Expensive Doesn’t Always Mean Better: Looking for Ways to Keep Medical Costs Down

A candle flickers. Steam from a loaf of freshly baked bread entwines with the candle smoke like ballroom dancers. I look at the wine list. A loud thud echoes throughout the intimate dining establishment as my jaw hits the floor. One bottle of wine commands a price tag comparable to three times my salary from my first job after college.

I pondered if this expensive wine was truly that superior. I am not the first to ask this question: Numerous others have posed it. Blind taste tests with wine experts are arranged, and a humble wine often prevails over the expensive one (Bell, 2012). In the tests, tasters had used metrics such as cost, winemaker labels or let personal expectations or biases sway their judgement.

These metrics are not only used in assessing wine quality, but also the quality of medical care. The newer, more expensive or fancier the technique, the more effective an intervention must be! Right? But, like the expensive wine, this is not always the truth. Recently, Consumer Reports found that primary-care doctor groups can provide high quality care for a lower cost compared to other groups involved in the analysis (Consumer Reports, 2012).

With healthcare costs sky rocketing and becoming too expensive for many people (even for those with insurance), the topic of cost-conscious care is an imperative one. In an article pertaining to medical waste, newly minted doctors tend to embrace the newest technology, but this technology tends to be pricey (Knowledge@Wharton, 2016). Most of these very same doctors also don’t receive formal training in cost-conscious care. Fortunately, many (but not all) residency programs are incorporating programs pertaining to cost-conscious care (Knowledge@Wharton, 2016).

Aside from learned habits driving the overboard use of unnecessary tests and treatments, fear of litigation can be another driver (Knowledge@Wharton, 2016). While improvements in training or changes to litigation policies may change how doctors approach medicine, improving diagnostic tests or diagnostic protocols may be another alternative that can reduce cost without sacrificing quality. On paper, this sounds achievable through initiatives set forth by the precision medicine movement (Personalized Medicine Coalition, 2017).

Recently, a physical exam regimen highlighted in Sciencemag and offered by Health Nucleus appears to be taking the cost saving opportunities offered by precision medicine in the opposite direction. For a mere $25,000 (This is definitely more than my salary from my first job.), the company offers a medical exam that includes full body magnetic resonance imaging, highly detailed imagery of how well the heart moves blood, other tests that look at heart function, sequencing of the bacteria in the gut, analysis of the metabolites found in the body, genomic sequencing, tests for brain function, and more (Cross, 2017; Health Nucleus, 2017).

A description of the “experience” certainly makes one feel that they are receiving state-of-the-art medical care, but at a high cost. At this price, many insurance companies are not likely to rapidly adopt this type of care. A “bargain package” exists, but costs $7,500 (Cross, 2017). It is doubtful that even Cadillac insurance policies will cover this “bargain” testing.

These expensive diagnostic packages show promise in catching problems early (Perkins et al., 2017), but can researchers produce a diagnostic test that can yield just as comprehensive medical insights at a lower cost? If so, would doctors, patients, and insurance companies readily adopt cheaper, but highly effective tests? Would these lower-cost diagnostics be judged as equivalent or superior to more expensive options? These questions are tougher than deciding which wine to pair with my evening meal. Maybe a blinded assessment is in order?

References

Bell, K. K. (2012). Is There Really A Taste Difference Between Cheap and Expensive Wines? Forbes. Retrieved from https://www.forbes.com/sites/katiebell/2012/07/09/is-there-really-a-taste-difference-between-cheap-and-expensive-wines/#2c42b7253ae2

Cross, R. (2017, May 12) This $25,000 physical has found some ‘serious’ health problems.

Others say it has serious problems. Retrieved from http://www.sciencemag.org/news/2017/05/25000-physical-has-found-some-serious-health-problems-others-say-it-has-serious

Health Nucleus (2017, May) Retrieved from https://www.healthnucleus.com/clinical-tests-and-imaging.

Medical care cost vs. quality: You don’t have to pay the highest prices to get quality care.

