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Fingerprint science should be like medical science

This article in Nature looks at the science behind identification by fingerprints. As you read it, you will note how the technical side of identification meshes with practical and empirical reality, and how biases can and will be introduced. A good place for “kappa” studies, and examining a complex human system rationally.

Cancer biology. We know a lot, we don’t know quite a bit …

As we look at natural history in 513, it’s a good idea to remember that being a physician scientist involves having an open mind. We all have in our memories the standard picture of the rise and progression of cancer. One bad cells leads to two, then four etc. In pictures, a little ball of cells becomes a bigger and bigger ball. The message is that bigness is badness, and getting rid of the bigness is in some sense actually attacking the roots of cancer.

Pictures are not reality. This picture might reflect the underlying biological reality. But it might not. The facts we know are reality, and more than one picture might be compatible with the underlying facts. Take a look at this article in Science, which talks about circulating tumor cells and what they might mean. This ties in with an idea in cancer science that the important cells in cancer might actually be a small (actually tiny) subset of the tumor which are cancer stem cells.

The most important disease(s) is(are)?

Judging by television news, you might think that breast cancer is the only disease that exists. If we wanted to spend money on the disease or group of diseases that results (by a considerable margin) in the greatest lost of quality of life years the world over, denying young (and older) people of their lives and quality of life, we would spend our money on mood disorders, schizophrenia, and bipolar illness.

Psychiatry is often knocked by the rest of medicine as being relatively unscientific (ie its all about talking). But the psychiatric community has probably gone farther than most in putting (with some success) their discipline on a scientific basis. One of the remarkable things about psychiatry is the presence of a codified scientifically based diagnostic process. This is diagnosis at the RDC or gold standard. How this is done is quite a remarkable story in itself. Science has an ongoing series of article about the latest revision of the DSM. The articles so far are 1) Proposed Revisions to Psychiatry’s Canon Unveiled, 2) DSM-V at a Glance, 3) Behavioral Addictions Debut in Proposed DSM-V, and 4) Experts Map the Terrain of Mood Disorders.

CONNECT VIA MYVPN TO GET WORKING LINKS TO SCIENCE!

Replacing an immune system … it’s hard to do a study

Science (2010-Feb-12) has an article about ablating and replacing the immune system in various autoimmune conditions. It appears that some people have ongoing remission from their conditions (MS, scleroderma, lupus etc). The problem is that some people die from the intervention. The intervention is now being down only at very late stages of the illness because doctors can’t risk death at earlier stages. But it seems reasonable that the intervention would be more efficacious earlier. Would you sign up for a trial? What kinds of studies are sufficient to implement this therapy?

Brawling over mammography

A wonderful look at the recent controversy over mammography for women in the 40-50 age range is in the Feb 19 issue of Science (remember myVPN connection to UBC network). A great discussion of the intersection of evidence with the wonderful spectrum of humanity.

The most beautiful place on earth … will have the least chronic disease on earth … if only …

As outlined in the Vancouver Sun, Health Minister Kevin Falcon came across a striking finding reading a British newspaper last summer. He read that “people who take regular exercise, stay slim, eat a healthy diet and never smoke reduce their chances of developing chronic disease by almost 80 percent.” Thinking about this, he realized that “this issue of health promotion has to go far beyond just printing brochures and telling people they ought to live a healthier life.” Going on, he says “I think we have to figure out how we can be much more aggressive in pushing that kind of a health promotion onto British Columbians.”

Canadians tend to smile at American exceptionalism. These are difficult questions that no society, seemingly, has figured out up to now. Thankfully our Ministry of Health is onto this, and our province will lead the world to a solution, albeit aggressively. Hopefully this won’t involve Tasering people who actively resist the aggression that’s for their own good.

“It’s devastating … no going back to normal.”

Friday’s Globe and Mail had an article about women with breast cancer. These women were/are given a choice of four cycles of Taxotere, or twelve cycles of Taxol for their cancer. The efficacy of these two alternatives is about the same (apparently).

