Showing posts sorted by date for query dementia. Sort by relevance Show all posts
Showing posts sorted by date for query dementia. Sort by relevance Show all posts

Monday, July 01, 2024

Gabapentin, Alzheimer's, fake science, and the National Library of Medicine

Gabapentin was developed as a focal seizure medication and has been found to be effective for neuropathic pain syndromes in diabetic neuropathy and postherpetic neuralgia.

Gabapentin is also widely used in America for a variety of pain syndromes including sciatica. The well done wikipedia article has a good overview of what we know about these uses. In general the benefits of gabapentin for many pain syndromes are not clear; as usual more research is needed. The evidence for nerve healing benefit is weak. I am confident we would almost never use gabapentin for chronic sciatic pain if opioids were not cursed by tolerance, dependence, dosage escalation, respiratory suppression, and diversion to recreational use. Without opioids we have acetominophen and ibuprofen and not much else.

In addition to doubts about efficacy some patients report significant persistent side-effects of somnolence and fatigue, sleep disruption, and a withdrawal syndrome that resembles benzodiazepine withdrawal. In my own life I've taken gabapentin for months for spinal stenosis* and I have not experienced either obvious benefits or problems, but I believe reports that some people have unpleasant withdrawal syndromes.

The combination of unclear benefit outside of diabetic neuropathy and idiosyncratic withdrawal syndromes would be enough to make gabapentin unpopular. Beyond that there's a significant group of chronic pain patients who feel they would do much better on opioids; they believe they are getting a defective substitute because of an excessive reaction to physician overuse of opioids in the 1990s. It's easy to see why gabapentin is not loved.

Which brings me to the point of this post. I have seen claims from the community of chronic pain patients who have legitimate suspicion about the value of gabapentin that "gabapentin causes Alzheimer's" based on an article published out of TaiwanThe association between Gabapentin or Pregabalin use and the risk of dementia: an analysis of the National Health Insurance Research Database in Taiwan. The authors conclude "Patients treated with gabapentin or pregabalin had an increased risk of dementia. Therefore, these drugs should be used with caution, particularly in susceptible individuals".

Long ago I was an academic family physician who did the tedious work of evaluating research publications. Back then I'd have had to point out that this is an outrageous conclusion to draw from data mining a health insurance data set. If all the right boxes were checked and procedures followed the most one could conclude from this type of study is that maybe there's some signal that should be researched in animal models and maybe one day in a range of increasingly expensive and complex studies. In those days that conclusion in an abstract would be the end of my interest in the publication.

Sadly, these days, we don't even have to look that deeply. We start with looking at where an article was published. Front Pharmacol is a pay-to-publish eJournal. That's why you can read their articles without paying - the authors paid for you to read it.

You can find the publishers of this article in www.frontiersin.org and read about them in a wikipedia article on Frontiers Media. Nobody, absolutely nobody, would publish in Frontiers if they could get through peer review anywhere else. Derek Lowe is the most publicly accessible writer about this class of publication, you can read two of his recent pieces here and here. The garbage output of these fake journals to qualify for academic promotion is so bad that even PRC academic centers are turning against them: "... January 2023, Zhejiang Gongshang University (浙江工商大学) in Hangzhou, China, announced it would no longer include articles published in Hindawi, MDPI, and Frontiers journals when evaluating researcher performance."

In short, in our broken modern world, we don't have to dig into the particulars of this article. We don't have to even look at the absurd abstract conclusion. All we have to know is that the authors of this article paid to get it published by an enterprise that is almost certainly fraudulent.

It's not impossible that any substance that interacts with the human body might in some way increase the risks of Alzheimer's dementia. That, I suppose, includes cosmic rays. But there's no particular reason to suspect gabapentin more than other medications. This is a bullshit result published in a bullshit journal.

So why, a reasonable person would say, was this crap indexed by the National Library of Medicine, a division of the National Institute of Health funded by the American tax payer? That's a damned good question. I can guess why the NLM is effectively promoting fraud, and I can suggest workarounds for the problems I'm guessing they have, but I honestly don't know. I am, however, angry. As you might guess. I'm sick of this academic fraud.

* I'm now post-decompression surgery. That's a story for another day.

Monday, February 20, 2023

Be afraid of ChatGPT

TL;DR: It's not that ChatGPT is miraculous, it's that cognitive science research suggests human cognition is also not miraculous.

"Those early airplanes were nothing compared to our pigeon-powered flight technology!"

https://chat.openai.com/chat - "Write a funny but profound sentence about what pigeons thought of early airplanes"

Relax

Be Afraid

ChatGPT is just a fancy autocomplete.

Much of human language generation may be a fancy autocomplete.

ChatGPT confabulates.

Humans with cognitive disabilities routinely confabulate and under enough stress most humans will confabulate. 

ChatGPT can’t do arithmetic.

IF a monitoring system can detect a question involves arithmetic or mathematics it can invoke a math system*.


UPDATE: 2 hours after writing this I read that this has been done.

ChatGPT’s knowledge base is faulty.

ChatGPT’s knowledge base is vastly larger than that of most humans and it will quickly improve.

ChatGPT doesn’t have explicit goals other than a design goal to emulate human interaction.

Other goals can be implemented.

We don’t know how to emulate the integration layer humans use to coordinate input from disparate neural networks and negotiate conflicts.

*I don't know the status of such an integration layer. It may already have been built. If not it may take years or decades -- but probably not many decades.

We can’t even get AI to drive a car, so we shouldn’t worry about this.

It’s likely that driving a car basically requires near-human cognitive abilities. The car test isn’t reassuring.

ChatGPT isn’t conscious.

Are you conscious? Tell me what consciousness is.

ChatGPT doesn’t have a soul.

Show me your soul.

Relax - I'm bad at predictions. In 1945 I would have said it was impossible, barring celestial intervention, for humanity to go 75 years without nuclear war.


