First, this lady calls and says “can you tell me what this pill is if I describe it to you?” And all I can think is, “holy shit, you’ve got to be kidding me.” Fortunately, what came out of my mouth instead was: “that’ll be difficult, but I’ll try” (I mean, heck, we weren’t busy and I was twiddling my thumbs while sharing jokes with the pharmacist). “It’s a pink, oblong pill, with a weird ‘V’ on one side and ’3600′ on the other.” I’m thinking, “holy cow, I know what this is” (but I probably shouldn’t have been surprised since we fill so freakin’ much of it). I walk over to the hydrocodone to make a visual confirmation, and sure enough, it’s the generic Lortab 10/500. I walk back to the phone and ask for her name and where she filled the prescription. “Um, I can’t remember.”

Ok, at this point, I’m a bit suspicious; you don’t remember where you filled it, and you don’t have a freakin’ bottle? I’m thinking she bought this stuff off some dude in an alley. Anyway, I continue the conversation and explain to her what the medication is (most likely, since I’m trusting her to tell me what it looks like). She replies, “oh, ok, so they are 10s. thanks.” [click]

Sheesh. She was probably just confirming what she bought before she downed ‘em. And calling them “10s” certainly didn’t help me to think otherwise.

Ok, on to the second story, which is much funnier. Two minutes before close this lady walks up to the counter (thankfully not trying to fill a prescription — that was a job for the guy waiting behind her). “Um, excuse me, where are your deep vibrators?” Um, what?!?! HAHAHA! I had to try so freakin’ hard not to laugh. The best I could manage was: “um, what exactly are you looking for?” “Oh you know, those real deep vibrators, the ones that get in real deep when you get cramps.” The laughing voices in my head just exploded into a raucous guffaw. After having her say it a few more times and with some awkward gestures, I figure out she means something to massage her muscle cramps that she gets on the back of her legs. Just picture this: she’s rubbing the back of her leg/ass area asking me if we sell deep vibrators for her cramps. HAHA! Oh man, I’ll be laughing about that one for awhile. Sad to say, I don’t think we had what she wanted.

Concering the Nissen and Wolski NEJM paper, I have to ask: what’s the big fuss? The data is horrible in my opinion. Let me show you what I’m talking about.

You can click the thumbnail below to see the full table, but notice the confidence intervals. The first set is the odds ratio of having a heart attack while on the drug, and every set of data (except the overall combined meta-analysis) shows that there is no difference between rosiglitazone and the control group (and the p-values are really high which means there is a high probability of achieving these results by chance).

Ok, first important thing to note, is that each individual study was 95% confident that the risk of having a heart attack or dying while on rosiglitazone was no greater than their control group (in some cases placebo and in other cases it was medication like metformin or glyburide).

In studies like this, you always have to start with a null hypothesis, otherwise called a “no difference” hypothesis. This is the hypothesis that there is no difference between whatever you are testing, and a control group. The reason they can’t say there is any difference is because their confidence intervals INCLUDE odds ratio = 1. If your odds ratio equals 1, then that means there is not an increase (or decrease) in the odds of developing whatever result you’re watching for (MI or death) while taking the experimental treatment (compared to the control).

THE ONLY result that was significant was the meta-analysis of the insignificant trials. So, I have to wonder (like I did about the acupuncture-blood pressure result mentioned at the end of my last post), even though these results are statistically significant, are they clinically significant? This leads me to their experimental design.

In their Methods section they state that “trials in which patients had no adverse cardiovascular events in either group were excluded from analysis.”

Um, excuse me? WHY?! Am I just completely naive? Isn’t this throwing out data? I realize they are only looking at cardiovascular events and if the studies did not report results for cardiovascular events then obviously they can’t be used; but I think they’re saying something different here. And depending on how many data points they threw out, their results could be totally different! Am I wrong?

Also, they define the control group “as patients receiving any drug regimen other than rosiglitazone.”

