Between the Lines. Finding the Truth in Medical Literature [Book Review]

19 07 2013

In the 1970s a study was conducted among 60 physicians and physicians-in-training. They had to solve a simple problem:

“If a test to detect a disease whose prevalence is 1/1000 has a false positive rate of 5 %, what is the chance that a person found to have a positive result actually has the disease, assuming that you know nothing about the person’s symptoms or signs?” 

Half of the “medical experts” thought the answer was 95%.
Only a small proportion, 18%, of the doctors arrived at the right answer of 2%.

If you are a medical expert who comes the same faulty conclusion -or need a refresher how to arrive at the right answer- you might benefit from the book written by Marya Zilberberg: “Between the Lines. Finding the Truth in Medical Literature”.

The same is true for a patient whose doctor thinks he/she is among the 95% to benefit form such a test…
Or for journalists who translate medical news to the public…
Or for peer reviewers or editors who have to assess biomedical papers…

In other words, this book is useful for everyone who wants to be able to read “between the lines”. For everyone who needs to examine medical literature critically from time to time and doesn’t want to rely solely on the interpretation of others.

I hope that I didn’t scare you off with the abovementioned example. Between the Lines surely is NOT a complicated epidemiology textbook, nor a dull studybook where you have to struggle through a lot of definitions, difficult tables and statistic formulas and where each chapter is followed by a set of review questions that test what you learned.

This example is presented half way the book, at the end of Part I. By then you have enough tools to solve the question yourself. But even if you don’t feel like doing the exact calculation at that moment, you have a solid basis to understand the bottomline: the (enormous) 93% gap (95% vs 2% of the people with a positive test are considered truly positive) serves as the pool for overdiagnosis and overtreatment.

In the previous chapters of Part I (“Context”), you have learned about the scientific methods in clinical research, uncertainty as the only certain feature of science, the importance of denominators, outcomes that matter and outcomes that don’t, Bayesian probability, evidence hierarchies, heterogeneous treatment effects (does the evidence apply to this particular patient?) and all kinds of biases.

Most reviewers prefer part I of the book. Personally I find part II (“Evaluation”) as interesting.

Part II deals with the study question, and study design, pros and cons of observational and interventional studies, validity, hypothesis testing and statistics.

Perhaps part II  is somewhat less narrative. Furthermore, it deals with tougher topics like statistics. But I find it very valuable for being able to critically appraise a study. I have never seen a better description of “ODDs”: somehow ODDs it is better to grasp if you substitute “treatment A” and “treatment B” for “horse A” and “horse B”, and substitute “death” for “loss of a race”.
I knew the basic differences between cohort studies, case control studies and so on, but I kind of never realized before that ODDs Ratio is the only measure of association available in a case-control study and that case control studies cannot estimate incidence or prevalence (as shown in a nice overview in table 4).

Unlike many other books about “the art of reading of medical articles”, “study designs” or “Evidence Based Medicine”, Marya’s book is easy to read. It is written at a conversational tone and statements are illustrated by means of current, appealing examples, like the overestimation of risk of death from the H1N1 virus, breast cancer screening and hormone replacement therapy.

Although I had printed this book in a wrong order (page 136 next to 13 etc), I was able to read (and understand) 1/3 of the book (the more difficult part II) during a 2 hour car trip….

Because this book is comprehensive, yet accessible, I recommend it highly to everyone, including fellow librarians.

Marya even mentions medical librarians as a separate target audience:

Medical librarians may find this book particularly helpful: Being at the forefront of evidence dissemination, they can lead the charge of separating credible science from rubbish.

(thanks Marya!)

In addition, this book may be indirectly useful to librarians as it may help to choose appropriate methodological filters and search terms for certain EBM-questions. In case of etiology questions words like “cohort”, “case-control”, “odds”, “risk” and “regression” might help to find the “right” studies.

By the way Marya Ziberberg @murzee at Twitter and she writes at her blog Healthcare etc.

p.s. 1 I want to apologize to Marya for writing this review more than a year after the book was published. For personal reasons I found little time to read and blog. Luckily the book lost none of its topicality.

p.s. 2 patients who are not very familiar with critical reading of medical papers might benefit from reading “your medical mind” first [1]. 

bwtn the lines

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The Scatter of Medical Research and What to do About it.

18 05 2012

ResearchBlogging.orgPaul Glasziou, GP and professor in Evidence Based Medicine, co-authored a new article in the BMJ [1]. Similar to another paper [2] I discussed before [3] this paper deals with the difficulty for clinicians of staying up-to-date with the literature. But where the previous paper [2,3] highlighted the mere increase in number of research articles over time, the current paper looks at the scatter of randomized clinical trials (RCTs) and systematic reviews (SR’s) accross different journals cited in one year (2009) in PubMed.

Hofmann et al analyzed 7 specialties and 9 sub-specialties, that are considered the leading contributions to the burden of disease in high income countries.

They followed a relative straightforward method for identifying the publications. Each search string consisted of a MeSH term (controlled  term) to identify the selected disease or disorders, a publication type [pt] to identify the type of study, and the year of publication. For example, the search strategy for randomized trials in cardiology was: “heart diseases”[MeSH] AND randomized controlled trial[pt] AND 2009[dp]. (when searching “heart diseases” as a MeSH, narrower terms are also searched.) Meta-analysis[pt] was used to identify systematic reviews.

Using this approach Hofmann et al found 14 343 RCTs and 3214 SR’s published in 2009 in the field of the selected (sub)specialties. There was a clear scatter across journals, but this scatter varied considerably among specialties:

“Otolaryngology had the least scatter (363 trials across 167 journals) and neurology the most (2770 trials across 896 journals). In only three subspecialties (lung cancer, chronic obstructive pulmonary disease, hearing loss) were 10 or fewer journals needed to locate 50% of trials. The scatter was less for systematic reviews: hearing loss had the least scatter (10 reviews across nine journals) and cancer the most (670 reviews across 279 journals). For some specialties and subspecialties the papers were concentrated in specialty journals; whereas for others, few of the top 10 journals were a specialty journal for that area.
Generally, little overlap occurred between the top 10 journals publishing trials and those publishing systematic reviews. The number of journals required to find all trials or reviews was highly correlated (r=0.97) with the number of papers for each specialty/ subspecialty.”

Previous work already suggested that this scatter of research has a long tail. Half of the publications is in a minority of papers, whereas the remaining articles are scattered among many journals (see Fig below).

Click to enlarge en see legends at BMJ 2012;344:e3223 [CC]

The good news is that SRs are less scattered and that general journals appear more often in the top 10 journals publishing SRs. Indeed for 6 of the 7 specialties and 4 of the 9 subspecialties, the Cochrane Database of Systematic Reviews had published the highest number of systematic reviews, publishing between 6% and 18% of all the systematic reviews published in each area in 2009. The bad news is that even keeping up to date with SRs seems a huge, if not impossible, challenge.

In other words, it is not sufficient for clinicians to rely on personal subscriptions to a few journals in their specialty (which is common practice). Hoffmann et al suggest several solutions to help clinicians cope with the increasing volume and scatter of research publications.

  • a central library of systematic reviews (but apparently the Cochrane Library fails to fulfill such a role according to the authors, because many reviews are out of date and are perceived as less clinically relevant)
  • registry of planned and completed systematic reviews, such as prospero. (this makes it easier to locate SRs and reduces bias)
  • Synthesis of Evidence and synopses, like the ACP-Jounal Club which summarizes the best evidence in internal medicine
  • Specialised databases that collate and critically appraise randomized trials and systematic reviews, like www.pedro.org.au for physical therapy. In my personal experience, however, this database is often out of date and not comprehensive
  • Journal scanning services like EvidenceUpdates from mcmaster.ca), which scans over 120 journals, filters articles on the basis of quality, has practising clinicians rate them for relevance and newsworthiness, and makes them available as email alerts and in a searchable database. I use this service too, but besides that not all specialties are covered, the rating of evidence may not always be objective (see previous post [4])
  • The use of social media tools to alert clinicians to important new research.

Most of these solutions are (long) existing solutions that do not or only partly help to solve the information overload.

I was surprised that the authors didn’t propose the use of personalized alerts. PubMed’s My NCBI feature allows to create automatic email alerts on a topic and to subscribe to electronic tables of contents (which could include ACP journal Club). Suppose that a physician browses 10 journals roughly covering 25% of the trials. He/she does not need to read all the other journals from cover to cover to avoid missing one potentially relevant trial. Instead it is far more efficient to perform a topic search to filter relevant studies from journals that seldom publish trials on the topic of interest. One could even use the search of Hoffmann et al to achieve this.* Although in reality, most clinical researchers will have narrower fields of interest than all studies about endocrinology and neurology.

At our library we are working at creating deduplicated, easy to read, alerts that collate table of contents of certain journals with topic (and author) searches in PubMed, EMBASE and other databases. There are existing tools that do the same.

Another way to reduce the individual work (reading) load is to organize journals clubs or even better organize regular CATs (critical appraised topics). In the Netherlands, CATS are a compulsory item for residents. A few doctors do the work for many. Usually they choose topics that are clinically relevant (or for which the evidence is unclear).

The authors shortly mention that their search strategy might have missed  missed some eligible papers and included some that are not truly RCTs or SRs, because they relied on PubMed’s publication type to retrieve RCTs and SRs. For systematic reviews this may be a greater problem than recognized, for the authors have used meta-analyses[pt] to identify systematic reviews. Unfortunately PubMed has no publication type for systematic reviews, but it may be clear that there are many more systematic reviews that meta-analyses. Possibly systematical reviews might even have a different scatter pattern than meta-analyses (i.e. the latter might be preferentially included in core journals).

Furthermore not all meta-analyses and systematic reviews are reviews of RCTs (thus it is not completely fair to compare MAs with RCTs only). On the other hand it is a (not discussed) omission of this study, that only interventions are considered. Nowadays physicians have many other questions than those related to therapy, like questions about prognosis, harm and diagnosis.

I did a little imperfect search just to see whether use of other search terms than meta-analyses[pt] would have any influence on the outcome. I search for (1) meta-analyses [pt] and (2) systematic review [tiab] (title and abstract) of papers about endocrine diseases. Then I subtracted 1 from 2 (to analyse the systematic reviews not indexed as meta-analysis[pt])

Thus:

(ENDOCRINE DISEASES[MESH] AND SYSTEMATIC REVIEW[TIAB] AND 2009[DP]) NOT META-ANALYSIS[PT]

I analyzed the top 10/11 journals publishing these study types.

This little experiment suggests that:

  1. the precise scatter might differ per search: apparently the systematic review[tiab] search yielded different top 10/11 journals (for this sample) than the meta-analysis[pt] search. (partially because Cochrane systematic reviews apparently don’t mention systematic reviews in title and abstract?).
  2. the authors underestimate the numbers of Systematic Reviews: simply searching for systematic review[tiab] already found appr. 50% additional systematic reviews compared to meta-analysis[pt] alone
  3. As expected (by me at last), many of the SR’s en MA’s were NOT dealing with interventions, i.e. see the first 5 hits (out of 108 and 236 respectively).
  4. Together these findings indicate that the true information overload is far greater than shown by Hoffmann et al (not all systematic reviews are found, of all available search designs only RCTs are searched).
  5. On the other hand this indirectly shows that SRs are a better way to keep up-to-date than suggested: SRs  also summarize non-interventional research (the ratio SRs of RCTs: individual RCTs is much lower than suggested)
  6. It also means that the role of the Cochrane Systematic reviews to aggregate RCTs is underestimated by the published graphs (the MA[pt] section is diluted with non-RCT- systematic reviews, thus the proportion of the Cochrane SRs in the interventional MAs becomes larger)

Well anyway, these imperfections do not contradict the main point of this paper: that trials are scattered across hundreds of general and specialty journals and that “systematic reviews” (or meta-analyses really) do reduce the extent of scatter, but are still widely scattered and mostly in different journals to those of randomized trials.

Indeed, personal subscriptions to journals seem insufficient for keeping up to date.
Besides supplementing subscription by  methods such as journal scanning services, I would recommend the use of personalized alerts from PubMed and several prefiltered sources including an EBM search machine like TRIP (www.tripdatabase.com/).

