Saturday, February 17, 2018

Notes on managing a canine biliary system clearance disorder (intrahepatic cholestatic liver disease).

I was doing a bit of personal research today that might be of interest to a few others, so sharing here.

Kateva, of Kateva.org fame,  is 12 years old. Since she was about 9 she’s had liver enzyme elevation on her routine vet exams. In early 2017 she had intermittent vomiting — which is not unusual among dogs. A month or two later she became jaundiced (yellow sclera) and very ill. She was found to have obstructive jaundice, likely chronic, with a very large gall bladder. Post cholecystectomy she developed pancreatitis. She had 3 paws in the grave when a combination of Emily’s diligent home nursing [6] and oral ursodiol (ursodeoxycholic acid - aka UCDA, Actigall) pulled her back. [1].

As best we can tell, without a liver biopsy (risk, $, uncertain benefit), Kateva has a disorder of hepatic bile clearance. These “intrahepatic cholestatic liver diseases” have been increasingly recognized in humans over the past few decades. The ones we’ve named include primary biliary cholangitis [2], primary sclerosing cholangitis, granulomatous liver disease, a host of rare genetic disorders and more familiar things like hepatitis. When one considers how tricky it is to produce bile and clear it through the liver into the bowels it’s likely there are many currently unrecognized varieties of bile clearance disorders.

Many of the intrahepatic bile excretion disorders respond to ursodiol. I recall use of it to dissolve gallstones in the 1980s (with laporoscopic surgery this became less valuable), it has been used in humans for primary biliary cirrhosis since 1996 [3]. Ursodiol has pretty clear short term benefit but we don’t know how much it changes longterm outcomes. Within a few years of use in humans it was tried in dogs and cats, this 2011 discussion is pretty good.

I liked this description of the mechanism of action …

Ursodiol … is a naturally occurring bile acid that is a minor fraction of the bile acid pool in humans, but a major fraction in bears and other hibernating animals.  Ursodeoxycholic acid is more water soluble (hydrophilic) than cholic or chenodeoxycholic acid and is less inherently toxic to cells.  When given orally, ursodeoxycholic acid becomes a major component of the bile acid pool, the proportion rising from <2% to as much as 65%.  By replacing the hydrophobic or more toxic bile acids with ursodiol, the toxic effects of cholestasis are ameliorated …  Ursodiol was approved for dissolution of gallstones in 1987 and as a therapy of primary biliary cirrhosis in 1996. 

Kateva had a good year but she’s slowing now. I think without the liver diseases she’d be early old age, but either the underlying liver disorder is worsening or she’s moved on to liver failure or a malignancy … or some other disorder. Old dogs, like old people, usually have a few things going on.

At her age both cost and the least-misery principle limit what we’re likely to inflict on her. Obeticholic acid (Ocaliva) is a new and fantastically expensive alternative to Ursodiol — too costly to consider given limited added benefit. Colchicine is used, but it probably doesn’t do much and it’s nasty to take. Investigational drugs are often prohibitively expensive but a veterinary formulation of budenoside (a steroid that disproportionately acts on the liver) and fenofibrate [5] might be affordable.

I wrote this post to help think about what we might do for Kat. I think we could push her ursodiol and, if we can get an affordable veterinary formulation, we might try the budenoside. Or we could spend money on things she might like better, like steak [7].

- fn -

[1] The surgery and ultrasound were costly, but the truly expensive parts were all the things that intersect with human medicine — lab tests, intravenous fluids, medications, and the like. For better or worse we had some resources, so the limit was her misery. We were close to that. The longterm ursediol trial was an informed hail mary pass by my wife and I with veterinarian support.

[2] Thought to be due to “environmental trigger(s) acting on a genetically susceptible individual”.  I’m sure everyone in this field is now wondering if PBC is a CHIP (clonal hematopoiesis of indeterminate potential) disorder. We really don’t know what causes it. Immune system dysfunction seems a contributor but it’s suspicious how ineffective immune suppressants have been. I wouldn’t be shocked if there were a genetic disorder in bile formation though.

[3] With veterinary compounding it’s not cheap, but more affordable than most specialty human medications.

[4] Ref removed, but consulted UpToDate often in this writing.

