The forum is back up. That was one of the smoothest upgrades ever. So of course it didn’t fix all of the problems I created when trying to improve overall system response time.
I so hate open source software.
I’ll be installing a minor forum software upgrade on Sunday, 19 July 2015. AKA tomorrow. This is to fix some of the random weirdness that resulted from my botched attempt to improve overall system response time. The upgrade has nothing to do with what I did. I think recreating some of the modules during the upgrade process in the new environment will make the software happy. So the forum will be unavailable around 10:00 a.m Mountain time (1600 GMT) for no more than an hour or two. I hope.
The FDA approved a new med, Otsuka Pharmaceutical’s Rexulti (brexpiprazole), to treat schizophrenia and, instead of the traditional bipolar approval, as an add-on for MDD.
Taking a quick look at its pharmacology from Potentiation of neurite outgrowth by brexpiprazole, a novel serotonin-dopamine activity modulator: a role for serotonin 5-HT1A and 5-HT2A receptors:
Brexpiprazole is a potent partial agonist at human 5-hydroxytryptamine (5-HT) 5-HT1A (Ki=0.12 nM) and dopamine D2L (Ki=0.3 nM) receptors, and an antagonist at 5-HT2A receptors (Ki=0.47 nM) (Maeda et al., 2014a). It also shows potent antagonist activity at human noradrenergic α1B (Ki=0.17 nM) and α2C receptors (Ki=0.59 nM) (Maeda et al., 2014a). Furthermore, this drug displays moderate affinity for human D3, 5-HT2B and 5-HT7 receptors, as well as α1A, and α1D adrenergic receptors.
Rexulti looks like slightly enhanced Abilify. I.e. maybe there’s even less of a chance for weight gain. Otherwise Otsuka looks to be preserving its patent for the soon-to-be-generically-available Abilify.
Psychology Today ran the following article in response to the latest mass murder committed by someone who is dangerously sane: “Identifying The Next Mass Murderer—Before It’s Too Late” The article is all about profiling and, except for the title, it neither calls nor implies that the racist terrorist who did it is in any way mentally ill. One can infer Dylann Roof is crazy from the title only because the article is published in Psychology Today. I was ready to write yet another pointless, scathing essay on media stereotypes of the mentally interesting, but there is no media stereotype here.
The article is just annoying for other reasons.
The author buried the lede by leaving the whole bit about PUBLISHING MANIFESTOS ONLINE until 2/3rds the way through. You don’t need to know shit about profiling if someone frequently posts to Facebook their violent intentions toward the mud races.
Worst of all: completely ignoring that his advice has already been put into practice for years and dangerously sane racial terrorists like Roof, Wade Page, and Anders Breivik are being stopped by federal, state and local law enforcement all the time now.
Cops aren’t perfect in numerous ways, so they won’t be able to catch everyone. There will always be dangerously sane racial terrorists like Roof, dangerously sane fratricidal traitors like Nidal Hasan, and dangerously sane family annihilators like Bruce Pardo who manage to slip through holes in the tightest nets of distributed social media surveillance.
I’m supremely guilty of serial mansplaining, but this is taking it to a whole new level.
Research items of interest.
I’ve been saying for years that the chemical imbalance hypotheses of depression and schizophrenia were close, and that brain cooties of all kinds, including neurological conditions like epilepsy and migraines, are essentially forms of cerebral network dysfunction. The evidence is piling up that the few bleeding-edge researchers of the previous decade and I were right all along.
Remember when everyone was up in arms about antidepressants making anyone who took them go on a shooting spree?
Turns out the real killer drugs are Aspirin and Tylenol.
We should ban that shit immediately!
Has a biomarker been found for combat PTSD?
