Talk:Adverse effects of fluoroquinolones/Archive 2

Psychosis
I just read this article again. It says fluoroquinolones cause psychosis. So if a person has a family member that is "crazy", they may easily conclude that the medicine caused it.

This article needs to put things in perspective. Hundreds of thousands of people take it without becoming psychotic. Try to write that and you could be accused of original research. Leave it out and we don't have an accurate article.

This is one of the reasons why this type of article may be unencyclopedic. It's a difficult question because some editors clearly want to write about it. I think if this article is kept, it needs a major rewrite, also explaining what is adverse effects are in the big picture. It also needs renaming as toxicity is when you overdose or get poisoned.Chergles (talk) 16:07, 16 February 2009 (UTC)

major error discovered
I just looked up online the package insert (USA) of a fluoroquinolone and psychosis is NOT listed. So the Wikipedia article is wrong. Chergles (talk) 16:12, 16 February 2009 (UTC)


 * Copied from above - Package inserts are not useful sources. They simply list every single reaction encountered during phase II and phase III testing. If someone caught a cold while in a trial, this will be listed. Rather, this information needs to be sourced to peer-reviewed secondary sources. JFW | T@lk 07:28, 16 February 2009 (UTC)
 * So psychosis was never found even if the listing err on the side on listing more things. Chergles (talk) 16:14, 16 February 2009 (UTC)

Both the prescribing info for Levaquin and Cipro list psychosis, as well as the articles below... Page 10 of the prescribing information for Cipro from the Bayer website says under Central Nervous System Disorders: ...toxic psychosis have been reported in patients receiving fluoroquinolones, including ciprofloxacin... and rarely, suicidal thoughts or acts.

Section 6.3 Table 8 Postmarketing Reports of Adverse Reactions from the Levaquin prescribing information also lists psychosis and isolated reports of suicide attempts and suicide ideation.

Mulhall JP, Bergmann LS (July 1995). "Ciprofloxacin-induced acute psychosis". Urology 46 (1): 102–3. doi:10.1016/S0090-4295(99)80171-X. . http://linkinghub.elsevier.com/retrieve/pii/S0090-4295(99)80171-X.

Reeves RR (1992). "Ciprofloxacin-induced psychosis". Ann Pharmacother 26 (7-8): 930–1. . Respectfully submitted Dbcipro (talk) 18:29, 16 February 2009 (UTC)

I looked up the package insert for Vigamox online. The insert says it is a fluroquinolone. The insert (see http://ecatalog.alcon.com/pi/Vigamox_us_en.pdf ) does not say psychosis. Therefore, we have an error in Wikipedia. Anyone dispute this? Chergles (talk) 20:06, 16 February 2009 (UTC)

Vigamox looks like Moxifloxacin eye drops to me. Doesn't seem to me like eye drops would pass through as many bodily systems or pass the blood brain barrier as an ingested or IV drug could. Bayer's formulation of Moxifloxacin (Avelox) lists hallucinations, confusion, and rarely, suicidal thoughts, that could occur after only one dose. Dbcipro (talk) 20:40, 16 February 2009 (UTC)


 * So by not distinguishing Vigamox, the reader may have false negative opinion of Vigamox. So if Vigamox were a person, that would be a potential BLP violation.  So let's be careful and write the article well. Chergles (talk) 21:37, 16 February 2009 (UTC)

Errr what? Why are we comparing an eye drop solution to Living persons policy? We have enough issues on this page raised. I think that we should forget about what happens if a simple minded person can't figure out an eye drop solution is not the same as an oral systemic therapy, at least for now. After the other issues have been resolved maybe then we can return to an "eye drop" versus "systemic therapy" adverse effects debate.-- Literature geek |  T@1k?  22:04, 16 February 2009 (UTC)

Regarding psychosis you said that "what happens if" a person reads psychosis as a side effect and then thinks, maybe my psychosis was caused by an antibiotic years ago when in their individual case it was not. This is an encyclopedia, which reports the facts. We can't just delete facts "just incase" someone wrongly attributes something as causing their psychosis. We could go and delete psychosis from all sorts of prescription drugs as a side effect, from illicit drugs. We could actually completely delete korsacoffs syndrome. Heck lets just delete the entire wikipedia database or even the entire internet and television, media, newspaper, ban them all just incase someone misattributes factual information to themselves wrongly. I had someone make a similar argument on another article about content that it might "frighten the elderly" and therefore needs deleting. I know I sound rude and that is not my intention but I am trying to make you realise what wikipedia is about and not about.-- Literature geek |  T@1k?  22:16, 16 February 2009 (UTC)

Renaming article
See the section immediately above. Toxicity is when you eat a crate full of the medicine. This article is not about the LD50. It is about not so common side effects. So the article name may imply bias. This is clearly a hot topic. I hope it's possible to reach a conclusion through polite discussion. Chergles (talk) 16:17, 16 February 2009 (UTC)
 * I totally agree. Toxicity is when you overdose. The current article discusses side effects with a negative bias. I propose to move to Side effects of fluoroquinolones. --Steven Fruitsmaak (Reply) 19:30, 16 February 2009 (UTC)

I respectfully disagree for the following reason: Toxicity is not limited to overdosing as you have implied. Peanuts are toxic to those who have an allergy to them. One peanut is not considered to be an overdose, but it is toxic to such a person. Toxic is defined as "containing or being poisonous material especially when capable of causing death or serious debilitation". And the article is about the fact that the fluoroquinolone class has been documented, since 1962, to contain a poisonous substance(s) or metabolites that are capable of causing death and serious debilitation with as little as ONE dose. It has little to do with how much of the drug you consume, though this is a factor, it is not the sole reason for the toxicity of this class. It has everything to do with the damage done as a result of such consumption. Toxicity is the degree to which a substance is able to damage an exposed organism. How then are you continuing to argue that describing such a toxicity is discussing side effects (which is not even a part of the article to begin with, as the article discusses adverse reactions) with a negative bias? Is there a positive way to discuss adverse reactions? Are they somehow beneficial to the patient? If so please explain how you believe this to be so.

I too do not wish to be argumentative but you are continuing to argue a frivolous position. How does one present an article that deals with the negative side of an issue in a postive light? Somehow doing so negates the whole purpose of the article to begin with. For example how does one do an article on the holocaust in a positive light and make Hitler out to be the good guy? Which comparatively speaking you feel should be done with this article if I understand you correctly here. How specificaly do you feel we have presented the facts in such a manner that a negative bias is present? Let us work on correcting that rather than dealing with your own bias opinions regarding the safety profile of this class. I have freely admitted to my own bias when I first started working on the article and have asked folks to point them out to me with suggestions for correcting them. So to correct this problem cite to the specific sentence(s) that needs to be worked on, rather than speaking in generalizations, or condemning the whole article and perhaps we can resolve this impass like gentlemen. But it appears that someone had already changed the name and relocated the page before a concensus had been reached, so perhaps I am arguing in vain here to keep the name as is.Davidtfull (talk) 01:31, 17 February 2009 (UTC)

I hate to be argumentative, but toxicity actually refers to death,,, or damage usually long lasting. See definition in online medical dictionary. Quinolones meet all 3 definitions listed in the medical encyclopedia. Toxicity is an accurate terminology for what the article is talking about. However, renaming the article to side effects of fluoroquinolones or fluoroquinolone adverse reactions, may actually serve the purpose of giving the web page more exposure in search engines since most people will be more likely to type in side effects than toxicity. For search engine optomisation a name change might have benefits in greatly increasing the volume of readers but the term toxicity I still feel is the most accurate. I can be swayed on a name change (for search engine purposes) but am on the fence at the moment.-- Literature geek |  T@1k?  19:49, 16 February 2009 (UTC)


 * We shouldn't be caring less about search engines, certainly while this article is under dispute. If you are supporting for that reason, please oppose. --Steven Fruitsmaak (Reply) 19:57, 16 February 2009 (UTC)

I believe in discussion and compromise. Here's an idea, not necessarily the one I favor, just one that I thought of. We keep the name of the article. We discuss toxicity. We also have a section on side effects (which would cover the bulk of the article). Chergles (talk) 20:02, 16 February 2009 (UTC)

I believe toxicity is an appropriate term for this article. Quinolones have been shown to be neurotoxic, chrondotoxic, cardiotoxic, and hepatoxic, even at minimal doses. All these adverse reactions are the result of direct chemical harm to living organisms. JamesLockson (talk) 12:58, 17 February 2009 (UTC)


 * Goldfrank's toxicology refers to what we are talking about as adverse events. Goldfrank's is basically the final word in the field.  Therefore changed the name to reflect this.-- Doc James  (talk · contribs · email) 09:57, 19 February 2009 (UTC)

rewrite
I am better at reaching consensus through discussion rather than re-writing a controversial article so even though I've made 1-2 edits, I'll not do too many.

How about the following general framework.

1. Intro to the class of drugs, name the drugs.

2. Discussion of risk and benefits. (Going to the cinema runs a risk of car theft and robbery, it is not 100% safe).

3. Discussion of toxicity, what kills rats.

4. Discussion of common side effects, how they vary with each drug.

5. Discussion of less common side effects. Otherwise we run a risk of listing gobs of horrible and rare conditions.

6. Discussion of history of regulatory changes (that Dear Doctor section).

How's that for a start. By doing so, it would be a major revamp of the article. Let's work peacefully and slowly since there is controversy. Chergles (talk) 20:19, 16 February 2009 (UTC)
 * I'm having enough on my plate so I won't be able to help here any time soon, but for good examples of toxicity articles on the wiki see paracetamol toxicity or serotonin syndrome. Granted this one appears more complex. Xasodfuih (talk) 00:59, 17 February 2009 (UTC)

I'm confused as to why you would think that the article should be a carbon copy of the package insert, (which follows the exact pattern that you are suggesting). The article is about a specific syndrome that is induced by a specific class of drugs. Toxic is defined as "containing or being poisonous material especially when capable of causing death or serious debilitation". And the article is about the fact that the fluoroquinolone class has been documented, since 1962, to contain a poisonous substance(s) or metabolites that are capable of causing death and serious debilitation with as little as ONE dose. The article first explains what drugs we are talking about. It then describes the various events that are associated with this syndrome in a linear fashion. And we took it even one step further, and attempted to describe the mechanisms of action by which this takes place, if they were known. In this regard the article is factual. There is no reason for controversy concerning that aspect.

The only argument and controversy should be the manner in which the evidence is to be presented so that it remains neutral and unbias, not whether or not that the proven facts are somehow in error. With well over a couple of hundred citations sheparded from a database of well over 4000 we have pretty much provided a citation that supports every statement made. No doubt that a few statements can and should be reworded to comply with neutral/bias concerns. I have asked for such assistance before I even wrote the article. And stronger citations when found can be subsituted as well. Digging through a mountain of data is both time consuming and tedious so this alone should take a better part of half a year. But you cannot pick and choose what facts you will use and what facts you will not, to accomplish this. A fact is fact. Either it is proven to be or it is not. If it cannot be proven then of course we should remove it. But if it can be proven it should remain. If a statement is ambiquous or misleading in any particular it can always be rewritten as needed. That is what wikipedia excels at.

Risk/benefit should not be a part of such an article or a neutral/bias discussion in my opinion. We are not offering medical advice or attempting to treat a patient. We are writing an article on a medical syndrome induced by a specific class of drugs. Benefit is immaterial and irrelevant to such an article, risk however is indeed relevant. If you are interested in the risk/benefit then please take a look at the various articles written for each drug in this class as well as the worthless package insert, or better yet have such a discussion with your treating physician. Not here.

As such we should endeavor to state the facts that describe the known risk of suffering such a syndrome. The problem is that there is no consensus amongst the medical community that allows us to do so. Since we cannot create original research, where pray tell are we to find the known risk factor to cite too? Particulary when we are dealing with an issue that the medical community is in denial concerning. Bottom line is if it cannot be cited, it cannot be used. Hence my reason for not even attempting to do so within the article in the first place. Anything that we would present would be an educated guess at best, an opinion, not a fact. And someone else's at that, who in my opinion, would be far more bias in the other direction. As such if you wish to include a risk section then please provide us with citable sources that describe what it may be and I would be more than happy to add such a section and make reference to them. But to do so I need proven facts, not opinions.

As I was not involved in the naming the article I shall remain neutral as far as that issue is concerned and will defer to others who will debate and form a concensus as to what it shall be. I will accept whatever they decide without further comment or complaint. Other than to state that the original title is an accurate description of what was being written about. It stated the class of drugs, the fact that they are considered to be toxic (by definition) and again by definition are associated with a specific syndrome.

Please try and understand something else here as well. There is a DISTINCT difference between what is to be considered a side effect and what is to be considered an adverse reaction. The two terms CANNOT and should not be used interchangeably. To help you understand this basic concept allow me to present an example: The excessive consumption of alcohol has both a side effect and an adverse reaction. The hangover you get the following morning is to be considered a side effect. It dissapates once the alchohol leaves your system. The resultant damage to your liver, however, is an adverse reaction. It does NOT abate after the alcohol has left your system. In some cases this ends up being permanent damage that is fatal. No amount of absentance will correct the problem, it will only prevent it from getting worse. In time perhaps the body will heal, perhaps not.

