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  1. Cases Journal should follow Venning's quarter-century old example

    Iain Chalmers, James Lind Library

    21 May 2008

    I am sure that I am not the only person to be delighted by the return of the prodigal Richard Smith to medical editing, and by his obvious commitment to this new publishing venture. Case reports can indeed lead to improved care of patients; but it is important to remember that they can also be lethal (1). For over twenty years I have been drawing attention - most recently through The James Lind Library ( - to Geoffrey Venning's pioneering cohort study done to assess the extent to which interpretation of case reports had been validated subsequently by more carefully controlled research (2). Indeed, I have noted that Venning actually underestimated the value of case reports in detecting adverse effects of drugs. However, as Richard Smith quotes Enkin and Jadad with approval for suggesting that randomized trials should be "taken off their pedestal", I thought that it might be worth reproducing a passage (1) about case reports published in a book co-authored by Murray Enkin 20 years ago (3).

    In 1952, Austin Bradford Hill - the medical statistician who play such an important part in introducing the randomized controlled trial to medical research –'In my indictment of the statistician, I would argue that he may tend to be a trifle too scornful of the clinical judgments, the clinical impression. Such judgments are, I believe, in essence, statistical;. The clinician is attempting to make a comparison between the situation that faces him at the moment and a mentally recorded but otherwise untabulated past experience' (4). Twenty years later, Sam Shuster - a clinician - warned that these impressions can be seriously misleading: 'There are lies, damned lies, and clinical impressions' (5). Both Bradford Hill and Shuster are right, of course: informal evaluation of care based on impressions, and formal evaluation based on well-controlled comparisons of alternative forms of care, both play essential roles in the promotion of more effective care during pregnancy and childbirth.

    Two anecdotes may help to illustrate the strengths and dangers of impressions about the effects of care based on case reports. During the 1960s, an obstetrician interested in the physiology of parturition had the impression that lambs whose mothers had been given corticosteroids to initiate labour showed signs of respiratory distress less often than might have been expected. Further observations made in the context of controlled experiments in sheep confirmed that lambs born after maternally-administered corticosteroids were indeed less likely than control lambs to develop respiratory distress. Together with a paediatric colleague, the obstetrician went on to conduct further well-controlled investigations in humans, and demonstrated that ante¬natal administration of corticosteroids prior to preterm delivery resulted in an important reduction of neonatal morbidity. Because of the possibility that there might be long term adverse consequences of fetal exposure to corticosteroids, long term follow-up of the steroid-exposed and control babies was conducted; so far no adverse effects have been detected.

    The second anecdote refers to another obstetrician who, in the early 1950s, encountered a number of research reports from prestigious institutions in the United States in which the clinical investigators had concluded that diethylstilboestrol (DES) was an effective drug for the 'support of placental function'. Consulted by a woman who had had two previous stillbirths, the obstetrician prescribed the drug from early pregnancy onwards. The pregnancy ended with the birth of a liveborn child, as did a subsequent pregnancy similarly managed. Reasoning that the woman's 'natural' capacity for successful childbearing may have improved over this time, the obstetrician withheld medication during the woman's fifth pregnancy: the baby died in utero from 'placental insufficiency'. During her sixth and final pregnancy, the obstetrician and the woman were in no doubt that prescription of diethylstilboestrol should be resumed: the pregnancy ended with the birth of another liveborn child. The impression gained of the apparent effects of diethylstilboestrol (three livebirths following treatment with diethylstilboestrol, and three intrauterine deaths when the drug had not been used) led both the obstetrician and the woman to infer that it was a useful drug.

    As these two anecdotes illustrate, impressions about the effects of care are sometimes right, and sometimes wrong. In the first, an informal impression initiated a series of well-designed investigations and a discovery which must rate as one of the most important ever made in obstetrics. In the second case the impression left on the obstetrician and the mother was never substantiated in the properly controlled studies that were being conducted and reported during the years over which the woman was receiving care. Tragically, this evidence was widely ignored, for not only was diethylstilboestrol ineffective, it was actually harmful. The drug caused a variety of abnormalities, including cancer, in many of the children of the millions of women who had taken it during pregnancy (1).