Um… great. To my knowledge, only ONE trial (out of the 42 that met their criteria) actually had a placebo as the control. All of the others used comparator drugs. And the study with the placebo wasn’t testing diabetics (like the other groups were). They were testing people “at high risk” of type 2 diabetes. This makes it harder in my opinion to say that these effects (heart attack and death) are due to the experimental variable (rosiglitazone). Obviously, Avandia was approved by the FDA because the data at the time said it was safe. This study certainly doesn’t convince me otherwise.

If I’m going to accept someone’s conclusions, they’re going to have to SELL them to me. Convince me. So far, this paper isn’t convincing. I don’t see why I should accept a poorly designed meta-analysis (with missing data!) over the previous studies that determined Avandia is safe.

Also important to note: in a prospective cohort trial (more powerful than the Avandia case reports) studying a drug in the same TZD (thiazolidinedione) class called pioglitazone (Actos), they determined that pioglitazone actually has a protective effect against heart attack and death AND another study comparing lipid and glycemic effects of these drugs in type 2 diabetics found that both drugs increased cholesterol levels, but Actos raised HDL cholesterol greater than Avandia, whereas Avandia increased the LDL cholesterol higher than Actos (both cited in Nissen and Wolski’s paper). And Actos even lowered the overall triglyceride levels, whereas Avandia raised them.

In any case, the researchers have qualified this study by saying that they did not have access to all of the original data. But still, just because you got a result that was barely significant, and it was really difficult to organize the data into a powerful meta-analysis, you shouldn’t shout to the world that this drug is killing people.

If I’m completely wrong, I’d appreciate someone explaining their rationale to me.

• The Evilutionary Biologist: Is There Anything Phages Cannot Do?

  Bacteriophages break up beta-amyloid plaques? Take a look…

• Newly discovered antibody may be body’s natural defense against Alzheimer’s
  

  “Since beta amyloid oligomers are much less abundant in the body than the single-molecule variety, the relatively high amount of oligomer-specific antibody found in human blood suggests that the immune system recognizes these aggregates to be a particularly noxious threat.”

• Alzheimer’s disease to quadruple worldwide by 2050

  We better get crackin’…

• Also see the post about dimebon at The Chem Blog (linked later in this post in the “drugs” section).

Continuing the stem cell buzz:

• Human stem cells treat Parkinson’s in monkeys – health – 11 June 2007 – New Scientist
• Sandwalk: The Ethics of Stem Cell Research
• Sandwalk: Reprogramming Somatic Cells
• denialism blog: Reprogramming adult cells into embryonic stem cells

Some nice drug posts:

• Rimonabant, Out In the Light. In the Pipeline:
  

  “It’s the first antagonist targeting the cannabinoid CB-1 receptor, and at one point it looked like it was going to make people lose their excess weight, shed their addictions, and for all I know refinance their mortgages.”

• The Chem Blog » Dimebon can cure Great Grandma!
  

  “A startup in San Fran has discovered and announced that this simple indole compound can treat Alzheimer’s with a significant advantage over placebos.”

• Gabapentin Shown Effective for Fibromyalgia Pain
  

  “Although gabapentin has little, if any, effect on acute pain, it has shown a robust effect on pain caused by a heightened response to stimuli related to inflammation or nerve injury in animal models of chronic pain syndromes. Researchers have suspected that it might have the same effect in people with fibromyalgia. The new research, published in the April 2007 edition of Arthritis & Rheumatism, indicates the suspicions were correct.”

• BioWizard – 16S ribosomal RNA methylation: emerging resistance mechanism against aminoglycosides.
• Researchers shed light on mechanism of action used by anti-cancer drug

Miscellaneous:

• A Shocking Idea: Nerves Might Run on Sound, Not Electricity

  Wow. There’s a fringe theory. I’m not holding my breath.

• A selection of quotes from Aldo Leopold « Laelaps

  I’m really going to have to check this book out. Thanks Laelaps!

• Pharyngula: Religion—our maelstrom of ignorance

  Ugh! Just LOOK at the trend! Could the culprit be any more obvious?!

