A 75 year old Alzheimer’s dementia patient. Parathyroid hormone (PTH) levels were ordered.
Why order PTH?
PTH is ordered to assess for hyperparathyroidism. There are two forms of hyperparathyroidism: primary and secondary. Primary hyperparathyroidism can be caused by a parathyroid (PT) adenoma, PT hyperplasia, or a non-PT malignancy such as squamous cell cancer or multiple myeloma. Secondary hyperparathyroidism occurs in response to hypocalcemia which can arise from insufficient intake of vitamin D or chronic renal failure (which results in insufficient vitamin D). There is weak evidence suggesting a positive correlation between PTH and cognitive decline.(1, 2) Progression of cognitive decline is slowed when PTH and vit D levels are normalized.
Action of PTH: PTH is a peptide hormone that controls calcium levels in the blood. It is secreted as a prohormone and is cleaved in the blood. The 34 residue N-terminal fragment is active and has a half-life of about 5 minutes. The C-terminal end has a half-life or 2 hours and is diagnostically insignificant because it is physiologically inactive. PTH activates receptors on osteoclasts which causes them to release bone calcium. PTH also increases renal synthesis of 1,25 OH2 vitamin D which, in turn, increases intestinal absorption of calcium.
What would make the PTH level fluctuate so much?
This is most likely a case of incipient normocalcemic primary hyperparathyroidism (NPH).(3-5) PTH levels are higher than normal but calcium levels are normal. PTH levels tend to fluctuate. Calcium can also be sometimes elevated as well. The disease is thought to be a mild or early form of hyperparathyroidism and 20 percent of patients go on to develop worsening hyperparathyroidism. How should NPH be managed? Parathyroidectomy or monitoring are the primary alternatives; however, the best way to manage this disease is unknown.
Lourida I, Thompson-Coon J, Dickens CM, et al. Parathyroid hormone, cognitive function and dementia: A systematic review. PLoS ONE 2015;10.
Björkman MP, Sorva AJ, Tilvis RS. Does elevated parathyroid hormone concentration predict cognitive decline in older people? Aging Clinical and Experimental Research 2010;22:164-9.
Shlapack MA, Rizvi AA. Normocalcemic primary hyperparathyroidism-characteristics and clinical significance of an emerging entity. Am J Med Sci 2012;343:163-6.
Lowe H, McMahon DJ, Rubin MR, Bilezikian JP, Silverberg SJ. Normocalcemic primary hyperparathyroidism: Further characterization of a new clinical phenotype. Journal of Clinical Endocrinology and Metabolism 2007;92:3001-5.
Crowley RK, Gittoes NJ. Elevated PTH with normal serum calcium level: A structured approach. Clinical Endocrinology 2016;84:809-13.
-Robert Schmidt, MD, PhD, MBA, MS is currently an Associate Professor at the University of Utah where he is Medical Director of the clinical laboratory at the Huntsman Cancer Institute and Director of the Center for Effective Medical Testing at ARUP Laboratories.
Hello again everyone! Every few posts on Lablogatory I like to take a small departure from updates about my medical school experience and my Zika public health initiative. This time is more of a shameless plug: I am thrilled and honored to be considered one of ASCP’s Top 40 Under Forty for 2017!
Looking through the rest of the honorees, I can certainly say I’m in great company. Each person on that list is a prime example of the working values, lessons, and vision that ASCP recognizes in our dynamic field. So, to celebrate my and others’ place on this list, I’ve put together a few thoughts that truly reflect our hard work, talent, and potential as laboratory professionals and what that might mean for each of us. Here are what I consider the “Top 40” lessons that a career in medical laboratory science and laboratory medicine have taught me:
The laboratory is the best melting pot –How many awesome pot-lucks have you had in your breakroom? How many words in new languages have you picked up? All that cultural exposure really contributes to a profound sense of community and humility.
If everything is STAT, nothing is… – need I say more? We know the value of prioritizing and triaging what’s important for patients.
You know a little about a lot of things, and sometimes a lot about a few things – To all my fellow generalists and specialists out there: how good does it feel to directly contribute to a patient’s positive outcome?
Everyone’s got a different TAT – To turn a phrase, we’re all at various stages. Some laboratorians are just starting out and some can “smell” a tricky differential…
Quality control protects everyone – If QC is good, instruments are good. If instruments report good values, results are good.
Accountability is key – Owning up to failures and successes are both important!