[5] Curiously fenofibrate drug information lists primary biliary cholangitis as a contraindication!

[6] Emily is an excellent physician, but she also has a knack for nursing.

[7] In the last few years I’ve done end-of-life management for two parents (mine), three gerbils (Kangaroo, Adric, and Pipsqueak), and now a dog. All of the considerations were very similar though budgets varied. The parents were the easiest decisions. The gerbil and dog decisions were much harder.

Sunday, January 28, 2018

Arthritis update (personal note)

My familial arthritis showed up in one finger a few years ago, but in December of 2015 it became a bigger deal [1]. It looked like an early and fast moving symmetric osteoarthritis (OA), but then so did my mother’s before it morphed into something like RA (which ate lungs, joints, etc). OA is really a junk drawer diagnosis so I ended up calling it “familial arthritis”.

After a bit of personal research I ended up with an eclectic rheumatologist who suggested hydroxychloroquine (HCQ). This is a popular Lupus and RA med that started life as an antimalarial. It’s generally well tolerated with one minor side-effect — you can lose your vision. [2]

HCQ has been since tested experimentally in osteoarthritis — and it didn’t seem to do anything. [3] It did work for my mother’s RA though (where it is known to work), and her disease started out looking like mine …

So I’ve been on the HCQ for about two years.

Has it worked?

There’s no way to know, I can only present circumstantial evidence for one person. I have no idea what the disease would have done without treatment.

The joint deformity has not progressed much. To track joint changes I bought a ring sizing set and I use it to measure a selection of PIP (small, distal finger joint) and PIP (join in mid finger) sizes. There hasn’t been much change in joint deformity over the past two years; interestingly the worst measurements were the first set. That’s probably measurement error or some initial soft tissue swelling that’s diminished. 

I don’t have any finger joint redness or pain any more. Sometimes I forget to take the HCQ and I imagine I have some hand stiffness and joint aches — but that seems too fast to be a med effect. I think it’s my imagination. (Though we don’t have a good story for how HCQ works, so who knows.)

My knees aren’t worse; they are better than they were before I started the HCQ. I still do 230 lb CrossFit deep back squats. (I’m a wimp. Average strong guys do well over 350 lb.)

And, yes, I’m still doing the CrossFit. The rheumatologist approves. I thought I’d have to take up underwater hockey instead but I put that one off for now. 

It’s only been two years though. I’ll be more impressed if this is still true in two more years.

- fn -

[1] When I search the blog I see a few prior posts on knee and wrist exercise related aches that were, in retrospect, part of the arthritis.

[2] There are eye exams to try to spot this early, but we know in animal models that the chorea disease progresses for some time after the medication stops. We don’t know the real frequency of this complication — there’s at least a 1/20 chance I’ll get it.

[3] OA, like autism and schizophrenia, is an ill defined collection of things that’s damnably hard to study.

Wednesday, January 24, 2018

Scientific American forgot to tell me how to activate my digital subscription. Here's how.

When I renewed Scientific American last September I had a “deal” that included 1 or 2 freebies and digital service for $40. (Today I’d use Amazon — $35, much easier to manage, great subscription manager, etc).

The magazine eventually showed up but not the free extra book/special edition and not the digital service. Maybe there was an email that went into my spam filter, but I have gotten other email from them.

Turns out I had a digital service all along. I went to their customer service site and followed a link to manage my subscription account. From there I saw a link to activate digital service. That worked.

Now I have to figure out what happened to the freebies.

Sunday, January 21, 2018

Year one of post-imperial America

The Berlin Wall fell on November 9, 1989. That was the end of Russia’s Empire, the end of the USSR. I was 30 years old. I may still have a newspaper from that day.

When did America’s empire end? It’s not so clear. Was it 9/11/2001 when the towers fell? Was it 3/20/2003 when the US split from its NATO allies and invaded Iraq?

Historians will decide, but I think most will settle on the election of Donald Trump on November 8, 2016, 27 years after the fall of the USSR. The symmetry is irresistible.