• Atheist Self: The Natural World
  

  “My nature was the product of several billion years of refinement. It has matured, like a fine wine. It is mysterious and wonderful because I don’t assume that it happened for a reason, or at the hand of a master designer. Because I don’t assume that human beings have lived on this planet but for a fraction of a percent of its existance.”

  “The only way to truly appreciate the grandeur and splendour of the universe is by not taking it for granted. By explaining away our existence in just a few of pages in Genesis, we are making up answers to questions that deserve a lot more attention. A lot more … reverence.”

• Jim Plagakis » Pay for our knowledge and experience?
  

  “There has been discussion about getting paid for our [pharmacists] knowledge and experience. OTC counseling comes to mind. Medical advice too. We are the point person of triage for the entire stack. How many people without money come to the pharmacist to see if they REALLY NEED TO SEE THE DOCTOR? I say a lot. If they don’t have money, most will come see you. Where else can you get the kind of attention we give for nothing?”

• BioWizard – Randomized Trial of Acupuncture to Lower Blood Pressure.

  What the heck? Acupuncture works?! Ok, the results ARE statistically significant, but are they clinically significant? Barely. The researchers are 95% confident that acupuncture will lower your systolic BP between 3.5 and 9.2 mm Hg and your diastolic BP between 1.6 and 5.8 mm Hg. Significant? Maybe as a last resort…

• Daily Kos: Getting “Tough” on Maliki

  Didn’t we always know that we were there for oil?

• Opinion: Over-the-counter Plan B long overdue – Breaking Bioethics – MSNBC.com

  “Emergency” contraception does the exact same thing (and uses the same hormones) as “regular” (medication) contraception. So why the big fuss?

  “Emergency contraception is not an abortion pill. It is basically a big dose of one of the key ingredients in an ordinary birth control pill.

  [snip]

  The pill acts in two ways. Primarily, it prevents the ovaries from releasing an egg so no fertilization can occur. Then in the rare event that an egg has already been released by the ovaries, the pill also changes the chemistry of the lining of the uterus so that any fertilized egg cannot implant.

  Is this an abortion pill? No. For the most part the pill simply stops an egg from being available to come in contact with sperm. And even if there happens to be an egg present when sex occurs there is no disruption of an implanted embryo. The only way the pill can be seen as inducing an abortion is if one holds the view that non-implanted, fertilized eggs are fetuses — a view which few doctors, pharmacists, scientists or Americans subscribe to.” (my emphasis)

• Drugs and Poisons: A brief history of antidepressants

  Great, simple run-through of antidepressants.

• Incinerating Presuppositionalism: The Moral Uselessness of the 10 Commandments

  Thanks for writing this. I wish more people were able to see this.

• Edge: WHY DO SOME PEOPLE RESIST SCIENCE By Paul Bloom and Dena Skolnick Weisberg

  Great commentary and insight. Definitely worth a look, and several re-reads. Here’s a teaser:

  “The strong intuitive pull of dualism makes it difficult for people to accept what Francis Crick called “the astonishing hypothesis.” Dualism is mistaken — mental life emerges from physical processes. People resist the astonishing hypothesis in ways that can have considerable social implications. For one thing, debates about the moral status of embryos, fetuses, stem cells, and non-human animals are sometimes framed in terms of whether or not these entities possess immaterial souls.

  [snip]

  But this rejection of science would be mistaken in the end. The community of scientists has a legitimate claim to trustworthiness that other social institutions, such as religions and political movements, lack. The structure of scientific inquiry involves procedures, such as experiments and open debate, that are strikingly successful at revealing truths about the world. All other things being equal, a rational person is wise to defer to a geologist about the age of the earth rather than to a priest or to a politician.

  Given the role of trust in social learning, it is particularly worrying that national surveys reflect a general decline in the extent to which people trust scientists. To end on a practical note, then, one way to combat resistance to science is to persuade children and adults that the institute of science is, for the most part, worthy of trust.” (my emphasis)

• Daily Kos: Book Review: Al Gore’s “Assault on Reason”

  I’m so totally getting this book. This post makes me drool in anticipation. (But is that really saying much? I have a whole bunch of unread books sitting on my shelf right now that make me drool when I think about reading them; in a good way).

