generalist – Page 27

One Part Interpreter

I’m thoroughly convinced that in order to change laboratory information systems (LIS) and get the new LIS to work correctly you need a mixture of one part laboratory professional, one part information technology (IT) specialist, and one part interpreter. Add together and then vortex vigorously.

The laboratory professional is a given. It is absolutely necessary to have a person or people who understand the lab tests inside and out, from linear range to reference intervals to instrument capabilities to antibiotic susceptibilities to type and cross-match. There must be people with an understanding of how the tests work and what type of information is needed in order to ensure that when a test result appears in the electronic medical record for the doctor to see, it is an accurate result that makes sense and is interpretable.

The IT specialist is also a given. This person or people must completely understand not only how to program the system, but what type of programming is possible – what the computer system is capable of doing – or not doing. Being currently immersed in changing LIS systems at my institution, I have come to appreciate more and more how these two individual types must be able to communicate with each other and work together to design and implement an LIS that is functional for everyone.

Which brings us to the “interpreter”. Sometimes IT and lab people simply don’t speak the same language. I know I sometimes feel as though the IT people have begun speaking in tongues. I’m occasionally amused by the totally blank looks on the faces around me, and no doubt on my own. Thus what a project like this requires is a facile communicator with enough knowledge of both the lab and the programming to successfully interpret between the experts. I’m calling this person an “interpreter”, but calling him/her a communicator would be just as accurate.

In my institution the interpreter role is most frequently filled by laboratory technologists who have gone over to the Dark Side, otherwise known as Information Technology. Much as I hate to lose them as medical laboratory scientists, they are pretty nearly worth their weight in gold as interpreters when changing LIS systems. To continue the analogy, without their input in the mix, the vigorous vortexing necessary often results in an emulsion, not a smooth mixture. The finished product may not function as desired simply because the programmer did not understand what was needed, or the laboratory professional did not understand the inherent capabilities of the LIS.

With any luck, we have enough interpreters in our mix to end up with a functional LIS we can all live with. I know the current meetings are going as smoothly as they are due to these people’s work.

-Patti Jones PhD, DABCC, FACB, is the Clinical Director of the Chemistry and Metabolic Disease Laboratories at Children’s Medical Center in Dallas, TX and a Professor of Pathology at University of Texas Southwestern Medical Center in Dallas.

Are Feasibility Limits Feasible?

In the laboratory we’re constantly seeking ways to check that the test results that we put out are accurate. Our primary reason for doing this is that we want to make sure the patient is treated appropriately based on the results of the tests we run. Also, it’s nice not to release values that appear to be nonsense. A tool that is sometimes used to help us check results is something called feasibility limits.

Lab computer systems often allow you to enter feasibility limits for your test results or for your test parameters. These are values outside of which you would not expect to find an analyte concentration in a living person. For example, you might expect a serum creatinine of 200 mg/dL (17,680 µmol/L) in a zombie, but you wouldn’t expect to find one in a living human being. Setting feasibility limits helps you catch things that make no sense before the physician calls you on them, for instance if you have a decimal malfunction and mistakenly try to report a plasma calcium value of 90 mg/dL (22.5 mmol/L) instead of 9 mg/dL (2.25 mmol/L). The trick to feasibility limits is deciding on the highest or lowest value you might expect to see in a living human being. In the case of calcium, upper feasibility limits of 20 mg/dL (5 mmol/L) may give you wiggle room without letting you report nonsense. However, feasibility limits have their drawbacks also. One of those drawbacks is that I’ve found that with human beings, nearly anything is feasible, especially in the pediatric realm. I finally removed the feasibility limits from the LIS in my institution, after a couple of different episodes led me to that conclusion.

One was a body temperature on a blood gas analysis. Under normal circumstances one would not expect to encounter a body temperature much below 90° F (32.2 °C) ever. But of course hospitals are not known for their populations being “under normal circumstances”. The body temperature of the patient in question was 70° F (21°C) on a patient who had been cooled down for surgery. The blood gas instrument accepted the temperature, but the lab computer system would not because of the feasibility limits set in the computer. The patient’s blood gas results could not be released in the computer until we took the temperature feasibility limits out.

Another example was with sodium. It would seem reasonable to have an upper feasibility limit of 180 mmol/L for sodium. Yet we had a patient whose sodium was 199 mmol/L when he arrived in the ED. Reasonably expecting some sort of contamination issue, we requested another sample, which had a sodium of 204 mmol/L, followed by 200 mmol/L in the next sample. These were real sodium results and over the course of several days’ time the physicians managed to get the patient’s electrolytes normalized. Again, feasibility limits interfered with result reporting and had to be removed from the computer.

