Author: Aceso Under Glass

You may have noticed a drop off in both post quantity and quality.  I noticed too, but I couldn’t figure out why.  Turns out I had an infection in my jaw and while I was able to suppress conscious knowledge of the pain, it was still causing quite a lot of it and that made it impossible to concentrate long enough to do the long form deep dive science posts I’m really proud of.  I’m having surgery to remove the infection tomorrow, and hopefully after I recover I’ll be able to tackle my backlog, which includes

• ASMR
• zinc for colds
• common misconceptions about diabetes and obesity
• More crisis chat observations
• Why NSAIDs are hard on your GI tract (inspired by recent events)
• Words I keep hearing while I watch House, the smartest show I am currently capable of watching
• How narcotics work and why they just don’t in some people (inspired by past events that I am being reminded of in the present)
• The neurochemistry of learning
• Non traditional treatments for sensory integration disorders AKA how my occupational therapist learned to stop worrying and love video games
• The cool stuff my dentist did to help bone regrow perfectly after he removed the gangrenous part that totally worked (anticipated)
• How much better life is after all my pain and chronic infection went away (desperately hoped for) 

But I don’t have the energy for any of those.  Instead, I’d like to share an essay I wrote the first time I had this surgery, 18 months ago.

My dental surgery was originally scheduled 5 weeks in advance. The pain got worse, they gave me antibiotics. The pain still got worse. It felt like biting tinfoil, which meant whatever it was was interacting directly with the nerve. This would make me nervous if I didn’t already have a broken oral nerve. The periodontist agreed to work outside her usual hours to fit me in in a week (three weeks earlier than scheduled). The pain did get better, but it came in waves and I decided I didn’t want to reschedule again, so I didn’t tell them. The surgery was today.

In many ways, it was the best possible outcome. 30 seconds after cutting (just long enough to clear out the pus), she found aberrations big enough to cause the problem, but no bigger. There was a sliver of broken tooth, presumably left over from my wisdom teeth removal (which was over four years ago), and a lesion that is assumed to be a bacterial cyst unless the biopsy says otherwise.* The lesion was within a few millimeters of the nerve, but not touching it. This is good, because if it was on the nerve my choices would have been nerve damage or never clear the infection.

I don’t have good data on this and the doctor was patently uninterested in playing what-if with me, but it certainly seems plausible that the three weeks between the new date and the old would have been enough to grow the cyst all the way to the nerve. I already have nerve damage on one side and it’s awful, I don’t know what I’d do about both. it’s entirely possible the reason this got so bad was that I’m so good at not hearing pain from my mouth that I didn’t notice it. I know I didn’t report it to the dentist at first because I was too fucking stressed out to deal with it, I just wanted to do the right thing and get my teeth cleaned and I’d deal with the chronic stuff later. If I hadn’t gone in for the intensive cleanings, who knows when this would have been caught? So there’s two paths that lead to nerve damage.

I think this got treated faster in America than it would have in any other country. As I understand it (and good data is woefully hard to find), countries with national health care operate on a pretty strict queue system, and doctors have no incentive to work extra hours. I assume you can jump the queue if you can prove you have a more serious problem, but because the cyst was soft tissue it didn’t show up on an x-ray; the only metric we had was my pain. While my periodontist believed me enough to reschedule the surgery, it was clear that seeing the size of the cyst** caused her to retroactively give my complaints a lot more credence. A queue that can be jumped by claiming more pain won’t do it’s job, so in an NHS world I probably would have been stuck with my original number, which undoubtedly would have been longer than the 8 weeks between my dentist popping the first (smaller, exterior) cyst and now. Socialized medicine could easily have caused me permanent nerve damage.***

On the other hand, I only got seen and operated on that quickly because I have money. Lots of money. Enough money to see my dentist 16 times a year, to take the first available periodontist appointment without worrying about paying for it, to take the first available surgery slot without worrying about paying for it. More subtly, having and growing up with money makes it easier to have the entitled attitude that led me to tell the periodontist this couldn’t wait. When I told (not asked) my boss I needed to move the surgery earlier, but this was better timing for the company anyway, he said “well, it really doesn’t matter how the timing affects us, if you need it now you need it now.” This exactly the sort of care you can make yourself believe doesn’t need to be treated right away, giving the infection time to spread. People die of this.

