RFK Jr. is a famous anti-vaxxer. How does this make him qualified for President?

I’ve written about the anti-vaccine movement and its many proponents more times than I can count. So why write about it again? Because one of them is running for President of the United States.

Robert Kennedy Jr. is famous for two things: first, he’s famous because he’s the son of a former Senator and the nephew of a former president. His father, Robert Kennedy Sr., served as Attorney General under President John Kennedy and then as a US Senator. Tragically, both JFK and RFK were assassinated in the 1960s, and RFK might very well have been elected president in 1968, as he was leading the Democratic field when he was killed.

Having a politician as one’s father does not qualify anyone for office, although many children of politicians use their famous name to win elections. That’s clearly what RFK Jr. is now hoping for.

But what RFK Jr. is really famous for now, and for the past 20 years, is something entirely different. As I wrote nearly a decade ago, Kennedy is obsessed with the notion that vaccines cause autism. He’s particularly obsessed with the thoroughly discredited idea that thimerosal, a preservative used in some vaccines, causes autism.

His efforts to convince people of the harms of vaccines landed Kennedy in the number two position on the infamous list of “The Disinformation Dozen,” This list, created by the Center for Countering Digital Hate, contains “the twelve anti-vaxxers who are responsible for almost two-thirds of anti‑vaccine content circulating on social media platforms.” Yes, this is what RFK Jr. has been focusing his energy on, at least until he decided to run for President.

Ten years ago, Kennedy published an entire book on this topic, called “Thimerosal: Let the Science Speak,” and he promoted it both in the press and in the halls of Congress. He had personal meetings with then-U.S. Senator Barbara Mikulski and Sen. Bernie Sanders to try to convince them to take action based on his claims. Why is it that a scientifically unqualified anti-vaccine advocate got a private audience with two U.S. Senators? Because he’s a Kennedy.

RFK Jr. gives hundreds of speeches a year, and up until the early 2000s, he spoke mostly on environmental issues. I heard one or two of his interviews during that era, and he was quite convincing. His usual argument was that large corporations were engaged in some kind of conspiracy to damage the environment so that they could increase their profits. That made sense to me!

But then he found the thimerosal issue and went completely off the rails. One example was a Salon.com and Rolling Stone article (jointly published in both magazines) that he wrote in 2005, which claimed not only that thimerosal-containing vaccines cause autism, but that “the government” knew about it and had been covering it up. Kennedy wrote that

“The story of how government health agencies colluded with Big Pharma to hide the risks of thimerosal from the public is a chilling case study of institutional arrogance, power and greed.” [quote from RFK Jr.]

Alarming-sounding stuff. The article was full of dramatic claims like this one. The only problem was, all of them were false.

To explain, let’s review what thimerosal is and why it has probably saved many lives. There was never a conspiracy because there was nothing to hide.

Thimerosal is a preservative that was used in many vaccines for decades. Why? Well, as I’ve explained before, early vaccines (back in the pre-WWII era) were administered from multi-dose bottles, in which bacteria would sometimes grow. In one particularly disastrous incident in 1928, 12 children in Australia died from staph infections after receiving the diptheria vaccine from the same multi-dose bottle. After the introduction of thimerosal, bacterial infections caused by vaccination virtually disappeared.

Why the panic from RFK Jr. and others about thimerosal? Well, it’s a mercury-based preservative, and RFK assumed (wrongly) that the tiny amounts of ethylmercury in vaccines caused autism or other neurological problems. One problem with this idea is that ethylmercury is very different from environmental mercury, which is called methylmercury and which can indeed be toxic. Ethylmercury is cleared from the body far more quickly–and the minuscule amounts in vaccines have never been shown to cause any harm.

But many anti-vaxxers, especially RFK Jr., have continued to spread alarming stories about vaccines (particularly through Children’s Health Defense, an organization founded by Kennedy), and a disturbing number of parents have withheld vaccines from their children because they didn’t know who to believe.

In the late 2000's, in an effort to address the concerns of anti-vaccine alarmists, a special U.S. vaccine court conducted three lengthy hearings in which the anti-vax advocates were asked to present their best cases. One of the cases focused specifically on the question: does thimerosal in vaccines cause autism? In that case, the judge concluded:

“The numerous medical studies concerning the issue of whether thimerosal causes autism, performed by medical scientists worldwide, have come down strongly against the petitioners’ contentions. Considering all of the evidence, I find that the petitioners have failed to demonstrate that thimerosal-containing vaccines can contribute to the causation of autism.”