Taxol, the cheaper generic, has “a very tiny risk of permanent hair loss.” Taxotere has a 3 in 100 chance of permanent hair loss (alopecia universalis). This means permanent loss of all body hair (eyebrows, everything). Another study puts this likelihood as high as 6 in 100.

Most women, when given a choice, choose Taxol.

The company’s (Sanofi) response to this is: “We fully understand that persistent alopecia may be a burden for patients, but still we consider it’s certainly something which is not life-threatening or is not something which impairs the likelihood of survival.” In other words, “we saved your life, so there.”

Sounds  like a case of POEM, and a situation where values enter the equation. CDA anyone?

Blood-pressure cuff can curb damage of heart attack

Having an open mind is part of being a scientist. The Globe and Mail has an article about a clinical trial resulting from an idea of Dr. Andrew Redington (Hospital for Sick Children, Toronto). During the ambulance ride to hospital, people with suspected MI were randomized to having a blood pressure cuff inflated and deflated for alternating five minute periods (repeated four times). Once at the hospital they received usual care. You can see the whole writeup at TheLancet.com (type Redington into the search field to find the article).

More Avandia

From the “you’ve got to be kidding me” file, here is an article from the New York Times, about how GlaxoSmith-Kline attempted to co-opt Dr. Steven Nissen (Cleveland Clinic) when they found out about his upcoming study about the risks of Avandia. Highlights: a scientist who is reviewing Dr. Nissen’s manuscript sends a copy to GSK, GSK then starts lying, and just can’t stop once they start. Dr. Nissen tapes his meeting (legally) with GSK. The lies can’t be denied.

How does medical science move forward if this is how things work?

How’s this for freedom of expression?

A British science journalist, Simon Singh, wrote in an editorial in the Guardian newspaper that certain aspects (eg spinal manipulation for asthma) of chiropractic were “bogus.” He was successfully sued and is now appealing this decision. Read about it here, and thank your lucky stars that in Canada we would probably (in the US certainly) be allowed to say what Mr. Singh said.

Efficacy and effectiveness are different! Effectiveness matters!

As you read the guidelines for your major project, you read in the AFP article that you should think about and emphasize POEM (Patient Oriented Evidence that Matters) rather than DOE (Disease Oriented Evidence). Although we hardly ever need new terminology, the authors decided to come up with new terms for efficacy (DOE) and effectiveness (POEM).

Recently in the US Senate, there has been a discussion that has to do with POEM rather than DOE. It’s interesting that EBM makes it to the political arena.

The American discussion has to do with rosiglitazone (Avandia) and pioglitazone (Actos). Here’s the distinction between efficacy and effectiveness. If you look at these two drugs in terms of efficacy, they are both good, in that they both do what they are supposed to do (lower blood sugar) about as well. This is DOE.

Unfortunately, “The senators cited internal FDA findings that: “[T]here is no evidence that rosiglitazone [the generic name for Avandia] confers any unique health benefits over pioglitazone [Actos] while there is strong evidence that rosiglitazone confers an increased risk of [heart attacks] and heart failure compared to pioglitazone.” [Financial Times, 2010-Feb-22]

If you had a choice of taking Actos or Avandia, you would want to know this, and it would MATTER. This is information about effectiveness. I personally would not choose Avandia for myself. Because I read not only the DOE, but also the POEM. I want effectiveness as well as efficacy.

Another excellent summary of this discussion is in the New York Times. [Research Ties Diabetes Drug to Heart Woes, February 19, 2010-Feb-19]

Publish or perish (in China)

Nature (2010-Jan-14) has a couple of articles about what happens when real humans (and these are scientists) are rewarded in certain ways. Humans are humans everywhere, and misconduct happens. This article has a discussion of the amount and importance of activities like ghostwriting, bypassing peer review, and forgery. In China there are 800+ websites involved in such activity, with 210,000 hits per day. “There is a massive production chain for the entire publishing process.”