Both left and right agree, America is no longer a hegemonic power. The GOP’s collapse and Trump’s incoherence have made America a mighty but brainlessly blundering behemoth. The world has shifted from a unipolar to a multipolar system ten years earlier than expected. Everything frozen is in motion, from Korea to the West Bank. The sun has set on the American Empire, Putin’s revenge has been poetically perfect [1].

Was America’s Empire a good thing? I think the rebuilding of Europe and Japan was a good thing. I think containment of the Soviet Union was good. The long peace, without direct conflict between world powers, was good. Avoiding the end of human civilization was probably good too. Most of this came between 1945 and 1989 though. The record over the last 27 years has been more mixed. Perhaps the world will do better without America.

Where do we go now? I have given up on the prediction business. What I hope happens is that the GOP is swept from power on November 3, 2020. By then much of America’s federal government will be severely damaged or devastated, but we now know that our system was rotten and ready for a fall in 2016. After 2020, without the burden of empire, the United States can begin rebuilding. Like a city leveled by flood or earthquake, we can return better than we were.

- fn -

[1] Do read that Atlantic article. I’d forgotten Anna Chapman from 2008! Among other things we learn that Russia is justly proud of its astounding coup, but not entirely sure it was a good idea:

… The original aim was to embarrass and damage Hillary Clinton, to sow dissension, and to show that American democracy is just as corrupt as Russia’s, if not worse. “No one believed in Trump, not even a little bit,” Soldatov says. “It was a series of tactical operations. At each moment, the people who were doing this were filled with excitement over how well it was going, and that success pushed them to go even further.”…

… The head of the FSB’s elite cyber unit and his deputy were forced out; two other top officers from the unit ended up in Moscow’s most notorious jail.  “They’re now under incredible pressure both from the inside and the outside,” Soldatov said. “Sometimes,” says Michael Hayden, a director of the National Security Agency under George W. Bush, “you have successful covert operations that you wish hadn’t succeeded.” …

… What Russia showed in the 2016 election—and what it has continued to show in the election’s aftermath—is not so much its own strength, but American vulnerability: that it doesn’t take much to turn the American system on itself. “Covert-influence operations don’t create divisions on the ground; they amplify them,” says Michael Hayden, the former NSA chief. John Sipher, the former CIA operative, agrees. “If there’s anyone to blame, it’s us,” he says. “If we accept the stoking, it’s our fault.”

Saturday, December 30, 2017

Tech regressions: MORE, Quicken, PalmOS, iOS, Podcasts, Aperture, Music, iPad photo slide shows, and toasters.

One of the odder experiences of aging is living through technology regressions. I’ve seen a few — solutions that go away and are never replaced.

Symantec’s classicMac MORE 3.1 was a great outliner/editing tool with the best style sheet implementation I’ve seen. It died around 1991. The closest thing today would be Omni Outliner — 16 years later. There’s still no comparable Style Sheet support.

Quicken for DOS with 3.5” monthly diskette records of credit card transactions was the most reliable and useable personal accounting tool I’ve experienced — though even it had problems with database corruption. I think that was the 1980s. Today I use Quicken for Mac, a niche product with unreliable transfer of financial information, questionable data security, and limited investment tools.

PalmOS Datebk 5 was an excellent calendaring tool with good desktop sync (for a while the Mac had the best ‘personal information management’ companion). That was in the 1990s. When PalmOS died we went years without an alternative. I briefly returned to using a Franklin Planner. Somewhere around year 3 of iOS we had equivalent functionality again — and a very painful transition.

iOS and macOS have seen particularly painful combinations of progressions and regressions. OS X / macOS photo management was at its best somewhere around the end of Snow Leopard and Aperture 3.1 (memory fuzzy, not sure they overlapped). OS X photo solutions had finally reached a good state after years of iPhoto screw-ups — the professional and home products more or less interoperated. All Apple needed to do was polish Aperture’s rough edges and fix bugs. Instead they sunset Aperture and gave us Photos.app — a big functional regression. Apple did something similar with iMovie; it’s much harder to make home “movies” than it once was.

iOS was at its most reliable around version 6. So Apple blew it up. Since that time Podcasts.app has gone from great to bad to not-so-bad to abysmal. The iPad used to have a great digital picture frame capability tied to screen lock — Apple took that away. For a while there was a 3rd party app that worked with iCloud photo streams, I could remotely add images to my father’s iPad slideshow digital picture frame. There’s nothing that works as well now; as I write this I’m working through a web of bugs and incompetence (I suspect a desperate timeout stuck into iTunes/iOS sync) to sneak some photos from Aperture to an iPad.