Consumer Reports (2012, October). Retrieved from http://www.consumerreports.org/cro/magazine/2012/10/when-costlier-medical-care-isn-t-better/index.htm

Medical Waste: Why American Health Care Is So Expensive. Knowledge@Wharton (2016,

August 18). Retrieved from http://knowledge.wharton.upenn.edu/article/medical-waste-american-health-care-expensive/

Perkins, B. A., Caskey, C. T., Brar, P., Dec, E., Karow, D., Kahn, A., . . . Venter, J. C. (2017). Precision Medicine Screening Using Whole Genome Sequencing And Advanced Imaging To Identify Disease Risk In Adults. bioRxiv. doi:10.1101/133538

The Personalized Medicine Report 2017 Opportunity, Challenges, and the Future. Personalized

Medicine Coalition (2017). Retrieved from http://www.personalizedmedicinecoalition.org/Userfiles/PMC-Corporate/file/The-Personalized-Medicine-Report1.pdf

More Than Meets The Eye: The Growing Complexity Of Genomics

I’m mystified. It sounded so easy on paper and more accurate than gazing into a crystal ball to see what my future has in store. I only had to give a sample and let the experts decipher my future encased within my genetic code. Yet, science indicates that forecasting with the genetic code may be no more accurate than gazing into a crystal ball. Let me explain…

First, our genetics are only predictive. Just because we carry a gene does not mean that it is being actively used by our bodies. It could just be going along for the ride or be negated by external factors.

Second, many of us (if not all) are walking around with a smorgasbord of genomes. Evidence exists that people can have different genomes in different parts of their body. The acquisition of multiple genomes can happen in the early days in the womb between twins (Boklage, 2006), between mother and fetus (Boddy, Fortunato, Wilson Sayres, & Aktipis, 2015; Stevens, 2016) or because an embryonic cell develops a mutation that gets perpetuated to various parts of the body (but not the entire body) (Lupski, 2013). Also, genomes can be picked up from other people, such as via a bone marrow transplantation (Hung et al., 2009). As we age, mutations can occur in localized parts of the body too, which can contribute to cancer or age-related issues (Aguilera & Garcia-Muse, 2013). Pending the location that the sample was taken from, one can obtain very different genetic test results from the same person!

Third, the procurement of the genetic knowledge could have been compromised. It is not uncommon for samples to pick up mutations during the sequencing of the DNA, which were not present in the original sample (Chen, Liu, Evans, & Ettwiller, 2017).  Hence, the resulting data set has become damaged. In a recent publication, it was found that 41% of the 1000 Genomes project and 73% of The Cancer Genome Atlas data sets showed damage (Chen et al., 2017). This can play significant havoc when inferring from the data sets or determining a course of medical treatment based on damaged data sets.

From sequencing our genetic material, we must step aside and ask ourselves what it is that we want to learn. If it is to see that we are 10% (insert favorite ethnicity here), then wonderful. If it is to glean serious medical information, we must remember that the information is only predictive, not absolute and could be an incomplete picture of our multigenome. It is also probable that an error occurred during the DNA sequencing, and does not truly reflect a change in the sequence of the gene in question. To complement genetic testing, additional parameters that may glean more insight about what is actively going on our bodies must be measured too.

References

Aguilera, A., & Garcia-Muse, T. (2013). Causes of genome instability. Annu Rev Genet, 47, 1-32. doi:10.1146/annurev-genet-111212-133232

Boddy, A. M., Fortunato, A., Wilson Sayres, M., & Aktipis, A. (2015). Fetal microchimerism and maternal health: a review and evolutionary analysis of cooperation and conflict beyond the womb. Bioessays, 37(10), 1106-1118. doi:10.1002/bies.201500059

Boklage, C. E. (2006). Embryogenesis of chimeras, twins and anterior midline asymmetries. Hum Reprod, 21(3), 579-591. doi:10.1093/humrep/dei370

Chen, L., Liu, P., Evans, T. C., Jr., & Ettwiller, L. M. (2017). DNA damage is a pervasive cause of sequencing errors, directly confounding variant identification. Science, 355(6326), 752-756. doi:10.1126/science.aai8690

Hung, E. C., Shing, T. K., Chim, S. S., Yeung, P. C., Chan, R. W., Chik, K. W., . . . Lo, Y. M. (2009). Presence of donor-derived DNA and cells in the urine of sex-mismatched hematopoietic stem cell transplant recipients: implication for the transrenal hypothesis. Clin Chem, 55(4), 715-722. doi:10.1373/clinchem.2008.113530

