How a Valentine’s Editorial about Chocolate & Semen Lead to the Resignation of Top Surgeon Greenfield

27 04 2011
Children's Valentine in somewhat questionable ...

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Dr. Lazar Greenfield, recently won the election as the new President of  ACS (American College of Surgeons). This position would crown his achievements. For Greenfield was a truly pre-eminent surgeon. He is best known for his development of an intracaval filter bearing his name. This device probably has saved many lives by preventing blood clots from going into the lungs. He has been highly productive having authored more than 360 scientific articles in peer-reviewed journals, 128 book chapters as well as 2 textbooks.

Greenfield also happened to have a minor side job as the editor-in-chief of Elsevier’s Surgery News. Surgery News is not a peer-reviewed journal, but what Greenfield later defines as a monthly throw-away newspaper (of the kind Elsevier produces a lot).

As an-editor-in chief Greenfield wrote open editorials (opinion pieces) for Surgery News. He found a very suitable theme for the February issue: Valentine’s day.

Valentine’s Day is about love, and the editorial was about romantic gut feeling possibly having a physiological basis. In other words, the world of  sexual chemical signals that give you butterflies-feelings. The editorial jumps from mating preferences of fruit flies, stressed female rotifers turning into males and synchronization of menstrual cycles of women who live together, to a study suggesting that “exposure” to semen makes female college students less depressed. All 4 topics are based on scientific research, published in peer review papers.

Valentines Day asks for giving this “scientific” story a twist, so he concludes the editorial as follows:

“So there’s a deeper bond between men and women than St. Valentine would have suspected, and now we know there’s a better gift for that day than chocolates.”

Now, everybody knows that that conclusion ain’t supported by the data.
This would have required at least a double-blind randomized trial, comparing the mood-enhancing effects of chocolate compared to …….  (yikes!).

Just joking, of course…., similar as dear Lazar was trying to be funny….

No, the editorial wasn’t particularly funny.

And somehow it isn’t pleasant to think of a man’s love fluid wrapped in a ribbon and a box with hearts, while you expect some chocolates. Furthermore it suggests that sperm is something a man just gives/donates/injects, not a resultant of mutual love.

However this was the opposite of what Greenfield had in mind:

The biochemical properties of semen that were reviewed have been documented in peer-reviewed journals and represent the remarkable way that Nature promotes bonding between men and women, not something demeaning.”

Thus the man just tried to “Amuse his readers” and highlight research on “some fascinating new findings related to semen.”

I would have appreciated a more subtle ending of the editorial, but I would take no offense.

….Unlike many of his fellow female surgeons.  The Women in Surgery Committee and the Association of Women Surgeons considered his editorial as “demeaning to women” (NY-Times).

He offered his sincere apologies and resigned as Editor-in-Chief of the paper. The publication was retracted. As a matter of fact the entire February issue of Surgery News was taken off the ACS-website. Luckily, Retraction Watch published the editorial in its entirety.

Greenfield’s apologies weren’t enough, women surgeons brought the issue to the Board of Regents, who asked him to resign, which he eventually did.

A few weeks later he wrote a resentful letter. This is not a smart thing to do, but is understandable for several reasons. First, he didn’t he mean to be offensive and made his apologies. Second, he has an exemplary career as a longtime mentor and advocate of women in surgery. Third, true reason for his resign wasn’t the implicit plead for unprotected sex, but rather that the editorial reflected “a macho culture in surgery that needed to change.” Fourth, his life is ruined over something trivial.

Why can’t one write a lighthearted opinion-piece at Valentine’s day without getting resigned? Is it because admitting that “the “bond between men and women” is natural and runs deep” is one of those truths you cannot utter (Paul Rahe).

Is this perhaps typically American?

Elmar Veerman (Dutch Journalist, science editor at VPRO) comments at at Retraction Watch:

(…) Frankly, I don’t see the problem. I find it rather funny and harmless. Perhaps because I’m from Europe, where most people have a more relaxed attitude towards sex. Something like ‘nipplegate’ could never happen here (a nipple on tv, so what).  (…) I have been wondering for years why so many Americans seem to think violence is fine and sex is scary.

Not only female surgeons  object to the editorial. Well-known male (US) surgeons “fillet” the editorial at their blogs: Jeffrey Parks at Buckeye Surgeon ( 1 and 2), Orac Knows at Respectful Insolence (1 and 2) and Skeptical Scalpel (the latter quite mildly).

Jeffrey and Orac do not only think the man is humorless and a sexist, but also that the science behind the mood-enhancing aspects of semen is crap.

Although Jeffrey only regards “The “science” a little suspect as per Orac.”…. Because of course: “Orac knows.”

Orac exaggerates what Greenfield has said in the “breathtakingly inappropriate and embarrassing article  for Surgery News”, as he calls it. [1]:  “Mood-enhancing effects of semen” becomes in Orac’s words  the cure for female depression and  “a woman needs a man to inject his seed into her in order to be truly happy“.
Of course, it is not fair to twist words this way.

The criticism of Orac against the science that supports Dr. Greenfield’s joke is as follows: The first two studies are not related to human biology and the semen study” is “about as lame a study as can be imagined. Not only is it a study in which causation is implied by correlation, but to me the evidence of correlation is not even that compelling.”  

Orac is right about that. In his second post Orac continues (in response to the authors of the semen paper, who defend Greenfield and suggest they had obtained “more evidence”):

(..)so I was curious about where they had published their “replication.” PubMed has a wonderful feature in which it pops up “related citations” in the right sidebar of any citation you look up. I didn’t recall seeing any related citations presenting confirmatory data for Gallup et al’s study. I searched PubMed using the names of all three authors of the original “semen” study and found no publications regarding the antidepressant properties of semen since the original 2002 study cited by Dr. Greenfield. I found a lot of publications about yawning and mental states, but no followup study or replication of the infamous “semen” study. color me unimpressed” [2](..)