Apple Music is following the path of Podcasts.app as Apple moves to ending the sale of music (probably 2019). At the same time iTunes is being divided into dumbed down subunits (iBooks regression). The last 2-3 revisions of iTunes have been so bad that this feels almost like a mercy killing.

We don’t have a  way to avoid these regressions. Once we could have gotten off the train, now the train stations are dangerous neighborhoods of lethal malware. We need to keep upgrading, and so much is bundled with macOS and iOS that we can’t find 3rd party alternatives. Data lock is ubiquitous now.

I think regressions are less common outside digital world. It’s true toasters aren’t what they were, but since 2006 Chinese products have become better made and more reliable. Perhaps the closest thing to tech regressions in the material world is the chaos of pharma prices.

This takes a toll. There are so many better ways to spend my life, and too few minutes to waste. I wonder what these regressions do to non-geeks; I don’t think it goes well for them.

Friday, December 29, 2017

Did an autonomous Tesla kill its first cyclist?

This Nov 2017 crash hasn’t gotten enough attention …

Tesla Strikes and Kills UK Cyclist | Bicycling.com

… An 80-year-old man was killed Friday when a Tesla Model S, an electric car with some autonomous capabilities, struck him as he rode his bike near the U.K. village of High Shincliffe.

The cyclist—identified as Fred Heppell, a former bank manager from Lanchester, U.K.—was airlifted to a nearby hospital, where he later died. Initial news reports did not indicate if the driver faces any charges, although police are reportedly seeking eyewitnesses to the crash.

While not a fully self-driving vehicle, the Model S has an autopilot feature that allows the car to steer itself in certain circumstances. Promotional videos online show test drivers letting go of the steering wheel while the vehicle maintains speed and control on relative straightaways. (It tops out at 90 miles per hour in autopilot mode, according to the company website.) The car can also change lanes and park on its own.

It’s unclear if the driver in Friday’s crash had applied the autonomous technology at the time of the collision. U.K. reporters described the road where the crash occurred as “predominantly a straight road with gentle inclines.” Heppell was, by all accounts, an experienced rider.

“Fred averaged 10,000 miles per year on his bike and with his wife by his side had cycled across America, Australia, Argentina, Chile, New Zealand, and a host of European countries in his retirement years,” Heppell’s family told the British press…

I was unable to find any follow-up. I am skeptical of Tesla’s approach to autonomous vehicles: I think it is reckless. Any Tesla in autonomous or semi-autonomous mode should run a 360 video to ensure accidents are well understood and permits should not be issued without testing response to cyclists.

I think Google’s autonomous vehicles may, in time, be a boon to cyclists and pedestrians. Tesla, no so much.

Sunday, December 10, 2017

NYT moves columnist blogs into a controlled venue -- with some deprecated RSS

The NYT has moved Krugman’s blog to a new platform. I presume this is true for all their journalists. The NYT RSS index still points to his now frozen blog at nytimes.com/blogs/krugman. 

So what’s the new platform?

K wrote that posts will show up on his regular columnist page: nytimes.com/column/paul-krugman. That page has an RSS feed. Of course, as is the norm these days, the page does not indicate the feed exists. It has an odd structure

www.nytimes.com/svc/collections/v1/publish/https://www.nytimes.com/column/paul-krugman/rss.xml

When I added the feed to Feedbin it displayed in a strange sequence — without the publication date. So the source RSS may be malformed. It’s possible the NYT will fix this.

I note that the footer for the post from 12/9/2017 still points to his old blog “The Conscience of a Liberal”. 

It looks like the NYT is sort-of keeping it’s RSS feeds around, but the transition is at least a bit messy. I can’t tell how one distinguishes K blog posts from his “print” articles, they seem to share one stream. That has to make his writing more formal and more controlled. Which is perhaps the point. 