Lupski, J. R. (2013). Genetics. Genome mosaicism–one human, multiple genomes. Science, 341(6144), 358-359. doi:10.1126/science.1239503

Stevens, A. M. (2016). Maternal microchimerism in health and disease. Best Pract Res Clin Obstet Gynaecol, 31, 121-130. doi:10.1016/j.bpobgyn.2015.08.005

Regeneration Powers Activated! Regrowing the Liver from Stem Cells

“Form of rhino! Form of tidal wave!” The Wonder Twins from the TV show, Super Friends, fascinated me as a small child. With a simple uttered phrase the twins could transform into a rhino surfing a tidal wave. The hitch to their power was that it took both to transform. The adult science me finds this fact very reminiscent of stem cells that rely on communications from neighboring cells to transform into a specific cell type.

What is the power phrase uttered to adjacent stem cells? Do the cells require physical contact like the Wonder Twins to transform? To answer these questions, Asai and colleagues investigated the requirements for stem cells to transform into the form of a liver (Asai et al., 2017). They tested if the cells had to contact one another to initiate transformation, the key requirement for the Wonder Twins. In a special chamber, the group placed different types of stem cells. They found that while the stem cells could differentiate into liver cells, they could not fully form a liver-like structure unless they touched. To understand the power phrases uttered by stem cells, Asai and colleagues used the SOMAscan assay to tease out the communications between stem cells and their neighbors to transform into a liver. They found that the power phrases, which consisted of protein signals, changed depending on which types of cells were present.

This work is a large step forward in understanding the mechanisms employed by the body to regenerate the liver. These insights will no doubt will be invaluable to the research and medical community who seek to understand the secrets of the Wonder Stem Cells.

References

Asai, A., Aihara, E., Watson, C., Mourya, R., Mizuochi, T., Shivakumar, P., . . . Bezerra, J. A. (2017). Paracrine signals regulate human liver organoid maturation from induced pluripotent stem cells. Development, 144(6), 1056-1064. doi:10.1242/dev.142794

Moving Beyond Potential

Gripping a steering wheel sheathed in supple leather and driving down a winding road in a luxury car with ultra-responsive handling and superb performance… What could be more fun or exhilarating? Now, imagine if we swapped out the engine with a hamster and its wheel. The very same drive would not be as fun. Clearly, what goes on under the hood of the car is as important as the shining exterior and trimmings.

The SOMAscan® assay, like a fine luxury car, relies upon superb components to provide the customer with what they want—accurate measurement of relative protein levels in a biological sample. SomaLogic scientists finely craft each of these components, known as SOMAmers® (Slow Off-rate Modified Aptamer), to bind a specific target protein. The quality of each SOMAmer is rigorously assessed to ensure that it binds its target, and thus gives each customer exquisite data.

To check the specificity, each SOMAmer is tested for cross-reactivity with commercially available proteins that are similar to the original target. Scientists assess the strength of any off-target interactions, and if possible gauge the SOMAmer’s capabilities of engaging its target in plasma.

As is true of all high-performance vehicles, occasionally a flaw arises. If a SOMAmer binds strongly both to the original target and to very similar proteins, a redesign of the SOMAmer is initiated. After the SOMAmer engineers give the go ahead, the new SOMAmer is added to the next version of the SOMAscan assay.

Recently the SOMAmer engineers evaluated the entire SOMAmer fleet in the current SOMAscan assay. They observed that the vast majority of the SOMAmers bound specifically to their target. Also, a small fraction of the SOMAmers bound to  related proteins with a similar affinity to the original target protein or weakly. Complete information is available in a newly released White Paper.

SomaLogic is committed to ensuring the accuracy of its core technology by giving unequalled attention to the design, quality and performance of the SOMAmer reagents at the heart of the SOMAscan assay. Knowing the quality of the components under the hood gives us great confidence in where the whole vehicle takes us.

Hot Proteins: Intrinsically Disordered Proteins – A True Source of Super Powers

Mutant spider bites, exposure to radiation, freakish lab accidents, huge sums of wealth or just innate abilities give rise to figures that young and old adore. Super heroes! Their stories can sound just as fantastic as their powers. What if I were to tell you that some fantastic powers are real and transferable? Would you believe me?