A few New England Journal of Medicine articles:

• NEJM — Religion, Conscience, and Controversial Clinical Practices

  Damn MD’s and their woo. Some won’t even refer a patient to another MD if they have personal objections to certain procedures. Who are the offenders? Religious, male MD’s. {shudder}.

• NEJM — Interleukin-1-Receptor Antagonist in Type 2 Diabetes Mellitus

  Just because I’m researching IL-6: “At 13 weeks, in the anakinra group, the glycated hemoglobin level was 0.46 percentage point lower than in the placebo group (P=0.03); C-peptide secretion was enhanced (P=0.05), and there were reductions in the ratio of proinsulin to insulin (P=0.005) and in levels of interleukin-6 (P less than 0.001) and C-reactive protein (P=0.002).”

• NEJM — Effectiveness of Adjunctive Antidepressant Treatment for Bipolar Depression

  Antidepressants don’t help if the patient’s are already taking mood stabilizers.

A Cross-section of posts on sponges and proto-synapses:

• Thinking for Free: The Nerve of Some Sponges!

  First to report (to my knowledge).

• Pharyngula: Sponges have synapses?

  Great PZ post (this time with actual science!)

• Sea sponges have the makings of a nervous system « Neurophilosophy

  Super quality post; great writing, excellent explanations. Here’s a teaser:

  “In the new study, Kenneth Kosic and his colleagues analyzed the Amphimedon genome, and found that it contains 36 families of genes known to encode proteins of the post-synaptic density. So, even though it has no neurons, this sea sponge synthesizes an almost complete set of post-synaptic density proteins. A comparison of the DNA sequences from the 36 sea sponge genes with the homologous sequences from humans, Drosophila melanogaster (fruit flies) and Nematostella vectensis (a cnidarian with a simple nervous system, consisting of a loose network of nerves) revealed striking similarities between the genes in all four species. One gene, called dlg, encodes a crucial component of the post-synaptic density scaffold. The protein product of that gene contains a number of regions that form the protein-protein bonds that hold the scaffold together. The segment of the dlg gene encoding these binding regions was found to be highly conserved – the DNA sequences in the sea sponge gene were identical to the human sequences. This suggests that in the sea sponge these proteins interact in exactly the same way as they do in the human post-synaptic density.” (my emphasis)

Some highly appropriate satire:

• Daily Kos: Paris Hilton for President

]]> http://eclecticesoteric.wordpress.com/2007/06/11/links-for-61107-my-netnewswire-tabs/feed/ 0 jryanstevens http://eclecticesoteric.wordpress.com/2007/06/11/teachers-and-churchstate-separation/ http://eclecticesoteric.wordpress.com/2007/06/11/teachers-and-churchstate-separation/#comments Mon, 11 Jun 2007 06:46:12 +0000 jryanstevens http://eclecticesoteric.wordpress.com/2007/06/11/teachers-and-churchstate-separation/ ]]> Some teachers in one Virginia school district reject church state separation: “The WorldNetDaily has it all wrong. Teachers don’t have a ‘right’ to decide not to hand out something ‘they’ find objectionable. Teachers, as well as administrators, are considered agents of the state (through compulsory education attendance laws and previous court cases) and any action they take is seen as an act of the state. If a teacher is so offended by what they are asked to do as part of their contracted job and duty as an agent of the state, then maybe they don’t need to work in a public school. There are plenty of sectarian private schools that might make them feel better.”

(Via Secular Left.)