*but I would broaden it to find all aggregate evidence, including ACP, Clinical Evidence, syntheses and synopses, not only meta-analyses.

**I do appreciate that one of the co-authors is a medical librarian: Sarah Thorning.

References

  1. Hoffmann, Tammy, Erueti, Chrissy, Thorning, Sarah, & Glasziou, Paul (2012). The scatter of research: cross sectional comparison of randomised trials and systematic reviews across specialties BMJ, 344 : 10.1136/bmj.e3223
  2. Bastian, H., Glasziou, P., & Chalmers, I. (2010). Seventy-Five Trials and Eleven Systematic Reviews a Day: How Will We Ever Keep Up? PLoS Medicine, 7 (9) DOI: 10.1371/journal.pmed.1000326
  3. How will we ever keep up with 75 trials and 11 systematic reviews a day (laikaspoetnik.wordpress.com)
  4. Experience versus Evidence [1]. Opioid Therapy for Rheumatoid Arthritis Pain. (laikaspoetnik.wordpress.com)




Can Guidelines Harm Patients?

2 05 2012

ResearchBlogging.orgRecently I saw an intriguing “personal view” in the BMJ written by Grant Hutchison entitled: “Can Guidelines Harm Patients Too?” Hutchison is a consultant anesthetist with -as he calls it- chronic guideline fatigue syndrome. Hutchison underwent an acute exacerbation of his “condition” with the arrival of another set of guidelines in his email inbox. Hutchison:

On reviewing the level of evidence provided for the various recommendations being offered, I was struck by the fact that no relevant clinical trials had been carried out in the population of interest. Eleven out of 25 of the recommendations made were supported only by the lowest levels of published evidence (case reports and case series, or inference from studies not directly applicable to the relevant population). A further seven out of 25 were derived only from the expert opinion of members of the guidelines committee, in the absence of any guidance to be gleaned from the published literature.

Hutchison’s personal experience is supported by evidence from two articles [2,3].

One paper published in the JAMA 2009 [2] concludes that ACC/AHA (American College of Cardiology and the American Heart Association) clinical practice guidelines are largely developed from lower levels of evidence or expert opinion and that the proportion of recommendations for which there is no conclusive evidence is growing. Only 314 recommendations of 2711 (median, 11%) are classified as level of evidence A , thus recommendation based on evidence from multiple randomized trials or meta-analyses.  The majority of recommendations (1246/2711; median, 48%) are level of evidence C, thus based  on expert opinion, case studies, or standards of care. Strikingly only 245 of 1305 class I recommendations are based on the highest level A evidence (median, 19%).

Another paper, published in Ann Intern Med 2011 [3], reaches similar conclusions analyzing the Infectious Diseases Society of America (IDSA) Practice Guidelines. Of the 4218 individual recommendations found, only 14% were supported by the strongest (level I) quality of evidence; more than half were based on level III evidence only. Like the ACC/AHH guidelines only a small part (23%) of the strongest IDSA recommendations, were based on level I evidence (in this case ≥1 randomized controlled trial, see below). And, here too, the new recommendations were mostly based on level II and III evidence.

Although there is little to argue about Hutchison’s observations, I do not agree with his conclusions.

In his view guidelines are equivalent to a bullet pointed list or flow diagram, allowing busy practitioners to move on from practice based on mere anecdote and opinion. It therefore seems contradictory that half of the EBM-guidelines are based on little more than anecdote (case series, extrapolation from other populations) and opinion. He then argues that guidelines, like other therapeutic interventions, should be considered in terms of balance between benefit and risk and that the risk  associated with the dissemination of poorly founded guidelines must also be considered. One of those risks is that doctors will just tend to adhere to the guidelines, and may even change their own (adequate) practice  in the absence of any scientific evidence against it. If a patient is harmed despite punctilious adherence to the guideline-rules,  “it is easy to be seduced into assuming that the bad outcome was therefore unavoidable”. But perhaps harm was done by following the guideline….

First of all, overall evidence shows that adherence to guidelines can improve patient outcome and provide more cost effective care (Naveed Mustfa in a comment refers to [4]).

Hutchinson’s piece is opinion-based and rather driven by (understandable) gut feelings and implicit assumptions, that also surround EBM in general.

  1. First there is the assumption that guidelines are a fixed set of rules, like a protocol, and that there is no room for preferences (both of the doctor and the patient), interpretations and experience. In the same way as EBM is often degraded to “cookbook medicine”, EBM guidelines are turned into mere bullet pointed lists made by a bunch of experts that just want to impose their opinions as truth.
  2. The second assumption (shared by many) is that evidence based medicine is synonymous with “randomized controlled trials”. In analogy, only those EBM guideline recommendations “count” that are based on RCT’s or meta-analyses.

Before I continue, I would strongly advice all readers (and certainly all EBM and guideline-skeptics) to read this excellent and clearly written BJM-editorial by David Sackett et al. that deals with misconceptions, myths and prejudices surrounding EBM : Evidence based medicine: what it is and what it isn’t [5].

Sackett et al define EBM as “the conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients” [5]. Sackett emphasizes that “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.”

Guidelines are meant to give recommendations based on the best available evidence. Guidelines should not be a set of rules, set in stone. Ideally, guidelines have gathered evidence in a transparent way and make it easier for the clinicians to grasp the evidence for a certain procedure in a certain situation … and to see the gaps.

Contrary to what many people think, EBM is not restricted to randomized trials and meta-analyses. It involves tracking down the best external evidence there is. As I explained in #NotSoFunny #16 – Ridiculing RCTs & EBM, evidence is not an all-or-nothing thing: RCT’s (if well performed) are the most robust, but if not available we have to rely on “lower” evidence (from cohort to case-control to case series or expert opinion even).
On the other hand RCT’s are often not even suitable to answer questions in other domains than therapy (etiology/harm, prognosis, diagnosis): per definition the level of evidence for these kind of questions inevitably will be low*. Also, for some interventions RCT’s are not appropriate, feasible or too costly to perform (cesarean vs vaginal birth; experimental therapies, rare diseases, see also [3]).

It is also good to realize that guidance, based on numerous randomized controlled trials is probably not or limited applicable to groups of patients who are seldom included in a RCT: the cognitively impaired, the patient with multiple comorbidities [6], the old patient [6], children and (often) women.

Finally not all RCTs are created equal (various forms of bias; surrogate outcomes; small sample sizes, short follow-up), and thus should not all represent the same high level of evidence.*

Thus in my opinion, low levels of evidence are not per definition problematic. Even if they are the basis for strong recommendations. As long as it is clear how the recommendations were reached and as long as these are well underpinned (by whatever evidence or motivation). One could see the exposed gaps in evidence as a positive thing as it may highlight the need for clinical research in certain fields.

There is one BIG BUT: my assumption is that guidelines are “just” recommendations based on exhaustive and objective reviews of existing evidence. No more, no less. This means that the clinician must have the freedom to deviate from the recommendations, based on his own expertise and/or the situation and/or the patient’s preferences. The more, when the evidence on which these strong recommendations are based is ‘scant’. Sackett already warned for the possible hijacking of EBM by purchasers and managers (and may I add health insurances and governmental agencies) to cut the costs of health care and to impose “rules”.

I therefore think it is odd that the ACC/AHA guidelines prescribe that Class I recommendations SHOULD be performed/administered even if they are based on level C recommendations (see Figure).

I also find it odd that different guidelines have a different nomenclature. The ACC/AHA have Class I, IIa, IIb and III recommendations and level A, B, C evidence where level A evidence represents sufficient evidence from multiple randomized trials and meta-analyses, whereas the strength of recommendations in the IDSA guidelines includes levels A through C (OR D/E recommendations against use) and quality of evidence ranges from level I through III , where I indicates evidence from (just) 1 properly randomized controlled trial. As explained in [3] this system was introduced to evaluate the effectiveness of preventive health care interventions in Canada (for which RCTs are apt).

Finally, guidelines and guideline makers should probably be more open for input/feedback from people who apply these guidelines.

————————————————

*the new GRADE (Grading of Recommendations Assessment, Development, and Evaluation) scoring system taking into account good quality observational studies as well may offer a potential solution.

Another possibly relevant post at this blog: The Best Study Design for … Dummies

Taken from a summary of an ACC/AHA guideline at http://guideline.gov/
Click to enlarge.

References

  1. Hutchison, G. (2012). Guidelines can harm patients too BMJ, 344 (apr18 1) DOI: 10.1136/bmj.e2685
  2. Tricoci P, Allen JM, Kramer JM, Califf RM, & Smith SC Jr (2009). Scientific evidence underlying the ACC/AHA clinical practice guidelines. JAMA : the journal of the American Medical Association, 301 (8), 831-41 PMID: 19244190
  3. Lee, D., & Vielemeyer, O. (2011). Analysis of Overall Level of Evidence Behind Infectious Diseases Society of America Practice Guidelines Archives of Internal Medicine, 171 (1), 18-22 DOI: 10.1001/archinternmed.2010.482
  4. Menéndez R, Reyes S, Martínez R, de la Cuadra P, Manuel Vallés J, & Vallterra J (2007). Economic evaluation of adherence to treatment guidelines in nonintensive care pneumonia. The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology, 29 (4), 751-6 PMID: 17005580
  5. Sackett, D., Rosenberg, W., Gray, J., Haynes, R., & Richardson, W. (1996). Evidence based medicine: what it is and what it isn’t BMJ, 312 (7023), 71-72 DOI: 10.1136/bmj.312.7023.71
  6. Aylett, V. (2010). Do geriatricians need guidelines? BMJ, 341 (sep29 3) DOI: 10.1136/bmj.c5340




What Did Deep DNA Sequencing of Traditional Chinese Medicines (TCMs) Really Reveal?

30 04 2012

ResearchBlogging.orgA recent study published in PLOS genetics[1] on a genetic audit of Traditional Chinese Medicines (TCMs) was widely covered in the news. The headlines are a bit confusing as they said different things. Some headlines say “Dangers of Chinese Medicine Brought to Light by DNA Studies“, others that Bear and Antelope DNA are Found in Traditional Chinese Medicine, and still others more neutrally: Breaking down traditional Chinese medicine.

What have Bunce and his group really done and what is the newsworthiness of this article?

doi:info:doi/10.1371/journal.pgen.1002657.g001

Photos from 4 TCM samples used in this study doi/10.1371/journal.pgen.1002657.g001

The researchers from the the Murdoch University, Australia,  have applied Second Generation, high-throughput sequencing to identify the plant and animal composition of 28 TCM samples (see Fig.). These TCM samples had been seized by Australian Customs and Border Protection Service at airports and seaports across Australia, because they contravened Australia’s international wildlife trade laws (Part 13A EPBC Act 1999).

Using primers specific for the plastid trnL gene (plants) and the mitochondrial 16S ribosomal RNA (animals), DNA of sufficient quality was obtained from 15 of the 28 (54%) TCM samples. The resultant 49,000 amplicons (amplified sequences) were analyzed by high-throughput sequencing and compared to reference databases.

Due to better GenBank coverage, the analysis of vertebrate DNA was simpler and less ambiguous than the analysis of the plant origins.

Four TCM samples – Saiga Antelope Horn powder, Bear Bile powder, powder in box with bear outline and Chu Pak Hou Tsao San powder were found to contain DNA from known CITES- (Convention on International Trade in Endangered Species) listed species. This is no real surprise, as the packages were labeled as such.

On the other hand some TCM samples, like the “100% pure” Saiga Antilope powder, were “diluted” with  DNA from bovids (i.e. goats and sheep), deer and/or toads. In 78% of the samples, animal DNA was identified that had not been clearly labeled as such on the packaging.

In total 68 different plant families were detected in the medicines. Some of the TCMs contained plants of potentially toxic genera like Ephedra and Asarum. Ephedra contains the sympathomimetic ephedrine, which has led to many, sometimes fatal, intoxications, also in Western countries. It should be noted however, that pharmacological activity cannot be demonstrated by DNA-analysis. Similarly, certain species of Asarum (wild ginger) contain the nephrotoxic and carcinogenic aristolochic acid, but it would require further testing to establish the presence of aristolochia acid in the samples positive for Asarum. Plant DNA assigned to other potentially toxic, allergic (nuts, soy) and/or subject to CITES regulation were also recovered. Again, other gene regions would need to be targeted, to reveal the exact species involved.