But the hangover will always dissapate if you quit drinking. A side effect is what takes place while the drug is in your system and this too dissapates once the drug has been cleared. An adverse reaction however is the DAMAGE done while the drug WAS in your system and such damage may continue long after the drug has LEFT your system. And continue to manifest long afterwards as well, some times forever. As such, common side effects should play no part in the article, common adverse reactions however should, as the article deals with the adverse reactions of this class, NOT its common side effects.

Sorry if I come off a bit harsh, (the written word is always devoid of the body language by which we pick up clues concerning a persons benevolence) but copying the package insert is NOT an acceptable solution to Dr. Steve's concerns in my opinion. Best to eliminate the article completely instead, for doing so (copying the package insert) would not educate those who remain ignorant of this syndrome. And what is the sole purpose of an encyclopedia? To educate and eliminate ignorance. What is the SOLE purpose of this article? To do the same. Let us try to keep that in mind as we discuss these issues further.

On a side note would it not be considered proper etiquette to NOT be deleting or re-arranging the article, moving it to another location, changing it's title, etc, or otherwise attempt to change the whole focus of the article until a concensus has been reached? Or is it common on wikipedia to make the changes first, and then discuss the changes made after the fact? Since I am new here I am a little bit confused regarding this. Making such drastic changes without the benefit of a discussion and the reaching of a concensus seems a little heavy handed to me. Perhaps I am mistaken.Davidtfull (talk) 01:33, 17 February 2009 (UTC)

I think if talking about damage toxicity is a more accurate term. While adverse reaction is perhaps better term, adverse reaction is used sometimes instead of side effects. But anyway the article should not be laid out like a package insert. First of all it is not general article on a specific drug. These are guidelines for such an article.WikiProject_Pharmacology/Style_guide They do not apply to this article though as it is addressing a specific topic of a drug and is not a general article.-- Literature geek |  T@1k?  02:04, 17 February 2009 (UTC)

Neutrality please tell me we are close to agreement
Ok, if anyone has checked the recent edit history they will notice that there has been some recent changes to the lead/introduction section. Steve introduced some content to resolve neutrality and then I followed up with some edits to resolve neutrality as well. Whilst there may be 1 or 2 sentences which may or may not be in dispute, are Steve and David and other editors feeling we are approaching a more neutral article? Is the dispute getting closer to being resolved? I am kind of getting tired of all the texting on wiki and hope so. What do you reckon Steve and David?-- Literature geek |  T@1k?  02:04, 17 February 2009 (UTC)

I reckon it best that I resign from this project. The other editors may do with the article as they see fit. It has become yet another attempt to white wash and trivalize the safety profile of this class and my continuing participation would only continue this controversy needlessly. I appreciate the help and guidance I have received from the others here and have enjoyed the experience. Unfortunately this article has proven to be in an exercise in futility. Feel free to use the citations found on the research site as you see fit, and I will continue to update the articles concerning the various drugs in this class as time allows.Davidtfull (talk) 02:57, 17 February 2009 (UTC)

This is a prime example of why I now feel I can no longer participate in this article: "Conjunctivitis and eye pain are possible adverse effect in moxifloxicin." Period. That is all that was said about the severe vision problems associated with this class.

Even though vision loss (both temporary and permanent) have been cited to being associated with a number of other drugs in this class, and myself being blinded by these drugs (permanent double vision and partial loss of vision), adverse reactions to the use of eye drops including retinal detachment (which has also been reported), etc., etc., my adding this information to the above stub would create yet another area of controversy and we would be off and running yet again. Best to simply admit defeat and part as friends and let Dr. Steve and his peers rewrite this article, rather than continue to try and provide cited input from the perspective of those who actually experienced such avoidable tragedies.Davidtfull (talk) 03:21, 17 February 2009 (UTC)

I think that you are over-reacting with due respect. When I scroll down the page I see brain damage credibly cited, dna damage credibly cited, hearing damage and so forth. I can't see that it is a white wash at all and to use an example I am sure the drug companies would agree with me and disagree with you! Not that the article is meant to be aimed as an attack on the drug companies, the article aim is to documenting factual encyclopedic data. The toxicities are documented in the article. Can I point out (or remind you) that one of the administrators recommended that package inserts are not good sources to use. The example that you used of conjunctivitis and eye pain is referenced to a package insert. Therefore there is nothing to stop you from deleting that part of the article. The person (username Chergles) who added that data is just a regular member of the public and not a staff member, I am not a staff member either. Anyone can edit wikipedia. What is to stop you from citing a reliable source and adding data about permanent visual damage? My comment regarding eye drops was specifically to counter the claim that psychosis does not occur with quinolones when it does. I NEVER said that eye drops do not have their own specific toxicities particularly local toxicities which may be severe and permanent. You are reading things into this which aren't there and were never said by me or anyone. No one denied local toxicities from eye drops, no one said eye drops had no adverse reactions. I think in all honesty you have set the bar too high and unfortunately on wikipedia it is rare that an editor gets an article completely the way they want it to be, due to neutrality. Unfortunately I doubt there are editors on wikipedia who have the knowledge of the literature to improve this article to the extent that you have. It is a shame that you are giving up so easily on this article. I would encourage you to not get down trodden over small changes to the article. I think someone with an interest in fluoroquinolone adverse effects would learn a lot more from this article than they would from a package insert so don't take things so seriously would be my advice and don't set the bar so high. Anyway I am off to bed, I just got up to get a drink of water and checked wikipedia.-- Literature geek |  T@1k?  03:48, 17 February 2009 (UTC)

If all that I see were small changes I would not have a bone to pick here with anyone. I am not downtrodden or discouraged in the least. It is not a matter of my setting the bar to high or others setting it too low. It is a matter of stating the truth whatever it may be found to be. If that is setting the bar too high, then I plead quilty as charged. But the following I do take rather seriously. I simply can't help it, so please bear with me for a moment. I know you are tired of reading long winded postings on the talk page, but you have treated me fair and square so far so I think you are entitled to a more detailed explanation regarding my decision. I do not consider the changes that have been made so far to be "small" or "minor" in the least, to wit:

Fluoroquinolone (or simply quinolone) antibiotics have a generally mild to moderate adverse drug reaction profile. Blatantly false statement. More than half of these drugs have been removed from clinical use due to severe toxicity. This is not to be considered “generally mild to moderate”

Fluoroquinolones (of which cipro-, levo- and moxifloxacin are the most widely used) are a popular class of antibiotics, and newer generations have a broad spectrum including Gram positive, negative, atypical and anaerobic bacteria, although resistance is also increasing.

Frivolous information. It is well known that these drugs treat bacterial infections. The physician rarely if ever chooses these drugs based upon 24-48 hour cultures. They are broad spectrum and that is all he needs to know or cares about. Collateral damage is not even given a moments consideration, let alone what bacteria they erradicate.

With increasing popularity of this class of antibiotics in sometimes benign indications, adverse events could become more frequent, and prudent use seems warranted.[4] Like any drug, the benefits of treatment should outweigh the risk of harm.

False and misleading. The scripting abuse involving these drug is, and has been, rampant for decades. This is NOT a new occurrence. Rarely if ever are they used properly. In one study 99% of the physicians got it wrong and more than seventy percent of the prescriptions written were for benign conditions. This is NOT “sometimes” this is ‘MOST OF THE TIME”.

The most common adverse drug reactions of quinolones are gastrointestinal upsets (diarrhea and nausea), central nervous system complaints (headache and dizziness) and skin problems (especially phototoxicity or skin rash following sunlight exposure).

Yet again false and misleading and if I may be so bold: “bullshit”. Any number of studies clearly refutes this line of crap from the manufacturers.

These are usually mild, reversible and do not require discontinuation of treatment.

Yet another misrepresentation.

In clinical trials, discontinuation rates of currently available quinolones amount to less than 4%, and quinolones with higher discontinuation rates (such as trovafloxacin or grepafloxacin) are no longer available.

Again not true and not supported within the studies submitted to the FDA.

Whilst for most patients the side effects reported were mild to moderate

They are NOT being reported as being mild to moderate by the patients. They are being reported as such by the investigators. Just take a look at the list of reactions these investigators are judging to be mild. They are anything but.

At the first sign of psychiatric, neurological or hypersensitivity reactions it is strongly recommended that therapy with fluoroquinolones be discontinued to prevent serious toxicity from occurring.

False and misleading. These reactions are NOT hypersensitivity reactions but direct toxicity. The serious toxicity had already occurred at the first sign of such events. Discontinuing the drug does NOT reverse such events or prevent serious toxicity from occurring. It had already taken place.

The controversy of fluoroquinolones is not the incidence rate of side effects but of the sometimes prolonged nature of certain adverse effects which for some people leads to prolonged suffering and sometimes permanent disability

Again misleading. The controversy is indeed the incidence rate of side effects together with the prolonged nature. These two issues are NOT separate.

Uncommon and potentially severe adverse events...

False and misleading. The whole controversy involves the false claims of the manufacturers that such events are “rare”. The failure to recognize such events contribute to them being considered “uncommon” and this statement supports such a contested view.

Their use has traditionally been avoided in children based on experimental observations of cartilage damage in young dogs and rats, although they are sometimes prescribed to children in clinical practice

False and misleading. It has already been established as far back as 1996 that this damage occurs in the pediatric population. Cited to within the 67 meeting.

Concers regarding growth plate damage are not adequately supported by human safety data (sic) Bullshit. Read the studies submitted to the FDA for pediatric exclusivity for starters then read the 67th meeting.

and the use of quinolones is not precluded in children if no other safe and effective antibiotic is available

Debatable. It is not a licensed use. Which would preclude its legal use in children. Any number of studies have stated that the use in the pediatric population is unacceptable, under any circumstances.

“If no other safe and effective antibiotic is available, then and only then, would this not be precluded in children” would be a factual way of stating this.

If a patient is predisposed to adverse events (for example because of diabetes, previous psychiatric or seizure disorder), a serious risk-benefit consideration is advisable.

If predisposed then the use is contraindicated. Period. A serious risk/benefit should be performed no matter what the circumstances may be. Whether the patient is predisposed or otherwise. Failure to do otherwise is sufficient grounds for a malpractice suit.

Certain quinolones are more strongly associated with a particular side effect, although a class effect is present in most cases. For example, moxifloxacin carries a higher risk of QTc prolongation,[18] and gatifloxacin has been most frequently linked to disturbed blood sugar levels, although all quinolones probably carry these risks

ALL QUINOLONES CARRY THESE RISKS. No “probably” about it. Have I not provided enough citations to prove this beyond a reasonable doubt all ready? Why is there NO mention of the fact that gatifloxacin had been removed from clinical use due to “disturbed blood sugar levels” that were found to be killing the patients?

Some quinolones were withdrawn from the market because of these adverse events (for example, sparfloxacin was associated with phototoxicity and QTc prolongation, thrombocytopenia and nephritis were seen with tosufloxacin and hepatotoxicity with trovafloxacin

SOME QUINOLONES? Try 50%. That is NOT “some” and notice that gatifloxacin, which was removed just last year, is NOT included within the above list. Perhaps the good doctor is unaware of this? OR simply choosed to ignore it?

For example, simultaneous use of corticosteroids is present in almost one-third of quinolone-associated tendon rupture

“one-third of quinolone-associated tendon rupture” Unsupported in the literature. This is an opinion, not a fact.

These are the kinds of things I find to be a white wash and a trivialization regarding these issues. It is not a matter of me giving up too quickly or over reacting. I have been down this road so many times it is pathetic. All that this recent editing has done is substitute the manufacturer’s line of b.s. and Dr. Steve’s own bias point of view in the place of my original text, which he had claimed to be too bias. The bias continues, only it has swung to other end of the spectrum.

The above text is not balanced, it is not neutral, it is not factual in some instances, it sways the reader by the use of exclusions and it sure as hell is just as bias my original text was accused of being. In fact it contains far more factual errors, opinions and presumptions in my opinion.

So what is the point of me arguing about all of this? There is no point. It is an argument that cannot be won by using citations. It is a matter of arriving at a middle ground we all can live with.

But the views being expressed now are so diametrically opposed to my own I am ashamed to even be associated with this article. Hence it best for all that I simply take my toys back to my own sandbox rather than do battle with such closed minded individuals. They will not be swayed no matter how much evidence I present. The outcome has already been predetermined. Why prolong the agony and make life miserable for everybody?

I’m not bitter, or angry, frustrated or anything else of that nature. I do not feel that I am over reacting in the least. Just being realistic is all. I knew this would be the end result before I even started. Guess I’m too much of an optimist for my own good some times.

I had high hopes, but even I knew them to be unattainable. I’ve had to deal with this so often over the past decade that I am far beyond taking any of this personal. As they say if you are not part of the solution you are part of the problem. It is utterly impossible for me to be part of the solution to making this article fair and balanced without a knock down dragged out fight. And after a decade of such battles this one simply is not worth the effort.

It is only a matter of time before the articles I had written for the various drugs are dismantled in the same fashion. I’ll save what little fight I have left in me for those instead. This was your baby to begin with. The individual drug articles I would consider to be mine. So you fight for you and yours, and I will do battle for what I consider to be mine when the time comes.