Exposure to war zone stressors is common, yet only a minority of soldiers experience clinically meaningful disturbance in psychological function. Identification of biomarkers that predict vulnerability to war zone stressors is critical for developing more effective treatment and prevention strategies not only in soldiers but also in civilians who are exposed to trauma. We investigated the role of the serotonin transporter linked polymorphic region (5-HTTLPR) genotype in predicting the emergence of post-traumatic stress disorder (PTSD), depressive and anxiety symptoms as a function of war zone stressors. A prospective cohort of 133 U.S. Army soldiers with no prior history of deployment to a war zone, who were scheduled to deploy to Iraq, was recruited. Multilevel regression models were used to investigate associations between 5-HTTLPR genotype, level of war zone stressors, and reported symptoms of PTSD, depression and anxiety while deployed to Iraq. Level of war zone stressors was associated with symptoms of PTSD, depression and anxiety. Consistent with its effects on stress responsiveness, 5-HTTLPR genotype moderated the relationship between level of war zone stressors and symptoms of emotional disturbance. Specifically, soldiers carrying one or two low functioning alleles (S or LG) reported heightened symptoms of PTSD, depression and anxiety in response to increased levels of exposure to war zone stressors, relative to soldiers homozygous for the high functioning allele (LA). These data suggest that 5-HTTLPR genotype moderates individual sensitivity to war zone stressors and the expression of emotional disturbance including PTSD symptoms. Replication of this association along with identification of other genetic moderators of risk can inform the development of biomarkers that can predict relative resilience vs. vulnerability to stress.
Some images from my collection of old medical reference books.
First up, a peek inside of Dr. Benway’s little black bag from 100 years ago:
Eli Lilly Aseptic Metal Pocket Case model #23. From Lilly’s Handbook of Pharmacy and Therapeutics Sixth Revision. 1919.
100 years ago doctors used to walk around with 20 doses (each) of Apomorphine, Codeine, Heroin, and Morphine in their little black bags. And in case something went wrong, nitroglycerin and digitalis.
Next up is the human head section of an 1885 anatomical flip book by L.W. Yaggy & James J. West. These came from a sample copy – known as a salesman’s dummy – of The New Century Family Physician and Cyclopedia of Medical Reference.
More or less. Here’s what’s new on Crazymeds:
10 June 2015
1 June 2015
Now that I finally got around to upgrading this shitty blog to WP version 4.whatever and reactivating Akismet I’ve turned post comments back on. Not that anyone other than spambots have bothered to comment.
Along similar lines I’m allowing anyone – at least anyone who isn’t a spambot – to post med reviews. This is happening when I convert a med to a less-mobile-device-hostile format. AKA the more ad-rich, multipage format that is so popular on all the way-more-popular-than-Crazymeds sites WebMD owns.
I’m just giving the people what they seem to want.
Acetaminophen, an effective and popular over-the-counter pain reliever (e.g., the active ingredient in Tylenol), has recently been shown to blunt individuals’ reactivity to a range of negative stimuli in addition to physical pain.
Next time someone whines about a mood stabilizer working in terms of preventing hypomania, sorry, their emotions being all blunted and shit, and if anyone knows of a med that’s more “activating”, I now know where to point them.
Predisposition to respond to placebo treatment may be in part a stable heritable trait.
Candidate placebo response pathways may interact with drugs to modify outcomes in both the placebo and drug treatment arms of clinical trials.
Genomic analysis of randomized placebo and no-treatment controlled trials are needed to fully realize the potential of the placebome.
Placebos are indispensable controls in randomized clinical trials (RCTs), and placebo responses significantly contribute to routine clinical outcomes. Recent neurophysiological studies reveal neurotransmitter pathways that mediate placebo effects.
First of all it’s another reason to require an active placebo (a med, usually an old one like Thorazine or desipramine, that is already approved to treat whatever the new med is being tested to treat).
Secondly, and more importantly, it explains why, when people who write about their bad experiences with meds and include anecdotes about that their parents and/or grandparents who were able to deal with their problems using vitamins or whatever, the placebos worked for said ancestors.
Hey, as long as it works. Have a placebo party. Good luck and find another site to rave about whatever you’re taking to fix whatever it is you think is wrong with you.
A Canadian woman who had declined to have her children immunized against pertussis, better known as whooping cough, has changed her position now that all seven of her children have come down with the disease.
I consider it a bit of misapplied karma for the antivaxxer parents whose kids gave my daughter pertussis – thanks to her birth family’s neglect regarding her booster shot, as it turns out – which subsequently developed into asthma.
I’m lucky to have had a booster shot about ten years prior to when that happened. Influenza shots don’t do me a damn bit of good, but the pertussis vaccine works perfectly for me.
I’ve updated the Brand vs. Generic and FDA vs. Teva/Impax vs. Reality pages to reflect the bioequivalence testing data on Budeprion XL the FDA quietly released … however long ago they quietly released it … along with their somewhat more stringent standards for generic crazy meds.
At least the first couple of new generics for any given med. My money is on their still letting most of them get by on paperwork alone and no actual BA/BE testing.
Various news items.