Again, I agree with Orac: the authors didn’t publish any confirmatory data.
But looking at related articles is not a good way to check if related articles have been published: PubMed creates this set by comparing words from the title, abstract, and MeSH terms using a word-weighted algorithm. It is goal is mainly to increase serendipity.

I didn’t have time to do a proper Pubmed search, which should include all kinds of synonyms for sperm and mood/depression. I just checked the papers citing Gallups original article in Google Scholar and found 29 hits (no Gallop papers indeed), including various articles by Costa & Brody i.e. the freely available letter (discussing their research): Greater Frequency of Penile–Vaginal Intercourse Without Condoms is Associated with Better Mental Health. This letter was a response to an opposite finding by the way.

I didn’t look at the original articles and I don’t really expect much of it. However, it just shows the Gallop study is not the only study, linking semen to positive health effects.

Assuming Greenfield had more than a joke in mind, and wanted to reflect on the state of art of health aspects of semen, it surprises me that he didn’t dig any further than this article from 2002.

Is it because he really based his editorial on a review in Scientific American from 2010, called “An ode to the many evolved virtues of human semen” [3,4], which describes Gallup’s study and, strikingly, also starts with discussing menstrual synchrony.

Greenfield could have discussed other, better documented, properties of semen, like its putative protection from pre-eclampsia (see references in Wikipedia)[5]

Or even better, he could have cited other sexual chemical signals that give you butterflies-feelings, like smell!

In stead of “Gut Feelings” the title could have been “In the nose of the beholder” or “The Smell of Love” [6].

And Greenfield could have concluded:

“So there’s more in the air than St. Valentine would have suspected, and now we know there’s a better gift for that day than chocolates: perfume.

And no one would have bothered and would have done with the paper as one usually does with throwaways.

Notes

  1. Coincidentally, while reading Orac’s post I saw a Research Blogging post mentioned in the side bar: masturbation-and-restless-leg-syndrome. …Admittedly, this was a friday-weird-science post and a thorough review of a case study.
  2. It would probably have been easier to check their website with an overview of publications
  3. Mentioned in a comment somewhere, but I can’t track it down.
  4. If Greenfield used Scientific American as a source he should have read it all to the end, where the author states: I bid adieu, please accept, in all sincerity, my humblest apologies for what is likely to be a flood of bad, off-color jokes—men saying, “I’m not a medical doctor, but my testicles are licensed pharmaceutical suppliers” and so on—tracing its origins back to this innocent little article. Ladies, forgive me for what I have done.”
  5. Elmar Veerman has written a review on this topic in 2000 at Kennislink: http://www.kennislink.nl/publicaties/sperma-als-natuurlijke-bescherming (Dutch)
  6. As a matter of fact these are actual titles of scientific papers.




FDA to Regulate Genetic Testing by DTC-Companies Like 23andMe

14 06 2010

Direct-to-consumer (DTC) genetic testing refers to genetic tests that are marketed directly to consumers via television, print advertisements, or the Internet. This form of testing, which is also known as at-home genetic testing, provides access to a person’s genetic information without necessarily involving a doctor or insurance company in the process. [definition from NLM’s Genetic Home Reference Handbook]

Almost two years ago I wrote about 23andMe (23andMe: 23notMe, not yet),  a well known DTC company, that offers a genetics scan (SNP-genotyping) to the public ‘for research’, ‘for education’ and ‘for fun’:

“Formally 23andMe denies there is a diagnostic purpose (in part, surely, because the company doesn’t want to antagonize the FDA, which strictly regulates diagnostic testing for disease). However, 23andme does give information on your risk profile for certain diseases, including Parkinson”

In another post Personalized Genetics: Too Soon, Too Little? I summarized an editorial by Ioannides on the topic. His (and my) conclusion was that “the promise of personalized genetic prediction may be exaggerated and premature”. The most important issue is that predictive power to individualize risks is relatively weak. Ioannidis emphasized that despite the poor evidence, direct to consumer genetic testing has already begun and is here to stay. He proposed several safeguards, including transparent and thorough reporting, unbiased continuous synthesis and grading of the evidence and alerting the public that most genetic tests have not yet been shown to be clinically useful.

And now these “precautionary measures” actually seem to happen.
Last week the FDA sent 5 DTC-companies, including 23andMe a letter saying “their tests are medical devices that must receive regulatory approval before they can be marketed.” (ie. see NY-times article).

Alberto Gutierrez, who leads diagnostic test regulation at the FDA, wrote in the letters:

“Premarket review allows for an independent and unbiased assessment of a diagnostic test’s ability to generate test results that can reliably be used to support good health care decisions,”

These letters are part of an initiative to better explain the FDA’s actions by providing information that supports clinical medicine, biomedical innovation, and public health,” (May 19 New England Journal of Medicine commentary, source: see AMED-news)

Although it doesn’t look like the tests will be taken from the market, 23andMe does take a quite a rebellious attitude: one of its directors called the FDA “appallingly paternalistic.”

Many support this view: “people have the right to know their own genetic make-up”, so to say. Furthermore as discussed above, 23andMe denies that their genetic scans are meant for diagnosis.

In my view the latter is largely untrue. At least 23andMe suggests that knowing a scan does tell you something about your risks for certain diseases.
However, the risks are often not that straightforward. You just can’t “measure” the risk of a multifactorial disease like diabetes by “scanning” a few weakly predisposing  genes. Often the results are given in relative risk, which is highly confusing. In her TED-talk the 23andMe director Anne Wojcicki said her husband Sergey Brin (Google), had a 50% chance of getting Parkinson, but his relative risk (RR, based on the LRRK2-mutation, which isn’t the most crucial gene for getting Parkinson) varies from 20% to 80% , which means that this mutation increases his absolute risk of getting Parkinson from 2-5% (normal chance) to 4-10% at the most. (see this post).

