DNA methylation assays as epigenetic biomarkers

Quantitative comparison of DNA methylation assays for biomarker development and clinical applications

A new milestone has been achieved in Medicine. Tracking epigenetic alterations is crucial to understand a disease. However, epigenetic biomarkers are needed to assess such changes. Its precision (sensitivity-specifity) is  paramount for its clinical application. Now a group of international researchers has certified its performance (partially). Have a look at this Nature article:

Genome-wide mapping and analysis of DNA methylation has become feasible for patient cohorts with thousands of samples, and epigenome-wide association studies have been conducted for numerous biomedically relevant phenotypes. To translate relevant epigenome associations into clinically useful biomarkers, it is necessary to select a manageable set of highly informative genomic regions, to target these loci with DNA methylation assays that are sufficiently fast, cheap, robust and widely available to be useful for routine clinical diagnostics, and to confirm their predictive value in large validation cohorts.

Among its conclusions I would like to highlight three of them:

(i) Absolute DNA methylation assays are the method of choice when validating DNA methylation differences in large cohorts, and they are also an excellent technology for developing epigenetic biomarkers.

(ii) Relative DNA methylation assays are not a good replacement for absolute assays. However, experiences of scientists in the contributing laboratories suggest that carefully selected, designed and validated relative assays can cost-effectively detect minimal  races of methylated DNA against an excess of unmethylated DNA.

(iii) Global DNA methylation assays suffer from noisy data and divergent results between technologies. Locus-specific assays (possibly combined with prediction) provide a more robust alternative

That's it. Very soon will see the epigenetic biomarkers in routine clinical use. And afterwards,  epigenetic drugs and treatments. Then, we'll confirm that the promise of precision medicine is a reality. The implications for medicine as a scientific discipline and clinical decision making are huge, and specifically, healthcare organizations will need to adapt to new knowledge and technologies.

PS. Neuroepigenetics: DNA methylation and memory

Food and risk perception

Food and the Risk Society: The Power of Risk Perception

This is the main message of the book: Do not send generic messages on food and its risks, the time for segmentation has arrived,

A generic approach, involving the provision of vast amounts of information to the general public, stands a real risk of leading to information overload, bewilderment and lack of interest among mainstream consumers. A more effective approach to change consumer food buying and consumption behaviour, is to focus on segmenting the population according to their information needs, and developing information with high levels of personal relevance to specific groups of respondents who may be at greater risk than the rest of the population. Such information is more likely to create attitudinal change and subsequent behavioural change as the perceived personal relevance is high.

Is the government already prepared for the task?

Voluntary health insurance, it's role and regulation

Voluntary health insurance in Europe: Role and regulation
Voluntary health insurance in Europe: country experience

A long time has passed since WHO published a book on voluntary health insurance, just a decade (!). Therefore, there are many reasons to review again what's going on, and this is precisely what you'll find in two recent books.
Before any recommendation, it is good to have a good analysis. And the best analysis comes from reliable data. Somebody should check the published data in the book. In the case of Spain it says 10% of suplementary insurance, while it is around 16% (!) (p.50) (and it is duplicate really according to OECD classfication). And beyond that, it says that there is 3% of voluntary health insurance that is substitutive, while it is exactly 0% (!). Therefore take care. I'll not comment anything else.

Why is it useless to predict future health expenditures?

National spending on health by source for 184 countries between 2013 and 2040

The Lancet has just published a new estimate of the size of health expenditures in the future up to 2040. Too often nobody looks backward and check what predictions said before. If somebody does it, it will get a surprise for the first time, however the following ones he will convey that predictions are useless, because there are too many uncertain situations to take into account. Basically most of the hypothesis are flawed. Take this statement from the article:

Despite remarkable health gains, past health fnancing trends and relationships suggest that many low-income and lower-middle-income countries will not meet internationally set health spending targets and that spending gaps between low-income and high-income countries are unlikely to narrow unless substantive policy interventions occur. Although gains in health system efficiency can be used to make progress, current trends suggest that meaningful increases in health system resources will require concerted action.

Is there anybody that can tell me what "internationally set health spending targets" are?.  Who sets them?. If anybody wants to check what I'm saying, have a look at the cutbacks from the great recession and the estimates by OECD or EU. Everybody was saying that technology innovation and aging would boost health expenditures forever, and now we know that this is not true. Forget the article. Distrust the fortune-tellers.

Is there room for healthcare in blockchain? (2)

THE BUSINESS BLOCKCHAIN: Promise, Practice and Application of the Next Internet Technology

Last month I was saying that business strategy à la Porter required a new perspective, the platform view. Beyond that, blockchain represents a potential disruption of current business and information and communication technologies as of today.
My suggestion is to have a look at the crucial book by Mougayar on The Business Blockchain. You'll get a clear understanding that a deep transformation is in process.

Some key concepts from the book:

• How to think holistically about the blockchain as a meta technology, a business model disruptor, and legal/regulatory policies challenger.
• The 10 properties exhibited by the blockchain (beyond its most popular one, as a distributed ledger)
• Blockchains as a new Internet layer, comprised of the new breed of decentralized applications.
• The unbundling of trust and how a new form of trust inserts itself between peer-to-peer relationships, and brings a new level of transparency, trust and truth.
• The rise of New Intermediaries. Just as the Internet replaced some intermediaries, now the blockchain is replacing other intermediaries, while simultaneously creating new ones.
• Industry cases in healthcare, energy and government, including an in-depth review of financial services.
• Practical recommendations for implementing the blockchain within the enterprise.
• The blockchain as the operating system that enables decentralization, and its technological, political and societal implications.
• The birth of a crypto economy that creates its own wealth via new business models, and peer-to-peer transactional relationships between producers and consumers.
• A new flow of value, with the blockchain acting as the digital leveler that moves value across a new variety of markets.
• 47 blockchain predictions about a not-so-distant future, when blockchain technology permeates our world and creates new companies and new services.