Most newspapers emphasized that the study has brought to light “the dangers of TCM”

For this reason The Telegraph interviewed an expert in the field, Edzard Ernst, Professor of Complementary Medicine at the University of Exeter. Ernst:

“The risks of Chinese herbal medicine are numerous: firstly, the herbs themselves can be toxic; secondly, they might interact with prescription drugs; thirdly, they are often contaminated with heavy metals; fourthly, they are frequently adulterated with prescription drugs; fifthly, the practitioners are often not well trained, make unsubstantiated claims and give irresponsible, dangerous advice to their patients.”

Ernst is right about the risks. However, these adverse effects of TCM have long been known. Fifteen years ago I happened to have written a bibliography about “adverse effects of herbal medicines*” (in Dutch, a good book on this topic is [2]). I did exclude interactions with prescription drugs, contamination with heavy metals and adulteration with prescription drugs, because the events (publications in PubMed and EMBASE) were to numerous(!). Toxic Chinese herbs mostly caused acute toxicity by aconitine, anticholinergic (datura, atropa) and podophyllotoxin intoxications. In Belgium 80 young women got nephropathy (kidney problems) after attending a “slimming” clinic because of mixup of Stephania (chinese: fangji) with Aristolochia fanghi (which contains the toxic aristolochic acid). Some of the women later developed urinary tract cancer.

In other words, toxic side effects of herbs including chinese herbs are long known. And the same is true for the presence of (traces of) endangered species in TCM.

In a media release the complementary health council (CHC) of Australia emphasized that the 15 TCM products featured in this study were rogue products seized by Customs as they were found to contain prohibited and undeclared ingredients. The CHC emphasizes the proficiency of rigorous regulatory regime around complementary medicines, i.e. all ingredients used in listed products must be on the permitted list of ingredients. However, Australian regulations do not apply to products purchased online from overseas.

Thus if the findings are not new and (perhaps) not applicable to most legal TCM, then what is the value of this paper?

The new aspect is the high throughput DNA sequencing approach, which allows determination of a larger number of animal and plant taxa than would have been possible through morphological and/or biochemical means. Various TCM-samples are suitable: powders, tablets, capsules, flakes and herbal teas.

There are also some limitations:

  1. DNA of sufficient quality could only be obtained from appr. half of the samples.
  2. Plants sequences could often not be resolved beyond the family level. Therefore it could often not be established whether an endangered of toxic species was really present (or an innocent family member).
  3. Only DNA sequences can be determined, not pharmacological activity.
  4. The method is at best semi-quantitative.
  5. Only plant and animal ingredients are determined, not contaminating heavy metals or prescription drugs.

In the future, species assignment (2) can be improved with the development of better reference databases involving multiple genes and (3) can be solved by combining genetic (sequencing) and metabolomic (for compound detection) approaches. According to the authors this may be a cost-effective way to audit TCM products.

Non-technical approaches may be equally important: like convincing consumers not to use medicines containing animal traces (not to speak of  endangered species), not to order  TCM online and to avoid the use of complex, uncontrolled TCM-mixes.

Furthermore, there should be more info on what works and what doesn’t.

*including but not limited to TCM

References

  1. Coghlan ML, Haile J, Houston J, Murray DC, White NE, Moolhuijzen P, Bellgard MI, & Bunce M (2012). Deep Sequencing of Plant and Animal DNA Contained within Traditional Chinese Medicines Reveals Legality Issues and Health Safety Concerns. PLoS genetics, 8 (4) PMID: 22511890 (Free Full Text)
  2. Adverse Effects of Herbal Drugs 2 P. A. G. M. De Smet K. Keller R. Hansel R. F. Chandler, Paperback. Springer 1993-01-15. ISBN 0387558004 / 0-387-55800-4 EAN 9780387558004
  3. DNA may weed out toxic Chinese medicine (abc.net.au)
  4. Bedreigde beren in potje Lucas Brouwers, NRC Wetenschap 14 april 2012, bl 3 [Dutch]
  5. Dangers in herbal medicine (continued) – DNA sequencing to hunt illegal ingredients (somethingaboutscience.wordpress.com)
  6. Breaking down traditional Chinese medicine. (green.blogs.nytimes.com)
  7. Dangers of Chinese Medicine Brought to Light by DNA Studies (news.sciencemag.org)
  8. Chinese herbal medicines contained toxic mix (cbc.ca)
  9. Screen uncovers hidden ingredients of Chinese medicine (Nature News)
  10. Media release: CHC emphasises proficiency of rigorous regulatory regime around complementary medicines (http://www.chc.org.au/)




Silly Sunday #50: Molecular Designs & Synthetic DNA

23 04 2012

As a teenager I found it hard to picture the 3D structure of DNA, proteins and other molecules. Remember we didn’t have a computer then, no videos, nor 3D-pictures or 3D models.

I tried to fill the gap, by making DNA-molecules of (used) matches and colored clay, based on descriptions in dry (and dull 2D) textbooks, but you can imagine that these creative 3D clay figures beard little resemblance to the real molecular structures.

But luckily things have changed over the last 40 years. Not only do we have computers and videos, there are also ready-made molecular models, specially designed for education.

O, how I wished, my chemistry teachers would have had those DNA-(starters)-kits.

Hattip: Joanne Manaster‏ @sciencegoddess on Twitter: 

Curious? Here is the Products Catalog of http://3dmoleculardesigns.com/news2.php

Of course, such “synthesis” (copying) of existing molecules -though very useful for educational purposes- is overshadowed by the recent “CREATION of molecules other than DNA and RNA [xeno-nucleic acids (XNAs)], that can be used to store and propagate information and have the capacity for Darwinian evolution.

But that is quite a different story.

Related articles





Jeffrey Beall’s List of Predatory, Open-Access Publishers, 2012 Edition

19 12 2011

Perhaps you remember that I previously wrote [1] about  non-existing and/or low quality scammy open access journals. I specifically wrote about Medical Science Journals of  the http://www.sciencejournals.cc/ series, which comprises 45 titles, none of which having published any article yet.

Another blogger, David M [2] also had negative experiences with fake peer review invitations from sciencejournals. He even noticed plagiarism.

Later I occasionally found other posts about open access spam, like the post of Per Ola Kristensson [3] (specifically about Bentham, Hindawi and InTech OA publishers), of Peter Murray-Rust [4] ,a chemist interested in OA (about spam journals and conferences, specifically about Scientific Research Publishing) and of Alan Dove PhD [5] (specifically about The Journal of Computational Biology and Bioinformatics Research (JCBBR) published by Academic Journals).

But now it appears that there is an entire list of “Predatory, Open-Access Publishers”. This list was created by Jeffrey Beall, academic librarian at the University of Colorado Denver. He just updated the list for 2012 here (PDF-format).

According to Jeffrey predatory, open-access publishers

are those that unprofessionally exploit the author-pays model of open-access publishing (Gold OA) for their own profit. Typically, these publishers spam professional email lists, broadly soliciting article submissions for the clear purpose of gaining additional income. Operating essentially as vanity presses, these publishers typically have a low article acceptance threshold, with a false-front or non-existent peer review process. Unlike professional publishing operations, whether subscription-based or ethically-sound open access, these predatory publishers add little value to scholarship, pay little attention to digital preservation, and operate using fly-by-night, unsustainable business models.

Jeffrey recommends not to do business with the following (illegitimate) publishers, including submitting article manuscripts, serving on editorial boards, buying advertising, etc. According to Jeffrey, “there are numerous traditional, legitimate journals that will publish your quality work for free, including many legitimate, open-access publishers”.

(For sake of conciseness, I only describe the main characteristics, not always using the same wording; please see the entire list for the full descriptions.)

Watchlist: Publishers, that may show some characteristics of  predatory, open-access publisher
  • Hindawi Way too many journals than can be properly handled by one publisher
  • MedKnow Publications vague business model. It charges for the PDF version
  • PAGEPress many dead links, a prominent link to PayPal
  • Versita Open paid subscription for print form. ..unclear business model

An asterisk (*) indicates that the publisher is appearing on this list for the first time.

How complete and reliable is this list?

Clearly, this list is quite exhaustive. Jeffrey did a great job listing  many dodgy OA journals. We should watch (many) of these OA publishers with caution. Another good thing is that the list is updated annually.

(http://www.sciencejournals.cc/ described in my previous post is not (yet) on the list 😉  but I will inform Jeffrey).

Personally, I would have preferred a distinction between real bogus or spammy journals and journals that seem to have “too many journals to properly handle” or that ask (too much ) money for subscription/from the author. The scientific content may still be good (enough).

Furthermore, I would rather see a neutral description of what is exactly wrong about a journal. Especially because “Beall’s list” is a list and not a blog post (or is it?). Sometimes the description doesn’t convince me that the journal is really bogus or predatory.

Examples of subjective portrayals:

  • Dove Press:  This New Zealand-based medical publisher boasts high-quality appearing journals and articles, yet it demands a very high author fee for publishing articles. Its fleet of journals is large, bringing into question how it can properly fulfill its promise to quickly deliver an acceptance decision on submitted articles.
  • Libertas Academia “The tag line under the name on this publisher’s page is “Freedom to research.” It might better say “Freedom to be ripped off.” 
  • Hindawi  .. This publisher has way too many journals than can be properly handled by one publisher, I think (…)

I do like funny posts, but only if it is clear that the post is intended to be funny. Like the one by Alan Dove PhD about JCBBR.

JCBBR is dedicated to increasing the depth of research across all areas of this subject.

Translation: we’re launching a new journal for research that can’t get published anyplace else.

The journal welcomes the submission of manuscripts that meet the general criteria of significance and scientific excellence in this subject area.

We’ll take pretty much any crap you excrete.

Hattip: Catherine Arnott Smith, PhD at the MedLib-L list.

  1. I Got the Wrong Request from the Wrong Journal to Review the Wrong Piece. The Wrong kind of Open Access Apparently, Something Wrong with this Inherently… (laikaspoetnik.wordpress.com)
  2. A peer-review phishing scam (blog.pita.si)
  3. Academic Spam and Open Access Publishing (blog.pokristensson.com)
  4. What’s wrong with Scholarly Publishing? New Journal Spam and “Open Access” (blogs.ch.cam.ac.uk)
  5. From the Inbox: Journal Spam (alandove.com)
  6. Beall’s List of Predatory, Open-Access Publishers. 2012 Edition (http://metadata.posterous.com)
  7. Silly Sunday #42 Open Access Week around the Globe (laikaspoetnik.wordpress.com)




Happy Anniversary Highlight HEALTH, ScienceRoll & Sterile Eye!

13 12 2011

Starting a blog is easy. But maintaining a blog costs time and effort. Especially when having a job/while studying (and having a private life as well).

This blog almost celebrates its 4th year (February 2012).

I’m happy to notice that many established (bio)medical & library blogs, that inspired me to start blogging, are still around.

Like one of the greatest medical blogs, CasesBlog by Dr Ves Dimov. And the medlib blogs The Search Principle blog by Dean Giustini and the Krafty Librarian by Michelle Kraft.

All these blogs are still going strong.

The same is true for the blog ScienceRoll by Bertalan Mesko (emphasis on health 2.0), that celebrated its 5th anniversary last month. That same month Sterile Eye (Life, death and surgery through a lens) celebrated its 4th year of existence.

This month Highlight Health (main author Walter Jessen) celebrates its 5th year anniversary.

And the nice thing is that Highlight Health celebrates this with prize pack giveaways.

There are 4 drawings. Each prize pack consist of the following:

All you have to do is to subscribe to the blog in the form of an email alert. People, like me, who are already subscribers are also eligible to participate in the drawings. (see this post for all info)

With so many ‘golden oldies’ around, I wonder about you, my audience. Do you blog? And if you do, for how long? Please tell me in the poll below.

