Examples of Outcome Reporting Bias in Vaccine Studies: Illustrating ...

What A Newly Banned Painkiller Tells Us About The Limits Of Endurance

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On January 1, 2024, a new World Anti-Doping Agency rule will kick in that officially bans tramadol, an opioid painkiller. It's been a long time coming: the abuse of tramadol has been an open secret in cycling, with rumors swirling about its use by Team Sky and British Cycling. "It kills the pain in your legs, and you can push really hard," former Team Sky rider Michael Barry claimed. WADA testing in 2017 found tramadol in 4.4 percent of all samples from cyclists, leading to worries that tramadol-addled riders would cause crashes in the peloton. For some athletes, like British soccer goalkeeper Chris Kirkland, tramadol was a gateway to full-blown opioid addiction. The International Cycling Union banned it in 2019, but WADA continued to take a wait-and-see approach.

The data that finally changed WADA's mind has now been published in the Journal of Applied Physiology, where it's free to read. A group led by Alexis Mauger of the University of Kent in Britain put 27 highly trained cyclists through a series of performance tests with either 100 milligrams of tramadol (a modest dose: Kirkland was taking as much as 20 times that amount at once) or a taste-matched placebo. The riders were, on average, 1.3 percent faster in a 25-mile time trial when taking tramadol. WADA's rules require that a substance fulfill two of three conditions to be banned: it enhances performance, has the potential to harm the athlete, and violates the spirit of sport. Mauger's data sealed tramadol's fate.

That's the simple part of the story. Or at least, the relatively simple part. Admittedly, previous studies of tramadol's performance-boosting effects have produced mixed results. Mauger and his colleagues argue that these previous studies have featured performance tests that weren't long or hard enough for pain control to matter, failed to exclude participants who had side effects like vomiting from the drug, or muddied the waters by having cyclists complete cognitive tests while they tried to race. It's also worth asking whether the benefits of a painkiller might be exaggerated in a test where the subjects are forced to fixate on their own discomfort, giving continuous ratings of exactly how much they're hurting, compared to the real world. Still, the new results make a strong case that tramadol boosts performance and should thus be banned. The harder question is why it works.

In 2010, Mauger published some remarkable data showing a 2 percent boost for cyclists taking a simple dose of Tylenol. He has followed up with other studies using various techniques like saline injections to manipulate exercise-associated pain. In Mauger's view, pain is one of the sensations that causes us to slow down or stop during endurance exercise, so the tramadol results make perfect sense.

Not everyone agrees, though. When I wrote about Mauger's research on pain in 2020, I noted that other researchers such as Walter Staiano and Samuele Marcora believe that subjective perception of effort ("the struggle to continue against a mounting desire to stop") is more important than pain ("the conscious sensation of aching and burning in the active muscles"). Staiano and Marcora have published some interesting data supporting their contention that we quit when effort maxes out, even when the pain we're experiencing is still tolerable. There may be ways of reconciling these two views: perhaps the cognitive effort of managing increased pain makes exercise feel more effortful, for example. But it's still an open debate, which makes any new data on the question particularly interesting.

And the details of Mauger's data, it turns out, are indeed curious. For starters, here are the five-mile splits for the tramadol (open circles) and placebo (closed circles) conditions in the 25-mile time trial:

(Illustration: Journal of Applied Physiology)

The tramadol riders are pulling ahead right from the first split, and continue to widen their lead throughout the trial. One interesting wrinkle: riders who scored higher on a psychological test of pain resilience—that is, those who felt they had better ability to regulate their emotions and thoughts about pain—tended to get a bigger performance boost from tramadol. To be honest, this is the exact opposite of what I expected: I would have guessed that those who struggle most with managing pain would get the biggest benefit from reducing it.