There is a time and place for everything, and fighting about this article here on wikipedia, is neither the time nor the place. I will just clean up the missing citations within the article and leave it at that. No hard feelings in the least and if any editor cares to consult me regarding the article I am more than willing to work with them any way I can. I just will not be writing anything further for this article is all. At the moment I am ashamed to have my name even associated with it. But that is my problem, my problem alone, and I have no intention of making it yours or anybody elses. As such do the best you can and I will assist you in any manner you may require. I've simply lost the desire to try to change the minds of folks who do not wish to be further confused by the facts. I will leave that task to you now. They have already exhausted me and we have yet to begin to even fight about these issues in earnest. So, God speed my friend. Now if you would be so kind as to lend a hand to this decrepit old man I will get off my soap box and say no more concerning this as I see the line has already formed to left of me to dispute all that I have just stated.Davidtfull (talk) 06:46, 17 February 2009 (UTC)

First of all you seem to take issue with people's lack of knowledge and expect people to have a photographic indepth knowledge of fluoroquinolone toxicity literature when you know that there is probably only a couple of dozen if that people who have close to the indepth knowledge of fluoroquinolone toxicity so I do believe that you are being unreasonable and are expecting a marathon type approach in the article and people's knowledge from how you are reacting. We cannot help it if the papers are misrepresenting the severity of reactions. If you know of peer reviewed papers that document adverse effects in your eyes accurately and the author comes to the same conclusion as you then please do cite them. Otherwise your disagreement is misdirected by blaming editors on wiki when it is really a matter of bias in drug company clinical trials. Many of the problems you have raised didn't need to be raised on the talk page but you could have tweaked, reworded etc the article text and left a short summary in the edit summary box to explain why a sentence was inaccurate. I was visiting your web site last night looking for citations and to be quite honest the vast majority of the medical literature whilst acknowledging serious toxicities generally conclude that such adverse effects are rare. One example is Dr Flockhart who I have seen mentioned several times on your website as an expert. He states in this citation that CNS side effects generally go away when the drug is stopped and that rarely they trigger an underlying condition. So he is clearly downplaying the established fact that quinolones are neurotoxic and claim persisting effects (which are rare in his opinion) are due to triggering of underlying mental health conditions. Toxic effects of drugs are often attributed by drug companies and drug enthusiasts as underlying conditions. A very pseudoscience speculative theory when the data would suggest a more rational theory is direct toxicity and neurotoxicity for persisting or long lasting CNS effects. I am not attacking flockhart, he has written some very good info on quinolones and has done a lot of good by my brief review of his writings and he is a respected senior pharmacology and expert in his field. My point IS that it is easy to disect and totaly demonise anyone and any article and any expert if one is to focus only on negative things a person or article says. So the question is why do you associated yourself with these opinions and experts on your website? I could easily disect statements by experts in more depth and medical papers on your site and ask the valid question why do you host such content or why do you promote or associate with experts who make such statements? You see my point is you are coming down very heavily on editors here when you yourself have medical abstracts, medical experts who say things which are more down playing the toxicity on your very own website. I am not down playing your efforts of advocacy or the quality of your website which is probably the most indepth website on fluoroquinolone toxicity. I am trying to show that it is impossible to reach perfection based on the medical literature and experts because humans are only human and are not God so imperfections exist in the literature. You have clearly contributed an amazing amount of data and helped and saved I am sure many thousands of peoples lives via your website perhaps 10's of thousands if we include your successful efforts of getting the black box onto quinolones in the USA. What I am trying to say is that neither wikipedia, nor the medical articles on your website are completely free of error and readers of either your web site or wikipedia will find some inaccuracies which are misleading. This is NOT your fault nor is it wikipedia's fault but is the fault of the peer reviewed data focusing on benefits and ignoring risks or the paper authors not having such an indepth knowledge of the data as what you have. Neither you nor wiki can help bias and promotional medical papers and articles focusing on the positive or repeating industry based clinical trial data rather than the negatives as well. You are blaming the wrong people. I would love to see more articles from reliable sources where the author comes to the same conclusion as you, then maybe we can cite them, otherwise wikipedia will be an imperfect article based on your standards if it can't be verified. Don't doubt me I believe these are toxic drugs, I believe that they should be treated similarly to aminoglycosides in that they should be restricted to hospital use only with strict safety guidelines or else if used outside of hospital only as 2nd or 3rd line drugs with strict safety guidelines. What is the exact number or even a reasonable guess as to what percent have long lasting symptoms from quinolones? I dunno. Is it 0.5% 5%, 10% in the general public, anyones guess unless we have a good quality study. But even if 1% of people get severe prolonged or permanent effects from these drugs we are talking about a huge number of people perhaps hundreds of thousands or more world wide who are chronically damaged with their lives adversely affected or even ruined when safer alternatives existed. If you are right about the severity of the high rate of misdiagnosis then who knows perhaps it is even millions who have had their health adversely affected chronically in one way or another. Sorry to be critical, I feel like piggy in the middle here. I have found myself getting in heated debates with you, with Steve, with other people on wikipedia and on wikipedia pharmacology and honestly you all are causing me too much drama and stress LOL. I honestly feel that I have tried to be diplomatic and have tried to make both you and Steve see some sense. Maybe I am the crazy one! Maybe I am being unreasonable?!? I dunno. If I am I plead guilty and my defense is I am human. I just wish you people could be more calm and reasonable. I have tried to be fair and now feel like David is angry at me, Steve is pissed at me and several other members aren't happy with me. It is not nice to be in the position I am in. I hope you understand my frustration as I understand yours. I would like you to stay around wikipedia and take a more relaxed approach to editing, with less debate and more productive editing. The moxifloxacin article needs developing as do other articles so there is much work needed on wiki on the quinolone articles. Even if the apocolypse happened and half your edits got deleted, the readers of wikipedia would still be very much more enlightened by the remaining edits whilst prior to your arrival on wiki readers wouldn't even know there was toxicity issues with quinolones. I think you are aiming for perfection which is rarely possible, we live in a imperfect world sadly. I think you are focusing on the negatives than the positives. I can pluck out lots of edits most of which have been done by you which are very favourable to your point of view of quinolone toxicity but you insist on focusing on the negatives and imperfections and mistakes. Prior to your edits on wiki there was virtually no good info on toxicity, now there is good info. That is progress from your point of view like it or not!-- Literature geek |  T@1k?  08:11, 17 February 2009 (UTC)

I am close to walking away from this article to as there is too much drama and it is simply unnecessary and I do think an overreaction. I couldn't be bothered argueing who is over reacting anymore either LOL. We seem to debate everything on this page and it is getting ridiculous.-- Literature geek |  T@1k?  08:11, 17 February 2009 (UTC)

I do not agree with Steve's edits to this article. It must be noted that quinolone reactions are not at all similar to other drug reactions. David has provided good research towards this, and they are not biased at all. Steve, please announce all your COI, including pharmaceutical company shares, etc. JamesLockson (talk) 07:05, 17 February 2009 (UTC)


 * JamesLockson, you are welcome to edit as long as you use reliable sources to back-up your claims, and you have even more reliable ones to contradict the statements from other reliable sources.
 * I will try and post a COI statement today at User:Stevenfruitsmaak/COI; but basically, I'm six months away from starting to earn as a doctor, I don't have any shares, I never even got anything from a drug representative. --Steven Fruitsmaak (Reply) 08:07, 17 February 2009 (UTC)

In Steve's defense. I do not believe Steve works for the drug companies. He is an established editor and administrator on wikipedia and respected.-- Literature geek |  T@1k?  08:24, 17 February 2009 (UTC)

In that case, I apologize for any insinuations. Steve probably isn't malicious, probably just misinformed. It is hard to comprehend the real life existence of such serious reactions, if you have not personally seen what these drugs can do to someone. JamesLockson (talk) 09:44, 17 February 2009 (UTC)

Off Topic: Talking about drug companies, here is a video of an actual Pharmaceutical Representative who has been suffering a horrendous reaction, even after many years. http://www.youtube.com/watch?v=qpDkN_KJmdA&fmt=18 Pretty ironic isn't it? JamesLockson (talk) 13:04, 17 February 2009 (UTC)

A sad video to watch, hopefully he will recover. He looked in a lot of pain from his peripheral neuropathy and other damage.-- Literature geek |  T@1k?  19:41, 17 February 2009 (UTC)

Honestly, I am not angry with anyone here. I do not believe that Dr. Steve or anyone else here has any ulterioir motives or bad intent. And I am certainly not trying to put anyone in an ackward position. Or cause any kind of drama. The reasons you see such a variety of research on the research site is the fact that that it what it is. A research site. It contains the good, the bad, and the ugly. People read what they care to and draw their own conclusions. Just as you would viewing pubmed. But the purpose of the article started out to be a report about a specific syndrome. It has changed to a report about the possible adverse effects of this class and the concensus is now that it should no longer be a report about this syndrome. In fact even the name "syndrome" has been removed. As such I would rather not be a part of it. No drama. I know if I continue to edit it I will be trying to redirect it to its original intent and others will edit it to bring in back to being a report about the possible adverse reactions. And THAT would cause drama and friction. And those editing it, unfortunately as you have stated, lack the specific knowledge required. So let it be a report about the possible adverse events and let it be cited to the popular view within the medical community, rather than trying to change this view, which I thought to be the original intent to begin with. I have no problem with that. Nor am I angry with anyone deciding this would be the best way to develop the article. I've been outvoted and accept that without complaint. I am not on a quest for perfection. But if the boat is heading south and you wish to travel north, does it not make sense to simply leave the boat rather than try to persuade the captian to turn it round solely for your benefit? Particulary if the other passengers wish to continue south? Seems to me that this is what logic would dictate that you do and hence this is what I have done. Makes perfect sense to me.

On a side note regarding Dr. Flockhart, after big pharma built him a new clinic he pretty much stopped all advocacy regarding the quinolones and started toting the company line. Since his work with Stephen Fried he has done little to nothing concerning these reactions. In a recent podcast interview following the black boxed warnings he in fact tended to downplay them considerably. He is indeed considered by some to be an expert to a degree and like all experts his funding comes directly from the manufacturers. He has received numerous research grants from big pharma which is not at all unusual for a college professor. In fact it is the norm. He has done some decent things in the past concerning these issues so his older work has value. His recent work however has been tainted. The research site contains both and I let people judge for themselves. I'm not Stalin and I don't purge just because people are later influenced by the drug companies. History is history and I don't try to rewrite it on the site. Just display it.Davidtfull (talk) 15:20, 17 February 2009 (UTC)

I am happy to hear that you are not angry with anyone. Syndromes and disorders are determined usually by panels of experts such as the American Medical Association or American Psychiatric Association etc. The very least that wikipedia needs is for a reliable peer reviewed source calling it a syndrome. Wikipedia can't say what is or isn't a syndrome. It is beyond wikipedia's scope. It doesn't matter if all the common sense and evidence says syndrome. As explained previously wikipedia can only go by what the citations say and the authors conclude. If that means saying that severe reactions only occur occasionally there is nothing that can be done unless you can provide a citation which concludes that severe reactions occur in the majority of users. We can cite sources of which I believe there is at least one already in the article that adverse and toxic effects of fluoroquinolones are often overlooked or misdiagnosed by doctors. Above that nothing can be done unless reliable sources can be provided. You would be asked to do the same if submitting a paper to a peer reviewed journal. I don't think that long term damage (peripheral nerve damage, CNS toxicity, tendon damage etc) is in dispute nor the effect on individual victims lives but what is in dispute is the incidence rate of such severe toxicity. Most if not all medical sources I have looked at on your website seem to suggest that such severe and/or prolonged reactions either occur occasionally or rarely but I admit I have not reviewed all of the peer reviewed literature you have cited on your website. Anyway I can see from what you have said that you feel staying here is going to cause a headache for yourself as well as everyone else as the direction of the article is not going the way you want it to go and thus you want to disassociate yourself from it. I understand your position. I don't know if you are disassociating yourself just from this article or are leaving editing wikipedia completely. Pitty about Dr Flockhart. That explains some of his conflicting statements. Anyway we have a number of editors Steve, myself and Jameslockson and a couple of others who may or may not continue to develop the article. Wikipedia relies on reliable sources and that is basically the crux of wikipedia.-- Literature geek |  T@1k?  19:37, 17 February 2009 (UTC)

I am curious about something you had stated previously. Why would Dr. Steve be pissed at you about anything? His dispute was resolved in his favor through private negations rather than public debate and consensus. And as a result I decided to withdraw from this article. That presented a win win for him, not something for him to be angry about in the least I would think. The resolution of this dispute presented a moral and ethical dilemma for me as it presented a conflict of interest that I felt I could not overcome. As I strongly disagree with the direction it was decided that the article should take it is only reasonable that I not participate in its continuation. But I was afforded an opportunity to present my arguments and proofs and they were rejected. Not something for me to be angry with either. I don’t expect to win every argument I engage in. I was treated with reasonable respect, everybody behaved rather well, and a decision arrived at.