I can’t say it much better than that. I seem to be finding a bunch of stuff I just want to quote into my blog today…


]]> http://eclecticesoteric.wordpress.com/2007/06/11/teachers-and-churchstate-separation/feed/ 0 jryanstevens http://eclecticesoteric.wordpress.com/2007/06/10/avandia-round-2-the-angry-pharmacist/ http://eclecticesoteric.wordpress.com/2007/06/10/avandia-round-2-the-angry-pharmacist/#comments Sun, 10 Jun 2007 23:44:59 +0000 jryanstevens http://eclecticesoteric.wordpress.com/2007/06/10/avandia-round-2-the-angry-pharmacist/ ]]> Avandia – Round 2 (The Angry Pharmacist): “Avandia questions are still coming in waves. We actually have doctors who gave us blanket statements to switch all of his/her patents from Avandia -> Actos.

Now my question about this:
1. Kickbacks? Oh, I think so.
2. Doesnt he/she know that the risks from Avandia are a class effect? So when GSK gets its head out of its ass and publishes a paper showing the exact same risks are present in Actos, what are we supposed to say? Your doctor is an idiot?
3. I thought that drug treatment was supposed to be individualized to the patients, you know, practice medicine. Sweeping mass changes of Avandia -> Actos sorta goes against that dont you think?

Now for the doctors in the crowd: Is he doing this to prevent himself from getting sued? We all know that study isnt worth the paper to wipe my ass with, yet people are seriously freaking out about it and switching all their patients. Hell, lets switch them to all Metformin, because Lactic Acidosis isnt nearly as scary *sigh*.

When are people going to realize that Rx medication is a controlled poison?”

(Via The Angry Pharmacist.)

Wow. My thoughts exactly. It feels good to know there is still some sanity in the world.


]]> http://eclecticesoteric.wordpress.com/2007/06/10/avandia-round-2-the-angry-pharmacist/feed/ 0 jryanstevens http://eclecticesoteric.wordpress.com/2007/06/10/your-pharmacist-may-hate-you-i-lied-blog-postings-will-remain-highly-irregular-i-will-soothe-your-disappointment-with-some-highlights-from-todays-pill-counting-action/ http://eclecticesoteric.wordpress.com/2007/06/10/your-pharmacist-may-hate-you-i-lied-blog-postings-will-remain-highly-irregular-i-will-soothe-your-disappointment-with-some-highlights-from-todays-pill-counting-action/#comments Sun, 10 Jun 2007 23:41:22 +0000 jryanstevens http://eclecticesoteric.wordpress.com/2007/06/10/your-pharmacist-may-hate-you-i-lied-blog-postings-will-remain-highly-irregular-i-will-soothe-your-disappointment-with-some-highlights-from-todays-pill-counting-action/ ]]> Your Pharmacist May Hate You: … Highlights From Today’s Pill Counting Action.: “… a woman came up to the counter to tell me that some of the ink from a shopping bag she had been carrying around had come off and made her hand blue. She asked for a suggestion. I struggled for a professional sounding way to say ‘wash your hands’

This was followed up by a woman who came running up from the liquor department. She had just broken a bottle of vodka and wanted to know what to do. She smelled really good.

She was not injured in any way, but wanted to know what I would recommend in case she might have got some glass in her hand, despite the fact there was no glass in her hand. God she smelled good. I think it was Grey Goose.

Ten minutes before closing I get the customary ‘WHAT TIME DO YOU CLOSE? THIS IS AN EMERGENCY!!!!’ call…..the customer wanted to know if we sold nails.

Emergency nails. I didn’t ask details, I just transferred him to the front and pranced out the door into the sweet, sweet arms of scotch…..happy that I made it through the day without throwing any nuts.”

(Via Your Pharmacist May Hate You.)

Damn. This is priceless. You are not alone!


