americans. According
direct and indirect costs of the disease
estimated to be nearly $330 billion in
2002.1
ations in cholesterol management practices of US
physicians. J Am Coll Cardiol. 1997;29:139-146. to the American Heart Association,1 Dyslipidemia is recognized as a
more than 1.1 million new or recurrent major modifiable risk factor for the devel-
5. Bramlett DA, King H, Young L, Witt JR,
Stoukides CA, Kaul AF. Management of hyper- myocardial infarctions occurred in 2000 opment and progression of CHD.
cholesterolemia: practice patterns for primary care and more than 500,000 Americans died Numerous clinical trials have demon-
providers and cardiologists. Am J Cardiol. of CHD-related causes. Coronary heart strated that CHD-related morbidity and
1997;80:39H-44H.
disease also places a significant finan- mortality is reduced after aggressive
cial burden on the US economy with intervention that includes both lifestyle
Dr Rogers, a practicing cardiologist, is a clinical
professor in the Department of Internal Medicine
at the Michigan State University College of Osteo-
Dr Clearfield is a professor of medicine and associate dean for clinical research at the University of
pathic Medicine in East Lansing.
North Texas Health Science Center at Fort Worth/Texas College of Osteopathic Medicine. Dr Clearfield
E-mail: fjrogers@aol.com
represented the American Osteopatic Association, a member organization of the National Cholesterol
Education Program Coordinating Committee, which approved the Third Report of the National Choles-
terol Education Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults.
This educational program was developed from Dr Clearfield is a member of the speakers bureau of AstraZeneca, Merck & Co, Pfizer Inc, and
information presented during a scientific sym-
Sankyo Pharma Inc, and he has received grant/research support from AstraZeneca and Pfizer Inc.
posium conducted on October 11, 2002, in Las
Vegas, Nevada, at the 2002 Annual Convention Correspondence to Michael B. Clearfield, DO, Associate Dean for Clinical Research, Office of the Dean,
and Scientific Seminar of the American Osteo- Texas College of Osteopathic Medicine, University of North Texas Health Science Center at Fort Worth,
pathic Association. 855 Montgomery St, Fort Worth, TX 76107-2699.
E-mail: mclearfi@hsc.unt.edu