If you are a (bio)medical, library or science blogger (blogging in English), I would appreciate if you could fill in this spreadsheet as well. You are free to edit the spreadsheet and add names of other bloggers as well.





Grand Rounds Vol 8 nr 5: Data, Information & Communication

26 10 2011

Welcome to the Grand Rounds, the weekly summary of the best health blog posts on the Internet. I am pleased to host the Grand Rounds for the second time. The first time, 2 years ago, was theme-less, but during the round we took a trip around the library. Because, for those who don’t know me, after years of biomedical research I became a medical librarian. This also explains my choice for the current theme:

DATA, INFORMATION & COMMUNICATION

The theme is meant to be broad. According to Wikipedia:

Information in its most restricted technical sense is a message (utterance or expression) or collection of messages that consists of an ordered sequence of symbols, or it is the meaning that can be interpreted from such a message or collection of messages. Information can be recorded or transmitted (…) as signs, or conveyed as signals by waves. Information is any kind of event that affects the state of a dynamic system. (…) Moreover, the concept of information is closely related to notions of … communication.. dataknowledge, meaning, .. perception. .. and especially entropy.

I am pleased that there were plenty submissions on the topic. I love the creative way the bloggers used the theme “information”. In line with the theme the information will be brought to you according to the Rule of Entropy, seemingly chaotic. Still all information is meaningful and often a pleasure to read. Please Enjoy!

INDIA, WISDOM & IMAGESIMAGING

From: IBN-live (India): Book News: “Kama Sutra is about sexual & social relations”

IMAGES are a great way to tell information, especially if you don’t understand the language. The picture above is from the Kama Sutra, an ancient Indian Hindu work on human sexual behavior in Sanskrit literature. Did you know the original Kama Sutra is not all about sex and does not have any pictures? Only words, no graphic. And sadly, as a text, it isn’t widely read.

Yes, we start our trip where it ended last week, in INDIA

Our host of last week, Sumer Sethi of Sumer’s Radiology Site, shows very clear (MRI)-images of partially recanalized internal jugular vein thrombosis, in a patient with MS, possibly supporting the theory that MS is a result of chronic venous insufficiency. As readers of this blog know Laika is not impressed by n=1 data, although it may be a good starting point. However, Sumer underpins this link with a paper in J Neurol Neurosurg Psychiatry 2009. Still, a quick look at the citing papers shows many new studies don’t confirm the association of MS with cerebrospinal venous insufficiency…

Another great radiologist, also from India, isVijay Sadasivam (@scanman). No recent posts, but at Scanman’s Casebook you will find an archive of interesting radiological cases, in the form of case reports.

The quite tech savvy surgeon Dr. Dheeraj (aka Techknowdoc) explores the alternatives to the invasive and uncomfortable colonoscopy procedure at Techknowdoc’s Surgical Adventures! This post is a short illustrated guide, visualizing the differences between regular colonoscopy, capsule endoscopy and Virtual Colonoscopy. It is not hard to imagine which approach people would prefer.

Pranab (aka Skepticdoctor) makes an urgent appeal to fellow Indians to help Amit Gupta and other Indian people to get a bone marrow transplant when they need one. Amit has Acute Leukemia, but South Asians are very poorly represented in bone marrow registries, so his odds of getting a match off the registries in the US are slim. The chances are even worse for the less well-off Indians. Read at Scepticemia how you can help. For Amit, for India, for you, or worse, someone you love more than yourself….

Dr. Jen Gunter ridicules Cosmo’s to-go version of the Kama Sutra in a short series! For the “sex positions of the days” are just an offensive alliteration and woeful ignorance of female anatomy… Looking up medical information is the 3rd most common on-line activity. While there are good sites with great information that can help people be empowered about their health, there are also tons of terrible sites marred by bias and rife with the stench of snake oil. In an other post at Dr. Jen Gunter (wielding the lasso of truth) Jen reveals 10 red flags that will help you separate the wisdom from the woo.

THE POWER OF WORDS, MUSIC AND VISUAL ARTS

http://www.flickr.com/photos/isfullofcrap/5147100521/

Yes, a picture is worth a thousand words. And this is also true for other audiovisual arts. 

Yet, some Medical Bloggers master the art of storytelling, they convey of events in words, images and sounds. And here, words have the same powerful strength. Often these posts of these storytellers are about communication and they know how to communicate that.

One of the master storytellers is Bongi, a general surgeon from South Africa. He submitted the post die taal (that language), which is clearly about communication but in a language (“Afrikaans”), that I can understand, but many of you don’t. Therefore I choose another post at Other Things Amanzi, which is also about communication: “It’s all in the detail”

Another great storyteller, and the winner of the best literary medical blog category of Medgadget contest in 2009 and 2010 is StorytellERdoc. In the beautiful post The Reminder – EKG #6, he tells us how the 6th abnormal EKG in a presentation of one of the residents, brought back memories to the technician who made that EKG: “There is something more important about this EKG than it’s tracing, I began” ….

Robbo (Andrew Roberts) is a pharmacist from one of the most remote parts of Australia working full time in Aboriginal Health. His blog BitingTheDust often covers topics like aboriginal art and pharmacy. There is also a category “information-resources”. His latest post in this category explains how condoms are made and how they work. A video goes with it.

Øystein of  The Sterile Eye (Life, death and surgery through a lens) uses photos throughout his blog. His latest post is about a brochure “LEICA – Fotografie in der Medizin” (Photography in Medicine) that was published by Leitz in 1961.

Another blogger, unique in its kind, “raps” his stories. Yes I’m talking about Zubin, better known as ZDoggMD. Watch how he and his mates colleagues rap “Doctors Today!” where he “informs” folks of what it’s like to actually practice primary care medicine on the front lines. Want to know more about this medical rapper, then listen to this radio interview with a med-student run radio (RadioRounds). It’s about using video to “inform” patients and healthcare providers about health-related issues in a humorous way.

Movies are also a good way to “tell a story” and pass information. Ramona Bates reviews the Lifetime’s Movie “Five” at her blog Suture for a Living. Five is an anthology of five short very emotional (but not sentimental) films exploring the impact of breast cancer on people’s lives.

We have had pictures, music, videos and movies as data carriers. But here is a post that is based on the good old book. Dr. Deborah Serani (who has a blog of her own: Dr. Deb: Psychological Perspectives) submits a review from PsychCentral about her new book “Living with Depression.” My first intuitive response: how can a psychologist or psychoanalyst write about “living with“. But it seems that Deborah Serani has faced a lifelong struggle with depression herself. This memoir/self help book seems a great resource for anyone in the health field looking for information about mood disorders, treatments and recommendations. The review makes me want to read this book.

SOCIAL MEDIA & MOBILE APPS

http://www.flickr.com/photos/verbeeldingskr8/4507350257/

What about social media as a tool for medical communication and a source of information?

At Diabetes Mine Allison B. and Amy Tenderich review numerous new mobile apps for managing diabetes. Their reviews “Diabetes? There’s An App For That” and “Glooko: iPhone Diabetes Logging Made Super-Easy” may help to choose diabetes patients among the bevvy of diabetes apps.

Twitter is seen as offering more noise than signal, but there’s valid medical data that can be uncovered. Ryan DuBosar at the ACP internist blog highlights how a researcher uses Twitter to track attitudes about vaccination and how they correlate with vaccination rates. The study adds to a growing body of evidence that social networking can be used to track diseases and other natural disasters that affect public health.

Hot from the press, I can’t resist to include a post from the web 2.0 pioneer Dr. Ves at CasesBlog. Ves Dimov usually writes many short posts, but today he explains Social media in Medicine in depth and guides you “How to be a Twitter superstar and help your patients and your practice”. According to his interesting concept two Cycles, the cycle of Patient Education and the Cycle of Online Information and Physician Education, work together as two interlocking cogwheels.

Mayo Clinic started using social media for communication with patients well before all the recent hype and it organized tweetcamps back in 2009. David Harlow made the pilgrimage to Rochester, MN and spoke at the Mayo Clinic Center for Social Media’s Health Care Social Media Summit last week. According to David “A ton of information was presented, through traditional channels and through some multimedia demos as well”. He shares conference highlights in this post at HealthBlawg, like “It is impossible to transplant a successful program from one location to another without taking into account myriad local conditions”. And “health care providers will have to do more with less”. Therefore e-Patient Dave suggests in his closing keynote to “Let Patients Help”.

Nicholas Fogelson of Academic OB/GYN notes that an operating room without incentives is very expensive. He proposes to install a cheap digital toteboard in every operating room in the USA, that would read how many dollars have been spent on that case at that moment. The idea is that surgeons who know exactly what they are spending, would compete to spend less wherever they could.

According to Bryan Vartabedian the social and technological innovations cause doctors to slowly change from analog physicians to digital physicians. He mentions 6 differences between these doctors. The first is that the information consumption of the digital physician is web-based, while the analog doctor consumes information through paper books and journals, often saying curious things like, “I like the smell of paper” or “I’ve gotta be able to hold it.” By the way, Bryan’s blog 33 Charts is all about social media and medicine.

Blogging doctors are digital doctors per definition, but that doesn’t mean they don’t want to discuss things and see each other in real life. Dr. Val of Better Health and cofounder of this Grand Rounds announces a blog conference in Los Angeles, the Blog World Expo, on November 4th, 2011. Her talk is about “physicians engaging online in social health”, but she is actually hoping that many members of the medical blogging community will be out there IRL! At her blog you can get discount tickets.

The online presence of doctors at social media places can have serious drawbacks. The post of Anne Marie Cunningham about derogatory and cynical humour as displayed by medical personnel at Twitter and Facebook has made it to the Daily Telegraph, other UK newspaper, and to my blog…. This post at Wishful thinking in medical education is a must read for healthcare providers embracing social media.

Many physicians have an online presence, but do they really use social media for decision making, wonders Chris Nickson. From his post and the ensuing reactions at Life in the Fast Lane it appears that tools like Twitter and the comments sections on blogs enable a constant, ongoing dialogue with emergency physicians and critical care experts around the world regarding puzzling clinical issues. Rarely, however, there is a direct ‘tweet’ for clinical help. Rather Twitter contributes to the serendipitously finding of relevant and significant information.

Perhaps direct clinical questions are not asked because Twitter (and Facebook to some extent) are open social media. Bertalan Mesko of ScienceRoll mentions that some French doctors actually perform case presentations on Google+, taking advantage of the very simple privacy settings of Google+. They upload information about the case, discuss it with other peers and get to a final diagnosis.

E-Patient Dave announced a seven hour event about information transfer during transitions of care. This event was webcasted, tweeted and discussed on Google+. (also see Brian Ahier’s post about it on Government Health IT). Dave gives some examples that highlight that without reliable information transition, the care transition can become dangerous. Yes, good IT can help.

DATA, DATABASES, OPEN ACCESS, EBM

http://www.flickr.com/photos/verbeeldingskr8/4029292954/

We now arrive at a clinical librarian topic, medical information via databases, journals and the role of EBM.

The first post bridges this and the previous topic. Jon Brassey is co-founder of  the TRIP-database, a clinical search tool designed to rapidly identify the highest quality clinical evidence for clinical practice. At his blog Liberating the Literature he expresses his view that search is -at best- a partial solution. He is passionate about answering clinician’s questions and would rather see an answer machine than a search engine. Jon is very tempted to allow users to upload their own Q&As, thereby creating an open repository of clinical Q&As. I am more skeptical, because this kind of EBM sharing might be at the expense of the quality of evidence.

What do you think? Can social media and EBM reinforce each other or not? Please tweet your ideas to Anabel Bentley (@doctorblogs at Twitter) who is giving a talk at Evidence 2011 (#ev2011) tomorrow on social media & EBM and asks for your input. You might also want to read my older post about The Web 2.0-EBM Medicine split.

Dean Giustini reviews PubMed Health at The Search Principle Blog. Dean describes PubMed Health as follows. It is as a consumer version of PubMed – a metasearch tool that gathers evidence from Cochrane Collaboration, Nice and other EBM sources to see clinical studies and “what works” in human health. One major benefit of PubMed Health is that any search performed on PubMed Health also runs in PubMed.” Sounds like worth trying.