See also:

  • All posts tagged as skynet
  • Scott Aaronson and the case against strong AI (2008). At that time Aaronson felt a sentient AI was sometime after 2100. Fifteen years later (Jan 2023) Scott is working for OpenAI (ChatGPT). Emphases mine: "I’m now working at one of the world’s leading AI companies ... that company has already created GPT, an AI with a good fraction of the fantastical verbal abilities shown by M3GAN in the movie ... that AI will gain many of the remaining abilities in years rather than decades, and .. my job this year—supposedly!—is to think about how to prevent this sort of AI from wreaking havoc on the world."
  • Imagining the Singularity - in 1965 (2009 post.  Mathematician I.J. Good warned of an "intelligence explosion" in 1965. "Irving John ("I.J."; "Jack") Good (9 December 1916 – 5 April 2009)[1][2] was a British statistician who worked as a cryptologist at Bletchley Park."
  • The Thoughtful Slime Mold (2008). We don't fly like bird's fly.
  • Fermi Paradox resolutions (2000)
  • Against superhuman AI: in 2019 I felt reassured.
  • Mass disability (2012) - what happens as more work is done best by non-humans. This post mentions Clark Goble, an app.net conservative I miss quite often. He died young.
  • Phishing with the post-Turing avatar (2010). I was thinking 2050 but now 2025 is more likely.
  • Rat brain flies plane (2004). I've often wondered what happened to that work.
  • Cat brain simulator (2009). "I used to say that the day we had a computer roughly as smart as a hamster would be a good day to take the family on the holiday you've always dreamed of."
  • Slouching towards Skynet (2007). Theories on the evolution of cognition often involve aspects of deception including detection and deceit.
  • IEEE Singularity Issue (2008). Widespread mockery of the Singularity idea followed.
  • Bill Joy - Why the Future Doesn't Need Us (2000). See also Wikipedia summary. I'd love to see him revisit this essay but, again, he was widely mocked.
  • Google AI in 2030? (2007) A 2007 prediction by Peter Norvig that we'd have strong AI around 2030. That ... is looking possible.
  • Google's IQ boost (2009) Not directly related to this topic but reassurance that I'm bad at prediction. Google went to shit after 2009.
  • Skynet cometh (2009). Humor.
  • Personal note - in 1979 or so John Hopfield excitedly described his work in neural networks to me. My memory is poor but I think we were outdoors at the Caltech campus. I have no recollection of why we were speaking, maybe I'd attended a talk of his. A few weeks later I incorporated his explanations into a Caltech class I taught to local high school students on Saturday mornings. Hopfield would be about 90 if he's still alive. If he's avoided dementia it would be interesting to ask him what he thinks.

Sunday, June 13, 2021

Alzheimer's and Amyloid: How even a perfect aducanumab could help some and hurt others.

Representational drift, if validated, tells us that a memory is a set of relationships, not the specific neurons that embody those relationships. This sentence might be rendered in electrons or ink, but it has the same meaning.

Reading an article about this reminded me about an old concern with drugs that aim to treat Alzheimer's by reducing amyloid accumulation in neurons. Drugs like the recently approved (and seemingly minimally effective) monoclonal medication aducanumab. The root problem is that we don't know why neurons accumulate amyloid. There's been a growing suspicion over the past few years that amyloidization might in some way be helpful.

I wrote about one way this might play out in a twitter post which I've revised here:

Representational drift reminds me of a theoretical problem with aducanumab and amyloid therapy for Alzheimer’s dementia. It begins with recognizing that we don’t know why neurons accumulate amyloid. 
Many suspect amyloid has a physiological reason to appear in neurons. Suppose, for example, amyloid is the way old crappy neurons are "retired" from forming memory relationships. Amyloidization would then be the brain equivalent of marking a SSD region as unusable. 
A system like this would have 2 kinds of bugs. It might be too aggressive or not aggressive enough. 
If the retirement mechanism is too aggressive then neurons will be amyloidized prematurely. They could have still formed useful memories, but now they're dead. The brain can only produce so many neurons so it runs out prematurely. Early dementia develops. In this case a drug that cleared amyloid could help -- as long as it wasn't too aggressive. The balance may be fine and hard to get right. 
If the retirement mechanism is too permissive then a lot of flaky neurons accumulate without much amyloid. Dementia follows from this too -- but it might look clinically quite different. In this case a drug that cleared amyloid would make the dementia worse! Even more flaky neurons would accumulate. 
Even if the balance is just write we do run out of viable neurons. Even a very healthy centenarian has only a fraction of the cognition they once had. Again, in this case, an amyloid clearing drug would make the brain worse. 
If this was the way the brain worked then an amyloid reduction drug would make some dementia worse and some better. The net effect would be quite small -- even if the medication worked perfectly and was dosed correctly. 
All speculative. Come back in 5 years and see how it turned out.

Wednesday, June 09, 2021

Why did the patient's leg swell up?

I'm a physician. Ok, so it's a very part-time practice; I'm mostly a bureaucrat trying to keep civilization together. Still I have the degree and the board status and I listen to The Curbsiders religiously. So I was really annoyed when my left leg swelled up after a modest knee injury and I didn't know why. 

It wasn't just me; neither did my physician wife nor my colleagues nor the veteran ER doc I saw nor my CrossFit Physician colleagues. Nobody had an explanation. My rheumatologist had a story though, and I'll get to that one.

Legs swell for several reasons, but the textbook ones I know of are infection, bad veins, bad lymphatics and a backed up/overloaded drainage system (heart failure, kidney failure - usually both sides same). Less common causes are muscle damage (compression syndrome, rhabdomyolysis) and (rarely) tumors. Inactivity, esp sitting, makes most things worse.

My leg wasn't infected. I didn't think my veins had obstructed but I have a family history of clot [1] so I did get an ultrasound -- all good. My muscle, heart and kidneys are all reasonable for age. I didn't think my familial [1] "osteoarthritis" (better called mysterious arthritis) had messed up my lymphatics.

So I was mystified. Why had a knee tweak turned my left (below) leg* into a painless swollen ("edematous") bag with a good half-inch of tough pitting edema over my shin? True, I have an old somewhat arthritic cartilage-depleted knee ill-suited to 150 double-under badly executed rope jumps. True, after the jumps my knee had some kind of meniscal tear and a medial ligament strain. Still, it seemed disproportionate.

I bought a cheap Amazon compression sock that worked better than I expected and I did my usual careful injury care. Meaning I did a lot of mountain and road biking and whatever CrossFit my injured knee could handle. Sitting made the leg swell, sleep and exercise with the compression sock (esp. biking) made it better.

Over the course of about 3-4 weeks the knee improved and the leg swelling mostly resolved. I still didn't know what was going on though. For a while I wondered if I'd ruptured a Baker's cyst (an arthritis thing) doing a heavy squat, but my knee effusion didn't flatten out and the volume seemed too high and persistent.