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modifications and pharmacologic triglycerides to less than or equal
therapy.2-5 In May 2001, the Adult Treat- to 200 mg/dL.
ment Panel (ATP) of the National Choles- Checklist Further, ATP III recognizes that the
terol Education Program (NCEP) issued heightened emphasis on risk assessment,
its third set of guidelines (NCEP ATP III) the inclusion of CHD risk equivalents,
for the identification and management  Challenges and the more aggressive treatment goals
 Identify patients at risk for CHD
of dyslipidemia.6 Building on ATP I  Implement effective therapy will significantly increase the number of
(1988) and ATP II (1993), ATP III pays  Ensure that patients meet target patients eligible for therapy and chal-
increased attention to the identification goals lenge physicians and the healthcare
and quantification of risk factors for CHD  Emphasis
delivery system to implement the guide-
and therefore vastly expands the number  Risk assessment lines. Therefore, ATP III also presents
of Americans eligible for lipid-lowering  Reduction of low-density strategies for promoting adherence
therapy. lipoprotein cholesterol (LDL-C) as totherapeutic lifestyle changes (TLC) and
primary goal of therapy
With these changes, ATP III presents  Adjustment of intensity of therapy
drug therapy.
a challenge to physicians and the health- to degree of risk
care system to identify at-risk patients,  Importance of lifestyle changes to Assessment of risk for
implement effective therapy, and ensure include: coronary heart disease
— weight loss
that patients meet target goals (Figure 1). — dietary modifications The Framingham risk scoring system
Osteopathic physicians, many of whom — increased physical activity incorporated into ATP III quantifies the
focus on primary care with an emphasis 10-year risk for a coronary event. Point
on treating the entire patient, are in the  New features scores are calculated according to the
 Use of a risk assessment tool based
vanguard for the reduction of CHD risk. on data derived from the presence of five major CHD risk factors
Therefore, osteopathic physicians are Framingham Heart Study (age and gender, total cholesterol, sys-
uniquely positioned to have an impact on  Identification of diabetes as a tolic blood pressure, HDL-C level, and
the implementation of the new guide- coronary heart disease (CHD) risk smoking status), with each risk factor
equivalent
lines.  More aggressive lipid target goals worth a certain number of points. When
 Intensified lipid-modification added together, the sum yields an esti-
New features of the therapy for patients with the mate of the risk for having a coronary
metabolic syndrome
ATP III guidelines  Raising target for high-density
event in 10 years. A properly conducted
Consistent with previous editions, the lipoprotein cholesterol level (to assessment places patients into one of the
new ATP guidelines provide an evi-  40 mg/dL) three risk categories and forms the basis
dence-based approach for the detection  Lowering target for triglyceride for all subsequent treatment decisions.
concentration (to  200 mg/dL)
and treatment of lipid disorders. Adult  Strategies for promoting adherence
Patients with documented CHD and
Treatment Panel III follows ATP II by to treatment regimens CHD risk equivalents are automatically
continuing to focus on reduction of low- placed in the highest risk category. The
density lipoprotein cholesterol (LDL-C) Figure 1. Challenges, emphasis, and new CHD risk equivalents carry a risk for a
as the primary goal of therapy and advo- features of the Adult Treatment Panel III major coronary event equal to that of
cates that the intensity of therapy be guidelines. established CHD and include diabetes,
adjusted to the degree of risk. The ATP III peripheral vascular disease, symptomatic
set of guidelines also reiterates the impor- CHD risk (high, moderate, low) and carotid artery disease, and abdominal
tance of lifestyle changes such as weight identifies specific LDL-C treatment goals aortic aneurysm. The new set of guide-
loss, dietary modifications, and increased for each (Figure 2). The LDL-C target lines places patients with these condi-
physical activity in reducing CHD risk levels for patients with CHD and CHD tions in the same risk category as those
(Figure 1). risk equivalents (highest risk) are now with clinically evident CHD (eg, 20%
New features of the guidelines less than 100 mg/dL. For patients with 10-year risk of CHD). The LDL-C treat-
include the use of a risk assessment tool two or more risk factors (moderate risk), ment goal for patients in this high-risk
based on data derived from the Fram- the target level is less than 130 mg/dL, category is less than 100 mg/dL.
ingham Heart Study,7 the identification and for patients with zero or one risk In patients without documented
of diabetes (with or without clinically factor (low risk), the goal is less than CHD or CHD equivalents, assessment
evident CHD) as a CHD risk equivalent, 160 mg/dL. of CHD risk using the Framingham risk
more aggressive lipid target levels, and Adult Treatment Panel III also rec- quantification system is essential to deter-
the recognition that patients with the ognizes the role high-density lipoprotein mine the most appropriate course of
metabolic syndrome should be provided cholesterol (HDL-C) and triglycerides therapy. Patients with two or more major
intensified lipid-modification therapy play in modifying CHD risk and there- risk factors are considered to be at a mod-
(Figure 1). fore raised the target level for HDL-C erately increased risk for CHD, with a
Adult Treatment Panel III places from less than 35 mg/dL to less than 10-year risk of less than 20%. Therapy
patients into one of three categories of 40 mg/dL and lowered target goals for for the patients in this category should be

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uptake. Physical activity raises HDL-C
levels and decreases the concentration of
very low-density lipoprotein cholesterol
Adult Treatment Panel III and triglycerides. Smoking cessation also
results in a reduction of CHD risk.