I prefer a market-based health care system not because our system is working particularly well, but because I believe it has to capability to improve in a way the NHS does not. This ability to change comes at a terrible price, and no matter how much money I donate to dental charities, I’m not the one paying it.

*Me: so is there anything the biopsy could reveal I should be worried about?
doctor: no.
Me: Then why are we doing it?
Doctor: something something best practice

I assume that there is a small but present chance this is something awful, like cancer, and she doesn’t want to have to talk to me about it until we have actual data. Which I’m sympathetic to, but I’m also pissed that I was being asked to decide whether this was worth my money and the cost of a false positive while I was under a quarter milligram of a benzoate, massive amounts of whatever local anesthetic they gave me (which does make me feel mentally weird), and the stress of surgery. This was a predictable outcome of the procedure and they should have asked me ahead of time. 

**Biggest she’d ever removed. She had to leave behind a plug so the gum tissue wouldn’t collapse in on itself, any bigger and it would have required a graft.

***Possible relevant and even more frightening: antibiotics would not have fixed this. My cyst was that huge despite me finishing a course of amoxicillan a week prior.

 

Looking back on it now, I certainly feel some bitterness that they apparently missed some infection, and that that provider blew me off when I brought my continuing pain to her.  I’m very afraid that there is or will be nerve damage, especially because that makes the chewing that will ultimately solve my digestive problems painful.  But given that I have this problem, I’m still incredibly lucky.  I have even better insurance now than I did last time.  That time I just had the money to take off work, now I have truly astonishing disability insurance. It is hard to feel lucky when your jaw is in screaming pain, and the NSAIDs you took to stop it made your stomach join it, but I still am.

The Washington Post reports that hurricanes with female names kill more people than hurricanes with male names, because people take them less seriously.  This sounds like amazing hard proof  of sexism in America… except that the data dates back to 1950, when all hurricanes were female.  They didn’t start using male names until 1979.

I tracked down the actual article, and it isn’t any better.  They brag about using multifactor analysis taking into account the gender associated with the name and minimum pressure, which I assume is a measure of severity of the storm.  What they do not account for is the year the storm took place.  So the empirical data that female names are associated with higher casualties could be explained entirely by improved building standards and warning systems.

They’re not that dumb, of course.  They did a set of lab experiments that would usually really impress me, asking people how they’d react to various hurricanes of different characteristics and varying the gender of an otherwise identical hurricane.  People really do seem to respond differently to the hypotheticals when the hurricane gender changes. I was all set to dismiss this anyway, because leaving out the detail about the change in naming patterns was so ridiculous I couldn’t trust them.  But then I found an addendum, noticing exactly my concern.  The sample showed the same pattern, with less statistical significance on account of the smaller size.  So my brilliant plan to demonstrate my intelligence by tearing others down has been foiled, and I am forced to once again confront the unpleasant reality of sexism in America.  

Every pharmaceutical product that comes into direct contact with your blood is tested via a process that involves kidnapping horseshoe crabs, forcefully bleeding them, dropping them off somewhere far away, and then mixing their blood with your future medicine.  I have so many thoughts on this.

One, I miss you, Mitch Hedberg.

Two, we are going through a lot of trouble to not kill the crabs (although up to 30% of the crabs die before being released, and those that survive seem to be less fertile).  This either a sign of a great yet extremely specific compassion, or because we’re concerned about depopulation and this is easier than domesticating them.