The invitation to join the editorial board of a relatively new online, open access journal, without receiving any compensation triggered Skeptic Scalpel to ponder about the tangible benefits of open access publishers (coined as “predatory open access” by a commenter) and about how many journals are really needed? Who has the time or interest to read 25 journals on a relatively specialized topic? And what about the quality of the articles in all these journals?

Indeed as The Krafty Librarian explains  the “good guys” (open access) are making just as much profit as the “bad guys.”  They both are for profit. Open Access is not the panacea that many think it is.

Tasha Stanton of Body in Mind asks the intriguing question what to do if systematic reviews on the same topic don’t all give us the same conclusions, whereas you would expect they would collate the same evidence. Tasha finds this disconcerting as for some conditions this could take ages before we could ‘trust’ the evidence. In the example discussed here an Umbrella review was helpful in assessing the evidence. Also the quality of systematic reviews is improving.

SCREENING & DIAGNOSIS. BALANCING BENEFITS & HARMS. 

From: http://www.naturalnews.com/025768_radiation_cancer_mammograms.html as seen at Science Based Medicine

Many people think screening is always a good thing and will prevent or cure a disease. But not every test is a good test and often there are both harms and benefits. It is difficult for patients to understand the true value of tests. 

Margaret Polaneczky, MD was touched by a beautiful essay in the NY Times written by a mother of a child born with Tay Sachs disease. While the mother in her loved the essay, the doctor in her cringed, because a single paragraph about the mother’s experience with prenatal screening had the potential to misinform and even frighten readers. Margaret writes a bit of a primer on Tay Sachs screening at the Blog That Ate Manhattan, mainly to set realistic expectations about what prenatal testing can and cannot accomplish.

David Williams at the Health Business Blog reasons that the US Preventive Services Task Force (USPTF) recommendations against routine use of the PSA blood test in healthy men should not have been delayed because of the the firestorm of controversy created by the 2009 screening mammography guidelines… Because uh-oh well, PSA testing is different (and David is right)…  It’s all about what kind of info we can expect from screening and where it leads us.

This month is breast cancer awareness month, meant to highlight issues of breast cancer and try to call attention to new discoveries about breast cancer. Personally I have mixed feelings about the pink ribbon exploitation of this month”, but David Gorky at Science Based Medicine points at a worse misuse: quacks seize the opportunity to spread their message against science-based modalities for the detection and treatment of breast cancer and to promote their “alternative” methods. (see Fig. above).

BIOMEDICINE, BRAINS AND THE PROCESSING OF INFORMATION

http://www.flickr.com/photos/caseorganic/3675792814/ [CC]

Dr Shock MD PhD reviews a Dutch trial that shows that availability bias contributes to diagnostic errors made by physicians. Availability bias means that a disease comes more easily to the mind of a doctor who diagnoses this disease more often. This study also suggests that analytical or reflective reasoning may help to counteract this bias.

In an intriguing post counseling psychologist Will Meek, PhD covers some of the recent research on two information processing systems as identified by Daniel Kahneman: Intuition and Reasoning. A simple experiment confirms (in my case) that we use intuition for most of the day, and occasionally use reasoning to answer more complex problems. Some people may also frame this as “head vs heart”. Both systems have their pros and cons and both are needed to make good decisions. Otherwise common problems can arise.

David Bradley of ScienceBase discusses recent research by Gallant and colleagues who were able to reconstruct a video image presented to a subject in a functional MRI machine. David dreams of uploading our dreams to Youtube and of developing a mind-machine interface to allow people with severe disabilities to communicate their thoughts and control a computer or equipment. But David is more of a scientist than a dreamer and he interviews Gallant to find out more about the validity of the technique.

Computational Biologist Walter Jessen highlights “National Biomedical Research Day” at Highlight HEALTH. “National Biomedical Research Day” was proclaimed by Bill Clinton in 1993 on the 160th anniversary of Nobel’s birth. This day celebrates the central role of biomedical research  in improving human health and longevity.

MISINFORMATION, WRONG INFORMATION AND LACK OF INFORMATION

http://www.flickr.com/photos/truthout/3901813960/
This image was paired with the story: Insurers Shun Those Taking Certain Meds

Philip Hickey at Behaviorism and Mental Health discusses homosexuality. Philip: “homosexuality is a complex phenomenon which defies simplistic explanations. Unfortunately in this field valid information and communication often take a back seat to bigotry and prejudice.”

In his post “Want go Dutch…or German…or French?” at HUB’s LIST of medical fun facts Herbert Mathewson, MD argues that “Before trying to copy other nation’s health care systems we should probably actually learn about them.” The outcomes of the Dutch switch from a system of mandatory social insurance administered by nonprofit sick funds to mandatory basic insurance that citizens had to buy from private insurance companies (“managed competition”) are appalling! I can imagine that the idea that the Dutch reforms provide a successful model for U.S. Medicare seems bizarre. (Herbert’s post is based on a NEJM article “Sobering Lessons from the Netherlands”).

Henry Stern of InsureBlog notes that as far as RomneyCare© (Massachusetts health care reform) is concerned it’s not so much lack of information per se that’s the problem. It’s information that’s wrong that gets you in trouble.

Robert Centor of Medrants simply submitted one sentence:
“I am a physician, not a provider, and Groopman agrees. – http://www.medrants.com/archives/6505″
This distinction between physicians and providers is similar to the distinction between consumers and patients, and I agree.

Rich Fogoros (DrRich) of The Covert Rationing Blog discusses recent article in the New York Times about whether nurses with a doctorate degree ought to be addressed as “doctor.” Most doctors think calling a nurse “doctor” is not appropriate and confusing for patients.
A medical student running the blog The Reflex Hammer agrees: medical students with a doctoral degree don’t introduce themselves as “Doctor” to a patient either, don’t they?
Dr Rich, an old hand, thinks otherwise. While it is indeed comforting that doctors should be so concerned about patients knowing everything they’re supposed to know, the fact (according to dr. Rich) is that the doctor-nurse controversy is a distraction.

INFORMATION YOU NEED


http://www.flickr.com/photos/nirak/1386793065/
credit: mattahan.deviantart.com/
Note: this is a librarian!!

And of course you always hope that you find the information you need or that you can inform people the right way.

Medaholic wonders whether you still would be a medical doctor if you knew that it didn’t pay as much? What sorts of information would help you determine whether this is a career worth pursuing?

The post, by Chris Langston, at the John A. Hartford Foundation blog, Health AGEnda details how interested health professionals can get information about how to apply for a new fellowship with the Center for Medicare & Medicaid Innovations office, and urges health professionals interested in improving health care for older adults to apply.

Hospital antimicrobial stewardship programs are prompting more appropriate prescribing of antibiotics, leading to improved patient care, less microbial resistance and lower costs, three studies show. The trick is how to convey this information so hospitals will implement these programs, as only one-third of U.S. facilities currently do. Read more at ACP Hospitalist, in the second contribution of Ryan DuBosar to this round.

We all know that adherence to prescriptions is a problem. But will the Star Ratings system increase adherence? The big question, according to Georg van Antwerp, author of Enabling Healthy Decisionsis whether consumers care about Star Ratings or just focus on lowest price point and access to pharmacies or specific medications.

Louise of the Colorado Health Insurer Insider summarizes her submission quite aptly: “Our submission is about the new Health Insurance Exchanges that will be starting here in the US soon. This post discusses how consumers will get INFORMATION about the health plans through the exchanges. Currently, consumers get their information through health insurance brokers or directly through the insurance carrier. If there are people to answer questions for consumers with the exchanges, how will the plans be more or less expensive”

The post that Reflex Hammer submitted (the one above was just picked by me) concerns informing young children about vegetables. A few weeks ago he and a classmate were invited to give a presentation to 1st graders at an inner-city school. Wishing to combat obesity, they developed a lesson plan about vegetables. They were heartened by how much the adorable kids already knew about vegetables and how enthusiastic they became about eating their greens. An adorable initiative and a great post to end this Grand Rounds, since it illustrates the importance of doctors who enjoy to take their time to inform people.

I just want to mention one other post, by Mike Cadogan at Life at the fast Lane. Mike doesn’t blog a lot lately, because he is preparing presentations for an important Emergency Medicine meeting. But Mike does share some of this journey with us in The 11 Phases Of Grief  Presentation Preparation. Reading these 11 stages, the similarities between writing a lecture and writing for Grand Rounds struck me. Except that beer had to be replaced by wine….

Mike is in stage 7-9, I am in stage 10-11. Stage 11 is Evaluation: What will I do different next time? First, I won’t go for two blog carnivals at the same time, I won’t plan a Grand Round when I’m away for the weekend* (I just need a lot of time) and I should refrain from adding posts that weren’t even submitted….

Will you remind me next time?

I hope that you enjoyed this Grand Rounds and that it wasn’t too much information. I enjoyed reading and compiling all our posts!

Related articles





Your Medical Mind. How to Decide What is Right for You [Book Review]

3 10 2011

I enjoyed reading “Your Medical Mind” from start to end. The style of this book was light, but the content was not. Jerome Groopman, oncologist, and Pamela Hartzband, endocrinologist, are to be congratulated on their ability to write clearly about a difficult topic. They explain all aspects about making the right medical choices, in a way that is comprehensible to all.

What makes their book so enlightening is that Groopman and Hartzband illustrate each aspect of medical decisionmaking with real patient stories. In fact the entire book is largely based on interviews with scores of patients of different ages, of different economic status and with different medical conditions.

The authors also drew on research and insights from doctors, psychologists, economists and other experts to shed more light on forces that can aid or impede our thinking when we have to make those decisions.
For those who want to explore things further, there are 213 notes (appr. 80 pages!) and a bibliography of 20 pages at the end of the book.

The first chapter “Where am I in the numbers” deals… right… with numbers, or basic statistics. A topic that patients (and quite some doctors!) often find difficult to understand. This chapter explains Relative Risk Reduction (RRR), Control Event Rate (Basic Risk), Absolute Risk Reduction (ARR) and Numbers Needed to Treat (NNT) without hardly mentioning these terms.

The authors illustrate these and other principles with the story of Susan. Susan is a bit overweight and has a high cholesterol “of the bad kind” (LDL). Her GP concludes: “Since you’re active and already follow a healthy diet, I think it is time for medication. Fortunately, we have a good treatment for this [statins]. Here is a prescription. I’ll see you again in a month”.

But Susan doesn’t take the prescription. Why? First Susan is a doubter and a minimalist. She wants the minimum necessary, certain that “less is more”.  For this is how she was raised. Second, Susan is very much like her father, who had a similar high cholesterol, never took a pill, yet lived a long, full and healthy life. Therefore she believes that for people like her these high levels of LDL-cholesterol are not necessarily dangerous. Third, she  meets an acquaintance who suffers from debilitating muscle pain as a side effect of the statins.

When Susan’s GP hears that she decided not to take her medicine, her face tightens in concern: “It s very important to take this medication. You really need it”. She explains that statin pills will lower her risk of a heart attack over the next 10 years by as much as 30 % [RRR]. She adds that the risk of side effects is very small and often reversible.

Sinds 30% less risk of myocardial infarction (heart attack, MI) sounds impressive, Susan promised her doctor to reconsider her decision. As many other people she searches the Web for medical information. After months (!) she finds a government-sponsored link with objective patient information and a 10-year heart attack risk calculator. By entering all the requested information, she finds out that her basic MI risk is 1%. This means that 1 of 100 (or 3 of 300) people with this level of risk will have a heart attack in the next 10 years (background risk without taking treatment).

Let’s apply that benefit to a group of 300 women like Susan, where 3 of them would have a MI without taking statins. If we treat them all, we would prevent one MI—because we prevent 1 MI in 3 women (30% RRR). The other 2 women would still have a MI despite taking the medicine. The remaining 297 would not have had a heart attack even without the medication, so they wouldn’t have benefited from taking it. Thus 300 persons with this background risk need to be treated to prevent one heart attack. This is the number needed to treat (NNR).