As such I fail to see why any of the other pharmacy editors would be upset with you regarding anything concerning the resolution of this dispute or why Dr. Steve would be angry about the resolution of this dispute as it was decided in his favor. It allows the article to go forward without any further interference from me. Seems to me that everybody here should be pleased that the dispute had been resolved in a reasonable amount of time, the debaters showed reasonable restraint, and there now is no need for further debate. Seems this too is a win win for all concerned.

Should the editors change thier minds and decide that the article should head north, rather than south as it is now, there would no longer be a conflict of interest on my part and I would then be allowed (by my conscience) to continue to contribute to the article. But for the moment the article is heading south and I am not willing to sacrifice my ethics, morals and integrity by contributing to an article that rather than draw attention to a syndrome, provides the treating physician with yet another source to deny its proven reality. I may be a "bitch" to deal with at times as I am rather outspoken as well as opinionated regarding these issues, but I am not a "whore" that can be bought and sold like some of those found within the medical community that have written the citations we have reviewed.

I will continue to be a part of wikipedia, I will continue to work on the other fluoroquinolone articles, and if I am asked again to sacrifice the outrageously high standards I have set for myself I will simply decline and withdraw from that particular article. If I find that I cannot in good conscience edit an article due to the conflict of interest such a sacrifice would entail, the only option is not to participate further on that article. Just as I have done here. Wikipedia requires this from all its editors, and even with my ten years of study and expertise regarding these issues I am not to be an exception to this rule. Nor should anyone else for that matter. I may be new here but I fully understand the above rule and agree with it and will follow it to the best of my abilties.Davidtfull (talk) 23:40, 17 February 2009 (UTC)

I disagreed with both of you during this dispute, so I tread on both of your toes. You have added a lot of verifiable data to the article which will not be deleted so I don't think that there will be any winners. A person's side of the debate on wikipedia is only as good as the reliable citations. The same policies apply to all wikipedia articles. If you have a good secondary source saying that fluoroquinolones have an unfavourable risk/benefit ratio or a generally severe adverse/side effect profile then please do cite it. You could convert every editor on this page to your view on fluoroquinolones and you still wouldn't win because data must be reliably cited. Maybe your next battle should be with the National Institute for Health to try and get them to study say 1,000 randomised members who receive fluoroquinolones and follow symptoms up over a course of a year and document them. Then we will have an idea what percent get acute serious ADRs and what percent have persisting ADRs of users and then once published return to wikipedia and cite it. Not very likely to succeed in getting such a study done but who knows, you did achieve the black box warnings after all. Nice to hear that you are going to stay on wikipedia. By the way I have been in a similar position to you when I first joined wikipedia. I got off to a bumpy start on wikipedia when large blocks of my edits were challenged. I wasn't aware of the rules and very enthusiastic on the articles I was editing.-- Literature geek |  T@1k?  02:11, 18 February 2009 (UTC)

I've never considered someone disagreeing with me to be stepping on my toes. Everyone is entitled to an opinion and are free to express it, in my opinion. We don't have to agree on anything, all we have to do is discuss things in a rational manner and if a concensus cannot be reached agree to disagree and leave it at that. I never take such debates personal in the least, so you have yet to offend me in any way. But if for some reason you ever do, I will discuss it off line with you and see if we can resolve the issue privately.Davidtfull (talk) 02:49, 18 February 2009 (UTC)

Good. :--) Sounds like a good plan and good way to handle things. By the way you probably wouldn't want to be associated with a study that involved administrating a fluoroquinolone so maybe one which involves randomly selecting patients who have already taken a fluoroquinolone, but you get my idea.-- Literature geek |  T@1k?  02:55, 18 February 2009 (UTC)

"This was your baby to begin with. The individual drug articles I would consider to be mine."

I just noticed this part of your post that you made a couple of days ago, I must have missed it. I only started the article with cited data off of your talk page. You added the bulk of the material, (in record speed, I have never seen an article develop so fast). As you are new to wikipedia I would refer you to this page.Ownership_of_articles. I don't own this article, just because I edited it first. Nobody can claim ownership of an article, although defending articles against vandals and being enthusiastic in developing them and taking a special interest in an article's development process is perfectly fine.-- Literature geek |  T@1k?  19:35, 18 February 2009 (UTC)


 * That was just an expression, it was not intended to be taken literally. The point being you had started something and I had volunteered to help with it.  As such I would think it be a bit courteous of me to defer to you in regards to certain matters is all.  I realize this is a group effort and nobody has absolute rights to anything.  It is community property.  But with all community property there is always someone who takes an greater interest in its well being and such folks should be granted a degree of respect concerning thier wishes.  They certainly do not have to be followed, but they should at least be given serious consideration.  That was the point I was trying to make is all.  I have an annoying habit of using metaphors to explain a situation or a point of view, they are not to be taken literally.  But any group effort tends to generate a leader of sorts, a straw boss if you will, I was just pointing out that at the moment that someone, in my view, appeared to be you, and not I.Davidtfull (talk) 00:17, 19 February 2009 (UTC)

Use of
This is not a reliable source because it is an Internet-based study; this is more a hypothesis-generating study than a reliable source (see WP:MEDRS). For starters, it is a primary source and not a review. --Steven Fruitsmaak (Reply) 07:49, 17 February 2009 (UTC)

As long as the data in that article are not misused, given undue weight or misinterpreted or used to synthesise it is reliable. I think its use is fine if used cautiously. I read MEDRS. Primary sources are allowed. Also it is not a featured article so there is not such a focus on aiming for perfection. You all are making me stressed out! Sorry.-- Literature geek |  T@1k?  08:21, 17 February 2009 (UTC)

I agree with Literaturegeek. One should not conclude that just because data was collected over the internet, it is "not a reliable source". It is a very useful source that validates the existence and characteristics of various side effects. It was this source that prompted the FDA to include "Irreversible" Neuropathy as a side effect.

Steve, I do believe that this article has great potential. Why don't you come back in a few weeks, as right now they are doing a lot of editing and restructuring. All this arguing is not going to help at the present moment. JamesLockson (talk) 08:24, 17 February 2009 (UTC)

Yea and much of the adverse effects and many facts in that study can be verified using secondary sources anyway if it is demanded. Thanks james for understanding, a break is maybe a good idea.-- Literature geek |  T@1k?  08:27, 17 February 2009 (UTC)

odds ratio and relative risk
It appears David has mistakenly thought that these mathmatical calculations mean percent and as a result has inflated the data thousands of times what it is. Can someone track down this article Fluoroquinolones and Achilles tendinopathy in renal transplant recipients and see if it is talking about percent, relative risk or odds ratio? It is an easy mistake to make if not knowledgable in mathmatics. I have no doubt not all quinolone injuries are picked up by the FDA and the incidence for tendonopathy is higher than 4 per 100,000. I have heard anywhere from only 1% - 10% of serious adverse reactions are reported to regulatory bodies but still multiplying the data by many many thousands of times what it is by a mathmatical mistake is grossly distorting the data.-- Literature geek |  T@1k?  11:58, 17 February 2009 (UTC)

That paper is actually where you live Belgium Steven, so if you can track it down at least you will bee able to understand it! :=)-- Literature geek |  T@1k?  12:15, 17 February 2009 (UTC)

Actually I think that it is in an english journal.-- Literature geek  |  T@1k?  12:16, 17 February 2009 (UTC)

Don't know what exactly is your question, but according to that paper, the incidence of tendon rupture in renal transplant patients who received a quinolone was 12%. Though I am certain I have read a published article showing that less than 10% of all ADRs are reported to the FDA, I'll see if I can find the article for you. Quinolones are definitely more underreported as the adverse reactions are almost always misdiagnosed, or delayed. Who would think your chronic insomnia came from an antibioitic you took months ago? How can an athlete attribute their tendon rupture to a few pills of antibiotics? JamesLockson (talk) 12:47, 17 February 2009 (UTC)

I was able to verify it from another peer review publication that quoted it. The stats in that article are correct. The other citations had multiplied the stats by many thousand fold by changing relative risk or odds ratio into percent. Looks like everything is ok now and cited properly. I fixed errors in article. Yea I hear what you are saying about people and doctors not attributing symptoms to a drug reaction. Drug reactions get misdiagnosed all the time though, not just quinolones. I know of other horror stories from friends and relatives with other drugs. One example was severe muscle wasting that put a friend in hospital for 3 months. Doctors were baffled why he was wasting away in in crippling agony and also why he was getting neuropsychiatric problems. It was an adverse reaction to a statin. Who would think a cholestoral drug would make you lose your memory and mind and destroy your muscles? Trust me he suffered, it wasn't benign and it could have led to permanent damage or even death if it wasn;t eventually correctly diagnosed,,,, 3 months later. The problem is doctors fit symptoms into a category and make a diagnosis without trying to do detective work and find the cause and think ok what is the recent drug history around the time these symptoms developed? Did patient recently start or abruptly stop a medication? I have a personal friend who spent several months in a psychiatric unit after an adverse drug reaction to a psychotropic drug. They kept them on it and even increased the dose and made her even more psychotic before a new doctor checked her history and diagnosed an adverse reaction and stopped the medication. She could have ended up a permanent mental health patient had the reaction not been spotted, permanently on antipsychotics to treat "psychosis" or schizophrenia or whatever. This happens all the time and lives are sometimes ruined and health destroyed. That is not to say medicine is evil, there are good drugs on the market and good doctors that use drugs sensibly.-- Literature geek |  T@1k?  13:16, 17 February 2009 (UTC)

I said 1 - 10% because I have seen studies showing as low as 1% report adverse reactions but I am thinking of the uk yellow card scheme scheme but should be similar in usa.-- Literature geek |  T@1k?  13:32, 17 February 2009 (UTC)

This is the text of the article in question, took me less than sixty seconds to find it:

Br J Clin Pharmacol > v.48(3); Sep 1999 Stricker, B. Br J Clin Pharmacol. 1999 September; 48(3): 433–437. .

Copyright © 1999 Blackwell Science Ltd Achilles tendinitis associated with fluoroquinolones P D van der Linden,1 J van de Lei,2 H W Nab,1,4 A Knol,3 and B H Ch Stricker1 1Pharmaco-epidemiology Unit, Departments of Epidemiology and Biostatistics and Internal Medicine, Erasmus University Medical School, Rotterdam, The Netherlands 2Department of Medical Informatics, Erasmus University Medical School, Rotterdam, The Netherlands 3General Practitioner, Groningen, The Netherlands 4Dutch Medicines Evaluation Board, Rijswijk, The Netherlands Correspondence: Dr B. H. Ch. Stricker, Department of Epidemiology & Biostatistics, PO Box 1738, 3000 DR Rotterdam, The Netherlands. Received September 18, 1998; Accepted May 17, 1999.

This article has been cited by other articles in PMC.

Aims To determine whether there is an association between use of fluoroquinolones and tendinitis in a large population under everyday circumstances.

Methods A retrospective cohort study was carried out in a dynamic population. Data came from the IPCI-database which consists of all data on consultations, morbidity, prescriptions and other interventions, as registered by GPs in a source population of approximately 250 000 persons. For this study data were collected from 41 general practices in the period from January 1st, 1995 through December 31st, 1996. All persons treated with either fluoroquinolones, amoxicillin, trimethoprim, cotrimoxazole or nitrofurantoin were followed from the first day of treatment until the outcome of interest, death, transfer to another practice, or end of the study period, whichever came first. The risk window was defined as the legend duration +1 month. Potential cases were defined as a registration of a tendinitis or tendon rupture. Patients with a history of tendinitis or tendon rupture, preceding trauma or inadequate diagnoses were excluded on the basis of a review of the patient profiles and additional clinical data, blinded as to the exposure status. Results were adjusted for age, gender, concurrent corticosteroid exposure and number of GP visits.

Results There were 1841 users of fluoroquinolones and 9406 users of the other antibacterial drugs with an average duration of 9 and 7 days, respectively. Tendinitis or tendon rupture was registered in 97 profiles, but after review only 22 complied with the case definition. The adjusted relative risk of tendinitis to fluoroquinolones was 3.7 (95%CI: 0.9–15.1) for Achilles tendinitis and 1.3 (95%CI: 0.4–4.7) for other types of tendinitis. Achilles tendinitis to ofloxacin had a relative risk of 10.1 (95%CI: 2.2–46.0) and an excess risk of 15 cases per 100 000 exposure days.

Conclusions Although the numbers in our study are small, our results suggest that some fluoroquinolones may increase the risk of Achilles tendinitis, and that this risk increase is highest for ofloxacin.