Record everything – This is how we protect patients and ourselves as well as improve.
Teamwork is a necessity – It takes a village or, in this case, a full staff…
We’re not magicians, but sometimes we are – Impressing other clinicians with our ability to analyze and get results is just part of what we do.
Nurses are our friends – Really, when you’ve got great relationships with the nursing staff you know just how that can make an enormous difference in your work.
Doctors are our friends, too – The best doctors value the laboratory, and its staff!
Ultimately, we’re here for our patients – That’s what it’s all about!
We celebrate each other – How many of your labs have a ‘tech of the year’ award, or service awards? We make sure that we recognize each other’s talents.
We share everything – Life events, stories, experiences, swapping shifts…
Toxic techs are real, but they can be your friend too – All too real in many labs; often they’ve got lots of experience and can be a positive voice for change. Are we listening?
What happens if everyone retires? – Staff turnover can be a challenge, but a combo of great training and communication are key.
What happens if no one retires? Ever? – This occurs too, staff gridlock can be tough to manage and laboratory leadership is part of our role as well.
We ALL have prior experiences – From brand new to near retirement, we’ve all had experience in healthcare; even as patients!
Sometimes, QC just won’t come in range – That’s why relying on protocol and documentation can make all the difference.
Sometimes, things happen even when QC was perfect – Bad days happen! Our drawing board is based on what we do best: analyzing, interpreting, and taking action.
No one can tolerate as much as we can – How many of you have been blamed for hemolysis, or scrutinized for TAT statistics? Let’s call it “character-building experience.”
Trust your training – It’s really your best resource.
Taking initiative is a built-in perk – There will be times when it comes down to one lab tech on a night shift, or one pathologist who’s been paged, to take charge and make decisions.
Watch something, do something, teach something – What better place than a clinical lab to see everything, learn it hands-on, and teach the next person?
Never ending details – All those SOPs really make one appreciate the vast number of details that go into planning anything.
We’re the best part of the hospital for metrics and progress – Diagnostic data comprises 70% of patient information, and 100% of laboratory performance.
Lab week is the best – It feels great to be part of a large family of clinicians in this shared field. It’s also usually around my birthday, so that’s been a personal perk…
Some teachers have years of experience on you – They’ve seen things you may never get the chance to!
Some people will teach you something, even if you’re their supervisor – Everyone brings something to the table, or lab bench, or conference table, or shared microscope.
We choose our words carefully – “These cells are suspicious and require pathology consult with further clinical correlation…” We know our scopes and practices.
We word our choices carefully too – “This specimen was forwarded for pathology review because of our criteria…” We know we’ve got to back up our actions with evidence.
We know office politics, just a little more intense than most people realize – Every hospital has a hierarchy, but laboratorians know we’re all on the same team.
We’ve got an SOP for that – Literally, we have one for everything.
We can come up with solutions with very limited information – Requisitions don’t always carry the highest level of clinically relevant guidance. (Test: Hgb A1c, Note: repeat from 1 hour ago).
Sometimes we cannot find a solution, despite endless information – There are times when laboratory data is not enough to definitively make diagnoses, that’s just part of medicine.
We all have the potential to be laboratory leaders – We’ll all have moments to take initiative and demonstrate our talents at one point or another.
We are all real clinical scientists – The change to calling it “medical laboratory scientists” is one of the best changes ever. In my opinion, we are true clinical and critical scientists.
It’s our job to promote our role and our field!
Never stop learning!
I think the last two points need no explanation. Thank you for taking the time to read my “Top 40” Laboratory Lessons. If you have a great lesson you’ve learned, add it to the comments below! Don’t forget to check in next month for another update on my work and don’t forget to vote for ASCP’s Top Five! All the Top 40 Under Forty nominees are eligible to be in the Top Five based on your votes and comments!
–Constantine E. Kanakis MSc, MLS (ASCP)CM graduated from Loyola University Chicago with a BS in Molecular Biology and Bioethics and then Rush University with an MS in Medical Laboratory Science. He is currently a medical student at the American University of the Caribbean and actively involved with local public health.
A 100 year old female was seen for follow-up for her hypertension, mild renal impairment, and fatigue. The patient also stated a three week duration of pain in the area of the right upper quadrant that radiates to her back. No other symptoms or concerns were expressed.