Immediately before the time trial, the cyclists did a 30-minute ride at a hard but steady predetermined pace, while rating their perceived effort every five minutes and continuously noting any changes in their perceived pain. Here's what that data looked like (pain above, effort or RPE below):

(Illustration: Journal of Applied Physiology)

Now we have a conundrum. Tramadol, an opioid painkiller, appears to have had no effect whatsoever on the pain experienced during cycling. On the other hand, it significantly lowered the perception of effort, which in turn—as predicted by Staiano and Marcora—improved performance. Mauger and his colleagues aren't sure how to explain this: they suggest that the continuous self-reporting of pain, as opposed to being asked about it every five minutes, might have made it harder to pick up small changes. I'm not sure what to make of this finding, but it reaffirms my sense that we still have a lot to learn about how pain and effort and other related constructs like mental fatigue influence our performance.

As for tramadol, its new status will end the longstanding ambiguity about its use. Nairo Quintana, the Colombian cycling star, tested positive for tramadol—twice—during the 2022 Tour de France, and was stripped of his sixth-place finish. But it was deemed a medical issue rather than a doping positive, since tramadol wasn't banned by WADA, and thus carried no suspension. Starting next year, any athlete caught using it won't be so lucky.

For more Sweat Science, join me on Twitter and Facebook, sign up for the email newsletter, and check out my book Endure: Mind, Body, and the Curiously Elastic Limits of Human Performance.

Tiny Homemade Injection Molder

With 3D printing continually gaining ground, some hackers might not see the need for traditional injection molding. After all, you can tweak the code or the model and print dozens of different iterations with fairly minimal lead time. Things get trickier when you need to print hundreds or thousands of the same thing and that ten-hour print time adds up quickly. [Actionbox] built a tiny injection molder they dubbed INJEKTO to speed up their manufacturing.

The design was optimized to be accessible as it is held together with brackets and cheap aluminum flat stock. The hardest part to source is the heating chamber, as it is a piece of turned aluminum. A PID controller keeps the temperature relatively stable and heats the plastic pellets you can dump in the top. Next, you'll need an external air compressor to power the dual 2″ pneumatic pistons. The pistons push the plastic out of the spring-loaded extruder nozzle. [Actionbox] is already planning on a second version with 4″ pistons that provide significantly more force to extrude larger amounts of plastic as the current version tops out at about 27 grams.

Injection molding still needs a heavy-duty mold to inject into, which can be hard to machine. So until we can 3D print an injection mold, this multi-head 3D printer is something in between a 3D printer and an injection molder, as it can print a dozen of the same thing, speeding up that print time.

Are Steroid Injections Safe And How Often Might I Need Them?

Dr. Christo answers the question: 'Safety, Frequency Of Steroid Injections?'

ByPaul Christo, M.D., Director, Pain Treatment Center, Johns Hopkins Hospital and Health System

— -- Question: Are Steroid Injections Safe And How Often Might I Need Them For My Pain?

Answer: Steroid injections can be safely used for the treatment of pain, but the drugs cause effects on several organ systems in the body. If you have medical conditions like congestive heart failure, kidney disease, or diabetes, you should alert your doctor before steroids are injected.

Steroids are often injected to reduce the pain associated with a herniated disc. This procedure is called an epidural steroid injection. Growing evidence suggests that spinal nerves become irritated by chemicals that are released by a herniated disc and that this irritation causes back and shooting leg pain or neck and shooting arm pain. Steroids inhibit these chemicals, reduce inflammation, and suppress abnormal firing from injured nerves. As a result, epidural steroids can help control the pain associated with a herniated disc.

Epidural steroid injections are more effective if your pain shoots from your back or buttock down your leg and past your knee. Or shoots from your neck down your arm, and if your pain has lasted for less than six months. Your response to the steroid injection should help dictate the number of injections you receive.

The beneficial effects of the steroid, that is improvement in pain and in level of function, decrease in time. Therefore, several injections may be needed. However, you should discuss the number of injections needed with your doctor.

Remember, the goal in using epidural steroid injections is to help reduce your pain, allow you to participate in physical therapy, and to assist you in resuming your previous level of activity.

Next: What Is A Trigger Injection And When Might I Need One?

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