Furthermore, as reported by Venture in Nature (October 8, 2009): For seven diseases, 50% or less of the predictions of two companies agreed across five individuals (i.e. for one disease: 23andMe : RR 4.02, and Navigenics RR: 1.25). On the other hand *fun* diagnoses could lead to serious concern in, or wrong/unnecessary decisions (removal of ovaries, changing drug doses) by patients.

There are also concerns with regard to their good-practice standards, as 23andMe just flipped a 96-wells plate of costumer DNA (see Genetic Future for a balanced post), which upset a mother noticing that her son didn’t have compatible genes. But lets assume that proper precautions will prevent this to happen again.

There are also positive aspects: results of a preliminary study showed that people who find out they have high genetic risk for cardiovascular disease are more likely to change their diet and exercise patterns than are those who learn they have a high risk from family history. (Technology ReviewGenetic Testing Can Change Behavior).

Furthermore, people buy those tests themselves and, indeed, there genes are their own.

However, I agree with Dr. Gutierrez of the FDA saying: “We really don’t have any issues with denying people information. We just want to make sure the information they are given is correct. (NY-Times). The FDA is putting the consumers first.

However, it will be very difficult to be consistent. What about total body scans in normal healthy people, detecting innocent incidentilomas? Or what about the controversial XMRV-tests offered by the Whittemore Peterson Institute (WPI) directly to CFS- patients? (see these posts) And one step further (although not in the diagnostic field): the ineffective CAM/homeopathic products sold over the counter?

I wouldn’t mind if these tests/products would be held up to the light. Consumers should not be misled by the results of unproven or invalid tests, and where needed should be offered the guidance of a healthcare provider.

But if tests are valid and risk predictions correct, it is up to the “consumer” if he/she wants to purchase such a test.

—————–

What Five FDA Letters Mean for the Future of DTC Genetic Testingat Genomics law Report is highly recommendable, but couldn’t be accessed while writing the post.

[Added: 2010-06-14 13.10]

  • Problem assessing Genomics Law Report is resolved.
  • Also recommendable: the post “FDA to regulate genetic tests as “devices”” at PHG Foundation. This post highlights that simply trying to classify the complete genomic testing service as “a device” is inadequate and will not address the difficult issues at hand. One of the biggest issues is that, while classifying DTC genetics tests as devices is certainly appropriate for assessing their analytical validity and direct safety, it does not and cannot provide an assessment of the service, thus of the predictions and interpretations resulting from the genome scans.  Although standard medical testing has traditionally been overseen by professional medical bodies, the current genomic risk profiling tests are simply not good enough to be used by health care services. (see post)
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Haiti still needs help

21 01 2010

Usually, I don’t grant requests for help “to get the word out”. But I will make an exception for a good cause: Haiti.

You could help Haiti by supporting the International Medical Corps (IMC).

The IMC is a global, humanitarian, nonprofit organization, founded by volunteer doctors and nurses in 1984 and dedicated to saving lives and relieving suffering through relief and development programs. Their emergency response team is in Haiti responding in force, but there are still thousands of patients seeking treatment of which approximately 80% are in need of surgery and are running out of time – especially with the tremendous aftershocks still devastating this country. The team is treating crush injuries, trauma, substantial wound care, shock and other critical cases with the few available supplies – And they’re in it for the long haul.

You can help by donating funds, volunteering in Haiti, or just spreading the word (i.e. putting a widget on your site or or Tweeting this )

Want to know more about IMC’s rescue efforts, see:  http://www.imcworldwide.org/haiti

Here you can also donate to help people of Haiti.

Donating $10 to help the people of Haiti is as simple as sending a text message of the word “haiti” to 85944. But other ways are also possible, i.e. click on the red widget on the left.

Importantly, IMC is highly efficient as 92% of their resources go directly to program activities.

————————————
Nederlanders kunnen ook deze internationale organisatie ondersteunen.

Daarnaast kunt ook terecht bij het oude vertrouwde noodhulp gironummer 555, dat nu speciaal opengesteld is voor Haiti (zie bijvoorbeeld NRC-next). U steunt daarmee wel andere organisaties, die noodhulp geven.

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Friday Foolery #10. 6 x X-Rays

7 11 2009

“X-rays” were in the news this week, at least there was an illuminating exposure on Twitter. Here are 6 stories, half serious and half not so serious.

[1] First, voters have picked the X-ray machine as the most important scientific invention (objects in science, engineering, technology and medicine), in a poll to celebrate the centenary of the Science Museum in London. As a matter of fact medical inventions were in the top three places in the poll (1. X-ray machines 2. Penicillin and 3. DNA double helix), ahead of the Apollo 10 capsule (no. 4) and the steam engine (8).

BBC: http://news.bbc.co.uk/2/hi/health/8339877.stm
BMJ: http://www.bmj.com/cgi/content/short/339/nov05_3/b4602?rss=1

[2] Margaret Daalman came to hospital complaining of stomach ache – and one glance at her X-ray showed why:  the 52-year-old woman’s stomach contained an entire canteen of cutlery. She had to go under the knife to remove the (78!) forks and spoons. (see fotos here) The woman told the doctors: ‘I don’t know why but I felt an urge to eat the silverware – I could not help myself.’ She was somewhat picky however, as she never ate knives.
The images were actually taken over 30 years ago, but they were published for the first time this week in a Dutch medical magazine. Yes the woman was Dutch. At least according to the Daily Mail…….

However, the actual story published as a case in Medisch Contact is somewhat different.They actually state below the article:

Mededeling redactie

Over deze casus is in de populaire media foutieve berichtgeving gaande. De in andere media opgevoerde ‘mw Daalmans’ heeft niets te maken met deze casus. Het betreft, in tegenstelling tot wat elders wordt beweerd ook geen casus van 30 jaar geleden.