An abdominal CT was performed which showed a 6.6 x 2.1 cm soft tissue mass in the right posterior chest wall that also encases the 11th rib. Given the concern for a malignant process, a core needle biopsy was obtained for histology only.
The H&E stained sections show a diffuse infiltration of atypical lymphoid cells that are large in size with irregular nuclear contours, vesicular chromatin, and some with prominent nucleoli. Frequent apoptotic bodies and mitotic figures were seen. By immunohistochemistry, CD20 highlights the infiltrating cells, which are positive for BCL2, BCL6, and MUM1 (major subset). CD10 is negative within the atypical lymphoid population. CD3 highlights background T-cells. Ki-67 proliferation index is approximately 70%. EBER ISH is negative.
Overall, the findings are consistent with diffuse large B-cell lymphoma, NOS with a non-GCB phenotype by the Hans algorithm.
Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell lymphoma in adults comprising 30%-40% of new adult lymphomas. Approximately 50% of patients will be cured, even in advanced cases; however, those that fail conventional therapy ultimately succumb to their illness.1 Up to 30% of patients have refractoriness or relapse after initial therapy with rituximab based regimens, particulary R-CHOP (ritixumab, cyclophosphamide, doxorubicin, vincristine, and prednisone).
In the era of new molecular techniques and in the context of the heterogeneous nature of DLBCL, it has become important to accurately assess cell of origin (COO) as this has prognostic implications. With the seminal paper from Alizadeh and colleagues, gene expression profiling (GEP) by a microarray platform produced the concept of germinal center (GCB) versus activated B-cell (ABC) types of DLBCL.2 In the context of prognosis and R-CHOP therapy, the GCB type has a 3 year PFS of 75% as opposed to the ABC type that has a 3 year PFS of 40% (P<.001).3 Although GEP analysis is considered the ideal modality for determining COO, however, given the constraints of most modern hematopathology practices, surrogate immunohistochemical algorithms were developed to aid in COO determination. Of the multiple algorithms, the Hans algorithm is the most widely used and accepted for IHC determination of COO.
The COO determination has revealed multiple genetic alterations that are shared between the GCB and ABC phenotype while distinct changes have been identified in each type. Molecular mechanisms at play include, but are not limited to, histone modification, blocks to terminal differentiation, cell cycle activation, PI3K/AKT signaling activation, mTOR pathway activation, as well as a multitude of other signaling cascades. A common shared dysregulated pathway between GCB and ABC types include mutations in CREBBP and EP300, which is in approximately 30% of DLBCL cases and slightly enriched in the GCB group. Mutations/deletions in these genes result in inactivation and alter histone modification subsequently thought to contribute to acetylation of BCL6, which is a key regulatory protein in lymphomagenesis. Up to 33% of DLBCL have mutations in MLL2, which has a broad effect on chromatin regulation and epigenomic alteration. Approximately 35% of DLBCL cases with up to two- to three-fold increase in ABC type cases have genetic alterations in BCL6, particularly chromosomal rearrangements and mutations in the 5’ sequence. Pasqualucci et al also described other factors that lead to BCL6 inactivation, including mutations in MEF2B and FBXO11.4
ABC type DLBCL often displays canonical pathway activation of NF-ƙB signaling, which ultimately promotes survival, proliferation, and inhibition of apoptosis. This potentially is a result of alterations in the CBM signalosome (CARD11, BCL10, and MALT1) with up to 10% of ABC-DLBCL cases having a mutation in CARD11. Another modality of ABC activation is through the B-cell receptor signaling pathway in which 20% of cases harbor a CD79A or CD79B mutation. Interestingly enough, recurring mutations in MYD88 occur in ~30% of ABC-DLBCLs, which results in upregulation of NF-kB and Janus kinase-signal transducers. Other important genetic alterations include involvement by signaling pathways of spleen tyrosine kinase (SYK), PI3K, Bruton tyrosine kinase (BTK), and protein kinase C-β (PKC-β).
GCB type DLBCL often expresses CD10, LMO2, and BCL6 and has a less understood and distinct pathway when compared to ABC-DLBCL. The most common alterations include t(14;18) IGH-BCL2 (30-40%), C-REL amplification (30%), EZH2 (20%) and PTEN mutations (10%). These changes are almost never seen in ABC-DLBCL.