Three, can horseshoe crabs feel pain or fear?  If they can, catch, bleed, and release seems less humane than a clean kill and draining all their blood.  Human pain has two components: nociception, which is the peripheral nervous system “ouch”, and your brain’s interpretation and reaction to that pain. That’s why the same sensation can have a very different emotional component depending on the source.  Horseshoe crabs have a  nervous system, so they can feel nociception, but with such limited brains and no endocrine system at all it’s unlikely they’re feeling pain by this definition.  Certainly less than the bunny rabbits that previously filled this role.  Probably little enough that I’m willing for them endure it to lessen human suffering.  But not so little there’s no room for improvement.  Which pharmaceutical companies are working on.  Not so much because this method is creepy, but because it is expensive.

Fourth, this sounds a lot like human descriptions of alien abductions, and would answer the nagging question “why do aliens smart enough to traverse light years want to anal probe so many humans?.” Maybe our anal secretions contained a key element of their biotech development process.  Maybe they happened to create a synthetic version right around the time camera phones came into vogue.

When people visit the crisis chat I volunteer at, I have three options:

1. Listen, no follow up
2. Listen, refer to specialist for concrete help (example: a woman being abused by her husband comes in to chat.  I validate her feelings and ideally help her move to a mental/emotional state where she is emotionally ready to leave.  I then refer her to the National Domestic Violence Hotline for help with the specifics of actually leaving).
3. Listen, call for emergency government interference. There are two circumstances I must do this: someone under 18 is being neglected or abused by a guardian (-> call Child Protective Services or equivalent), or I believe someone is likely to attempt suicide in the next 24 hours (-> call local 911 for an emergency rescue, high likelihood they are involuntarily committed to a psychiatric hospital).

Since I started I’ve called CPS twice and watched other people call two or three times, and never seen a 911 call.  However, I’ve talked to a lot of visitors who are really scared of me calling 911.  I have complicated feelings about this.

I believe people have a right to commit suicide.  I believe my visitors when they say that psych wards are stressful and leave them worse off than they were before.   Active rescues take away people’s power, and when so much of suicide is driven by a feeling of powerlessness, that’s dangerous.   I spoke to a woman with sensory integration disorder for whom a psych ward was pretty much hell on Earth.  If a person is depressed over money, an expensive hospital stay and days of missed work will make it worse.  

I also believe active rescue is really beneficial for some people, and we cannot perfectly predict who falls in that category.  I think it’s safe to say that people coming to crisis chat are more likely to benefit from/want a rescue than the general suicidal population, and I am ultimately willing to tolerate a certain number of unwanted active rescues in exchange for a certain number of wanted ones.

A non-trivial number of people use my chat service rather than the phone line specifically because they (correctly) believe it is harder for us to find their physical location, so they can reach out without fear of the police knocking down their door.  The fact that these people exist indicates to me that this is a good service to provide.  There is a big gap being suicidal thoughts and suicidal acts, and having place to bring light to those thoughts without bringing your world down around you can be the first step towards letting them go.

Thus far my compromise is that if a visitor is voicing concern about me calling 911 on them and telling me they do not want to be committed, I tell them how to avoid having me call.  They can tell me about their wish to die as much as they want, they can even tell me their plan, as long as they also tell me they don’t plan on acting on them in the next 24 hours.  Is it possible people will lie to me?  Yes.  And I would be sad if I found out there was a suicide I could have prevented.  But I would also be sad if an unwanted rescue kept someone from reaching out later.  And I suspect that the truly imminently suicidal are less likely to lie about it/be able to lie about it.  For one, lying is mentally taxing, and the very depressed don’t have the space cycles.  For two, lying requires planning, and the biggest risk for suicide isn’t depression, it’s impulsivity.  My hope is that the same impulsivity that causes suicide will cause people to tell me about it.  I also hope, but will never have the data to back this up, that I’ll be able to recognize impulsivity and make a different deal with the person.  I don’t know what I’d do in that case, I just have this gut feeling that all the people who’ve asked me this so far needed a sense of control more than they needed a rescue, and I’d act differently if I didn’t think that was the case.

Jezebel has a post up discussing the link between Accutane and suicide.  I link to the Jezebel post and not the new article because I find the comments interesting.