I am reminded again of an unfortunate side-effect of the ad-funded internet. “Free” media streams now target the easily manipulated populations, typically to serve causes of the corporate and wealthy, often to persuade  the credulous to act against their own interests. They are essentially parasitic. Pay streams can be excellent, but they are only accessible to a small minority.

Tuesday, December 05, 2017

Weinstein, The Enquirer, Pecker and Trump - a curious set of friendships

From NYT essay on Weinstein and his enablers an interesting set of misogynistic relationships …

Weinstein’s Complicity Machine - The New York Times

… Mr. Weinstein held off press scrutiny with a mix of threats and enticements … He was so close to David J. Pecker, the chief executive of American Media Inc., which owns The Enquirer, that he was known in the tabloid industry as an untouchable “F.O.P.,” or “friend of Pecker.” That status was shared by a chosen few, including President Trump.

Via Twitter, how Trump is fighting sexual harassment in DC.

DQVfRSgVoAAJJh4

Saturday, November 11, 2017

Taxing the externalities of the attention economy

The Economist has an excellent overview of the risks of the attention economy (11/4/17). The Gamergate connection is particularly good.

There is so much to say about all of the perverse consequences of funding the net through a tax on attention. I’m sure we don’t fully understand all of the implications; the reality may be even more grim than we know. It’s already grim enough though. So grim that the Russian assisted collapse of the US government has seized a fraction of our distracted attention.

It appears that most Americans are easily manipulated through modern meme-injectors like Facebook and Twitter. Vulnerability increases with lower education levels (among the privileged education is a rough proxy for cognition), but few are completely immune to distraction. We resemble a people who have never seen alcohol a few months after the whisky trade arrives.

If we believe the attention/ad funded economy is the mene equivalent of fentanyl or tobacco, what do we do about it? There are lessons from managing addictive and health destroying substances such as tobacco. It begins with with taxation.

We tax cigarettes heavily. We can similarly tax net advertising. Our goal should be to increase the cost of online advertising several fold. We raise the cost until few advertisers can afford it. At that point Facebook has to turn to other revenue sources to maintain services — such as charging a yearly fee to users.

This is obviously not sufficient, but it’s a beginning.

Sunday, October 15, 2017

What percent of white women voted for Trump - really?

I’d read that 53% of white women voted for Trump and 45% of college-educated white women. I’ve quoted those numbers. Today I looked for an update. It was a bit harder than I expected, many numbers didn’t split out the white from non-white vote. In Jan 2017 FiveThirtyEight wrote

…Trump won among white women by an average of 6.5 percentage points, according to exit polls, and he did particularly well with white women without a college degree, winning among that group by about 24 percentage points…

That article cited a CNN exit poll last updated Nov 23 2016. It had what I was looking for:

2016whitevote

and

2016agegender

The numbers that stand out for me …

  • 94% of black women voted for Clinton. Sanity lives in one cohort.
  • 44% of college-grad white women voted Trump. I’d thought it was closer to 50%. This is still horrible of course.
  • The white gender gap is smaller than I thought — 10%. White women are almost as a bad as white men.
  • Among whites college made a 17% difference - much bigger than gender.
  • 53% white college men voted T vs. 61% white non-college women. Among all whites college was a 17% gap. Education (or cognitive ability) was more important than gender.
  • There’s a 48% gap between black and white women T voters. Sisterhood died in 2016.
  • And, yes, 52% of white women, the majority, did make a horrible mistake.

The CNN page is worth remembering - my memory was only off by 1%. My takeaway was that race mattered above all, next education (or cognitive ability), and least of all gender.

Personal note - Google Scholar discovers something I maybe wrote and forgot long ago

Funny personal note.

While testing Google Scholar's new features I ended up creating a profile based on my (limited) academic publications.

It turned up one from 1981.

https://scholar.google.com/scholar…

The SURFEQL/MINEQL Manual.

I remember doing SURFEQL FORTRAN code for my friend Jim Young around 1980-81 as a Caltech undergrad (at the time Jim was a grad student and my boss). I imagine I might have written something at the time, but maybe Jim wrote the manual and put my name on it. I have absolutely no memory of this.

What a weird echo.