So I asked my rheumatologist. He claimed I had "reflex sympathetic dystrophy"- see also fpnotebook's great summary. Textbook RSD (now more often called "complex regional pain syndrome") is a badly understood and ill-defined disorder with a dismal prognosis. Patients I've seen with it usually have debilitating chronic pain and often have mental health issues that predate the injury. 

I had no pain that I noticed but he claimed this was not unusual in his experience. Reading the online references as a grumpy old seasoned physician I can confidently say we have no idea why things swell in RSD and that the handwaving talk about autonomic dysfunction and inflammation is mostly bullshit. I do believe there's a genetic component [1] and that the articles are correct to recommend exercise and compression. Once again my exercise addition led to a good outcome [2].

So, yeah, I'll go with RSD, which in this case translates as "it swells because you have a (somewhat rare) genetic malfunction in your injury response and the correct treatment is compression and exercise". It didn't show up in the differential of the textbooks I read, but I'll see if my friend Dr. Scott Moses will add it to his fpnotebook article on unilateral edema.

* technically and pedantically the leg is part of the lower limb below the knee but of course we use it to mean lower limb.

[1] All courtesy of my beloved mother who died age 87 of every possible medical condition (she lived on pure wilfullness). I inherited all her bad genes and, yes, she had bad leg edema. My father by contrast had only a bad back and post-90yo dementia but I inherited his back and probably the dementia disposition too. Happily my children are adopted.

[2] My back praises the Romanian deadlift.

Update 11/7/2021, wow, that's one ugly looking photo. I don't know what it was, or why it happened, but I guess I'll go with RSD plus some dubious lymphatics. My knee got better over 8-10 weeks and the edema resolved over 4 to 16 weeks. Sometimes I have trace pre-tibial edema but mostly nothing.

Update 4/12/2023: Never came back. So weird.

Sunday, February 23, 2020

Someone is hacking at my Vanguard account and Vanguard can't stop them locking me out

So this has been happening.

Every few days for the past few weeks I have received an email from Vanguard like this:

Of course it's not me. Someone (some bot most like) is running passwords against my Vanguard user name. When they fail I'm locked out.

It's not supposed to work this way. This was a common problem in the 1990s, but then security teams learned to use timeouts to reduce the risk of password attacks. The chance that anyone will guess my quite long and random unique password is infinitesimally low.

I don't know the motivation. It might be harassment or it might be someone locking out the password so they can then do a social engineering attack. Given Vanguard's approach to lockout security I think there's a good chance they'll succeed.

I've written Vanguard about the problem but the representative tells me there's nothing they can do. Their security is working as it should.

I've gone through their password reset several times. It's the usual - last 4, birthdate, name of first boss, then text a code. The usual poor quality reset process that's been routinely broken. (Of course the answers to my secret questions are also unique strings unrelated to the question.)

Since Vanguard can't fix the lockout problem I'll have to try changing my username to a random string. That will take a phone call with Vanguard and a bit of hassle but I really don't have a choice.

Although the account rep didn't know this, there's an option to restrict logon to only recognized computers. This is a bad long term solution, but I've enabled it for now.

There's no relationship between the wealth of a corporation and the quality of their security.

Update 3/1/2020: Vanguard responded:
Our Fraud Team has reviewed your profile and the incidents you described.
They have determined that your account was locked multiple times by another client with a similar user name. Fraud has recommend you re-register for account access to change your user name to avoid this situation  going forward.
In other words, not a malevolent hacker, just someone who is not very good with credential management (maybe a bit further ahead on the dementia curve than I am). Based on my username it's probably a distant relative (it's a County Leitrim Ireland name, small cohort). Vanguard should be using time delay management of password attacks, instead they're locking me out. The re-register option is a real nuisance.

For now I've configured Vanguard to only allow access from my Mac (presumably a cookie). Maybe after a few weeks of getting a different error message my confused relative will figure out they're using the wrong damned username. Then I can try returning to standard access.

Update 3/13/2020: Locked out again, so the restricted access trick didn't help. I'll undo that. I really hate to have to change my username just because Vanguard can't implement 10 yo security technology.

Update 3/28/2020: Finally logged back in again doing the usual reset. Except now I discover the "restrict logon" is implemented by a cookie -- and I cleared my Safari cookies a week or two ago. So even with the reset I can't log in. It didn't work to stop my nemesis, but it sure stopped me.

I had a chance to review Vanguard's troubleshooting pages and looks like they haven't been updated for 5-10 years. So now I have to phone them some time during their limited service hours.

Update 11/7/2021: About 6 months ago I finally quit Intuit's Quicken software. After I did that I didn't have any more Vanguard lockouts. Despite my disabling Intuit's online account feature I think they were polling and storing my Vanguard financial records. They weren't logging in successfully, but they did lockout my account.

Wednesday, August 09, 2017

CrossFit 58

I’ve had a habit around each birthday to review where I’m at with my exercise addiction. This past week was the 58th. I bought myself a Canon SL2 and Emily made me a fabulous Black Forest cake. So time for an update.

I started on the hard stuff at 53. I’d done some exercise before that - mostly road biking, nordic skiing, inline skating and other soft stuff. At 53 though, I fell into CrossFit. Actually, I was pushed. By a friend.

Four and a half years later I’m 58 and I’m still a regular at CrossFit St Paul. I average 3-4 CF workouts a week, mountain bike 1-2 times a week, and do 1-2 days a week of recovery weights or road biking or ice hockey or nordic skiing.

I’ve had soft tissue strains and pains from all of those things, but by now I’m good at rehab. I have a suite that covers hamstring/gluteal/“piriformis”, lower back strain, shoulder things, achilles stuff, chondromalacia patellae and more. “More” includes a familial arthritis syndrome affecting my hands and knees. Sooner or later that will do me in, but hydroxychloroquine seems to slow the progression. When it was diagnosed 2 years ago I figured I’d be out of CF by now, but the arthritis hasn't been a big deal yet.

I work the rehab into my workouts. It’s all one thing. Mostly I’m pretty good.

Over time I lost about 20 lbs of fat and gained about 5 lbs of muscle. Alas, at 58 I have no more muscle stem cells — those seem to go away in the 30s. I may yet get a bit stronger with practice, but not a lot. I’ve bumped up some of my weightlifting records, but recently my overhead squat and snatch have sucked. Seems the small amount of muscle I added to my shoulders came along with decreased range of shoulder motion. Gives me something else to work on.