As a lawyer, Kennedy should have been able to understand this. The science agrees with the court: in study after study, scientists found no link between thimerosal and autism or any other kind of neurological disorder. That should have been the end of the matter, but of course it wasn’t.

Furthermore, as RFK Jr knows, thimerosal was removed from childhood vaccines in the U.S. over 20 years ago, and the rate of autism diagnosis continued to rise after that. This fact alone contradicts his major claim: if thimerosal was fueling an autism epidemic, then cases should have declined after vaccines stopped including it.

What was shocking to me, the first time I heard Kennedy talk about thimerosal in vaccines, was how absolutely certain he was. He came across as a man who remained utterly convinced that vaccines cause autism, despite the mountain of evidence against him.

After RFK Jr.'s Salon article appeared, scientists responded quickly and convincingly, pointing out its numerous flaws and distortions. Salon tried to fix the problem, issuing five corrections before throwing up their hands and removing the article entirely from their website. Rolling Stone also took down the article. Salon’s editor-in-chief wrote an apology, saying

“I regret we didn’t move on this more quickly, as evidence continued to emerge debunking the vaccines and autism link. But continued revelations of the flaws and even fraud tainting the science behind the connection make taking down the story the right thing to do .”

Kennedy has steadfastly refused to admit any errors, ever. When I wrote about him in the past, his website still displayed the original Salon article, without even the small corrections that Salon.com had made. (That website, robertfkennedyjr.com, no longer exists now that he’s running for President.)

Kennedy also published another anti-vaccine book just last year, titled “Vax-Unvax: Let the Science Speak.” (In case you didn’t notice, Kennedy has zero credentials to write a book about vaccine science, but that has never slowed him down.) And in case there’s any doubt about his leanings, early in 2024 Kennedy hired Del Bigtree, a “top anti-vaccine activist,” as his campaign communications director.

By ignoring the scientific evidence that shows that thimerosal and vaccines have no link to autism, Robert Kennedy placed himself firmly in the camp of conspiracy theorists and cranks. He’s also demonstrated breathtaking arrogance. He believes that despite his lack of scientific training, he knows the truth that every scientist who’s studied this issue has missed.

Even worse, Kennedy has used his fame to spread anti-vaccine misinformation, which grew far worse during COVID. Though I doubt he will listen to me (he’s ignored everyone else), Kennedy needs to take a hard look at the harm he’s causing to defenseless children, the elderly, and cancer patients, and anyone else with a weak or compromised immune system.

When I heard Kennedy talk about environmental topics, where I agreed with him, I was impressed by his passion and his seeming command of the issues. But having heard him speak about thimerosal and vaccines, I now realize that he’s a dangerous ideologue, willing to distort the truth so thoroughly that he can’t be trusted on any topic, even ones where I agree with him. His campaign for President, although certainly doomed to fail, is likely to increase the spread of his harmful anti-vaccine tropes.

Finally, I couldn’t help but notice that the bio on RFK Jr’s campaign’s website makes no mention of his anti-vaccine activism, even though it’s been his top priority for the past 20 years, and it’s the main reason he has the visibility he has today. It does mention “his nonprofit, Children’s Health Defense” but doesn’t say that the primary work of that nonprofit is to spread scary misinformation about vaccines. I’m just guessing here, but it appears that some of his campaign advisers have decided that being a famous anti-vaxxer might not be the best qualification for President.

Update, May 28, 2024: Since this story was published on May 27, RFK Jr. has been contacted for comment.  

Hormone replacement therapy is beneficial and safe, it turns out

 

A new study that just appeared in the Journal of the American Medical Association has some good news for women who take estrogen replacement therapy.

To jump to the punch line: estrogen therapy helps to alleviate hot flashes and other symptoms of menopause, and it carries little risk. And even better news: the study also reported that estrogen-only therapy might actually decrease the risk of breast cancer.

Why does this matter? Because about 20 years ago, millions of women stopped taking estrogen, even if it was helping them, because of a report that hormone replacement therapy might increase (not decrease) the risk of breast cancer.