On a third planet revolving about a yellow sun resides a being possessing the ultimate defenses. This entity has been hurled into the vacuum of space or abandoned in the driest of places only to survive (Boothby et al., 2017; Jonsson, Rabbow, Schill, Harms-Ringdahl, & Rettberg, 2008). No matter what the “evil” scientists can think of the “hero” thwarts their attempts and survives. Who is this remarkable protagonist? It is the lowly water bear (a.k.a. Tardigrades).

Poked and prodded for centuries, the mighty water bear finally revealed a source of its power to a team of scientists (Boothby et al., 2017). The secret lay within the water bear’s tardigrade-specific intrinsically disordered proteins, which lack a rigid structure and resemble spaghetti. Upon the water bear’s exposure to dry conditions, these proteins weave around things within the cells, essentially freezing everything in place. This act places the water bear in a suspended animation-like state. The water bear can survive in this state for years if not decades, until favorable conditions present themselves.

With the source of the power identified, the scientists transferred the formidable water bear’s power (i.e., they inserted the gene) into their usual lab minions, yeast and bacteria. The transfer was successful: The bacteria and yeast recipients could now withstand the harsh dry conditions too.

Not as exciting as lasers coming out eyeballs or leaping tall buildings in a single bound, the water bear’s transferable superpower still holds potential for helping mankind (Boothby et al., 2017). For example, the technology could help feed the masses through the engineering of drought-tolerant crops. It could also prolong the shelf-life of life-saving medicines and research supplies.

Only one more question remains regarding the superhero water bear: What would its costume look like?

References

Boothby, T. C., Tapia, H., Brozena, A. H., Piszkiewicz, S., Smith, A. E., Giovannini, I., . . . Goldstein, B. (2017). Tardigrades Use Intrinsically Disordered Proteins to Survive Desiccation. Mol Cell, 65(6), 975-984 e975. doi:10.1016/j.molcel.2017.02.018

Jonsson, K. I., Rabbow, E., Schill, R. O., Harms-Ringdahl, M., & Rettberg, P. (2008). Tardigrades survive exposure to space in low Earth orbit. Curr Biol, 18(17), R729-R731. doi:10.1016/j.cub.2008.06.048

Goodbye Poke, Hello Pee: Alternatives to Plasma for Heart Disease Diagnosis

I admit it: The sight of needles gives me the shivers. The moment the doc requests a blood sample, I want to hightail it to the next state over. And I am not alone in this viewpoint. Many people despise needles. This apprehension can be bad enough that people forgo medical treatment just to avoid the poke.

How nice would it be if lab samples could be collected without involving pain? Happily, this idea is becoming a reality.

Researchers at SomaLogic and the University of California San Francisco have sought to minimize the use of the dreaded needles by utilizing urine instead of plasma to assess heart health (Hraha et al., 2016). When arteries start to harden (arteriosclerosis), changes occur throughout the body, even in kidneys. And certain changes in the kidneys could potentially be observed through fluctuations in protein signatures in urine.

With access to urine and plasma samples from people with stable coronary heart disease, the researchers began their quest. To identify potential biomarkers, they used a version of the SOMAscan® assay that measured 4316 protein concentrations simultaneously. These measurements were compiled with the patients’ medical histories to yield a panel of markers that could predict an oncoming cardiovascular event. The panel performance for urine samples was comparable to a panel developed for plasma, which itself already performed better than standard prediction methods (Ganz et al., 2016).

Jubilation! It is foreseeable that urine collection can replace blood collection in the near future, helping ease people’s minds. It may make them more inclined to go to the doc and not forgo medical treatment.

References

Ganz, P., Heidecker, B., Hveem, K., Jonasson, C., Kato, S., Segal, M. R., . . . Williams, S. A. (2016). Development and Validation of a Protein-Based Risk Score for Cardiovascular Outcomes Among Patients With Stable Coronary Heart Disease. JAMA, 315(23), 2532-2541. doi:10.1001/jama.2016.5951

Hraha, T., DeLisle R., Ash, J., Ostroff R., Williams S., Ganz P. (2016, November). Urinary Proteome and Its Application to Predict Cardiovascular Risk in Patients with Stable Coronary Heart Disease. Poster session presented at American Heart Association Scientific Sessions, New Orleans, LA.