I still can’t do consecutive double-unders, I have to mix singles and dubs. I may set a record for longest time practicing without success. It’s a coordination thing — I’ve always been clumsy but age sucks. I’ll try a fourth jump rope; some say a slower, heavier rope works better for the old. I have a rope for every occasion now.

I haven’t been able to do a muscle-up - neither bar nor ring. I work on it. Maybe someday.

I got into this to keep my formerly bad back better and because the only things that seem to slow dementia onset are sleep and exercise. I need to slow the dementia - family circumstances mean my brain has to work until about 85, when I can finally keel over and die. It’s too early to tell if it works for the dementia, but my back is pretty good.

Happily I enjoy CrossFit. I travel for work and always drop in on a CF gym — they are almost everywhere (not Hot Springs South Dakota though). I’m almost resigned to being the slowest and weakest person in the box.

It’s a living.

Friday, August 19, 2016

Crab Bucket

Terry Pratchett taught me about “crab bucket” in Unseen Academicals [1]. I don’t know if it’s a metaphor of his part of England, or if it’s unique to the Discworld.

… She reached down and picked a crab out of a bucket. As it came up it turned out that three more were hanging on to it…

… ‘Oh that’s crabs for you,’ said Verity … ‘Thick as planks the lot of them. That’s why you can keep them in a bucket without a lid. Any that tries to get out gets pulled back…’

Crab bucket, thought Glenda … That’s how it works. People from the Sisters disapproving when a girl takes the trolley bus … Practically everything me mum ever told me…

I did find a wikipedia entry for “crab mentality”, which led to a 1994 article

When teachers at Frank W. Ballou … talk about the crab bucket syndrome …

But the author doesn’t describe where the term comes from. It’s a useful concept; reminds me again how much we need to recreate anthropology.

[1] Written when Pratchett was well into his eventually terminal dementia syndrome, so while it’s very enjoyable for fans it’s not his best work.

Sunday, July 31, 2016

In defense of Donald Trump.

Trump is more racist and sexist than most 70+ yo white men. He is amoral and a con man. He may be a sociopath and probably has a narcissistic personality disorder. He is living proof that we need drug and dementia testing for presidential nominees. He is dim. Even by the standards of presidential contenders he is a nasty person.

Trump is the anti-Obama. Irrational, impulsive, thoughtless, intemperate … it’s a long list.

Trump makes paranoid H. Ross Perot look good. He exceeds the sum of the worst of GWB and Richard Nixon. I cannot think of a post WW II major party candidate this bad.

He may be worse that Cruz.

Yeah, America’s two leading contenders for the GOP nomination in 2016 were both awful. Two of the worst options in the past 100 years. That means something. It means despite our immense wealth and overall prosperity, despite our social and environmental progress, America is in trouble. Trump isn’t America’s festering abscess, he’s the fever. It’s not enough to treat the fever. We need to drain the abscess.

So where is the abscess? Why did the GOP drift further and further from reality? How did a political party that once supported science become anti-evolution and, most insanely, pro CO2 production?

I think Noah Smith has a part of the answer. The GOP had deep internal divisions and over the past 15 years the glue gave way.  The Party is broken, it has to reform.

Maybe that’s the whole story. I don’t think it is though. I think the abscess is the bottom 40% of white America. The great unwanted. The Left Behind. The new disabled. A cohort that has seen 40 years of shrinking opportunity. The economy has moved on; we don’t have vast office buildings full of thousands of people who move paper from cabinet A to cabinet B.

The odds are we’ll fix the Trump fever. Hell, even the Koch brothers favor Clinton. Obama is in the game and on top of his form. Women are starting to realize sexism is no more dead than racism.

But the abscess will still be there.

Sometimes fever is a friend. It tells you something bad is happening.

Monday, September 14, 2015

Google Trends: Across my interests some confirmation and some big surprises.

I knew Google Trends was “a thing”, but it had fallen off my radar. Until I wondered if Craigslist was going the way of Rich Text Format. That’s when I started playing with the 10 year trend lines.

I began with Craigslist and Wikipedia...

  • Craigslist is looking post-peak
  • Wikipedia looks ill, but given how embedded it is in iOS I wonder if that’s misleading.
Then I started looking at topics of special relevance to my life or interests. First I created a set of baselines to correct for decliniing interest in web search. I didn’t see any decline
  • Cancer: rock steady, slight dip in 2009, slight trend since, may reflect demographics
  • Angina: downward trend, but slight. This could reflect lessening interest in search, but it may also reflect recent data on lipid lowering agents and heart disease.
  • Exercise: pretty steady
  • Uber: just to show what something hot looks like. (Another: Bernie Sanders)
Things look pretty steady over the past 10 years, so I decided I could assume a flat baseline for my favorite topics.That’s when it got fascinating. 

Some of these findings line up with my own expectations, but there were quite a few surprises. It’s illuminating to compare Excel to Google Sheets. The Downs Syndrome collapse is a marker for a dramatic social change — the world’s biggest eugenics program — that has gotten very little public comment. I didn’t think interest in AI would be in decline, and the Facebook/Twitter curves are quite surprising.

Suddenly I feel like Hari Seldon.

I’ll be back ...

See also:

Thursday, January 01, 2015

Gene-environment interactions and the modesty of 2014 personalized medicine: Obesity, Reefer madness

Between 2007 and 2008 my work life got unusually exciting. Most of the time I work on software development in well understood aspects of medicine, but back then we were, once again, super-excited about genomics and “personalized medicine”. I made a couple of funded trips to meet with Stanford research teams maintaining genomic ontologies. I had a blast using exciting tools for navigating poorly maintained and unreliable massive web UI databases of gene-phenotype relationships.

At last we were going to realize the NIH predictions of 1994 — 10 years late, but better late then never.

Then the hammer fell. My 2008 post on schizophrenia [1] doesn’t talk about the work I was doing then, but it explains why we gave up. The disorders we cared about, schizophrenia, diabetes, lipid disorders, depression and so on, didn’t have a handful of generic recipes. Turns out there are hundreds, or thousands, or “recipes” for schizophrenia made up of environment (especially intra-uterine) and lots and lots of interacting genes. Even worse — lots of seemingly “normal” minds run on brains built with buggy genomics. Turned out “family” (genetic relative) history was a much more useful guide to predicting disease and treatment than genomic analysis — and that didn’t justify big investments.