A group of 14 state attorneys general on Thursday asked the U.S. Congress to investigate the herbal supplements industry after a New York probe of the products turned up ingredients that were not listed on labels and raised safety concerns.
The group, led by New York Attorney General Eric Schneiderman and Indiana Attorney General Greg Zoeller, also asked Congress to consider giving the U.S. Food and Drug Administration more oversight of herbal supplements.
Here’s the best part:
In February, four major retailers, GNC Holdings Inc, Target Corp, Walgreens and Wal Mart Stores Inc, halted sales of certain supplements after being subpoenaed by the New York attorney general. DNA tests had failed to detect plant materials listed on the majority of products tested.
On Monday, GNC reached an agreement with Schneiderman to adopt more stringent testing standards than the FDA requires, and began to resell the supplements.
A study found the products were within FDA guidelines, Schneiderman said. GNC said tests also showed its products were safe, pure, properly labeled and in full compliance.
The way I read it the problem was whatever was promised on the label wasn’t in the bottle, and not there was stuff in there that wasn’t on the label. It doesn’t really matter which of the two happened, because, as I point out on the Meds and Supplements page, as long as the stuff isn’t toxic it’s legal. GNC can sell you stale peppermint and call it St. John’s Wort and the FDA can’t do shit about it. The FTC might, but I wouldn’t be surprised if their hands are tied.
On the subject of toxicity…
researchers also have found other problems, including high levels of lead, mercury and arsenic in certain supplements.
Size matters. And in this case smaller is better.
Hippocampal structure may be an important indicator of electroconvulsive therapy (ECT) outcome and, potentially, the outcomes of other treatments in patients with major depression, new research suggests.
Investigators at the University of California, Los Angeles (UCLA) found that patients who had smaller hippocampal volumes at baseline were more likely to show clinical improvement after the initial phase of ECT treatment.
“Smaller hippocampal volumes at baseline predict a more robust clinical response,” first author Shantanu H. Joshi, PhD, assistant professor of neurology at UCLA, said in a statement.
Results For all-cause mortality, the pooled relative risk of mortality among those with mental disorders (from 148 studies) was 2.22 (95% CI, 2.12-2.33). Of these, 135 studies revealed that mortality was significantly higher among people with mental disorders than among the comparison population. A total of 67.3% of deaths among people with mental disorders were due to natural causes, 17.5% to unnatural causes, and the remainder to other or unknown causes. The median years of potential life lost was 10 years (n = 24 studies). We estimate that 14.3% of deaths worldwide, or approximately 8 million deaths each year, are attributable to mental disorders.
Don’t you read what I write?
At any dosage it will make you crave doughnuts. Seriously. You will want to invest in Krispy Kreme stock (or maybe something along similar lines that isn’t tanking); as Remeron’s antagonism of the serotonin 5HT2C and H1 receptors gives you the munchies for carbohydrates and sugars like you were 16 and smoking the best pot ever in the parking lot of a strip mall with a 24-hour doughnut shop beckoning you with glazed and jelly-filled ecstasy. People dipping spoons into a bag of sugar and eating it as is – not unheard of when on Remeron. This stuff is nothing more than legal marijuana, and if I knew crap about biochemistry I could probably prove that crazy statement.
People who take Wellbutrin don’t want to eat anything. It’s the “happy, skinny, horny pill”, remember? People who take Remeron want to eat doughnuts all day long.
I’ve updated the site stats page. I managed to track down the source of something that has been bothering me: why is there such a big discrepancy between the numbers reported by Alexa, Google Analytics and Awstats? I haven’t found out why, but at least I know where: the Crazy Talk forum (especially people using the Tapatalk app), and this blog.
The truly sad stat: the most popular page on this blog, the one that gets THREE TIMES as much traffic as the main / home / default page, is the admin panel login. There are more annoying little 1337 4aX0rs trying to crack this piece of shit than there are people interested in reading it.
Some bug in the forum software has allowed people to log onto the forum and read it while it was offline COMPLETELY DEFEATING THE PURPOSE OF TAKING IT OFFLINE TO SPEEDUP THE REBUILD!!!! THANKS LOADS, EVERYONE!!!
I’ve had to put in a hard restriction of the forum to my IP address. Hence the 403 forbidden message.
No wonder the maintenance during some of the upgrades took for fucking ever. That wasn’t cache weirdness I was seeing in the online users list. Those were people logged on when I said not to be logged on.