Pharmacologic therapy
Although ATP III emphasizes the impor-
Treatment goal level tance of nonpharmacologic therapy, it
Risk stratification (low-density lipoprotein recognizes limitations of such therapy
cholesterol)
and encourages the addition of drug
therapy if TLC fails to move a patient to
goal after 3 months. High-risk patients
will most likely require drug therapy
High risk of coronary heart
disease (CHD) along with TLC from the onset of treat-
 100 mg/dL ment. As stated earlier, treatment goals
(documented CHD or CHD
risk equivalent) and lipid thresholds for initiating drug
therapy are based on the patient’s degree
of risk.
 For patients with the highest risk for
Moderate (two or more risk
coronary events, the LDL-C threshold
 130 mg/dL for initiation of therapy is greater than
factors)
or equal to 130 mg/dL (after a 3-month
trial of TLC) and the goal is less than
100 mg/dL. For patients with LDL-C
between 100 mg/dL and 129 mg/dL,
drug therapy is optional and physicians
Low (zero to one risk factor)  160 mg/dL are encouraged to use their professional
clinical judgment to determine the nature
of therapy required to reduce CHD risk.
 For patients with moderate risk
Figure 2. Low-density lipoprotein cholesterol goals according to risk factor stratification. without definite CHD or CHD risk
(Source: Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood
equivalents but with more than two
Cholesterol in Adults (Adult Treatment Panel III) Full Report. Available at: http://www.nhlbi.
major risk factors and a 10-year risk of
nih.gov/guidelines/cholesterol/atp3_rpt.htm. Accessed December 2, 2002.)
10% to 20%, the threshold is greater than
or equal to 130 mg/dL and the target is
sufficient to enable them to achieve an Therapeutic lifestyle changes also less than 130 mg/dL.
LDL-C target level of less than First-line therapy for all patients is TLC  For patients at moderate risk but with
130 mg/dL. Patients at the lowest risk and may be substantial enough in groups a 10-year risk of less than 10%, the
are those with one or fewer major risk at lower risk to reach their LDL-C goals. threshold for LDL-C is greater than or
factors. In all but rare cases, these indi- Components of TLC that have demon- equal to 160 mg/dL and the target is less
viduals have a 10-year risk of less than strated effectiveness in lowering LDL-C than 130 mg/dL. For patients without
10%. The target LDL-C level in this group include eating a healthy diet, regular CHD and with zero to one major risk
of patients is less than 160 mg/dL. physical activity, smoking cessation, and factor, drug treatment should be consid-
weight loss. Dietary changes should ered if the LDL-C cholesterol level is
Current treatment trends include a reduction of saturated fats to greater than or equal to 190 mg/dL after
With the increased emphasis on risk less than 7% of total calories, reduction of 3 months of TLC, with a goal of greater
assessment and aggressive new treatment intake of dietary cholesterol to less than than or equal to 160 mg/dL. In all cases
goals, it is estimated that the number of 200 mg/d, addition of plant sterols and of drug therapy, TLC should continue
patients eligible for CHD risk reduction stanols at a level of 2 g/d (commercially to be maintained and reinforced.
through lipid-modification therapy in the available in special margarines), and
United States is currently at 65 million. incorporating viscous fiber into the diet at Currently available
The type and extent of therapy is depen- a level of 10 g/d to 25 g/d. Weight reduc- lipid-modifying drugs
dent on the patient’s CHD risk. Two pri- tion can reduce LDL-C levels and ame- Four classes of lipid-modifying drugs
mary modalities advocated by ATP III liorate the risk factors associated with the are currently available in prescription
for lowering LDL-C, and therefore CHD metabolic syndrome by improving form, including bile acid sequestrants,
risk, are ATP TLC and drug therapy. insulin sensitivity and serum glucose nicotinic acids, fibric acid derivatives,