First, some background.  Accutane (generic name: Izotretinoin) is mostly an anti-acne medication, although it’s occasionally used for other skin disorders and cancers.  Depending on who you ask, it’s either a form of vitamin A or a close relative of vitamin A.  Vitamin A is fat soluble, which means if you take too much it will kill you (the livers of many arctic mammals are toxic for this reason).  One to two courses of Accutane (generally lasting 8-10 months) is usually enough to permanently cure severe acne.

Izotretinoin is a notorious teratogen, meaning it can cause serious birth defects if taken during pregnancy.  The cause appears to be that izotretinoin serves as a signalling molecule in a certain stage of pregnancy, but this is not definite.  In America, the relevant legal authority has responded with the iPLEDGE system.  Only prescribers registered with iPLEDGE can prescribe accutane. They must register recipients (with a detailed sexual and menstrual history) in the system and certify that they’ve been  warned about the risk of birth defects, and promised to take two forms of birth control.  Prescriptions must be picked up in a seven day window, lost prescriptions cannot be replaced, a prescription must be for exactly 30 days.  Recipients must take a blood (not urine) test for pregnancy every month before getting their prescription.  They recently relaxed the latter requirement for men and women of non-child-bearing age to pledge to take birth control, but still require a blood test.

This program represents some of the worst government interventions in health to me.  It imposes huge burdens of time, money, and privacy.  It infantilizes women by requiring a pregnancy test even if they report no sexual activity, yet takes their word on the whole birth control thing.  It very nearly requires hormonal birth control, and while I recognize hormonal birth control as a life changing intervention for many people, I think the dangers are understudied and under reported and dislike anything that dismisses its costs.  The timing restrictions seem to be designed to force users to adhere to pregnancy tests, which are predicated on the idea that you can’t trust women to notice they’re pregnant.  And of course, you have to do all this for people without working uteruses.  It’s also considerably more work than you need to do to take thalidomide, an even more notorious teratogen, which means the decision to impose iPLEDGE is being made based on something other than strict rational consideration of costs and benefits.

No one is quite sure how izotretinoin works.  It may induce cell death in the sebaceous glands.  It may act as an anti-microbial.  It may affect the expression of hundreds of genes.  It has shown promise as a cancer treatment, which means it probably inhibits cell growth.

Some people report that Accutane has psychological side effects, including suicide.  This is really tricky.

A lot of Accutane users are teenagers, who are already an emotionally chaotic group.  You can compensate for differing risk with a control group, but a higher variance is still more likely to lead to a false report of differing means.

Second, suicidality and depression are not as linked as you would think.  People at the absolute pit of depression are often too overwhelmed and apathetic to kill themselves. Suicide risk actually increases when treatment starts working (which may be why anti-depressants are linked to suicide in teenagers, and is definitely why mixed states are so dangerous).  Severe acne is socially isolating, which can lead to depression.  It’s entirely possible that getting better frees up enough emotional energy to feel bad, or that the first set back after an improvement feels unmanageable, and so while the drug has no direct psychoactive effects, it looks like it does through its effects on the skin.

On the other hand, it’s a known biohazard with no accepted explanation for why it works, and almost any disruption in physical systems can manifest as depression and anxiety.  The weird thing would be if it didn’t.  The Jezebel comment thread is full of people saying it induced terrifying psychosis in them.  It’s also full of people saying it saved their lives by clearing up their acne.  A 24 mouse study showed some increase in depression-like behavior in mice following injection.   An even smaller study showed that Accutane reduced cell growth in certain regions of the brain, which is terrifying for a drug we give to teenagers but hard to draw concrete conclusions from.

So what do you do, as a potential patient or parent of same, in the absence of good evidence?  Clearly you need to watch new patients closely for behavioral changes and discontinue if they occur, but what about the risk of subtle long term damage?    I don’t know how to weigh that.

Health stuff is often cyclic, and I’m in the unpleasant part of the cycle right now.  When the first derivative is negative it’s easy to feel like everything will get worse forever, so here’s a list of things that are objectively better than they were a year ago, even after the recent backsliding.