]]> http://eclecticesoteric.wordpress.com/2007/06/10/your-pharmacist-may-hate-you-i-lied-blog-postings-will-remain-highly-irregular-i-will-soothe-your-disappointment-with-some-highlights-from-todays-pill-counting-action/feed/ 0 jryanstevens http://eclecticesoteric.wordpress.com/2007/06/10/the-bronze-blog-doggerel-91-dont-force-your-views-on-us/ http://eclecticesoteric.wordpress.com/2007/06/10/the-bronze-blog-doggerel-91-dont-force-your-views-on-us/#comments Sun, 10 Jun 2007 23:35:59 +0000 jryanstevens http://eclecticesoteric.wordpress.com/2007/06/10/the-bronze-blog-doggerel-91-dont-force-your-views-on-us/ ]]>

The Bronze Blog: Doggerel #91: “Don’t Force Your Views on Us!”: “When a skeptic expresses a view, the only force behind it is that of logic, evidence, and so forth. Contrary to how woos like to imagine us, we do not have any sort of thought police going around threatening violence to people who hold contrary opinions. At most, we have people who make loud counter-arguments, which isn’t forcing in any sense, but woos often like to portray it as such anyway. Worse, is that these sorts will often hypocritically complain about the media’s failure to present both sides when their evidence-free crankdom is ignored.”

(Via The Bronze Blog.)


]]> http://eclecticesoteric.wordpress.com/2007/06/10/the-bronze-blog-doggerel-91-dont-force-your-views-on-us/feed/ 5 jryanstevens http://eclecticesoteric.wordpress.com/2007/06/10/even-the-bbc-disses-paris/ http://eclecticesoteric.wordpress.com/2007/06/10/even-the-bbc-disses-paris/#comments Sun, 10 Jun 2007 16:03:26 +0000 jryanstevens http://eclecticesoteric.wordpress.com/2007/06/10/even-the-bbc-disses-paris/ ]]> So, it’s probably unintentional (maybe), but this is what I saw when checking the BBC RSS feed today.



Now the actual page doesn’t state it like that. But I just had to laugh, that the BBC thinks Paris will “learn” something. LOL. What’s with the scare quotes?


]]> http://eclecticesoteric.wordpress.com/2007/06/10/even-the-bbc-disses-paris/feed/ 0 jryanstevens http://eclecticesoteric.wordpress.com/2007/06/05/feeling-cold-the-ion-gate/ http://eclecticesoteric.wordpress.com/2007/06/05/feeling-cold-the-ion-gate/#comments Tue, 05 Jun 2007 07:57:27 +0000 jryanstevens http://eclecticesoteric.wordpress.com/2007/06/05/feeling-cold-the-ion-gate/ ]]> Scripps research team sheds light on long-sought cold sensation gene: “TRPM8 codes for an ion channel found at the tips of sensory neurons, which innervate the skin. When opened, ions flowing through TRPM8 lead to the activation of the sensory neuron, which in turn sends a signal to the brain. The Patapoutian team’s results support the idea that activation of TRPM8 by temperature triggers cold sensation. ‘TRPM8 acts as a gate,’ says Dhaka, ‘At warm temperature it remains closed, but opens when exposed to cool temperature.’”

Now isn’t that interesting? I did a quick Pubmed search to find more information on these transient receptor potential proteins.

I found a chapter from the Handbook of Experimental Pharmacology. Interestingly, the ion channel is voltage-gated (like more traditional ion channels). So where’s the connection between temperature and action potential?

Cooling causes a robust but graded shift of the voltage dependence of activation from strongly depolarised potentials towards the physiological potential range (Voets et al. 2004b). Thus, cold activation of TRPM8 (and other thermoTRPs) should not be regarded as a threshold phenomenon, but rather as a gradual shift of voltage sensitivity.

So the temperature change lowers the voltage threshold closer to the resting potential of the neuron (presumably through a structural change of the protein?). As the temperature falls, TRPM8′s threshold approaches the resting physiologic potential, the ion gate opens and cations rush in the cell. These cations in turn quickly raise the membrane voltage causing the “normal” (voltage-dependent) ion channels to fire-off simultaneously resulting in a propogated action potential to the brain.

Brrrrrr!

The paper goes on to discuss the pharmacological side of things for those interested.


]]> http://eclecticesoteric.wordpress.com/2007/06/05/feeling-cold-the-ion-gate/feed/ 1 jryanstevens