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and 3-hydroxy-3-methylglutaryl coen- in patients at low risk for CHD who DOs must educate their patients about
zyme A reductase inhibitors (statins). require only a modest reduction in their the importance of taking responsibility
Statins, the most widely used lipid-mod- LDL-C level or for those who do not tol- for their own health through the incor-
ifying agent, decrease LDL-C by erate statin therapy.8 In addition, ezeti- poration of healthy lifestyle habits.
inhibiting cholesterol synthesis and mibe, when used in combination with a
reduce LDL-C by 25% to 50% in a dose- low-dose statin in patients at moderate to Comments
dependent manner. high risk for CHD, can elicit a reduction in The NCEP ATP III report updates the
The currently available statins are LDL-C comparable to reductions seen at clinical guidelines for the detection and
differentiated by the LDL-C lowering the highest statin doses.9 treatment of lipid disorders. Although
elicited at a given dose. Several large clin- the emphasis remains on reducing long-
ical outcomes trials have demonstrated Implementation of the ATP III term CHD risk by lowering the LDL-C
that statin use reduces the incidence of guidelines level, new features of the guidelines
CHD events, including myocardial infarc- The ATP III set of guidelines, with an include a scoring system for calculating
tion, coronary death, stroke, and total mor- emphasis on risk assessment and new CHD risk as well as the identification of
tality.2-5 Bile acid sequestrants are another treatment goals, presents an enormous CHD risk equivalents. The ATP III
commonly used agent. challenge to physicians and the health- emphasis on risk assessment will sub-
Bile acid sequestrants can be used as care system in terms of implementation stantially increase the number of indi-
monotherapy when moderate reductions and patient compliance. Previous guide- viduals considered to be at risk for CHD
in LDL-C are required to achieve goal or line adherence rates indicate that and will expand the number of patients
as add-on therapy to statins, particularly achieving the new goals will be difficult. who will be eligible for lifestyle and drug
in patients with severe dyslipidemia. The ATP II guidelines, although much interventions. The new recommenda-
A third class of agents is nicotinic less complex, were rarely followed in tions will significantly challenge physi-
acid, or niacin. Nicotinic acids provide patients with CHD, let alone in patients cians to screen and treat patients to more
a moderate LDL-C–lowering action, but with subclinical disease. Data from the aggressive target lipid levels.
the primary utility of these agents is in Lipid Treatment Assessment Project Osteopathic physicians are uniquely
combination with statins for patients who (L-TAP)10 demonstrated that only 18% positioned to implement the new guide-
have elevated triglyceride concentrations of those with CHD achieved ATP II goals lines and encourage patient compliance.
or low HDL-C levels or both. and that less than 40% of all patients on
Fibric acids, or fibrates, are a fourth lipid-modification therapy receive suffi-
class of lipid-modifying agents that pos- cient lipid lowering to reduce CHD risk. References
sess minimal LDL-C–reducing capacity, Because overall adherence and goal 1. American Heart Association. 2002 Heart and
Stroke Statistical Update. Dallas, Tex: American
but these agents are useful in patients achievement was low with previous Heart Association; 2001: pp 4, 11, 23.
with combined forms of hyperlipidemia. guidelines, the challenges inherent in
Fibrates are especially effective in patients achieving ATP III goals are clear. 2. Scandinavian Simvastatin Survival Study Group.
Randomised Trial of cholesterol lowering in 4444
who have severe hypertriglyceridemia. The ATP III acknowledges that pri- patients with coronary heart disease: the Scandi-
Despite the efficacy of statins in mary prevention of CHD offers the navian Simvastatin Survival Study (4S). Lancet.
modifying lipid levels and reducing coro- greatest opportunity for reducing the 1994;344:1383-1389.
nary events, alternative agents are clinical and economic burden of CHD in 3. West of Scotland Coronary Prevention Study
needed. Some patients are unable to tol- the United States. The clinical approach Group. Influence of pravastatin and plasma lipids
erate statins, or they are not candidates to CHD prevention begins in the pri- on clinical events in the West of Scotland Coro-
nary Prevention Study (WOSCOPS). Circulation.
for use of these agents because of either mary care office and requires an 1998;97:1440-1445.
or both tolerability and safety concerns. informed physician who does not focus
In these cases, physicians and patients solely on a specific symptom and who 4. Downs JR, Clearfield M, Weis S, Whitney F,
Shapiro DR, Beere PA, et al. Primary prevention
are forced to use bile acid sequestrants, implements early risk screening that of acute coronary events with lovastatin in men and
niacin, fibrates, or other less common includes an assessment of the overall women with average cholesterol levels: results of
modes of therapy. These agents, how- health of the patient. Because nearly 60% AFCAPS/TexCAPS. Air Force/Texas Coronary
Atherosclerosis Prevention Study. JAMA.
ever, vary in their effectiveness in of all osteopathic physicians practice in 1998;279:1615-1622.
reducing LDL-C levels owing to low effi- primary care and account for more than
cacy of the agent or poor compliance due 100 million primary care visits per year, 5. Sacks FM, Moyé LA, Davis BR, Cole TG, Rouleau
JL, Nash DT, et al. Relationship between plasma LDL
to undesired side effects. they are uniquely positioned to influence concentrations during treatment with pravastatin
A promising new alternative mode of the implementation of the ATP III guide- and recurrent coronary events in the Cholesterol
therapy was recently approved by the US lines. Thus, DOs can have a significant and Recurrent Events trial. Circulation.
1998;97:1446-1452.
Food and Drug Administration (FDA). impact on the reduction of CHD risks in
Phase II data suggest that ezetimibe, the their patients. 6. Expert Panel on the Detection, Evaluation, and
first selective inhibitor of intestinal choles- Osteopathic physicians also treat a Treatment of High Blood Cholesterol in Adults.
Executive Summary of the Third Report of the
terol absorption, appears to have sub- large number of patients who have lim- National Cholesterol Education Program (NCEP)
stantial potential for use as monotherapy ited access to healthcare. Consequently, Expert Panel on Detection, Evaluation and Treat-

S4 • JAOA • Supplement 1 • Vol 103 • No 1 • January 2003 Clearfield • The National Cholesterol Education Program Adult Treatment Panel III guidelines

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ment of High Blood Cholesterol in Adults (Adult
Treatment Panel III). JAMA. 2001;285:2486-2497.

