Reference Intervals vs. Reference Change Values

If we didn’t use reference intervals (RI), how would we know whether a person is “normal” or not? Or more accurately, how would we know whether a lab test result indicated health or disease? Reference intervals have been around as long as lab tests and they help clinicians diagnose and monitor a patient’s disease state. .

Most RI are developed using a specific patient population and should be used only with that population. However, some RIs are “health-based,” such as cholesterol and vitamin D. Both these analytes have RI that indicate what amount of the analyte should be present in a healthy individual, not how much is present in your specific population of patients. In general, health-based RI can be utilized in all populations, as long as the analyte assays are commutable. Thus these type of RI are often more useful than population-based intervals.

But should we be using reference intervals at all? One problem with population-based RI is that any given individual’s values may span a range that covers only part of the population RI due to biological variability. For example, an individual’s creatinine may be 0.6 – 0.9 mg/dL regularly. Since the RI for creatinine for his population is 0.4 – 1.4 mg/dL, a value of 1.2 mg/dL would not be flagged as be abnormal. However, 1.2 mg/dL may very well be an abnormal result for this individual We need to consider using reference change values (RCV) in addition to RI.

Reference change values are calculated values that are used to assess the significance of the difference between two measurements. Essentially, a RCV is the difference that must be exceeded between two sequential results for a change to be a significant change. The calculation requires knowledge of the imprecision of the analyte assay (CVA) and the biological variation (CVI) of the analyte. The formula for calculating RCV is: RCV=21/2 · Z · (CVA2 + CVI2)1/2 , where Z is the number of standard deviations for a given probability. Luckily, labs know the imprecision of their assays and there are tables available for biological variation.

It’s very likely that neither RI nor RCV by itself is adequate for interpreting analyte results. Using both may be a better alternative, especially using RCV for monitoring disease progression or therapeutic efficacy. Flagging sequential values that exceed the RCV—and reporting this change—should be considered.

-Patti Jones

Decisions, Decisions–Part 1

I’ve been reading a book called Leadership and Medicine by Floyd D. Loop. In it, he writes about decision making and its importance in leadership in all industries. In laboratory medicine, choices must be made quick and definitively. This skill can be observed early in a technologist’s career, often even as they train during their clinical rotations. As leaders we can pinpoint the quick thinkers and those who will have what it takes to make the larger decisions once they become leaders themselves. As leaders our decisions have more impact as we work our way up the ladder until the decisions we make affect entire organizations. Decision making at the executive level can be daunting and seal your fate as a success or the figurehead to blame.

The most important decision a leader can make is choosing their team members. Selecting a team that is similar to you may not always be the smartest decision. If you surround yourself with likeminded people, you will miss information and make ill-informed decisions. Contrary thinking will bring different sides of an issue to light. It can be hard to interview—let alone hire–someone you know doesn’t think like you, but their alternative view could strengthen your team. When I interview for leadership positions one of my first questions is, “Is this your first round of candidates or have you passed on any candidates?” If they have re-posted or passed on candidates they are not afraid to wait to find a person who fits their needs.

Most people make lists for projects that need completed. Ever write down a list of decisions that need to be made and their deadline? Former CEO of The Cleveland Clinic Dr. Loop writes, “Some leaders believe that all decisions must be grand in scope. The facts are that most decision making involves small details that add up to a larger goal.”

All of these decisions are null without one thing, trust. Trust in yourself as a leader as well as trust that you are a good decision maker from the people you lead. Decision making is at the heart of any organization and as leaders we must look for team members that can complement our weaknesses and build trust as we lead. With those two in hand you will find yourself making better decisions.

-Matthew Herasuta

Lab Product Friday

Nanosphere’s motto is “advancing diagnostics through the power of nanotechnology.” While I’ve read enough science fiction to quibble with the “nanotechnology” designation, Nanosphere does seem to have a handle on rapid molecular testing. The Verigene System can analyze samples for respiratory viruses (Influenza A, Influenza B, RSV, and 2009 H1N1, to name a few), C. difficle, and gram-negative or gram-positive organisms in positive blood culture bottles.

While other rapid molecular analyzers exist for C. difficle and respiratory viruses, I’m intrigued by the blood culture analysis. Literature from the company claims that analyzing one sample using one cartridge can give you identification and resistance information for organisms commonly implicated in septicemia. With the rising prevalence of multidrug resistant bacteria such as MRSA, CRE, and Acinetobacter baumanii, getting these results almost two days faster than current methodologies would have a positive impact on patient care.

A recent study suggests that this system does what it claims to do–rapidly identify organisms and resistance patterns in positive blood cultures.