Which means something like: in contrary to what has been stated by the popular press this case has nothing to do with Mrs Daalmans, nor did it happen 30 years ago.
In effect, the Daily Mail mentions both (?) Rotterdam and Sittard as towns where this should have taken place, but in Medisch Contact only Helmond was mentioned. The towns are far apart.

One wonders why, because the story is extraordinary enough.

Daily Mail: http://www.dailymail.co.uk/news/worldnews/article-1223563/The-woman-knife--swallowing-entire-canteen-cutlery.html
Twitter: http://twitter.com/drves/status/5403151285
Medisch Contact: http://medischcontact.artsennet.nl/blad/Tijdschriftartikel/Bestek-in-de-maag.htm

[3] An obese man died after refusing an X-ray taken in a machine for zoo animals because he was too large for the hospital’s X-ray machine, the maximum capacity of most hospital machines being around 200 kilo. Later his wife told that the man felt too humiliated to go to the zoo.

The Local (Germany news in English, Bild.de.) http://www.thelocal.de/society/20091103-22993.html

[4] Todays Friday Funny post of dr. Val at Better Health is Joyful Radiology or Merry X-Ray

engrish-funny-merry-xray

Better Health: http://getbetterhealth.com/the-friday-funny-joyful-radiology/2009.11.06

[5] A special X-Ray: CAT-scan

4076270034_aa19e6dd2b cat-scan

http://www.flickr.com/photos/robinkearney/ / CC BY-NC-SA 2.0

[6] When both your arm and the X-ray are broken:

Cyanide and Happiness, a daily webcomicCyanide & Happiness @ Explosm.net

Ooh, I wonder whether the great number of X-ray related posts has something to do with the upcoming overlooked holiday: X-ray day (November 8th).

Can someone put the light off?

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Does the insulin Lantus (glargine) cause cancer?

7 07 2009

Last week my eyes were caught by a post of Kevin MD at his blog entitled

Does insulin cause cancer, and should you stop taking Lantus?”.

Kevin linked to the blog of Dr. Mintz, a board-certified internist, who had a strong opinion on this. Dr. Mintz  posted 3 blog articles on the matter, entitled: A new problem with insulin: cancer (June 29), Lantus causes cancer! Why doesn’t anyone seem to care? (July 1) and Lantus and cancer – A closer look is not reassuring (July 2). Dr. Mintz’s conclusion was based on 4 recent publications in diabetologica (1-4)6-7-2009 10-14-07 dr Mintz + foto

Alarming. Especially since Dr. Mintz is an expert, often prescribing insulins. Also, I’m suspicious  about any substance with an IGF (insulin growh factor)-like action, because I know from previous work in the lab that some tumor cells (i.e. prostate and breast cancer) thrive on IGF. On the other hand there have been several examples in the past, where retrospective studies initially “showed” drugs to cause cancer, which have later been invalidated by more thorough studies (i.e. statins).

“Lantus causing cancer” is a serious allegation, that might cause panic in those many diabetic patients using Lantus. Are fears justified and should Lantus be “banned”?

After reading the publications (1-5), news articles and some blogposts (i.e. a balanced blogpost at Diabetesmine, a blog of a patient) and a very thorough blogpost in Dutch), I rather conclude that the recent publications in Diabetologica, dr Mintz* refers to, do not support a causal role for Lantus in cancer. However, they still give reason for some serious concern in a subset of patients (explained below).

Now what is Lantus and what have preclinical and clinical trials revealed?

Insulin glargine (Lantus) is the first of the long-acting insulin analogues, introduced in 2001. This analogue is a so called designer molecule made by the recombinant DNA technique. It has three amino-acid substitutions, that cause a lower solubility of the insulin molecule  at the injection site, forming a depot from which insulin is slowly released (9, 10).  The advantage is that stable 24hr blood glucose concentrations are reached by a once daily subcutaneous injection without a blood glucose peak upon injection as seen with the short acting insulins. However, insulin replacement remains far from ‘natural’, “the insulin is injected in the wrong site (subcutaneously instead of intraportally), in shots (instead of a continuous low secretion associated with a prompt release in response to a meal, with a total lack of the physiological pulsatile secretion”).lantus pen + kineticsInsulins not only bind to the insulin receptor, leading to the intended glucose lowering, but also to the insulin growth factor receptor (IGF-R), which mainly induces cell proliferation. Importantly, glargine has a much higher affinity for both receptors than insulin. This can lead to a sustained activation of the IGF-receptor, resulting in enhanced cell growth.

Indeed, Preclinical Research has shown that only glargine showed a significantly higher proliferative effect on breast cancer cells compared to regular insulin among a panel of short- or long-acting insulin analogues (6) . Futhermore,  insulin analogues display IGF-I-like mitogenic and anti-apoptotic activities in cultured cancer cells (thus they stimulate cell division and prevent programmed cell death of cancer cells (8).

Experimental animal studies haven’t shown a tumorigenic or teratogenic potential of glargine, except for histiocytomas in male rat (Product information Lantus). Such studies don not examine tumor promoting properties (see below)

Clinical Studies (published in Diabetologica 2009)

Based on the insulin analogue characteristics and the in vitro results there was already concern about possible increased cancer risk of glargine. But the concern was boosted by a prominent diabetes researcher forecasting an “earthquake” event compromising the safety profile of Lantus,  and the subsequent publication of five studies in  the European journal Diabetologia, the Journal of the EASD (European Association for the of Study of Diabetes).

Except for one small study, which was a post-hoc analysis of a randomized study by Sanofi-Aventis itself [5], all other studies were retrospective. The Sanofi study didn’t find an increase in cancer, but given its small size (1000 patients), it is not  convincing enough to exclude a higher risk of cancer.

The first, German, study [1] was submitted a year ago, but because of the uncertainties and the expected high impact, researchers from other European countries were asked to replicate the findings before announcing them formally. Studies were carried out using databases from Sweden, Scotland, and the UK.