7. Wilson PW, D’Agostino RB, Levy D, Belanger


AM, Silbershatz H, Kannel WB. Prediction of coro-
nary heart disease using risk factor categories. Cir- Underidentification
culation. 1998;97:1837-1847. and undertreatment of
8. Bays H, Drehobl M, Rosenblatt S, Toth P, Dujovne dyslipidemia
C, Knopp R, et al. Low density lipoprotein choles-
terol reduction by SCH 58235 (ezetimibe), a novel
inhibitor of cholesterol absorption, in 234 hyper-
cholesterolemic subjects: results of a dose-response Michael B. Clearfield, DO
study. Atherosclerosis. 2000;151:133. Abstract.

9. Davis HR, Watkins RW, Compton DS, Cook JA,


Hoos L, Pula K, et al. The cholesterol absorption
inhibitor SCH 58235 and lovastatin synergistically
lower plasma cholesterol and inhibit the develop-
ment of atherosclerosis. J Am Coll Cardiol. 2000;35(2
suppl):252A. Abstract. Despite increased attention placed on the identification and treatment of dys-
lipidemia, this condition remains undiagnosed and untreated in a significant
10. Pearson TA, Laurora I, Chu H, Kafonek S. The
Lipid Treatment Assessment Project (L-TAP): a mul- number of patients. The recently released National Cholesterol Education
ticenter survey to evaluate the percentages of dys- Program (NCEP) Adult Treatment Panel III (ATP III) set of cholesterol man-
lipidemic patients receiving lipid-lowering therapy agement guidelines increases to more than 65 million the number of Ameri-
and achieveing low-density lipoprotein cholesterol
goals. Arch Intern Med. 2000;160:459-467. cans eligible for lipid-modifying therapy. Recent data, however, suggest that
even with the availability of multiple regimens with proven efficacy, as many
as 50% of all patients do not have their cholesterol assessed and less than 45%
receive lipid-modifying therapy. In addition, less than 25% of patients are
treated to their NCEP target low-density lipoprotein cholesterol (LDL-C) level.
Persistence with therapy is another challenge, as more than 70% of
patients fail to maintain their therapy beyond 12 months. If a realistic attempt
is to be made to reduce the risk of coronary heart disease (CHD) among Amer-
icans, diagnosis of dyslipidemia and treatment to therapeutic targets must be
improved. This article discusses the underdiagnosis and undertreatment of lipid
disorders and reviews the role of osteopathic physicians in strategies achieving
ATP III LDL-C goals.
(Key words: Adult Treatment Panel III [ATP III], compliance, choles-
terol, dyslipidemia)

L arge numbers of patients have undi-


agnosed dyslipidemia, and those
who do receive a diagnosis are often
lipidemic individuals in the United
States may never be known because of
the enormity of effort and magnitude
given inadequate therapy. The Amer- of cost required for screening all at-risk
ican Heart Association1 estimates that individuals. Because more than 12.6 mil-
more than 100 million adults in the lion Americans have coronary heart dis-
United States have total cholesterol ease (CHD) and more than 500,000
levels greater than 200 mg/dL and at deaths are attributed to this disease each
least 40% of these individuals have year, physicians should be strongly
cholesterol levels in excess of encouraged to heed the advice of the
240 mg/dL. The true number of dys- National Cholesterol Education Pro-

Dr Clearfield is a professor of medicine and associate dean for clinical research at the University of North
Texas Health Science Center at Fort Worth/Texas College of Osteopathic Medicine. Dr Clearfield rep-
resented the American Osteopatic Association, a member organization of the National Cholesterol Edu-
cation Program Coordinating Committee, which approved the Third Report of the National Cholesterol
Education Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults.
Dr Clearfield is a member of the speakers bureau of AstraZeneca, Merck & Co, Pfizer Inc, and
Sankyo Pharma Inc, and he has received grant/research support from AstraZeneca and Pfizer Inc.
Correspondence to Michael B. Clearfield, DO, Associate Dean for Clinical Research, Office of the Dean,
Texas College of Osteopathic Medicine, University of North Texas Health Science Center at Fort Worth,
855 Montgomery St, Fort Worth, TX 76107-2699.
E-mail: mclearfi@hsc.unt.edu

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