Have any of you tried this system? If so, what are your thoughts?

ASCP Annual Meeting: Empowerment and Forward Thinking

Last week, I attended subspecialty talks as well as informative sessions on policies that will affect the future and practice of pathology at the 2013 ASCP Annual Meeting in Chicago. I also attended special events such as the Keynote given by Hillary Clinton, the Raible Lecture for Residents about the “Pathology of Bliss: Searching for the Happiest Place to Work,” the Training for Residents in Genomics (TRIG) workshop,  multiple receptions, and the president’s black tie dinner. To top it off, I also presented during the poster session and saw old friends as well as made new ones.

But what I am struck by most about the myriad of experiences and conversations that I had last week is that as 21st Century physicians, we need to be forward thinking to contribute at a systems or global level. Sometimes, as Americans, we can be insulated and shortsighted, and as physicians we are not exempt. In the midst of talk of multiple technologies, often expensive and not available routinely at many institutions, focus on resident boards review sessions, and subspecialty relevant talks, it is easy to forget that we can transform the delivery of healthcare in this country and throughout the world not just by what we learn but also by what we do, especially in resource limited settings.

Currently, over 70% of diagnostic and treatment decisions are made based on the results of laboratory tests in this country.  Much needed health reform will increase coverage for all but will also place an emphasis on outcomes based compensation. Therefore, we need to build interdisciplinary interactions between lab staff, pathologists, and other healthcare providers to work on common goals, and work together to perform the “right test, for the right person, at the right time”. We just have to work smarter, not harder. Our challenge as residents is to not bury our heads in our books or go through the motions, but to see the “bigger picture.”

-Betty Chung

Equipment Procurement in Resource Limited Settings

In the developing world, equipment procurement can be a huge challenge. Funding is usually the initial major road block. In countries where many people live on $2.00 per day, Ministries of Health and local hospitals do not have large budgets to buy necessary laboratory equipment. In such situations, well-meaning donors from developed countries may be inspired to donate their gently used equipment to labs in developing countries.

While this donation is certainly well intentioned, it does not solve the problem. Equipment donations often do not come with assisted installation, a maintenance package or end-user training. While it may be possible to receive technical support from various international companies in some of the larger cities throughout Africa, outside of a major city technical support is difficult to obtain. Therefore, without a clear maintenance package as part of an equipment purchase or donation, the machine may languish uninstalled. The analyzer could also be used for a period of time before an inevitable breakdown renders it inoperative.

Equipment donations often do not come with assisted installation, a maintenance package or end-user training.

The issue of voltage differences between the U.S. and many African countries creates another challenge when it comes to equipment procurement. Equipment that is manufactured for use in the U.S. will not have the correct voltage for use in many African countries. This is certainly a problem when it comes to donations from U.S. labs. When acquiring new items it is crucial that those involved in the procurement process know the voltage needs at the laboratory site.

Once the equipment challenges have been met, the next hurdle is reagent procurement. With both donor-provided machines and those purchased by the local government, MOH, or hospital, funding must remain available for reagents in order for the lab to continue using the machine. I have seen labs with beautiful, well-maintained machines sitting unused because there was no money to purchase new reagents. Without long-term funding for reagents and other supplies, the analyzer itself is ineffectual. No matter if it is the local government, hospital or lab staff, or a donor involved in the procurement of equipment, it is vital that equipment maintenance and reagent supplies be accounted for at all times. A brand new machine can do no good if there is not money to ensure that it keeps working.

Overcoming these challenges is certainly possible, but all players involved in equipment procurement must be conscious of every aspect of the process.

-Marie Levy

Are We Approaching the Post-Antibiotic Era?

While I was out of the office last week, Maryn McKenna wrote up a few informative blog posts about the CDC’s threat report. 

The first summarizes the lengthy report (114 pages) by highlighting the top three “urgent” threats–CRE, N. gonorrhoeae, and C. difficle. She also mentions that CDC’s director Dr. Tom Frieden states “If we are not careful, we will soon be in a post-antibiotic era. And for some patients and for some microbes, we are already there.”

Another post discusses the connection between agricultural antibiotic use and bacterial resistance in humans.

As an aside, if you’re as much of an emerging disease junkie as I am, check out McKenna’s blog on a regular basis. She’s also written a book on MRSA that should be required reading for all clinical microbiologists. It’s one part history, one part science lesson, and one part cautionary tale about this bacterium.

