1. family and parenting
2. motherhood
3. pregnancy

Despite high consumer demand for
online access to health information
and communication tools, providers lag in their health IT capabilities,
according to the Optum Institute’s new
“Meaningful Consumer Engagement”
report. The report summarized results
of an online survey that included more
than 4,000 physicians, hospital executives, and adult healthcare consumers.
The survey found that threequarters of patients want to view their
medical records and lab test results
online, but that only 41% of physicians
have electronic medical record (EMR)
systems that support timely access to
this information. Likewise, more than
60% of patients want to correspond
with their doctors via the Internet,
Snapshot
Key Online Healthcare Functions
Patient Demand Physician Capabilities
Medical records
Test results
Appointment
reminders
Doctor
correspondence
41%
75%
76%
41%
44%
46%
65%
62%
0 20406080
Source: Optum Institute Issue Brief, 2012
while only 44% of physicians have this
capability. Consumers both young and
old expressed their interest in engaging via health IT. For instance, 57%
of consumers over age 65 expressed
interest in online correspondence with
healthcare providers, a number that
is only slightly lower than the general
population.
In spite of the lag in online
physician-patient connections,
Optum’s survey did find a positive
trend in physician adoption of EMR,
with 70% of healthcare providers
having EMR systems capable of basic
functions such as recording diagnoses
and patient demographics. Over half
of physicians also have EMRs that
support basic care coordination; for
instance, 60% can access patients’ clinical lab and test results online.
Stage 2 of the Center for Medicare
and Medicaid Services’ Meaningful
Use Program (MU2) aims to improve
the sharing of such information with
patients by giving physicians incentive
payments to expand their IT capabilities. However, MU2 only requires 50%
of patients to have access to their
electronic health records, and 5% to
use online tools. Since the number of
consumers that want these capabilities is much higher, Optum believes
MU2 has set the bar too low to meet
consumer demand.
Clinical
Laboratory
News
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source for the
clinical laboratorian
november 2012
volume 38, number 11
w w w. a a c c. o rg
Thyroid Health in Pregnancy
Is it Time to Implement Universal TSH Screening?
By Genna Rollins
P
regnancy places unique demands on the thyroid gland
and thyroid function, and has been called a stress test
for this master regulator of metabolism. As many as
5% of pregnant women experience some sort of thyroid dysfunction, putting themselves and their babies
at risk for short- and long-term health complications. Yet these
common, potentially serious thyroid imbalances often are underappreciated and may go undetected. Now, two new guidelines not
only are raising the visibility of thyroid disease in pregnancy and
calling attention to issues in need of further research, but also underscoring the importance of close laboratorian-clinician collaboration around thyroid test ordering and interpretation.
“I don’t think thyroid disorders get the attention they deserve
in terms of research, publications, and awareness. One of the best
things about these guidelines is they make frontline physicians
think about thyroid health in pregnancy, because in terms of getting attention it’s way down the list. We’re always worried about
preeclampsia, preterm birth, growth restriction, obesity, and diabetes, so thyroid disorders tend to fall off the radar screen,” explained Scott Sullivan, MD. “Any information
labs can provide that guides doctors in knowing which tests to order and how to interpret pregnancy-specific
reference ranges would be helpful.” Sullivan, an associate professor of obstetrics and gynecology at the Medical University of South Carolina in Charleston, served on committees for the American Thyroid Association
(ATA) and the Endocrine Society, both of which recently issued guidelines on diagnosing and managing thyroid dysfunction in pregnancy (Thyroid 2011; 21:1081–125; J Clin Endocrinol Metab 2012;97: 2543–65).
See Thyroid & Pregnancy, continued on page 2
The Surge in Retail Clinics
Expansion of Services Signals More Testing
By Bill Malone
A
s the healthcare system prepares to cope with an influx of 30 million Americans who will have
health coverage as a result of the Affordable Care Act, a surging market of retail clinics is poised
to take on a wider role to relieve the bottleneck. No longer merely an anomaly or an experiment
of a few drug store chains, retail clinics have steadily expanded. While most only have a corner
of real estate inside their host retailer, these quick-service healthcare establishments are widening the scope of care they provide. Over the last few years, many have added more advanced services and tests,
partnering with health systems and insurers to become embedded in local healthcare ecosystems.
According to experts, quick-access clinics can be one part of the solution to improving access to basic healthcare. Some insurers and healthcare systems already have retail clinics in mind for more than just minor, acute
care visits, according to Tom Charland, chief executive of the research and consulting firm Merchant Medicine,
which tracks the retail medicine market. “Insurance companies are now recognizing that pharmacies and retail
clinics can do chronic disease management pretty efficiently. We are
in the early stages of this area, but the scope is definitely changing,”
he said.
Not only do insurers see retail clinics as facilitators of disease
management, but also as a stop gap measure for the growing shortage of physicians. “In geographies where there are critical shortages
of primary care physicians, some insurance companies are even paying retail clinics to act as a medical home,” Charland continued. “If
there is no primary care physician, the insurers would rather have
somebody than nobody. And they feel that nurse practitioners in
these clinics are fully able to act as patients’ primary care providers.”
See Retail Clinics, continued on page 5
Clinical Laboratory News
Physician Health IT
Capabilities Not Meeting
Consumer Demand
The American Association
for Clinical Chemistry, Inc.
1850 K Street, NW, Suite 625
Washington, DC 20006
news brief
in this issue
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FT4 Immunoassays Not Always Reliable
Risk Factors for Targeted Thyroid
Function Testing in Pregnancy
Thyroid & Pregnancy, from page 1
One of the challenges in raising the profile of thyroid health in pregnancy is that
the two most common thyroid problems,
overt and subclinical hypothyroidism,
present like normal pregnancy. “It’s difficult
to make the diagnosis of hypothyroidism in
pregnancy unless it’s really far advanced because a lot of the symptoms of pregnancy
are also symptoms of hypothyroidism. It’s
not that physicians aren’t capable of doing
so; it’s just that this condition can be crippling but in ways that are not obvious,”
observed James Haddow, MD. “Fatigue,
weight gain, and constipation are part of
our lives. So we have to be respectful that
it’s not an easy clinical diagnosis. That’s one
of the reasons I’m really strongly in sup-
port of routine thyroid function testing,
especially during pregnancy.” Haddow, a
research professor of pathology and laboratory medicine at Brown University in
Providence, R.I., has a long-time interest in
pregnancy-related thyroid issues, including
conducting seminal research on the relationship between thyroid deficiency and
pregnancy complications.
The Thyroid in Pregnancy
During pregnancy, rising human chorionic
gonadotropin (hCG) levels stimulate the
thyroid to produce more thyroid hormone,
causing thyroid stimulating hormone
(TSH) concentrations to dip below normal,
particularly in the first trimester. Elevated
hCG levels also lead to temporary increases
waters.com
®Age >30 years
®Family history of thyroid disease
®History of thyroid dysfunction or surgery
®Goiter
®Thyroid antibody positivity
®Symptoms suggestive of hypothyroidism
®Type 1 diabetes
®History of miscarriage or preterm delivery
®Autoimmune disorders associated with autoimmune thyroid
dysfunction
®History of head or neck irradiation
®History of infertility
®Morbid obesity
®Treatment with amiodarone, lithium, or levothyroxine
®Recent exposure to iodinated radiological contrast agents
®Current residence in a region with presumed iodine deficiency
Source: Thyroid 2011;21:1081–125; J Clin Endocrinol Metab 2012;97:2543–65.
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in free thyroxine (FT4) and free thyroxine
index (FT1) during the first trimester, but
in normal pregnancy these measurements
usually stay within the nonpregnant range.
Increased estrogen levels in pregnancy
also change concentrations of thyroid
hormones, most notably thyroid binding
globulin (TBG), which rises starting a few
weeks into pregnancy and levels off midterm at about two-to-three times above
normal, where it remains until delivery.
This increase, in turn, leads to higher levels
of total thyroxine (TT4) and total triiodothyronine (TT3) throughout pregnancy
(See Table, p. 3).
The body’s demand for iodine, which
is essential for thyroid function, also increases in pregnancy. Several mechanisms
are at play, including boosted thyroid hormone production brought on by higher
levels of hCG and estrogen. The mother’s
glomerular filtration rate also rises early in
pregnancy, thereby clearing more iodide,
and lowering the circulating pool of plasma
iodine. In addition, before week 12 of gestation, some maternal iodine stores transfer
to the fetus to enable its thyroid gland to
start functioning.
What’s the TSH Reference Range?
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Based on recent research, both the ATA
and Endocrine Society recommended
trimester-specific reference ranges for
TSH, with upper limits of 2.5 mIU/L in
the first trimester and 3.0 mIU/L in the
second and third trimesters. This compares with an upper limit of 4.0 mIU/L in
healthy, nonpregnant individuals. Black
and Asian women typically have TSH values 0.4 mIU/L lower than in Caucasians, a
difference that persists in pregnancy. ATA
emphasized the importance of lab- and
population-specific reference ranges (See
Table, below).
The guidelines define subclinical hypothyroidism as a serum TSH level above
the upper limit of the trimester-specific
reference range but with a normal FT4.
Overt hypothyroidism also involves a serum TSH level above the upper limit of
the trimester-specific reference range, but
with a decreased FT4 level. When pregnant
women have TSH levels >10 mIU/L, they
are considered to have overt hypothyroidism regardless of their FT4 levels. Two
thirds of undiagnosed pregnant women
in this category will become permanently
hypothyroid, and an average of 5 years will
elapse before a clinical diagnosis is made in
the absence of testing.
How Robust are FT4 Assays?
Both panels acknowledged challenges with
FT4 immunoassays, in that they are sensitive to changes in binding proteins. According to the ATA panel, “high TBG concentrations in serum samples tend to result in
higher FT4 values, whereas low albumin in
serum likely will yield lower FT4 values.”
The panel went on to suggest that even
though FT4 immunoassays perform reasonably well, values should be interpreted
using method- and trimester-specific ranges since studies have shown that reference
intervals vary widely between methods.