Research has shown that people respond most profoundly to “stories”. Statistics can help to merge science with stories and fit single anecdotes into the larger context of all people who are treated. Statistics (and “evidence” in general) allows people to make an informed choice. 

Susan’s story also illustrates that framing  is very important. When you hear that a statin lowers your risk by 30% (RRR), it sounds as if you are at 100% risk and thus have a great benefit. But reframing the effect as a chance of 1 in 300 persons to have a benefit, may shift the balance for you. Susan concluded that the benefits didn’t outweigh the risks. Others may look at it another way: If there is a chance I could be the one person out of the 300 who avoids a heart attack, then the statin is 100% effective for me. 

Pharmaceutic industries understand a great deal about how people decide whether to take a medicine. They frame information about benefit in the most favorable way and exploit the power of availability bias* using carefully crafted images and anecdotes, and giving implicit messages while  marginalizing side effects.

Various studies and patient stories discussed in the book clearly show that patients choose differently when they are given clearer information about benefits and risks. Surprisingly, their choice often differs from the treatment options the experts see as “best”.

As we have seen the attitude of the doctor and the way he/she frames the medical information also matters. Susan’s GP framed the information in such a way that it overemphasized the benefits of treatment with statins, the option she saw as “best”. This GP later refused Susan as a patient, because she didn’t follow her instructions. Her next doctor: “It is the old paternalistic way of dealing with patients. Ultimately you know, patients have final control of what goes on. (….) It is not like you just go: “Boom, boom, boom, here is the prescription”.

The irony is that most people will accept the default option: they assume that what is routinely recommended is best. If it turns out differently, however, they may feel strong regret. In contrast, if the risk is taken into account beforehand, people may experience side effects less seriously. Furthermore people have a tremendous ability to adapt.

The book learns us the differences between believers and doubters, maximalists and minimalists, naturalism and technology orientation and the importance of availability bias*, omission bias*, decisional conflict, loss aversion*, expected utility*, autonomy and control.

Our preferences about treatment, may depend on our personality, the way we were raised as kids and our previous experiences. This applies to both patients and doctors. As an example, the authors explain why one of them became a believer and a maximalist and the other a doubter and a minimalist. Until some bad experience with an aggressive and unsuccessful surgery made the maximalist a bit more risk-averse.

The book offers several examples of doctors  advocating treatments on basis of their beliefs or expertise. A surgeon wants to cure prostate cancer by surgery while focusing on the unacceptable sides of radiation, while radiation therapists emphasize unacceptable side effects of surgery. Yet others make a case for “watchful waiting”.
More than before, I realize that choices are highly personal and that I, too, have my own preferences. For instance, I tend to favor watchful waiting in case of low risk prostate cancer, possibly because I am a doubter in most respects, and have worked with Prof Schröder who supports watchful waiting. However, for some men this watchful waiting may become watchful worrying and they might just prefer to get the cancer out. Even at the cost of sexual and urinary function.

Interesting is also the notion that “the best” doctors or the “most renowned hospitals” may not always be the best for you. An expert who looks totally bored, saying you’re a “typical case” may give you an anonymous feeling. A nurse’s silent shrug when you express dismay about losing a lot of weight, may reinforce this sense. This can be a reason to clinch to your own community hospital and not choosing a large, bustling cancer center.

Another AHA moment for me was about end of life decisions, described in the touching chapter 8. The authors describe that nearly half of the patients were inconsistent in their wishes about what therapies they wanted, whether they had completed a living will or advance directive or not. This is because they often can’t imagine what they will want and how much they can endure when their condition shifts from healthy to sick and then to even sicker. On the other hand rigid sticking to directives may pose a dilemma to the carer. Are resuscitation and intubation allowed as temporary interventions if not meant to artificially sustain life?

In short, “Your Medical Mind” is an interesting and instructive book, that is not only of value for patients and carers, but also for doctors ànd future patients (and remember everyone is a patient sometimes).

Does this mean that “Your Medical Mind” is an “essential companion that will show us how to chart a clear path through this sea of confusion” as the book flap and introduction promise?

And is it true that the answer to the question “How do you know what is right for you? lies not with the experts, but within you?”

These seem too ambitious claims.

For a good decision process knowing your preferences and the forces that can influence your choice, is not enough. A good health literacy is important too. Apart from a chapter that deals with statistics, this book offers little info on that topic.

What about minimalistic naturalists who choose a homeopathic treatment for cancer? This choice might fit the medical mind of those patients, and of course they have every right to make their own decisions, but is it truly “right for them”?

I get the impression that the authors underestimate the value of “evidence”. They are very skeptical, not only about pharmaceutical companies, but also about recommendations in guidelines, whether they are evidence based or not.

In the examples all treatments are almost equally effective. This leaves a grey zone for where there is no black and white answer about when and how to treat. Often, some treatments are superior to others (for certain patient groups).

Thus, the authors give little attention to the importance of objective medical information itself, as a basis for decision making. They also pay no attention to shared decision making, as e-patient Dave emphasizes in his review.

Still, I loved the book. It completes my knowledge of EBM and information sources.

It also made me curious about another book by Groopman “How doctors think” , which has rapidly risen to the top of the New York Times bestseller list since its release in March 2007.  Dr Shock just reviewed it. Perhaps we should exchange our books….

Title: Your Medical Mind
Author: Jerome Groopman, M.D., Pamela Hartzband, M.D.
Publisher: The Penguin Press
Book: Hardcover, 320 pages
Buy: Amazon.com

  • availability bias: overweighting evidence that comes easily to mind.
  • loss aversion: the reluctance to risk side effects for what is pursued to be a small benefit
  • expected utility = [probability x outcome) X (utility of outcome)
  • omission bias: avoiding treatment because of anticipation of regret




Medical Black Humor, that is Neither Funny nor Appropriate.

19 09 2011

Last week, I happened to see this Facebook post of the The Medical Registrar where she offends a GP, Anne Marie Cunningham*, who wrote a critical post about black medical humor at her blog “Wishful Thinking in Medical Education”. I couldn’t resist placing a likewise “funny” comment in this hostile environment where everyone seemed to agree (till then) and try to beat each other in levels of wittiness (“most naive child like GP ever” – “literally the most boring blog I have ever read”,  “someone hasn’t met many midwives in that ivory tower there.”, ~ insulting for a trout etc.):

“Makes no comment, other than anyone who uses terms like “humourless old trout” for a GP who raises a relevant point at her blog is an arrogant jerk and an unempathetic bastard, until proven otherwise…  No, seriously, from a patient’s viewpoint terms like “labia ward” are indeed derogatory and should be avoided on open social media platforms.”

I was angered, because it is so easy to attack someone personally instead of discussing the issues raised.

Perhaps you first want to read the post of Anne Marie yourself (and please pay attention to the comments too).

Social media, black humour and professionals…

Anne Marie mainly discusses her feelings after she came across a discussion between several male doctors on Twitter using slang like ‘labia ward’ and ‘birthing sheds’ for birth wards, “cabbage patch” to refer to the intensive care and madwives for midwives (midwitches is another one). She discussed it with the doctors in question, but only one of them admitted he had perhaps misjudged sending the tweet. After consulting other professionals privately, she writes a post on her blog without revealing the identity of the doctors involved. She also puts it in a wider context by referring to  the medical literature on professionalism and black humour quoting Berk (and others):

“Simply put, derogatory and cynical humour as displayed by medical personnel are forms of verbal abuse, disrespect and the dehumanisation of their patients and themselves. Those individuals who are the most vulnerable and powerless in the clinical environment – students, patients and patients’ families – have become the targets of the abuse. Such humour is indefensible, whether the target is within hearing range or not; it cannot be justified as a socially acceptable release valve or as a coping mechanism for stress and exhaustion.”

The doctors involved do not make any effort to explain what motivated them. But two female anesthetic registrars frankly comment to the post of Anne Marie (one of them having created the term “labia ward”, thereby disproving that this term is misogynic per se). Both explain that using such slang terms isn’t about insulting anyone and that they are still professionals caring for patients:

 It is about coping, and still caring, without either going insane or crying at work (try to avoid that – wait until I’m at home). Because we can’t fall apart. We have to be able to come out of resus, where we’ve just been unable to save a baby from cotdeath, and cope with being shouted and sworn at be someone cross at being kept waiting to be seen about a cut finger. To our patients we must be cool, calm professionals. But to our friends, and colleagues, we will joke about things that others would recoil from in horror. Because it beats rocking backwards and forwards in the country.

[Just a detail, but “Labia ward” is a simple play on words to portray that not all women in the “Labor Ward” are involved in labor. However, this too is misnomer.  Labia have little to do with severe pre-eclampsia, intra-uterine death or a late termination of pregnancy]

To a certain extent medical slang is understandable, but it should stay behind the doors of the ward or at least not be said in a context that could offend colleagues and patients or their carers. And that is the entire issue. The discussion here was on Twitter, which is an open platform. Tweets are not private and can be read by other doctors, midwives, the NHS and patients. Or as e-Patient Dave expresses so eloquently:

I say, one is responsible for one’s public statements. Cussing to one’s buddies on a tram is not the same as cussing in a corner booth at the pub. If you want to use venting vocabulary in a circle, use email with CC’s, or a Google+ Circle.
One may claim – ONCE – ignorance, as in, “Oh, others could see that??” It must, I say, then be accompanied by an earnest “Oh crap!!” Beyond that, it’s as rude as cussing in a streetcorner crowd.

Furthermore, it seemed the tweet served no other goal as to be satirical, sardonic, sarcastic and subversive (words in the bio of the anesthetist concerned). And sarcasm isn’t limited to this one or two tweets. Just the other day he was insulting to a medical student saying among other things:“I haven’t got anything against you. I don’t even know you. I can’t decide whether it’s paranoia, or narcissism, you have”. 

We are not talking about restriction of “free speech” here. Doctors just have to think twice before they say something, anything on Twitter and Facebook, especially when they are presenting themselves as MD.  Not only because it can be offensive to colleagues and patients, but also because they have a role model function for younger doctors and medical students.

Isolated tweets of one or two doctors using slang is not the biggest problem, in my opinion. What I found far more worrying, was the arrogant and insulting comment at Facebook and the massive support it got from other doctors and medical students. Apparently there are many “I-like-to-exhibit-my-dark-humor-skills-and-don’t-give-a-shit-what-you think-doctors” at Facebook (and Twitter) and they have a large like-minded medical audience: the “medical registrar page alone has 19,000 (!) “fans”.

Sadly there is a total lack of reflection and reason in many of the comments. What to think of:

“wow, really. The quasi-academic language and touchy-feely social social science bullshit aside, this woman makes very few points, valid or otherwise. Much like these pages, if you’re offended, fuck off and don’t follow them on Twitter, and cabbage patch to refer to ITU is probably one of the kinder phrases I’ve heard…”

and

“Oh my god. Didnt realise there were so many easily offended, left winging, fun sponging, life sucking, anti- fun, humourless people out there. Get a grip people. Are you telling me you never laughed at the revue’s at your medical schools?”

and

“It may be my view and my view alone but the people who complain about such exchanges, on the whole, tend to be the most insincere, narcissistic and odious little fuckers around with almost NO genuine empathy for the patient and the sole desire to make themselves look like the good guy rather than to serve anyone else.”

It seems these doctors and their fans don’t seem to possess the communicative and emphatic skills one would hope them to have.

One might object that it is *just* Facebook or that “#twitter is supposed to be fun, people!” (dr Fiona) 

I wouldn’t agree for 3 reasons:

  • Doctors are not teenagers anymore and need to act as grown-ups (or better: as professionals)
  • There is no reason to believe that people who make it their habit to offend others online behave very differently IRL
  • Seeing Twitter as “just for fun” is an underestimation of the real power of Twitter

Note: *It is purely coincidental that the previous post also involved Anne Marie.





I Got the Wrong Request from the Wrong Journal to Review the Wrong Piece. The Wrong kind of Open Access Apparently, Something Wrong with this Inherently…

27 08 2011

Meanwhile you might want to listen to “Wrong” (Depeche Mode)

Yesterday I screened my spam-folder. Between all male enhancement and lottery winner announcements, and phishing mails for my bank account, there was an invitation to peer review a paper in “SCIENCE JOURNAL OF PATHOLOGY”.