Everything stopped, and then health care IT turned from the excitement of personalized medicine to the painful tedium of “meaningful use” and the more scientifically tractable domain of population health.

I still follow the field of course, and there has been slow but interesting progress …

Gene Linked to Obesity Hasn’t Always Been a Problem, Study Finds

… In 2007, researchers discovered that people with a common variant of FTO tend to be heavier than those without it. … Two copies of the gene bring 7 extra pounds — and increase a person’s risk of becoming obese by 50 percent.

… A new study shows that FTO became a risk only in people born after World War II.

… A variant of a gene called AKT1, for example, can raise the risk of psychosis — but only if the carrier smokes a lot of marijuana….

Small progress admittedly, but scientifically interesting. Exercise is good for most things — but we know that for most people moderate exercise [2] doesn’t add much to dietary control of weight. For people with the FTO gene though, exercise might indeed control weight. People with AKT1 are susceptible to persistent Reefer Madness — they really shouldn’t use marijuana [3]. In a related vein, there’s some evidence that the dementia protection of exercise is much stronger in the 14% of Americans with the APOE4 gene variant [4] than in APOE4 negative populations.

Progress — but darned slow. At this rate it will take decades to build what we expected before the year 2000.

- fn -

[1] Quite a good post, if I say so myself. I’d forgotten autism was once considered a variant of pediatric schizophrenia. We’re again merging both of those diagnostic categories.

[2] Extreme exercise is another matter, but one that’s rather hard to study. Though there is this recent NYT article on super-short higher intensity workouts that are to CrossFit as a snack is to a smorgasbord.

[3] Incidentally, marijuana legalization will be a boon to addiction medicine. Investors now include rehab clinics in the category of cannabis business opportunities.

[4] Why is a nasty gene so prevalent? The Wikipedia article mentions APOE4 helps with Vitamin D update — a particular problem in northern europeans. We presume it does have some survival advantage in some settings.

Saturday, June 28, 2014

Secular stagnation and the Beveridge curve - the role of frail boomer parents

American unemployment, as economist’s measure it, is back to our post-2000 “norm”. On the other hand economic growth is low; our last quarter would make a fine start to another recession. Krugman et al debate the cause of “secular stagnation” in general, and strangely low labor force participation and Beveridge Curve shift in particular.

The usual suspects are globalization and “IT” (increasingly “AI”, politely referred to as “robots”). I also suspect the dominance of the dysfunctionally powerful modern corporation plays an important role along with the related the rise of economic parasites.

Income inequality is inducing economic distortions that likely also contribute, though I think that effect is partly offset by corporate power. Slowdowns in scientific discovery and technological innovation aren’t helping.

That’s a long list - as one would expect in an eco-econ world where we have to treat economies as ecologies. It takes a lot to change a self-correcting system.

I think we can add more though - including the intersection of demographics and medicine.

Once upon a time, as “recently” (cough) as when I started medical school in 1982, parents died in their 60s and 70s. They weren’t as vigorous as today’s 70 yo’s but they weren’t particularly frail either. They ate poorly, smoked and exercised little — but that’s not enough to make someone frail. It just means that elders died relatively quickly of cancer, heart disease, and organ failure. Dementia was starting to become more common, but it wasn’t universal.

Today’s Boomer parents are different. They stopped smoking 20 or 30 years ago. They’ve had more education and they’ve benefitted from bypass surgery and far better medications for lipid and blood pressure control. Their diets are lousy and they never exercised much — but they’re not nearly as obese as we will be.

So they tend to last — into their 80s. Which is pretty much the end of the road for the human machine. So Boomer parents get to be frail - and demented. That’s an entirely different care burden than any previous generation has known - and it’s hitting the boomer peak of today’s demographic curve. As always, the burden falls largely on women.

The frailty burden is genuinely new. It’s not big enough to explain all of our economic transformation, but I think it plays a significant role.

Fortunately, there’s an obvious fix - and an investment opportunity.

I expect to see massive solar powered robotic dementia care facilities opening across the empty spaces of America — probably as extensions of Google’s data centers. With robotic caretakers, waste water recycling, soy lent green synthetic protein, and high bandwidth connections to companion AIs and VR-integrated remote children this should be quite pleasant.

I’m looking forward to my pod. (Oh, sh*t, I’m in it right no…..)

See also

[1] 

Saturday, November 30, 2013

Future Stunned: Earlier reality flux in the post-material world

When I was a child, I read Alvin Toffler's 1970 book Future Shock...

... Toffler argued that society is undergoing an enormous structural change, a revolution from an industrial society to a "super-industrial society". This change overwhelms people. He believed the accelerated rate of technological and social change left people disconnected and suffering from "shattering stress and disorientation"—future shocked...

For Toffler Future Shock came from physical changes, like a store that moved, or disposable lighters. In the 1970s we went from owning things for decades to owning them for months. We were a long way from the world of possessing a photo for seconds.

Toffler is still alive. I wonder what he thinks of Beijing.

Of course Future Shock turned out to be a relatively mild ailment. Even in China, we seem able to adapt to rapid change. Of course one day we may have more trouble; we may yet fall off the exponential curve.

I had a small taste of the latest version of Future Shock when my daughter accidentally downloaded a 1.5 GB movie and ran up a $136 AT&T data charge (which they reversed).

No, I'm not yet that old. The Future Shock didn't come because iOS 7 changed the rules about the location of our movies. Sure it's mildly disorienting that one day they were all on the phone and could be safely viewed, the next they were in the Cloud and could be viewed anywhere -- for a price. Call that Future Ouch.

The shock came because one day there were no iOS cellular settings on my iPhone (picture is from Emily's screen this morning as she still doesn't have the option):

IMG 2653

and 12 hours later there are (this is from my phone)...

Photo

Over at app.net some people have this option, some don't.  Our current theory is that my family is in the midst of an AT&T/Apple service transition. One or the other or both are newly enabling Video.app movie download to iOS 7 devices. As the feature rolls out, phones quietly gain a new setting - albeit with odd delays.

As a "happy accident" the setting defaults to On, so some AT&T customers are going to run up big data charges during the transition.