ATA also lauded solid phase extractionliquid chromatography/tandem mass spectrometry (LC/MS/MS) in dialysate or ultrafiltrate as a “major advance” with higher
specificity than immunoassays. Although
ATA cited the method as being “ideally
suited for generating reliable, reproducible
trimester-specific reference ranges for FT4,”
the panel acknowledged that LC/MS/MS is
not widely available. The Endocrine Society panel also recommended establishing
trimester-specific reference ranges for FT4,
but in addition suggested either using the
Recommended Trimester-Specific
TSH Reference Ranges
Pharmaceutical & Life Sciences | Food | Environmental | Clinical | Chemical Materials
© 2012 Waters Corporation. Waters, T he Science of W hat’s Possible, and MassTRAK are trademarks of Waters Corporation.
2 Clinical Laboratory News November 2012
First Second
Third
0.1–2.5 mIU/L
0.2–3.0 mIU/L
0.3–3.0 mIU/L
Source: Thyroid 2011;21:1081–125
Thyroid Function Test Results
in Thyroid Disease
Overt hypothyroidism
TSH
i
Free T4
m
Subclinical hypothyroidism
iNormal
Normal pregnancyNormalNormal
HypothyroxinemiaNormal
m
Overt hyperthyroidism
m
i
Source: ACOG Practice Bulletin 37, 2002; SFMF Consult from Contemporary OB/GYN,
August 2012
free T4 index or multiplying the nonpregnant TT4 range, 5–12 µg/dL, by 1.5.
“Many FT4 immunoassays are not terribly robust in pregnancy because the very
high TBG levels seem to throw off the results
in unpredictable ways. A number of studies suggest that most commercially available
FT4 assays may be unreliable in pregnancy,”
said ATA panelist Elizabeth Pearce, MD,
MSc. “The ATA official recommendation
was solid phase extraction LC/MS/MS,
which is available in select locations. It does
work very well, but almost no one has it. We
came to the conclusion on our panel that
in the absence of access to a gold-standard
assay you have to know your local assay, develop a feel for how it works in pregnancy,
and be aware that the TSH is a more reliable measure in most circumstances. The
Endocrine Society panel also had concerns
about the usefulness of most of the FT4
assays in pregnancy, but they specifically
recommended use of the free thyroxin index. That’s one of the more significant differences between the guidelines.” Pearce is
an associate professor of medicine at the
Boston University School of Medicine.
research involving pregnant women with
less severe hypothyroidism unrelated to iodine deficiency has yielded less consistent
findings. Haddow’s study from 1999 found
that children ages 7–9 years born to women
with overt, undiagnosed hypothyroidism
during pregnancy were more likely than
controls to have an IQ ≤85 as well as motor,
language, and attention delays, but the association was not statistically significant. To
the disappointment of many in the field, results from a long-awaited randomized trial
published in February found that antenatal screening and maternal treatment for
hypothyroidism did not lead to improved
cognitive function in children at 3 years of
age (N Engl J Med 2012;366:493–501).
Is Universal Screening Warranted?
Lack of research definitively linking screening and intervention for subclinical hypothyroidism to improved outcomes has
evoked considerable debate in the endocrine and obstetrical communities. The
ATA guideline committee ultimately determined that there was not enough evidence
to recommend for or against either universal TSH or FT4 screening in pregnant
women or preconception TSH screening
in women at high risk of hypothyroidism.
However, the committee did recommend
TSH testing early in pregnancy in women
at high risk for overt hypothyroidism (See
Table, left).
Reflecting the controversy in this area,
the Endocrine Society committee could
not reach a consensus on whether all newly
pregnant women should have TSH testing. Five panelists supported screening all
pregnant women at their first obstetrical
visit, while eight others were neither for nor
against universal screening, though they
strongly supported aggressive case finding to identify and test high-risk women.
Meanwhile, the American College of Obstetricians and Gynecologists and Society
See Thyroid & Pregnancy, page 4
Making the Outcomes Connection
The association between maternal thyroid
hormone and iodine levels and outcomes
for both mother and baby have been the
focus of considerable research and controversy. Overt hypothyroidism in pregnancy
clearly has been linked to increased risk
of premature birth, low birth weight, and
miscarriage. Evidence about how subclinical hypothyroidism affects pregnancy outcomes has been less consistent.
Studies also have associated maternal
hypothyroidism with cognitive challenges
in offspring, albeit with conflicting results.
Reports dating to the early 20th century
showed a correlation between mothers
with iodine deficiency and mental retardation in their babies, but in the modern era,
Thyroid in
Pregnancy
Learn more during AACC’s
upcoming Webinar,
Effective
Laboratory Testing
for Thyroid Health
during Pregnancy
November 13
Register online at:
www.aacc.org/events
or call 1-800-892-1400.
Clinical Laboratory News November 2012 3
Using TPO Ab Results Remains Challenging
Clinical
Laboratory
News
Thyroid & Pregnancy, from page 3
Editorial Staff
Editor—Nancy Sasavage, PhD
Senior Editor—Genna Rollins
Senior Editor—Bill Malone
Editorial Assistant—Christine DeLong
Contributors—Abigail Delaney, MD,
Jani R. Jensen, MD, and Dean Morbeck, PhD
Board of Editors
Chair—Amy Saenger, PhD
Mayo Clinic, Rochester, Minn.
Members—Lorin M. Bachmann, PhD, DABCC
VCU Health System, Richmond, Va.
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Juravinski Hospital and Cancer Center,
Hamilton, Ontario
Jacqueline Fisher, MS, C(ASCP)
Abbott Diagnostics Division, Boston, Mass.
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Siemens Healthcare Diagnostics, Newark, Del.
Pamela Steele, PhD
Covance, Inc., Indianapolis, Ind.
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FACB
President-Elect—Robert H. Christenson, PhD,
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Secretary—Elizabeth L. Frank, PhD, DABCC,
FACB
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4 for Maternal-Fetal Medicine recommend
against routine testing during pregnancy.
Sullivan summarized the divergent opinions and lively discussion on this subject.
“There’s a group of people who feel passionately for all the right reasons that everyone
should be screened. Other experts feel because of the lack of data and because of cost
it shouldn’t be done. Then there are people
in the middle, like me, who have sympathy for both points of view. Being on both
panels, I can’t count the number of hours
that I’ve heard the arguments. It was a close
call.” The endocrinology community, he
explained, “favors screening because they’re
really concerned about prenatal outcomes.
However, the obstetrical community is
more cautious and conservative. We’ve been
burned by screening programs in the past,
incompletely thought out and based on incomplete data, that now we’re stuck with.
We also have more of a medical liability crisis
than other specialties, so if there’s a recommendation or guideline and you stray from
it, you open yourself up to litigation.”
Supporters of universal screening now
are looking forward to results from an ongoing study of subclinical hypothyroidism
in pregnancy sponsored by the National
Institute of Child Health and Human Development, which is not expected to publish results for at least a couple of years.
The ATA panel acknowledged the evolving
science in this area. “The committee recognizes that knowledge on the interplay
between the thyroid gland and pregnancy/
postpartum is dynamic, and new data will
continue to come forth at a rapid rate. It is
understood that the present guidelines are
applicable only until future data refine our
understanding, define new areas of importance, and perhaps even refute some of our
recommendations,” wrote the panel.
Given the conflicting guidelines and incomplete and inconsistent evidence, TSH
testing patterns in pregnant women appear
to be all over the map. In a study published
last year, Pearce found that 85% of women
being followed at Boston Medical Center
were screened during their first obstetrical visit. Meanwhile, Quest Diagnostics
in 2012 reported that overall, 23% of the
more than 500,000 for whom it performed
pregnancy-related testing had TSH testing
(J Clin Endocrinol Metab 2012;97:777–84).
Haddow also reported finding that about
half the pregnant women in Maine were
routinely being tested for TSH levels.
“I think there’s a huge amount of regional variation,” observed Pearce. “In the
setting of conflicting guidelines, people
are doing a variety of different things, and
whatever they’re doing there’s probably a
guideline out there to support it.”
What’s the role of TPO Antibodies?
If the guidelines diverged somewhat on TSH
and FT4 testing, they concurred in not endorsing universal thyroid antibody screening in pregnancy. A recent prospective trial
and some retrospective studies have found
the risk of pregnancy complications to be
more pronounced in women who have both
subclinical hypothyroidism and who are
anti-thyroid peroxidase antibody (TPOAb)
positive. Both TPOAb and thyroglobulin
antibody positivity also have been associated
Clinical Laboratory News November 2012
with pregnancy loss, but noting that an association does not equate to causality, the ATA
panel found insufficient evidence for thyroid
antibody screening.
In Sullivan’s experience, confusion
about thyroid antibody testing causes it to
be underutilized, even in cases in which it
could help resolve other inconclusive tests.
This presents a real opportunity for laboratorians to step in and help clinicians, he
argued. “When I talk to other obstetricians,
they like to hear about iodine deficiency
and screening for subclinical hypothyroidism, but when I start talking about antibodies, they just tune me out. That’s an area
where we have a lot of work to do, because
there still remains a lot of confusion,” he
explained. “There are so many different
names for the same thing. TPO and antiperoxidase antibodies, for example. People
don’t know those are the same thing. When
I’ve spoken to non-specialist obstetricians
they’ve all but abandoned ordering these
tests because it’s so frustrating for them,
and that’s a disservice.”
User-friendly Testing
Experts consulted for this article agreed
that TSH by far is the most important test
of thyroid function in pregnant women,
although Haddow and others emphasized
the importance of establishing trimesterspecific reference ranges and providing
interpretive comments to aide physicians
in evaluating test results in the context of
patients’ clinical status.
“My feeling at the moment is that measurements of FT4 and TPO antibodies can
contribute useful supplementary information when TSH is outside the reference
range, even though there can be certain
instances when FT4 assay values don’t correlate with the original dialysis method. It
should be possible to perform them in a
straightforward manner,” observed Haddow. “That said, the obstetric community
is somewhat confused right now because of
the conflicting recommendations, and the
laboratory has a responsibility to provide
not just the test result but an interpretive
statement that’s based on the recommended trimester-specific cutoffs. That will go a
long way in terms of helping the physician.”
