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Thursday, February 4, 2016

"Chronomodulated therapy" - yet ANOTHER Health IT vector to track?

Interesting article from The Atlantic:
Medicine in the Fourth Dimension
In light of circadian research, prescriptions like “Take Once Daily” are terrifyingly vague.

...Set to rival the personalized medicine “revolution” in the breadth of its implications, the incorporation of circadian rhythms into our health care systems will require re-orientation on a paradigmatic scale.

The idea is that biological rhythms, daily oscillations in physiological processes, make the morning body a functionally different creature from the same body at night. There are peak times of day for each organ’s cell division and metabolism, as well as core temperature and gene expression. Moreover, our illnesses are rhythmic, and our pathogens have body clocks. It makes for a major strategic advantage over disease, and the current resistance in the medical field—a misconception that timing effects are somehow minor—is no longer tenable.

Oncology is forever chasing ways to separate the enemy within from its surrounding tissue and reduce ghastly treatment side effects. Just as each of our cells has a circadian cycle, tumor growth is rhythmic. Some lymphomas see a peak in cell division late in the evening, whereas gut lining divides 23 times as much in the early morning as it does at night. In this case, chemotherapy in the evening targets the tumor while doing away with excruciating effects on healthy tissue. The point is that distance between healthy and diseased tissue does not have to be spatial if you can separate them in time...
Yeah. But, imagine the difficulties in sorting out temporal efficacy for Rx's administered outside of controlled clinical trials or inpatient settings.
Messaging is going to be every bit as important as evidence in coming days. Because it’s not just cancer treatment that would have to be adjusted to get out of our static, 3-D mentality. The dosage of any drug is wildly approximate without a prescribed hour of administration, because all drugs undergo absorption, metabolism and elimination. And all of these processes are controlled by the circadian system—at the cellular level, the organ level, and in the body as a whole.

Even Paracetomol (Tylenol) is profoundly rhythmic in its bioactivity, and its liver toxicity. The practical limitation comes in identifying the optimal time for each patient, which may not be feasible for acute treatment but becomes critical in chronic diseases. In this light, the common prescription “Take Once Daily” becomes terrifyingly vague...
 OK, "is there an App for that?"
Text messaging helps people to remember their medication. So why don’t we do it?
Aaron Carroll, MD
...Researchers looked at all RCTs examining a mobile text messaging system to improve medication adherence in adults with chronic disorders. The main outcomes of interest were odds ratios of adherence.

They identified 16 RCTs. Five of them involved personalized messages. Half of them used two-way communication, and half sent a text message every day. Half of the interventions were 12 weeks of more.

The pooled analysis found that text messaging significantly improved medication adherence (aOR 2.1). The effect wasn’t different based on study characteristics or text messaging characteristics. Even after an adjustment for potential publication bias, the results were still statistically significant (aOR 1.7).

These are relative improvements, of course. But the authors cite literature that finds that baseline adherence rates in developing countries of people with chronic disease are about 50%. Using the odds ratio found in this study means that text messaging could be expected to increase this adherence rate to about 67.8%, or an absolute rate increase of 17.8%. That’s stunning.

There are still “short term” results. Many of them rely on self-reported adherence measures. But still… this is pretty impressive.

In the 11 studies that reported on text message acceptability, most showed moderate to high levels of satisfaction with programs. The study that used twice-daily text messaging found that only 6% of participants said the messages were intrusive and inconvenient.

This stuff works. It’s not expensive. People like it. Why aren’t we trying this more often in systems-level studies?
See also Dr. Carroll's post
Texting people actually gets them to improve their modifiable risk factors

...Researchers looked at patients with coronary heart disease being treated at a tertiary care center in Australia. They had to be older than 18 years and have one of the following: a prior myocardial infarction, coronary artery bypass graft surgery, percutaneous coronary intervention, or at least 50% stenosis in at least 1 major epicardial vessel. They were randomized to two groups. The first got “usual care” The second got usual care, but also received semi-personalized test messages which were tailored to provide advice, motivation, and information that aimed to help them change their diet, be more active, or stop smoking (if they were)...

"Chronomodulated tx," 'eh?

The other aspect, which goes more to the Omics-based "personalized medicine" idea, goes to dosage.

I lot of our quantification of things is simply rooted in the convenience arising from our arbitrary decimal number base system. Given that humans normally have two hands comprised of five digits each, we tend to round a lot of things off into 5's and 10's. (As I write, major hoopla is in the air in my Bay Area over the ostensible milepost "Superbowl 50!")

Like a lot of people in my age cohort, I'm on Lisinopril 10 mg. and Simvastatin 40 mg. Why not, e.g., "11.23 mg." and "37.68 mg." respectively? Clinically correlated ("personalized") to a raft of my vitals and bioassay metrics? (I take the recommended baby aspirin -- 81 mg. Why 81 and not "80" or "82"? And so on...)

Anyone (beyond mathematicians per se) with a programming background, who has necessarily spent any time mucking around in binary, octal, and hexadecimal, knows that number bases  -- and their associated rounded "mileposts" -- are arbitrary (you could use a numbering system of any "base"). We all sort of know this on the briefest intuitive reflection. Time? We track it down to base-10 "microseconds" and less (see, e.g., the Michael Lewis book "Flash Boys"), but then there are 60 seconds to the minute, 60 minutes to the hour, 24 hours to the day, and 365.25 days per year (adjusting for the quadrennial leap year).

