Health Tweeder. A Neat Visual Tool… But is it Useful?

First seen on ScienceRoll (February 1st) and later throughout the Twitterverse & Blogosphere: Health Tweeder (http://www.pixelsandpills.com/tweeder/), a tool launched by Pixels and Pills.

Health Tweeder is a  neat visual tool meant to aggregate tweets (Twitter messages) on specific health areas.

The Landing page consist of petri dishes, each corresponding to a specific medical discipline or disease. The size of the petri dish, and the number of cells in it, reflect the number of captured tweets. The health categories are also shown at the left, ranked by number of tweets. For instance, the second-largest category Pediatrics (in Orange) corresponds to the orange petri-dish of 170 tweets (accessed February 9th).

In Pixels and Pills own words:

The underlying idea was to build a visual tool so that people could review the dialog in specific areas in an interesting way. Using petri dishes to culture cells of dialog, each cell in a petri dish represents a distinct tweet that has been gathered using a range of search terms, hashtags, and people we’ve identified to follow. The cells grow and shrink based on the volume of content at any one time. In totality, they provide a dynamic view of the healthcare dialog on Twitter.

If you click on the orange petri-dish you see individual “cells” or Tweets. Moving the mouse over a particular cell [1] will show the corresponding tweet at the right. You can also search by page [2].

Health Tweeder looks pretty kewl. I love visual tools. They have a user-friendly, intuitive interface and it is fun to play with.  The concept of Health Tweeder -“cells of dialog cultured in petri dishes”- is also original. Perhaps it would have even be more consistent with the petri-dishes concept if each spot didn’t represent a tweet (cell) but a twitter person (cell clone or colony). But then, few clones would be present: the number of sources is very limited. There are only a few per health category. It looks as if the search criteria consist of very specific hashtags used by a very select group of people.

In the Pediatrics petri-dish there were mainly tweets seeded of Autism_Today, TannersDad, PeterBrownPsy, ADHD_News and MDLinx. The tweets didn’t seem extraordinary useful to me. The emphasis is on topics related to autism and ADHD, and incidentally on allergy or H1N1. Pediatrics must cover more than this?!

The same is true for other topics. Furthermore I can’t see any dialogs, as the makers of Health Tweeder suggest. Just one-way-tweets.

That made me wonder as to the real value of this tool.

For me, as a reasonable experienced Twitter user, searches for hashtags (sort of keywords), Twitter directories and Twitter Lists seem much more useful.

Possibly, this tool is suitable for less experienced Twitter users who prefer a narrow choice of Tweets on his/her area of interest. Still it seems rather cumbersome to follow tweets this way. Suppose I want to stay up-to-date on a particular topic. How do I know which tweets are new and which aren’t (if I merely use the petri-dish)?

The petri-dish is nice for stumbling upon, not for quick browsing, and certainly not for keeping up-to-date.

I searched on the Internet for other reviews of this tool, and without exception they were very positive.

Only at Andrew Spong’s blog STewM I found a comment of Sally Chuch, expressing a similar contrarian view. She was rather disappointed after checking out ‘cancer’ (her expertise).

What criteria is the tool using to search on? Are only certain Twitter handles defined as ‘kosher’ and used to select from their tweets?

In ‘cancer’ it includes mainly a couple of news outlets and one of two physicians, for example. There’s a lot more out there! (…)

Also, searching on ‘cancer’ will give you mainly solid tumours and not hematologic malignancies such as leukemias, lymphomas, myelodysplastic syndrome etc,

Andrew answered that he was more looking at the tool from the perspective of ‘what it could be’, not from the perspective of ‘what it actually is’. Andrew:

As we all head into the cloud and anticipate a time when much of the data we actually end up reviewing will be filtered according to our evolving preferences, it’s nice to begin to conceptualize a time when visualization tools will be added into the search mix.

So we will wait and see how this tool evolves…

The looks are great, the idea is original, but Love needs a little bit more.

video made by Andrew Spong

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#NotSoFunny – Ridiculing RCTs and EBM

I remember it well. As a young researcher I presented my findings in one of my first talks, at the end of which the chair killed my work with a remark, that made the whole room of scientists laugh, but was really beside the point. My supervisor, a truly original and very wise scientist, suppressed his anger. Afterwards, he said: “it is very easy ridiculing something that isn’t a mainstream thought. It’s the argument that counts. We will prove that we are right.” …And we did.

This was not my only encounter with scientists who try to win the debate by making fun of a theory, a finding or …people. But it is not only the witty scientist who is to *blame*, it is also the uncritical audience that just swallows it.

I have similar feelings with some journal articles or blog posts that try to ridicule EBM – or any other theory or approach. Funny, perhaps, but often misunderstood and misused by “the audience”.

Take for instance the well known spoof article in the BMJ:

“Parachute use to prevent death and major trauma related to gravitational challenge: systematic review of randomised controlled trials”

It is one of those Christmas spoof articles in the BMJ, meant to inject some medical humor into the normally serious scientific literature. The spoof parachute article pretends to be a Systematic Review of RCT’s  investigating if parachutes can prevent death and major trauma. Of course, no such trial has been done or will be done: dropping people at random with and without a parachute to proof that you better jump out of a plane with a parachute.

I found the article only mildly amusing. It is so unrealistic, that it becomes absurd. Not that I don’t enjoy absurdities at times, but  absurdities should not assume a live of their own.  In this way it doesn’t evoke a true discussion, but only worsens the prejudice some people already have.

People keep referring to this 2003 article. Last Friday, Dr. Val (with whom I mostly agree) devoted a Friday Funny post to it at Get Better Health: “The Friday Funny: Why Evidence-Based Medicine Is Not The Whole Story”.* In 2008 the paper was also discussed by Not Totally Rad [3]. That EBM is not the whole story seems pretty obvious to me. It was never meant to be…

But lets get specific. Which assumptions about RCT’s and SR’s are wrong, twisted or put out of context? Please read the excellent comments below the article. These often put the finger on the spot.

1. EBM is cookbook medicine.
Many define EBM as “make clinical decisions based on a synthesis of the best available evidence about a treatment.” (i.e. [3]). However, EBM is not cookbook medicine.

The accepted definition of EBM  is “the conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients” [4]. Sacket already emphasized back in 1996:

Good doctors use both individual clinical expertise and the best available external evidence, and neither alone is enough. Without clinical expertise, practice risks becoming tyrannised by evidence, for even excellent external evidence may be inapplicable to or inappropriate for an individual patient. Without current best evidence, practice risks becoming rapidly out of date, to the detriment of patients.

2. RCT’s are required for evidence.

Although a well performed RCT provides the “best” evidence, RCT’s are often not appropriate or indicated. That is especially true for domains other than therapy. In case of prognostic questions the most appropriate study design is usually an inception cohort. A RCT for instance can’t tell whether female age is a prognostic factor for clinical pregnancy rates following IVF: there is no way to randomize for “age”, or for “BMI”.

The same is true for etiologic or harm questions. In theory, the “best” answer is obtained by RCT. However RCT’s are often unethical or unnecessary. RCT’s are out of the question to address whether substance X causes cancer. Observational studies will do. Sometimes cases provide sufficient evidence. If a woman gets hepatic veno-occlusive disease after drinking loads of a herbal tea the finding of  similar cases in the literature may be sufficient to conclude that the herbal tea probably caused the disease.

Diagnostic accuracy studies also require another study design (cross-sectional study, or cohort).

But even in the case of  interventions, we can settle for less than a RCT. Evidence is not present or not, but exists on a hierarchy. RCT’s (if well performed) are the most robust, but if not available we have to rely on “lower” evidence.

BMJ Clinical Evidence even made a list of clinical questions unlikely to be answered by RCT’s. In this case Clinical Evidence searches and includes the best appropriate form of evidence.