Shannon Sullivan, MD, PhD, also argued for some way, either by electronic
health record or test requisition form, for a
physician to be able to inform the lab that a
patient is pregnant, thereby facilitating better communication between the two. “If a
pregnant woman came in with a TSH of 15
mIU/L, I’d consider that a critical lab value,
but it certainly would not be called into the
physician as critical because the lab typically wouldn’t be aware the patient is actually
pregnant,” she said. “On the lab requisition
form there could be a box the physician
could check to indicate that the patient is
pregnant. I’ve never seen that before, but it
would give the person who is running the
test and reporting back to physicians any
critical values a heads up that this lab value
is abnormal for a pregnant person.” Sullivan, unrelated to Scott Sullivan, is an endocrinologist at Washington Hospital Center
and an assistant professor of medicine at
Georgetown University School of Medicine
in Washington, DC.
Another area of concern to both Sullivans is occult iodine deficiency. Both
guidelines recommend 250 µg iodine daily
in pregnant women. However, probably in
deference to the U.S. overall being an iodine replete country, the Endocrine Society
guidelines explicitly do not advise as part
of normal practice measuring urine iodine
concentration (UIC), which, while being
a validated measure of population iodine
status, is not reliable for individuals, due to
wide day-to-day and diurnal variations. Yet
both Sullivans are seeing in their respective
practices growing numbers of patients who
are iodine deficient, sometimes severely
so. Both attributed this to a confluence of
factors, including public health advisories about the need to decrease salt intake
and for pregnant women to avoid tuna,
the growing popularity of non-iodized
sea salts, and reliance on processed foods,
which do not use iodized salt. In addition,
not all prenatal vitamin formulations contain iodine.
How this trend will be incorporated
in future guidelines or factored into testing patterns remains to be seen. In the
meantime, experts emphasized that laboratorians are important players in guiding
physicians through the complex and sometimes confusing domain of thyroid funcCLN
tion testing in pregnancy.
References and Resources for
Thyroid Disease in Pregnancy
®De Groot L, Abalovich M, Alexander EK, et al. Management of thyroid
dysfunction during pregnancy and postpartum: An endocrine society
clinical practice guideline. J Clin Endocrinol Metab 2012;97:2543–65.
®Negro R, Mestman JH. Thyroid disease in pregnancy.
Best Pract Res Clin Endocrinol Metab. 2011;25:927–43.
®Stagnaro-Green A, Abalovich M, Alexander E, et al. Guidelines of the
American Thyroid Association for the diagnosis and management of
thyroid disease during pregnancy and postpartum.
Thyroid 2011;21:1081–125.
®Gronowski AM, Haddow J, Kilpatrick S, et al. Thyroid function during
pregnancy: Who and how should we screen? [Epub ahead of print]
Clin Chem June 6, 2012 doi:10.1373/clinchem.2012.185017.
®Vissenberg R, van den Boogaard E, van Wely M, et al. Treatment of
thyroid disorders before conception and in early pregnancy:
a systematic review. Hum Reprod Update 2012;10:361–77.
®Yazbeck CF, Sullivan SD. Thyroid disorders during pregnancy.
Med Clin N Am 2012;96:235–56.
Clinics Expand Locations, Services
Retail Clinics, continued from page 1
Growth Signals Turnaround
Retail clinics first began making news in
2000, but after an initial jump, some closed
their doors only a few years later, with some
observers calling the model a failure. Since
the mid 2000s, however, the industry has
rebounded, with more than 1,300 clinics
around the country and nearly 12% growth
in 2011, according to Charland. Industry
leader MinuteClinic opened 19 new clinics
just in September.
While CVS Pharmacy’s MinuteClinic
and Walgreens’ Take Care Clinic still dominate, Target and Walmart are expanding
their clinic presence, and dozens of health
systems are opening their own retail-style
clinics, such as Geisinger’s Careworks
walk-in clinics (See Box, p. 6).
Retail clinics are also adding new tests
that go far beyond caring for scraped knees
and scratchy throats. The growing list of
tests includes lipid panels, HbA1c, microalbumin, HIV, fecal occult blood, influenza A
and B, and even screening for methicillinresistant Staphylococcus aureus. Clinics offer many of these tests as part of adult and
child physicals, and more recently, Medicare wellness visits (See Box, p. 7).
A recent study found that patient traffic
to retail clinics doubled every year between
2007 and 2009, reaching nearly 6 million
visits in 2009 (Health Aff 2012;31:2123–
29). Patients spent an average of $78 per
visit, which translated into about $460 million in 2009. While a significant amount of
this volume was attributed to flu shots—an
area in which pharmacies now compete
more than they did in 2009—the study
showed that consumers increasingly accept and value the convenience of clinics.
The authors noted that nearly 50% of retail clinic visits take place during hours that
physician offices are not open.
Laboratorians will feel little comfort
knowing they are not the only healthcare
professionals worried about a staffing
shortage. The American Association of
Medical Colleges warns that by 2020, the
nation will face a shortage of 45,000 primary care physicians. This crisis will become especially serious when, in 2014 and
beyond, the healthcare reform law reaches
full effect, pulling some 30 million people
into the healthcare system through Medicaid and subsidized private insurance.
The expected influx of newly insured
patients under the Affordable Care Act provides both opportunity and uncertainty for
the retail clinic model, according to the lead
author of the study, Ateev Mehrotra, MD.
“If more people are seeking primary care,
and there is no dramatic increase in the
number of primary care physicians, we
could face a situation of increased demand
and worsening access. Without an alternative, more patients may go to a retail clinic,”
he said. “The flipside is that a significant
segment of patients who go to a retail clinic
don’t have a primary care physician. If under healthcare reform more people gain
access to primary care physicians, it’s still
possible they could choose the physician’s
office over the retail clinic.” Mehrotra is a
policy analyst at the RAND Corporation
and an associate professor of medicine
at the University of Pittsburgh School of
Medicine.
Notably, in Mehrotra’s study, nearly 70%
of patients were covered by insurance. This
figure was no surprise to Charland, who
emphasized that retail clinics cater mainly to
middle-class families. “The biggest driver for
retail clinics is still convenience. There is this
fallacy out there that all these clinics do is cater to the uninsured. And that’s just not true,”
Charland said. “It’s busy, dual-income, educated, working parents whose kids are also
busy. When someone gets sick in the household, it’s chaos. And for the doctor’s office
to say they can only see you on a certain day
at a certain time, that just doesn’t cut it anymore.” Charland has been involved in retail
medicine since 2003. He served as senior vice
president of strategy and business develop-
ment at MinuteClinic and helped develop
the company’s early relationship with CVS
Pharmacy, as well as with insurers.
In addition to more patients with insurance, changes to insurance plans themselves will drive patients to retail clinics as
well, Charland predicted. “High-deductible
health plans, which are expected to become
more common, will also mean growth for
retail clinics,” he said. “The transparency of
pricing is important to people because it’s
now coming directly out of their pockets.
And you don’t have the situation where you
don’t know what you paid until 60 days later when the explanation of benefits comes
in the mail. Healthcare is the only industry
in this country where you can buy something, and you don’t know what you paid
for it. But that’s not the case with retail clinics, and people are drawn to that.”
Collaborations Deepen
Ties to Healthcare System
Early on, the largest chains of retail clinics
entered the market as an extension of national pharmacies, such as MinuteClinic
in CVS and Take Care Clinic in Walgreens.
Today, many clinics partner with health systems outside the walls of the store in which
they reside. For example, MinuteClinic now
has deals with 18 health systems, representing more than 150 hospitals. Walmart also
has deals with more than 12 health systems
or physician groups, representing some 137
clinics.
In one of the most recent collaborations, the University of California, Los
Angeles (UCLA) announced in July that
UCLA Health System physicians will serve
as medical directors for 11 MinuteClinics
See Retail Clinics, continued on page 6
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Clinical Laboratory News November 2012 5
Chronic Disease Care Irks Docs
Retail Clinics Expand, Diversify
Retail Clinics, continued from page 5
in Los Angeles County. They also will work
together on patient education and disease
management programs. Tightening the relationship, MinuteClinic and UCLA already
have started to work toward fully integrating their electronic health record (EHR)
systems in order to share medical histories
and visit summaries with other UCLA locations. In announcing the deal, UCLA Health
System president David Feinberg, MD,
noted that UCLA hoped to “explore new
and innovative ways to deliver patient care
and manage chronic conditions.”
UCLA’s Bernard Katz, MD, told CLN
that for the most part, physicians at UCLA
have supported the partnership. “There
may be some primary care physicians who
feel that this is a competition for the same
patients, but I think that most understand
that these clinics are facilities where their
patients can get care in a kind of outreach
setting that is like an extension of their office,” he said. “In these days of more and
more difficult access to primary care, we
think this partnership will open up new
avenues for our patients to get the highquality care that they need.”
Katz, who is the physician coordinator of the MinuteClinic collaboration, also
noted that MinuteClinic will ask patients if
K-ASSAY ®
they have a primary care relationship, and
if they don’t, encourage them to establish
one. The plans for how MinuteClinic might
help UCLA manage chronic conditions
such as diabetes and hypertension are still
in the early stages, but they revolve around
sharing information via EHR.
As health systems move toward an accountable care organization (ACO) model
that emphasizes outcomes and efficiency,
collaborations with retail clinics could be
part of the strategy. “Because accountable
care is about population management,
MinuteClinic could be a great way for patients who are part of the UCLA health
system to have better access to care that is
convenient and still coordinated through
the EHR in an ACO model,” he said. UCLA
is still in the process of assessing how it will
adapt to the ACO model.
Widening Scope of Care Sparks Criticism
As retail clinics have grown in number and
ventured into the sphere of chronic disease
management, they have also met with stern
criticism from some physician groups,
such as the American Medical Association
(AMA) and the American Academy of
Family Physicians (AAFP).
AAFP has been vocal in opposing any
expansion of the scope of service in retail
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OperatorClinics
MinuteClinic588
TakeCare356
Walmart Partners
143
The Little Clinic
89
Target Clinic
53
FastCare31
RediClinic29
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13
Aurora QuickCare
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Lindora Health Clinics
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Family Quick Care
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clinics that approaches managing chronic
conditions. It believes that high quality and
coordinated care depend on relationships
with primary care physicians—a relationship with which retail clinics interfere.