Discussion References IntroductionIn the past few years, there has been a marked increase in the number of spontaneous reports of tendinitis associated with fluoroquinolones [1–7]. In the vast majority of cases, the Achilles tendon was affected with symptoms compatible with painful tendinitis or with rupture, usually during the first 2 weeks of treatment. Fluoroquinolones form a relatively new class of antibacterial agents which act by inhibiting bacterial DNA gyrase [8]. The most frequently observed adverse effects are of gastro-intestinal origin, followed by CNS disorders and skin reactions [8]. Although in several case reports tendinitis has been attributed to fluoroquinolones, the epidemiological confirmation of the association is scanty. In order to assess whether there is an association between fluoroquinolones and tendinitis, and to determine the incidence and relative risk of tendinitis to the different products, we conducted a retrospective cohort study in a large population under everyday circumstances. Data source Data were obtained from the Integrated Primary Care Information (IPCI) system, a research-orientated database with data from computerized patient records of general practitioners (GPs) throughout the Netherlands which was developed by the Department of Medical Informatics of the Erasmus University Medical School. The database includes all demographic information, patient complaints, symptoms, laboratory tests, diagnoses, discharge and consultant letters, and prescription details (including drug name, dosage form, dose, quantity prescribed, and indication). GPs write the prescriptions directly from the computer, thus ensuring automatic recording. Medication codes are based on the national database of drugs, maintained by the Royal Dutch Association for the Advancement of Pharmacy. A modification of The International Classification for Primary Care [9] is the coding system employed for patient complaints, diagnoses, and indications but these can also be entered as free text. At present, the IPCI-project monitors a population of about 250 000 patients on a continuous basis. The data used for this study were collected from 41 general practices in the period between January 1st, 1995 and December 31st, 1996.

Cohort definition The cohort consisted of all patients of 15 years and older with a permanent status who were treated in the study period with one of the following antibacterial drugs: fluoroquinolones (index group), amoxicillin, trimethoprim, cotrimoxazole and nitrofurantoin (reference group). The latter four drugs were chosen as a reference because these are commonly used drugs with a well-known safety profile, and have not been associated with tendinitis. Subjects had to have a computer-recorded history of at least 3 months duration prior to the date of first prescription in order to be eligible to participate in this study. All coded prescriptions were considered with the exclusion of dermatological and ocular preparations. The patients entered the study cohort on first prescription of one of the study drugs at which time contribution to person-time experience started. Subjects were followed until the outcome of interest, transfer to another practice, death, or end of the study period, whichever came first. Patients were excluded if gender, age, or dosage of the study drugs were unknown, if they were chronic users of the drugs under study (more than 60 days in 1 year), and if there was a history of inflammatory joint disease (e.g. rheumatoid arthritis, SLE), Reiter’s syndrome, polymyalgia rheumatica, gout or AIDS.

Exposure and outcome definition For each prescription, the legend duration was calculated as the amount of prescribed drug divided by the daily dose. The total exposed period of each subject was calculated as the sum of the legend durations, corrected for refill prescriptions. The risk period was defined as the exposed period plus 1 month. The month was added because any increased risk during exposure will have a carry-over effect and because a notification in GP-records may be delayed when patients present themselves with tendinitis several days after onset. Concomitant users of fluoroquinolones and one of the reference drugs during this risk period were excluded. To ensure maximal sensitivity and specificity, we followed a two-step selection procedure of case-finding (step 1) and case-validation (step 2). In step 1, potential cases of the outcome of interest were defined as the registration of one or more of the diagnoses or symptoms mentioned in Table 1 within the risk period. Moreover, all records were studied for a notification of ‘tendinitis’, ‘tendon disorder’, ‘tendon rupture’, ‘coup de fouet’ or ‘pain upper leg’ in the free text of each patient file. In step 2, for all selected patients a patient profile was generated and printed, where all prescriptions, GP medical diagnoses, laboratory results, hospital referrals and GP remarks were listed. The exposure to the study drugs in these patient profiles was blinded. Following an independent review of the patient profile by two GPs, patients were excluded if the patient had a history of tendinitis or tendon rupture before use of the study drugs, if another cause of the tendinitis was likely (e.g. trauma), or if the diagnosis was wrong (e.g. bursitis). In case of disagreement, the data were independently reviewed by a third medical practitioner. To confirm the adequacy of the validation procedure, the GPs of potential cases were sent a questionnaire requesting details of some of the clinical features and any correspondence available related to the diagnosis of interest. All patients’ personal identifiers were suppressed before sending.

Table 1 List of ICPC-codes included in the case definition.

Analysis The first outcome-related event that occurred was used in the analyses. The incidence density (ID) was calculated by dividing the number of events occurring in the risk windows by the total risk period, and was expressed as the number of events per 100 000 days at risk. Incidence densities for exposure to fluoroquinolones were compared with those for the reference drugs. The relative risk (RR) of tendinitis was calculated as an incidence density ratio, dividing the two incidence densities. The excess risk was calculated by subtracting the incidence densities in index and reference group. Confidence (95%) intervals for the crude and adjusted relative risks were estimated with Poisson regression analysis. Adjusted estimates of the RR were controlled for the potentially confounding effects of gender, age, number of GP visits and concurrent corticosteroid use. Results

In the study period, 11 812 patients of 15 years and older received 18 428 prescriptions for the study drugs. Of these, 786 patients were excluded because dosage was unknown (n = 34), because of concomitant use of fluoroquinolones and the reference drugs in the risk period (n = 653) or because they were chronic user (n = 99). Furthermore, 226 patients were excluded because they had a history of rheumatoid arthritis (n = 76), SLE (n = 3), polymyalgia rheumatica (n = 28), gout (n = 118) or AIDS (n = 1). Hence, the study population consisted of 10 800 patients. During the study period, there were 1841 users of fluoroquinolones and 9406 users of the other antibacterial drugs (fluoroquinolones as well as one of the reference drugs may have been prescribed to the same patient outside the risk period), with an average duration of 9 and 7 days, respectively (Table 2). In total, 418 patients received 500 prescriptions for ofloxacin, 456 patients received 556 prescriptions for ciprofloxacin and 1030 patients received 1362 prescriptions for norfloxacin, with an average duration of 10, 9 and 8 days, respectively. Most index and reference drugs were used for urinary or respiratory tract infections at the recommended daily dosage. There was no significant difference in indication between index and reference group. The reference group consisted of relatively more female patients. The mean age in the index group was higher; patients in the index group visited the GP more often, and had a higher prevalence of renal failure (Table 2). During the total risk period of 548 919 days, possible cases of tendinitis or tendon rupture were registered in 97 patient profiles. After more extensive review of the computerized profiles of these potential cases by the medical reviewers, 68 (70%) cases were excluded from further analysis: 26 (38%) because the diagnosis was not tendinitis but mostly bursitis, 12 (18%) because tendinitis was probably caused by a trauma and 30 (44%) because there was a history of tendinitis or tendon rupture before intake of the study drugs. Concerning the remaining 29 cases, questionnaires were sent to the GPs which were all returned after some reminders. After blinded review, 7 additional patients were excluded: 2 cases because the diagnosis was not tendinitis, and 5 because tendinitis was caused by trauma. Consequently, 22 cases (all tendinitis; no rupture) complied with the case definition. In 8 of these patients, the Achilles tendon was affected. Of the 22 cases, 7 occurred during fluoroquinolones and 15 during use of a reference drug. The incidence density of tendinitis during fluoroquinolones was 7.74 per 100 000 days at risk and 3.27 for the reference drugs, which is compatible with a RR of 2.4 (95% CI: 0.96–5.80). Ofloxacin had a significantly increased crude RR of tendinitis of 6.5 (95%CI: 2.14–19.45), which declined after adjustment to 4.9 (95%CI: 1.57–15.06). No significant association was found for ciprofloxacin and norfloxacin (Table 3). After stratification for Achilles tendinitis and other types of tendinitis, fluoroquinolones as a group had an elevated RR of Achilles tendinitis of 4.4 (95% CI: 1.27–20.27), which declined after adjustment to 3.7 (95% CI: 0.93–15.14), while no association was found for the other types of tendinitis. Ofloxacin was associated with an increased RR of 10.1 for Achilles tendinitis (95% CI: 2.20–46.04), whereas no association was found with the other types of tendinitis for the different fluoroquinolone agents (Table 3). The risk difference between fluoroquinolones and the reference drugs was 4 cases per 100 000 days for tendinitis, and 4 cases per 100 000 days for Achilles tendinitis. Ofloxacin was associated with a risk increase of 15 cases per 100 000 days. A duration-or dose effect relationship could not be assessed as almost all courses were given for similar short periods and because the large majority of fluoroquinolone users took the recommended daily dose.

Table 2 Characteristics of the patient in the index group and in the reference group.

Table 3 The incidence densities stratified for achilles tendinitis and other tendinopaties among the drugs under study and relative risks stratified for achilles tendinitis and other tendinopaties. In this study, we found that the risk of tendinitis with fluoroquinolones was higher than the risk with a reference group of four commonly used antibacterial agents with a known safety profile. As these are not known to cause tendinitis, they represent the background risk and even if some actually cause tendinitis, this would tend to underestimate the RR of fluoroquinolones. Ofloxacin had the strongest association with Achilles tendinitis. Although age, gender, and number of visits to the GP differed significantly between the fluoroquinolone users and the users of other antibacterial drugs, adjustment for these factors did not eliminate the association with tendinitis. None of the cases had renal failure, which has been suggested as a possible risk factor for tendinitis [7]. Use of corticosteroids, a suggested risk factor for tendon rupture, was not related to tendinitis in this study.

The validity of epidemiological studies may be endangered by selection bias, information bias, or confounding. As the association between fluoroquinolones and tendinitis was only recently widely recognized and as proven risk factors for tendinitis, such as physical training, are not a contra-indication for fluoroquinolones selection bias is unlikely. One of the advantages of a study using automated GP data is that information on disease and exposure are gathered by GPs who are not aware of the research hypothesis at the time of registration. Hence recall bias or other types of information bias are not very likely in this study. To avoid observer bias we conducted a review of the patient profiles which was blinded to exposure status. Another important aspect concerning the validity of follow-up studies with automated data resources is the proportion of unidentified eligible cases (false negatives) through the initial computerized search. We have tried to minimize this problem by performing not only a search on a wide range of ICPC-codes but also a text string search in the database. This explains in part why only 22 out of 97 possible cases passed the validation procedure. In the IPCI-project information is gathered only from GPs who are fully automated and do not use paper resources. Even if cases of tendinitis have been misclassified, misclassification was probably random. Hence, this will not affect the RR in a cohort study but might have some effect on the risk difference. Confounding by indication in this study is not very likely, as there was no association with indication, and because urinary-and respiratory tract infections are not a risk factor for tendinitis.

Apart from several case reports [1–7], a large case series in France reported on 100 cases which had been notified between 1985 and 1992 [10]. The Achilles tendon was affected in 96 patients and tendon rupture occurred in 31 persons. The average time between the start of the treatment and the onset of the symptoms was 13 days (range, 1–90 days). Long-term corticosteroid therapy was an associated risk factor. Pierfitte estimated the incidence rate of tendinitis among fluoroquinolone users at 15–20 per 100 000 prescriptions [11]. Others concluded that there was no increased risk of Achilles tendon rupture to ciprofloxacin [12]. In a study with prescription-event monitoring, the frequency rate of tendinitis, tenosynovitis or tendon rupture was 1/11 000 patients for ciprofloxacin, 3/11 000 patients for norfloxacin and 11/11 000 patients for ofloxacin, respectively [13]. Although the relatively high rate with ofloxacin is in line with our results, the incidence in our study is higher.

The pathophysiological mechanism linking tendinitis to fluoroquinolones remains unknown. Experimental data are restricted to cartilage injuries in immature animals [14, 15]. Some authors described the histological findings in damaged Achilles tendons and considered these changes to be due to an ischaemic process [16]. Other have considered the tendon disorders to be caused by a toxic effect on collagen fibres [17]. Furthermore, a role of mechanical factors has been suggested [18], and an autonomic nervous system disturbance or immuno-allergic phenomenon cannot be excluded [16].

Although the findings of our study support the hypothesis that fluoroquinolones are associated with tendinitis, definite conclusions should be drawn cautiously. Numbers of patients with tendinitis in our study are relatively small and follow-up is limited to only 2 years. In addition, the 95% confidence intervals of the risk estimates of the different fluoroquinolones do not differ significantly. Nevertheless, our results indicate that ofloxacin is strongly associated with Achilles tendinitis.