This, as you might have guessed, is Future Shock 2013. It's when people with 50 yo brains aren't sure whether they just missed seeing something, or whether it really wasn't there. It's a state of reality flux that used to start around age 80, but is steadily moving downwards. Call it Future Stunned, or less kindly, premature dementia.

It's going to get worse.

Friday, August 23, 2013

CrossFit at 54

There was a competition underway when I first visited CrossFit St Paul; it had pounding beats, tattoos, (relatively) young people. Something new for an old guy. I felt dorky, but I'm good with that. I decided if I lasted a few months I'd have something worth sharing -- one old guy's experience with the relatively new fad of high intensity workouts.

Four months and one back injury later, I'm still at it. My initial exposure was misleading; I'm usually the oldest person in my regular classes -- but often not by much. There's one guy who might be about 60; he's a lot stronger than me. I'm getting used to the beats, and even wearing short socks and semi-fashionable gym shorts -- though my shoes aren't the right tech. Contrary to my initial impression my CrossFit classes are about half women.

So why did I start with CrossFit, how has it worked for me, and what's the downside?

I started because 50 is not the the new 40. It is same as its ever been -- early old. Among other things that means getting noticeably weaker from year to year. For me it also meant calorie restriction took as much muscle as fat. I need to keep up with my kids, so I needed a lot more exercise.

No problem -- I like exercise. Not running mind you -- I've not done that since undergrad days. Lots of other stuff though - cycling, swimming, nordic skiing, hiking, hockey.

Problem is my version of 54 comes with a lot of family obligations, not to mention (still and for the moment) a job. My life is good, but rich. The only thing I can cut out now is sleep -- and I need more of that. So I needed lots more exercise, but I had only a couple of hours to spare.

So that's why I took a look at CrossFit five months ago. Group psychology to drive effort, coach driven but cheaper than a private trainer, no contract, extreme variety, enough danger to keep me awake (more on that later), lots of sessions I can fit into a packed and variable schedule, facility directly on my weekly commute, engaging franchise owners - it was a good fit.

Ok, Andrew, it was also because you kept bugging me about it.

There was one other motivation - a big one. I didn't believe the late 90s reports that significant exercise delayed dementia onset, but the evidence has continued to accumulate. I suspect it's not as beneficial in humans as it is in animal studies, and I suspect it works better for some genotypes than others -- but it's all we have. Nothing else makes much difference. I need to keep my brain until my youngest is in college - 8 years from now. So moe exercise.

I did a private "on boarding" -- extra cost but it let me work around my schedule and my health status. I learned I was even less fit than I'd expected. After I joined the regular program I experienced three phases over 4 months. In the first phase I had remarkable muscle soreness, which led me to wonder about bursts of apoptosis. In the second phase my muscles did better, but I was limited by my poor endurance. In the third phase I was able to run a few miles for the first time in 30 years, and I was no longer always the slowest or weakest participant.

Sometime around the last phase, I had my first CrossFit injury - a back strain. I'm familiar with that problem, and the rehab routine went well. I'll get back to the injury bit.

I now do CrossFit twice a week; that's about as much as I have been able to safely handle. I currently need 3 days to heal between each session. Between sessions I do my usual 2 hours of bike commuting one day a week, 1-2 hours of inline skating with my #2 son, and 40 minutes of conventional Cybex workouts with my #1 son, focusing on back, abdomen and some base arm strengthening. Time spent with #1 son is considered family duty, so the new regime added about 2 hours to my week. I made that up by spending less time writing on my blogs, I manage my writing compulsion by microblogging with Pinboard, PourOver and app.net.

After five months, despite my back strain injury, St Paul CrossFit has worked well for me. I haven't developed much visible muscle, but I'm significantly stronger and I can handle more exertion. My weight didn't decrease until about month 4, since then I dropped 8 lbs and am close to my optimal weight.

The net effect is that physically I perform and feel more like I did at 44 than at 54. That's a big difference; if I feel at 62 the way I was at 52 I'll be content.

I'm not as keen on CrossFit as some but I enjoy the people, the exercise, and the game of staying within my limits. My two sessions a week are well worth the $135/month I'm paying; I'll probably go to three times a week when ice and snow stop my bicycle commute.

Which brings me to injury risk, and Jason Kessler's CrossFit experience ...

 Why I Quit CrossFit (Jason Kessler)

On my very first day of CrossFit, I threw up. It happened my second day, too. And the third. And pretty much all of the first month...

For the next three years, I squatted, pulled, pushed ...

… CrossFit was unlike any workout I had ever done before. It throws out the traditional-health-club model of machines and isolated exercises and replaces them with a whole-body approach rooted in the real world. Calisthenics, Olympic lifting, and gymnastics combine to form a workout that emphasizes ten basic physical skills: cardiovascular and respiratory endurance, flexibility, stamina, strength, speed, coordination, power, accuracy, balance, and agility. Every day, a new workout (called the Workout of the Day, or WOD) is written on a whiteboard, and everyone in a class completes the same workout no matter what fitness level they’re at.

... Your typical CrossFitter wants to zap his fitness tank down to zero by the end of a workout. He’s not content to be just sweaty — he wants to collapse into a heap on the floor...

…. quickly amped up the frequency of my visits from three to four, then five days per week. Without even realizing it, I became that evangelizing asshole who makes people think that CrossFit is a cult...

… Not everyone gets injured to the point where he has to get knee surgery, but I did. I also developed a chronic shoulder injury that to this day, eight months after my last CrossFit workout, is still a constant reminder ... the penalty for not executing movements with perfect form, but I’ve come to believe that having perfect form 100 percent of the time is literally impossible...

Jason was lifting an awesome amount of weight but even for less ambitious athletes the injury risk is real - largely because of the focus on technique-critical Olympic style free weight lifting and on continuous improvement. At 54 I'm into managed-decline rather than improvement, but at 34 I'd have been tempted. CrossFit workouts are intense -- and I'm not sure five or even four workouts a week makes sense for most 35+ bodies.

My gray hair means I get gentle encouragement that I can use or ignore, but younger, keener people could get in trouble. I think CrossFit could do a better job of teaching early recognition of injury and ways to respond to it. Since we pay based on our use rate there is a bit of a perverse incentive at work here, but the St Paul franchise has added Yoga and other lower intensity programs that can round out 2-4 high intensity workouts.