“AAFP believes that the best healthcare
comes from a patient-centered medical
home, where you have a strong primary
care focus with comprehensive, coordinated, and continuing care,” said AAFP president Jeffrey Cain, MD. “When retail clinics
start talking about managing chronic disease or performing well adult exams, that’s
further fragmenting an already fragmented
health system. We believe patients will have
better care and better quality if they find
that care within an ongoing relationship to
a primary care physician who knows that
person.” Cain is chief of family medicine
at Children’s Hospital Colorado and associate professor in the Department of Family Medicine at the University of Colorado
Health Sciences Center in Aurora.
According to Cain, family physicians
have responded to the demand for greater
flexibility by expanding access to appointments. “Family doctors have responded so
that about 75 percent of their offices have
open-access, same-day appointments and
about half have evening or weekend office
hours,” he said. Results from an AAFP physician survey also found that about 31% of
respondents offered weekend appointments.
Both AMA and AAFP are urging insurers not to give patients an incentive to use
retail clinics, warning of the potential for
duplicative tests and treatments, higher
costs, and lower quality.
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Tine Hansen-Turton, executive director
of the Convenient Care Association (CCA),
which represents retail clinics, admits that
retail clinics amount to “disruptive innovation.” However, she emphasized that the industry has committed to quality and safety
standards. These include sharing information with patients’ primary care providers,
using EHRs, referring patients without
primary care physicians to these providers, making prices transparent, and using
evidence-based guidelines.
CCA member clinics also are committed to patient follow-up. For example,
nurse practitioners regularly call patients
after visits—usually the next day—to check
their status and confirm whether any prescriptions were filled. “The nurse will also
take the opportunity to again encourage
the patient to get connected to a primary
care practitioner if they aren’t already,”
Hansen-Turton said. “I think that is how
we have gained a lot of credibility in the local medical communities where our clinics
operate, because they are feeders now into
primary care.”
Charland believes that some physician
groups oppose the expansion of retail clinics simply because of a concern over competition. “It’s interesting that this argument
against fragmented care only emerged
when retail clinics came to be. I don’t really
buy this argument or the quality argument.
I think it’s purely economic. These are the
bread and butter, easy visits for physicians.
If it’s fragmented care, it’s been there for a
lot longer than retail clinics have been, and
it’s fragmented because physician offices
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make it that way, by making it so inconvenient that people are forced to find alternatives.”
Charland emphasized that he sees little
difference between a physician overseeing a
nurse practitioner in a doctor’s office versus
reviewing what nurse practitioners document after seeing patients in retail clinics.
“When physicians have nurse practitioners
in their offices, they certainly don’t see every patient the nurse sees. So now with a
retail clinic there is a nurse practitioner a
quarter mile down the street. There is no
difference than when the physician looks
at a record after the fact for the patient in
either case. This is an economic impact on
the physician, no two ways about it.”
No one has specifically studied the
quality of testing at retail clinics. However, other CLIA-waived sites such as doctors’ offices that the Centers for Medicare
and Medicaid Services (CMS) has studied
do not have a perfect record. CMS began
studying CLIA-waived testing sites in 2002,
and found that more than 20% of those
surveyed didn’t perform quality control as
detailed in manufacturers’ instructions and
13% didn’t even have these instructions.
According to CMS, the agency continues to
survey about 2% of CLIA-waived labs each
year, and finds similar results. CMS has
plans for a new educational program to try
and improve upon these numbers.
More testing also goes hand-in-hand
with the desire of clinics to enhance their
offerings and avoid depending on services
for which demand can come and go with
the seasons, such as flu shots or children’s
sports physicals. “I think retail clinics in
general would love to be able to provide
more services, and certainly more tests
would facilitate that,” said Mehrotra. “The
limitation is that usually they only have one
nurse practitioner on site, and blood draws
add a level of complexity.”
Like the growth of other services retail
clinics offer, payers ultimately will be the
driving force behind more testing, according
to Charland. “What will generate testing volume is insurance companies putting an incentive out there for people to go get tests—
and that could be a carrot or a stick,” he said.
“In an ACO type of risk arrangement, where
a health system takes on the risk of a population’s health, they’ll want to find ways to
efficiently monitor chronic diseases. If that
health system decides that MinuteClinic is
the most efficient way to get that done, that’s
what will change it. It will be some sort of
incentive for the patient. And we definitely
see that starting to happen.”
Courting the Walk-In Patient
As healthcare becomes more competitive,
more patient-focused, and more sensitive to cost, retail clinics and other nontraditional outreach settings could be essential for health systems. “A key benefit of
retail clinics run by health systems is that
they serve as an entry point for new patients,” Mehrotra commented. “Drawing
new patients into their primary care and
specialty system is critical.”
With health systems and retail clinics
experimenting with new services and new
partnerships, the lines between urgent care
centers, retail clinics, and other kinds of
outreach settings also will blur, Charland
predicted. “There used to be three unique
markets, but there is now significantly
more convergence as they compete with
each other for that walk-in patient,” he
said. “And there is all kinds of activity in
this space that I think is positioning it for
the future, which is when we will no longer
pay for healthcare mostly on a transactionby-transaction basis, but instead will pay
for outcomes, the ACO concept. If that
really takes hold, the economic incentives
change, and suddenly there is not a threat,
but rather an incentive to find a way to get
that illness treated in the most efficient way
CLN
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With Expansion, More Testing Likely
Experts on retail clinics agree that services
will continue to broaden, but what this
will mean for diagnostics is uncertain. For
the most part, retail clinics rely on CLIAwaived tests that they can perform on-site,
and the small space and need for speedy
appointments limits the kind of tests that
can be performed.
Hansen-Turton noted that diagnostic
companies regularly approach CCA seeking to find a place for their rapid tests. “A lot
of different companies come to us from the
diagnostic area, and we often bring them in
to our members to get their thoughts,” she
said. “We try and help our members take
advantage of some of these new technologies from diagnostic companies that can
work within a very small footprint. We are
going into a new expansion, and you will
notice more growth and an evolution of
services, but still within the framework of
what can you do in a 15 to 20 minute visit.”
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CLN
11/12
Clinical Laboratory News November 2012 7
CLN’s
improving
healthcare
through
laboratory
medicine
Fertility Testing
series
By Abigail Delaney, MD, Jani R. Jensen, MD, and Dean Morbeck, PhD
How Laboratory Tests Contribute
to Successful Infertility Treatments
I
nfertility is a common clinical problem affecting an estimated 15% of couples worldwide. According to the
2006 National Survey of Family Growth, approximately 7.4 million women age 15–44 in the U.S. reported
receiving any type of infertility service. But with current technology, women who undergo infertility treatments enjoy much improved success rates.
Infertility treatments can consist of an extensive clinical evaluation, including multiple laboratory and
imaging studies. Laboratory testing for female hormones plays a large part in both the work up for infertility and
monitoring during treatment. This review will discuss the laboratory tests commonly used for these purposes,
including tests of importance during in vitro fertilization (IVF) cycles.
Follicle Stimulating Hormone
Human females are born with a finite
amount of oocytes. Oocyte loss via apoptosis occurs throughout the lifespan, even
in prepubertal females. For reproductive
age females, cyclic cohorts of oocytes begin development in any given menstrual
cycle, but typically only one becomes fully
mature and is ovulated. Although there is
significant individual variation, in general,
oocyte quantity and quality begin to decline rapidly around age 37 and continue to
fall until the oocyte supply is exhausted in
menopause.
Determining a woman’s relative ovarian
reserve, or quantity and quality of oocytes,
is a critical early part of the initial infertility
evaluation. Although testing protocols vary,
most IVF centers use a combination of laboratory studies and ovarian imaging via ultrasound to determine ovarian reserve and
help guide fertility therapy.
High serum follicle stimulating hormone (FSH) concentrations in the early
part of the menstrual cycle are a wellknown predictor of reproductive aging;
therefore, clinicians for many years have
8 Clinical Laboratory News November 2012
used FSH testing as a component of ovarian reserve testing. To determine ovarian
reserve, clinicians measure a woman’s FSH
value at its nadir early in the follicular phase,
cycle days 2–3. While FSH is strongly associated with reproductive age, it also varies during a woman’s lifetime, as well as
throughout a typical menstrual cycle. Given
this large amount of variation, many studies
have demonstrated that maternal age, rather
than FSH value alone, may be more predictive of IVF success (1). FSH values >10 IU/L
seem to have high specificity for predicting poor response to ovarian stimulation,
but the sensitivity at this value is low unless
FSH is at a high threshold value.
Very high levels of FSH, however, seem
to be predictive of poor pregnancy outcome.
In one recent study, FSH levels >18 IU/L
resulted in no live births (2). Consequently,
some fertility programs have FSH thresholds
above which women are not offered IVF services due to the low probability of success.
Estradiol
Estradiol (E2) is a steroid hormone secreted into circulation by granulosa cells of
developing ovarian follicles. Clinicians also
commonly measure E2 levels in women
as part of ovarian reserve testing. Levels of
this hormone in reproductive age women
fluctuate from 10–300 pg/mL, depending
on timing of the menstrual cycle (3). For
ovarian reserve testing, clinicians typically
assess E2 levels at their nadir early in the
menstrual cycle, at days 2 or 3.
Assessing levels of these hormones at
a consistent time point in the menstrual
cycle allows clinicians to make meaningful
interpretations of the values. For example,
a high basal FSH or E2 level suggests impaired oocyte development early in the
menstrual cycle—a worrisome sign of reproductive aging and/or poor ovarian reserve. In addition, because estradiol exerts
negative feedback on FSH secretion from
the pituitary gland, high E2 (>100 pg/mL)
can inhibit FSH secretion, resulting in an
artificially low FSH value.
Despite being a simple, inexpensive,
and effective screening tool, basal E2 levels
alone have a low predictive value for IVF
outcome. In a systematic review of 3,352
patients being treated for IVF, researchers
actually found conflicting results (4). In
some studies, lower IVF success rates were
reported for both low and high E2 levels,
whereas others found that baseline E2 levels
have no effect on IVF success. In yet another study, researchers discovered that a basal
estradiol level >75 pg/mL was associated
with poor IVF outcomes and pregnancy
rates (3). Given these inconsistencies, the
best use of E2 levels in combination with
baseline FSH values has been in determining the appropriate medication doses to
start an IVF cycle or for deciding to forego
treatment altogether when the probability
of success is low.