In conclusion, our results suggest that the risk of Achilles tendinitis to fluoroquinolones, especially ofloxacin, is higher than the risk to the other antibacterial drugs. To our knowledge, this is the first epidemiological study which demonstrates an increased risk. It should be emphasized, however, that the absolute numbers in our study are small and that an extra number of cases of Achilles tendinitis of 15 per 100 000 days may be acceptable when prescribed for severe infections. References 1.Huston, KA. Achilles tendinitis and tendon rupture due to fluoroquinolone antibiotics. N Engl J Med. 1994;331:748. [PubMed] 2.McEwan, SR; Davey, PG. Ciprofloxacin and tenosynovitis. Lancet. 1988;2:900. [PubMed] 3.Pierfitte, C; Gillet, P; Royer, RJ. More on fluoroquinolone antibiotics and tendon rupture. N Engl J Med. 1995;332:193. [PubMed] 4.Ribard, P; Audisio, F; Kahn, MF, et al. Seven Achilles tendinitis including 3 complicated by rupture during fluoroquinolone therapy. J Rheumatol. 1992;19:1479–1481. [PubMed] 5.Szarfman, A; Chen, M; Blum, MD. More on fluoroquinolone antibiotics and tendon rupture. N Engl J Med. 1995;332:193. [PubMed] 6.Zabraniecki, L; Negrier, I; Vergne, P, et al. Fluoroquinolone induced tendinopathy: report of 6 cases. J Rheumatol. 1996;23:516–520. [PubMed] 7.Donck, JB; Segaert, MF; Vanrenterghem, YF. Fluoroquinolones and Achilles tendinopathy in renal transplant recipients. Transplantation. 1994;58:736–737. [PubMed] 8.Hooper, DC; Wolfson, JS. Fluoroquinolone antimicrobial agents. N Engl J Med. 1991;324:384–394. [PubMed] 9.Lamberts, H; Woods, M. International Classification of Primary Care. Oxford: Oxford University Press; 1987. 10.Royer, RJ; Pierfitte, C; Netter, P. Features of tendon disorders with fluoroquinolones. Therapie. 1994;49:75–76. [PubMed] 11.Pierfitte, C; Royer, RJ. Tendon disorders with fluoroquinolones. Therapie. 1996;51:419–420. [PubMed] 12.Shinohara, YT; Tasker, SA; Wallace, MR; Couch, KE; Olson, PE. What is the risk of Achilles tendon rupture with ciprofloxacin? J Rheumatol. 1997;24:238–239. [PubMed] 13.Wilton, LV; Pearce, GL; Mann, RD. A comparison of ciprofloxacin, norfloxacin, ofloxacin, azithromycin and cefixime examined by observational cohort studies. Br J Clin Pharmacol. 1996;41:277–284. [PubMed] 14.Corrado, ML; Struble, WE; Peter, C; Hoagland, V; Sabbaj, J. Norfloxacin: review of safety studies. Am J Med. 1987;82:22–26. [PubMed] 15.Kato, M; Takada, S; Kashida, Y; Nomura, M. Histological examination on Achilles tendon lesions induced by quinolone antibacterial agents in juvenile rats. Toxicol Pathol. 1995;23:385–392. [PubMed] 16.Jorgensen, C; Anaya, JM; Didry, C, et al. Arthropathy with achilles tendon involvement induced by pefloxacin. Apropos of a case. Rev Rhum Mal Osteoartic. 1991;58:623–625. [PubMed] 17.Franck, JL; Bouteiller, G; Chagnaud, P; Sapene, M; Gautier, D. Rupture des tendons d’achille chez deux adultes traites par pefloxacine dont un cas bilateral. Rev Rhum Mal Osteoartic. 1991;58:904. [PubMed] 18.Blanche, P; Sereni, D; Sicard, D; Christoforov, B. Tendinopathies achileennes induites par la pefloxacine. A propos de 2 cas. Ann Med Interne (Paris). 1992;143:348. [PubMed] Davidtfull (talk) 01:50, 18 February 2009 (UTC)

Thanks David, a good ref, some good quality data.-- Literature geek |  T@1k?  02:14, 18 February 2009 (UTC)

Vigamox
There are some that seem to say "it's only eye drops". Eye drops is medicine. What we are seeing here is that different medicines are different. So a re-write is necessary to clearly cover the different side effects for different medicines (they are not all the same), toxicity, etc. Wikipedia is also balanced so the end product should not be that the reader thinks they will become psychotic and have orthopedic problems after taking a pill. This advice is to give the article some credibility. The way it is now is, intentionally or unintentionally, it looks like a angry and disgruntled patient's diary. Good luck on the rewrite. Some has already been done by someone else. Chergles (talk) 15:56, 17 February 2009 (UTC)

Rapid decay of good intro into the same mess as before
I'm quite disappointed in how the editors working here are rapidly causing decay of the introduction I used with proper references to something that is basically the same from which we started. I see many edits but little productivity here. --Steven Fruitsmaak (Reply) 18:53, 17 February 2009 (UTC)

I did fix data on odds ratio and relative risk, some good edits have been done. :--) I was disappointed with some of the deletions as well. Some good data on risk factors was deleted. I don't think that we can avoid saying that severe reactions are anything more than occasional due to lack of citations provided by those protesting. The only citations showing high rates are in the debilitated like organ transplant patients and so forth or other high risk groups. I would have thought that high risk groups for toxic reactions info is valuable encylopedic information for the reader and the health professional but some of it was deleted.-- Literature geek |  T@1k?  19:57, 17 February 2009 (UTC)

How about you make some edits to the lead and then we take it from there? The sooner we get the neutrality issues resolved the better.-- Literature geek |  T@1k?  22:09, 17 February 2009 (UTC)

Perhaps part of the problem is the citations Dr. Steve had used to support the opening statements, as they fail to support the premise presented, to wit:

This is the first citation that Dr. Steve referenced:

Iannini PB (June 2007). "The safety profile of moxifloxacin and other fluoroquinolones in special patient populations". Curr Med Res Opin 23 (6): 1403–13. doi:10.1185/030079907X188099. .

This article states that: “Overall, fluoroquinolones have predictable and mild-to-moderate adverse-event profiles and are generally well tolerated.” This is a “net opinion” with no reference as to how this decision was reached or what it is being based upon. It is of no value as a reference in support of the statement that “Although quinolones are generally considered to have a relatively moderate adverse drug reaction profile...” It appears in my opinion that this will prove to be a propaganda piece in support of moxifloxacin as I believe when the full text is reviewed that (“should lead to better antimicrobial agent selection”) the selection being referred to here will no doubt be moxifloxacin. I may be wrong so I will wait till I can review the full text before making a decision.


 * It is the conclusion of a review in a peer reviewed journal, this is the kind of evidence we should use based on WP:RS. I don't have any reason to suspect that it is a propaganda piece; are you going to say this about all reviews? --Steven Fruitsmaak (Reply) 21:24, 18 February 2009 (UTC)


 * No, just those that are used to market a specific drug to a specific audience, rather than present an unbias review. Just those that show a bias towards one drug over another without peer reviewed double blind studies that support such a view.  Those that fail in this I will state to be propaganda if the text warrants such an accusation.  If it does not, then I will not.  Again, had the full text been available to me then I would have been in a position to judge fairly.  Since it was not I expressed my opinion and even stated that I may be wrong in the above case.Davidtfull (talk) 02:44, 19 February 2009 (UTC)

“Fluoroquinolones, are associated with rare, but clinically important, adverse events in special patient populations (including the elderly; those with hepatic, renal, or glycemic disorders; and those at risk for cardiovascular events).”

Yet again a net opinion as no reference as to how these reactions were determined to be “rare”. Stating that something is “rare” without citing to what methods were employed that actually proves this statement is referred to in the legal circles as a “net opinion”. We find no citation to professional standards or customs that point to establishing the existence of a standard by which this conclusion was reached. We only find that they did a search on pubmed for articles and may have parroted what these other articles may have stated. The full text of this citation should be available so that we can determine how the authors arrived at this conclusion and whether or not the conclusion reached was valid. However this is yet another “pay to view” article when googled. If someone has the full text please be so kind as to send me a copy via my email.

The second citation used by Dr. Steve also does not support the premise

Owens RC, Ambrose PG (July 2005). "Antimicrobial safety: focus on fluoroquinolones". Clin. Infect. Dis. 41 Suppl 2: S144–57. doi:10.1086/428055. .

Once again Dr. Steve is using a “pay to view” article to support his statements.


 * First of all, I'm not a doctor and I would prefer if you change your tone. Second of all, Clin. Infect. Dis. is a top-notch peer reviewed journal in the field of infectiology, it is an excellent source to use. Yes, unfortunately it is payable; most quality sources are, and I used all the reviews I could find on this topic, so there's really no bias or hidden agenda. Third, the statements were adequately supported by the references, your case arguing that they don't support the sentences is clearly wrong because they are almost litteral quotes. --Steven Fruitsmaak (Reply) 21:24, 18 February 2009 (UTC)


 * The references were not made available as you did not post a link to the full article. This is what I considered to make them invalid.  There was no method made available to verify your statements.  I do believe that there are more than two reviews on this subject.  If you used all the reviews, where are the rest of them?  You cited to two articles within that opening statement.  As you had bought these papers then please make them available for others to read.  Perhaps then you would not have been challenged.  More to the point I did NOT edit anything within the opening statement.  If you think that I had you are seriously mistaken.


 * You state that you are NOT a doctor. Duly noted.  Quid pro quo would require that you change your tone as well.  I am not your enemy here and I believe I have bent over backwards to remain both civil and courteous to you throughout this entire dicussion.  Why then would you believe I have been anything BUT civil to you?  I would PREFER that you do not consider yourself to be superior to me and bring such arrogance to the table, as I do not consider myself to be superior to you.  We are both equals and I would appreciate it if you would treat me with the same respect that you are now demanding.  You had stated that you were soon to be starting a medical practice, as such it was NOT disrespectful to refer to you as "Doctor".  It is a title you had spent a small fortune on to achieve.  It was not meant to be disrespectful.  It was meant to indicate your level of inteligence regarding these issues.  Had I put that title in quotes then perhaps your complaint would have some substance.  AS that would have been an indication of displeasure, not respect.  I believe you are protesting too much here over a percieved slight where none existed in the first place.

“The currently marketed quinolones are well tolerated, with safety profiles similar to those of other antimicrobial classes.” It is obvious that this statement is false. No other antibiotic is associated with spontaneous tendon ruptures that I am aware of.


 * A safety profile is a general assessment. Further down the intro, it was stated that there were specific side effects which are more common than others, like musculoskeletal, and tendon rupture was amply stressed. Furthermore, if you find any quality references that state the opposite, please provide them instead of saying "I know this for a fact". --Steven Fruitsmaak (Reply) 21:24, 18 February 2009 (UTC)


 * "with safety profiles similar to those of other antimicrobial classes"

The key word here is "similar". There is nothing similar between the two clases of drugs concerning tendon rupture, toxicity to mammalian cells, and the number of drugs removed from clinical practice due to toxicity issues. This would make the quinolone class, and its safety profile distinct, not similar. I do not wish to get into a citation war with you. It is aggravating enough that you would use a citations where you cannot read the whole paper, just the abstracts. But to appease you please refer to: The Cohen study, the 60 day cipro study, the 62 Meeting of the Anti-Infective Drugs Advisory Committee, as well as ( [PubMed - indexed for MEDLINE]) where it is stated that "the quinolone is highly toxic to mammalian cells in culture" for starters. I do not believe that the other antimicrobial classes have been shown to be toxic to mammalian cells and associated with spontaneous tendon ruptures, but then again I may be mistaken. If so please cite to where it is stated that other antimicrobial classes are toxic to mammalian cells and associated with spontaneous tendon ruptures. Or for that matter what other antimicrobial classes carry BLACK BOXED WARNINGS concerning tendon ruptures? NONE that I am aware of. How many other antimicrobial classes are associated with 50% of the marketed drugs within any specific class having been removed from clincal practice due to toxicity issues? As such it is reasonable to declare this to be a fact without providing a dozen of citations that repeat common knowledge. The two classes do NOT have similar safety profiles, generally speaking of course. The additional warnings and fifty percent failure rate due to toxicity issues, and the demonstrated toxic to mammalian cells should be sufficent proof of this all in itself. Without me providing the citations you have requested.Davidtfull (talk) 02:44, 19 February 2009 (UTC)

“Overall, discontinuation rates from clinical trials were <4% for the currently marketed quinolones.” Again a false statement:

The overall discontinuation rates found with the six studies for levaquin (NDA for levaquin) are as follows:

293/11	3.8% 329/12	3.5% 187/30	16% 248/18	7.5% 295/44	15% 264/31	12%

Mean average 9.63% this is considerably higher than the <4% being cited above. More than double. This may be the reason another editor decided to change the opening statement. The citations used do not support it.Davidtfull (talk) 03:05, 18 February 2009 (UTC)


 * I don't know where you got that information, I just cited the article. --Steven Fruitsmaak (Reply) 21:24, 18 February 2009 (UTC)


 * That information came directly from the studies submitted with the NDA (circa 1996) for levaquin. Which any reasonable person would assume to be the best possible studies that Johnson and Johnson had to offer.  They are readily available on line at the FDA site:

http://www.accessdata.fda.gov/scripts/cder/drugsatfda/


 * Just do a search for levaquin and review the drug's history. The NDA is at the bottom of the history list, and then review the STAT documents.  You will find similar stats within the other drug's NDA studies as well.  As such, stating that the mean average for drop out rates found within the clinical studies is <4% (discontinuation rates )is not supported by the studies found within the NDAs, which contrary to what these authors had stated.Davidtfull (talk) 02:44, 19 February 2009 (UTC)

Those stats aren't relevant to this article, but if can be cited to a reliable source might be relevant to the levofloxacin article. I think though we don't need to mention discontinuation rates in this article and article is too big too be adding more data to anyway.-- Literature geek |  T@1k?  01:00, 19 February 2009 (UTC)

It looks like we have reached a reasonable compromise between both sides of the argument. Special thanks to LiteratureGeek and Mccready for their unbiased edits. Because of this, I believe we can do away with the Neutrality notice for now. JamesLockson (talk) 11:03, 18 February 2009 (UTC)


 * Clearly not, the introduction as I read it just now is entirely, 100% negatively biased. Please don't remove the tag before you have actually addressed any concerns. --Steven Fruitsmaak (Reply) 21:24, 18 February 2009 (UTC)

Is there a review article on the safety and tolerabilty of fluoroquinolones which you would prefer to use as a citation? Would you prefer to use this article which says that the discontinuation rate was 9.63%? Please find a good secondary source which you feel is least biased from your point of view and bring it to the talk page for discussion.