-Kelly Swails

Thoughts Without Borders

I recently attended the ASCP Annual Meeting in Chicago and was once again energized professionally. As an ASCP Global Outreach Volunteer it was exciting for me to find so much focus on the international work being done. It was a common thread in all the general sessions, including keynote speaker Hillary Clinton, who highlighted the work of the Clinton Foundation and its partnerships in global health. There were presentations on “Pathologists Without Borders,” “Laboratorians Without Borders,” even “Diseases Without Borders.”  Well, the diseases were always without borders—but now they have unprecedented transport advantages! The meeting also hosted guests from far-away places such as Lesoto and Viet Nam, who have been working hand in hand with ASCP consultants to build their educational programs and strengthen their lab workforce for a sustainable future.

During the conference my thoughts collided with themselvesas I remember trips to African and East Asian nations, and the experiences of working with colleagues around the globe—truly a bit of “Thoughts Without Borders” for me. The relationships we build are the backbone and platform for global health improvements around the world, and so much can be accomplished with on-site work. Our technology to both perform laboratory analyses and to communicate and store data is so advanced it’s mind-boggling. Yet even with our achievements in this age of “digital everything,” there is still no substitute for a handshake, eye contact, working together face to face, enjoying cultures and language lessons over coffee, and breaking bread while sharing recipes and family stories. THAT is what makes volunteering as a consultant in international health so engaging. I, for one, hope that global health and international outreach will always include professional exchange opportunities for working together in both host countries and in ours!

Next time I’ll get back on track with some travel adventures, as promised. In the meantime, if you happen to be wandering through Chicago, go by the ASCP office and say “Howdy” to the Global Outreach Team whose work and dedication make it possible for me to do what I love and give back to this crazy profession we have chosen. And be sure to get yourself some Chicago style pizza and enjoy a bit of blues while you’re there—two things that are definitely part of our American Culture! If you need a recommendation, send me a note at bsumwalt@pacbell.net.

-Beverly Sumwalt

ASCP’s Annual Meeting Recap

If you didn’t make it to ASCP’s Annual Meeting this year in Chicago, here are just a few opportunities you missed:

-Over two hundred hours of continuing education

-An inspirational keynote address by former Secretary of State Hillary Clinton

-A chance to talk with exhibitors

-Networking with fellow laboratory professionals.

Perhaps the biggest benefit can’t be quantified or advertised. Attendance at the Annual Meeting brings with it a renewed sense of purpose. After chatting with fellow professionals, attending seminars, and learning new aspects of Laboratory Medicine, I remember why I entered this profession in the first place. When every day is filled with the uncertain realities of today’s healthcare, it’s easy to focus on the negatives. However, at the Annual Meeting, every seminar, analyzer demonstration, and luncheon is a reminder that the driving force of the profession is excellent patient care through the study and diagnosis of disease. It reaffirms the notion that each of us makes a positive difference in a patient’s life. That alone is worth the price of admission.

-Kelly Swails

How My Interactions with Lab Staff Refined My Perspective

During PGY-1, my effort was mostly focused on navigating and finding where I fit into the system that is known as residency. Having not been the most clinically oriented medical student and unfamiliar with gathering patient info from electronic medical records (we had paper charts during medical school), I initially found the task of working up a patient difficult. I was often so focused on not missing an important detail that I missed the forest and only saw the trees. But in clinical medicine, it’s most important to discern what the most relevant facts are and integrate them quickly to uncover the big picture.

Being a resident is not like being a student and we eventually have to outgrow these growing pains or get left behind. It’s no longer a situation where the consequence of not doing well only impacts oneself. The stakes are higher because patient safety is involved. I know friends who were let go from their programs, not because they were not hard working, but because they could not adapt, multi-task, and keep up the required pace.

As pathology residents, we do not often see patients and it is easy to become disconnected from them.

What really refined my outlook was when I began to interact more with the lab technicians during my hematopathology rotation. They identified patients with concerning peripheral blood smears and often asked follow-up questions to find out what happened to that particular patient. Even though they could not access medical records, they still wanted to know how that particular patient fared, even though they scanned many other patients’ smears that day. I find the same with the technicians on my current molecular pathology rotation and I look forward to these interactions each day.

As pathology residents, we do not often see patients and it is easy to become disconnected from them. The many hours grossing, putting together tumor boards and morbidity and mortality presentations, and following up on critical values and inappropriately ordered tests can leave us jaded. I find that I follow up on patients more now even after the case is signed out. I credit working more closely with our technicians for my rejuvenated interest in patients as more than a case number. So, my advice to residents out there is to interact with and learn as much as you can from your technical staff because they really do have much to offer if asked.

I’ll be at the ASCP Annual Meeting this week to present a poster and receive a resident leadership award, so next blog post, I’ll let you know how it turned out!

-Betty Chung