In addition to baseline ovarian function, clinicians frequently evaluate women’s E2 levels in a controlled-ovarianhyperstimulation (COH) setting to monitor follicular development. As follicles develop, E2 levels steadily increase. During a
spontaneous cycle, E2 levels typically peak
between 250–300 pg/mL as ovulation approaches. In contrast, when superovulation
—release of more than one mature oocyte
—is the goal, women in a COH cycle have
significantly higher E2 values (Figure 1).
In both COH and IVF cycles, clinicians
use E2 levels to determine the risk of ovarian
hyperstimulation syndrome (OHSS), a selflimited but occasionally severe response to
ovarian hyperstimulation. In a retrospective analysis of IVF patients, researchers
defined OHSS risk groups according to
estradiol levels (5). In 637 IVF cycles, no
patients developed OHSS with peak E2 levels <3500 pg/mL, 1.5% developed hyperstimulation with peak E2 levels 3500–5999
pg/mL, and 38% developed OHSS with E2
levels >6000 pg/mL. While many factors
contribute to cycle monitoring and prevention of OHSS, studies have shown that
monitoring E2 levels reduces incidence of
OHSS. Although the upper threshold of E2
that confers the highest risk of OHSS is inconsistent in the literature, most clinicians
agree that risk of OHSS with a peak E2 level
<3000 pg/mL is low risk (1).
Figure 1
Estradiol and Follicular Diameter
in IVF by Day of Stimulation
Anti-Müllerian Hormone
Anti-Müllerian hormone (AMH) is a dimeric glycoprotein and a member of the
transforming growth factor-beta superfamily, which, like estradiol, is secreted by
granulosa cells of pre-antral and antral
follicles in the ovary. Serum AMH levels reflect the overall follicular pool, and
several research teams have evaluated
AMH as a marker of ovarian reserve. In
general, high AMH levels correlate with
good ovarian reserve and vice versa. Furthermore, AMH is undetectable 3–5 days
following bilateral ovariectomy. Several
research groups also have demonstrated a
correlation between low AMH levels and
menopause (6).
In addition to its role in evaluating ovarian reserve, researchers have studied AMH
as a predictor of response to gonadotropin
stimulation during ovulation induction.
Over the natural course of ovarian stimulation, AMH levels gradually decline. Administering FSH exogenously to women
leads to an increase in follicular size and E2
levels, both of which have been implicated
as regulators of AMH secretion.
Several studies also have demonstrated
a strong correlation between basal AMH
levels and number of oocytes retrieved
Both estradiol and average follicular diameter increase throughout a typical cycle.
during an IVF cycle, including one in which
basal AMH levels were found to be 2.5 fold
higher in patients who had >11 oocytes retrieved. In a meta-analysis, AMH appeared
to be a better predictor of response to ovarian stimulation than patient age and day-3
FSH, E2, or inhibin B levels (7). The studies
comparing AMH to antral follicle count for
predicting response to ovarian stimulation
found no significant difference between
these two analytes (7).
Poor response to ovarian stimulation
occurs in approximately 2–30% of IVF
cycles. While not all IVF programs use the
same definition, most classify women as
poor responders based on low follicle number (<3–5) and retrieved oocytes (<3–5),
as well as on cancellation of a cycle due to
inadequate stimulation. La Marca et al (7)
published the first study evaluating AMH
as a tool for predicting poor response to
controlled ovarian hyperstimulation. They
found AMH had a sensitivity of 80% and
specificity of 93%; however, the accuracy
of AMH for predicting poor response to
COH was not consistently reproducible.
These findings suggest that a low response
is not a good reason to exclude patients
from IVF.
On the opposite end of the spectrum,
AMH also may be useful for predicting
OHSS. This hypothesis is based on the idea
that an exaggerated response to gonadotropins may be secondary to high AMH.
Two prospective trials have demonstrated
that basal levels of AMH >3.5 ng/mL are
associated with OHSS. Further studies are
needed to determine whether stimulation
Table 1
Laboratory Tests Used for Fertility Testing
Laboratory Test
Follicle Stimulating
Hormone (FSH)
Estradiol (E2)
Normal Values
5–20 mIU/L
20–400 pg/mL
When to Measure
Important Points
Follicular phase, days
2–3 of menstrual
cycle
FSH values >10 IU/L predict poor response
to ovarian stimulation (1)
Follicular phase, days
2–3 of menstrual
cycle
Helpful in combination with FSH to establish
baseline ovarian reserve
Not cycle dependent
so can be measured
at any time
Low values (0.2–0.7 ng/mL) predict poor
response to COH but are not useful in
predicting pregnancy (6)
FSH values >18 IU/L predictor of poor
pregnancy outcome (2)
Use with monitoring of COH. Low risk of
OHSS with E2 value <3000 pg/mL
Anti-Müllerian
Hormone
0.9–9.5 ng/mL
Inhibin B
<139 pg/mL during Follicular phase, days
the follicular phase 2–3 of the menstrual
cycle
Serum levels <45 pg/mL have been
associated with poor response to
gonadotropins (9)
Progesterone
Follicular phase:
<3 ng/mL
One week prior to
expected menses to
assess for ovulation
Values <3 ng/mL during the secretory phase
indicate anovulation
Mid-follicular phase
Studies vary in regard to clinical value of LH
Secretory phase:
5–30 ng/mL
Lutenizing
Hormone (LH)
5–20 mIU/mL
Abbreviations: COH: controlled-ovarian-hyperstimulation; OHSS: ovarian hyperstimulation syndrome.
treatment should be stratified based on
AMH levels to avoid OHSS (7).
Inhibin B
Inhibin B is one of the beta subunits of the
dimeric protein inhibin, and like AMH, it
is produced by pre-antral and early antral
follicles. Inhibin B values vary during a
woman’s reproductive lifetime and menstrual cycle. In addition, changes in inhibin
B levels that occur with reproductive aging
are similar to those of FSH and AMH. As
women age, FSH levels increase, and both
inhibin B and AMH decrease. Decline in inhibin B level is a late marker of diminished
ovarian reserve; therefore, inhibin B values
cannot be used to predict ovarian failure or
menopause (8). Currently, inhibin B levels
are not regarded as a standard and/or reliable assessment of ovarian reserve (6).
Administering exogenous gonadotropins for controlled ovarian stimulation results in an increase in inhibin B, and studies
have demonstrated that poor responders
generally have lower inhibin B levels. In
fact, serum levels of inhibin B <45 pg/mL
have been associated with poor response to
gonadotropins, as well as high rates of cycle
cancellation, reduced IVF retrieval, and
lower clinical pregnancy rates (9).
Progesterone
Progesterone levels are a simple measurement of ovarian function. Progesterone levels remain low during the follicular phase
(<1 ng/mL), rise on the day luteinizing
hormone (LH) surges (1–2 ng/mL), and
increase steadily until they peak approximately 1 week after ovulation. Progesterone
levels <3 ng/mL imply anovulation, except
when assessed immediately after a woman
ovulates or prior to menses when progesterone levels are at a physiological low. To
assess for presence or absence of ovulation,
clinicians typically assess a woman’s progesterone levels approximately 1 week before the expected onset of menses (6).
Clinicians often use gonadotropinreleasing hormone (GnRH) analogues
to induce ovulation and suppress the
Clinical Laboratory News November 2012 9
pituitary, thereby preventing premature
LH surge and subsequent ovulation.
However, many studies describe a finding called premature luteinization that
occurs in 5–30% of cases. This happens
when patients’ serum progesterone levels
rise higher than a defined threshold value
of 0.9–1.2 ng/mL, despite their having
received GnRH. Some clinicians suspect
that if a woman’s serum progesterone is
elevated on the day ovulation is induced,
the success of the IVF cycle is adversely affected, although this has been the subject
of debate for many years. A recent metaanalysis of 12 studies concluded that the
probability of clinical pregnancy in IVF
cycles did not differ significantly between
patients with elevated progesterone and
those with normal levels on the day of
administering the human chorionic gonadotropin trigger (10).
Luteinizing Hormone
As stated in the previous section, inhibiting
premature LH surge during ovarian stimulation for IVF has been a clinical standard
for many years. Multiple studies have been
conducted on the role of LH concentrations with regard to both oocyte quality and
the endometrium. Two prospective studies
suggested that the higher the mid-follicular
endogenous LH level, the lower the probability of ongoing pregnancy achieved via
IVF. In comparison, a recent meta-analysis
demonstrated there was no association between low LH levels and decreased success
of an ongoing pregnancy achieved via IVF
(11).
Reasons to Celebrate
Today, more than 1% of all infants are
born with assisted reproductive technology, a statistic expected to rise as mean
maternal age continues to increase.
While the workup for infertility can be
extensive, laboratory tests can help determine primary diagnosis and assess
ovarian reserve (Table 1). Most importantly, the results of these tests provide a
predictive framework for managing and
treating infertility.
As technology continues to improve,
laboratory testing will undoubtedly become a more accurate and sensitive predictor of response to COH, making treatment
of infertility safer and more effective for
women. There are many reasons to celebrate now, however, as more and more
infertile couples welcome babies born with
CLN
these assisted technologies.
References
1. Broekmans FJ, Kwee J, Hendriks DJ, et
al. A systematic review of tests predicting
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Abigail Delaney, MD, is a
chief resident at the University of Nebraska Medical
Center in Omaha, Neb.
Email: [email protected]
Jani R. Jensen, MD, is a
consultant in the Division of
Reproductive Endocrinology
and Infertility at Mayo Clinic
in Rochester, Minn.
Email: [email protected]
Extensive Lipid Profile
HDL • LDL • sLDL • Chol • Lp(a) • Trigs • HCY • Apo A-1 • Apo A-11
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Dean E. Morbeck, PhD, is
IVF Laboratory director at
Mayo Clinic in Rochester,
Minn.
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Email: [email protected]
Disclosure: The authors have nothing to
disclose.
*Certain assays FDA clearance pending
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ovarian reserve and IVF outcome. Hum
Reprod Update 2006;12:685–718.