These episodes caused us to remove most of our feasibility limits from the computer. They also helped me to remember and important point: Tools are fine, but you must understand their uses and their limitations in order to use them appropriately. Feasibility limits can be useful as long as you keep in mind that with humans, you often see the unfeasible.

Education Proposals for ASCP’s 2016 Annual Meeting

Are you interested in presenting an education course at ASCP’s 2016 Annual Meeting? If so, the call for proposals is now out. You can find it at the direct link below.

ASCP’s 2016 Annual Meeting will be held at the Mandalay Bay Hotel & Casino in Las Vegas, NV on September 14-16, 2016.

Click here to access the 2016 Call for Proposals submission site

AMP Submitts Written Testimony about LDTs

From the press release:

“The Association for Molecular Pathology (AMP), the premier global, professional society serving molecular diagnostics professionals, yesterday submitted written testimony to the House Energy and Commerce Subcommittee on Health for their hearing on “Examining the Regulation of Diagnostic Tests and Laboratory Operations.” AMP urged the Committee to use AMP’s proposal to modernize the Clinical Laboratory Improvement Amendments (CLIA) at the Centers for Medicare & Medicaid Services (CMS) as the basis for legislation that would preserve innovative patient care by building upon the current CMS-based system for oversight of laboratory developed procedures (LDPs).

‘Molecular pathologists are highly trained professionals and our professional judgment is used throughout the design, validation, performance, ongoing monitoring, and interpretation of test results. It is our mission to ensure that patients have access to innovative, accurate, reliable, and medically useful laboratory testing procedures,’ said Roger D. Klein, MD, JD, AMP Professional Relations Chair. ‘The AMP CLIA Modernization proposal preserves patient access to essential laboratory services that would no longer be offered if a costly FDA-based regulatory system were imposed upon academic medical centers, cancer centers, hospitals and small independent laboratories,’ he added.”

To read the press release in full, visit www.amp.org.

Radiation in the Lab

Radioactivity is no longer common in most clinical laboratories. At one point in my career, radioimmunoassays were commonly found in laboratories, and most labs had institutional radiation safety plans and carefully followed the CAP checklist for handling and dealing with radioactivity. With the advent of enzyme-linked immunoassays, sensitive nephelometers, various fluorescent and chemiluminescent technologies, and then mass spectrometry, radiation was quickly replaced in most clinical labs. The general prevailing thought was: Why deal with radiation if you don’t have to? Now days, radioimmunoassays are essentially only found in reference labs and utilized for esoteric analytes or those which cannot be measured any other way.

Despite that being true, it’s important for a lab to know what to do if radioactive materials should appear in the lab. How likely is that to happen? Perhaps more likely than you may think. Last week a sample shipped to us from an outside institution set off the radioactivity monitor on our hospital loading dock. The package was on a delivery cart with other packages so per protocol, the whole cart went to nuclear medicine where it was determined that the radioactive package was for the lab and it was brought to us. The radioactive sample turned out to be a urine sample for VMA/HVA analysis from a patient on a new cancer treatment protocol. The urine was indeed radioactive.

The shipping institution was contacted and the packaging personnel had no idea either that the sample was radioactive, although they were aware a new protocol was going into place. Working with our nuclear medicine department and the institutional radiation safety group, we have now once again put appropriate processes in place to handle and deal with radioactivity. And we’ve dusted off our old CAP checklist regulations as well.

This episode actually turned out to be a benefit to us, as we discovered that our own nuclear medicine department will be starting this new protocol soon, and had not thought ahead to possible radioactive samples sent to the lab. We are now working closely with them to ensure proper procedures and safeguards, and have a plan of action clearly in place. We also continue to work with the institution that sends us samples. The very next sample from them was properly labeled as potentially radioactive.

Times are Definitely Changing

Just returning from the ASCP 2015 conference in Long Beach, California, I can’t help but reflect on what a wonderful experience I had. The weather was picturesque, attendees at an all time high, and a variety of educational offerings and speakers on point.

The highlight for myself (and I know I am not speaking out of line when I mention the four other amazing ladies) was being recognized as ASCP’s Top Five from the 40 Under Forty program this year. I cannot begin to tell you how refreshing and energizing it is to be a part of an amazing group of five women who are all dedicated to advancement in Pathology and Laboratory Science.