1. where there are good reasons to think the intervention is not likely to be beneficial or is likely to be harmful;
2. where the outcome is very rare (e.g. a 1/10000 fatal adverse reaction);
3. where the condition is very rare;
4. where very long follow up is required (e.g. does drinking milk in adolescence prevent fractures in old age?);
5. where the evidence of benefit from observational studies is overwhelming (e.g. oxygen for acute asthma attacks);
6. when applying the evidence to real clinical situations (external validity);
7. where current practice is very resistant to change and/or patients would not be willing to take the control or active treatment;
8. where the unit of randomisation would have to be too large (e.g. a nationwide public health campaign); and
9. where the condition is acute and requires immediate treatment.
   Of these, only the first case is categorical. For the rest the cut off point when an RCT is not appropriate is not precisely defined.

Informed health decisions should be based on good science rather than EBM (alone).

Dr Val [2]: “EBM has been an over-reliance on “methodolatry” - resulting in conclusions made without consideration of prior probability, laws of physics, or plain common sense. (….) Which is why Steve Novella and the Science Based Medicine team have proposed that our quest for reliable information (upon which to make informed health decisions) should be based on good science rather than EBM alone.

Methodolatry is the profane worship of the randomized clinical trial as the only valid method of investigation. This is disproved in the previous sections.

The name “Science Based Medicine” suggests that it is opposed to “Evidence Based Medicine”. At their blog David Gorski explains: “We at SBM believe that medicine based on science is the best medicine and tirelessly promote science-based medicine through discussion of the role of science and medicine.”

While this may apply to a certain extent to quack or homeopathy (the focus of SBM) there are many examples of the opposite: that science or common sense led to interventions that were ineffective or even damaging, including:

• protective effects of beta-carotene on lung cancer (opposite)
• protective effects of vitamin E on cardiovascular disease (opposite) or certain cancers (neutral)
• protective effects of the prone sleeping on Sudden Infant Death Syndrome (opposite)
• Protective effects of corticosteroids in severe head trauma (opposite)
  etcetera.

As a matter of fact many side-effects are not foreseen and few in vitro or animal experiments have led to successful new treatments.

At the end it is most relevant to the patient that “it works” (and the benefits outweigh the harms).

Furthermore EBM is not -or should not be- without consideration of prior probability, laws of physics, or plain common sense. To me SBM and EBM are not mutually exclusive.

Why the example is bullshit unfair and unrealistic

I’ll leave it to the following comments (and yes the choice is biased) [1]

Nibu A George,Scientist :

First of all generalizing such reports of some selected cases and making it a universal truth is unhealthy and challenging the entire scientific community. Secondly, the comparing the parachute scenario with a pure medical situation is unacceptable since the parachute jump is rather a physical situation and it become a medical situation only if the jump caused any physical harm to the person involved.

Richard A. Davidson, MD,MPH:

This weak attempt at humor unfortunately reinforces one of the major negative stereotypes about EBM….that RCT’s are required for evidence, and that observational studies are worthless. If only 10% of the therapies that are paraded in front of us by journals were as effective as parachutes, we would have much less need for EBM. The efficacy of most of our current therapies are only mildly successful. In fact, many therapies can provide only a 25% or less therapeutic improvement. If parachutes were that effective, nobody would use them.
While it’s easy enough to just chalk this one up to the cliche of the cantankerous British clinician, it shows a tremendous lack of insight about what EBM is and does. Even worse, it’s just not funny.

Aviel Roy-Shapira, Senior Staff Surgeon

Smith and Pell succeeded in amusing me, but I think their spoof reflects a common misconception about evidence based medicine. All too many practitioners equate EBM with randomized controlled trials, and metaanalyses.
EBM is about what is accepted as evidence, not about how the evidence is obtained. For example, an RCT which shows that a given drug lowers blood pressure in patients with mild hypertension, however well designed and executed, is not acceptable as a basis for treatment decisions. One has to show that the drug actually lowers the incidence of strokes and heart attacks.
RCT’s are needed only when the outcome is not obvious. If most people who fall from airplanes without a parachute die, this is good enough. There is plenty of evidence for that.
EBM is about using outcome data for making therapeutic decisions. That data can come from RCTs but also from observation

Lee A. Green, Associate Professor

EBM is not RCTs. That’s probably worth repeating several times, because so often both EBM’s detractors and some of its advocates just don’t get it. Evidence is not binary, present or not, but exists on a heirarchy (Guyatt & Rennie, 2001). (….)
The methods and rigor of EBM are nothing more or less than ways of correcting for our imperfect perceptions of our experiences. We prefer, cognitively, to perceive causal connections. We even perceive such connections where they do not exist, and we do so reliably and reproducibly under well-known sets of circumstances. RCTs aren’t holy writ, they’re simply a tool for filtering out our natural human biases in judgment and causal attribution. Whether it’s necessary to use that tool depends upon the likelihood of such bias occurring.

Scott D Ramsey, Associate Professor

Parachutes may be a no-brainer, but this article is brainless.

Unfortunately, there are few if any parallels to parachutes in health care. The danger with this type of article is that it can lead to labeling certain medical technologies as “parachutes” when in fact they are not. I’ve already seen this exact analogy used for a recent medical technology (lung volume reduction surgery for severe emphysema). In uncontrolled studies, it quite literally looked like everyone who didn’t die got better. When a high quality randomized controlled trial was done, the treatment turned out to have significant morbidity and mortality and a much more modest benefit than was originally hypothesized.

Timothy R. Church, Professor

On one level, this is a funny article. I chuckled when I first read it. On reflection, however, I thought “Well, maybe not,” because a lot of people have died based on physicians’ arrogance about their ability to judge the efficacy of a treatment based on theory and uncontrolled observation.

Several high profile medical procedures that were “obviously” effective have been shown by randomized trials to be (oops) killing people when compared to placebo. For starters to a long list of such failed therapies, look at antiarrhythmics for post-MI arrhythmias, prophylaxis for T. gondii in HIV infection, and endarterectomy for carotid stenosis; all were proven to be harmful rather than helpful in randomized trials, and in the face of widespread opposition to even testing them against no treatment. In theory they “had to work.” But didn’t.

But what the heck, let’s play along. Suppose we had never seen a parachute before. Someone proposes one and we agree it’s a good idea, but how to test it out? Human trials sound good. But what’s the question? It is not, as the author would have you believe, whether to jump out of the plane without a parachute or with one, but rather stay in the plane or jump with a parachute. No one was voluntarily jumping out of planes prior to the invention of the parachute, so it wasn’t to prevent a health threat, but rather to facilitate a rapid exit from a nonviable plane.

Another weakness in this straw-man argument is that the physics of the parachute are clear and experimentally verifiable without involving humans, but I don’t think the authors would ever suggest that human physiology and pathology in the face of medication, radiation, or surgical intervention is ever quite as clear and predictable, or that non-human experience (whether observational or experimental) would ever suffice.

The author offers as an alternative to evidence-based methods the “common sense” method, which is really the “trust me, I’m a doctor” method. That’s not worked out so well in many high profile cases (see above, plus note the recent finding that expensive, profitable angioplasty and coronary artery by-pass grafts are no better than simple medical treatment of arteriosclerosis). And these are just the ones for which careful scientists have been able to do randomized trials. Most of our accepted therapies never have been subjected to such scrutiny, but it is breathtaking how frequently such scrutiny reveals problems.

Thanks, but I’ll stick with scientifically proven remedies.

parachute experiments without humans

* on the same day as I posted Friday Foolery #15: The Man who pioneered the RCT. What a coincidence.