Promising contributions to healthcare:

The theory is attractive: publish your medical record safely on the blockchain and be assured that you or an authorized person can access it anywhere in the world. That is what the government of Estonia has done—a good case of blockchain technology in healthcare. Using Guardtime’s large scale keyless data authentication, in combination with a distributed ledger, citizens carry their ID credentials which unlock access to their healthcare records in real-time. From that point forward, the blockchain ensures a clear chain of custody, and it keeps a register of anyone who touches these records, while ensuring that compliance process is maintained.

Other healthcare usages might include:

• Using a combination of multisignature processes and QR codes, we can grant specific access of our medical record or parts of it, to authorized healthcare providers.
• Sharing our patient data in the aggregate, while anonymizing it to ensure privacy is maintained. This is helpful in research, and for comparing similar cases against one another.
• Recording and time-stamping delivery of medical procedures or events, in order to reduce insurance fraud, facilitate compliance and verification of services being rendered.
• Recording the maintenance history of critical pieces of medical equipment, for example, an MRI scanner, providing a permanent audit trail.
• Carrying a secure wallet with our full electronic medical record in it, or our stored DNA, and allowing its access, in case of emergency.
• Verifying provenance on medications, to eliminate illegal drug manufacturing.
• “CaseCoins:” originating specific altcoins that create a cryptocurrency market around solving a particular disease, such as FoldingCoin, a project where participants share their processing power to help cure a disease, and get rewarded with a token asset.

Definitely, this is a key book to understand blockchain and again, there is room for healthcare. Wether the promise will become a reality, it's uncertain today.

Is there room for healthcare in blockchain?

BLOCKCHAIN REVOLUTION: How the Technology Behind Bitcoin is Changing Money, Business, and the World

Blockchain, the technology behind bitcoin, the virtual currency, could be the new tool that could change the current state of health records and healthcare information. Up to now we have been discussing about interoperability between systems. What would happen if the citizen is the owner of the information and he has all data available everywhere anytime?. This is what certain initiatives try to define right now. Something like this initiated by the physician would be the data owned by the patient:

 

We are at the begining of a great transformation. I don't now if the appropriate word is revolution. Anyway, if you are interested in the topic you may check som details here.

However if you want a deep review of whats going on in 12 critical disruptions, read chapter 6 of the book "Blockchain revolution". You'll find there the potential impact on health:

In the health care sector, professionals use digitization to manage assets and medical records, keep inventory, and handle ordering and payments for all equipment and pharmaceuticals. Today, hospitals are full of smart devices that oversee these services, but few communicate with one another or take into account the importance of privacy protection and security in direct patient care. Blockchain-enabled IoT can use emerging applications to link these services. Applications in development include monitoring and disease management (e.g., smart pills, wearable devices to track vital signs and provide feedback) and improved quality control. Imagine an artificial hip or knee that monitors itself, sends anonymized performance data to the manufacturer for design improvements, and communicates with a patient’s physician, “Time to replace me.” Technicians will be unable to use specialized equipment if they haven’t taken prerequisite steps to ensure their reliability and accuracy. New smart drugs could track themselves in clinical trials and present evidence of their effectiveness and side effects without risk of modified results.

If you are interested in innovation and want to follow the next wave, the internet of value, then you need to read such book. Definitely, there is wide room for health in blockchain.

Clinicians' wisdom of crowds

The Wisdom of Crowds of Doctors: Their Average Predictions Outperform Their Individual Ones

The book on "Wisdom of crowds" became popular claiming that  the aggregation of information in groups achieved decisions that are often better than could have been made by any single member of the group. Now in Medical Decision Making you'll find an article that applies such reasoning to clinicians. And it says:

Little research has been done on whether the average of clinicians making predictions is more accurate than the individual clinicians themselves or whether their average prediction compared favorably to statistical predictions. The purpose of the present study is to examine the predictive accuracy of the average of individual clinician predictions and to compare this average to the accuracies of individual clinicians and to a published statistical model.

And the four conclusions are:

First, it would appear that the averages of the clinicians perform better than clinicians individually. All the clinicians on their own performed with a concordance index of 0.628. However, averaging the predictions of just a pair of clinicians had better performance. Second, the performance tends to improve as more clinician predictions are averaged. Interestingly, at least in this study of a limited number of clinicians, although performance was seen to continually improve as clinicians were added, there was decreasing marginal return for increasing group sizes. Third, as the group size increased (see Figure 2), the performance of the averaged clinicians approached that of the best individual clinician (from Figure 1), suggesting that much larger clinician groups are needed for the performance of the average to be better than that of the best clinician. And fourth, even averaging all of the clinicians’ predictions was inferior to that of the statistical model.

The authors recognise their study limitations, however some insights are useful to take into account. Let's ponder on how many "second opinions" would be approppriate.

This Wednesday at Saló del Tinell in Barcelona, great concert by Capella de Ministrers on Ramon Llull,the last pilgrimage