Later in this issue, you can read about a new journal that took articles from existing journals and just replaced all the previous branding. They were otherwise happy with the original electronic typesetting!

Remember to connect to the UBC Library via MyVPN to view these links!

A perfect way to while away a boring interlude in 513 …

Just a reminder that Chancewiki has lots of clinical epidemiology stuff. Have you hit a boring patch of 513? Got a computer in front of you? Head over to http://chance.dartmouth.edu/chancewiki/index.php/Main_Page!

Take a look at Chance News 58, where they talk about negative data. And reverse confounding.

Clinical epidemiology in Canada

Today’s Toronto Globe and Mail has an article about the funding crisis in Canadian clinical epidemiology.

Are there problems with the meta-analytic approach?

In short, yes. Can they be biased? Yes. Can they be unbiased? Yes. Kind of like everything else. An article in the New York Times looks at some of the issues when looking at a recent meta-analysis of antidepressants.

How effective is influenza vaccine?

This article from the Atlantic provides an overview of the ideas I mentioned in class about overall effectiveness of influenza vaccination. They call the membership bias “healthy user effect.” It gives enough information for you to be able to hunt down original sources if you care. Before, this gets controversial, let me say that I got both my flu shots this year. But then I’m one of those people (albeit only a “semi-healthy user” ) who might have produced the bias, right?

Alzheimer’s, Parkinson’s, ALS, Huntington’s: could they all be prion diseases?

An article in Science outlines the hypothesis that all these diseases are caused by prions. There is a UBC angle re Dr Neil Cashman’s work on ALS. Good medical/science journalism: priceless!

Our very own scandal, again!

In case you can’t get to the Medical Post article mentioned previously, here is a link to a story in the Montreal Gazette about our very own academic leader who apparently published (as single author), an article she didn’t write. Fortunately the contents of the article (about estrogen) are all true, and can guide us when we think about estrogen as a therapy.

We (Canada) botched mammography!

Referring to the CNBSS trial at the Radiologists Society of North America annual meeting recently, Dr. Dan Kopans, a prominent American radiologist states the study was “botched”, although he apparently didn’t give any supporting statements. In response, Dr. Steven Narod, a Toronto epidemiologist and leader in breast cancer research, called Dr. Kopans remarks “scientific misconduct.” Dr. Narod also is quoted in the Medical Post article here as stating that “I think he knows absolutely nothing about epidemiology.”

Why do we need to know epidemiology anyway?

PS: YOU MIGHT NEED TO NOW ENROLL IN “www.CanadianHealthcareNetwork.ca” TO GET ACCESS TO MEDICAL POST CONTENT. SORRY ABOUT THE INCOVENIENCE.

Great medical journalism at the New York Times

Being a scientist involves always having an open mind. Today’s New York Times has an article here by Gina Kolata about the work of Dr. Mina Bissell on the cause of cancer.

In 513, you’ll hear me say over and over that we don’t know much natural history of disease, and this is probably the source of a lot of “muddiness” in epidemiology. Here is a link to another Kolata article, in which results of a study on natural history of breast cancer suggest that some cancers go away spontaneously.

How likely is a woman to get breast cancer?

Do women actually have diseases other than breast cancer? You might wonder what the most important diseases are for women (kind of like the WHO’s Global Burden of Disease approach). The Medical Post (2009-Nov-17, page 52) has an article from an academic who contrasts SEER’s risk numbers with those based on other cohorts. The Medical Post seems to have changed their web access policies recently, so I can’t post a link now. Look at the hard copy they mail physicians.

A classic from ChanceWiki

Is it possible that all illness relates to subluxation of your vertebrae? I guess it is, huh? Everyone wants evidence nowadays, so let’s get some. Take a look at chiropractors’ take on what counts as evidence at http://chance.dartmouth.edu/chancewiki/index.php/Chance_News_42. The section titled How People Are Fooled by Ideomotor Action.

