Pain has a couple of very interesting piece amidst the murine model papers I've never been able to appreciate.  First, an editorial about current research that buprenorphine not only has analgesic effects but also anti-hyperalgesic effects (as in opioid-induced hyperalgesia), via kappa-opioid receptor antagonism.  The editorial of course refers to an actual article in Pain, but for the average reader (like me) I'd suggest sticking with the editorial.  "Today, opioids cannot only be considered for their potency to reduce nociceptive symptoms but also for their ability to oppose active processes leading to pain hypersensitivity. This might be a new and beneficial approach for preemptive analgesia and improving the treatment of some forms of chronic pain dominated by central sensitization."
And then, the article which explains several life-long habits of mine:  chewing gum relieves pain.  I'm not going to bother to critique this one--it's actually really interesting with a lengthy discussion about serotonin in nociception, speculation about the the necessity of rhythmic chewing to achieve the nociception, and a brief review of the chewing & analgesia literature. I do want to highlight my appreciation of the authors' quietly funny prose however:
"The NFR recording and stimulating electrodes were attached to the subject. All recording and stimulation electrode sites were cleaned and gently abraded. The reflex was induced by transcutaneous electrical stimulation of the sural nerve at the right ankle while the subject reclined in a comfortable armchair with the lower legs bent to an angle of less than 150 degrees so as to achieve a state of muscular relaxation."

November's Mayo Clinical Proceedings has several important articles ( table of contents for the entire issue). 
First, is a lengthy summary and discussion of the, as they put it, Terri Schiavo "saga," that grew out of a grand rounds at Mayo.  It is quite thorough and a good read, and one hopes--probably unrealistically--that certain public officials and prominent opinion makers will read this with an open mind.  It ends with several pages of addressing the specific ethical questions the case raised, as well as asking "Is there a better way?"  Which brings up something I meant to blog a while back:  I attended a speech given by Michael Schiavo (at an end of life ethics conference) & he said a few interesting things.  First, given that it is often mentioned as an unclear point in the Schiavo history (including this article), Michael Schiavo stated that it was, indeed a conflict over money/the settlement that caused the rift between him and the Schindlers.  The second, and much more interesting point, is that Mr. Schiavo said it's his belief that there's nothing doctors/the medical community could have done to prevent the conflict, that it was a family/personal conflict, & not a failure of Terri Schiavo's docs or anyone else.  As a doc, that sounds reassuring to me, and on reviewing the case in this article, it seems like he's right.  Despite being touchstones for all of us, cases like Schiavo's going to the courts are rare; and while getting the courts involved is generally undesirable her case seems like a reasonable one for the courts (to establish what her wishes would be given there was intractable conflict within the family & no written evidence of her wishes).  What went tragically wrong with the case was not this but the extra-judicial involvement, the political intervention--"Terri's Law," Jeb Bush, Bill Frist's speech, Tom Delay's intimations of violence against "activist judges," President Bush flying back from Crawford, Judge Greer getting death threats and booted out of his church, etc.  That's the problem & promoting advanced directives isn't going to fix that....
I've already blogged too long tonight, but there's also a review of the medical and ethical aspects of long-term enteral tube feeding.  Thorough, and despite being written by a bunch of MD's, seems to have a distinct speech-pathologist flavor to it.  It presents much of the same material as the JAMA 2004 review of tube feeding, with more stuff on post-stroke & cancer patients. 
And finally, there's a review of adult acute lymphoblastic leukemia for those of you interested.

The current NEJM has a review on the medical management of depression.  It's solid.  One sentence of it caught my attention however, in the section about discontinuing treatment:  " The discontinuation syndrome is sometimes called the withdrawal syndrome, erroneously implying drug dependence."  Am I wrong in thinking this is a weird and misleading statement, especially from a psychiatrist?  I have been taught that (physical) drug dependence is in fact defined by the occurance of a withdrawal syndrome if the drug is discontinued (which usually prominently includes somatic symptoms and not necessarily "cravings").  I'm not sure if the author meant to write "erroneoulsy implying drug addiction" or if there's some custom of only using the term "dependence" in relation to drugs of (potential) abuse/addiction.  If so, that seems wrong to me, and not based in physiology.  Correct me, however, if there's something I'm missing.