These latest results come from the long-running Women’s Health Initiative, a National Institutes of Health-funded study of more than 160,000 women who were given various hormone therapies and then followed for up to 20 years. The WHI was responsible, somewhat notoriously, for the cancer scare in 2002, when the NIH reported–without consulting many of the scientists leading the study–that hormone replacement therapy increased the risk of breast cancer. This was wrong, as I explained in this column a few years ago, but as a result, many women stopped taking estrogen, and physicians stopped recommending it.

The confusion stemmed from the use of two different types of hormone therapy: (1) estrogen alone, or (2) estrogen plus progestin. The increased risk occurred solely in the combination therapy group (estrogen plus progestin), and not in the estrogen-only group. Despite this crucial difference, the WHI halted the studies of both treatments in 2002, and their press releases didn’t fully explain the difference.

And yet, as Dr. Robert Langer explained in 2017, the WHI trial of estrogen alone (without progestin) continued to track its subjects, and in 2004 that study reported that estrogen-only therapy led to a reduction in breast cancer, and a reduction in coronary heart disease as well.

(Aside: the Women’s Health Initiative website boasts that their 2002 report contains “revolutionary findings about combined hormone therapy,” emphasizing only the harm. I couldn’t find any comparable highlight describing the benefits of estrogen-only therapy.)

The new study, which appeared in JAMA on May 1, confirms several earlier studies that have reported a cancer benefit for estrogen therapy. In addition to its beneficial effects on menopause symptoms (which are widely acknowledged), the new study found that, after an average of 10.7 years, “rates of breast cancer were significantly lower in the CEE group [estrogen only] compared with the placebo group (HR, 0.77).” That HR value means that women who took estrogen had a 23% reduction in their risk of breast cancer.

Further supporting these findings is a 2022 study from NIH, available as a preprint in medRxiv here, which found that women taking estrogen only, compared to no hormones at all, had “significant risk reductions for all study cancers, breast, lung, endometrial, colorectal and ovarian” as well as a 20% reduction in mortality. The 2022 NIH study also found, similarly to the 2002 findings from WHI, that when estrogen was combined with progestin, the risk of breast cancer increased.

And there’s more. This 2012 study out of Denmark studied women who received estrogen-only therapy for 10 years starting in the early 1990s. They then followed these women for another 16 years, and found that women taking estrogen had a lower risk of heart attack, heart failure, or death–and no increased risk of cancer.

(As another aside: the new JAMA paper also reported results on a completely separate study of calcium plus vitamin D. They found that taking supplemental calcium+D didn’t provide any benefit in reducing the risk of bone fractures, confirming what I wrote in a recent column, here.)

So what’s the bottom line? We now have a raft of evidence showing that for post-menopausal women, estrogen therapy can offer significant benefits not only in treating hot flashes and other “bothersome menopausal symptoms” (to quote JAMA), but also in reducing the risk of some types of cancer. In contrast, hormone replacement therapies that use progestin, which is commonly used in birth control pills, might increase the risk of cancer and should be avoided.

As with most medical treatments, the true picture is complicated, but millions of women today might benefit from estrogen therapy. If you think you might be one of them, talk to your physician.

Calcium and Vitamin D Supplements Still Don't Work, New Study Says

I think I’ll have to add calcium to my list of the Top Six Supplements You Should Not Take. Here’s why.

A year and a half ago, I reported on a very large study of 26,000 men and women that asked if vitamin D helps to prevent bone fractures, as many people (including some doctors) believe.

Well, it doesn’t. That study found that people who took vitamin D had exactly the same risk of bone fractures as those who didn’t. It didn’t matter how much vitamin D they took, nor did it help if they also took supplemental calcium: either way, vitamin D had no effect.

(Aside: everyone needs vitamin D, but most people get all they need from a normal diet. Alternatively, just 10 minutes of sunlight gives you about 4 times your daily recommended vitamin D requirement.)

Well, now there’s a huge new study, just out in the Annals of Internal Medicine, that followed over 36,000 older women, looking at the effects of a combination of vitamin D and calcium over a 22-year period. (That’s a really long time for a study, and kudos to the authors for their determination and effort.) The scientists leading the study looked not only at the effects of supplements on hip fractures, but also whether supplements changed the risk of dying from cancer or heart disease.

