"Subscribe" to the Bench & Bedside Journal Club

You can now subscribe to the Bench & Bedside Journal Club at Google Groups. All postings on the blog will automatically be sent to the Group, and it may also facilitate other discussion. So, enjoy!

Do science and medicine under-utilize technology?

It seems under-utilization of technology is a common topic these days in science and medicine (e.g. Nature 438:531 and NEJM 348:2526). For a field that spends SO much on its own technology, and that has so many smart people, why is the everyday stuff so backwards? I think this could be an interesting discussion point. Here are just a couple of examples.

Internet: Science tends not to use blogs, wikis, online discussion forums, or even mailing lists and online publication to the fullest. For example, my labmates that graduate next week were still required to provide print copies of their thesis for binding, the theses are being copied to microfiche, and there was no method to include videos or digital-quality images (in the end, one of the individuals included a CD in the printed thesis, enclosed in a binder-type slip case). Even search engines (e.g. PubMed), one of the most common uses of the internet in biomedicine, doesn't fully take advantage of the internet, having only recently added any cross-referencing between websites, and still limiting searches to a few fields rather than linking to other databases (e.g. allowing searches by title, author, and journal citation index).

Communication: Even internet communication seems to catch on slowly, as many older professors are hesitant to use email while my grandparents, and those of many of my friends and family, love using it. Beyond email, how many doctors have Blackberry PDA's or smartphones (pagers are still the standard!)? How many use internet chat to communicate within their laboratory or institution?

Data Management: Excel still seems the standard, if not state of the art. Even clinical management software is ages behind, often looking like an old Telnet interface, or a really lousy GUI. Nothing begins to approach the ease and accessibility of modern games and word processors, and certainly only the most advanced systems use decent implementations of SQL, XML, etc.

I hope those commenting on this post will cite other examples, as there's no shortage.

What's the best format for an online journal club?

First off, I should define a journal club. I will go beyond Wikipedia's definition to say that I specifically think the term should refer to an interactive discussion about the primary literature. I contrast this with just posting interesting papers (e.g. Faculty of 1000), providing a customizable search service (e.g. CiteTrack), and discussing non-primary material (e.g. reviews or textbooks or class material). All the things have their place, and here I'm talking about the journal club, where individuals can share thoughts, learn about new papers, critique those papers, etc.

So, if this were to be done online, how should it be done? I give several possible examples, but please feel free to post others.

Email: It's easy and almost everyone has it, but I have my concerns about formatting consistency and accessibility - it isn't guaranteed that everyone emails out every comment to every person. To maintain an open discussion format, things would actually become more complicated than need be. You could do a mailing list, but I still feel this loses some of the power of the internet.

Chat Rooms: Sounds great, except your locked into the look & feel of the chat room, and it's live only. Sure, this uses the geographic strength of the internet, i.e. that you can be anywhere and participate, but it doesn't take advantage of the potential temporal aspects, i.e. "asynchronous" discussion taking place on each participant's time frame.

Discussion Forums: This method, in which I'll lump "Groups" at Friendster, Google, Yahoo!, MSN, etc., seems ideal. It allows for posting and commenting, organizes comments by discussion thread, and is relatively secure. The catch is that it seems they're just generally unappealing visually.

Blogs: For a "moderated" journal club, this seems ideal, but as I'm learning, non-members can only post in comments. As such, anyone wanting to post a new article needs to run the risk of it being buried in comments, or needs to contact the blog owner to become a member or to have the article posted. Otherwise, I love the look and feel, the security, and the versatility.

Wikis: Again, seems like a great idea, but I haven't explored the wiki farms out there very well. I like the idea that anyone can edit in that it allows anyone to post content at equal level. However, this format would require some considerably respect, or else some degree of moderation, to prevent abuse.

I have no doubt I'm missing many meaningful categories of online publishing formats. I haven't even begun to discuss the options for customized webpages or internet-based custom software packages. Please feel free to post comments on any aspect of this idea, as I'm eager to hear what people think.

COX-2 Inhibitors

• NEJM 352(11), March 17, 2005
• Lancet 360(9339):1071-1073, 2002
• J. Clin. Invest. 116:1391-1399, 2006

Okay, I'm hoping SOMEONE comments on this post, but since it seems noone even visits the page, that seems unlikely....

The NEJM issue features the articles that recently described the increased cardiovascular risk of Vioxx leading to an industry chaos.

The Lancet article is one of many that details these risks long before they were talked about openly, thus precipitating the fury with Merck and the FDA.

The JCI article gives a hint of possible ways around the problems.

Anyone want to stand up for Bayer?

Where's the papers?

Unfortunately, this blog doesn’t have a “number of visits” counter, so I don’t know if anyone is reading this. Maybe I’ll add one – can I do that? I’d think so, it is HTML content compatible. Anyway….