1.  My overbite.  I’ve had it since childhood.  I was prescribed braces, but my mom eventually convinced my dentist my teeth were so bad that the increase in plaque due to difficulty in brushing would be even worse for me.  Two months ago, it disappeared.  I still pull my lower jaw in when I chew because I ground my back teeth down in the pattern of my overbite, but the resting position is now almost perfect.

2.  My dental health.  I’ve had on 4x/cleanings since childhood, and my last dentist spoke in terms of great Game of Thrones like battles to fight back the plaque.  She noticed a marked improvement as soon as I went on HCl, without me telling her anything had changed.  I just started with a new dentist and he’s less bracing for winter and more trying to make sure things tay as awesome as they are now.

3.  Oranges.  I used to hate oranges.  Two or three drops of orange juice in a full glass of water were all I could stand.  Now I eat them whole, without HCl.

4.  Auditory sensitivity (increased).  When I noticed discontinuities in the sound of my last audiobook (slight changes in the volume or tone) I put it down to cheap recording not standardizing between sessions.  But my current book does it too.  I wonder if every book has these, and I just didn’t notice until now.

I am so tired of medical shows having brave doctors lie to the evil transplant committee that is heartlessly denying a transplant request because the patient is deemed ineligible due to some stupid technicality.  Most recently I saw this on House, where a woman destroyed her heart with bulimia, which is apparently a disqualification for transplant, but it comes up on practically every medical show eventually.  The transplant rules didn’t arise out of some Puritan sense of punishing people for their sins: it’s because eating disorders have a high relapse rate, and a relapse would destroy the new heart too.  By lying and getting her the heart, Dr. House killed whoever would have gotten the transplant instead. 

I’m sure that transplant committees make mistakes, that they’re manipulated by fame and money, and that the guidelines are imperfect.  But they’re not there to be mean, or to “punish” people for their transgressions.  They’re there because there are far fewer donor organs available than are needed, and in light of that scarcity, we want to make sure the organ goes to the person who will get the most additional life out of it.   If a patient has a condition that will lessen the use they get out of the heart, that lowers their priority for a transplant.

Maybe I’m wrong.  I don’t know what went into creating the rules, maybe they’re biased and terrible.  But if so, the appropriate reaction is to say that and fight them.  Not kill someone else because it will make you sad to tell your patient they’re going to die.

Similarly, House, stop lying to get ineligible patients into clinical trials.  You mean well, but there are two options:  the treatment doesn’t work, and you bought your patient nothing, or it does, and you just artificially worsened the numbers, potentially taking it away from everyone else who would have benefited from it.

The other day I posted a link to this blog post on facebook.  The post reported on a study that showed a large difference in how law partners reacted to the same paper when told it was written by a black or white student- they wrote more negative comments, were less encouraging, and found more typos.  A friend of mine responded with “I believe there is systemic racism, but…”, which is never a great start.  He went on to make a bunch of criticisms which would have been  extremely fair to make in a journal club discussing a peer reviewed study, but in context came across as reinforcing the cultural pattern of “I refuse to believe in racism is a factor until it’s proven in each specific case.” Forcing victims of systemic discrimination to prove the discrimination gives them an additional burden on top of all that discrimination.  It’s not right and it’s not fair.  It’s also heavily intertwined with the idea that falsely believing something was affected by race is worse than ignoring discrimination.  

At the same time, I dislike the argument “you’re technically correct ” (which he absolutely was- the study was done by some consulting firm and didn’t even include statistics beyond the mean) “but don’t say it because it will encourage racists.”  Nothing good comes from quieting science.

Now that I know what inflammation is and have given you my personal view of depression, I can talk about depression as an inflammatory disease.  Most specifically, the article “So depression is an inflammatory disease, but where does the inflammation come from?” from BiomedCentral Medicine.  I’ll do some additional research as warranted, but mostly I want to talk about this article.  Prepare for deep dive.