** Don’t forget to read the comments to the article. They are often excellent.

Photo Credits

• www.Army.mil http://www.flickr.com/photos/soldiersmediacenter/ / CC BY 2.0
• EBM triad: http://knol.google.com/k/evidence-based-medicine-ebm#
• Royal Army Parachute Dog http://www.flickr.com/photos/wurzeltod/ / CC BY-NC 2.0
• Somewhere Over the Rainbow http://www.flickr.com/photos/daybeezho/ / CC BY-NC-SA 2.0

References

1. Smith, G. (2003). Parachute use to prevent death and major trauma related to gravitational challenge: systematic review of randomised controlled trials BMJ, 327 (7429), 1459-1461 DOI: 10.1136/bmj.327.7429.1459
2. The Friday Funny: Why Evidence-Based Medicine Is Not The Whole Story”. (getbetterhealth.com) [2010.01.29]
3. Call for randomized clinical trials of Parachutes (nottotallyrad.blogspot.com) [08-2008]
4. Sackett DL, Rosenberg WM, Gray JA, Haynes RB, & Richardson WS (1996). Evidence based medicine: what it is and what it isn’t. BMJ (Clinical research ed.), 312 (7023), 71-2 PMID: 8555924

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are very well edged off

Practicing Medicine in the Web 2.0 Era

Many people don’t get Web 2.0 – and certainly not Medicine 2.0.

Just the other day a journalist asked me if the redesigned PubMed could be called PubMed 2.0.
I said: “well no….no… not at all” ….Web 2.0 is not merely tools or fancy looks, it is another way of producing and sharing information and new web tools facilitate that. It is not only simplicity, it is participation. PubMed has changed it looks, but it is not an interactive platform, where you can add or exchange information.

Well anyway, I probably didn’t succeed to explain in just a few sentences what Web 2.0 is and what it isn’t. For those that are unfamiliar with Web 2.0 and/or how it changes Medicine, I highly recommend the following presentation by Bertalan Mesko (of ScienceRoll and Webicina), who explains in a clear and nontechnical way what it is all about.

By the way Bertalan is a finalist with ScienceRoll in the 2009 Medical Weblog Awards (category Best Medical Technologies/Informatics Weblog). He could surely use your vote. (here you can vote in this category). You can see all Finalist here.

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Friday Foolery #15: The Man who pioneered the RCT

This BMJ video certainly belongs on a blog like this, focussing on EBM. This video shows “John Crofton who pioneered the randomised controlled trial in a 1948 BMJ paper which looked at the antibiotic streptomycin to treat TB. Now in his 90s, Dr Crofton talks to Colin Blakemore about the importance of randomisation and blinding, and how it has helped to make medicine more evidence based.”

First seen on the Clinical Cases and Images: CasesBlog of Ves Dimov.

I’ve got Good News and I’ve got Bad News

If someone tells you: “I’ve got Good News and I’ve got Bad News”, you probably ask this person: “Well, tell me the bad news first!”

Laika’s MedLibLog has good and bad news for you.

The Bad News is, that this blog didn’t make it to the Finals of the sixth annual Medical Weblog Awards, organized by Medgadget. (see earlier post)

The Good news is that this keeps me from the stress that inevitably comes with following the stats and seeing how your blog is lagging more and more behind. Plus you don’t have to waste time desperately trying to mobilize your husband to just press the *$%# vote button (choosing the right person: me), no matter how many times he says he doesn’t care a bit – (“and wouldn’t it be better to spend less time on blogging anyway?”)

This reminds me of something I’ve tried to suppress, namely that this blog didn’t make it to the shortlists of the Dutch Bloggies 2009 either (see Laika’s MedLibLog on the Longlist of the DutchBloggies!)

The Good news is that many high quality blogs did make it to the finals. Including The Blog that Ate Manhattan, Clinical Cases and Images, Musings of a Distractible Mind (Best Medical Weblog) , other things amanzi (Best Literary Medical Weblog), Allergy Notes, Clinical Cases and Images, Life in the Fast Lane (Best Clinical Sciences Weblog), ScienceRoll (Best Medical Technologies/Informatics Weblog).

Best of all, the superb blog I nominated for Best Medical Weblog:  Dr Shock MD PhD made it to the finals as well!!

But it is hard to understand that blogs like EverythingHealth and Body in Mind with many nominations are not among the finalists. That underlines that contests are very subjective, but so are individual preferences for blogs. It is all in the game.

Anyway you can start voting for your favorite blogs tomorrow. Please have a look at the finalists here at Medgadget, so you can decide who deserves your votes.

Finally I would like to conclude with positive news concerning this blog. This week’s “Cochrane in the news” features the post on Cochrane Evidence Aid. It is on the Cochrane homepage today.

Photo Credit

http://www.flickr.com/photos/notionscapital/ / CC BY 2.0

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Best Literary Medical Weblog

Cochrane Evidence Aid for Catastrophes like Haiti’s Earthquake. “Helping by doing what we do best”

How it started [1]
2005. December 26th. Someone* working for the Cochrane Collaboration was on the Internet when he accidentally saw the AOL’s home page mentioning a powerful earthquake in the Indian Ocean, triggering a powerful tsunami that swept the coasts of neighboring countries. The story and the horror unfolded over the next hours and days. From the first reports of a few thousand dead to, within a day, a few thousand dead and tens of thousands missing in one part of Indonesia alone.

“What can we do?” he thought “Aid needs evidence on what works and what doesn’t work. It is no good and, worse, might be harmful, to deliver health care that is ineffective. The Cochrane Library already contains several reviews of relevance. There are Cochrane reviews on overcoming the effects of dehydration and the treatment of injuries, both physical and psychological. Those of us who work in the production of evidence can, therefore, deliver our own form of aid: information. The provision of reliable information on the effects of health care is the way that many of us can contribute to alleviating its effects. We need to recognize the privileged position that we are in: we can help by doing what we do best.”[1]

As reader of this blog, you probably know that the Cochrane Collaboration (http://www.cochrane.org/) is an international not-for-profit and independent organization, dedicated to making up-to-date, accurate information about the effects of healthcare readily available worldwide. It produces and disseminates systematic reviews of healthcare interventions  in the Cochrane Library, which is available through subscription. The information on which these are based is drawn together collaboratively by a global network of dedicated volunteers, supported by a small staff.

Evidence Aid: what it is and what it does. [2, 3, 4, 5]
That Christmas, the idea was born to set up “Evidence Aid”. A working party was established early January 2005 of people in the region and elsewhere.  Emails were send to people from the affected countries to express sympathy and support, and to ask for suggestions on how The Cochrane Collaboration might help.

Then, a list of over 200 interventions relevant to health care in the aftermath of the tsunami was made in consultation with all Cochrane entities, Cochrane members from affected countries, and members of other agencies such as the World Health Organization, Oxfam (one of the main UK charities working in the region), and the publishers of BMJ’s Clinical Evidence (http://clinicalevidence.com).

A prioritization was made, and subsequently lists were made of topics for which up-to-date Cochrane reviews were available and lists for which reviews were not yet available (see updated lists of  available and not currently available topics).

Concise summaries of evidence on the priority topics were offered in one place with “one-click” access to all contents, available free of charge (http://www.cochrane.org/docs/tsunamiresp​onse, now changed into http://www.cochrane.org/evidenceaid/index.htm)

The summaries link to the full evidence, which is already available on the Cochrane Library. If a summary is not currently available but there is a relevant Cochrane review in the Cochrane Library, a link takes people straight to that review. If a suitable Cochrane review is not available, links are included to other identified sources of evidence, in particular, to topics in Clinical Evidence .