Such an invitation doesn’t belong in the spam folder, doesn’t it? Thus I had a closer look and quickly screened the letter.

I don’t know what alarmed me first. The odd hard returns, the journal using a Gmail address, an invitation for a topic (autism) I knew nothing about, an abstract that didn’t make sense and has nothing to do with Pathology, the odd style of the letter: the informal, but impersonal introduction (How are you? I am sure you are busy with many activities right now) combined with a turgid style (the paper addresses issues of value to our broad-based audience, and that it cuts through the thick layers of theory and verbosity for them and makes sense of it all in a clean, cohesive manner) and some misspellings. And then I never had an invitation from an editor, starting with the impersonal “Colleagues”… 

But still it was odd. Why would someone take the trouble of writing such an invitation letter? For what purpose? And apparently the person did know that I was a scientist, who does -or is able to- peer review medical scientific papers. Since the mail was send to my Laika Gmail account, the most likely source for my contact info must have been my pseudonymous blog. I seldom use this mail account for scientific purposes.

What triggered my caution flag the most, was the topic: autism. I immediately linked this to the anti-vaccination quackery movement, that’s trying to give skeptic bloggers a hard time and fights a personal, not a scientific battle. I also linked it to #epigate, that was exposed at Liz Ditz I Speak of Dreams, a blog with autism as a niche topic.

#Epigate is the story of René Najeraby aka @EpiRen, a popular epidemiologist blogger who was asked to stop engaging in social media by his employers, after a series of complaints by a Mr X, who also threatened other pseudonymous commenters/bloggers criticizing his actions. According to Mr. X no one will be safe, because all i have to do is file a john doe – or hire a cyber investigator. these courses of action cost less than $10,000 each; which means every person who is afraid of the light can be exposed”  In another comment at Liz Ditz’ he actually says he will go after a specific individual: “Anarchic Teapot”.

Ok, I admit that the two issues might be totally coincidental, and they probably are, but I’m hypersensitive for people trying to silence me via my employers (because that did happen to me in the past). Anyway,asking a pseudonymous blogger to peer-review might be a way to hack the real identity of such a blogger. Perhaps far-fetched, I know.

But what would the “editor” do if I replied and said “yes”?

I became curious. Does The Science Journal of Pathology even exist?

Not in PubMed!!

But the Journal “Science Journal of Pathology” does exist on the Internet…. and John Morrison is the editor. But he is the only one. As a matter of fact he is the entire staff…. There are “search”, “current” and “archives” tabs, but the latter two are EMPTY.

So I would have the dubious honor of reviewing the first paper for this journal?…. 😉

  1. (First assumption – David) – High school kids are looking for someone to peer review (and thus improve) their essays to get better grades.
    (me: school kids could also be replaced by “non-successful or starting scientists”)
  2. (Second assumption – David) Perhaps they are only looking to fill out their sucker lists. If you’ve done a bad review, they may blackmail you in other to keep it quiet.
  3. (me) – The journal site might be a cover up for anything (still no clue what).
  4. (me) – The site might get a touch of credibility if the (upcoming) articles are stamped with : “peer-reviewed by…”
  5. (David & me) the scammers target PhD’s or people who the “editors” think have little experience in peer reviewing and/or consider it a honor to do so.
  6. (David & me) It is phishing scam.You have to register on the journal’s website in order to be able to review or submit. So they get your credentials. My intuition was that they might just try to track down the real name, address and department of a pseudonymous blogger, but I think that David’s assumption is more plausible. David thinks that a couple of people in Nigeria is just after your password for your mail, amazon, PayPal etc for “the vast majority of people uses the same password for all logins, which is terribly bad practice, but they don’t want to forget it.”

With David, I would like to warn you for this “very interesting phishing scheme”, which aims at academics and especially PhD’s. We have no clue as to their real intentions, but it looks scammy.

Besides that the scam may affect you personally, such non-existing and/or low quality open access journals do a bad service to the existing, high quality open access journals.

There should be ways to remove such scam websites from the net.

Notes

“Academic scams – my wife just received a version of this for an Autism article, PhD/DPhil/Masters students beware that mentions a receipt of a similar autism”
Related articles




#FollowFriday #FF @DrJenGunter: EBM Sex Health Expert Wielding the Lasso of Truth

19 08 2011

If you’re on Twitter you probably seen the #FF or #FollowFriday phenomenon. FollowFriday is a way to recommend people on Twitter to others. For at least 2 reasons: to acknowledge your favorite tweople and to make it easier for your followers to find new interesting people.

However, some #FollowFriday tweet-series are more like a weekly spam. Almost 2 years ago I blogged about the misuse of FF-recommendations and I gave some suggestions to do #FollowFriday the right way: not by sheer mentioning many people in numerous  tweets, but by recommending one or a few people a time, and explaining why this person is so awesome to follow.

Twitter Lists are also useful tools for recommending people (see post). You could construct lists of your favorite Twitter people for others to follow. I have created a general FollowFridays list, where I list all the people I have recommended in a #FF-tweet and/or post.

In this post I would like to take up the tradition of highlighting the #FF favs at my blog. .

This FollowFriday I recommend:  

Jennifer Gunter

Jennifer Gunter (@DrJenGunter at Twitter), is a beautiful lady, but she shouldn’t be tackled without gloves, for she is a true defender of evidence-based medicine and wields the lasso of truth.

Her specialty is OB/GYN. She is a sex health expert. No surprise, many tweets are related to this topic, some very serious, some with a humorous undertone. And there can be just fun (re)tweets, like:

LOL -> “@BackpackingDad: New Word: Fungry. Full-hungry. “I just ate a ton of nachos, but hot damn am I fungry for those Buffalo wings!””

Dr Jen Gunter has a blog Dr. Jen Gunther (wielding the lasso of truth). 

Again we find the same spectrum of posts, mostly in the field of ob/gyn. You need not be an ob/gyn nor an EBM expert to enjoy them. Jen’s posts are written in plain language, suitable for anyone to understand (including patients).

Some titles:

In addition, There are also hilarious posts like “Cosmo’s sex position of the day proves they know nothing about good sex or women“,where she criticizes Cosmo for tweeting impossible sex positions (“If you’re over 40, I dare you to even GET into that position! “), which she thinks were created by one of the following:

A) a computer who has never had sex and is not programmed to understand how the female body bends.
B) a computer programmer who has never has sex and has no understanding of how the female body bends.
C) a Yogi master/Olympic athlete.

Sometimes the topic is blogging. Jen is a fierce proponent of medical blogging. She sees it as a way to “promote” yourself as a doctor, to learn from your readers and to “contribute credible content drowns out garbage medical information” (true) and as an ideal platform to deliver content to your patients and like-minded medical professionals. (great idea)

Read more at:

You can follow Jen at her Twitter-account (http://twitter.com/#!/DrJenGunter) and/or you can follow my lists. She is on:  ebm-cochrane-sceptics and the followfridays list.

Of course you can also take a subscription to her blog http://drjengunter.wordpress.com/

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HOT TOPIC: Does Soy Relieve Hot Flashes?

20 06 2011

ResearchBlogging.orgThe theme of the Upcoming Grand Rounds held at June 21th (1st day of the Summer) at Shrink Rap is “hot”. A bit far-fetched, but aah you know….shrinks“. Of course they hope  assume  that we will express Weiner-like exhibitionism at our blogs. Or go into spicy details of hot sexpectations or other Penis Friday NCBI-ROFL posts. But no, not me, scientist and librarian to my bone marrow. I will stick to boring, solid science and will do a thorough search to find the evidence. Here I will discuss whether soy really helps to relieve hot flashes (also called hot flushes).

…..As illustrated by this HOT picture, I should post as well…..

(CC from Katy Tresedder, Flickr):

Yes, many menopausal women plagued by hot flashes take their relief  in soy or other phytoestrogens (estrogen-like chemicals derived from plants). I know, because I happen to have many menopausal women in my circle of friends who prefer taking soy over estrogen. They rather not take normal hormone replacement therapy, because this can have adverse effects if taken for a longer time. Soy on the other hand is considered a “natural remedy”, and harmless. Probably physiological doses of soy (food) are harmless and therefore a better choice than the similarly “natural” black cohosh, which is suspected to give liver injury and other adverse effects.

But is soy effective?

I did a quick search in PubMed and found a Cochrane Systematic Review from 2007 that was recently edited with no change to the conclusions.

This review looked at several phytoestrogens that were offered in several ways, as: dietary soy (9x) (powder, cereals, drinks, muffins), soy extracts (9x), red clover extracts (7x, including Promensil (5x)), Genistein extract , Flaxseed, hop-extract  and a Chinese medicinal herb.

Thirty randomized controlled trials with a total of 2730 participants met the inclusion criteria: the participants were women in or just before their menopause complaining of vasomotor symptoms (thus having hot flashes) for at least 12 weeks. The intervention was a food or supplement with high levels of phytoestrogens (not any other herbal treatment) and this was compared with placebo, no treatment or hormone replacement therapy.

Only 5 trials using the red clover extract Promensil were homogenous enough to combine in a meta-analysis. The effect on one outcome (incidence of hot flashes) is shown below. As can be seen at a glance, Promensil had no significant effect, whether given in a low (40 mg/day) or a higher (80 mg/day) dose. This was also true for the other outcomes.

The other phytoestrogen interventions were very heterogeneous with respect to dose, composition and type. This was especially true for the dietary soy treatment. Although some of the trials showed a positive effect of phytoestrogens on hot flashes and night sweats, overall, phytoestrogens were no better than the comparisons.

Most trials were small,  of short duration and/or of poor quality. Fewer than half of the studies (n=12) indicated that allocation had been concealed from the trial investigators.

One striking finding was that there was a strong placebo effect in most trials with a reduction in frequency of hot flashes ranging from 1% to 59% .

I also found another systematic review in PubMed by Bolaños R et al , that limited itself only to soy. Other differences with the Cochrane Systematic Review (besides the much simpler search 😉 ) were: inclusion of more recently published clinical trials, no inclusion of unpublished studies and less strict exclusion on basis of low methodological quality. Furthermore, genestein was (rightly) considered as a soy product.

The group of studies that used soy dietary supplement showed the highest heterogeneity. Overall, the results “showed a significant tendency(?)  in favor of soy. Nevertheless the authors conclude (similar to the Cochrane authors), that  it is still difficult to establish conclusive results given the high heterogeneity found in the studies. (but apparently the data could still be pooled?)

References

  • Lethaby A, Marjoribanks J, Kronenberg F, Roberts H, Eden J, & Brown J. (2007). Phytoestrogens for vasomotor menopausal symptoms Cochrane Database of Systematic Reviews (4) : 10.1002/14651858.CD001395.pub3.
  • Bolaños R, Del Castillo A, & Francia J (2010). Soy isoflavones versus placebo in the treatment of climacteric vasomotor symptoms: systematic review and meta-analysis. Menopause (New York, N.Y.), 17 (3), 660-6 PMID: 20464785




Science Asks to Retract the XMRV-CFS Paper, it Should Never Have Accepted in the First Place.

2 06 2011

Wow! Breaking!

As reported in WSJ earlier this week [1], editors of the journal Science asked Mikovits and her co-authors to voluntary retract their 2009 Science paper [2].

In this paper Mikovits and colleagues of the Whittemore Peterson Institute (WPI) and the Cleveland Clinic, reported the presence of xenotropic murine leukemia virus–related virus (XMRV) in peripheral blood mononuclear cells (PBMC) of patients with chronic fatigue syndrome (CFS). They used the very contamination-prone nested PCR to detect XMRV. This 2 round PCR enables detection of a rare target sequence by producing an unimaginable huge number of copies of that sequence.
XMRV was first demonstrated in cell lines and tissue samples of prostate cancer patients.

All the original authors, except for one [3], refused to retract the paper [4]. This prompted Science editor-in-chief Bruce Alberts to  issue an Expression of Concern [5], which was published two days earlier than planned because of the early release of the news in WSJ, mentioned above [1]. (see Retraction Watch [6]).