If you are visiting the blog (which, if you’re reading this, obviously you are), I’ve not recently posted any new articles partially because I didn’t like the ones I’ve read, partially because the ones I liked I want to read more carefully, and partially because noone seems to care, based on lack of discussion. PLEASE feel free to post your own favorite articles and/or discuss articles. That is, after all, what a journal club is all about.

A Randomized, Placebo-Controlled Trial of Natalizumab for Relapsing Multiple Sclerosis

• Polman et al., NEJM 354 (9): 899-910, 2006
• PMID: 16510744

(see also: Rudick et al., NEJM 354 (9): 911-923, 2006)

Natalizumab is a monoclonal antibody against alpha-4 integrins. The alpha-4 family of adhesion molecules on lymphocytes (most importantly T-cells) binds to Ig-superfamily receptors (notably VCAM-1) on endothelium during early phases of the extravasation process. By blocking these interactions, T-cells can be prevented from entering tissue and thus inflammation can be prevented.

Natalizumab has been tested in Crohn’s disease and multiple sclerosis. The drug has been largely successful, but a series of major adverse events last year temporarily halted all trials (see references 25-27 in title paper). A subsequent evaluation of the data concluded that studies could continue, but this situation raises serious issues about the balance between drug risks and drug benefits. Adhesion molecule inhibition promises to be a potent strategy for blocking inflammation, especially where organ- and process-specific targets can be found (e.g. alpha-4 integrins are reportedly most relevant in the brain and gut). However, the consequences of such therapies must be considered. Certainly we are in an era where the concept of "do no harm" must be viewed in context (i.e. drug toxicity is a given), but inducing death in any fraction of patients where there was no imminent risk seems like an excessive trade-off.

While monoclonal antibodies are clearly powerful drugs, they may sometimes be too powerful, taking too long to wash out if an adverse event is reported and/or too potently inhibiting the target systems. Note similarities between this case and the reactivation of tuberculosis in patients treated with infliximab (Remicade). Perhaps the use of less-specific yet more pharmacokinetically manipulable drugs, e.g. designer small molecules, is the answer in such cases, or else more advanced monitoring need be implemented. Remicade has been successful with the added safety net of proper TB screening - could natalizumab succeed safely if we ensure proper PML screening?

Variable hematologic presentation of autoimmune gastritis: age-related progression from iron deficiency to cobalamin depletion

• Blood 107 (4): 1673-1679, 2006
• PMID: 16239424

As many of you likely already know, H. pylori has reached the penultimate in scientific fame as winner of the 2005 Nobel Prize in Physiology or Medicine. Independently of that, the topic of infectious triggers to autoimmune disease has been popular for some time, too. This article ties these two topics together nicely.

This study examines three cohorts of patients with autoimmune gastritis: those with iron deficiency anemia (IDA), those with normocytic blood indices, and those with macrocytic anemia. They find that all groups have evidence for an autoimmune polyendocrine syndrome and for antibodies against intrinsic factor, suggesting a similar pathologic process occurring. The IDA group was largely younger with a high incidence of H. pylori seropositivity, while the macrocytic anemia group, all meeting the criteria for pernicious anemia, was older with a low incidence for H. pylori infection. The RBC indices additionally show positive correlation with increasing age. The authors suggest that these data suggest that the three cohorts may be different phases of the same disease process. If true, this would open new doors to understanding pernicious anemia, and possibly help devise earlier routes for intervention prior to full-blown disease development.

The authors admit that this study is simply correlative and suggest that a study be done to follow the IDA cohort over time to determine if they really develop PA as per the model proposed. I would ask that if their model is strictly true, why is the serologic incidence of antibodies against H. pylori so low in the PA group? Does anyone know whether IgG against H. pylori really disappears that reliably after eradication?

Glucocorticoids exacerbate obesity and insulin resistance in neuron-specific proopiomelanocortin-deficient mice

• J. Clin. Invest. 116:495-505, 2006
• PMID: 16440060
• Available on PubMed Central
• Evaluated by Faculty of 1000 Biology

Well, hear it is, my attempt at a first article choice for Bench & Bedside.

This isn't my area of expertise, but I figured I had to start with something with wide-spread appeal. This article integrates genetics, neurology, endocrinology, physiology, and more, and has clear clinical implications. To reinforce the importance of the topic, and hopefully spark conversation, I point out that Nature Medicine did a recent focus on metabolic syndrome. The article also has obvious connections to the management of diabetes and pre-diabetic conditions, recently a major focus in The New York Times.

Please feel free to comment on any aspect of this article - the science, each individual figure, the implications, other related articles, projected clinical strategies, etc. I don't really know how this experiment in online journal clubs will mature, so hopefully we can all figure that out together.

Thanks, and happy reading!