In addition The Cochrane Library (http://www.thecochranelibrary.org) was made freely available in the effected countries for a six-month period. (This was before the Cochrane Library became freely available in India through funding)

Evidence matters, an example [4,5,6]
One helpful Cochrane Review was the Cochrane systematic review on the effects of brief “debriefing” [6], which is a procedure aimed to reduce immediate psychological distress and to prevent the subsequent development of psychological disorders, notably Post Traumatic Stress Disorder (PTSD). The review shows that this strategy is unlikely to be helpful and may even be harmful and cause an increase in PTSD.
After the tsunami, many teams of well-meaning people rushed to one of the worst hit areas in India, offering brief debriefing to survivors in each village, and then rushing on to the next of the 93 tsunami-affected villages in the district. Prathap Tharyan, Professor of Psychiatry and Coordinator of the South Asian Cochrane Network, found the relevant Cochrane review on debriefing and urged that this type of single session debriefing should not be provided. This message was incorporated into the content of counselor training workshops, along with evidence for interventions supported by the results of systematic reviews and other high quality research.[5]

Evidence Aid for Haiti [7]
After the tsunami it was decided to continue with Evidence Aid in natural disasters and other healthcare emergencies, drawing on knowledge gathered.

Tweets of @cochranecollab about various Evidence Aid Reviews for Haiti

Following the devastating earthquake in Haiti, The Cochrane Collaboration is working with colleagues in the World Health Organization (WHO), Pan American Health Organization (PAHO), the Centre for Reviews & Dissemination (UK), Cochrane Review Groups and others to identify Cochrane reviews and other systematic reviews of immediate importance. These, along with available Evidence Update summaries, were made available in a special Evidence Aid collection on Cochrane.org on 15 January, and have been shared with WHO and PAHO.

The information has been translated into French (thanks to the Cochrane Francophone Network) and Spanish (thanks to the Iberoamerican Cochrane Centre). At the moment, the collection includes reviews from several Cochrane Review Groups, including the Bone, Joint and Muscle Trauma Group; Depression, Anxiety and Neurosis Group; Infectious Diseases Group; Injuries Group; Renal Group and Wounds Group. [7]

Access to Evidence Aid resources for Haiti: The summaries are available at http://www.cochrane.org/evidenceaid/haiti/index.html and The Cochrane Library is freely available in the region through a variety of means. One is the Biblioteca Cochrane Plus via the Virtual Health Library BIREME interface (in English, Spanish or Portuguese).  Also, the PDF versions of all the highlighted Cochrane reviews are now available free to all on The Cochrane Library website.[7]

Is this enough?[4]
A PLOS article on Evidence Aids in 2005 already concluded: “No, not nearly enough”.[4]

Not all topics on the list have been covered by an up-to-date, good-quality systematic review. And, similar as in 2005, not all reviews have conclusions that can guide practice, because of a lack of relevant good-quality studies. After all, reviews are only as good as the studies they review. Therefore it is important to fill the gaps with good quality reviews and new practical trials on the most urgent topics.
Although things have certainly changed, i.e. more topics are now covered, there still remains room for further improvement.

If you would like to suggest additional material not yet covered, please contact Mike Clarke (mclarke@cochrane.ac.uk). You can also contribute to Evidence aid in other ways.

* This person signed the Gem [1] with “Insider”. It is not difficult to gather that the Insider is Mike Clarke, professor of clinical epidemiology at the University of Oxford, director of the UK Cochrane Centre and convenor of the working group which has set up the initiative.

Afterword: Last Monday, tweets mentioning Cochrane Evidence Aid topics appeared in my twitterstream (see Fig). As I was not profoundly familiar with this initiative, I wanted to gain more knowledge about it and summarize my findings in a post. I’m thankful to Mike Clarke and Nick Royle for instantly responding to my request for more information and Mike in particular for sending me the draft he compiled for CC-info [7] and an older cochrane gem [1], that explained how Evidence Aid arose.
Disclaimer: I’m employed as a Trial Search Coordinator of the Dutch Cochrane Centre for one day per week. The opinions expressed at this blog, however, are my own.

References:

1. Cochrane Gem for week commencing 4 January 2005, written by “Insider”. Gems are weekly highlights one of new reviews or sometimes important news. Gems are available at the CKS database here.
2. http://news.cochrane.org/view/item/review_one.jsp?j=177 assessed 24-01-2010
3. Lynn Eaton (2005) Evidence based research for coping in emergencies goes online BMJ 330(7497):926 (23 April), doi:10.1136/bmj.330.7497.926-a
4. Tharyan P, Clarke M, Green S (2005) How the Cochrane Collaboration Is Responding to the Asian Tsunami. PLoS Med 2(6): e169. doi:10.1371/journal.pmed.0020169
5. World Health Organization (2005) Three months after the Indian Ocean earthquake-tsunami: Health consequences and WHO’s response. Available: http://www.who.int/hac/crises/internatio​nal/asia_tsunami/3months/en/index.html . Accessed 24-01-2010.
6. Rose SC, Bisson J, Churchill R, Wessely S. Psychological debriefing for preventing post traumatic stress disorder (PTSD). Cochrane Database of Systematic Reviews 2002, Issue 2. Art. No.: CD000560. DOI: 10.1002/14651858.CD000560. Edited (no change to conclusions), published in Issue 1, 2009.
7. Draft written for CC-INFO (January 21, 2010) by Mike Clarke. It will become available at the CC-info archive.

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Haiti still needs help

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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http://www.imcworldwide.org/haiti

Food for Thought

Food is important. Without food we starve, but too high caloric intake or eating too much of certain foods can result in diabetes type 2, cardiovascular diseases and other health problems. On the other hand foods can also protect us against  diseases. For instance cauliflower and broccoli can reduce the risk to get certain cancers.

Nowadays, obesity is a major health problem, not only among adults, but even among children and teenagers.

According to the CDC:

The prevalence of obesity among children aged 6 to 11 more than doubled in the past 20 years, going from 6.5% in 1980 to 17.0% in 2006. The rate among adolescents aged 12 to 19 more than tripled, increasing from 5% to 17.6%. Obesity is the result of caloric imbalance (too few calories expended for the amount of calories consumed) and is mediated by genetics and health.

Childhood obesity also rising rapidly in the Netherlands, as well as in other countries all over the world.

Fat often gets the blame for obesity and health problems.

As a result some parents are avoiding fats in their food and keep fats from the diets of kids as well. Elise Buiting, chair of the youth service medical association (Artsen Jeugdgezondheidszorg Nederland , AJN) urges that the low-fat trend is disadvantageous for young children. This causes them to be to thin and too short for their age. A child’s diet should contain 30–40% of energy from fat. Furthermore, children need fat for their developing brain. And too low fat intake may lead to a too low intake of certain fat-soluble vitamins. (see recent interview in “de Pers“[NL]

In one other interview [EN] she said:

‘Children under the age of six need fat. We recommend full-fat yogurt for example,’ (..) ‘Children who are given the same light products as their parents eat do not get enough.’

Some parents not only omit butter and full-fat diary but may use low-fat products with relatively large quantities of artificial sweetener, but children should keep away from the  aspartame that they contain.

Buiting bases her ideas on the reports from child health centers and from the The Dutch National Food Consumption Survey (DNFSC). In their 2005/2006 report the authors of the DNFSC conclude:

A food consumption survey of young children (2 to 6 years of age) in the Netherlands has shown the diet to be adequate in terms of the proportions of total fat, carbohydrates and protein. However, the fatty acid composition of the diet is unfavourable, because fish consumption (rich in fish fatty acids) is low, and saturated fatty acid intake especially in 4 to 6 year-old children is high. Only a small proportion of children meet the recommended vegetable intake. For fruit the situation is slightly more favourable (one in four). Furthermore, one in seven children was found to be overweight or obese.

