14 replies to this topic

[YBC]

I don't know what to make out of this:

Abstract
OBJECTIVE: To evaluate the relation of topical tretinoin, a commonly used retinoid cream, with all-cause mortality in the Veterans Affairs Topical Tretinoin Chemoprevention Trial (VATTC). The planned outcome of this trial was risk of keratinocyte carcinoma, and systemic administration of certain retinoid compounds has been shown to reduce risk of this cancer but has also been associated with increased mortality risk among smokers. DESIGN: The VATTC Trial was a blinded randomized chemoprevention trial, with 2- to 6-year follow-up. Oversight was provided by multiple independent committees. SETTING: US Department of Veterans Affairs medical centers. PATIENTS: A total of 1131 veterans were randomized. Their mean age was 71 years. Patients with a very high estimated short-term risk of death were excluded. INTERVENTIONS: Application of tretinoin, 0.1%, or vehicle control cream twice daily to the face and ears. MAIN OUTCOME MEASURES: Death, which was not contemplated as an end point in the original study design. RESULTS: The intervention was terminated 6 months early because of an excessive number of deaths in the tretinoin-treated group. Post hoc analysis of this difference revealed minor imbalances in age, comorbidity, and smoking status, all of which were important predictors of death. After adjusting for these imbalances, the difference in mortality between the randomized groups remained statistically significant. CONCLUSIONS: We observed an association of topical tretinoin therapy with death, but we do not infer a causal association that current evidence suggests is unlikely. Trial Registration clinicaltrials.gov Identifier: NCT00007631

Any thoughts from the initiated?

Edited by YBC, 09 March 2009 - 02:36 PM.

[Ben]

Yes two:

"Post hoc analysis of this difference revealed minor imbalances in age, comorbidity, and smoking status, all of which were important predictors of death."

and

"but we do not infer a causal association that current evidence suggests is unlikely"

[kismet]

Honestly I wouldn't be surprised if there really was a minor increase in all-cause mortality. Vitamin A supplementation is strongly associated with mortality and retinoids, vitamin A derivatives, are systemically absorbed to some degree (although the absorption is very low). Add to that multivitamin use (already high in vitamin A and betacarotene) and we may see the tretinoin tip the scale.

However, considering that it's mostly high dose vitamin A supplementation which is associated with mortality and that twice daily application of tretinoin would result in sub-RDA vitamin A blood levels, I'm inclined to go with Ben-Aus on this one.

So take your vitamin D, apply tretinoin once daily and hope that Dr. Cannell is right (it's the vitamin D antagonism which makes vitamin A dangerous).

Edited by kismet, 09 March 2009 - 03:47 PM.

[immortali457]

My face is gonna look damn good lying in that coffin.

[Fredrik]

My face is gonna look damn good lying in that coffin.

Haha. Tretinoin and formaldehyde is the shit. Stalin is still looking good.


Researchers Unable to Find Causal Link Between Tretinoin and Mortality

MARY ANN MOON (Contributing Writer)


A recently reported association between topical tretinoin and increased mortality is not causal and most likely is due to chance, according to a recent report. The interim finding of an unexpected rise in lung cancer incidence and all-cause mortality prompted the premature halt of the Department of Veterans Affairs Topical Tretinoin Chemoprevention (VATTC) trial, a large 6-year study that was designed to determine whether the treatment could prevent basal and squamous cell skin cancers in patients who already had at least two such keratinocyte carcinomas.

Increased lung cancer incidence and mortality had previously been reported with systemically administered compounds closely related to tretinoin.

Dr. Martin A. Weinstock of the Providence (R.I.) VA Medical Center, and his associates in the VATTC trial conducted a post hoc analysis of the mortality data and confirmed an association with mortality—but no definitive causal links. "We do not conclude that this trial provides appropriate grounds for hesitating to use topical tretinoin in clinical practice," they wrote in the Archives of Dermatology.

In an editorial comment that accompanied the report, Dr. Lisa M. Schilling and Dr. Robert P. Dellavalle said that even though the investigators "chalk their results up as a chance finding," debate about the safety of topical tretinoin will probably continue. Until further evidence emerges to definitively establish the safety or harmfulness of the treatment, physicians should "at a minimum" discuss the VATTC results with their patients who use tretinoin cream—particularly with elderly men, who composed the bulk of the study population.

"This dialogue should include that the results of the VATTC may have been due to chance, but also that the outcome of death was not initially anticipated," Dr. Schilling and Dr. Dellavalle noted.

In addition, "owing to the ad hoc analysis, various important risk factors, such as smoking status, might not have been completely ascertained," they wrote.

In their post hoc study, Dr. Weinstock and his associates at six VA medical centers randomly assigned 566 patients to use tretinoin 0.1% cream on the face and ears once or twice daily, and 565 patients to use only the vehicle cream as a control. The mean patient age was 71 years, and 97% were men.

Six months before the scheduled end of the trial, the intervention was terminated because of a statistically significant excess of deaths at that time (82 deaths) in the treatment group, compared with the control group (53 deaths). More deaths were later identified, for a total of 122 in the intervention group and 90 in the control group.