The German study (n= 127,031 patients, exclusively on human insulin or on one type of insulin analogues (lispro, aspart or glargine; glargine: n=23,855 ; mean follow-up time 1.63 years) found an overall increase in cancers, independent of the insulin used. After statistical modeling, a dose-dependent increase in cancer risk was found for treatment with glargine compared with human insulin (p<0.0001): with an adjusted HR of 1.31 (95% CI 1.20 to 1.42) for a daily dose of 50 IU, meaning that out of every 100 people who used Lantus insulin one additional person was diagnosed with cancer over the study period. The baseline characteristics were different between the groups. It was not possible to break the analysis down to type of cancer.

The Swedish and Scottish studies [2-3], both based on matching of national databases for cancer and diabetes, showed no overall increase in cancer, but an increased incidence rate of breast cancer in women using insulin glargine monotherapy (no other types of insulin or combination) as compared with women using types of insulin other than insulin glargine. Although this can be caused by chance, it is striking that both studies had a similar outcome. The enhanced risk was abolished in patients using glargine together with other insulins. These were mostly younger patients with diabetes type 1.

The fourth smaller study [4] found that patients on insulin were more likely to develop solid cancers than those on metformin, and combination with metformin abolished most of this excess risk. No harmful effect on cancer development, including breast cancer were observed: there was only a higher risk versus metformin, which has known anti-cancer properties.

In Conclusion:

  • Diabetes patients using insulin should never stop using insulin, as this is very dangerous.
  • Long term studies have shown ‘natural’ insulins to be effective and safe.
  • The reported studies do NOT show that Lantus can CAUSE cancer. Moreover, the time span (less than two years) is too short for any drug to cause cancer.
  • The enhanced risk was only observed for breast cancer (2-3) and/or if Lantus was used on its own, thus not with other insulins (1-3) or metformin (4). The association was clearest in type 2 diabetes patients. It is not clear whether the association reflects the effects of Lantus or the inherent differences between for instance diabetes I/younger  and diabetes II/older patients (also because the latter often use Lantus alone ). In addition, it should be noticed that diabetes patients already have a higher cancer risk (possibly related to overweight, often seen in type 2 diabetes)
  • At the most Lantus might promote existing cancer to grow and divide. Lantus might for instance provide a survival advantage of percancerous or cancerous cells. This would be consistent with its in vitro mitogenic effect on breast cancer cells.
  • On the basis of the current evidence there is no need to switch to other treatments when a long acting insulin is necessary to keep blood glucose under control. However, Lantus treatment could be reconsidered in diabetes II patients, with good control of blood glucose, for whom a clear benefit of Lantus has not been shown or  in patients with a higher cancer risk.
  • Levamir is considered as a good alternative by some, because this long acting insulin analogue lacks the greater affinity for IGF-R. However, absence of proof is no proof of absence: Levamir has only recently been introduced, it has not been included in these studies and clinical experience is limited.
  • More conclusive evidence is to be expected from analysis of the large combined analysis of the databases available worldwide, by EASD and sanofi-aventis. Results are expected within a few months.

Video-editorials featuring Prof. Ulf Smith, Director EASD, and Prof Edwin Gale, editor-in-chief Diabetologica (part 1 and 2)

*dr Mintz reformulated this in his last post, where he stated that “it is unlikely that Lantus actually causes cancer alone, because it takes years to develop most cancers. However, it is more likely that Lantus causes existing cells to grow and divide more rapidly.

Journal ArticlesResearchBlogging.org

  1. Hemkens, L., Grouven, U., Bender, R., Günster, C., Gutschmidt, S., Selke, G., & Sawicki, P. (2009). Risk of malignancies in patients with diabetes treated with human insulin or insulin analogues: a cohort study Diabetologia DOI: 10.1007/s00125-009-1418-4 (Free full text)
  2. Jonasson, J.M., Ljung, R, Talbäck, M, Haglund, B, Gudbjörnsdòttir, S, & Steineck, G (2009). Insulin glargine use and short-term incidence of malignancies—a population-based follow-up study in Sweden Diabetologia (Free full text)
  3. SDRN Epidemiology Group (2009). Use of insulin glargine and cancer incidence in Scotland: A study from the Scottish Diabetes Research Network Epidemiology Group Diabetologia (Free full text)
  4. Currie, C., Poole, C., & Gale, E. (2009). The influence of glucose-lowering therapies on cancer risk in type 2 diabetes Diabetologia DOI: 10.1007/s00125-009-1440-6 (Free full text)
  5. Smith, U., & Gale, E. A. M. (2009). Does diabetes therapy influence the risk of cancer? Diabetologia (Free full text)
  6. Mayer D, Shukla A, Enzmann H (2008) Proliferative effects of insulin analogues on mammary epithelial cells. Arch Physiol Biochem 114: 38-44
  7. Arch Physion Biochem (2008), vol 1141 (1) is entirely dedicated to “Insulin and Cancer”, i.e. see editorial of P. Lefèbvre: Insulin and cancer: Should one worry?” p. 1-2
  8. Weinstein D, Simon M, Yehezkel E, Laron Z, Werner H (2009) Insulin analogues display IGF-I-like mitogenic and anti-apoptotic activities in cultured cancer cells. Diabetes Metab Res Rev 25: 41-49 (PubMed record)

Information about Lantus

9.  http://content.nejm.org/cgi/content/extract/352/2/174

10. http://products.sanofi-aventis.us/lantus/lantus.html

11. http://www.informapharmascience.com/doi/abs/10.1517/14656566.2.11.1891?journalCode=eop





Martin Bril: the Author, his Death and his Cancer

23 05 2009

Martin BrilMartin Bril is dead.

No “news“, it happened a month ago: April 22.

Martin Bril was a well known Dutch writer, poet and columnist – and the man who invented “skirt day”.