To be honest, I was a little nervous going into the meeting… What would the other honorees be like? What would they think of me? Am I going to be completely out of my league there? Well let me tell you, everyone that I met was wonderful! We discussed a variety of topics, and even tossed around an idea for future collaboration.

Yes, I could go on and on about my new friends, but I think what I want to point out is that it cannot, and should not go unnoticed that the Top 5 this year consisted of all women, all WELL deserving women at that. How were we chosen? Yes, we blogged, but don’t forget that we also submitted CVs and biographies. We wrote essays as well as recorded videos (some of us spending hours re-shooting and cringing at ourselves). Not to mention, votes were cast by a dedicated panel as well as online voters. Your 40 Under Forty, including the Top Five, came from all over the country and represent various specialties in our field.

Unfortunately, at some point I had to come down from the “girl power” high. I returned to Milwaukee and thought to myself, I wonder what the ratio of men to women is in our laboratory alone? A few short minutes later, I crunched the numbers and it was easy to see that women make up 85% of laboratory staff at our organization. The totals are inclusive of all laboratory departments and shifts as well as administrative support, Pathologists, and Directors at Children’s Hospital of Wisconsin.

It was during these thoughts on women in science and recognition, that I remembered an article I had read quite a while back. The article had discussed how historically, women occupied most of the laboratory jobs (the strange term, “lab gals” sticks out in my mind). This was thought to be the case because it was believed that women had more patience, were more detail oriented, and therefore were trained to perform the work that doctors did not want to do. At the same time, men typically occupied the higher-level decision making positions (those that required an advanced degree, PhD, and MD). I thought to myself that even today, it sure does seem that there are more women in the laboratory profession. However, we have come a long way and are seeing an increase in women being honored for their education, professional achievements, and advancements in the field. Every single lead technologist and laboratory manager at our institution as well as the CEO of our health system currently is female. Interestingly, more than HALF of the 40 Under Forty Honorees this year are highly educated women with advanced degrees!

We all know full well that more than 70% of critical medical decisions are based on laboratory results. Therefore, if the field of laboratory professionals is made up of mostly women, it appears that our attention to detail is instrumental in making some major decisions. Yes, there still may be gender gaps when comparing men to women in academia however, what once was a field dominated by the male PhDs and MDs, appears to be shifting majorly as more and more women are making their presence known in Pathology and Laboratory Science.

I applaud everyone who was honored this year as one of ASCPs 40 Under Forty. Women are the past, present, and the future of laboratory science and medicine and it brings a little extra smile to my face to know that so many well deserving women are being recognized by ASCP this year.

2015 ASCP 40 Under Forty Top Five: Amanda Wehler, Tiffany Channer, Jennifer Dawson, LeAnne Noll, and Kimberly Russell

-LeAnne Noll, BS, MB(ASCP)^CM is a molecular technologist at Children’s Hospital of Wisconsin and was recognized as one of ASCP’s Top Five from the 40 Under Forty Program in 2015.

Ammonia and Hyperammonemia

Ammonia is a small molecule that is produced as a part of normal tissue metabolism. Its formation results from the breakdown of compounds containing nitrogen, such as the amino groups in proteins and the nitrogenous bases in nucleic acids. In the tissues, ammonia is stored mainly in the form of amino acids, specifically the amino acid glutamine which has three amino groups. Normally, the body can remove excess ammonia easily via the liver pathway known as the urea cycle. This short, 4-step cyclical pathway converts two ammonia molecules into a small, water soluble urea molecule, making it able to be easily excreted in the urine. Without a functional urea cycle however, the body has no other adequate mechanism for getting rid of the ammonia that is constantly being produced by metabolism.

Liver damage or disease can disrupt the urea cycle, causing blood ammonia levels to rise. This is the most common cause of elevated ammonia in the adult population. In a pediatric patient, elevated ammonia is frequently seen as a consequence of an inborn error of metabolism (IEM). Many IEM, especially those in the urea cycle pathway, will result in elevated blood ammonia levels. In addition, in IEM causes, the ammonia concentrations may be well over 1000 µmol/L, when the normal range of ammonia is generally in the 30 – 50 µmol/L range. Elevated blood ammonia concentrations are serious because ammonia is toxic to the brain. The higher the ammonia concentration is, and the longer it stays high, the more brain damage that will occur.