Although the findings in GCB and ABC type DLBCL are described, they are not absolute and multiple studies done by whole exome sequencing (WES) and whole genome sequencing (WGS) have elucidate further complexities and genetic changes. In 2015, data from Novak and colleagues revealed CNAs and mutations that were associated EFS, which also underscored the important 24 month milestone for survival.5 Morin et al in 2013 described 41 novel genes in DLBCL which demonstrated just how complex and heterogeneous DLBCL truly is (see figure below).6
As common as DLBCL is, there is much to be understood not only for lymphomagenesis, but for correct classification and risk stratification. Many targeted therapies have been designed and are in trials at the moment, but given the nature of DLBCL and its heterogeneity, more work on the molecular front is needed. Modalities for assessing COO are currently on the market but are not widely used. Perhaps COO determination by IHC may be an antiquated method, but it is currently the standard by which most pathologists practice. Overall, DLBCL in all its forms is not a uniform entity that can easily be defeated, but requires thought and diligence in achieving a cure.
Lohr, JG et al. “Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing,” Proc Natl Acad Sci USA. 2012; 109(10): 3879-3884
Alizadeh AA, et al. “Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling,” Nature 2000, 403:503-11
Sehn, L and Gascoyne, R “Diffuse large B-cell lymphoma: optimizing outcome in the context of clinical and biologic heterogeneity,” Blood. 2015;125(1):22-32
Pasqualucci, L and Dalla-Favera, Riccardo, “The Genetic Landscape of Diffuse Large B Cell Lymphoma,” Semin Hematol. 2015 April; 52(2): 67-76
Novak, AJ et al. “Whole-exome analysis reveals novel somatic genomic alterations associated with outcome in immunochemotherapy-treated diffuse large B-cell lymphoma,” Blood Cancer Journal (2015) 5
Morin, R et al. “Mutational and structural analysis of diffuse large B-cell lymphoma using whole-genome sequencing,” 2013;122(7):1256-1265
-Phillip Michaels, MD is a board certified anatomic and clinical pathologist who is a current hematopathology fellow at Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. His research interests include molecular profiling of diffuse large B-cell lymphoma as well as pathology resident education, especially in hematopathology and molecular genetic pathology.
A 34 year old female presented to the emergency department with a chief complaint of nausea, vomiting and diarrhea as well as tenderness in her extremities. These symptoms had been present for the previous 4 days with multiple episodes of diarrhea, associated low grade fevers & chills and she had poor oral intake as a result. Her past medical history was significant for human immunodeficiency virus (HIV) and chronic kidney disease. She has not be compliant with her anti-retroviral therapy and infectious disease prophylactic medications. Her vitals were within normal range and her physical exam elicited tenderness to palpation of her extremities and torso. No rashes and no erythema are seen. Routine laboratory tests as well as infectious disease work up, which included blood, stool & urine cultures, C. difficile and ova & parasite exam, were ordered. Notable findings included a slightly elevated white blood count (11.3 TH/cm2), creatinine of 7.1 mg/dL, HIV RNA viral load of 671 VC/mL and an absolute CD4 count of 7 cells/cm2. Two days after collection, her blood cultures were signaled as positive by the automated instrument.
The pathogen of interest grew from two sets of blood cultures and the direct Gram stain showed Gram negative cocci arranged in pairs (Image 1). After 48 hours incubation, small, whitish colonies were observed on blood and chocolate agars. No growth was seen on the MacConkey plate (Image 2). The isolate was positive for both catalase and oxidase. It was identified as Neisseria gonorrhoeae by both MALDI-TOF MS and a Vitek NH card.
N.gonorrhoeae is the second most common sexually transmitted infection (STI) in the United States, only surpassed by Chlamydia trachomatis and they are often acquired together as a co-infection. Uncomplicated infections with N. gonorrhoeae typically present as acute urethritis with discharge. Asymptomatic infection occurs in 10% of males and upwards of 50% of females. As a result, females are at risk for the development of ascending infections and pelvic inflammatory disease leading to further reproductive issues. Disseminated gonococcal infection is uncommon (less than 1% of all gonococcal infections) but can occur and manifests as purulent arthritis with or without an accompanying dermatitis. In the case of our patient, her tenderness to palpation of the extremities could be a symptom of this disseminated septic arthritis.