    Validated case reports can lead to improvements in the care of patients; invalid case reports can kill them. I wish the new Cases Journal well; but if it does indeed wish to support the counter-reformation called for by Enkin and Jadad, I hope it will follow the methodological lead set by Geoffrey Venning quarter of a century ago (2). The journal should establish a prospective cohort study now to assess the extent to which its case reports about purported treatment effects lead to reliable evidence about ways of improving the care of patients.


    1. Chalmers I. Evaluating the effects of care during pregnancy and childbirth. In: Chalmers I, Enkin M, Keirse MJNC, eds. Effective care in pregnancy and childbirth. Oxford: Oxford University Press, 1989:3-38.

    2. Venning GR. The validity of anecdotal reports of suspected adverse drug reactions – the problem of false alarms. BMJ 1982;284:249-252.

    3. Jadad AR, Enkin MW: Randomized controlled trials: questions, answers and musings. Oxford: Blackwell Publishing; 2007.

    4. Chalmers I, Enkin M, Keirse MJNC, eds. Effective care in pregnancy and childbirth. Oxford: Oxford University Press, 1989.

    5. Hill AB. The clinical trial. New England Journal of Medicine 1952;247:113-119.

    6. Shuster S. Primary cutaneous virilism or idiopathic hirsutes? BMJ 1972;2:285-286.

    Competing interests

    None declared

  2. The tyranny of the hierarchy of evidence

    George Thomas, St. Isabel's Hospital, Chennai, India

    23 May 2008

    For a doctor practicing medicine in a country of vast disparities like India, the hierarchy of evidence is often a source of discomfort. For one thing, the evidence is mainly from the Caucasian West, because they are the only ones with the money to mount expensive randomised trials. For another, there may be plenty of evidence on the lifestyle diseases now common in the West, but very little on the many horrible pathogens still common in the hot zones of the world. But worse than all this, is the situation where your patient fits the evidence, but your resources do not. Take for example, a poor patient aged 50 with rheumatoid arthritis of the hip affecting both joint surfaces. The patient is in severe pain. The best option is a replacement where both the acetabular surface and the femoral surface are replaced. But this costs ten times what a replacement of the femoral head alone will. The patient, who has to pay for the surgery cannot afford it. The surgeon who does the hemireplacement with the knowledge that it will give some relief of pain but will last perhaps only for five years, has to contend with his conscience, because he has not followed the evidence. He also has to contend with the ridicule of his peers. The so-called best can often be the enemy of the good.

    Competing interests


  3. It is a very important journal

    Alaa Abd-Elsayed, Faculty of Medicine, Egypt.

    2 June 2008

    launching Cases Journal is a very smart idea, it will help in buidling a very good evidence based medicine data base. Physicians from all over the world need to learn about all cases not only the unique ones. Cases Journal will provide help to all physicians to manage their cases and to share their experiences.

    Competing interests


  4. On support of the value of Case Journal and Case Report

    Ahmed Ghanem, The Queen Elizabeth Hospital, Gayton Road, KIngs Lynn PE30 4ET

    2 June 2008

    Dr Richard Smith

    Editor-in Chief

    Cases Journal

    May 26th. 2008.


    Re: Why do we need Cases Journal?

    Congratulation, commendation and thank you for starting this Cases Journal at BMC.

    Congratulation because Cases Journal has Gold shine success from day one.

    Commendation is deserved as this simple yet ingenious idea of Cases Journal is of admirable and enviable bravery. It signifies a seriously important message that intelligence capable of contribution to the advancement of medicine and science exists outside research centres of excellence!

    Commendation again because with your expertise, capability and history as one of the most successful, influential and exciting medical editor in the field, starting Cases Journal is hugely significant and important too. Endorsing case reports as a source of EBM at the age of worshiping RCT is a revolutionary concept with great gain to medical community. This is not only because you were a keen supporter of RCT but also because case reports has regained a deserved right of importance as another source for EBM that has long been ignored, denied, undervalued and/or discredited.


    Thank you because you seem to have heard my prayers! You must have read some of my letters that I nagged you with in writing and as Rapid Responses (RR) during your previous life as Editor of BMJ! It all remain there at the RR section- just search by author's name and you find some eye opening and thought provoking ideas- if a reader does not find it educational and entertaining- money back guaranteed!)! Or, have been peeking into my Computer hard disc and reading some of the letters, case reports/series, observational studies and essays that I have written over the last quarter of a century awaiting literature asylum. Some were published, most were rejected and many may come your way as Editor of the new Cases Journal.

    Thank you again for making me feel so "excited, young, fool and hungry" again! It feels magic as if falling in love all over again (with medical sciences and literature that is!). This is perhaps my way of phrasing what you reported as Cacteau's quote: "Take a commonplace, clean it and polish it, light it so that it produces the same effect of youth and freshness and originality and spontaneity as it did originally, and you have done a poet's job. The rest is literature". In many ways this is what you did by re-inventing Cases Journal!

    This also precisely describes my collection of case reports. They may seem ordinary usual cases being seen daily by thousands of doctor but few would give them a second look or thought and non can see through them with the amazement and curiosity I feel or with the clarity that surpasses their description in a textbook! However, being as old as I am now, and hopefully a bit wiser, I might avoid some of the foolish mistakes I did before!

    You explained well why do we need Cases Journal". I admire the brilliance of reinventing a simple idea whose only silliness is why has it took you so long?

    I am delighted with your return as Editor-in-Chief of this new Cases Journal. You have been truly missed when you left the editorial arena. Welcome back. There is one other great editor I badly miss but I am not mentioning names here!

    Conflict of Interest?

    Reading both of your editorials and case report at "Cases Journal", has indeed rejuvenated an old wonderful feelings of delight and satisfaction. I experienced that feeling when BMJ published my first pieces at the correspondence section in 1985 & 7 [1,2]. This is when I became engaged and married to my greatest love of scientific medical research and writing. It has since become permanent incurable addiction that no pain, sleepless nights, frustration, depression, battering of repeated of rejection, endured over a life sentence, could cure me of it. However, it is the best thing that has ever happened to me in my whole life and I am grateful to the Editor of BMJ for it!

    The Lancet Editor is equally great as he was also kind to publish couple of letters in 1985-8 [3-5], so did the editor of British Journal of Urology reported a first letter in 1988 [6]. It all tasted so sweet I just couldn't give it up.

    I acted like a deprived child who was allowed a shopping spree in a sweet or toy shop! I wanted more and always returned for a fix at whatever cost and taxes it took from me! My list of precious little publications grew bigger and taller while the list of journals grew broader and wider. I do not wish to make it sound like personal advertising or recitation of my CV here. This not a conflict of interest either as the point I am making here is that I found myself best expressed in letters that may contain one or more Case Reports. Whenever I got a chance to do proper research of RCT or observational study, I did and reported- or tried to.

    The first letter [1] reported at BMJ in 1985 was brainstorming on a new hypothesis on the transurethral resection syndrome (TURS) that lead to some serious research and results on related physics, physiology and medicine. Full research articles of unique quality and original contents were reported later in 1991 [7] and 2001 [8]. As this arena became closed shut in my face, I changed the subjects in 2002 [9,10].

    The second letter [2] reported at BMJ in 1987, in fact, contained two case reports as anecdotal evidence on the life-saving effectiveness of 5% Hypertonic Sodium Chloride (5%NaCl) in treating acute hyponatraemia and the TURS patients. This was at an era when such therapy was contra-indicated! I had affirmed the effectiveness of 5%NaCl in my first research article reported in 1991 [7]- rejuvenating the therapy from its original introduction into clinical practice for treating the TURS by Harrison et al [11] as based on earlier animal research reported in series of articles by Danowski TS, Winkler AW, Elkington JR [11]. The therapy of 5%NaCl was later restored and approved by the authorities in 1993 as the treatment of choice of acute hyponatraemia.

    The remaining of some 15+ TURS case series stayed dormant in my MD Thesis book [13] after an article was rejected by some journals while the prospective RCT study was reported [7] . The research was done at the DGH Eastbourne, UK and Thesis presented at The Institute of Urology, Mansoura Egypt in 1988 [13]. I gave The article on Cases Series on the TURS a musical name of "Hypo-osmotic Shock", also used as a chapter heading in my MD Thesis ( I would still use it today on merits!). The pain and drag of repeated rejections of case reports and observational studies had put me off re-submission and caused withdrawal lasting at times a couple of dormancy years. I tried to nurse it as some form of "writer's retreat" and waited patiently for the right opportunity in order to re-bounce back!

    Having said that, I can't help expressing a sense of shame here talking about my personal pains due to obstruction of publication when compared to that of the fellow who- I think- said the Earth is not flat: Isn't he the one the crowd throw alive into boiling oil? Thank God, and I am grateful, for being in an Era and Land of Her Majesty that values diversity, tolerance and freedom where nobody gets fried or tortured for expressing an opinion or trying to advance science or medicine!

    The pain and frustration that I have never really been able to adapt to was not the personal one of being rejected but that caused by persistent obstruction preventing the publication of knowledge that could have saved thousands of patients much pain and misery, and might also have saved millions of lives the World over! Meantime the dormant documents seem to mature like wine over the years! Those years have just affirmed and strengthened my believe that my observations have proved dead accurate and my hypotheses are precisely correct!

    The TURS vanishing or reincarnating "Back to the Future"?

    The TURS is currently vanishing from urology for various reasons, but please do not hold its burial service yet! It will resurrect itself "Back to the Future" perhaps with a new name and features. Not only in the future but it is here yesterday and today and tomorrow! It remains to affect patients in many medical and surgical specialties. The incidence and prevalence of morbidity and mortality of acute hyponatraemia in current hospital practice as evidenced by many recent reports is overwhelming and astonishing! Has the lesson of the TURS been learned, its cause been understood and the effective life-saving therapy of 5%NaCl been correctly used?

    No. No. No..

    More important than the TURS, is demonstrating its link with the adult respiratory distress syndrome (ARDS) that was later renamed as the multiple vital organ failure (MVOF) syndrome, and renamed again as the systemic inflammatory response syndrome (SIRS). Has the importance of such link been realized? Can RCT provide answers on any of these conditions under currently received wisdom and knowledge?

    No and not in a million, respectively!

    The answers are in fact available today, at least in part, and it has been in print since 1991 and 2001 when I reported an impeccable prospective study at The British Journal of Urology [7] and another unique work at the Medical Hypothesis [8]- thanks to another two great late Editors. (I do not mention names because some guy wrote somewhere that authors can't use names without "consent for acknowledgement"- please see comments on "The policies of Cases Journal").

    Being overlooked, not really understood or deliberately ignored by peers of the scientific and medical community is hard to tell. Hence, I have long come to realize- like you have- that describing the cases as I saw them and reporting it perhaps as series, or with some luck as observation study may help others to see what I could clearly and unmistakably recognize over the years! I never really had much luck with research articles and observational studies since 1991 (Save those mentioned [6-10]-thanks only to the bravery and caliber of these journal' Editors) so I continued with case reports and communication letters. Then when you invented the RR section of BMJ, I showered it with series of articles. Is Cases Journal the one I have been waiting for?

    Only case reports and observational studies can provide understanding and solutions to current most complex medical problems of patients with multiple co-morbidities such the MVOF syndrome where thousands of expensive RCT have failed to deliver. This is particularly so when reported at Cases Journal supported by an editor of your caliber! For the same reason I can predict that your Cases Journal shall prove be a phenomenal success! The role of RCT and statistics as well as team work comes later to affirm or refute the evidence or hypothesis outlined in case reports or series or an essay article on new hypothesis- so far a challenging closed door for me. Please also note that observational studies like case reports have been discredited until recently, again because of the trendy era of worshiping RCT and Statistics!.

    As I stated before in some of my RR letters at the BMJ: "RCT cannot investigate an unknown condition or hypothesis and certainly cannot make a discovery neither in science nor in medicine". Case reports and observational studies can and will!". Observation and mental experimentation are the most potent tools for discovery and invention, and their practitioners have accurate visions that can tell if an experiment, study or test may succeed or not- even before it is done in a laboratory or in a clinical trial! In other words, one cannot find something unless he knows exactly what is he looking for: observation spots at first sight while mental experiments analyze it, extract its value and importance, and conjure experiments that are safe and ethical needed to prove it. A lone researcher or team should deliver results in 25 or 1-2 years, respectively!

    Digging Deep!

    Hence, in fact, thanks to an energy boost induced by your announcement of Cases Journal I did some considerable digging today in order to excavate some of the buried case reports and articles from a mass Graveyard on my Hard Disc Drive! The most recent case report was written over 6 years ago and some go as far back as 15 or 20 years. They require nothing more than little "clean and polish" putting it in the format of Cases Journal, and I have already downloaded the template. Then there you have it "clean and polished"! for Cases Journal to "light it so that it produces the same effect of youth and freshness and originality and spontaneity as it did originally, and you have done a poet's job. The rest is literature".

    Many of it were rejected by your previous and other journals in the field when the whole medical community was blinded by the illusion that EBM can only come from RCT!. Some thoughts were later reported as correspondence and many as RR at BMJ- hopefully your colleagues and students there may realize their mistake and bring it back from that cyber graveyard into a proper section of their journal- just wishful thinking!? I am not really sure where does it stand and whether reporting it again elsewhere may be considered "Duplicate Publication"? However, your quality as editor with pioneering vision, originality and bravery is rare and may be hard even to imitate. Major articles on studies remain unreported. But, no experience is wasted and no knowledge is forgotten.

    In fact, as you mentioned and demonstrated above, every study of both observational and prospective types that I had done during my career life had always started with one case that became a series that became study worthy of reporting its results. Such full studies may just have to wait for your next true Science 2.0 journal. Cases Journal is currently version 1.2 in my estimation- explanation shall follow. I just can't face sending mine again to rejecting journals and I do not care what Impact Factor they might have. Your Case Journal currently have Zero Impact Factor as a new journal but watch its steep curve- you may have to raise your chin to the level of your eye brows to see where it is going!

    Science 2.0 and Medicine 1.2 judged by Art 1.0

    A true Science 2.0 journal in medicine such as an imaginary journal "Observational Studies Journal" and/or "The Free Scientific Medical Author Journal" of true Net 2.0) need total liberation from all the old restrictive rules of RCT, complete disinfection from its the bugs, viruses and Trojans - without discarding or discrediting the importance of Science and Medicine 1.0, and a new role of the editorial team their journal's policies! The editorial team and peer reviewers will remain most important with a challenging and exciting new task but need to evolve and adapt. They may perhaps continue to use the same old tools1.0 used for judging art, poetry and literature. The journal will have a style too but the author should remain free of all restrictions. Such new virtual " Intellectual Products Journal" like a supermarket should have a system and rules with organization tools. Such true 2.0 may attract the best fresh produce of "grey matter juice" of varied most delicious flavours from all over the World!

    Your Story, My Story!

    Now back to your exciting new Cases Journal, and why am I so excited about it too? You put it in a punch word: "Story". A story that will not only cure a state of boredom by providing quality entertainment but will also prove educational and useful! Tell me a good story that grabs my attention, delight and entertain, even if you stole it from the One Thousands and One Arabian Nights Book, and do not you worry about your message being received or lesson being learnt- trust me it always does"

    You made me laugh when I read your statement: "Perhaps some of our contributors will attempt to write case histories like those of Sigmund Freud." And again: "if somebody can produce a report that has both the length and nuance of a Dostoevsky novel or a Freud case report then the world will be a richer place." I wondered if you were careful enough when you made such wish- and what will you do if it comes true? The reason was that just shifting through some titles as I searched my hard disk made me realize that you may regret saying that- if I decided to send you every case report I have and article I wrote! This document is a sample written specially and freshly for you! On second thought I have divided it, the one you are reading and more will posted later.

    As I laughed, an old true story that happened back in 1977 came to mind that I think is relevant and with which I reciprocate. After passing the PLAB test and before finishing a month of clinical attachment in Northampton, I was desperate to find my first job due to cash running short fast. I asked the consultant if there was a job for me, he said no. I asked how can I find one and would he give me a reference? He said the back section of BMJ is full of it and he would be happy to. I sat down the whole next weekend and systematically wrote application letters to every advertisement of SHO jobs at the latest couple of issues of BMJ (Not realizing some were repeated), and posted it on a Monday morning! While at it I had my first look at the front section and thought someday I should be a contributor!

    Before the end of that week, I was summoned by the consultant at his office in private. The furious look at his face triggered thoughts: "Oh my God! I must have done something drastically wrong. I couldn't have killed a patient while acting in an observant capacity- could I!?. I do not know what is it but I know I have done nothing wrong". As a matter of fact I didn't, or rather couldn't, say much at that meeting. The gentleman explained the problem as he must have diagnosed my condition of "no condition to talk", he did all the talking and reassurance as he was making coffee.

    I could not take mine but only nodded thanks so he put it on a side table. He at last smiled as he talked: "I have received over 200 requests for references from hospitals all over the country! How many interviews have you been called for and where do want to work? I answered briefly in a barely heard voice: "Only 8 and I want to work in UK!". He burst into laughter while I watched in bewilderment being clueless why was he laughing! (To be continued if life continues!).

    Yours Faithfully

    Ahmed Ghanem, MBChB, MD (Urology), FRCS

    The Urology Department,

    The Queen Elizabeth Hospital,

    Gayton Road, Kings Lynn, Norfolk PE30 4ET

    (Future Address from mid June will be provided as soon as confirmed)

    an_ghanem@hotmail.comEmail :

    Mobile: 07772977348


    1. Ghanem AN. Hypoalbuminaemic hyponatraemia: a new syndrome. Br Med. Jour. 1985; 291: 1502

    2. Ghanem AN. Wojtulewski JA, Penney MD. Dangers in treating hyponatraemia. Br Med J. 1987; 294: 837.

    3. Ghanem AN, Powley JM. Hepatic outflow obstruction. Lancet 1985; ii: 675.

    4. Ghanem AN. Serum Osmolality Gap. Lancet 1987; ii: 223-4.

    5. Ghanem AN. Hyponatraemia and hypo-osmolality. Lancet 1988; ii: 572.

    6. Ghanem AN, Ward JP. Fluid absorption during urological surgery. Br J Uro, 1988; 61: 168-9.

    7. Ghanem AN, Ward JP. Osmotic and metabolic sequelae of volumetric overload in relation to the TURP syndrome. Br J Uro 1990; 66: 71-78 (Award Winner of Princess Alice Memorial Award, UK 1988).

    8. Ghanem AN. Magnetic field-like fluid circulation of a porous orifice tube and relevance to the capillary-interstitial fluid circulation: Preliminary report. Medical Hypotheses 2001 Mar; 56 (3): 325-334.

    9. Ghanem AN. Experience with cystoprostadenectomy with “prostatic capsule sparing” for orthotopaeic bladder replacement: overcoming the problems of impotence, incontinence and difficult urethral anastomosis. BJU Int. October 2002; 90(6): 617-620

    10. Ghanem AN. Leading Article. Features and Complications of Nephroptosis Causing the Loin Pain and Haematuria Syndrome: Preliminary Report. Saudi Med. J. 2002 Feb;23(2): 447-455

    11. Harrison III RH, Boren JS, Robinson JR. Dilutional hyponatraemic shock: another concept of the transurethral prostatic reaction. J Uro. 1956; 75 (1): 95-110.

    12. Danowski TS, Winkler AW, Elkington JR. The treatment of shock due to salt depression; comparison of isotonic, of hypertonic saline and of isotonic glucose solutions. J. Clin. Invest. 1946; 25: 130.

    13. Ghanem AN. The Transurethral Prostatectomy (TURP) Syndrome: An Investigation of the Osmotic and Metabolic sequelae of Volumetric Overload (VO). MD Thesis. Institute of Urology & Nephrology, Mansoura University, Egypt. November 6, 1988.

    Competing interests

    Competing intersts: None other than declared in the text.