Interestingly, the concentration of ammonia in the blood may not correlate with the neurological symptoms that are seen. Usually if the ammonia concentration is <100 µmol/L, the person will show no symptoms at all. Concentrations of ammonia in the 100 – 500 µmol/L range are associated with a wide variety of symptoms including: loss of appetite, vomiting, ataxia, irritability, lethargy, combativeness, sleep disorders, delusions and hallucinations. These patients may present with an initial diagnosis of altered mental status, and if there is no reason to suspect an elevated ammonia, the symptoms may lead to drug or alcohol testing. When ammonia concentrations are >500 µmol/L, cerebral edema and coma may be seen, with cytotoxic changes in the brain. Ammonia concentrations in the 1000+ µmol/L range are extremely critical and are treated aggressively with dialysis to pull the ammonia out of the system. In particular, urea cycle defects require close monitoring of ammonia and glutamine concentrations, with immediate response when they rise.

Laboratory testing for ammonia is often problematic as contamination can occur from a number of sources including atmospheric ammonia, smoking and poor venipuncture technique. In addition if the sample is not centrifuged and analyzed promptly, ammonia is formed by the continuous deamination of amino acids and the concentration increases by 20% in the first hour and up to 100% by 2 hours. Consequently samples to be tested for ammonia should be placed on ice immediately after being collected and transported to the lab for analysis as soon as possible. Many minimally elevated ammonia results are a consequence of poor sample handling. However, a truly elevated ammonia is a critical lab finding that should be addressed immediately.

Philosophical Repose

A recent episode of much-needed filing in my office uncovered some prior contributions I had written for the Journal of the Kentucky Medical Association as part of its editorial board. One of these, written over a decade ago, resonated with me. The editorial represented what at the time I had termed a “daily devotional.” How timely that I should discover and reread this as it came on the heels of several (and not uncommon) frustrating days in the office.

The article highlighted a beautiful mosaic in the lobby of the hospital where I had my practice for 20 years. It featured Maimonide’s Prayer. Maimonide was a 12^th century physician and philosopher. Here is a copy of the script:

Almighty Father of Mercy,
I begin once more my daily work,
Grant that I may be able to devote myself,
Body and soul, to Thy children who suffer from pain.
In all my efforts to heal the sick may I be filled with love for my fellow man.

One needn’t be particularly religious to understand and appreciate the very simple meaning of this prayer. It reminds us, that as laboratory professionals, we, as part of the healthcare team, ultimately need to remember that our personal daily devotion is to patient care. It is good from time to time to have a moment of philosophical repose.

I believe the next time daily events are extremely exasperating, when frustrations of practice threaten to overshadow my day, I shall have a copy of Maimonide’s Prayer close by to provide a bit of realignment and re-commitment to this professional purpose.

-Dr. Burns was a private practice pathologist, and Medical Director for the Jewish Hospital Healthcare System in Louisville, KY. for 20 years. She has practiced both surgical and clinical pathology and has been an Assistant Clinical Professor at the University of Louisville. She is currently available for consulting in Patient Blood Management and Transfusion Medicine. You can reach her at cburnspbm@gmail.com.

Body Fluid Testing

When I started my career in laboratory medicine, we tested any fluid that was handed to us, for any analyte requested by the doctor. We did this for a number of reasons that we thought were good ones including that the doctor is a medical professional who knows what he wants and needs, and that the test results will help diagnose and treat the patient. We were trying to be helpful. Along the way though, laboratory professionals have come to understand that testing like this may not provide accurate results and may be doing more harm than good.

Now days, CLIA has clearly mandated that if the manufacturer of an FDA-approved assay system has not validated that system for a specific fluid type, the lab must perform that validation before testing and reporting results on that fluid type.

This is sometimes a hard rule to explain to the medical staff who have been trained in medical school to order such things as amylase on peritoneal fluid to look for pancreatic injury, or glucose on nasal fluid drainage when a CSF leak is suspected. And these doctors often have literature references for what they wish to have measured, although in general the references are not recent. I have a three-pronged approach to the explanation I give doctors as to why I won’t analyze the sample they sent me.

First, and probably most importantly, I cannot guarantee the accuracy of the result. Matrix effects are real and a test designed for serum will not perform the same on urine. Similarly, a test designed for serum and urine will not perform the same on a pharmacy preparation or an ascitic fluid sample. The result I provide if I test that sample could very well be wrong.