He loved live -and love- in all it’s simplicity. He needed few words to describe the essence of things or as he would say: “The surface is deep enough”. But you know, it is looking at one drop of water and understanding the ocean.

Other expressions: “Good is better than bad” and “You’ve people that bang the guitar really hard for hours, but I rather hear J.J. Cale. Always finished within 4 minutes, but the music stays with you.”

I liked his stories/columns most of the time, they often made me smile.

It is always sad when somebody dies young (Martin was 49), whether a “celebrity” or not. Especially when he leaves two young children and a wife.

I didn’t expect it and it really hit me. Why? I knew he had had cancer, but I thought it had gone. So did he a few years ago. I found a video-interview with him in 2007, where he said: “soon I will be declared “cured” – but then you will see it will return the other day.” In another interview I read: You never beat cancer”, that’s Lance Armstrong-language. Cancer goes away or it stays. It often stays.

I always thought he had colon cancer, but it was esophageal cancer. That’s the trouble with Dutch:Martin Bril Donkere Dagen

  • esophagus = slokdarm,
  • jejunum, ileum = dunne darm
  • colon = dikke darm.

Notice they all have “darm” in them. Mostly colon cancer is called “darmkanker” (or “dikke darmkanker”), and because esophagus is called slokdarm, slokdarmkanker is mistaken for darmkanker, which is quite another disease with other prospects.

Stupid, journalists keep on using the wrong name. Not that it matters a lot now, but still.

More “incorrect” was the fact that I first saw the announcement of his death in a newsletter from dokterdokter.nl (below). It is an online medical information site for patients. I have been getting their newsletter for years now, because -for one thing or another- I’m unsuccessful in unsubscribing to it. Dokterdokter.nl is typically a website that gives very general information, mostly leading to the advise “to check your doctor first”.

dokterdokter Martin Bril geheel

What struck me (besides the fact that I was taken by his death) was that his death was presented as Medical News, next to an enormous “oral sex” headline and the headline “what happens if you die?”. As if it was a tabloid. The message (he died the day before):

Martin Bril finally succumbed to esophageal cancer at the age of 49. Esophageal cancer has a bad prognosis. Why?
(if you click: )

“Martin Bril, the well known author …, died of esophageal cancer at the age of 49. He was a real hedonist. Cigarettes and alcohol were part of his life. Many years he had fought cancer, but Wednesday April 22 he lost his fight. Few people really completely recover from this illness.”

(….) Generally, the disease has to do with your lifestyle. In Western Countries, smoking and excessive alcohol consumption are the most important causes of esophageal cancer.

And then it continues summarizing the brochure of the Dutch Cancer Society (KWF- kankerbestrijding)

Whereas most medical sites (including the Dutch Cancer Society, from which all the information was taken) just neutrally say that the cause is unknown, but that alcohol and smoking are known risk factors for esophageal cancer, -and even more so in combination- dokterdokter puts a direct link between Martin’s lifestyle and his death, as if it was his own fault. Maybe it was, but at that moment I didn’t want to know. It didn’t matter. I found it disrespectful, tasteless. I’m quite interested in health and medicine and mechanisms, but the reason of his death -at this moment- was less important than his death itself.

As a matter of fact, Martin stopped using liquor and cocaine in 1997 after given an ultimatum by his wife (“you have two young kids!”) and after attending a trial of a drug baron (Johan V., de Hakkelaar) (to write about). He also wanted to quit smoking. I don’t know whether he succeeded, but he helped STIVORO (“for a smokeless future”) with their campaign (2002) by writing a beautiful column and making a video about (the difficulty of) quitting smoking. “I stopped smoking, because I didn’t like it anymore. Moreover, my kids didn’t want me to die because of smoking……..”

How much better was the reaction of STIVORO to the death of Martin, saying “we have lost a talented author” and thanking him for his input. Just a short notice and ending with the column Martin had written for them: “Did you ever tried to quit smoking?…I did”.

——————73554771_f75ce49f1a rokjesdag

Bij Nederlanders hoef ik Martin Bril nauwelijks te introduceren. Dat ik hier over hem schrijf heeft vooral te maken met het stukje dat ik in de nieuwsbrief van Dokterdokter.nl las. In feite was het dit bericht, waardoor ik wist dat hij gestorven was. Voor mij een schok. Ik lees de Volkskrant niet meer, dus het was mij ontgaan dat het slecht met hem ging. Het is ook een jonge vent, jonger dan ik, met twee dochters, net als ik. Zo kom het altijd nog een beetje dichterbij. En hij kon mooi schrijven. “De oppervlakte was diep genoeg,” zo zei hij, maar het was bij hem net of je in een druppel de hele oceaan kon zien.

Voor het eerst zag ik trouwens dat hij slokdarmkanker had. De meeste journalisten spraken van darmdanker, waar men in de regel toch dikkedarmkanker mee bedoelt. Slokdarmkanker is een heel andere ziekte, met een heel andere prognose. Vreemd dat het meerendeel van de journalisten het toch steeds over darmkanker heeft

Maar dit terzijde. Ik vond het vreemd, dat het bericht als een “nieuwsaankondiging” stond naast de kop “orale sex” en “hoe voelt het als je dood gaat”. Misschien had Martin er wel om kunnen lachen, maar ik vond het bizar. Het verhaal zelf vond ik ook nogal ongepast.

Wat stond er?

De ziekte slokdarmkanker werd schrijver Martin Bril op zijn 49e fataal. Het is een ziekte met slechte vooruitzichten, mede omdat het vaak laat wordt ontdekt.

“Schrijver Martin Bril, bekend van boeken als De kleine keizer en Arbeidsvitaminen en van zijn columns in de Volkskrant, is op 49-jarige leeftijd aan slokdarmkanker overleden. Hij was een echte levensgenieter, sigaretten en alcohol waren een vast onderdeel van zijn leven. Al vele jaren streed hij tegen kanker, maar woensdag 22 april was zijn strijd gestreden. Maar weinig mensen weten volledig te herstellen van deze ziekte.”De ziekte heeft meestal te maken met de leefstijl van mensen. Roken en overmatig alcoholgebruik zijn in Westerse landen de belangrijkste oorzaken voor het ontstaan van slokdarmkanker.