The VATTC trial data showed no dose-response relationship between exposure to topical tretinoin and death risk, as well as no interaction between the medication and smoking in mediating mortality risk. Moreover, "we found it difficult to construct biologically plausible mechanisms that would explain a direct causal link … and we were unable to conceive of a plausible mechanism by which tretinoin could indirectly lead to a fatal outcome," they wrote (Arch. Dermatol. 2009;145:18-24).

That implausibility, together with "lack of specificity of causes of death, inconsistency with previous experience, weakness of other supportive evidence in our data, and weak statistical signal" led the researchers to their conclusions.

In their editorial comment, Dr. Schilling and Dr. Dellavalle of the VA Medical Center in Denver noted that, unlike other researchers, Dr. Weinstock and the VATTC investigators publicized their unexpected mortality data (Arch. Dermatol. 2009;145:76).

"We highly commend Weinstock et al. for reporting and highlighting these results," they wrote in their editorial.

Dr. Weinstock has received support from Galderma Laboratories L.P., Johnson & Johnson, and Ligand Pharmaceuticals Inc.




The trial does not provide 'appropriate grounds for hesitating to use topical tretinoin in clinical practice.' DR. WEINSTOCK


Source:
http://skinandallerg...700105/fulltext

Edited by Fredrik, 12 March 2009 - 08:16 PM.

[immortali457]

Ah the infamous Fredrik posts again. Just want to say I've learned alot from your posts. Dont be a stranger.

Edited by immortali457, 12 March 2009 - 09:24 PM.

[Bryce]

My face is gonna look damn good lying in that coffin.

lol.

[trance]

I don't know what to make out of this:

Abstract
MAIN OUTCOME MEASURES: Death, which was not contemplated as an end point in the original study design. RESULTS: The intervention was terminated 6 months early because of an excessive number of deaths in the tretinoin-treated group. Post hoc analysis of this difference revealed minor imbalances in age, comorbidity, and smoking status, all of which were important predictors of death. After adjusting for these imbalances, the difference in mortality between the randomized groups remained statistically significant. CONCLUSIONS: We observed an association of topical tretinoin therapy with death, but we do not infer a causal association that current evidence suggests is unlikely. Trial Registration clinicaltrials.gov Identifier: NCT00007631

Any thoughts from the initiated?

So far, no matter what one applies to one's face, death has always been the eventual end point ...

[niner]

Topical application of tretinoin caused me to quickly develop eczematous lesions in locations other than where I applied the drug. Maybe I had some cross contamination since I wasn't being super cautious when I tried it, but it looked like "action at a distance." Retinoids are potent compounds, and it would be hubristic to say that we fully understand every activity they have in all persons. So these guys took 566 old geezers, and had them apply 0.1% tretinoin once or twice a day? Holy crap. If I used .1% twice a day, I think I'd die too.

[TheFountain]

Topical application of tretinoin caused me to quickly develop eczematous lesions in locations other than where I applied the drug. Maybe I had some cross contamination since I wasn't being super cautious when I tried it, but it looked like "action at a distance." Retinoids are potent compounds, and it would be hubristic to say that we fully understand every activity they have in all persons. So these guys took 566 old geezers, and had them apply 0.1% tretinoin once or twice a day? Holy crap. If I used .1% twice a day, I think I'd die too.

Why is that? I've been using 0.1% for about 3 weeks with no noticeable side effects.

[kismet]

Systemic absorption is minuscle. The whole thing doesn't make any sense. If you're worried because of retinoids, don't supplement vitamin A (and don't eat no carrots).

[rephore]

Why is that? I've been using 0.1% for about 3 weeks with no noticeable side effects.
[/quote]

Just wanted to follow up. It's been several months now. Any improvements to the face after using the 0.1%?

I did an experiment with Retin A before. I asked about 100 people (mostly acquaintances or people that I just met who ask for my age, I tell them to guess it.) They are pretty much correct in guessing my age. Sometimes they'll guess older than what I really am.

Then I used Retin A for several months and did the same experiment. This time no one even guessed my real age or even older but I averaged 4 years younger than my real age. Retin A works and it works well.

[drunkfunk]

too bad it bleaches you to ghostly paleness

[immortali457]

too bad it bleaches you to ghostly paleness

Your in the minority in that dept.
It gives me nice rosey glow. As does it most people.

[tommix]

People should not forget that there is a war on nature gifts as this. Cause there is no better option from cosmetic companies, they can't make anything better. And with such low price as this. So you better be prepared for bullshit in "trials"... learn from history. Many good working and safe natural drugs was killed by FDA and national Cancer Institute. Many dirty technics was used to kill those things. We're talking about billions of dollars here so don't be surprise when someday Tretinoin become a cancerogenic :D

[offtopic]
This is like a flu... dies few people in the world from flu so USA forces vaccination and vaccination cause more deaths. Also people who gets vaccination - gives a flu to non vaccinated people. and this is what causes flu epidemics -the vaccinations.

Edited by tommix, 16 November 2012 - 10:41 AM.