Background: We now know that depression is associated with a chronic, low-grade inflammatory response and activation of cell-mediated immunity, as well as activation of the compensatory anti-inflammatory reflex system. It is similarly accompanied by increased oxidative and nitrosative stress (O&NS), which contribute to neuroprogression in the disorder. The obvious question this poses is ‘what is the source of this chronic low-grade inflammation?’

Translation:

• As I painstakingly established last week, inflammation means a chronic dilation of blood vessels allowing more stuff to leak into tissue.
• cell-mediated immunity involves producing new white blood cells in response to a specific antigen, as opposed to producing new antibodies in response to a specific antigen, or non-specific immunity that is not a response to anything in particular (example: skin).
• Almost every system in your body is moderated by a complex series of signals that can aid or inhibit one another.  Rather than just produce less of an activator to reduce a reaction, your body instead introduces an inhibitor.   Having high levels of both activators and inhibitors has similar primary effects to having low levels of both, but can be either cause weird secondary effects or be a symptom of something weird going on.  It’s also plain more stressful, just like keeping yourself steady against a strong wind is harder than standing still.  “[A]ctivation of the compensatory anti-inflammatory reflex system” implies that depressed people are falling in the “high levels of both” category.
• In the course of the day, your body naturally produces many types of molecules.  Some of those molecules contain oxygen, or nitrogen and oxygen, and a net negative charge.  These are the home wreckers of the molecular neighborhood, luring parts of other molecules to dump their other halves and bond with them instead.  This is a problem if that other molecule is doing something important, like being the blueprint for every other protein in your body.  The damage these homewreckers cause is called oxidative stress.  Your body has ways to contain it, but not perfectly.  Oxidative/nitrosative stress can arise either from producing too many of the reactive molecules, or from a deficiency in the post-processors.
• Fun fact: we don’t know if Nitric Oxide is a pro- or anti-inflammatory messenger.  It looks the answer may be “anti- under normal circumstances, pro- under times of stress”, which implies but doesn’t prove that it’s primary effects are anti-inflammatory, but the containment mechanisms break down under stress and cause a lot of damage.

Discussion: This review explores the role of inflammation and oxidative and nitrosative stress as possible mediators of known environmental risk factors in depression, and discusses potential implications of these findings. A range of
factors appear to increase the risk for the development of depression, and seem to be associated with systemic inflammation; these include psychosocial stressors, poor diet, physical inactivity, obesity, smoking, altered gut permeability, atopy, dental cares, sleep and vitamin D deficiency.

Translation:

• Two very common bad things seem to have a lot in common.  I think there’s a lot of merit to their hypothesis, but this venn diagram does not impress me.

Summary: The identification of known sources of inflammation provides support for inflammation as a mediating pathway to both risk and neuroprogression in depression. Critically, most of these factors are plastic, and potentially amenable to therapeutic and preventative interventions. Most, but not all, of the above mentioned sources of inflammation may play a role in other psychiatric disorders, such as bipolar disorder, schizophrenia, autism and post-traumatic stress disorder

Translation:

• If we are right, this suggests several really easy ways to treat, cure and prevent depression, and potentially other psychiatric issues.

Oh wow, apparently you can induce depression-like symptoms by activating the immune system, either by triggering it with a toxin or just injecting some cytokines (a broad class of messenger, many of which signal the immune or inflammatory system) directly.  SSRIs (the most common class of anti-depressants) decrease production of proinflammatory cytokines,* and a return of symptoms is often associated with the loss of these effects.

The authors then go on to cover in detail various things you already knew were bad or good for you (Sleep- good.  Chronic stress- bad).  The research isn’t at the stage where it’s generating novel recommendations yet.  Which is not a criticism, it’s an impressive set of basic science work and it takes time to translate that into practice.If you are deeply interested in the biochemistry I encourage you to check it out, but I have no more to add.

*SSRI stands for selective serotonin reuptake inhibitor.  Because serotonin is a neurotransmitter, we originally assumed SSRIs treated depression by making serotonin more available.  Except serotonin levels change within hours of taking an SSRI, but the anti-depressant effects takes weeks to show up (unless you’re bipolar, in which case they can trigger a manic phase almost immediately).