In the laboratory, N. gonorrhoeae can be fastidious and requires special media such as chocolate, Martin-Lewis, modified Thayer-Martin or New York City agars as well as an enhanced CO2 environment in order to grow. The Gram stain of N. gonorrhoeae is described as Gram negative cocci with adjacent flattened sides and helpful biochemicals include catalase and oxidase (both positive). Traditionally, in order to further speciate members of the Neisseria genus, sugar fermentation was necessary. N. gonorrhoeae only ferments glucose, while another notable member, N. meningitides, ferments both glucose and maltose. Additionally, N. lactamica ferments glucose, maltose and lactose. Currently, commonly used methods of identification include API NH strips and automated instruments such as Vitek and MALDI-TOF MS.
Susceptibility testing for N. gonorrhoeae is usually limited to testing for beta-lactamase activity, although CLSI guidelines are available if deemed necessary. Current therapeutic guidelines recommend empiric treatment of uncomplicated infections with intramuscular ceftriaxone and oral azithromycin.
-Kristen Adams, MD, is a fourth year Anatomic and Clinical Pathology resident at the University of Mississippi Medical Center.
-Lisa Stempak, MD, is an Assistant Professor of Pathology at the University of Mississippi Medical Center in Jackson, MS. She is certified by the American Board of Pathology in Anatomic and Clinical Pathology as well as Medical Microbiology. She is the director of the Microbiology and Serology Laboratories. Her interests include infectious disease histology, process and quality improvement and resident education.
When it comes to the herb cilantro, people either love it or they hate it because it tastes like soap. Conflict is much the same way: either you see it as constructive or destructive. In my case, I used to think cilantro tasted like soap and it would ruin any food it came near. When I became a teenager, my taste buds changed. Now I will eat an entire bunch of cilantro on top of a taco or khao tom. Similarly, I used to feel conflict was a destructive force, and now I sometimes even look forward to a conflict (assuming it’s handled effectively) because it is an essential stage of team development.
The Thomas-Kilmann Conflict Mode Instrument (TKI) gives you insights into how you prefer to manage conflict, whether that is through:
Knowing what your go to method is for handling conflict allows you to actively increase your skills in the other conflict modes and applying each mode when the situation requires it. Having more than one or two management skills will allow you to respond to different types of conflict effectively and nip unnecessary conflict in the bud.
-Lotte Mulder earned her Master’s of Education from the Harvard Graduate School of Education in 2013, where she focused on Leadership and Group Development. She’s currently working toward a PhD in Organizational Leadership. At ASCP, Lotte designs and facilitates the ASCP Leadership Institute, an online leadership certificate program. She has also built ASCP’s first patient ambassador program, called Patient Champions, which leverages patient stories as they relate to the value of the lab.
Do you know that we have a comfort zone when we are handling conflicts? The Conflict Management course conducted by ASCP’s Leadership Academy offers an assessment of your conflict management style using the Thomas-Kilmann Conflict Mode Instrument (TKI). This assessment is eye-opening and helped me gain a better appreciation of my management style.
I scored high on “accommodating skills” on the TKI, meaning that when in conflict, I tend to be reasonable and accommodating with others, creating goodwill in the process. This method is particularly helpful for managers who inherit a new department through restructuring and aim to preserve harmony and avoid disruption to the work process. It is also helpful for building social credits to be use in the future for more important tasks that need larger buy-ins. As companies in the healthcare and diagnostic testing sectors evolve and adapt to the new regulatory and fiscal environment, departments within companies will continue to be restructured to ensure efficiency and relevancy. In my current position as a manager, I find these skills to be immensely useful, particularly as I’m recently given oversight responsibilities of new departments. The skills are helpful to ensure seamless transition while continuing to provide patients with unsurpassed diagnostic insights and innovation.
The course also asks us to look at our blind spots. I find that I tend to spend too little time discussing issues in depth and hashing out personal differences. “Collaborating mode” encourages us to work through issues, think outside the box, and to create a win-win solution. I’m learning to set aside time to proactively reach out to others with varying views and to understand their thoughts and evaluate their viabilities and applications. This gives me an opportunity for integrative solutions to merge insights from people with different perspectives on a problem and gain commitment from various stakeholders.
The ASCP Leadership program and the TKI gave me important revelations into my conflict management comfort styles and provided insights into my blind spots. While my favorite conflict behaviors are results of both my personal predispositions and the requirements of my work situations, I try to utilize other management styles based on the specifics of the situation. I have no doubt that the leadership program has augmented my management tool box. Now I have different tools at my disposal, whether it be “kill your enemies with kindness” (accommodating), “two heads are better than one” (collaborating), “Leave well enough alone” (avoiding), “might makes right” (competing), or “split the difference” (compromising), to approach future conflicts.