Secondly, I have no way to interpret the results of the test on an un-validated fluid type. There are no established reference intervals that allow us to determine the meaning of the result we’re providing. For example, who knows how much glucose is normally present in nasal drainage? I would assume no one knows, because why would you measure it in normal nasal drainage, and for that matter, what constitutes normal nasal drainage? Thus if I test that unknown sample for the analyte requested, I’m providing a possibly inaccurate result that is uninterpretable. And the physician is going to treat the patient on the basis of that result. In most cases, the physician changes his or her mind at this point in the discussion.

However, if that isn’t enough, I bring out the big guns. The agencies under which the lab operates forbid me from analyzing this sample for this analyte unless I validate the sample fluid type in my lab using the stringent validation criteria described in CLIA. This validation would take a considerable amount of time and resources and enough patient samples to set a reference interval.

If a doctor would still like to be able to order that test on that sample type after the discussion, I request that the doctor be involved in the validation process. First of all, I will want to know that enough of these tests will subsequently be ordered that the time and effort spent to validate the test will be worth it. In addition, the doctor will need to collect sufficient numbers of that sample type to allow us to perform an adequate validation and reference interval study. Also, QC material with the same matrix as the fluid type will need to be used and may have to be made in-house as it’s generally not commercially available. Biannual proficiency testing for that fluid type will need to be performed also, with internal PT developed for it. All of these considerations mean that the number of body fluid types and analytes we have validated is small, but we do not analyze un-validated fluid types. We will often try to locate a reference lab who does analyze them for a doctor. When that fails we will try to help the doctor find an answer to his medical question through use of other, legitimate tests.

Sweat Testing

August in Texas is a good time to write a blog post about sweat. In this case though, I’m going to specifically talk about testing collected sweat samples for chloride concentration. Sweat chloride concentrations are measured in people who are suspected of having Cystic Fibrosis (CF). Because CF has classically been considered a disease of childhood, sweat chloride testing is performed almost exclusively in pediatric institutions.

CF is a disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. This is a large gene which codes for a large, transmembrane protein that acts as a chloride channel. More than 1500 mutations have been detected in the CFTR gene, not all of which are known to cause disease. Thus, even though the full gene has been sequenced, CF remains a diagnosis which is made by a combination of the presence of characteristic clinical features, or history of CF in sibling, or a positive newborn screen, PLUS identification of a disease-causing mutation in the gene or protein or laboratory evidence of chloride channel malfunction such as an elevated sweat chloride level.

Collecting a sweat sample for testing is an interesting manual process. The first step involves stimulating the sweat glands to produce sweat. This is accomplished by a process called iontophoresis, in which a sweat-gland-stimulating compound called pilocarpine is driven into the skin using a small electrical current between a set of electrodes applied to the skin. After a 5 minute stimulation, the electrodes are removed, the skin is cleaned, and the sweat that is subsequently produced in that stimulated area is collected for the next 30 minutes. The collection is either via absorption of the sweat into a piece of gauze or filter paper, or by a collection device which funnels the sweat into a small plastic tube as it’s produced. The amount of sweat collected after 30 minutes is determined by weight if gauze or filter paper is used, and by volume if the tubing is used. There is a lower acceptable limit for both cases, below which the sweat collection is insufficient (QNS) and must be repeated. The process sounds simple, however collecting a sufficient quantity of sweat can be problematic, and collecting too little may cause falsely elevated results.

After collection, the amount of chloride present in the collected sample is measured. In a normal sample, the amount of chloride present is well below the measurement range of the usual chloride ion-selective electrodes found in chemistry or blood gas instruments. For this reason, the chloride concentration in a sweat sample is most commonly measured using a method called coulometric titration in which a silver electrode placed in the sample gives off silver ions during a current flow. The silver ions complex with the chloride and precipitate as silver-chloride. This reaction continues until all the free chloride is gone, at which point a timer stops. Quantification is accomplished essentially by comparing the time necessary to complex all the patient’s chloride versus the time necessary to complex a known concentration of chloride in a standard. Calculations are performed using the time and the weight or volume of the sweat collected, among other parameters.

The entire test is very manual. Collection of appropriate sweat samples requires training and practice. In general the QNS rate – how often an adequate collection is not achieved – is carefully monitored by the lab, the CF clinic and the CF Foundation which accredits the clinic. In addition, measuring the chloride in the sweat by chloridometer is not an automated process of placing the sample on an instrument and pushing a button to go. For these reasons, the CFF recommends not performing sweat testing unless you perform a minimum number per year in order to stay proficient. In this day and age of increasing automation, sweat chloride testing remains the anomalous, old fashioned test requiring significant technologist time and expertise.