The results? Well, the study found no reduction in the risk of hip fractures, which isn’t surprising given that earlier studies found the same thing. But because it was such a lengthy study, following people for more than 20 years, they could ask something else: did vitamin D and calcium have any effect on mortality? Or to put it more bluntly, did the supplements prevent death?

Well, no. But the report was a bit more nuanced than that. It turns out that deaths from cancer went down a tiny bit, and deaths from heart disease went up a tiny bit.

First, though, let me explain the overall experiment. Approximately half the women in the study, just over 18,000, were assigned to take both vitamin D and calcium every day. They were given pills with 1000 mg of calcium carbonate (400 mg of elemental calcium) and 400 IU of vitamin D3 daily. The other half of the participants took placebo pills, but neither group knew whether their pills were placebos or not.

Over the course of 22 years, 1817 women taking supplements died of cancer, compared to 1943 women in the placebo group who died of cancer. That sounds kind of good, right? The study authors report that this result – 126 fewer deaths – was statistically significant (just barely), but there are good reasons to be skeptical of this “significance” claim.

On the other hand, 2621 women taking supplements died of heart disease, versus 2420 women in the placebo group. So there were 201 more deaths from heart disease among women taking vitamin D and calcium: not so good.

Combining both causes of death, we see that in the women taking supplements, there were 75 more deaths from either cancer or heart disease. The study also reported numbers for all causes of death, and there were still very slightly more deaths in the supplement group. (The annual death rate increased from 2.14% to 2.15% for those taking supplements, a non-significant change.)

So on the whole, taking supplements didn’t seem to provide any benefit at all, and it certainly didn’t reduce the risk of death.

Why would supplemental vitamin D and calcium increase the rate of heart disease, or decrease the rate of cancer? Well, first I should emphasize that it’s entirely possible that these supplements have no effect at all, and the difference in death rates must just be random variation. There have been multiple studies speculating on how vitamin D might help to prevent cancer, but the effect, if any, is very small. And as for heart disease, maybe, as the authors of the new study speculate, long-term calcium supplements create calcifications in coronary arteries, which would be a bad thing. For now, this is merely a hypothesis.

So here is my new list of the top 7 (no longer 6) supplements that you should not take:

  1. Vitamin C
  2. Vitamin A and beta carotene
  3. Vitamin E
  4. Vitamin B6
  5. Multi-vitamins
  6. Vitamin D
  7. Calcium

You can read more about the first five, some of which can be downright bad for you, in The Top Five Vitamins You Should Not Take.

What’s left? Well, if you don’t have a deficiency, there’s no reason to take any supplemental vitamins at all. If you want to spend a little more money at the grocery, buy some fresh fruit instead. You’ll be healthier for it.

As a final caveat, I should point out that although routine supplementation is worthless and megadoses of vitamins can be harmful, if you think you have a vitamin deficiency, consult with your doctor. Serious vitamin deficiencies might be the result of other health problems that your doctor can help you address, and treatments for specific conditions or diseases may include vitamins.

Why did humans lose our tails? Blame a "jumping gene"

 

Most animals have tails, including almost all mammals. For some reason, we humans don’t. This difference has been the source of much speculation among scientists over the years, and many arguments have been made about why we don’t tails.

One line of reasoning goes like this: tails are very useful for animals that live in trees, but once our ancestors came down from the trees and started living on the open plain, they didn’t need those tails any more. But why lose them? Lots of animals don’t live in trees, and they still have tails.

Even among the primates, most species have tails, but chimpanzees, gorillas, orangutans, and bonobos–the great apes–don’t. In fact, one way to tell great apes apart from other apes is by the presence of a tail. We humans are simply great apes without so much hair. Or, as the English scientist Desmond Morris called us in his famous book, humans are “The Naked Ape.”

So why am I writing about this now? Well, in a newly published article in Nature, a group of scientists from NYU, led by Itai Yanai and Jef Boeke, seem to have figured out what made us lose our tails. It’s all due to a piece of DNA that copies itself and jumps around our genome.

It’s a bit geeky, but stay with me and I’ll try to explain.

It seems that sometime around the divergence of the great apes from other primates, about 15-20 million years ago, a “jumping gene” popped into a gene called TBXT in our ancestor. (The B in TBXT stands for brachyury, which means “short tail.”)