For me the risk feels less than pickup hockey (head, knee, face, laceration) or serious downhill skiing (knees), but a bit higher than inline skating (head) or road biking (cars -> infrequent but serious injury). In other words, it's in the risk range I'm used to, even though it's higher risk than traditional gyms or high intensity Pilates. Honestly, for me, managing the risk is part of the appeal. I suspect as CrossFit evolves, however, there will be tracks that deemphasize the riskier weight maneuvers and more focus on early response to injury.

Will I still be doing CrossFit at 64? It seems unlikely, but it's not impossible. I'll let you know.

Update 9/23/2013

Still enjoying CrossFit and staying injury free, but I do wonder if our gym is a little atypical...

Getting Fit, Even if It Kills You - New York Times 12/2005

... For his first CrossFit session, he swung a 44-pound steel ball with a handle over his head and between his legs.. ... That night he went to the emergency room, where doctors told him he had rhabdomyolysis, which is caused when muscle fiber breaks down and is released into the bloodstream, poisoning the kidneys. He spent six days in intensive care.

... The short grueling sessions aren't for the weekend gym warrior. The three-days-on, one-day-rest schedule ... "Murph," a timed mile run, 100 pull-ups, 200 push-ups, 300 squats and then a second mile run. (A weighted vest is optional.)

Mr. Glassman, CrossFit's founder, does not discount his regimen's risks, even to those who are in shape and take the time to warm up their bodies before a session.

"It can kill you," he said. "I've always been completely honest about that."

... "If you find the notion of falling off the rings and breaking your neck so foreign to you, then we don't want you in our ranks," he said.

I rather doubt I'll be doing "Murph" in this life, and I like 1 day on, 2-3 days of something else. Good thing I've never run into "Coach" Glassman.

Monday, August 20, 2012

How much of America's healthcare crunch is dementia care?

US healthcare costs were 2.6 trillion in 2010; about 18% of the 2011 US economy. Of that, dementia care costs about $200 billion, or about 8% of our total health care bill.

Demographics, and our failure to prevent brain deterioration, means dementia costs will grow. Since demented patients often exhaust all personal and family financial resources, these costs will show up as medicaid expenditures.

Even so, dementia is less of a problem than I had long thought. Even if costs were to increase by another 50% over the next decade, it still wouldn't break the bank.

Faced with the facts, I'm now forced to examine my unexamined assumptions. I can now imagine why dementia might turn out to be a bit of a bargain.

Many, if not most, dementia patients no longer receive aggressive medical care. They do need hands-on care, but in the modern economy there's no lack of people reasonably happy to do that work for comparatively little money. Demented people don't eat that much, and they don't require costly ingredients or food preparation. They don't demand the latest gadgets or costly bandwidth or cutting edge architecture or modern art on the walls. They can live where land is cheap.

In many ways, demented people are cheaper to maintain than non-demented people of similar ages. Given that neither produce wealth, from an economic accounts perspective dementia might be a money-saver.

Even as our dementia population grows, increasing costs may be offset by advances in robotics and remote monitoring, and, in time, by widespread acceptance of euthanasia [1].

Of course dementia and pre-demential can bankrupt individual families, but in our income skewed economy those bankruptcies don't add up to all that many billions.

To answer my title question then, dementia care does not appear to be a uniquely large part of our healthcare crunch. Obesity, for example, may be more important.

That's too bad, because many of us have a personal interest in a business case for dementia prevention...

[1] I want my kids to have a robust financial incentive to pull the off switch on my future demented self.

Thursday, July 26, 2012

You're 50 now. It's time to start plan 0.

Ken Murray hit a nerve when he wrote "how doctors die" last November. Now he's back with Doctors Really Do Die Differently.

Briefly, physicians are relatively good at dying. Maybe we just think about it more. Certainly we have a better idea than most civilians of what medicine can do (heart transplants) and what it can't do (run an effective code after respiratory arrest, prevent dementia, etc).

So I'm thinking now about plan 0.

No, not wills and living wills and the like -- Emily and I took care of that stuff decades ago and we've redone them several times. There's still work I need to do on digital archive plans and transferring domain names, but it's manageable.

No, not contingency plans for password and account information access. (Though, come to think of it, I do need to update the danged password archive. That's getting harder these days.)

Plan 0 isn't about those things. It's about emulating Molly Thunderpaws Squirrelbane. She lived to be an old dog, maybe a bit forgetful but good company. One day she's sick with some abdominal cancer. Heartbroken we feed her high cost lamb for her last few days. Which turned out to be 340 last days. It got quite expensive, since we obviously couldn't stop the therapeutic lamb. Cheaper than vincristine though, and tastier. Finally, her legs give out, friends gathered, and the vet made a house call. Perfect.

I have a bit of time to figure out plan 0, probably 30 years or so assuming a good morbidity compression strategy [1]. First I need to get euthenasia legalized, then I need to give the kids a financial incentive to bump me off, but not too much of an incentive ...

[1] Based on family history, health habits, current health, mortality curves and assuming medical progress continues to be very slow.

Tuesday, July 10, 2012

Health care: We don't want more stuff, we want more years.

Stanford's Chad Jones and Robert Hall tell us health care spending really is different ...

Why Americans want to spend more on health care (Louis Johnston, MinnPost, 7/6/12)

... Income elasticity measures how much more of a good or service a person will buy if their income goes up by 1 percent. For most goods and services this number is less than 1; that is, if income rises then people will buy more of most goods but they will increase their purchases by less than 1 percent. 

Years of life are different. If you have a medical procedure that extends your life, then the first, second, third and however many extra years you receive are all equally valuable. So if your income rises by 1 percent, you will increase your spending on medical care by at least 1 percent, and possibly more.

Jones, along with Robert E. Hall (also of Stanford) embedded this idea in an economic model and found that it does a good job predicting the path of health care expenditures from 1950 to 2000. Further, they show that if this is true, then the share of GDP we devote to health care could easily rise to 30 percent or more over the next 50 years as people choose to spend more on health care to obtain more years of life.

Thinking about the rise in medical spending this way puts health care policy in a different light. People want to live longer, better lives, and they are willing to pay for it. They don’t want more stuff, they want more life...

Life extending [1] health care is an inexhaustible good. That's what simplistic happiness studies, like a pseudo-science [2] article claiming that $75,000 is "enough", usually miss. They implicitly assume, or indirectly measure, good health [3].