So the latter data do point in another direction for the majority of young children in the Netherlands: high energy-intake, an unbalanced diet and too much saturated fat. A healthy balanced diet would also mean sufficient fat intake, in particular of the unsaturated kind.

You might also like:

Some sugars worse than others.The bittersweet fructoseglucose debate (laikaspoetnik.wordpress.com)

Photo Credit

Thin & ʞɔıɥʇ button: http://www.flickr.com/photos/ntr23/ / CC BY-NC-SA 2.0

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The 2009 Medical Weblog Awards: it is time to nominate your favorite blogs

The 2009 Medical Weblog Awards are here again!

MedGadget is asking for nominations for the best of medical blogs.  This is the sixth year of the competition and these awards are designed to showcase the best medblogs, and to highlight the exciting and useful role that the medical blogosphere plays in medicine and society.

You can make your nominations here by leaving a comment with your choice. Nominations will be accepted until Sunday, January 24, 2010. The finalists will be announced the next day.

The categories for this year’s awards are:

– Best Medical Weblog

– Best New Medical Weblog (established in 2009)

– Best Literary Medical Weblog

– Best Clinical Sciences Weblog

– Best Health Policies/Ethics Weblog

– Best Medical Technologies/Informatics Weblog

– Best Patient’s Blog

Perhaps you remember that this blog made it to the finals last year in the category “Best New Medical Weblog“, but was -of course- beaten by Life In The Fast Lane, the blog that is nominated at least 20 times in the current contest.

Since you obviously can’t be nominated for Best New Medical Weblog (2008) twice, I didn’t expected this blog to be nominated again. Considering the competition, I was very surprised (and certainly honored) that Laika’s MedLibLog was nominated in the section Medical Technologies/Informatics Weblog, i.e. by Chris Nickson (precordialthump on Twitter), saying:

# Best Medical Technologies/Informatics Weblog: Laika’s MedLibLog – http://laikaspoetnik.wordpress.com/ A brilliant guide to the art and science of discovering the medical information you need.

By the way, I was alerted to the nomination by Novoseek on Twitter.

Many of my favorite blogs have already been nominated, like Life In The Fast Lane, ScienceRoll,  Bitingthedust , other things amanzi, Clinical Cases and Images, Respectful Insolence and Found In Cache. Below are my nominations. I gave preference to those blogs that have not yet been nominated, but certainly deserve a place among the other nominees.

• Best Medical Weblog : Dr Shock MD PhD, a beautiful lay-out, frequently updated, a mix of web 2.0 & medical subjects brought in an easy-to-digest way.
• Best New Medical Weblog (established in 2009) Body in Mind, excellent new blog that fulfills its promise: “both interesting and accurate.”
• Best Literary Medical Weblog: Other things amanzi – Love to read the stories. Real, rough (surgeon & South Africa) and beautifully written. (of equal quality is Bitingthedust -both already nominated)
• Best Clinical Sciences Weblog: Sutures for a living Blog of a plastic surgeon with a lot of noteworthy information on many different subjects including surgery and quilting.
• Best Health Policies/Ethics Weblog: The Skeptical OB writes skeptic research posts as well as  interesting stories about patients.
• Best Medical Technologies/Informatics Weblog: The Palmdoc Chronicles. The source to consult to keep updated with the latest Medical PDA News and Updates.
• Best Patient’s Blog :  Survive the Journey. I ‘m a real fan of this blog, written by a patient with Cushing’s Disease. It contains real life stories and researchblogging. Robin has recently started another blog  “365 days with Cushing“. I almost nominated this blog, but realized in time it just started this year.

By the way it is very difficult to fit some blogs in. It would be nice to include other categories, like “Medical Education”, Evidenced Based Medicine (Science Based Medicine/Theoretical Medicine) and “Medical Student, Nurses & other health care workers”. And what about microblogs?

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When more is less: Truncation, Stemming and Pluralization in the Cochrane Library

I’m on two mail lists of the Cochrane Collaboration, one is the TSC -list (TSC=Trials Search Coordinator) and the other the IRMG-list. IMRG stands for Information Retrieval Methods Group (of the Cochrane). Sometimes, difficult search problems are posted on the list. It is challenging to try to find the solutions. I can’t remember that a solution was not found.

A while ago a member of the list was puzzled why he got the following retrieval result from the Cochrane Library:

ID Search Hits
#1 (breast near tumour* ) ….. 254
#2 (breast near tumour) …… 640
#3 (breast near tumor*) ….. 428
#4 (breast near tumor) …… 640

where near = adjacent (thus breast should be just before tumour) and the asterisk * is the truncation symbol.  At the end of the word an asterisk is used for all terms that begin with that basic word root. Thus tumour* should find: tumours and tumour and thus broaden the search.

The results are odd, because #2 (without truncation) gives more hits than #1 (with truncation), and the same is true for #4 versus #3. One would expect truncation to give more results. What could be the reason behind it?

I suspected the problem had to do with the truncation. I searched for breast and tumour with or without truncation (#1 to #4) and only tumour* gave odd results: tumour* gave much less results than tumour. (to exclude that it had to do with the fields being searched I only searched the fields ti (title), ab (abstract) and kw (keywords))

Records found with tumour, not with tumour*, contained the word tumor (not shown). Thus tumour automatically searches for tumor (and vice versa). This process is called stemming.

According to the Help-function of the Cochrane Library:

Stemming: The stemming feature within the search allows words with small spelling variants to be matched. The term tumor will also match tumour.

In addition, as I realized later, the Cochrane has pluralization and singularization features.

Pluralization and singularization matches Pluralized forms of words also match singular versions, and vice versa. The term drugs will find both drug and drugs. To match either just the singular or plural form of a terms, use an exact match search and include the word in quotation marks.

Indeed (tumor* OR tumour*) (or shortly tumo*r*) retrieves a little more than tumor OR tumour: words like tumoral, tumorous, tumorectomy. Not particularly useful, although it might not be disadvantagous when used adjacent to breast, as this will filter most noise.

tumor spelling variants searched in the title (ti) only: it doesn't matter how you spell tumor (#8, #9, #10,#11), as long as you don't truncate (while using a single variant)

Thus stemming, pluralization and singularization only work without truncation. In case of truncation you should add the spelling variants yourselves if case stemming/pluralization takes place. This is useful if you’re interested in other word variants that are not automatically accounted for.

Put it another way: knowing that stemming and pluralization takes place you can simply search for the single or plural form, American or English spelling. So breast near tumor (or simply breast tumor) would have been o.k. This is the reason why these features were introduced in the first way.

By the way, truncation and stemming (but not pluralization) are also features in PubMed. And this can give similar and other problems. But this will be dealt with in another blogpost.

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Going Away & Coming Together

The theme of the next Grand Round (held at Teen’s Health) is “Coming Together”.

But sorry, I had no time and no inspiration, because we (my family and I) finally found some time to go away for a weekend together.

…In Bruges (Brugge), a small medieval town in Belgium, famous for its lace. We came there to taste the Christmas atmosphere. And we were very lucky, because there was a lot of snow (the downside of this was that the horse drawn carriage tours were canceled).

And as you can see we had a very peaceful weekend together … (double click to see!)

Enjoy your holidays!

Overproduction of Th1 and Th17 Cytokines may be the Clue to why some H1N1 Patients get very ill

The present H1N1 influenza virus (nvH1N1, nv=new variant) behaves very differently from other influenza strains. The majority of nvH1N1 infections are mild and self-limiting in nature, but a small percentage of the patients require hospitalization and sometimes emergency care. Unlike the seasonal flu virus, the people who seem to suffer serious complications from this flu are not those over age 65, but for instance pregnant women, children, obese people, asthma patients and immunocompromised patients.