Andere bronnen -ook de KWF-brochure, waar dit stuk aan ontleend is, schrijven steevast dat de oorzaak niet bekend is, maar dat roken en alcohol (vooral in combinatie) de belangrijke risicofactoren zijn. Mogelijk is zijn leefwijze inderdaad de belangrijkste reden geweest dat hij slokdarmkanker heeft gekregen. Nou en? Is het nodig om dit zo op te schrijven? Een dag na zijn dood? Ik vond het nogal oneerbiedig. Misschien dacht men bij dokterdokter.nl dat het schrikeffect mensen zou weerhouden om veel te roken en te drinken, want “kijk, daar krijg je slokdarmkanker van!!” Behalve dat dokterdokter niet bepaald het juiste publiek (de “zelfkanters” en “hedonisten”) zal bereiken, zal zo’n actie sowieso weinig zoden aan de dijk zetten. Dan was Martin’s bijdrage aan de Stivoro campagne “stoppen met roken” (2002/2003) waarschijnlijk veel effectiever. Hij schreef een column voor ze en werkte mee aan een video.

Martin zei: “Ik stopte met roken omdat ik er geen zin meer in had. Bovendien; mijn kinderen vonden dat ik er niet dood aan moest gaan”. Eerder, na een ultimatum van zijn vrouw en het bijwonen van een zitting tegen de drugsbaron de Hakkelaar, was hij al gestopt met alcohol en coke.

Zo anders was ook de reactie van Stivoro. Niets vingertje wijzen: “zie je wel!”, maar dit:

“Samen met de rest van Nederland treurt STIVORO om het heengaan van een bijzonder mens en groot schrijver: Martin Bril

STIVORO heeft Martin leren kennen toen hij zich enthousiast inzette voor onze ‘Stoppen met roken’ campagne van 2002/2003. Hij was toen bereid zijn persoonlijkheid en zijn schrijftalent voor deze campagne in te zetten.

Wij zijn dankbaar dat we met hem hebben mogen samenwerken. We wensen zijn familie en andere dierbaren heel veel sterkte toe.

Hij schreef voor ons de volgende column:

“Bent u wel eens gestopt met roken?
Ik wel……..”

Photo Credit (CC):





Twitter goes Viral: Swine Flu Outbreak – Twitter a Dangerous Hype?

30 04 2009

twitter-network-and-virusTwitter has been praised for its actuality and news breaking character. Remember the earthquakes and the two recent airplane crashes (Hudson River, Schiphol). Twitter often was the first to bring the news.

Twitter’s power lies in its simplicity, -the 140 character limit-, its speed and it’s domino-effect. Tweets (twitter messages) can be read by your followers (I have appr. 650). If they find something important, funny or whatever they could “RT” or Retweet (i.e. resend) the message, and their friends could retweet it as well. Via these secondary networks Twitter can go viral (in its replication and spread).

Below a friends of a friend network of a well known twitter personality Robert Scobleizer, as obtained by Twitterfriends. Only the “relevant network” is shown, directed to someone in particular: tweets beginning with @ (followed by the twitter name of your friend). The actual reach of tweets not starting with @ is greater, because they can be read by all followers.

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Apart from following specific tweople one can also search for certain words or (hash)tags via Twitter Search or #hashtags.

Pushed by celebrities, such as Ashton Kutcher and Oprah Winfrey, who recently joined Twitter. Twitter’s traffic was poised to double and the number of tweeting people has steeply increased.

Twitter has been glorified by the stars. They created a real (meaningless) twitter mania.

But what raises high, can drop low.

Several sources dethroned Twitter because of it’s viral role in the recent swine flu outbreak. One of the first and most serious critiques came from a blog (Foreign Policy: Net Effect). It’s title: Twine flu: Twitter’s power to misinform.swine-flu-totThis is a serious allegation. Evgeny Morozov‘s main critiques:

  1. The “swine flu” meme has led to misinformation, fear and panic. Wrong info includes: fear that it “could be germ warfare” or “that one should not eat pork and certainly not from Mexico”.

  2. Unlike a simple Google search Twitter gives too much noise (irrelevant or wrong information).

  3. Messages from trustworthy sources have as much weight as those from uninformed people.

  4. There is very little context you can fit into 140 characters, even less so if all you are doing is watching a stream.

  5. Evgeny also worries about a future misuse of Twitter by cyber-terrorists shaping conversations on serious topics. A number of corporations are already monitoring and partially shaping twitter conversations about particular brands or products.

In addition some posts highlight that most of the Tweets belong to the category “witty or not so witty”. (also see this post)
And after these comments many similar comments were to follow: In fact these comments and critiques were going viral as well: take a look at this Google Search for Twitter Swine Flu and note the negative sound of most of the headlines.
The CNN website quotes Brennon Slattery, a writer for PC World,

“This is a good example of why [Twitter is] headed in that wrong direction, because it’s just propagating fear amongst people as opposed to seeking actual solutions or key information (..). The swine flu thing came really at the crux of a media revolution.”

Is Twitter just a hype and useless as an information source? Is it dangerous when a wide number of people would turn to Twitter in search of information during an emergency? Or have people just found a stick to beat the dog?

I will go to several aspects of the twitter flu coverage as I have encountered it.

Number of tweets

Indeed, as brought forward by Mashable, Tweets about “Swine Flu” are *now* at 10,000 per hour!!