-Paul Chiou, MPH, SCT (ASCP) CM is a supervisor of Cytology and FISH at Miraca Life Sciences. Paul is a CAP inspector and an active member of the laboratory community having served on various professional committees over the years.
Healthcare organizations are under increasing pressure to increase value. It is well known that a significant portion of laboratory testing is unnecessary. As a result, many organizations have started laboratory utilization management programs (LUMP) to reduce the waste associated with laboratory orders. Each month, I’ll address a series of topics related utilization management.
Conceptually, LUM is not difficult. It is much like any other improvement process such as Deming’s PDSA cycle (Plan Do Study Act) or the DMAIC (define, measure, analyze, improve, and control) cycle used by Six-Sigma. In the context of LUM, one must identify opportunities for improvement, design and implement an intervention, and study the results. Most organizations are familiar with these approaches and utilization management is nothing more than directing these improvement methodologies to laboratory testing.
The success of a LUMP depends on the proper organization of the program. Top management support is very important. At my hospital, the LUMP was driven by an initiative called Value Driven Outcomes which was started by the Dean of the Medical School, Vivian Lee.(1) This program affected all parts of the organization – including the lab. We formed a LUM committee that was chaired by the Chair of Internal Medicine and included high-level representatives from Information Technology, Pathology, Finance, and education. The high-level support made it possible to overcome resistance and move quickly. I speak to many clinicians and managers across the country who are involved in LUM. Almost invariably, those who have top-level support are more satisfied with their progress. In contrast, those who approach LUM from the bottom up are less satisfied. They make progress, but the path is more difficult.
Identifying opportunities for improvement is the most challenging part of UM Opportunities are usually identified by comparing performance against a guideline. Unfortunately, the number of tests (~2500) far outnumbers the availability of guidelines (~200).
Benchmarking is alternate approach that can be applied to almost any test. In benchmarking, one compares testing patterns across a number of organizations and looks for outliers(2). The presumption, which is not necessarily true, is that unusual order patterns are associated with unusual order patterns and that tests with unusual order patterns are most likely high-yield targets.
There are several good sources of guidelines. The Choosing Wisely campaign provides a good list of tests that are obsolete. A forthcoming CLSI document on utilization has a chapter that provides a long list of targets. Repeat testing is also a common target and several recent guidelines have been published on testing intervals. (3-5)
Although there remains much to be discovered with respect to guidelines, interventions are fairly static. I haven’t seen much new since the 1990’s. A recent review categorized interventions as education, audit and feedback, system-based, or penalty/reward.(6) All of these seem to work, but there is a lot of variation across studies – even within one intervention. A forthcoming CDC study will add to this literature.
Overall, the bottleneck in LUMPs are finding guidelines and doing the analysis to determine whether an opportunity exists. National organizations such as CLSI do a great service by compiling this information.
That is the overview. Next time, I’ll pick a more specific topic.
Kawamoto K, Martin CJ, Williams K, et al. Value Driven Outcomes (VDO): a pragmatic, modular, and extensible software framework for understanding and improving health care costs and outcomes. Journal of the American Medical Informatics Association 2014:amiajnl-2013-002511.
Signorelli H, Straseski JA, Genzen JR, et al. Benchmarking to Identify Practice Variation in Test Ordering: A Potential Tool for Utilization Management. Laboratory medicine 2015;46:356-64.
Janssens PMW, Wasser G. Managing laboratory test ordering through test frequency filtering. Clinical Chemistry and Laboratory Medicine 2013;51:1207-15.
Orth M, Aufenanger J, Hoffmann G, et al. Recommendations for the frequency of ordering laboratory testing. LaboratoriumsMedizin 2015;38.
Kobewka DM, Ronksley PE, McKay JA, Forster AJ, Van Walraven C. Influence of educational, audit and feedback, system based, and incentive and penalty interventions to reduce laboratory test utilization: A systematic review. Clinical Chemistry and Laboratory Medicine 2015;53:157-83.
-Robert Schmidt, MD, PhD, MBA, MS is a clinical pathologist who specializes in the economic evaluation of medical tests. He is currently an Associate Professor at the University of Utah where he is Medical Director of the clinical laboratory at the Huntsman Cancer Institute and Director of the Center for Effective Medical Testing at ARUP Laboratories.