2. Scott RT Jr, Elkind-Hirsch KE, StyneGross A, et al. The predictive value for in
vitro fertility delivery rates is greatly impacted by the method used to select the
threshold between normal and elevated
basal follicle-stimulating hormone. Fertil
Steril 2008;89:868–78.
3. Buyalos RP, Daneshmand S, Brzechffa
PR. Basal estradiol and follicle stimulating hormone predict fecundity in women
of advanced reproductive age undergoing
ovulation induction therapy. Fertil Steril
1997;68:272–7.
4. Kosmas I, Kolibianakis E, Devroey P.
Association of estradiol levels on the day
of hCG administration and pregnancy
achievement in IVF: a systematic review.
Hum Reprod 2004;11:2446–53.
5. Asch RH, Li HP, Balmaceda JP, et al.
Severe ovarian hyperstimulation syndrome
in assisted reproductive technology: definition of high-risk groups. Hum Reprod
1991;6:1391–9.
6. Speroff L, Fritz MA. Clinical gynecologic endocrinology and infertility, 8th
Ed. Philadelphia: Lippincott Williams and
Wilkins 2011:1293–1383.
7. La Marca A, Sighinolfi G, Radi D, et
al. Anti-Müllerian hormone (AMH) as a
predictive marker in assisted reproductive
technology (ART). Hum Reprod Update
2010;16:113–30.
8. van Rooij IA, Broekmans FJ, Scheffer
GJ, et al. Serum antimullerian hormone
levels best reflect the reproductive decline
with age in normal women with proven
fertility: a longitudinal study. Fertil Steril
2005;83:979–87.
9. Seifer DB, Lambert-Messerlian G, Hogan JW, et al. Day 3 serum inhibin-B is predictive of assisted reproductive technologies outcome. Fertil Steril 1997;67:110–4.
10.Venetis CA, Kolibianakis EM, Papanikolaaou E, et al. Is progesterone elevation
on the day of human chorionic gonadotrophin administration associated with the
probability of pregnancy in in vitro fertilitzation? A systematic review and meta-analysis. Hum Reprod Update 2007;13:343–54.
11.Kolibianakis EM, Venetis CA, Tarlatzis
BC. Role of the endocrine profile for the
achievement of pregnancy with IVF. Reprod Biomed Online 2009;18:37–43.
04/10/2012 11:31
Introducing SYCL SnapShots
Welcome to SYCL SnapShots, a new quarterly column in CLN describing essential skills and practices for effective
laboratory management. Here, members of AACC’s Society for Young Clinical Laboratorians (SYCL) will present a
snapshot of a topic, such as business basics, data analysis and statistics, or online tools. We hope CLN readers will
find this new column valuable and we welcome your feedback.
Christopher McCudden, PhD
SYCL Chair
The Ottawa Hospital
Ottawa, Ontario, Canada
Email: [email protected]
Practical Considerations for Implementing a New Lab Analyzer
By Julie Shaw, PhD
A
s clinical chemists, we play a
major role in evaluating and
implementing new methods
and analyzers. During fellowship training, we become
well-versed in the method evaluation process, mainly from a theoretical point of view.
Written guidelines, such as those published
by the Clinical and Laboratory Standards
Institute (CLSI), describe the technical components of a method evaluation in detail,
including imprecision, method comparison,
linearity, analytical sensitivity, carry-over and
verification of reference intervals. But what
happens after the decision has been made
to purchase a new analyzer? This process
is much less well-defined and lacks written guidelines. Furthermore, trainees may
not get much exposure to this more practical side of laboratory operations. The flow
chart presented here outlines these less welldocumented steps, from the time the decision is made to purchase an analyzer until
the beginning of patient testing.
Going Step-by-Step
First, a team must champion the implementation. Ideally, members would include
laboratory bench, senior technical, and
laboratory information system (LIS) staff.
The team should assume primary responsibility for managing the project, including
communicating with other departments
within the hospital, as well as with external
contacts, to facilitate a smooth transition.
The team also should plan both a realistic
and ideal “go-live” date for implementation, taking into account the needs of facilities management, information technology
(IT), and laboratory operations.
Each stakeholder has specific needs that
the team should take into account. Facilities management needs to be advised of the
physical and environmental requirements
for the new instrument. Changes may be required to the existing laboratory infrastructure, such as electrical and water. Larger-scale
renovations may even be necessary. How the
instrument will be delivered is a consideration, too. For example, is the service elevator
large enough to accommodate the analyzer?
The IT department needs to be advised
of changes required for specific tests that are
being moved to the new analyzer and of any
new tests being added to the existing menu.
For example, the following would affect the
LIS: changes to reference interval values, cut
off values, critical values, and interpretative
comments. These changes also will influence how results are reported in electronic
medical records, so it is important to communicate and collaborate with the staff involved in making these changes.
Within the laboratory, consideration
should be given to whether additional staff
will be needed, especially if the instrument
adds completely new tests to the lab’s menu.
Staff running the new analyzer also will require comprehensive, hands-on training,
either on-site or off-site. Off-site training
adds time and expense to the project.
Another consideration is test volume.
The team should estimate the new workload so that sufficient reagents can be ordered, as well as check on whether licensing
is needed for any new tests.
Planning for QC and PT
Another step is setting up appropriate quality
control (QC) procedures. The team should
decide which QC material the lab will use
and set quality goals for each method. These
decisions should be based on the method
evaluation data, clinical need, and published
requirements, such as those defined by Clinical Laboratory Improvement Amendments
(CLIA) or other national programs.
An external quality assessment (EQA)
or proficiency testing (PT) program is
required for each test performed in the
laboratory. The team should notify PT providers of any changes in methodology and
request PT surveys for new tests. For some
analytes, PT is not available and an alternative scheme must be developed, such as
inter-lab comparison. As part of total quality management within the laboratory, the
team should prepare standard operating
procedures for each new pre-analytical, analytical, and post-analytical process associated with the new analyzer and tests. If an
analyte will be measured on more than one
instrument, inter-instrument comparisons
also will be required.
Communicate!
Finally, prior to the go-live date, laboratory staff needs to communicate the impending changes to both internal and external clients, including the date on which
the changes will occur. Communications
should be planned well in advance so that
there is ample time for client education
about changes to reference ranges, cut off
values, turnaround time, and new interpretive comments.
Celebrate Success
When the analyzer and new tests are up
and running, it is always a good idea to review what went well and what didn’t. And
don’t forget to thank committee members
CLN
for all their hard work!
Julie Shaw, PhD, is a clinical
biochemist at The Ottawa
Hospital in Ottawa, Ontario,
Canada and an assistant
professor in the Department
of Pathology and Laboratory Medicine at the University of Ottawa.
Email: [email protected].
For more information on AACC’s SYCL,
visit www.aacc.org/members.
Practical Steps for Implementing a New Analyzer
Full Method Evaluation
Decision to Purchase
Create Implementation Committee
Choose Desired “Go Live” Date
Contact IT
Contact Facilities/
Engineering
Space Requirements
Water Requirements
Electrical Requirements
Temperature/Humidity
Requirements
LIS Connectivity
Reference Intervals
Critical Values
Comments
Reflex Testing
Autoverification
Delta Checks
Within-lab
Organization
Electronic
Patient Record
Staffing Requirements
Hire New Staff?
Training
Scheduling
Supplies
Ordering
Storage/Inventory
Lab license
Implementation
Internal and
External Clients
Cost
TAT
Reference Intervals
Communications
SOPs
Pre-analytical
Analytical
Post-analytical
Quality Control
Material
Levels
Frequency
Quality Goals
EQA
Ordered or Alternative
Scheme Plan
After the decision is made to purchase a new analyzer, a team should map out a plan for bringing it online in
the lab.
Clinical Laboratory News November 2012 11
profiles
r e g u l at o r y
CMS Launches Pay-forPerformance Initiatives
I
n October, the Centers for Medicare and
Medicaid Services (CMS) launched two
initiatives that aim to reward hospitals for
outcomes and quality: the Hospital ValueBased Purchasing Program and the Hospitals Readmissions Reductions Program.
Created under the Affordable Care Act,
both programs aim to save Medicare money and boost quality.
Under the value-based purchasing
program, Medicare will withhold 1% of
regular reimbursements to acute care
hospitals and redistribute the resulting
approximately $850 million based on
certain performance criteria. Taken from
money that Medicare otherwise would
have spent, the size of the fund will gradually increase over time, resulting in a shift
K-ASSAY ®
from payments based on volume to payments based on performance, according
to CMS.
The quality metrics include: ensuring
that patients who may have had a heart
attack receive care within 90 minutes;
providing care within a 24-hour window
to surgery patients to prevent blood clots;
communicating discharge instructions to
heart failure patients; and the results of
patient satisfaction surveys. The better a
hospital does on its quality measures, the
greater its reward.
The second pay-for-performance program focuses on hospital readmissions.
Similar to the value-based purchasing
program, the Hospitals Readmissions Reductions Program withholds up to 1% of
reimbursements, but only for hospitals
that show too many readmissions within
30 days of discharge for heart attack, heart
failure, and pneumonia. CMS plans to add
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other conditions to the list in the future.
Some experts have estimated that nearly
two-thirds of hospitals could face penalties
of more than $100,000, with hospitals overall losing about $280 million in reimbursement this year.
Penalties for readmissions will increase
over time, from 1% this year, to 2% next
year, and 3% in 2015. According to CMS,
about 2 million Medicare beneficiaries
treated in hospitals return within 30 days
annually, costing more than $17 billion.
More information about the programs
is available from www.healthcare.gov.
ACLU Pushing for Supreme Court
Review of Gene Patents Case
T
he American Civil Liberties Union
(ACLU) and the Public Patent Foundation are asking the U.S. Supreme Court
to again review and invalidate BRCA1 and
BRCA2 patents held by Myriad Genetics
and the University of Utah Research Foundation.
In May 2009, The College of American
Pathologists and the Association for Molecular Pathology, among others, joined an
ACLU lawsuit challenging the patents used
for breast cancer risk testing.
On March 29, 2010 a New York federal
court ruled that the patents on the BRCA1
and BRCA2 genes were invalid. The U.S.