Is there a paper that questions the overall safety of fluoroquinolones or even that they are controversial?

You are not going to get very far without citations or saying which citations you would prefer were used.-- Literature geek |  T@1k?  12:53, 18 February 2009 (UTC)

I added back some data. I included adding back discontinue if hypersensitivity occurs. I looked into that a bit more and they (medical guidelines) were talking about anaphylaxis, ie allergy. I don't see any benefit or reason removing the warning to discontinue if signs of allergy develop. Infact I think that it would be unethical. Hypersensitivity is due to the immune system attacking itself eg anaphylaxis or over-reacting (eg anaphylaxis) and is not a direct toxicity of fluoroquinolones by definition although fluoroquinolones can like other allergens induce such a reaction which may be life threatening hence why I think we should leave the discontinuation warning. I added back some of the material regarding interactions and at risk groups that Dr Steve had initially added that was deleted and I reworded it. I do not think that that material should have or needed to be deleted but perhaps just needed reworded and tweaked, which I have done with a few small corrections. I think the way the "background" section is now is approaching a more neutral state now. Any views?-- Literature geek |  T@1k?  19:51, 18 February 2009 (UTC)

Hello Steve, I was thinking the only way that we can achieve neutrality is to quote the review paper saying that they have been reviewed and found to have a mild to moderate safety profile,,,,,,. Then add,, However,, This is disputed with a number of law suits launched and legal action by consumer groups who dispute that fluoroquinolones are as safe as claimed. ,,, then add a citation. That way the reader will hear both sides of the "controversy" without bias. We need to eliminate bias from the introduction I agree and I feel this is the only way we can resolve this.
 * Actually, I think this is an excellent suggestion. --Steven Fruitsmaak (Reply) 21:58, 18 February 2009 (UTC)

Clearly there is dispute over he safety profile when you have class action suits and national consumer rights groups petitioning the government in the USA. Public Citizen was set up by Ralph Nader, who has run for president of USA a number of times, certainly a notible organisation who don't take on cases for the fun of it. He was one of the first people who lobbied and took legal action to state that benzodiazepines could cause withdrawal symptoms when the vast majority of the medical profession thought no withdrawal could happen.
 * The fact that there is a lobby should not influence Wikipedia in any way, imho. There is a lobby supporting pedophiles, there is a lobby that says that vaccines cause autism. Minority viewpoints should not be treated the same per WP:NPOV. However, in an article discussing a controversy, there is room for views of both parties, and what you suggest would be a great way to solve things. --Steven Fruitsmaak (Reply) 21:58, 18 February 2009 (UTC)

Here is one class action law suit with multiple litigants. I think that one of the problems are allegations that drug company clinical trial data has been watered down in their favour so all reviews are going to be using a large amount of their data on safety profile from drug company clinical trials. I remember resolving a dispute on temazepam tolerance when conflicting papers stated opposite things by citing "controversy" and citing peer reviewed bias in clinical trials for hypnotics. See Temazepam. Maybe we can resolve dispute here similarly as suggested?-- Literature geek |  T@1k?  21:51, 18 February 2009 (UTC)

Glad that you liked my suggestion. I have made some edits. Yea but the lobby group is a very respected one in USA. For example Public Citizen were the ones that fought the car industry and got seat belts in cars. They (or was it Ralf Nader the founder of Public Citizen before he set up that org) also were the group that got package inserts for added to drugs in USA. Read up about Ralf Nader and Public Citizen. They aren't fringe per se, granted they aren't peer reviewed scientists but Ralf Nader and Public Citizen have done a lot of high profile campaigns and are often vindicated and found to be correct in the end from what I can tell. Fair point there are all sorts of lobby groups (even pedophiles) for almost anything. As for vaccines, I have read a bit about the mercury autism vaccine controversy. I dunno enough about them to have a firm opinion but I think they are overused with many vaccines for many infections which have a very low death rate. So probably I think vaccines should be reduced and/or delayed until a child's blood brain barrier is more fully developed to avoid unnecessary exposure to mercury and controversially possible toxicity. Many vaccines don't need to be given as soon as a child is born from what I have read. Have we triggered another debate? I hope not! :=)-- Literature geek |  T@1k?  23:48, 18 February 2009 (UTC)

Ok, I have made some edits towards neutrality. I seriously recommend that people accept the edits to the introduction section which I made towards neutrality. We can of course discuss wordings tweak things, fix any errors in wordings if people spot any inaccuracies or whatever. I have left a request on David's talk page so we may or may not be able to track down some better citations than the current ones on the safety issues of quinolones. I know David you might think we are being harsh but I have to say that now Steve has compromised I am in agreement with him in how we need to resolve the dispute. I will suggest to you that you accept the neutrality of having both the peer reviewed review cited as well as your side of the argument cited in the intro. I can assure you that if a representative of Bayer shows up and challenges an unneutral article they will not be as reasonable as Steve and myself and you are unlikely to get as satisfactory result wwhen resolving neutrality with a drug representative, so it is better to resolve the neutrality with senior editors and wiki pharm administrators than to wait a few weeks or months until someone who really does have a conflict of interest disputes neutrality. It will only back fire if you have a 1 sided article in a journalistic rather than encyclopedic tone as such an article WILL eventually be challenged by drug company reps. I have got into disputes with people who I strongly suspect are from drug companies so I speak from personal experience. Check out a before dispute and after dispute on temazepam to see what I mean with special attention on history, dependence and abuse epidemic sections. I didn't do much editing to the temazepam article and was not responsible for the poor use of citations and unencyclopedic tone but got drawn into the dispute on that page anyway. Most of the editors work on temazepam page ended up getting deleted after months of disputing back and forth. Check paroxetine talk page and review edit history for an example of what happens if neutrality is disputed by drug companies.-- Literature geek |  T@1k?  23:59, 18 February 2009 (UTC)


 * As I had noted I have declared a COI regarding the introduction, and as such I HAVE NOT and will not be editing any part of that. But I see no problem with Steve's suggestion in the least. Sound reasonable to me.  It appears what has been suggested is fair and about as unbias as we can hope for.  My concern is, and will continue to be, is the fact that we have no real way to state an opinion as fact.  But I see no reason why we cannot state two oppossing opinions provided that the citations used are balanced, if we clearly note that these are opinions and not factual statements to be relied upon by anyone, either the physician or the patient, or the casual reader.  This has been my position from the beginning of this dispute regarding the presentation of risk.  It is one thing if someone does a study, declares the manner in which the study was done, provides the raw date used, provides access to the full paper and the citations relied upon, and THEN presents the results of the study.  The results then can be considered factual in nature, unless an error of some sort is found.  One plus one equals two in that situation and anyone can check the math.


 * But a net opinion, where someone were to state "I reviewed a dozen or so papers and have arrived at the conclusion that ALL the quinolones are relatively benign..." would not be considered factual in nature. They keyword here is the use of "ALL".  It is an opinion based upon a significantly limited amount of information.  Older reviews that state this are useless as a number of these drugs were not even on the market at that time.  Yet another reviewer may view the same data and arrive at the conclusion that ALL quinolones are toxic and dangerous.  Yet again, another net opinion.  BUT if the person were to state that "within these twelves studies", and then list the studies used, "it was found that the quinolones APPEAR to be benign, BASED UPON THESE TWELVE ARTICLES", then this would be a factual statement.  As the contents of the 12 articles either support the statement made or it does not.


 * As such if we are to state specific percentages, then we need a study of patients that arrived at that particular number, not someone's review of the available liteature. As the liteature being relied upon may NOT be valid to begin with, and if the permise is not valid then the results cannot be stated as a fact.  Peer review, though useful, is not infallable.  There are any number of commercial sites available that I can submit an article to, state my desired results, and have the article peer reviewed by physicians to support the paper.  Expensive and unethical, no doubt.  But done all the time.


 * So within the introduction if it is the concensus that we may be stating all inclusive statements, as well as percentages, then the citations used to present EITHER VIEW, should be clinical studies, or case history studies, NDA's, etc. NOT net opinions.  If we can do this then I think we have the beginings of a fair presentation that we all can live with.   As such I am more than willing to search my archives for citations that meet this criteria, post the citations and the links to the full papers, and let others decide what would be appropriate to use.


 * If reference to the specific adr sections, I do not think such strictness is required. As we are only attempting to show an association.  Either the association exist, or it does not.  We are not attempting a risk/benefit discussion. Here again though, if a study shows percentiles, and the data used for the study supports the percentiles, then such a reference can be made.  But again, the numbers found within a liteature review should only be used as a supplemental citation, and the reference to specific numbers found therein should be avoided, unless stated as the authors opinion.  Is this something we all live with?  Or is there something more that needs to be discussed?


 * On a side note Ralph Nader no longer has anything to do with Public Citizen. Public Citizen is now ran by Dr. Sidney Wolfe and has been for about twenty five years now I think, perhaps even longer.  As he is a well respected physician and has a staff of physicians as well, who work on the petitions and lawsuits filed by Public Citizen I would not consider Public Citizen to be a "fringe" group by any means.  The drug companies hate him with a passion.  He also sits on one of the advisor y boards at the FDA. As such I think we can consider him to be a valid player regarding these issues.Davidtfull (talk) 02:44, 19 February 2009 (UTC)

regarding the current intro
May I suggest we use the full names rather than hyphenate them? i.e. : levofloxacin (levaguin), ciprofloxacin (cipro) and moxifloxacin (avelox) This would make it easier on the reader to then go to the seperate article for each drug. Not everyone reading the article would be aware that avelox and moxifloxacin are one and the same, or levofloxacin and levaquin. Davidtfull (talk) 04:55, 19 February 2009 (UTC)

Garbage
This article is currently garbage. The references due not support what is written in the lead. Will start working on getting it to some semblance of reality. What the references refer to are adverse events rather than true toxicities but that is a side point.

We start by talking about all the severe events this drug can cause and then the references talk about tendon problem! THIS IS DISHONEST and whoever added this should be ashamed. Will fix some of the most gross errors.-- Doc James (talk · contribs · email) 08:19, 19 February 2009 (UTC)

Doc, it was me who wrote it, I haven't added very much data to this article, mainly I have been playing piggy in the midddle between the two disputing parties. I will explain why I added those refs, Steve put "citation needed" beside is the

"syndrome of long term[5] adverse effects."

soooo I provided a citation of a long term effect,,,,, tendon damage

Steve put citation needed beside this sentence

Adverse reactions may manifest during, as well long after fluoroquinolone therapy has been discontinued.[8]

sooooo I provided a citation of delayed tendon rupture as an example.

There was absolutely nothing that I can see dishonest in those edits or are you talking about some other part I am missing?

I don't think accusations of people being dishonest and being shamed is the right way to approach things especially as I think that you are wrong in your accuations (unless you are talking about a different part of the article)?-- Literature geek |  T@1k?  08:54, 19 February 2009 (UTC)


 * My apologizes literature. What was there needed to be removed.  You did not add it so my accusations are not directed at you.  The line I have serious concerns with is "serious adverse reactions (including blindness, psychosis, brain damage and death) which can occur from use of fluoroquinolone antibacterial drugs" and than the references refer to tendon problems.
 * The wording as it was misleads the reader. Hope the new changes are acceptable to people.-- Doc James  (talk · contribs · email) 09:08, 19 February 2009 (UTC)

Okie dokie no problem. Blindness, psychosis and death are possible adverse reactions of fluoroquinolones but having them in the lead as the first sentence worded like that was causing neutrality issues. One of your recent edits I disagree with. Your addition of overdose data now makes it sound like seizures occur only in overdose. Firstly especially as the article is now adverse events I don't think that overdose info is relevant to this article, perhaps relevant to the drug overdose article as a small entry. At the moment it is misleading as Government medical guidelines (MHRA) give a UK equivalent of a black box warning for seizures which can occur in people with or without a history of them. It appears in the British National Formulary. I think that needs changing. If you trust my editing (I feel I have been reasonably neutral on editing this article) I can start working on this article with you. I do have a moderate knowledge of the literature on quinolones and antibiotics in general.-- Literature geek |  T@1k?  09:22, 19 February 2009 (UTC)


 * Yes I agree that probably eventually acute overdose info should be moved to it owns article. Goldfrank's is the leading book of medical toxicology.  You can get access to a limited view thru google books.
 * Happy to have your help editing. Uptodate is also a great source which I can get you access to if you are interested.  This article needs a complete rewrite.  It make it seem that all these exceeding rare events are common place with floroquinolones.  The biggest concern with this drug group is its interaction with warfarin ( I have had one person die from this complication ).  But that is a drug reaction and the death was due to human error rather than an intrinsic property of the drug.  I see hundred of people on these drug and almost never see complications.  I have seen one tendenopathy that resolved sponaneously.-- Doc James  (talk · contribs · email) 09:30, 19 February 2009 (UTC)