The jumping gene here is just a piece of DNA a few hundred letters long*, not really a gene all by itself. But once that jumping gene got into TBXT, it was in just the right position to make the cells in our ancestor produce a shorter version of TBXT. The shortened gene was missing one of its pieces, but it still worked – well, sort of. Our ancestors managed just fine, but they lost their tails.

(Aside: the piece that’s chopped out is called exon 6, for those who really want to know.)

Given that this happened over 15 million years ago, how did the scientists prove their hypothesis? Well, other mammals have the same gene, but they make a longer version. So the authors of the new paper created a version of the TBXT gene in mice that included the jumping gene–and, as predicted, some of the mice lost their tails entirely.

Admittedly, this doesn’t exactly prove that one jumping gene caused us to lose our tails. Without a time machine to take us back 15 million years (with a DNA sequencing machine in tow), we can’t truly prove what happened eons ago. But it’s a compelling story, because we know that our genomes, and those of other great apes, have this unique jumping gene that other mammals lack.

So now we know how we lost our tails. We still don’t know exactly why, though. Some scientists speculate that being tail-less might have helped us to walk upright, or that it might have been better to lose the tails once our ancestors stopped living in trees.

On the other hand, guinea pigs don’t have tails either, and they don’t walk on two legs. And koalas don’t have tails, even though they live in trees. Some of these questions may just have to remain a mystery.

*Technically, the jumping genes in this story are called Alu elements, and they occur all over our genome. Famed geneticist Haig Kazazian, a former Hopkins colleague who passed away just two years ago, explained in a 2004 paper that Alus are a form of “nonautonomous retrotransposon.”

Sadly, the Washington Post once again falls for acupuncture pseudoscience

It’s like playing whac-a-mole. No matter how many times I write a column showing that some wildly implausible practice is nonsense, new articles pop up claiming “Hey, look at this! It really works!”

So I’m going to try to whack another mole, because people can be harmed by bad information, especially when it comes in the form of medical advice.

Recently the Washington Post ran a column under the headline, “Does acupuncture work for chronic pain? Here’s what the science says.” (The column first appeared back in July, but the Post’s website promoted it again just last week.)

Before giving you the Post’s answer, let me give you the correct answer. No! Not “maybe” or “sometimes” or “we’re not sure.” Acupuncture doesn’t treat anything, and it carries a real risk of harm, particularly from infections. I’ll get to that below.

I’ve written on this topic many times before (in 2013in 2012in 2010, and more), and I’ve even called out the Washington Post for their pro-acupuncture pseudoscience (see this column, which I wrote in 2016). The physicians over at Science-Based Medicine have debunked more acupuncture studies than I can count; they’ve even created a special webpage (which I highly recommend) dedicated to explaining the bogus claims that acupuncture proponents make.

Acupuncture, in case you don’t know this, is a practice where people who call themselves acupuncturists (they are not doctors) stick needles into your body to “treat” various conditions. The claim is that these needles can manipulate your vital life force, or “qi”, which runs along supposed acupuncture lines throughout your body.

That’s just wrong. Modern biology has taught us a whole lot about human physiology, and there just aren’t any lines with mystical forces flowing through them. There are nerve fibers, true, but acupuncturists don’t use those. (And if their needles were piercing nerves, it would hurt like heck.)

Acupuncture and qi are part of Traditional Chinese Medicine, or TCM, a collection of largely ineffective and sometimes very harmful folk beliefs. TCM’s popularity started to grow in the mid-20th century when Chairman Mao launched a propaganda campaign pushing it. Mao himself never used TCM, but his government couldn’t afford real medicine, so they convinced people that inexpensive folk medicine was just as good. It wasn’t.

But I digress.

Acupuncturists claim to treat many conditions, but they especially like to claim that they can treat chronic pain, for at least a couple of reasons. First, pain is inherently subjective, so the only way to measure if a treatment is working is to ask the patient. This makes it hard to study objectively. And second, pain symptoms usually wax and wane, even without any treatment. Patients usually want treatment when the pain is at its worst, which means once the pain subsides, the patients will give credit to whatever they were doing at that time. So pain is fertile ground for people selling quack treatments.

Now let’s get to that column in the Washington Post. The column promises to tell you “what the science says,” and it quickly gets to the point, saying yes, it does! First it puts forward the logically flawed (and non-scientific) claim that hey, the U.S. Medicare system now covers acupuncture for back pain, so it must be effective.

