iPathology

iPod Touch 4th generation

After using a "classic" iPod for many years, I've upgraded to the new iPod Touch. This is obviously a big increment in terms of features, most importantly connectivity to the web via wifi. Calendering (via Google Calendar), email, Skype, Twitter, YouTube, blogs, news feeds, web browser, etc. are all features on this device that I previously accessed from desktop or laptop computers. And of course, it plays music and videos, downloads and plays movies from my Netflix account, and even has a rather basic camera. Many or all of these features are available on smartphones, but the iPod touch has no 2-year phone plan to subscribe to. Not a bad deal, I figured. I'll keep my old phone for now.

One feature that I found quite interesting is its ability to give my approximate location. There's no GPS chip in the device (as far as I know), but it can tell where I am, and shows me on Google Maps, by reference to local wifi hotspots. As long as the wifi transmitter is turned on, and I'm near a hotspot, it will locate me. That's pretty amazing technology when you think about it. Does it mean that Google has a map of the location of millions of wifi bases throughout the country? The world? If so, how did they collect that information? Maybe the location information was grabbed from people walking around with smartphones that have a GPS chip in addition to a wifi connection? Whatever, it's impressive.

So far, I haven't seen much that is directly relevant to the clinical labs in terms of apps for this device. Of course, any device that can connect the lab with a clinician has a lot of potential uses. If others know of useful software, I'd be interested to hear about it.

National Registry of Genetic Tests

DARK Daily Laboratory and Pathology News.

The above article is about the NIH's plan to establish a national and even international registry of laboratories that perform genetic tests and some details of those tests. There is a need for a centralized database that offers more than just the name of the test, i.e., what mutations are detected, what is the sensitivity of assays where applicable, what are the turnaround times, who certifies/accredits the labs, what are the qualifications of the lab directors, what interpretation of lab results is available, and what does a test cost? In light of the increasing expenditure on genetic testing, the last item would be of particular interest to many people.

Preparing for a Consumer-Driven Genomic Age

Preparing for a Consumer-Driven Genomic Age.

The above article is published in this week's New England Journal of Medicine. It's a very good overview of the issues that we face in exploiting the power of genomics without exploiting the consumer by offering unvalidated and essentially meaningless test results. In addition to the issues raised in the article, it's worth noting that the CLIA regulations still do not have a separate specialty called Genetics that covers the very unique technical challenges of performing testing on nucleic acids using technologies that didn't exist when the regulations came into effect nearly 20 years ago.

P4 Medicine: Predictive Preventive Personalized and Participatory

One of the best talks at the recent AACC Annual Meeting was given by Leroy Hood from the Institute for Systems Biology. His topic was P4 Medicine, a term he coined for "predictive, preventive, personalized, and participatory".

What he's describing will, I believe, have significant and exciting implications for Laboratory Medicine because the concepts are based on the idea of clinical laboratory genomic analysis for identification of disease risk alleles, blood analysis for early detection of disease by measurement of disease specific biomarkers, and interpretation of data by knowledgeable experts.

With the prospect of a $1000 genome sequence in the not-too-distant future, and rapid advances in protein analysis by mass spectrometry, it seems realistic to think that many of the technical limitations are surmountable. The question in my mind is how does one deal with the enormous amount of data from these analyses and distill it into something intelligible to physicians and patients alike?  And will patients really take an interest in modifying their lifestyle in response to new risk factors when it's so difficult for many people to adjust to well known disease risk factors today, such as smoking, diet, lack of exercise, and so on?

But back to Laboratory Medicine. What is being described as P4 Medicine is obviously very reliant on clinical laboratory analysis, and could bring about a new era for advanced Lab Medicine in specialized centers that can offer such testing.

A link to the ISB page is provided. I've highlighted (annotated) on Diigo some points I found interesting or controversial.

• Institute for Systems Biology: Predictive Preventive Personalized and Participatory - Annotated

2011 AACC Annual Meeting: Proposals Being Accepted Now

I am the chair of the 2011 American Association for Clinical Chemistry (AACC) Annual Meeting Organizing Committee. The meeting will be held in Atlanta, GA, July 24-28 2011, the venue where I first attended an AACC annual meeting over 20 years ago.

The call for proposals has gone out. Proposals are due no later than 5 p.m. EST Sept. 28th 2010. The website and instructions for proposals are at www.aacc.org/AM2011 .

Cystatin C reference material produced

At the recent AACC annual meeting in Anaheim, Dr. Anders Grubb from Lund University described the newly available cystatin C standard reference material produced in conjunction with the IFCC. The material is available for calibration of cystatin C assays (link) .