I'm back from my vacation & there are many, many articles to blog & I'll hopefully be slogging through them in the next couple of weeks.  Some brief follow-up:  last week I promised an expanded "recent posts" sidebar but will have to renege on that--it's impossible to do in Blogger without manually entering every post into html & unless someone wants to pay me to do that I don't have the time.  You can use the Blogger "search this blog" toolbar up above to look for topics or old posts etc. 

One quickie::  J of Urology has a review article on palliative care for urologic malignancies.  It's quite comprehensive and an interesting view of palliative care from urologists' perspectives.  These sorts of articles are also always so useful as reference sources (looking for a reference on the use of alum bladder irrigation to control bleeding from bladder cancer?--it's in this article). 

The current Pain presents another randomized, placebo-controlled trial looking at duloxetine in painful diabetic neuropathy.  348 people were enrolled who were not depressed and on no analgesics (traditional or adjuvant) other than acetaminophen & were randomized to 60mg qday, bid, or placebo.  Both the 60mg qday & bid were more effective than placebo (starting at about 1 week and lasting for the 12 weeks of the trial).  The effect, typical for neuropathic pain trials with adjuvants, was quite modest, about -2.5 on the 11 point pain scale (placebo was about -1.2), but statistically significant.  Importantly, 60mg daily provided equivalent relief to 60mg bid but with markedly fewer side effects.  For those of you who haven't used duloxetine (Cymbalta), it's a relatively new antidepressant that is both a serotonin and norepinephrine reuptake inhibitor and so has more promise as an analgesic than the traditional SSRI's.  It actually has an indication for treating painful diabetic neuropathy already but it seems the editors of Pain thought the world needed one more article about this.  I suspect there will be more RCTs involving it in other neuropathic pain states.

I fussed with the layout last night in Firefox but today am realizing that in Internet Explorer Pallimed's layout is screwy. Sorry & am trying to fix asap.

Addendum: as of 2pm CST it looks like the layout problems are resolved, at least in IE.

This week's JAMA has a meta-analysis examining the increased risk of death with atypical antipsychotics in demented patients.  The authors looked at only randomized placebo-controlled trials (although a couple of trials had haloperidol arms) for a total of ~3300 patients.  Generally, all the meta-analysis i's & t's were dotted and crossed.  The OR of death with atypicals vs. placebo was 1.54 & the authors calculated a number-needed-to-harm of 100 (with 95% CI NNH ranging from 53-1000).  They point out that the NNT for atypical antipsychotics in dementia is 4-12 & that, then, for every 9-25 patients helped in these trials there was 1 excess death.   This, I think, makes the NNH of 100 seem a bit less acceptable.  None of the novel antipsychotics were particularly worse than the others.  They did briefly analyze the mortality with the haloperidol patients and compared them to placebo & found that those patients receiving haloperidol died more too.   It's important to note as well that most of these trials followed patients for less than 12 weeks, meaning that the mortality difference was noticable in this relatively short time. 
So is it time to bring out the principle of double-effect for antipsychotics in dementia?  That these are drugs that may improve people's quality of life but also may hasten death in a few?  There are probably a few geriatricians amongst this blog's readers & I'd be interested in any comments.

On a mundane note I'm travelling this coming week &, depending on how busy I am, may not post much.  I've noticed that the last week I've been getting quite a few more hits than before and am creeping up to 50 a day sometimes which is astonishing to me.  Thank you, all who read.  Please leave me comments if you'd like:  in general I'm curious as to who, besides my mother & immediate colleagues, reads this blog, as well as any general feedback, criticism, etc.  You can leave comments anonymously if you want.  I'm going to try to lengthen the "recent posts" section to make reviewing past posts easier especially for new or infrequent readers.  I've also decided that I'm really angry at the Lancet website which makes you log-on just to read a simple abstract (unless you're visiting from a proxied server) & am going to try to put those links into PubMed.  The problem is that on occasion PubMed can be days or weeks behind electronic publication so sometimes there's nothing in PubMed to link to.