Understanding century 21 - IT, Globalization and urban-urban migration

In the 90s the world kind of made sense. Since then, not so much. I don’t know if teens truly are experiencing an anxiety epidemic, but any American growing up in the new millennium has reason to be anxious.

I think the root causes of our disruption are globalization (China and India) and information technology (AI, robots, advertising supported web, etc) leading to peak human/mass disability and the collapse of the GOP.

I’m now considering a third factor — namely urban-urban migration (though it may be a consequence of globalization and IT rather than a root cause). The population required to sustain a viable local economy keeps increasing; this is absolutely not what we expected when the net was young. Once a city of 10,000 was viable, then a city of 50,000, then a few hundred thousand. We seem too heading towards a million as baseline.

This is politically potent here because the structure of American government gives disproportionate power to low population density regions. The pain of these communities is politically consequential. This is usually described as a “rural” crisis, but these aren’t “rural” in the traditional sense. They are regions around large towns and small cities that are no longer economically viable.

I was a family medicine resident and a young physician in communities like these. Recent stories feel familiar — they remind me of my desolate drives along the Erie Canal and the IT driven end of the mill town. It’s a worldwide thing.

Humans have been migrating from rural areas to cities for centuries. It’s often been socially disruptive. It still is, particularly because of the way American government works. The dying regions have power, and as they lose their cognitive elite they are ever more desperate and easier to deceive.

See also

Wednesday, October 11, 2017

Saint Paul Minnesota mayoral race: bikes and peds

The extraordinary St Paul Bicycle coalition has a couple of useful references on our upcoming mayoral race:

They are careful not to make a recommendation; they need to work with the winner.

Pat Harris is the Dem establishment favorite. He’s not bad on pedestrians but relatively weak on bicycles. Melvin Carter is probably the progressive favorite - strong on bikes and peds. Elizabeth Dickinson is green party - and as supportive as one would expect. I’d put Dai Thao between Harris and Carter/Dickinson.

We have started doing ranked choice voting. It will be interesting to see how it plays out. Bike/ped/transit is big for my family, so I do like Mr Carter’s statements.

Sunday, September 10, 2017

Small traps to watch out for: My Merrill Lynch unexpected brokerage fees

Life has lots of small traps. Sharing this one in case it’s useful.

I once worked for a firm that granted me stock options that were held by Merrill Lynch. I appreciated them. When I left that firm I thought I’d cleaned out the brokerage account. I was warned I’d need to pay $65 a year to keep it so I wanted the money out.

I didn’t quite close it though [1], so a late dividend of $72 went into the account. I missed that — busy with other things and Emily manages our statements. When she was able to get me to look Merrill Lynch said I was too late — a yearly fee of $65 had left only $7.

This time I did close the account — so next year I won’t owe them $58!

Moral of the story — don’t leave inactive accounts lying around. They will bite you in the butt. Get the damned things closed.

[1] Actually, I thought I did close it. I wonder if the dividend reopened it. Maybe there really isn’t a useful lesson to this story … except to have as few accounts as possible so you can track the darned things …

Sunday, September 03, 2017

Elenco SnapCircuits 500 block layout

I have bought things for my children that I dreamt of as a child — but were out of my parent's price range.

Shockingly, my children have not always appreciated these gifts. For example — I think the Elenco Snap Circuits Pro 500 is a brilliant toy. I tried it on all 3 kids and was 0 for 3. No interest whatsoever.

Years later I needed to find a good home for it — but the parts had been scattered in a storage bin. Even though the components are in perfect shape the box had been water damaged by a minor basement flood and the “block layout” guide was unreadable. I tried to find one online but came up empty — though in writing this I discovered Elenco had it online all along. Happily I had a photo I’d taken and I found nothing was missing. I even have a candidate victim child to give the unused kit to.

Today, since I couldn’t find a photo on the web and Google couldn’t find the dang block layout, here’s one for anyone searching for it. (Assuming, of course, that Google indexes this page. It doesn’t index this kind of content anywhere near as well as it once did. Not coincidentally, once Google would have found that layout.)

SnapCircuits500 1

SnapCircuits500 2

I bought the extra books too!

SnapCircuits500 3

and here’s the box …

SnapCircuits500 4