Given the wide interest in biomarkers of kidney disease, this material should be of interest to IVD manufacturers and to laboratorians who are interested in offering cystatin C testing. Cystatin C has been proposed as a good alternative to creatinine (normally used for estimated GFR calculations) for detection of renal disease, but the lack of a reference material for calibration has been problematic up to now, and relatively few commercial cystatin C assays are available at present.

Questioning the benefits of routine finger stick glucose measurements in type 2 diabetes

The New York Times recently reported on Canadian studies that suggest that routine monitoring of glucose levels by type 2 diabetic patients using test strips may have limited clinical benefits and may not be an effective use of resources. It will be interesting to see how this plays out in the U.S. with the current emphasis on evidence based medicine and the pressing need to reduce health care costs.

More on Reference Ranges

I recently referred to an editorial in the Annals of Clinical Biochemistry that outlines ways to establish reference ranges and their attendant advantages and disadvantages. The authors of an editorial in January's Clinical Chemistry (55:15-17, 2009 [subscription required]) advocate "a new way of thinking about the relationship between biomarker measures and clinical decision-making". They envisage the use of lab results to generate a prediction of risk of disease, which actually sounds a lot like existing likelihood ratios. These predictions will be based on data other than simply a lab measurement, for example, they might include the patient's family and social histories, results of imaging studies, and even the patient's desire for treatment. A result might be of the form that given the results of the lab studies, imaging, history etc. the patient has X% risk of having heart disease, cancer, etc. Certainly I agree with the assessment that traditional reference ranges have important limitations. To move beyond reference ranges to presenting the clinician with more useful data, specifically data that integrate findings from the history, physical exam, imaging, treatment desires etc. will take a lot of effort, much of which will be informatics related.

"Rainbow Drawing"

 I first came across the term "rainbow draw" quite recently. It refers to the practice of drawing one of each blood tube type from a patient without a clear understanding of which tests are going to be performed. Some tubes have anticoagulants, of which there are there are several types (e.g., heparin, EDTA, citrate), some have serum separator gels, some are just plain tubes and so on. These tubes are recognizable by the different color of their caps and so the allusion to a rainbow. We use different tubes because some assays require serum (e.g., chemistry tests), some require anticoagulated blood (e.g., complete blood counts), some require plasma (e.g., coagulation assays) and so on.

A rainbow draw is a strange approach to sample collection! Some of these tubes are quite specialized, and it's unlikely that most patients would routinely need, for example, a tube collected for analysis of heavy metals. I understand that having to re-draw a patient is time consuming and perhaps uncomfortable for the patient, but drawing one of every tube is a waste of tubes, a waste of blood, and a substitute for rational thinking about which tubes are needed for different laboratory tests, and which tests are really needed.

Reference Ranges

An interesting editorial on the topic of reference ranges can be found in the January edition of the Annals of Clinical Biochemistry (46) 1-2, 2009, which also includes a couple of interesting papers on the approaches using "healthy" populations and real patient data. The editorial writer comments on these various approaches to defining reference ranges:

1. A classic based approach is to draw samples from a well defined cohort(s) of healthy people and typically take the middle 95% of values (mean +/-2 SD). This is required if there are variations between people of different age, gender, race etc. There are limitations to this approach: Who is healthy? Should there be a separate reference range for symptomatic people? How do we define ethnicity in populations that are composed of people of mixed ethnicity? For how long are samples stable prior to analysis?

2. The use of patient data to establish reference ranges. This may seem at first sight to be an odd way to establish a reference range. Almost by definition, patients have some health problems. On the other hand, many patients do in fact have concentrations of many analytes that are within the ranges found in healthy people. If one excludes the "outlier" values, it is possible to derive a reference range that at least approximates that seen in healthy individuals. The other objection to the use of patient samples is that there may be pre-analytical variation that is not seen in carefully collected samples used solely for the purpose of establishing a reference range. The answer to this objection is that "real" patient samples are usually drawn and transported under less than ideal conditions. If there is variation seen because of pre-analytic factors, then shouldn't it be reflected in the reference range?
A big advantage of using real patient data is that large numbers of data points are available and, importantly, from groups such as children, from whom it is generally extremely difficult to get samples to do a reference range study.

So we have a "purist" approach and a "pragmatist" approach to reference range establishment. (Yes, Laboratory Medicine has its own set of disputes!) Moreover, those are not the only ways to think about lab values that require a clinical response. Some people advocate Decision Limits. In a nutshell, these are values that trigger a clinical decision (e.g., a diagnosis or a therapeutic intervention). We talked about some of these in the context of cholesterol and glucose, and how those values that have clinical significance are not evident from a simple statistical analysis of the distribution of values in health or disease. These are what I refer to as a "reference range by committee".

When it comes to reference ranges, all of these different approaches need to be considered; there is no one approach that is clearly right or wrong in all circumstances.