One explanation for the heterogeneous response may be that some groups of patients are extra vulnerable to flu-related complications, like pneumonia. (i.e. in asthma and pregnancy). It is also conceivable that some people respond differently to the H1N1 virus.  A new study published in Critical Care [1] may provide the first potential immunological clue of why some people will develop severe pneumonia when infected by the pandemic H1N1 virus.

People that needed hospitalization and critical care had a different pattern of cytokines (signaling molecules) in the blood compared to each other and compared to outpatients. The pattern of lymphokines (cytokines produced by lymphocytes) is typical for the different groups of T helper cells that produce them.

——————————————————————————————————
T helper cells are T lymphocytes that assist B lymphocytes to mount an antibody response to viruses or other foreign bodies. There are different subtypes of helper cells, Th1, Th2 and the recently discovered Th17 cells [2]. These cells are required for protection, but act as a double-edged sword: Th2 have been implicated in asthma, and  Th1 and Th17 cells in many auto-immune diseases.  Interestingly, with respect to the present study, transgenic mice expressing IL-17 in lung epithelial cells showed substantial pulmonary pathology.[3]
——————————————————————————————————

How was this study done?
Both hospitalized and outpatients were recruited during the first pandemic wave in the months of July and August 2009 in ten different hospitals within the National Public Health System of Spain. Exclusion criteria were: bacterial infection, pregnancy, age (<16 yrs or >80 yrs) and patients whose samples were taken later than 5 days after hospital admission.

The following groups were studied:

1. 15 control subjects (healthy donors)
2. 15 outpatients (patients with mild, exclusively flu-like, symptoms)
3. 10 hospitalized, non-critically ill patients
4. 10 hospitalized patients, admitted to the intensive care unit due to respiratory insufficiency (these patients were slightly older than the other hospitalized patients); 3 patients ultimately died

Serum was analyzed for 30 different cytokines (and other mediators) and for determining viral load. Nasopharyngeal swabs were  taken for viral diagnosis.

Comparisons between groups were performed using the non parametric U-Mann Whitney test.

Results & Authors’ Conclusions:

1. Increased levels of innate-immunity mediators (IP-10, MCP-1, MIP-1β), and the absence of anti-nvH1N1 antibodies characterized the early response to nvH1N1 infection in all patients, whether hospitalized or not.
2. High systemic levels of type-II interferon (IFN-γ) and also of a group of mediators involved in the development of T-helper 17 (IL-8, IL-9, IL-17,IL-6) and T-helper 1 (TNF-α, IL-15, IL-12p70) responses were exclusively found in hospitalized patients.
3. IL-15, IL-12p70, IL-6 constituted a hallmark of critical illness.

The diagram below illustrates the authors’ conclusion.

“]”]

The diagram is taken from the (OA) article [1

Are the conclusions supported by the data?

Conclusions of the authors
The authors use the non parametric U-Mann Whitney test to compare all H1N1 infected groups to the control groups. Thus the conclusions seem justified as far as H1N1 groups (2, 3, 4) are compared to controls (1) and not to each other. It is correct to conclude that groups 2, 3, 4 have more inflammatory cytokines than controls, but not to make the subdivisions as they did in the diagram and in the supplemented table.
It also not justified to conclude that “IL-6 is the hallmark of critically ill patients”, as the authors did, because all nvH1N1-infected groups have higher levels of IL-6 versus control.
If you make more comparisons (30 cytokines) and compare more groups, you will definitively find more “significant results” by chance, not because the values are truly different (see Graphpad). Therefore more rigid statistical tests are needed. (Anova?)

Fig 2 from the article, adapted to show 4 out of 9 graphs

Conclusions of the media (and a Canadian co-author)
It is really surprising that all news articles I’ve seen on the subject report that levels of IL-17 in the blood appear to be culprit of causing severe symptoms in H1N1 infection (see Science Daily, News of the University of Toronto, Science Blog, Health Zone Canada). Weeks Update even produced the sensational headline: “Interleukin 17 (IL-17) responsible for death due to swine H1N1 flu”*

IL-17 is just one of the cytokines that is overexpressed in the present study. And -according to the above diagram-, it is less discriminative than IL-15 or IL-6. If we had to put the blame on something, it would be the Th1 and Th17 cells together, precisely as the title of the article indicates.

Perhaps the journalists mix up IL-17 with Th-17? But then, the Th1 subset producing TNF-α, IL-15, IL-12p70 seems more specific for critically ill patients than the Th-17 cells (at least on basis of the diagram).

Most news articles seem to be based on an interview with the Canadian senior study-author, dr Kelvin, who’s group did most of the IL-17 lab work. Excerpt from Health Zone Canada citing dr Kelvin and ted Ross:

The molecule, known as interleukin 17, may be the culprit causing severe symptoms in a host of seasonal influenzas and other respiratory ailments like SARS, he said.

It is this inflammatory function that is likely at play in flu sufferers with elevated levels, he said. “When we found that there were high levels of (interleukin 17) in severe patients and not in the mild patients, we thought that was a clue to what was driving the inflammation in the lungs of those severe patients.”

“If it’s high early in infection, it looks like you’re going to have a more severe outcome and therefore you can screen patients,” said Ross, in commenting on the paper.

Ross said interleukin 17 also presents a promising target for new drugs that could help patients recover from H1N1 pneumonias.

It seems that either the investigators know more than is published in the current paper or they base their ideas on what is already known in other infectious diseases and animal models. At any rate, these conclusions are not supported by the Spanish data. One look at the IL-17 results (Fig 2) makes it clear that -on basis of the current results- IL-17 can never be the sole predictor of a a severe outcome of H1N1 infection. It is also not known if IL-17 is a causative factor and if so, the only one. Therefore it seems much too early to conclude that IL-17 might be used to ’screen’ patients and/or as a treatment modality.

* the authors even wrote: “The patient who died five days after disease onset showed high viral load and undetectable IL-17 levels in serum. This could reflect a protective role of IL-17 in severe patients.”

References

1. Bermejo-Martin, J., Ortiz de Lejarazu, R., Pumarola, T., Rello, J., Almansa, R., Ramirez, P., Martin-Loeches, I., Varillas, D., Gallegos, M., Seron, C., Micheloud, D., Gomez, J., Tenorio-Abreu, A., Ramos, M., Molina, M., Huidobro, S., Sanchez, E., Gordon, M., Fernandez, V., del Castillo, A., Marcos, M., Villanueva, B., Lopez, C., Rodriguez-Dominguez, M., Galan, J., Canton, R., Lietor, A., Rojo, S., Eiros, J., Hinojosa, C., Gonzalez, I., Torner, N., Banner, D., Leon, A., Cuesta, P., Rowe, T., & Kelvin, D. (2009). Th1 and Th17 hypercytokinemia as early host response signature in severe pandemic influenza Critical Care, 13 (6) DOI: 10.1186/cc8208 ; free full text (OA) at http://ccforum.com/content/pdf/cc8208.pdf
2. Wynn, T. (2005). TH-17: a giant step from TH1 and TH2 Nature Immunology, 6 (11), 1069-1070 DOI: 10.1038/ni1105-1069
3. Park, H., Li, Z., Yang, X., Chang, S., Nurieva, R., Wang, Y., Wang, Y., Hood, L., Zhu, Z., Tian, Q., & Dong, C. (2005). A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17 Nature Immunology, 6 (11), 1133-1141 DOI: 10.1038/ni1261

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NOT ONE RCT on Swine Flu or H1N1?! – Outrageous!

Last week doctorblogs (Annabel Bentley) tweeted: “Outrageous- there isn’t ONE randomised trial on swine flu or #H1N1“

Annabel referred to an article at Trust the Evidence, the excellent blog of the Centre for Evidence-Based Medicine (CEBM) in Oxford, UK.