We are all fasciscts! Down with evidence!

As someone who uses evidence in your practice of medicine, and benefits from standard approaches to how to do this, you might want to know that people disagree with this viewpoint. I can’t do justice to this article here. Remember that the variation in human traits is what makes your life interesting! You will need to get this electronically from the UBC Library: Deconstructing the evidence-based discourse in health sciences: truth, power and fascism. Int J Evid Based Healthc 2006; 4: 180–186.

Down with the Cochrane Collaboration! Get your evidence from … well what are we supposed to do now? Go with (the negation of) evidence-based medicine?

There have been several episodes recently where people have submitted tongue-in-cheek, or ironic, articles to journals. Could this be one? Look at the grammar and development of ideas in this one. Can it be serious?

You can’t always do an RCT

Today’s New York Times has an article about a 43 hour surgery to remove an abdominal tumor that involved ex-vivo resection of the tumor. Read the article, and ask yourself how much evidence, of what strength, it would take to make you decide to have this operation if you had this condition. You won’t ever be able to find an RCT on the topic!

More on MS as a vascular disease

Today’s Vancouver Sun has an article here about patients coming to the False Creek Surgical Centre to get MRIs and ultrasounds to see if they have the venous outflow obstruction that Dr. Zamboni has hypothesized is causal in MS. There is an interesting discussion, including a mention of the apparently high rate that re-occlusion occurs after initial treatment etc.

One patient, who has MS, but apparently not the venous obstruction, says: “”The results in Vancouver were puzzling because my understanding is that Zamboni is saying that almost all MS patients have blockages, but none were found in my case. A doctor told me that there may be narrowing in veins that weren’t seen. Still, I’m not going to not go [to Italy].”

How likely do you think it is it that this will turn out to be a revolution in thinking about causation and treatment about MS?

You can read Dr. Zamboni’s article here. (VPN connection to eJournals at UBC Library; find Volume 50, Issue 6, Pages A1-A26, 1348-1358.e3 (December 2009) Think about what a reasonable next step would be given the information in the article.

Keep on reading chancenews at ChanceWiki

A reminder to check out chancenews at ChanceWiki. Do their puzzles. Think about chance and bias. Most of the ways that research goes wrong involves macro-, not micro-epidemiology.

chancenews is at http://chance.dartmouth.edu/chancewiki/index.php/Main_Page.

Slate.com articles on autism therapy

I’ve always been fascinated by the phenomenon of simultaneous demand for evidence and resistance to evidence. “Give us evidence, but only if it confirms this idea.” The autism field is what I term “evidence resistant.” Do you know of areas of your discipline that have this feature? I can’t remember the last time an EBM idea was in the title of an article in the popular press. Slate.com autism therapy article (pdf).

Why EBM? An interview with David Sackett

Why EBM? You might just say “because we have estrogen researchers in Canada.” But it’s more than that of course. Much of the rationale for starting the field is just as important today. Recognize your clinical department in his remarks? Check it out at: http://www.theglobeandmail.com/life/health/when-we-began-we-were-almost-pariahs/article1344833/.

Renowned Canadian researcher puts name on paper she did not write, stands by results!

Take a look at the Medical Post (www.medicalpost.com) for an interesting article. You need to register (it’s easy), then go to http://www.medicalpost.com/news/article.jsp?content=20090910_130117_13308. This is an ongoing story with many interesting aspects. You might get there also by Googling “Researcher ensnared by ghostwriting scandal stands by her estrogen work”. Personally, eminence counts for a lot when I read a paper! And “Canada Research Chair” makes my eyes open that much wider.

Is MS a vascular disease?

Take a look at this article from the Toronto Globe and Mail (Saturday Nov-21-2009), which describes how a researcher’s hypothesis about his wife’s MS led to a potential new treatment. There is a description of some trials of a new therapy.

Go out on a limb, now rather than later! How likely is it that we are witnessing an actual breakthrough?