Court of Appeals for the Federal Circuit
heard Myriad’s appeal of that ruling in
April 2011. In July 2011, the appeals court
ruled that companies can obtain patents
on the genes but cannot patent methods to
compare those gene sequences.
Finally, in March 2012, the U.S. Supreme
Court vacated the decision of the appeals
court and instructed the court to reconsider the case in light of Mayo v. Prometheus,
a Supreme Court decision unanimously
invalidating patents on methods for evaluating a patient’s response to a drug.
When ACLU lawyers argued before the
U.S. District Court judge in New York, they
said that medical research was being held
back by the BRCA1 and BRCA2 patents
and that these genes were “an ancient secret
of nature.” Attorneys representing Myriad
Genetics and the University of Utah Research Foundation countered that a ruling
making these patents invalid would “wreck
the foundation of the entire biotechnology
industry.”
More information about the case is
available from www.aclu.org/brca.
House Passes CLIA
Referral Legislation
T
he House of Representatives has passed
an AACC-endorsed bill that could ease
one of labs’ biggest problems with proficiency testing (PT) programs. The bill,
H.R.6118, “Taking Essential Steps for Testing Act,” gives the Centers for Medicare and
Medicaid Services (CMS) greater flexibility
on what penalties to impose on a laboratory that sends a PT specimen to an outside
laboratory.
Under current law, laboratories that refer PT specimens to an outside laboratory
lose their CLIA certificate for at least 1 year,
even if the specimen was not referred to intentionally cheat. Since many labs have policies that automatically refer certain specimens to another lab, the statute has been a
cause for concern for many years.
The House passed the bill just before
both houses of Congress recessed, but after the elections, the Senate could vote on
companion legislation during the lame
duck session that begins November 13.
The bill is available from the THOMAS
website, http://thomas.loc.gov.
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Discover Breaking News
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Assay Range:
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12 Clinical Laboratory News November 2012
2011.09 CLN Insulin.indd 1
8/5/2011 5:19:18 PM
Clinical Laboratory News@CLN_AACC
Sep 13, 9:25am
Endocrine Society and American Thyroid Association
issue new clinical guidelines for managing
hypothyroidism. ow.ly/dGpn4
Here’s How to Follow CLN
Twitter is a real-time information network built on short messages
called tweets. Each tweet is limited to 140 characters, but can include
links to websites, photos—or news stories like those in CLN. If you’re
new to Twitter, simply log on to www.twitter.com, sign up using your
email address and a password, and search for @CLN_AACC to follow
us. Each time you log in, you’ll see all of our tweets on your Twitter
home page.
profiles
industry
Illumina Buys Genomics-Based
Diagnostics Company BlueGnome
I
llumina purchased genomics-based diagnostics company BlueGnome for an
undisclosed sum. BlueGnome’s main offerings include 24sure, a preimplantation genetic screening test that shows the potential
to improve in vitro fertilization (IVF) success rates, and CytoChip, a first-line cytogenetic test for genetic abnormalities associated with developmental delay or complex
leukemias. The company’s focus on cytogenetics and IVF screening solutions supports
Illumina’s goal to become a leading provider in these areas. On BlueGnome’s side,
president and CEO, Nick Haan, said, “The
throughput and data quality of Illumina’s
sequencers enable us to consider revolutionary new approaches to genetic testing.”
Beckman Coulter to Acquire
IRIS International
B
UPMC Enters Data Warehouse
Initiative with Oracle, IBM, Others
T
he University of Pittsburgh Medical
Center (UPMC) has made a 5-year,
$100 million investment to create a data
warehouse with Oracle, IBM, Informatica,
L
Squibb have entered a master development agreement that creates a longterm partnership to develop companion
diagnostics. Life Technologies president
of medical sciences Ronnie Andrews said,
“As more and more targeted drugs come
onto the market in the next decade, there
will be a growing need for diagnostics that
can help predict which patients will benefit
from which drugs.” With its broad portfolio of genetic and proteomic analysis platforms, Life Technologies will be able to give
a pharmaceutical company such as BristolMyers a “flexible, cost-effective means to
manage the evolution of the companion
diagnostic assay through the drug development process,” added Andrews. The two
firms’ first project together will focus on
oncology, a specialty in which the demand
for companion diagnostics is predicted to
rise due to the hundreds of oncology drugs
currently in clinical trials.
PrimeraDx Awarded Grant to
Develop DLBCL Assay
T
he National Cancer Institute-sponsored
Innovative Molecular Analysis Technologies Program has awarded PrimeraDx
a grant to develop an assay to detect diffuse large B-cell lymphoma (DLBCL) subgroups. The assay will be designed for use
on PrimeraDx’s ICEPlex automated realtime PCR platform, and will test formalinfixed, paraffin-embedded specimens. This
assay has the potential to improve upon
gene-expression profiling (GEP) with snap
frozen tissues, the current method for classifying DLBCL subtype cells-of-origin. GEP
is not practical in many lymphoma cases
because it requires frozen tissue, a shortcoming that PrimeraDx’s novel approach
remedies.
T
rovagene finalized a deal with Quest
Diagnostics that grants Quest a nonexclusive license to incorporate nucleophosmin protein (NPM1) into research
and clinical testing services related to acute
myelogenous leukemia (AML). According
to Trovagene chief technology officer Charlie Rodi, PhD, this will help the company
expand patient access to the NPM1 marker
on a global scale. “Physicians need accurate
tools to assess prognosis, select therapies
and evaluate for bone marrow transplant,”
he said. “Use of this marker can help physicians more effectively treat patients with
AML.” Currently, chromosome analysis is
the most common method that provides
guidance for physicians treating AML patients. Because the method is effective in
only about half of AML cases, screening for
NPM1 mutations could become a valuable
addition to the array of available AML codiagnostics.
Sysmex America
Relocates Headquarters
S
ysmex America, the U.S. subsidiary of
Japanese company Sysmex Corporation, has relocated its corporate offices to
a new facility in Lincolnshire, Ill. This site
will serve as headquarters for the Americas along with the company’s logistics operations center in Buffalo Grove, Ill., and
its Mundelein, Ill., reagent plant. “Our new
building supports the infrastructure that
our continued growth requires, as well as
accommodates for future expansion,” said
John Kershaw, president and CEO of Sysmex America.
d
re
ea
Cl
he former diagnostics division of Wako
Chemicals USA, Wako Life Sciences,
has become a fully incorporated diagnostics company focused on developing and
commercializing microfluidic test systems
for the immunoassay and molecular diagnostic markets. The new company headquarters are in Mountain View, Calif., while
its research and development facilities and
commercial operations are in both Mountain View and Richmond, Va.
Trovagene Enters Licensing
ife Technologies and Bristol-Myers Agreement with Quest Diagnostics
A
FD
T
Life Technologies and
Bristol-Myers Collaborate
to Develop Co-Diagnostics
e
bl
la
ai
Av
Wako Life Sciences Joins Ranks
of Diagnostics Companies
AACC members elected Steven Wong, PhD, DABCC, FACB,
to serve as President of the association in 2014, announced AACC Secretary Elizabeth Frank, PhD. Also
newly elected are Dennis Dietzen, PhD, DABCC, FACB, and
Corinne Fantz, PhD, DABCC, FACB, to serve as members of
the Board of Directors, as well as Michael Bennett, PhD,
DABCC, FACB, as Treasurer. Four individuals were elected
to serve on the 2013 Nominating Committee: Shannon Haymond, PhD,
DABCC; Loralie Langman, PhD, DABCC, FACB; Stacy Melanson, MD, PhD;
and M. Laura Parnas, PhD, DABCC, FACB.
Wong takes his place as AACC’s 65th President, having been active in
the association since 1980. He is professor of pathology at Wake Forest
University School of Medicine and director of clinical chemistry and
toxicology in the core laboratory at Wake Forest Baptist Medical Center
in Winston-Salem, N.C., where he also is a member of the Point of Care
Testing Committee, and Co-Director of the Clinical and Translational
Mass Spectrometry Center.
Wong’s service to AACC includes time as a member on the Board of
Directors, chair of three AACC divisions and the North Carolina Local
Section, and a member of the organizing committee for a proteomics
conference.
During his presidency, Wong plans to focus on collaborating with
other medical associations, as well as government agencies such as the
National Institutes of Health, to advance personalized medicine.
w
No
eckman Coulter, Inc., a wholly-owned
subsidiary of Danaher Corporation,
announced a definitive merger agreement
with IRIS International, Inc. Beckman
Coulter will acquire IRIS, which produces
automatic in-vitro diagnostics systems, for
approximately $378 million at $19.50 per
share. “IRIS provides an excellent complement to Beckman Coulter’s core business,
as we continue to focus on our strategy of
serving the core hospital laboratory,” said
Tom Joyce, Beckman Coulter’s president
and Danaher’s EVP. With Beckman Coulter’s strong commercial infrastructure,
IRIS will be able to expand the reach of
its automated and semi-automated urinalysis products. Beckman Coulter might
also benefit from IRIS’s unique cell imaging technology, which could potentially
be used to improve Beckman’s hematology product lines. The deal between the
two companies is expected to close in the
fourth quarter.
and dbMotion that will focus on personalized medicine. The data warehouse will
include clinical, financial, administrative,
genomic, and other hard-to-analyze information from more than 200 sources
across UPMC, UPMC Health Plan, and
other labs and pharmacies. This information will be processed using advanced
analytic and predictive modeling applications to improve patient outcomes and
reduce healthcare costs. “UPMC, with
the help of the Carnegie Mellon Software
Engineering Institute, has methodically
studied best practices in analytics both
inside and outside of health care,” said
Lisa Khorey, UPMC vice president of enterprise systems and data management.
With this current initiative, she added,
UPMC aims to use what the organization
has learned to move towards a personalized medicine model.
AACC Elects New Officers
Steven Wong to Serve as President in 2014
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Clinical Laboratory News November 2012 13
profiles
studies to determine whether correcting
the condition preoperatively will mitigate
risks.
diagnostic
HMGB-1 Protein Best Predictor
of CF Complications
I
n a longitudinal study of patients with
cystic fibrosis (CF), researchers at the
University of Utah found that among the
sputum biomarkers measured, only high
mobility group box-1 (HMGB-1) protein was associated with future acute pulmonary exacerbations (APE) and time to
lung transplantation or death (PLoS One
2012;7:e42748). In comparison to percent
predicted forced expiratory volume in 1
second (FEV1%) and all other biomarkers
alone or in combination, sputum HMGB-1
measurement was a better predictor of subsequent APE and time-to-first APE.