The expression of concern also follows the publication of two papers in the same journal.

In the first Science paper [7] Knox et al. found no Murine-Like Gammaretroviruses in any of the 61 CFS Patients previously identified as XMRV-positive, using the same PCR and culturing techniques as used by Lombardi et al. This paper made ERV (who consistently critiqued the Lombardi paper from the startlaugh-out-loud [8], because Knox also showed that human sera neutralize the virus in the blood,indicating it can hardly infect human cells in vivo. Knox also showed the WPIs sequences to be similar to the XMRV plasmid VP62, known to often contaminate laboratory agents.*

Contamination as the most likely reason for the positive WPI-results is also the message of the second Science paper. Here, Paprotka et al. [9]  show that XMRV was not present in the original prostate tumor that gave rise to the XMRV-positive 22Rv1 cell line, but originated -as a laboratory artifact- by recombination of two viruses during passaging the cell line in nude mice. For a further explanation see the Virology Blog [10].

Now Science editors have expressed their concern, the tweets, blogposts and health news articles are preponderantly negative about the XMRV findings in CFS/ME, where they earlier were positive or neutral. Tweets like “Mouse virus #XMRV doesn’t cause chronic fatigue #CFS http://t.co/Bekz9RG (Reuters) or “Origins of XMRV deciphered, undermining claims for a role in human disease: Delineation of the origin of… http://bit.ly/klDFuu #cancer” (National Cancer Institute) are unprecedented.

Thus the appeal by Science to retract the paper is justified?

Well yes and no.

The timing is rather odd:

  • Why does Science only express concern after publication of these two latest Science papers? There are almost a dozen other studies that failed to reproduce the WPI-findings. Moreover, 4 earlier papers in Retrovirology already indicated that disease-associated XMRV sequences are consistent with laboratory contamination. (see an overview of all published articles at A Photon in the Darkness [11])
  • There are still (neutral) scientist who believe that genuine human infections with XMRV still exist at a relatively low prevalence. (van der Kijl et al: xmrv is not a mousy virus [12])
  • And why doesn’t Science await the results from the official confirmation studies meant to finally settle whether XMRV exist in our blood supply and/or CFS (by the Blood Working Group and the NIH sponsored study by Lipkin et al.)
  • Why (and this is the most important question) did Science ever decide to publish the piece in the first place, as the study had several flaws.
I do believe that new research that turns existing paradigms upside down deserves a chance. Also a chance to get disproved. Yes such papers might be published in prominent scientific journals like Science, provided they are technically and methodologically sound at the very least. The Lombardi paper wasn’t.

Here I repeat my concerns expressed in earlier posts [13 and 14]. (please read these posts first, if you are unfamiliar with PCR).

Shortcomings in PCR-technique and study design**:

  • No positive control and no demonstration of the sensitivity of the PCR-assay. Usually a known concentration or a serial dilution of a (weakly) positive sample is taken as control. This allows to determine sensitivity of the assay.
  • Aspecific bands in negative samples (indicating suboptimal conditions)
  • Just one vial without added DNA per experiment as a negative control. (Negative controls are needed to exclude contamination).
  • CFS-Positive and negative samples are on separate gels (this increases bias, because conditions and chance of contamination are not the same for all samples, it also raises the question whether the samples were processed differently)
  • Furthermore only results obtained at the Cleveland Clinic are shown. (were similar results not obtained at the WPI? see below)
Contamination not excluded as a possible explanation
  • No variation in the XMRV-sequences detected (expected if the findings are real)
  • Although the PCR is near the detection limit, only single round products are shown. These are much stronger then expected even after two rounds. This is very confusing, because WPI later exclaimed that preculturing PBMC plus nested PCR (2 rounds) were absolutely required to get a positive result. But the Legend of Fig. 1 in the original Science paper clearly says PCR after one round. Strong (homogenous) bands after one round of PCR are highly suggestive of contamination.
  • No effort to exclude contamination of samples with mouse DNA (see below)
  • No determination of the viral DNA integration sites.

Mikovits also stressed that she never used the XMRV-positive cell lines in 2009. But what about the Cleveland Clinic, nota bene the institute that co-discovered XMRV and that had produced the strongly positive PCR-products (…after a single PCR-round…)?

On the other hand, the authors had other proof of the presence of retrovirus: detection of (low levels of) antibodies to XMRV in patient sera, and transmissibility of XMRV. On request they later applied the mouse mitochondrial assay to successfully exclude the presence of mouse DNA in their samples. (but this doesn’t exclude all forms of contamination, and certainly not at Cleveland Clinic)

These shortcomings alone should have been sufficient for the reviewers, had they seen it and /or deemed it of sufficient importance, to halt publication and to ask for additional studies**.

I was once in a similar situation. I found a rare cancer-specific chromosomal translocation in normal cells, but I couldn’t exclude PCR- contamination. The reviewers asked me to exclude contamination by sequencing the breakpoints, which only succeeded after two years of extra work. In retrospect I’m thankful to the reviewers for preventing me from publishing a possible faulty paper which could have ruined my career (yeah, because contamination is a real problem in PCR). And my paper improved tremendously by the additional experiments.

Yes it is peer review that failed here, Science. You should have asked for extra confirmatory tests and a better design in the first place. That would have spared a lot of anguish, and if the findings had been reproducible, more convincing and better data.

There were a couple of incidents after the study was published, that made me further doubt the robustness of WPI’s scientific data and even (after a while) I began to doubt whether WPI, and Judy Mikovits in particular, is adhering to good scientific (and ethical) practices.

  • WPI suddenly disclosed (Feb 18 2010) that culturing PBMC’s is necessary to obtain a positive PCR signal.  As a matter of fact they maintain this in their recent protest letter to Science. They refer to the original Science paper, but this paper doesn’t mention the need for culturing at all!! 
  • WPI suggests their researchers had detected XMRV in patient samples from both Dr. Kerr’s and Dr. van Kuppeveld’s ‘XMRV-negative’ CFS-cohorts. Thus in patient samples obtained without a culture-enrichment step…..  There can only be one truth:  main criticism on negative studies was that improper CFS-criteria were used. Thus either this CFS-population is wrongly defined and DOESN’t contain XMRV (with any method), OR it fulfills the criteria of CFS and the XMRV can be detected applying the proper technique. It is so confusing!..
  • Although Mikovits first reported that they found no to little virus variation, they later exclaimed to find a lot of variation.
  • WPI employees behave unprofessional towards colleague-scientists who failed to reproduce their findings.
Other questionable practices 
  • Mikovits also claims that people with autism harbor XMRV. One wonders which disease ISN’t associated with XMRV….
  • Despite the uncertainties about XMRV in CFS-patients, let alone the total LACK of demonstration of a CAUSAL RELATIONSHIP, Mikovits advocates the use of *not harmless* anti-retrovirals by CFS-patients.
  • At this stage of controversy, the WPI-XMRV test is sold as “a reliable diagnostic tool“ by a firm (VIP Dx) with strong ties to WPI. Mikovits even tells patients in a mail: “First of all the current diagnostic testing will define with essentially 100% accuracy! XMRV infected patients”. WTF!? 
  • This test is not endorsed in Belgium, and even Medicare only reimbursed 15% of the PCR-test.
  • The ties of WPI to RedLabs & VIP Dx are not clearly disclosed in the Science Paper. There is only a small Note (added in proof!)  that Lombardi is operations manager of VIP Dx, “in negotiations with the WPI to offer a diagnostic test for XMRV”.
Please see this earlier post [13] for broader coverage. Or read the post [16] of Keith Grimaldi, scientific director of Eurogene, and expert in personal genomics, who I asked to comment on the “diagnostic” tests. In his post he very clearly describes “what is exactly wrong about selling an unregulated clinical test  to a very vulnerable and exploitable group based on 1 paper on a small isolated sample”.

It is really surprising this wasn’t picked up by the media, by the government or by the scientific community. Will the new findings have any consequences for the XMRV-diagnostic tests? I fear WPI will get away with it for the time being. I agree with Lipkin, who coordinates the NIH-sponsored multi-center CFS-XMRV study that calls to retract the paper are premature at this point . Furthermore, –as addressed by WSJ [17]– if the Science paper is retracted, because XMRV findings are called into question, what about the papers also reporting a  link of XMRV-(like) viruses and CFS or prostate cancer?

WSJ reports, that Schekman, the editor-in chief of PNAS, has no direct plans to retract the paper of Alter et al reporting XMRV-like viruses in CFS [discussed in 18]. Schekman considers it “an unusual situation to retract a paper even if the original findings in a paper don’t hold up: it’s part of the scientific process for different groups to publish findings, for other groups to try to replicate them, and for researchers to debate conflicting results.”

I agree, this is a normal procedure, once the paper is accepted and published. Fraud is a reason to retract a paper, doubt is not.

Notes

*samples, NOT patients, as I saw a patient erroneous interpretation: “if it is contamination in te lab how can I have it as a patient?” (tweet is now deleted). No, according to the contamination -theory” XMRV-contamination is not IN you, but in the processed samples or in the reaction mixtures used.

** The reviewers did ask additional evidence, but not with respect to the PCR-experiments, which are most prone to contamination and false results.

  1. Chronic-Fatigue Paper Is Questioned (online.wsj.com)
  2. Lombardi VC, Ruscetti FW, Das Gupta J, Pfost MA, Hagen KS, Peterson DL, Ruscetti SK, Bagni RK, Petrow-Sadowski C, Gold B, Dean M, Silverman RH, & Mikovits JA (2009). Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. Science (New York, N.Y.), 326 (5952), 585-9 PMID: 19815723
  3. WPI Says No to Retraction / Levy Study Dashes Hopes /NCI Shuts the Door on XMR (phoenixrising.me)
  4. http://wpinstitute.org/news/docs/FinalreplytoScienceWPI.pdf
  5. Alberts B. Editorial Expression of Concern. Science. 2011 May 31.
  6. Science asks authors to retract XMRV-chronic fatigue paper; when they refuse, issue Expression of Concern. 2011/05/31/ (retractionwatch.wordpress.com)
  7. K. Knox, Carrigan D, Simmons G, Teque F, Zhou Y, Hackett Jr J, Qiu X, Luk K, Schochetman G, Knox A, Kogelnik AM & Levy JA. No Evidence of Murine-Like Gammaretroviruses in CFS Patients Previously Identified as XMRV-Infected. Science. 2011 May 31. (10.1126/science.1204963).
  8. XMRV and chronic fatigue syndrome: So long, and thanks for all the lulz, Part I [erv] (scienceblogs.com)
  9. Paprotka T, Delviks-Frankenberry KA, Cingoz O, Martinez A, Kung H-J, Tepper CG, Hu W-S , Fivash MJ, Coffin JM, & Pathak VK. Recombinant origin of the retrovirus XMRV. Science. 2011 May 31. (10.1126/science.1205292).
  10. XMRV is a recombinant virus from mice  (Virology Blog : 2011/05/31)
  11. Science asks XMRV authors to retract paper (photoninthedarkness.com : 2011/05/31)
  12. van der Kuyl AC, Berkhout B. XMRV: Not a Mousy Virus. J Formos Med Assoc. 2011 May;110(5):273-4. PDF
  13. Finally a Viral Cause of Chronic Fatigue Syndrome? Or Not? – How Results Can Vary and Depend on Multiple Factor (laikaspoetnik.wordpress.com: 2010/02/15/)
  14. Three Studies Now Refute the Presence of XMRV in Chronic Fatigue Syndrome (CFS) (laikaspoetnik.wordpress.com 2010/04/27)
  15. WPI Announces New, Refined XMRV Culture Test – Available Now Through VIP Dx in Reno (prohealth.com 2010/01/15)
  16. The murky side of physician prescribed LDTs (eurogene.blogspot.com : 2010/09/06)
  17. Given Doubt Cast on CFS-XMRV Link, What About Related Research? (blogs.wsj.com)
  18. Does the NHI/FDA Paper Confirm XMRV in CFS? Well, Ditch the MR and Scratch the X… and… you’ve got MLV. (laikaspoetnik.wordpress.com : 2010/08/30/)

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