Ugh, where do I start? Well, like it or not, Medicare approval of a treatment doesn’t mean the treatment works. (And conversely, some treatments that work are approved for coverage by Medicare.) So that’s just a logical fallacy. I wish it were true that Medicare was purely science-driven, but both the federal and state government have been lobbied for years by acupuncturists (and other purveyors of dubious therapies) to provide public tax dollars to cover their practices. For a deeper dive into these lobbying efforts, I recommend the lengthy takedown by Jann Bellamy explaining that acupuncture is “legalized quackery.”

The Post article then goes on to discuss the science, for which it relies primarily on a single study, a meta-analysis published in 2019 by Andrew Vickers. (The column was written by Dr. Trisha Pasricha, who has sterling credentials, including training at Johns Hopkins Medicine where I also work. Alas, good credentials don’t always mean that you can trust the holder of those credentials, and this is one of those instances.)

Vickers has published multiple meta-analyses, and if he’s shown anything, it’s how easy it is to cherry-pick from the (extensive) acupuncture literature and find studies that prove whatever point you want to make. The Post column asserts that Vickers used 39 “high-quality” studies, but that is debatable. Many of the studies were done in China, which (as Science-Based Medicine physicians David Gorksi and Steven Novella have pointed out) virtually never publishes a negative study of acupuncture.

I’ve done a deep dive into one of Vickers meta-analyses of acupuncture–an earlier one–for one of my medical school classes, where I use it to illustrate how bad studies can be mis-reported by scientists themselves and by the media. I don’t have time to go through it here, but among other problems, Vickers doesn’t seem to understand how placebo controls work.

Here’s what I mean by cherry-picking. Vickers went through 100’s of studies to pick the 39 that he included. One of those supposedly high-quality studies looked at acupuncture for knee arthritis. That study found that both acupuncture and sham acupuncture (the placebo arm) and the same small effect on knee pain, and that patients who received no treatment at all reported more pain than patients. The authors of the study (and Vickers) concluded–wrongly–that because acupuncture was better than nothing, it must be working. Wrong! If you don’t beat the placebo, then your treatment fails.

For a drug trial, failing to beat the placebo means the game is over. But with acupuncture, it means “more studies are needed,” and the whac-a-mole game continues.

Oh, and I should add that as far as knee arthritis goes, the reduction in pain in both the acupuncture and placebo group was much less than has been reported in studies that use ibuprofen.

That’s right, ibuprofen is far better than acupuncture. Not to mention cheaper and more convenient.

If this weren’t enough, a more recent study has already contradicted the Vickers study as physician-blogger Steven Novella pointed out in a recent column. Novella wrote that “the evidence is too low quality to conclude that acupuncture works, as desperate as proponents are to say we can reach that conclusion.” So no, Dr. Pasricha, the latest science does not say that acupuncture works. Quite the opposite.

I’m still understating how badly acupuncture has failed every well-designed study to test its effectiveness. Studies have shown that placing the needles in random locations works just as well as using so-called acupuncture points. Other studies showed that sham acupuncture, where the needles don’t pierce the skin but where subjects believe they did, also works just as well. And “expert” acupuncturists can’t agree on the locations of acupuncture points.

And don’t get me started on acupuncture and the risk of infection. Acupuncturists aren’t trained in real medicine, and they don’t use proper sterile procedures. This means that they don’t necessarily sterilize their hands, or your skin at all of those points where they’re plunging needles into you. There have been thousands reports of infections due to acupuncture (dating back decades), some of them fatal. And because acupuncturists aren’t part of the medical system, we can be virtually certain that infections are under-reported.

Acupuncture isn’t going away any time soon, because people are making money from it, and no matter how many studies show that it’s nothing more than a fiction, those people will keep insisting on more studies. Plus they can point to hundreds of poorly-done studies that claim to show benefits, and argue–as the Post column does too–that “more research is needed.” I’m not making this up: that precise phrase appears in Dr. Pasricha’s article.

There are even scientific journals entirely devoted to acupuncture (here and here, for example), and they make money too, for the for-profit publishers that produce them. So you can be sure that more studies are coming, and some of them will be positive, even though acupuncture is utterly ineffective.

Even so, the Washington Post can and should do better. Here’s my (free) advice for those considering acupuncture: save your money, and just take some ibuprofen.