In the article “Is swine flu the most over-published and over-hyped disease ever?” Carl Heneghan first showed the results of a quick PubMed search using the terms ‘swine flu’ and ‘H1N1’: this yielded 4,475 articles on the subject, with approximately one third (1,437 articles) published in the last 7 months (search: November 27th). Of these 107, largely news articles, were published in the BMJ, followed by the Lancet and NEJM at 35 each.

Top News stories on H1N1 generated appr. 2000 to 4000 news articles each (in Google). Items included outbreak of a new form of ‘swine flu’ which prompted the United States and the World Health Organization to declare a public health emergency (April), Southern Hemisphere being mostly spared in the swine flu epidemic (May), Tamiflu, i.e. the effects of Tamiflu in children in the BMJ (co-authored by Carl) in August and the availability of the vaccine H1N1 vaccine clinics to offer seasonal flu shots in November.

According to Heneghan this must be the most over-hyped disease ever, and he wonders: “are there any other infections out there?”

Finally he ends with: “Do you know what the killer fact is in all of this? There isn’t one randomized trial out there on swine flu or H1N1 – outrageous.”

My first thoughts were: “is H1N1 really so over-published compared to other (infectious) diseases?”, “Is it really surprising that there are no RCTs yet? The H1N1-pandemics just started a few months ago!” and even “are RCT’s really the study designs we urgently need right now?”

Now the severity of the H1N1 flu seems less than feared, it is easy to be wise. Isn’t is logic that there are a lot of “exploratory studies” first: characterization of the virus, establishing the spread of H1N1 around the world, establishing mortality and morbidity, and patterns of vulnerability among the population? It is also understandable that a lot of news articles are published, in the BMJ or in online newspapers. We want to be informed. In the Netherlands we now have a small outbreak of Q-fever, partly because the official approach was slow and underestimated the public health implications of Q-fever. So the public was really underinformed. That is worse than being “overexposed”.

News often spreads like wildfire, that is no news. When I google “US Preventive Services Task Force” (who issued the controversial US breast cancer screening guidelines last month) 2,364 hits still pop up in Google News (over the last month). All papers and other news sources echo the news. 2,000 hits are easily reached.

4,475 PubMed articles on ‘swine flu’ and ‘H1N1’ isn’t really that much. When I quickly search PubMed for the rather “new” disease Q-fever I get 3,752 hits, a search for HPV (Alphapapillomavirus OR papilloma infections OR HPV OR human papilloma virus) gives 19,543 hits (1,330 over the last 9 months), and a quick search for (aids) AND “last 9 months”[edat] yields 4,073 hits!

The number of hits alone doesn’t mean much, certainly not if news, editorials and comments are included. But lets go to the second comment, that there is “not ONE RCT on H1N1.”

Again, is it reasonable to expect ONE RCT published and included in PubMed over a 9 month period? Any serious study takes time from concept to initiation, patient-enrollment, sufficient follow-up, collection of data, writing and submitting the article, peer review, publication, inclusion in PubMed and assignment of MeSH-terms (including the publication type “Randomized Controlled Trial”).

Furthermore RCTs are not always the most feasible or appropriate study designs for answering certain questions. For instance for questions related to harm, etiology, epidemiology, spreading of virus, characteristics, diagnosis and prognosis. RCTs may be most suitable to evaluate the efficacy of treatment or prevention interventions. Thus in case of H1N1 the efficacy of vaccines and of neuraminidase inhibitors to prevent or treat H1N1 flu. However, it may not always be ethical to do so (see below).

I’ve repeated the search, and using prefab “My NCBI filters” for RCTs discussed before I get the following results:

Using the Randomized Controlled Trials limits in PubMed I do get 7 hits, and using broader filters, like the Therapy/Narrow Filter under  Clinical Queries I even find 2 more RCTs that have not yet been indexed by PubMed. With the Cochrane Highly sensitive Filter even more hits are obtained, most of which are “noise”, inherent to the use of a broad filter.

The found RCTs are safety/immunogenicity/stability studies of subunit or split vaccines to H1N1, H3N2, and B influenza strains. This means they are not restricted to H1N1, but this is true for the entire set of H1N1 publications. 40 of the 1443 hits are even animal studies. Thus the total number of articles dealing with H1N1 only -and in humans- is far less than 1443.
By the way, one of the 15 H1N1-hits in PubMed obtained with the SR-filter (see Fig) is a meta-analysis of RCTs in the BMJ, co-authored by Heneghan. It is not about H1N1, but contains the sentence: “Their (neuraminidase inhibitors) effects on the incidence of serious complications, and on the current A/H1N1 influenza strain remain to be determined.”

More important, if studies have been undertaken in this field they are probably not yet published. Thus, the place to look is a clinical trials register, like Clinical trials.gov (http://clinicaltrials.gov/), The International Clinical Registry Platform Search Portal at the WHO (www.who.int/trialsearch) , national or pharmaceutical industry trials registers.

A search for H1N1 OR swine flu in Clinical trials.gov, that offers the best searching functions, yields 132 studies, of which 116 were first recieved this year.

Again, most trials concern the safety and efficacy of H1N1 vaccines and include the testing of vaccines on subgroups, like pregnant women, children with asthma and people with AIDS. 30 trials are phase III.
Narrowing the search to H1N1 OR swine flu | neuraminidase inhibitors OR oseltamivir OR zanamivir (treatment filled in in the filed “Interventions”) yields 8 studies. One of the studies is a phase III trial.

This yield doesn’t seem bad per se. However, numbers of trials don’t mean a lot and a more pertinent issue is, whether the most important and urgent questions are investigated.

Three issues are important with respect to interventions:

1. Are H1N1 vaccines safe and immunogenic? in subpopulations?
2. Do H1N1 vaccines lower morbidity and mortality due to the H1N1 flu?
3. Are neuraminidase inhibitors effective in preventing or treating H1N1 flu?

Question [1] will be answered by current trials.
Older Cochrane Reviews on the seasonal influenza flu (and updates) cast doubt on the efficacy of [2] vaccines (see the [poor*] Atlantic news article) ànd [2] neuraminidase inhibitors in children (Cochrane 2007 and BMJ 2009) ànd adults  (Cochrane 2006, update 2008 and BMJ 2009) against symptoms or complications of the seasonal flu. The possibility has even been raised that seasonal flu shots are linked to swine flu risk.

However, the current H1N1 isn’t a seasonal flu. It is a sudden, new pandemic that requires different actions. Overall H1N1 isn’t as deadly as the regular influenza strains, but it hits certain people harder: very young kids, people with asthma and pregnant women. About the latter group, Amy Tuteur (obstetrician-gynecologist blogging at The Skeptical OB) wrote a guest post at Kevin MD:

(…) the H1N1 influenza has had an unexpectedly devastating impact among pregnant women. According to the CDC, there have been approximately 700 reported cases of H1N1 in pregnant women since April.** Of these, 100 women have required admission to an intensive care unit and 28 have died. In other words, 1 out of every 25 pregnant women who contracted H1N1 died of it. By any standard, that is an appalling death rate. (……)
To put it in perspective, the chance of a pregnant woman dying from H1N1 is greater than the chance of a heart patient dying during triple bypass surgery. That is not a trivial risk.

The H1N1 flu has taken an extraordinary toll among pregnant women. A new vaccine is now available. Because of the nature of the emergency, there has not been time to do any long term studies of the vaccine. Yet pregnant women will need to make a decision as soon as possible on whether to be vaccinated. (Emphasis mine)

…. Given the dramatic threat and the fact that we know of no unusual complications of vaccination, the decision seems clear. Every pregnant woman should get vaccinated as soon as possible.