Years ago, when health care spending was a mere 12% of GDP (we're about 15% now), my partner, Dr. John H, saw no reason why it wouldn't, and shouldn't rise to a then unthinkable 15% or more. His point was that people like being healthy, and to the extent that health care works, they will want more of it.

Health care that is perceived to be effective is the ultimate growth industry.

That's why this is where we'll end up. We could do much worse.

[1] A shorthand for extending life that we care about, particularly life-years of loved ones. More years of dementia don't count, though significant disability has less impact that many imagine. I assume there's some amount of quality lifespan that would, depending on one's memory, have an income elasticity of less than one. Science fiction writers often put that at somewhere between 300 and 30,000 years.
[2] I read the published study; "Participants answered our questions as part of a larger online survey, in return for points that could be redeemed for prizes." Can you image a less representative population? Needless to say they didn't define what household income meant, yet they turned this into a NYT article.
[3] The Jimmy Johns' insultingly stupid parable of the mexican banker is a particularly egregious example. 

Saturday, May 26, 2012

Euthenasia will come to America within the next twenty years

Thirty years ago I was distressed by the NIH's relative disinterest in demential research. Anyone who could do arithmetic knew what was coming; the time for major action was 1982.

Now we have an "urgent" NIH program focusing on dementia [1] -- but it's 25 years too late. Post-boomers will face a deluge of former-people whose bodies outlast their brains. You'd call us Zombies, except that there will be a cure of sorts ...

Parent Health Care and Modern Medicine’s Obsession With Longevity -- Michael Wolff - New York Magazine

... after due consideration, I decided on my own that I plainly would never want what LTC insurance buys, and, too, that this would be a bad deal. My bet is that, even in America, even as screwed up as our health care is, we baby-boomers watching our parents’ long and agonizing deaths won’t do this to ourselves. We will surely, we must surely, find a better, cheaper, quicker, kinder way out.

Meanwhile, since, like my mother, I can’t count on someone putting a pillow over my head, I’ll be trying to work out the timing and details of a do-it-yourself exit strategy. As should we all.

Things that can't go on don't. One way or another, America will figure out how to shorten the duration of Boomer dementia. My own plan is to buy a cottage by a cliff with no railings.

[1] "Better treatments by 2025", a meaningless goal that is sure to be met. Funded with $50 million, or what modern CEOs make every four months. Wake me up when it's funded with $50 billion.

Saturday, May 19, 2012

Who were the crazy genius scientists?

Which famous scientists and/or mathematicians were also "crazy" (e.g. - far outside behavioral "norms") during their adult productive lives (excluding those, like Pauling, who became eccentric at an age where dementia is common)?

My current list is ...
  1. Newton: Perhaps autism spectrum, but he was so brilliant, and so bizarre, that he's untypable. He's outside of the human range. He may have hard mercury poisoning late in life, or perhaps a late-onset schizophrenia-like psychosis.
  2. John Nash: paranoid schizophrenic, though somewhat late-onset. His recovery is remarkable, as was Newton's -- but he was psychotic for a longer time period.
  3. Kurt Godel: schizotypal, later in life delusional beliefs with paranoid features.
  4. Nikolai Tesla: OCD, Autism spectrum?
  5. Henry Cavendish: social phobia, anxiety disorder.
  6. Boltzmann: bipolar disorder (classic)
Our classifications of mental illness are pretty weak even in normal IQ adults; this group is probably unclassifiable. Who else should be on the list?

Update: Philip K Dick wasn't quite in this group, but his late-onset pyschosis experience resembles Tesla's. Matt suggested Godel and Boltzmann. The pattern of schizotypal personality disorder behaviors with late-onset deterioration or psychosis might apply to Tesla, Newton and Godel. Botlzmann and Nash had more classic neurospychiatric disorders.

These are most extraordinary minds. It would not be surprising if they had extraordinary dysfunctions.

Update 6/7/2012: An academic opinion.

Monday, February 20, 2012

A GOP blog I can read

It hurts me to read blogs or editorials written by 2012 Republicans. Oddly enough people like Santorum don't bother me as much as the Romneys and Douthats and Friedmans [1].

Santorum doesn't cause me intellectual pain because he's logically consistent. His God has told him that Man should have Dominion over the earth, so environmental objections are the work of Satan and most Christians are thus Satan's pawns. Since his God promised no more Floods, Global Warming can't happen. He's an internally consistent Capitalochristian fundamentalist. Yes, he's crazy, but that alone doesn't bother me. Besides, he makes Romney mad, so he serves a social purpose.

Nothing here I haven't said before of course -- except recently a I found a Republican blog I can read.

Well, at least the author ran on the GOP ticket when I voted for him in 1994 (first and last time I voted that ticket). Now, however, Arne Carlson's blogger profile doesn't mention the R or G words. He probably voted for Obama last time. (The state GOP hated him in 1994 and hates him even more now.)

So maybe he's not much of a Republican by post-Reagan standards. Go back to President Ford though, and he'd have been northern GOP [2]. If America is to have a health democracy with a  reality-based GOP 2.0, he might be mainstream GOP again.

For now Arne is my token GOP voice - whatever they may call him

[1] Friedman isn't technically a Republican - yet. Given the flavor of his reasoning though, he's more than half-way there.
[2] Excepting sociosexual issues. Progress is funny. In the 1970s even Romney's current reactionary statements on Gay and Civil Rights would be unspeakably progressive, and Romney would be almost a mainstream feminist.
See also:

Tuesday, February 14, 2012

Slavery, technology, and the future of the weak

Reading 9th grade world history as an adult I read over the names of the wicked and the great. I round years to centuries, and nations to regions.

Other things catch my eye. Reading of slavery in ancient Rome and Greece, I think of India's untouchables. The theme of surplus built upon slavery runs constantly through human history, until it blends into an industrial model of market utilization of the "The Weak".

Yeah, progress happens. I'd choose a minimum wage job in Norway, or even in Minnesota, over slavery.

So what's next? In a globalized post-industrial world, does the labor of the "Weak" have sufficient value to support a life of health and balance? If it does not, if within the framework of the post-AI world 20% of the population is effectively disabled, then what do we do?

Slavery was one answer to the problem of the weak. Industrial and agricultural employment was another. If we are fortunate, we will provide a third answer.

See also: