The following is a letter to BJSM from Ralph S. Bovard MD:

Dear BJSM,

I have a question regarding the use of autologous platelet rich plasma (PRP) injections for tendinopathies of various sorts.  This procedure has been gaining favor with sports medicine clinicians for use in athletes with tendon injuries that are slow to respond or resistant to conservative therapies.  Despite the fact that it would appear to be a seemingly innocent matter of re-injecting one’s own spun down blood products, the World Anti-Doping Agency (WADA) most recent 2009 Prohibited List, if taken literally, would make it an illegal procedure for international competition or national competition under any NGB’s who endorse WADA.  The culprit substances in this case would be growth hormone (GH), Insulin-like Growth Factors (IGF-1), and Mechano Growth Factors (MGF’s).

The relevant section from the code is included below:

S2. HORMONES AND RELATED SUBSTANCES

The following substances and their releasing factors, are prohibited:
1. Erythropoiesis-Stimulating Agents (e.g. erythropoietin (EPO), darbepoietin (dEPO), hematide);
2. Growth Hormone (GH), Insulin-like Growth Factors (e.g. IGF-1), Mechano Growth Factors (MGFs);
3. Chorionic Gonadotrophin (CG) and Luteinizing Hormone (LH) in males;
4. Insulins;
5. Corticotrophins;
and other substances with similar chemical structure or similar biological effect(s).

[Comment to class S2:
Unless the Athlete can demonstrate that the concentration was due to a physiological or pathological condition, a Sample will be deemed to contain a Prohibited Substance (as listed above) where the concentration of the Prohibited Substance or its metabolites and/or relevant ratios or markers in the Athlete's Sample satisfies positivity criteria established by WADA or otherwise so exceeds the range of values normally found in humans that it is unlikely to be consistent with normal endogenous production.

If a laboratory reports, using a reliable analytical method, that the Prohibited Substance is of exogenous origin, the Sample will be deemed to contain a Prohibited Substance and shall be reported as an Adverse Analytical Finding.] The Prohibited List 2009 20 September 2008

It would thus seem that PRP is banned under “Class S2: Hormones and Related Substances”, rather than under “M1: Blood Doping”.  The re-delivery of blood is prohibited under blood doping; regardless of whether it is endogenous or exogenous.  There is no mention or attempt to discriminate between blood products that are re-injected immediately into soft tissues versus those that are shelved and re-infused by IV weeks or months later in the typical manner of “blood doping”.

The argument is made that while PRP indeed delivers  the athletes own growth factors to a musculoskeletal site, the platelets are concentrated to a level not normally achieved physiologically, and they are activated either chemically (via calcium addition) or mechanically (centrifugation) and thus degranulate  rapidly and deliver a bolus of factors never “normally” or physiologically achieved.

Given this stance it would seem that the use of platelet rich plasma injections is clearly prohibited.   Tendinopathies are not life threatening or otherwise serious medical conditions and as such the rational of applying for a therapeutic use exemption (TUE) would seem a difficult argument.   Yet how would PRP injections be detected other than by admission?  What is the opinion of the BJSM readership regarding this topic?

Thank you,

Raph S. Bovard MD

By John Orchard

One of the worst ever drugs in sport decisions - and there have been some shockers, such as Andrea Raducan losing a gymnastics Gold medal at the Sydney Olympics for taking a Sudafed tablet - was handed down by the International Tennis Federation late last week. Italy’s Filippo Volandri was banned for three months for ‘abuse’ of salbutamol, the drug better known as Ventolin, for treating an asthma attack.

Ventolin puffers are on the WADA (World Anti-Doping Agency) banned list, which in itself is bizarre given that they have not ever been shown to enhance sporting performance. However, there is sensibly an exemption process for asthmatic athletes to apply for which permits them to take salbutamol puffers if a doctor diagnoses asthma. Volandri at the time of this so-called doping incident had registered an exemption for salbutamol use which had been accepted by the International Tennis Federation (ITF) as valid.

The complaint of the ITF was that the recommended dose for Volandri on his exemption form was two puffs and the concentration found in his urine suggested a much higher dose. Volandri admitted that he had taken a much higher dose on the night before his drug test and had a completely reasonably explanation for having done so: he suffered a severe asthma attack in his hotel room and couldn’t breathe properly so continued to take his puffer until the attack subsided. This is more than just completely reasonable – Volandri would have possibly even died if he had not taken a high dose of Ventolin during such a severe attack. He was in a foreign city without recourse to an Italian speaking doctor and sensibly self-medicated to avoid being unable to breathe. The tribunal apparently accepted all of this, but still decided to suspend Volandri for 3 months (and fine him for most of his 2008 prizemoney and ranking points), because the dose he admitted taking was higher than the dose that he was registered to take on his WADA/ITF paperwork. Click to read the ITF’s outrageous press release and entire verdict. The rationale behind this draconian verdict can be seen, but the question is what the ITF/WADA could reasonably have expected Volandri to do in the circumstances (of a severe asthma attack)? Obviously their expectation is that he should not have self-medicated but instead, in Indian Wells USA at 3am have somehow found an Italian-speaking sports physician who was prepared to not only prescribe a higher salbutamol dose but who was also prepared to fax off a revised form to the ITF medical commission. Or perhaps take option B, which in the absence of such a doctor was to risk becoming one of the 5000 annual asthma deaths in the USA. At least in this instance he would have died as a cleanskin, rather than as a drug cheat.

Tennis has a chequered history of having let off 16 players in 2004 for positive drug tests for the anabolic steroid nandrolone. Nandrolone is a strongly performance-enhancing anabolic steroid and the rationale for not suspending the players who tested positive seems to have been that “the doping must have been inadvertent as it involved so many players”. So after having turned a blind eye to so many proven anabolic steroid positives, they are now coming down heavy on asthmatic taking their puffers during asthma attacks.

Other than WADA and the ITF, the international sports journalism community should also be ashamed that it has reported this case as a routine doping decision rather than one of the greatest scandals in tennis history. A young man’s life was saved by his sensible use of his own asthma medication but his career has been destroyed by a totalitarian doping agency. In August 2008, I wrote an article entitled “WADA is on the verge of losing the plot”. It has now officially been lost.

Science and football V: the proceedings of the 5th World Congress on Science and Football.

Edited by Thomas Reilly, Jan Cabri and Duarte Araújo.
Published by Routledge, 2005, pp 634.
ISBN: 978-0-415-48480-0 (paperback); 978-0-415-33337-5 (hardback); 978-0-203-41299-2 (electronic)

Target: Football elite and sub-elite sport science support

Appeal: Broad coverage necessary components sport science. As a sports physician it is not primarily targeted for me and so although it had components of interest, I would not personally purchase

In recent years, sport has by necessity evolved in many facets. Financial rewards have boomed. Information systems have fuelled intense exposure and scrutiny. Doping issues have come under intense publicity and accountability. All this intensifies need for sports to seek ethical advantage with evidence based front line measures.

To fulfill these demands is the immense expectation in sport science seeking that gain an edge in coaching, conditioning and medicine. To achieve this requires sport support services to be reliably informed. This is critical at the elite level to ensure peer parity and at the sub-elite level to provide exposure to elite concepts and portability to sub-elite programs as is practicable.

“Science and Football V: the proceedings of the 5th World Congress on Science and Football” is geared for sports science (conditioning and skill acquisition) rather than primarily sports medicine. It is ideal for coaching staff and strength and conditioning staff. Content is of sound background content for football medical support staff.

Authors are from a wide range of geographic national backgrounds, with strong emphasis on university sport science departments with particular interest in soccer reflecting its international predominance—but representing all codes. Content includes sections on biomechanics, fitness profiling, performance analysis, a small section on medical aspects, football conditioning, physiology and nutrition, paediatric issues and behavioural science.

Topics include coverage of those perennial “footballs”—stretching modes and benefits and relation to injury, warm-up, micronutrient levels and effect of diet and supplementation.

I believe this publication does deliver sound depth and a range of contemporary football sport science for coaching and conditioning support staff, as a summary for those fortunate enough to attend the conference, and as a reference for those particularly involved at the elite level of conditioning for high level teams. For those involved in sub-elite levels it provides an excellent insight into elite performance as a means of extracting ideas into the non-professional level.

Reviewer
P Baquie
Olympic Park Sports Medicine Centre,
Melbourne
Victoria
Australia

Analysis
Presentation 5
Comprehensiveness 5
Readability 5
Relevance 4
Evidence base 4

Martindale’s Drugs Restricted in Sport, Pocket Companion, 2008
Sean C. Sweetman (editor)
Publisher: Pharmaceutical Press, 2008
ISBN 978-0-85369-825-8
416 pages

“Martindale’s Drugs Restricted in Sport” is unique in its kind. It is the first pharmacopia that lists all the drugs that are on the WADA list of prohibited substances, drawing on the wealth of information and clinical expertise in the full reference work: “Martindale, the complete drug refeerence”. This is a great resource for sports medicine physicians, general practitioners and all other health care professionals working with athletes. It contains over 450 monograhs pertaining to individual drug substances that may be restricted in some or all sports, either in or out of competition.

The book is arranged alphabetically by drug substance. The international nonproprietary name or generic name is used, where one exists.

Other synonyms listed include British approved names, the French, Latin, Spanish, and Russian variants of generic names, names used in other European, Baltic, and Scandinavian countries, comon synonyms, and maufacturer codes.

The clinical profile is based on the full text of “Martindale: the complete drug reference” and describes the basis action and uses of the substance.

The WADA status indicates whether the substance is prohobited in or out of competition.

The WADA class gives an indication of the reason for the prohibition and gives more information about the range of substances covered in that class, plus any special circumstances. It is a great asset of the book that this is repeated with every substance, so you don’t need to go somewhere else to read all the information of the particular substances you are interested in. All the information is given right there where you need it.

A comprehensive index of over 15200 entries is to be found at the back of the book, and includes all names, synonyms, and proprietary (trade) names found in he tex. Even Cyrillic names are listed!

This is a great book for those of us who have been in the awkward situation where our athlete phones us, while away on a trip in Norway, Egypt or Russia, have gotten sick and are not sure of the medication the doctor has given him, and can only provide you, let’s say, the Russian trade name. What do you do?

The player is “strictly liable”, but is depending on you. And it is your name who will appear in the court case on internet for many years to go when you make a mistake. And there is no way you will find that Russian trade name on the WADA doping list!

So now there is a solution to all of these problems: Martindale’s Drugs Restricted in Sport Pocket Companion! The only thing missing is a short summary of the categories of the WADA list of prohibited substances and methods – it would be really helpful is that would be included at the front of the book as well.

Babette Pluim,
Sports physician

A recent editorial by Babette Pluim entitled, “A doping sinner is not always a cheat” [excerpt below], has created some fiery discussion amongst BJSM editors and readers this month.

The doping rules these days are really tough. The basic principle is: first offense gets a 2 year ban, second offence a lifetime ban. Everyone seems to agree that doping is cheating, and those who cheat should be sanctioned, so if an athlete provides a positive sample in any sporting situation, the inference must be that they are cheating. Unfortunately, both for the athlete and the anti-doping system, that is not always the case.

Here is a selection of BJSM editors’ & readers’ reactions:

“Drug cheats – or are they?”
By Dr Tim Wood, Chief medical officer for the Australian Open Tennis Championship and a member of Tennis Australia’s Anti-Doping Review Board

With the formation of the World Anti-Doping Agency (WADA) and the universal harmonization in the fight against the drug cheats in the late 90s everyone applauded. What we didn’t realize at the time was how many ’innocent’ victims would be caught up in the new rules and regulations. I therefore applaud Dr Babette Pluim’s BJSM editorial which reviews the positive doping cases recorded by the International Tennis Federation from 2001-07. She found that the majority of so-called ‘positive’ tests are no more than innocent mistakes by players and officials alike. Nevertheless, the trauma suffered and the tainting of these players is irreversible.

Having been involved in professional tennis for the last 7 years, I also experience frustration at the paperwork required to allow player with genuine medical conditions to take legitimate, scientifically proven drugs that certainly do not enhance performance. The most recent ‘crazy redtape’ is the requirement for a full Therapeutic Use Exemption (TUE) to allow an athlete to have intravenous fluid during elective surgery (Babette has some stories about that!).

Fortunately, it would appear that sanity may be about to prevail on at least three fronts. First, abbreviated TUEs (ATUES for those in the know, even though it sounds like a sneeze) that are currently required for intra-articular cortisone injections will be changed to notification via ADAMS (WADA’s web-based anti-doping management system). Second, ATUEs for beta-2 agonists will be valid for four years instead of needing to be renewed annually but this will come with more stringent proof of the player’s asthmatic status. And finally, many of us hope that the intravenous rule will revert to the 2007 ruling ‘… except for genuine medical situations’.

Everyone involved in professional sport strongly supports WADA and their efforts to catch the cheats but the rules shouldn’t catch innocent athletes, particularly those with genuine medical conditions.

“WADA is on the verge of losing the plot”
By John Orchard, Sports Physician

The idea to create the World Anti-Doping Agency (WADA) was a good one, particularly for international sports. It meant that rogue states like the USA, which had a track record of going soft on their own athletes who tested positive, could be forced to implement universal sanctions.

The big problem with WADA is that it is a monopoly. And it is being run increasingly like one, currently under the Presidency of our own ex-politician John Fahey. WADA’s aim should be to stamp out cheating in sport. This is quite difficult to do, as the cheats are usually very clever. WADA instead is trying to maximise scalps of athletes who “test positive for drugs”, without apparent concern for whether they are actually cheating. Instead of concentrating only on the genuinely performance-enhancing (and usually difficult-to-detect) drugs, the WADA banned list is ever-expanding. It now includes commonly used medications which are much easier to detect and “might conceivably” be used for performance-enhancing in rare circumstances. Whether these rare circumstances exist when an athlete tests positive don’t seem faze WADA, as there is a presumption of guilt rather than innocence.

Banned medications now include asthma puffers and cortisone injections, which are generally considered by doctors and scientists to not be performing-enhancing. Intravenous fluids, including those given for an anaesthetic as part of surgery, are now also banned as of 2008. The status quo is now the farcical situation that the vast majority of athletes are breaking the WADA code whenever they go in for elective surgery. In theory, the only thing stopping these athletes from being suspended is that drug testers aren’t (yet) following them into hospitals.

An editorial just published in the British Journal of Sports Medicine found that in the last 5 years of drug testing in tennis, it was accepted that 68% of the players who were banned for positive drug tests were not actually cheating. They were banned presumably because WADA wanted to increase their tally of convictions. They include cases such as known asthmatics taking puffers such as Ventolin for asthma attacks, but whose ‘permits’ to treat their asthma with appropriate medication had either recently expired or been faxed to the wrong number. In 2009, WADA has plans that asthmatics should apply to a panel to ‘prove’ they have asthma, or else they will be banned from sport for using their puffers. The Howard government basically held the funding gun to the head of all Australian sports in 2005 and forced them to sign up to WADA, despite many sports fearing the situation we are now in. This being that the universal drug code has become draconian and the sports have signed away all rights to do anything about it.

“Accidental cheating?”
By Giuseppe Lippi, Associate Professor of Clinical Biochemistry, Università di Verona

In an overview of the 40 most recent cases of doping in tennis, Babette Pluim highlighted that in only 13 of the cases (32%) was a prohibited substance taken to enhance performance, whereas most frequently banned substances were taken with no intent to enhance performance or without (significant) fault or negligence.1

I definitely agree that products that are on the list of prohibited substances should be critically reviewed, but I also emphasize that the current anti-doping policy is essentially a costly, repressive, zero tolerance approach, which seems only partly successful.2 It is also to mention, however, that there may be additional explanations to justify adverse findings on antidoping testing, which have little to do with cheating.

The use of dietary supplements is commonplace in sports, most elite athletes using some form of licit supplementation to burst athletic performance and improve recovery after training or competition. Nevertheless, there is widespread evidence that some of these legitimate products, especially those sold on the “black market”, contain banned substances that are not claimed as a result of poor manufacturing practice or adulteration.

Contaminants mostly include anabolic androgenic steroids, hormones, ephedrine and caffeine.3,4 Indeed, in some cases the adverse findings might be the consequence of deliberate cheating. However, we should still consider the possibility that some positive tests might arise from unintentional consumption of prohibited substances, contaminating dietary supplements. In this respect, not only antidoping agencies should focus on products that are truly harmful and performance-enhancing, but they should also issue a clear regulation on the use of nutritional supplements and establish appropriate bans for inadvertent use of banned molecules. Doping is always to blame, especially when the athletes use illicit methodsor substances that might produce a serious risk for their health. However, as different sanctions are imposed when crimes are intentional or preterintentional, bans should also be clearly differentiated from deliberate and unintentional positivity to banned substances.

References

1. Pluim B. A doping sinner is not always a cheat. Br J Sports Med 2008;42:549-50.

2. Kayser B, Smith AC. Globalisation of anti-doping: the reverse side of the medal. BMJ 2008 Jul 4;337:a584. doi: 10.1136/bmj.a584.

3. Maughan RJ. Contamination of dietary supplements and positive drug tests in sport. J Sports Sci 2005;23:883-9.

4. Linksvan der Merwe PJ, Grobbelaar E. Unintentional doping through the use of contaminated nutritional supplements. S Afr Med J 2005;95:510- 1.