"Personalized Rx dosage" factors in addition to "Chronomodulation"?

Yeah, the docs really want to have to keep up with all of that in their EHRs.


Interesting piece on the Apple "Swift Programming Language."
100 Days of Swift
Learning Apple’s new programming language
Since Apple announced Swift as the new modern language for their products, I’ve been wanting to learn it. Even though my background isn’t programming, I decided to give it a shot. A little more than a month ago, I finished my 100 Days of Swift Project...
What are some good resources to learn Swift?

I studied and read everything I could find on Swift. I also read plenty of material on programming concepts like Object-Oriented Programming and MVC Architecture. I think it’s more important to learn programming than it is to learn Swift syntax. I’ll speak more about that in the next section. In no particular order, here are some good places to start learning Swift:

  1. The Swift Programming Language by Apple: This book covers the Swift syntax. It’s also available online for people who prefer using their Web Browser. (Free)
  2. Developing iOS 8 Apps with Swift by Stanford: This is an iTunes U course taught by Paul Hegarty, he worked at NeXT with Steve Jobs. He teaches you how to build a few apps with Swift. (Free)
  3. Ray Wenderlich: This site has a huge team of talented people who make tutorials for a range of programmer levels. The free tutorials are more than enough to get started with. There’s also books and subscription only tutorials. (Free / Paid / Subscription)
  4. Design+Code by Meng To: He packs a considerable amount of material in his book. Meng teaches how to build an app from scratch using Xcode, Sketch, Swift, Spring Animation Library and more. He regularly updates the book with new material without charging previous purchasers. (Paid)
  5. Swift By Example by Brett Bukowski: This site helps you learn Swift Syntax by providing explanations for code in a simple side by side view. (Free)...
My Health IT BFF Jerome Carter, MD is now using Swift.
You Had Me at “Swift”

Some things are simply destined to happen.   I have written a few times about my multi-year journey in modern software development.   Over the last few years, I have studied software architecture, object-oriented analysis and design, discrete mathematics and workflow analysis and had a lot of fun.  Netbeans and Xcode are on my MacBook Pro, and I have discovered that I like PHP, Python, and C#.  I am also happy to report that the web application I have been working on for what seems like forever is still on schedule.

When first announced, Apple’s Swift programming language struck me as interesting, but I did not give any serious thought to using it for anything, being already occupied with the web application.  I played with it, but only in a summer romance kind of way.   Well…things change.

Swift has a few things that make it really attractive for me.  It is compiled, but acts like a scripting language.   Syntax-wise it seems very familiar, and thinking in Swift is coming easier than expected.  Going from Python and PHP to Swift is not the least bit jarring.  Even better, all of the OOP that I learned–patterns, interfaces, closures—is readily usable with Swift...
Go to, keyword search on "Swift." Bring a Snickers, you're gonna be a while.

From the Apple iBook:
About Swift
Swift is a new programming language for iOS, OS X, watchOS, and tvOS apps that builds on the best of C and Objective-C, without the constraints of C compatibility. Swift adopts safe programming patterns and adds modern features to make programming easier, more flexible, and more fun. Swift’s clean slate, backed by the mature and much-loved Cocoa and Cocoa Touch frameworks, is an opportunity to reimagine how software development works.

Swift has been years in the making. Apple laid the foundation for Swift by advancing our existing compiler, debugger, and framework infrastructure. We simplified memory management with Automatic Reference Counting (ARC). Our framework stack, built on the solid base of Foundation and Cocoa, has been modernized and standardized throughout. Objective-C itself has evolved to support blocks, collection literals, and modules, enabling framework adoption of modern language technologies without disruption. Thanks to this groundwork, we can now introduce a new language for the future of Apple software development...
Swift is friendly to new programmers. It is the first industrial-quality systems programming language that is as expressive and enjoyable as a scripting language. It supports playgrounds, an innovative feature that allows programmers to experiment with Swift code and see the results immediately, without the overhead of building and running an app...
Note that it supports OS X, the Apple desktop/laptop OS (which is my platform), so it wouldn't be just limited to "mHealth" apps.


Big Pharma’s big push to get patients to take their meds

Drug companies around the globe are spending big to push patients to take their pills.

The pharma industry loses tens of billions in worldwide sales each year when patients don’t fill, or refill, their prescriptions.

So drug makers from London to Tokyo to Cambridge, Mass., are pouring money into programs aimed at cajoling — or nagging — patients to take every last pill their doctors prescribe. The companies are investing in smart pills that will send alerts when they haven’t been swallowed at the prescribed time. They’re subsidizing gift cards to thank patients who remember to refill. They’re paying patients to go on talk circuits to tout the virtues of taking medication properly.

They’re even lobbying the federal government for permission to pay third parties, such as pharmacists, to encourage patients to take their pills.

Drug companies say these investments are focused on improving patients’ health. “We’re not pushing pills here, we’re pushing adherence,” said Joel White, president of the Council for Affordable Health Coverage, an advocacy group that works with the industry.

But Matt Lamkin, an assistant professor at the University of Tulsa College of Law who’s studied the issue, sees another motive.

Pharma companies have the sense “that they are leaving billions on the table” when medicine isn’t taken and prescriptions aren’t filled, Lamkin said. The push to improve adherence, he said, “reframes the goal of boosting sales as a goal of public service”...

More to come...

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