Well here are my honest views, I do not believe that 5% of people are getting tendon tears or 20% or whatever go psychotic on fluoroquinolones or whatever. I do not believe they have a mild side effect profile. They are 2nd behind clindamycin for causing C difficile for one and some hospitals and antimicrobial experts recommend now avoiding them whenever possible. I do think the type of adverse effects can be severe and for some people causing mental or physical disability lasting months or in severe cases years or even permanent, how common this is I dunno. I believe probably aminoglycosides would have "uncommon" severe adverse effects (ototoxicity, nephrotoxicity) of 1 or 2% perhaps(?) but they are severely restricted due to the fact they can cause long term or permanent damage. So I dispute the adverse effect profile more because of the severe consequences uncommon or not of fluoroquinolones. I do believe that often adverse effects are not connected to the patient, eg misdiagnosed with fibromyalgia, insomnia, anxiety, old age etc etc rather than FQ adverse effect. If you had an old lady and she developed muscle pain, insomnia and anxiety, you might diagnose flu symptoms and age related anxiety being in hospital environment. I have a next door who was on steroids and prescribed antibiotics and soon after his tendons or ligaments blew apart in his ankles and the doctors just said "they have no idea why it happened", they didn't attribute it to his antibiotic use. I have another neighbour who just finished a course of them and is perfectly fine. I know others who got CNS adverse effects. If the adverse effects were all acute and not potentially long lasting I wouldn't do anything more than add a list of adverse effects and move on editing elsewhere. We previously had a good secondary review article saying mild to moderate with uncommon severe adverse effects, then had a couple of sentences citing allegations of patient groups. I think we should add that back. Anyway time for me to join you editing. I do admit they are an important therapeutic tool and an effective antibiotic though. :=)-- Literature geek |  T@1k?  09:52, 19 February 2009 (UTC)

First of all, this article is NOT garbage. If you want to add something, REFERENCE it. DO NOT remove something just because you do not believe it. Of course these reactions are uncommon, but they obviously exist. I have to agree with Literaturegeek. Unless you see what these drugs can do in person, you will not believe it. JamesLockson (talk) 10:24, 19 February 2009 (UTC)

All of your page moves and reverts certainly aren't helping things James. I am about ready to just walk away from this article. People either want to draft the drug up like tetracycline based on manufacturer guidelines and the other people want to draft it up as pure evil and inflate the harm or number of people harm drastically above anything verifiable. I wanted things put into reality most people don't get severe long term adverse reactions but some people get them and they can cause long term disability, cite both sides but people either wanted a Foxnews or MSNBC journalistic hit peace or they want an official viewpoint from the manufacturers from a text book. There is not going to be a compromise, no middle ground. I am not in the mood to get involved in an edit war. I can't work anymore on such a controversial article with such opposing views. No harm to anyone, I actually like all of the editors here, which is why I think that I need to back away.-- Literature geek |  T@1k?  11:13, 19 February 2009 (UTC)

Moved
Moved the page to Adverse effects of fluoroquinolones. This is how Goldfrank's toxicology describe them. Less emotionally charge than toxicity and more NPOV.-- Doc James (talk · contribs · email) 08:42, 19 February 2009 (UTC)


 * Also adverse events at therapeutic doses of a medication is not in clinical practice referred to as toxicity, it is referred to as an adverse event. see uptodate http://www.uptodate.com/online/content/topic.do?topicKey=antibiot/8621&selectedTitle=1~150&source=search_result#24


 * Otherwise the title would limit the discussion to acute overdose and two very rare complications: acute renal failure and seizures.-- Doc James (talk · contribs · email) 08:59, 19 February 2009 (UTC)

I don't mind the name change and was neutral on this.-- Literature geek |  T@1k?  09:01, 19 February 2009 (UTC)

Delayed reactions
This section was bashing physicians without proper reference. Was misrepresenting reference and was OR.-- Doc James (talk · contribs · email) 09:48, 19 February 2009 (UTC)

Mortality
This section referred to the FDA If someone could find the actually reference maybe but we have no context.-- Doc James (talk · contribs · email) 09:48, 19 February 2009 (UTC)

Case reports?
This article says that MSK problems are one of the most common side effects THAN back up the statement with a CASE report!!! Common on. This is enough to make a guy pull out his hair. Case reports are NOT a reflection of a common disease. And quoteing a bunch of case report is OR.-- Doc James (talk · contribs · email) 10:11, 19 February 2009 (UTC)

Next concern
"multiple skeletal events have been reported since 1972" and when is the ref from 1972. Therefore this statement does not muiple events since 1972 only events in 1972 from one fluoro that is not longer used.-- Doc James (talk · contribs · email) 10:14, 19 February 2009 (UTC)

All this references to the FDA
Show me the evidence so that I may verify. Removed till than.-- Doc James (talk · contribs · email) 10:15, 19 February 2009 (UTC)

Lots more case reports removed
This is NOT good enough evidence.-- Doc James (talk · contribs · email) 10:18, 19 February 2009 (UTC)

Another mislead ref
There has not been one year since 1983 Self explanatory.-- Doc James (talk · contribs · email) 10:18, 19 February 2009 (UTC)

This article is about human not rabbits
Reports of tendonopathy occurring hours after a single dose further suggest direct cytotoxicity. -- Doc James (talk · contribs · email) 10:24, 19 February 2009 (UTC)

Adverse effect need to be put into context
For example "The risk of tendon disorders with fluorquinone use is 3 cases per 1000 patient-years of exposure. Risk of tendon rupture is even less with only 38 of 46,000 people treated with fluorquinone suffering a rupture of the achillies. This is 1.9 times the rate seen in the general population. "-- Doc James  (talk · contribs · email) 10:52, 19 February 2009 (UTC)

Studies
Removing all animal studies and case reports.-- Doc James (talk · contribs · email) 11:09, 19 February 2009 (UTC)
 * The only evidence cited in the hearing damage section were case reports and animal studies, so I replaced it with something more tangible, like recommendations from the Australian Society of Otolaryngology Head and Neck Surgery. Also removed some plagiarism. Serrin (talk) 11:35, 4 March 2009 (UTC)

Starting over
I have decided to basically start over. Rewriting the entire article based on recent reviews of the human literature rather than case studies and animal studies present as though they represent the usual.-- Doc James (talk · contribs · email) 13:04, 19 February 2009 (UTC)

Reviews
If anyone would like a copy of some of the reviews please let me know and I would be happy to email you one. -- Doc James (talk · contribs · email) 17:44, 19 February 2009 (UTC)

This is a list of full reviews I have available:

-- Doc James (talk · contribs · email) 18:25, 19 February 2009 (UTC)

This review here on pubmed I think is less bias and is more indepth or here for full text which I found on david's site.-- Literature geek |  T@1k?  02:58, 20 February 2009 (UTC)


 * Sure will look at it. Thanks.-- Doc James  (talk · contribs · email) 03:23, 20 February 2009 (UTC)  This has some great info on drug interacts which I think should be added.  It does not go into as much depth about rates of side effect but is a reasonable source.  Would support a reference to psychosis.-- Doc James  (talk · contribs · email) 03:28, 20 February 2009 (UTC)

What happened to info on PN as irreversible condition?
I know that the goal of all this editing is 'neutrality' but I would like to understand why the info on PN being an irreversible adverse reaction was edited out. The drug manufacturers and FDA have published this info, and irreversible PN sounds like a serious life threatening condition that should be in the article. Here is a quote from the Cipro PI:

Peripheral neuropathy: Rare cases of sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias and weakness have been reported in patients receiving quinolones, including Ciprofloxacin. Ciprofloxacin should be discontinued if the patient experiences symptoms of neuropathy including pain, burning, tingling, numbness, and/or weakness, or is found to have deficits in light touch, pain, temperature, position sense, vibratory sensation, and/or motor strength in order to prevent the development of an irreversible condition.

I am sure there is evidence of irreversible and untreatable tendonitis and tendon rupture as well.


 * We are basing this on reviews. I have copies of the ones list above if you are interested.  Please provide a review and not a case report to support you point of view.  I have provided three reviews that support the exsistance of tendonitis and tendon rupture and quantify how frequently it occurs. -- Doc James  (talk · contribs · email) 20:04, 19 February 2009 (UTC)

Can these sources be used to document the fact about irreversible PN conditions as adverse effect? http://www.medscape.com/viewarticle/491670 http://www.fda.gov/medwatch/SAFETY/2004/jul04.htm Both are reliable sources, as well as the product insert.


 * Yes will add the info from the FDA. It does not however say that it is irreversible it says these drugs should be stopped to prevent if from becoming irreversible.  If you wish to add irreversible you will need to find another source.  Cheers-- Doc James  (talk · contribs · email) 20:26, 19 February 2009 (UTC)

I didn't change the wording on the info from the FDA or the product info sheets. They are very clear about the possibility of development of an irreversible condition, which has been reported and as you can believe is very debilitating. Sorry if I cannot find another source about this right now. Perhaps with your access to Medline etc. you can. Dbcipro (talk) 22:02, 19 February 2009 (UTC)

Dear Doctor Letters
The info on Dear Doctor letters is not controversy, but important information that speaks to the safety profile of these drugs. This info has disappeared as well. There is citable info from the FDA and Public Citizen. Any takers on putting this back? Dbcipro (talk) 21:58, 19 February 2009 (UTC)


 * This is in my opinion trivia. We do not list this sort of information for other drugs.  I get dear doc letters all the time for all sorts of medications.  I do not see that it adds anything to the article.  It is a list and not in encyclopedic form.  Doc James  (talk · contribs · email) 22:04, 19 February 2009 (UTC)

No case studies
Case studies are not enough evidence to tie the outcome to the effect of the drug. People become psychotic all the time for many reason and without a proper trial one does not know what is due to what. Will try to find better info over the next week.-- Doc James (talk · contribs · email) 00:32, 20 February 2009 (UTC)

The problem is I think that it is highly unlikely any drug company is going to fund a study into long term effects and a health bureaucracy isn't likely to either as they either have ties to industry or else simply don't want a public scandal. I think that there should be some leeway given and this paper should be cited at least in the controversy section. Also if your stance is correct that long term effects are rare they are not going to show up in clinical trials or will only show up as individual case reports in the literature or else reports to the FDA and the like. With serious rare cases the best evidence you will ever get is an analysis of case reports. I am opposed to misusing the ref above to apply any epidemiology statistics to it. I think it is ok to use if it is used just to describe long term effects and not their frequency.-- Literature geek |  T@1k?  01:39, 20 February 2009 (UTC)

Sometimes rules need to be bent or flexable as well. See WP:UCS. Following guidelines very strictly can sometimes be a hinderance to good production of an article especially one of controversy as this.-- Literature geek |  T@1k?  01:56, 20 February 2009 (UTC)


 * Yes I agree sometimes rules should be bent but I do not think this is a case of that. Quoting case studies give undue weight and attempts to debunk a review with a primary research ( and low quality primary research at that ).  We need either a review or the FDA discussing psychosis.  I have to teach tomorrow so might take me a couple days.-- Doc James  (talk · contribs · email) 03:15, 20 February 2009 (UTC)


 * Also if we just give long list of possible side effects without a frequency how do we know they are more common than base line? If you look at trial of placebos you see rate of adverse events are common  http://psycnet.apa.org/?fa=main.doiLanding&uid=1977-04006-001 .  This is why we need placebo controlled trials or case controlled trial at least.  Case studies are not good enough for a controversial topic especially when they contradict the reviews.-- Doc James  (talk · contribs · email) 03:21, 20 February 2009 (UTC)

The problem is the review data is mostly a review of short term clinical trial data. Using a review of short term clinical trials to debunk a review of case reports of long term harm is also an abuse of references in my opinion. 2 week clinical trial data can't be used to debunk a group of individuals suffering long lasting symptoms. What you need is a review of long term followup studies. At present that has never been done and likely never will be done due to most clinical trials or the research money being tied to drug manufacturers. You will probably never likely ever get the evidence base that you want. So what do we do? I think the controversy section and the FDA and swedish reviews of individual case reports of individual toxicities and the analysis of case reports is the best that can be done.-- Literature geek |  T@1k?  22:05, 21 February 2009 (UTC)

Individual symptoms can for the most part listed in reviews anyway, so I think that we can avoid probably entirely using case reports for individual symptoms. I have occasionally used case reports and used my common sense and knowledge of a drug and can usually tell if a symptom is rare and place it in the rare category, something like liver damage is obviously rare, if it was typical or even occasional it wouldn't be on the market, at least for not very long. Many side effects in a drug index that you doctors will refer to are not from epidemiology studies or clinical trials (because the side effect is so rare) and may not even be mentioned in any review but are there because of case reports submited to regulatory bodies or medical journals. I also think that we do not need to mention every single possible side effect either. I think if we end up on an article with a huge side effect list we can trim it accordingly to the most notable. Side effects from placebo are usually mild to moderate. You wouldn't get psychosis or seizures very often as a result of taking a placebo for example! I think these issues can be resolved easily either using common sense or using talk page and delete the irrelevant. As for psychosis or seizures I think it would be rare (1 in 100 or less).-- Literature geek |  T@1k?  22:29, 21 February 2009 (UTC)


 * Reviews are sometimes of the entire literature not just brief trials.-- Doc James (talk · contribs · email) 03:23, 22 February 2009 (UTC)