Thus the anticipated risks must be balanced against the anticipated benefits, Amy urges pregnant women to get vaccinated, even though no one can be sure about side effects ànd about the true efficacy of the vaccine.

For scientific purposes it would be best to perform a double randomized trial with half of a series of pregnant women receiving the vaccine, and the other half a placebo. This would provide the most rigid evidence for the true efficacy and safety of the vaccine.

However it would not be ethical to do so. As “Orac” of Orac Knows explains so well  in his post “Vaccination for H1N1 “swine” flu: Do The Atlantic, Shannon Brownlee, and Jeanne Lenzer matter?” RCTs are only acceptable from an ethical standpoint if we truly do not know whether one treatment is superior to another or a treatment is better than a placebo. There is sufficient reason to believe that vaccination for H1N1 will be more efficacious than “doing nothing”. Leaving a control group unvaccinated will certainly mean that a substantial percentage of pregnant women is going to die. To study the efficacy of the H1N1 among pregnant women observational studies (like cohort studies) are also suitable and more appropriate.

Among the studies found in ClinicalTrials.gov there are a few H1N1 Vaccine Clinical Studies in Pregnant Women, including RCTs. But these RCT’s never compare vaccinated women with a non-vaccinated women. All pregnant women are vaccinated, but the conditions vary.

In one Danish study the arms (study groups) are as follows:

Thus two doses of H1N1 with adjuvant are compared with a higher dose H1N1 without adjuvant. As a control non-pregnant women are vaccinated with the adjuvant H1N1.*** The RCT is performed within a prospective, birth-cohort study recruiting 800 pregnant mothers between Q1- 2009 and Q4-2010. As a natural control women pregnant in the H1N1 season (Q4) will be compared with women outside the season. Please note that the completion date of this study will be 2012, thus we will have to wait a number of years before the study describing the results will be found in PubMed….

To give an impression of the idea behind the study, here is the summary of that trial in the register (not because it is particularly outstanding, but to highlight the underlying thoughts):

“Pregnant women are at particular risk during the imminent H1N1v influenza pandemic. The new H1N1v virus requires urgent political and medical decisions on vaccination strategies in order to minimize severe disease and death from this pandemic. However, there is a lack of evidence to build such decisions upon. A vaccine will be provided in the fourth quarter of 2009, but there is little knowledge on the immunogenicity. Particularly its clinical effectiveness and duration of immunity in pregnant women and their newborn infants is unknown. Therefore, it will be important to study the optimal vaccination regimens with respect to dosing and use of adjuvant to decide future health policies on vaccination of pregnant women. We have a unique possibility to study these aspects of H1N1v infection in pregnant women in our ongoing unselected, prospective, birth-cohort study recruiting 800 pregnant mothers between Q1- 2009 and Q4-2010. Pregnant women from East-Denmark are being enrolled during the 2nd trimester and their infant will undergo a close clinical follow-up. The H1N1v pandemic is expected to reach Denmark Q4-2009. The timing of this enrollment and the imminent pandemic allows for an “experiment of nature” whereby the first half of the mothers completes pregnancy before the H1N1v pandemic. The other half of this cohort will be pregnant while H1N1v is prevalent in the community and will require H1N1v vaccination.The aim of this randomized, controlled, trial is to compare and evaluate the dose-related immune protection conferred by vaccine and adjuvant (Novartis vaccine Focetria) in pregnant women and non-pregnant women. In addition the protocol will assess the passive immunity conferred to the newborn from these vaccine regimes. The study will provide evidence-based guidance for health policies on vaccination for the population of pregnant women during future H1N1v pandemics.”

Although with regard to H1N1-vaccination, appropriate studies are being done, it is feasible that certain measures might not be appropriate on basis of what we know. For instance, pretreating people in the non-risk groups (healthy young adults) with neuraminidase-inhibitors, because they are “indispensable employees”. Perhaps Heneghan, who as you remember is a co-author of the BMJ paper on neuraminidase -inhibitors in children with the seasonal flu, was thinking of this when writing his post.
If Heneghan would have directed his arrows at certain interventions in certain circumstances in certain people he might have had a good point, but now his arrows don’t hit any target. Revere from Effect Measure and Orac from Orac Knows might well have diagnosed him as someone who suffers from “methodolatry,” which is, as Revere puts it, the “profane worship of the randomized clinical trial as the only valid method of investigation.”

Notes

* But see the excellent post of Orac who trashes the Atlantic paper in Flu vaccination: Do The Atlantic, Shannon Brownlee, and Jeanne Lenzer matter? (scienceblogs.com). He also critiques the attitude of the Cochrane author Jefferson, who has a different voice in the media compared to the Cochrane Reviews he co-authors. Here he is far more neutral.

** There is no direct link to the data in the post. I’m not sure whether all pregnant women in the US are routinely tested for H1N1. (if not the percentage of H1N1 deaths among H1N1 infected pregnant women might be overestimated)

***In the US, vaccins given to pregnant women are without adjuvant.

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45,982

Empathy

The next Grand Rounds will be hosted by Barbara Olson of Florence dot com. The theme will be Simplify, identical to the theme of the annual conference of the Institute for Healthcare Improvement in Orlando. We are invited to share what’s on our mind about any healthcare-related topic indicating with one word why it is important.

My word is Empathy, because it is a versatile,  important skill doctors should have (besides knowledge and technical expertise to name a few other important skills). Empathy is especially important with vulnerable patients, the old and very young.

It strikes me that pediatricians are often very kind and pleasant doctors. They know how to ‘handle’ kids. GP’s also have to deal with kids a lot, but they’re often less patient and kind. At least that applies to our GP. I have had various issues with him, although never outspoken. He is a good doctor, but can be rude at times.

This is a funny story.

Once upon a time, we had to regularly visit our doctor, because my daughter, then 4 to 5 years old, had all kinds of small complaints.

Once she had (innocent) warts. He had to scrape them, but because my daughter found this painful, we had to pretreat the warts with EMLA plasters that numb the skin. I had to do that at home, but the plaster at the inner side of her knee had loosened after a half our walk to the doctor’s practice. He grumbled that I didn’t do it right and that I had to come back another time, meanwhile hard-handedly removing the other warts, forgetting half of them. My daughter didn’t enjoy the scrapings, the corners of her mouth trembling in her attempts not to cry.

After most of the warts had been removed, the doctor took a big flat box with all kinds of little presents, he obviously gave to children at the end of the ordeal.

“Here. You can choose a present!”

My daughter looked at all the minute presents, pondering which one to choose.

There were a lot of rings, with blue stones, red stones, pink stones. There were necklaces, little toys, games….

“Choose one”.

She choose a ring with a pink stone. But wait, that blue ring was nicer and she returned the ring with the pink stone .

But the little patience my doctor had was at an end.

He grabbed something from the box and put it into my daughter’s hand: “Here!”

It was a simple round cardboard with the most silly sheep drawing I have ever seen. With open mound my daughter received the present. Speechless she stared at the gift.

The doctor gestured we could leave the room. He apparently met his obligations with the gift.

With the door handle in my hand, I saw my daughter making a sudden turn. She took one last look at the sheep to throw it as an experienced pitcher straight at the doctor’s desk.

We heard a loud “Well, I never!”, when we left the room.

Added 2009-12-15:

Summary by Barbara at Florence.dot.com:

Jacqueline at Laika’s MedLibLog captures the arachnoid spirit, giving her post a one word title: empathy. The post shows how much we long for care that considers more about who we are than our “chief complaint” often reveals. If Jacqueline had been in the mood to spin longer, she could have called this post, “What comes around, goes around!”
Hit the nail on the head, Barbara!

Photo Credits:

“You are a lamb”, adapted from: http://www.flickr.com/photos/onegoodbumblebee/ / CC BY-NC-SA 2.0