Yesterday, 5 out of 10 twitter buzzwords were connected to Swine Flu:

  • # · Swine Flu
  • # · swineflu
  • # · Mexico
  • # · H1N1
  • # · Pandemic

Searching for information on Twitter
You can imagine that it is hardly useful to keep track of tweets mentioning *swine flu*, nor is searching for these buzzwords or hastags useful, if not combined with other terms or names, like CDC or laikas (just to find what you tweeted yourself).
I keep track of certain words via Tweetdeck in separate columns, accepting a certain “noise”, knowing this will only yield 20-50 tweets per day. It would not come to my mind to just blindly search for swineflu on Twitter.

The official media
It is said that Twitter doesn’t give useful or correct information, and indeed it hasn’t been designed for that (being merely a social Network). In its primitive form it is just online gossip or as The Register (UK) puts it- “it is not a media outlet. But odd enough, the official media did not behave differently. Cable television programmers went into crisis mode and a look at newspaper front pages and website home pages around the world showed a range of responses, from the almost hysterical to the concerned and more measured (Reuter’s Blog).

Look at this message from AJ Cann, that I retweeted :

laikas: RT @AJCann Totally irresponsible #swineflu journalism in the Dail Mail http://tinyurl.com/cms3km (expand) >>and they say twitter evokes global panic!
Is there really no reason to be worried?
Let’s face it. We don’t know an awful lot about this new virus strain. While it is true that the common flue has killed 13,000 people in the US since in a rather unnoticed way, and while there are relatively few swine flu casualties yet, one never knows how this new H1N1 epidemic will evolve. It might just fade away or it could kill millions of people. We just don’t know. It is a new, deadly virus. Not for nothing (as I learn from Twitter), the WHO has just raised the current level of influenza pandemic alert from phase 4 to phase 5. But this is only meant to be prepared and to inform, not to cause panic.
who-message
AJCann (on twitter)Ben, a doctor writing for the Guardian, excelling in critically informing the public about science (and quack) and a real valibrity, was invited all over by the media to be a naysayer on the “aporkalypse”.
How to deal with Twitter Noise?
Suppose you would listen to all radio channels at once: that would be an unbearable noise. Usually you choose a channel, your favorite one, and just listen what comes next. But you may switch to another channel anytime. And for news you might just go to a specific channel that you know is the most informative.
It is exactly the same with Twitter. I don’t follow everyone. Since I use Twitter mostly for my work (medicine, library, science, web 2.0) and not primarily for a chat or wit, I choose the tweople I follow carefully. If they produce too much noise I might unfollow them. They are my human filter to the news.

6a00d8341bfa9853ef0105368fcb5e970c-400wi-darmano

Furthermore among the ones I follow are News or Health Sources, like @CNN Health, sanjayguptaCNN, @BBC Health, @BreakingNews, @health and recently (because of retweets of friends): @WHOnews , @CDCemergency, Reuters_FluNews, Fluheadlines.

@BreakingNews and @health mentioning real casualties and the WHO calling an emergency meeting, I realized the seriousness of the problem. I was also pointed to @WHOnews and @CDCemergency, the most trustworthy sources to follow.
I also understood that the swine flu might be difficult to contain.

laikas: RT @BreakingNews: BULLETIN — WORLD HEALTH ORGANISATION CALLS EMERGENCY MEETING TO DISCUSS DEADLY SWINE FLU OUTBREAKS IN MEXICO AND THE U.S.

laikas: RT @health WHO, CDC concerned about possible epidemic following reports of 60+ people killed by new flu strain in Mexico http://bit.ly/d3JsO
laikas: RT @TEDchris: Swine flu outbreak. This is how it was SUPPOSED to have been contained. http://is.gd/us6r Worrying. >> WHO protocol
laikas: RT @BreakingNews: Reports of flu outbreak in New Zealand. 22 students may have been infected after a trip to Mexico. BNO trying to confirm. 3:25 AM Apr 26th from TweetDeck

laikas: RT @dreamingspires: RT @AllergyNotes Map of H1N1 Swine Flu of 2009 http://bit.ly/P2mcc (expand) 4:41 AM Apr 26th from TweetDeck

laikas: Map of H1N1 Swine Flu of 2009 http://bit.ly/P2mcc _ New Zealand added to the map. 4:42 AM Apr 26th from TweetDeck


Direct Link to H1N1 Swine Flu Google Map:

Somewhat later came the informative phase. Long before the official media were giving any useful information, some of my twitterfriends alerted me to their own or other (official) news.

@ajcann already wrote a post on his blog Microbiology Bytes (a blog with the latest news on microbiology) :10 things you should know about swine flu. (April 25th)

laikas: Reading @sciencebase Swine Flu http://bit.ly/y5Xqz 7:47 AM Apr 26th from web

laikas: RT @sanjayguptaCNN: I’ll answer your swine flu Q’s LIVE on CNN at 7:30a ET. call 1-800-807-2620. thanks 4he gr8 tweet Q so far.

laikas: RT @consultdoc: Great swine flu summary via @ubiquity http://bit.ly/DK0xV (expand) Thanks Greg.1:18 PM Apr 26th from TweetDeck

laikas: RT @BreakingNews: The WHO is holding a news conference on swine flu. Michael van Poppel is covering it live @mpoppel.
laikas: RT @stejules: RT @mashable HOW TO: Track Swine Flu Online http://tinyurl.com/dh68n8 (expand) (via @tweetmeme) (

At that point I became saturated with all information. I just follow the main news and read some good overviews

end-tweet-flu
Conclusion
For me, Twitter was the first and most accurate news source to get informed and updated on the swine flu pandemics. It was reliable, because “my friends” filtered the news for me and because I follow some trustworthy sources and news sites. Indirectly other tweople also pointed me at good and actual information.
And in my turn I kept my followers informed. The news has alarmed me, but I’m not in panic or frightened. I just feel informed and at the moment I can do nothing more than “wait and see”.

It has often been said: Twitter is what you make of it.
But keep in mind the golden rule:

Information on Swine Flu

News and Blogs

Photo Credits:

* wonderful those different names.








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