The investigators conducted the study
under the premise that biomarkers that
predict clinical outcomes might also identify causal mechanisms for airway disease
in CF, help determine quickly the efficacy
of new therapies, and distinguish patients
most in need of urgent interventions.
The study involved 97 adult CF patients recruited between 2004–2007 and
followed a median of 5.9 years. In addition
to HMGB-1 the researchers measured numerous other sputum biomarkers, including granulocyte macrophage colony stimulating factor (GM-CSF), interleukin-1β, 2,
5, 6, 8, 10, 12p40, 13, and 17, and tumor
necrosis factor-α, among others.
The authors conducted five different
statistical analyses, including biomarker
measurements and concurrent clinical
status, biomarker behavior with change in
patient status from stable to APE, relationship of biomarkers with APE-associated
clinical changes, prediction of future APE,
and HMGB-1 as an independent predictor of lung transplantation or death. After
all these analyses, HMGB-1 proved to be
the key biomarker; however, at APE onset,
GM-CSF was significantly associated with
APE-associated declines in lung function.
HDL-C SNP Carriers Not
At Reduced Risk for MI
A
large international consortium of researchers found that polymorphisms
related to plasma LDL cholesterol (LDL-C)
were consistently associated with risk of
myocardial infarction (MI), whereas the
same association did not hold for variants
related to plasma HDL cholesterol (HDL-C)
(Lancet 2012;380:572–80). The findings
suggest that some genetic mechanisms that
raise HDL-C do not lower risk of MI; hence
lifestyle or pharmaceutical interventions
that raise plasma HDL-C can’t be assumed
to lower risk of MI.
In a case-control design, the investigators first tested lipid-associated SNPs individually for association with risk of MI.
Next, they tested two instruments, a single
SNP, LIPG Asn396Ser, which is related to
plasma HDL-C, and a genetic score consisting of 14 common SNPs exclusively
14 Elevated RF Confers Long-term
Risk of RA in Healthy Individuals
associated with HDL-C. They tested LIPG
Asn396Ser in 20,913 MI cases and 95,407
controls from several different studies, and
the genetic score in 12,482 MI cases and
41,331 controls. In addition, they tested a
genetic score of 13 common SNPs associated exclusively with LDL-C.
The authors found that in comparison
to non-carriers, subjects who carried the
LIPG 396Ser allele had higher HDL-C but
similar levels of other lipid and non-lipid
risk factors for MI. The investigators estimated that carrying this allele should decrease risk of MI by 13%, but found it did
not, as individuals with this allele had an
odds ratio of 0.99. Observational epidemiology studies indicate that a 1 standard deviation (SD) increase in HDL-C is associated with reduced risk of MI; however, the
researchers found that a 1 SD increase in
HDL-C due to genetic score was not associated with risk of MI. In contrast, estimates
from observational epidemiology suggest
that a 1 SD increase in LDL-C is associated
with an increased risk of MI, with an odds
ratio of 1.54. This risk concurred with the
risk from the authors’ genetic score.
Preoperative Hyponatremia Predicts
Postoperative Complications
P
reoperative hyponatremia, even to a
mild degree, is common and predicts
postoperative morbidity and mortality,
even in relatively healthy patients, and in
those undergoing nonemergency surgery
(Arch Intern Med doi:10.1001/archinternmed.2012.3992). The findings suggest
that even mild changes in serum sodium
are not inconsequential and should not be
ignored. In addition, whenever possible,
the underlying cause of hyponatremia
should be uncovered.
The authors assembled a cohort of patients from the American College of Surgeons National Surgical Quality Improvement Program. In all, they found data from
964,263 patients who were at least 18 years
old, underwent any major surgery between
2005–2010, and in whom preoperative sodium measurements had been recorded.
Of these, 75,423 (7.8%) had hyponatremia,
defined as sodium <135 mEq/L. In comparison to patients with normal baseline
sodium levels, defined as 135–144 mEq/L,
those with hyponatremia had an adjusted
odds ratio of 1.59 for 30-day mortality, 1.21
for perioperative major coronary events,
1.24 for wound infections, and 1.17 for
pneumonia. The excess risk was present
even in patients with mild hyponatremia,
defined as 130–134 mEq/L. After controlling for all the covariates to account for differences in case mix, the investigators also
found hyponatremia to be associated with
a median 1 day longer hospitalization.
The researchers noted that controversy exists as to whether hyponatremia is
a marker or a mediator of mortality and
other adverse events, and called for further
Clinical Laboratory News November 2012
H
ealthy individuals in a general population with elevated rheumatoid factor
(RF) have up to 26-fold greater long-term
risk of rheumatoid arthritis (RA), and up
to 32% 10-year absolute risk of RA (BMJ
2012;345:e5244). These findings could lead
to revision of RA clinical practice guidelines to suggest that depending on RF test
results, early referral to a rheumatologist or
arthritis clinic might be warranted.
This prospective cohort study involved
9,712 adults without RA at enrollment.
Subjects provided blood samples between
1981–1983, which were frozen at -20°C.
The participants were followed until 2010,
when RF concentrations were measured
from the 1981–1983 samples. During
187,654 person years of follow-up, 183 individuals developed RA. Median age at diagnosis was 70 years and the median time
from providing a blood sample to developing RA was 15 years for those with RF levels <25 IU/mL, 12 years for those with RF
K-ASSAY ®
concentrations 25–50 IU/mL, and 7 years
for those with RF levels of either 50.1–
100 IU/mL or >100 IU/mL.
The cumulative incidence of RA increased with increasing RF levels. In comparison to individuals with RF levels <25 IU/mL,
multivariate adjusted hazard ratios for RA
were 3.6 for RF levels 25–50 IU/mL, 6.0 for
RF concentrations 50.1–100 IU/mL, and 26
for RF levels >100. The highest absolute 10year risk of RA was found in women 50–69
years old who smoked and had RF concentrations >100 IU/mL. The lowest risk was
in men at least 70 years old with RF levels
<25 IU/mL, irrespective of smoking status.
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July 28–
August 1
Houston, Texas
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f ro m t h e
BD Receives Clearance
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fda
HIV-1 Viral Load Test Approved
F
DA cleared the BD Diagnostics BD
Veritor System for Rapid Detection of
Flu A+B, for use in clinical settings. The kit
is designed for testing liquid specimens obtained via nasopharyngeal wash, aspirate,
or swab in transport media. The assay uses
BD’s proprietary advanced particle and
adaptive read technologies, which increase
the test’s sensitivity and reduce false positives, respectively.
FDA Clears RSV Test
B
D Diagnostics received clearance from
FDA for a respiratory syncytial virus
(RSV) test designed for use on the BD Veritor System. This is the third FDA-cleared
test for this platform. Like BD’s Rapid
Detection of Flu A+B for the BD Veritor
System, Rapid Detection of RSV tests nasopharyngeal wash, aspirate, and swab in
transport media specimens. It also couples
proprietary advanced particle and adaptive
read technologies with a digital display to
provide objective, easy-to-read test results.
Roche’s CoaguChek XS
Plus Granted CLIA Waiver
F
DA granted CLIA-waived status to
Roche’s CoaguChek XS Plus system,
a point-of-care anticoagulation monitor
that helps hospital staff manage prothrombin time/international normalized ratio
(PT/INR) testing. Quality controls built
into the system ensure the accuracy of
PT/INR results, while optional liquid quality controls accommodate facilities where
policy requires external quality control
measures. The system’s connectivity capabilities also help healthcare professionals
streamline organization and the regulatory
compliance process by allowing them to
connect and transfer data to IT solutions.
R
oche received FDA approval for an
HIV-1 test that uses the company’s proprietary dual-target approach to improve
physicians’ viral load monitoring capabilities.
The dual-target approach, as its name suggests, targets two highly conserved regions of
the HIV-1 genome and avoids regions that
are current drug targets. This strategy ensures
accuracy even when mutations are present in
the viral genome, leading to more reliable
test results. The test also combines the High
Pure System Viral Nucleic Acid Kit with the
COBAS TaqMan 48 Analyzer to provide
manual specimen preparation, and automated amplification and detection.
FDA Approves Group A Strep Test
F
DA has cleared Meridian Bioscience’s
diagnostic test for Group A Streptococcus on the Illumigene platform. The Group
A Strep bacterium causes a number of different illnesses, including pharyngitis, one
of the most common reasons for consultations with primary care physicians. Meridian’s test diagnoses pharyngitis by detecting
Streptococcus pyogenes in throat samples using loop-mediated isothermal DNA amplication (LAMP) technology. This procedure
takes less than an hour, and has the poten-
index to advertisers
Please visit these websites to learn more about the products in this issue.
ARK Diagnostics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
www.ark-tdm.com
BD Biosciences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
www.bdbiosciences.com/go/cd4
Cerilliant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
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Kamiya Biomedical Company . . . . . . . . . . . . . . . . . . . . . . . . . . . 6, 12, 14
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Nova Biomedical . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
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Randox Laboratories . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
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SDIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
www.sdix.com/cell
Waters Corporation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
www.waters.com/osm
Zeus Scientific . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
www.zeusscientific.com/products/technology-systems/ifa
tial to improve upon the accuracy and sensitivity of traditional pharyngitis diagnostics such as rapid antigen testing and throat
swab culture.
Cell Banking
In vivo Production Runs
(mg - kg capacity)
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Ab Purification
& Processing
T
he Focus Diagnostics Simplexa Flu A/B
& RSV Direct test on the 3M Integrated
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moderate-complexity categorization. The
test qualitatively detects and differentiates
RNA of influenza A and B viruses and the
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G
enMark Diagnostics received 510(k)
clearance from FDA for its eSensor
Respiratory Virus Panel (RVP). Intended
for use on GenMark’s XT-8 system, the test
can concurrently detect and distinguish between 14 major viruses that cause influenzalike illness, including rhinoviruses, enteroviruses, and clinically relevant adenoviruses.
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Clinical Laboratory News November 2012 15
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