Archive for the ‘In the news’ category

Pediatricians can’t always follow FDA medication labels

March 27, 2014

The Pediatric Insider

© 2014 Roy Benaroch, MD

You know those little packets of paper, folded over eight times, written in type that can’t possibly be seen? You’ve seen them glommed onto the side of stock bottles of medications, or shoved into the paper box alongside a tube of prescription ointment. That unreadable thing is the official “product information”, often called the “label”, required for every FDA-approved medication. It contains all sorts of information, including lists of side effects (Nausea! Anal leakage! Growing a tail!) and what a medicine is “supposed” to be used for.

But often, that information isn’t the best information. It’s just what the FDA approved. Science marches on, and new published information is not routinely included in the product insert. Doctors who pay attention know that there’s usually a whole lot of more-reliable, more-specific, and more-accurate information about here than what’s on the label.

The discrepancy is especially stark with babies and children. According to a new AAP report, “Off Label Use of Drugs in Children,” less than 50% of medications have information about pediatric usage in the FDA-approved product labeling. If you have a child who has been prescribed medication, it’s almost certain that at least some of them have been used “off-label,” in a way that is not specifically approved by the FDA.

As the AAP report outlines, using drugs in this way is not incorrect, unethical, or inappropriate:

The absence of labeling for a specific age group or for a specific disorder does not necessarily mean that the drug’s use is improper for that age or disorder. Rather, it only means that the evidence required by law to allow inclusion in the label has not been approved by the FDA.

Those sound like weasel legal words, I know—but it worth understanding what the FDA’s role here is. The FDA is empowered to regulate the manufacturing, labeling, advertisement, and safety of medications. For a drug to be “FDA approved” for sale in the US, a sponsor has to provide information usually including two large, randomized trials to prove that medicine is safe and effective. Safe in the population studied, and effective for the disease studied. The FDA “approves” the drug for sale using specific parameters from these studies, and does not allow the sponsoring company to promote the use of the medication for any other purpose.

But once a drug is approved, a licensed physician can legally prescribe it for any use. The FDA does not regulate the practice of medicine or how doctors use medication (that can be regulated by state medical boards, if a doctor does stupid or unethical things with a prescription pad.) It is up to licensed prescribers to use their own judgment, based on the totality of the evidence, to make prescribing recommendations. Limiting our knowledge to what’s in the product information sheet—which is seldom modified or updated after a drug is approved—would be unethical and foolish.

In most circumstances, using a drug off-label (for an indication or age not explicitly approved in the FDA label) is not “experimental” or “research.” As long as it’s in a patient’s best interests, using a medication this way does not require any specific information be shared with the patient, beyond what we should be talking about with any medication (risks, benefits, side effects, etc.) However, it’s usually best for doctors to talk about the off-label use in cases where off-label prescribing is unusual or cutting-edge. In pediatrics, that’s seldom the case. We write off-label meds every day, in ways that have sometimes been used for decades, and I would bet that most pediatricians don’t even know when they’re doing it.

That’s because the best therapeutic decision making is not based on the label. It’s based on all of the evidence out there: published studies, experience, judgment, and the best interests of the patient.

Does acetaminophen in pregnancy cause ADHD?

March 20, 2014

The Pediatric Insider

© 2014 Roy Benaroch, MD

Kelly and a few other readers contacted me about a recent study that links acetaminophen use in pregnancy to the later development of ADHD in children. Is Tylenol yet another thing pregnant women need to avoid?

The study, titled “Acetaminophen use during pregnancy, behavioral problems, and hyperkinetic disorders” was published this month in JAMA Pediatrics. Dutch researchers looked at about 60,000 children born from 1996-2002. Their parents have been filling out questionnaires and completing phone interviews from pregnancy onward about medication use, illnesses, and many environmental exposures. This study looked specifically at reports of whether mom took acetaminophen during pregnancy, based on multiple phone interviews during pregnancy and six months after each child was born. They also asked about mom’s health during the pregnancy, and about a possible family history of mental disorders. Then, the researches used multiple ways to determine whether these children had ADHD or ADHD-like symptoms at age 7. Parents completed a structured developmental screening tool, and ADHD diagnoses were further collaborated by mining the Danish Psychiatric Central Registry. They also looked at which children had ever filled prescription for a medicine typically used to treat ADHD.

They found that acetaminophen use during pregnancy was correlated with an increased risk all of their ADHD measures—not only the actual diagnosis of ADHD, but ADHD-like behaviors on rating scales and Ritalin prescriptions, too. The risk was increased by 15-40%, depending on the measure; and the risk increased with increasing acetaminophen exposure. Even when the authors factored out the influences of fevers and infections during pregnancy and mom’s mental health, the association remained strong.

So what does this mean? It’s too early to say if acetaminophen caused ADHD. It may be that there was some other factor that drove women to take acetaminophen, such as reduced coping skills or family support. But clearly, there is something going on here, and it is possible that acetaminophen really is the culprit. In this study, 56% of pregnant moms reported taking acetaminophen. Even if the causal factor only increased ADHD risk by a small amount, the net effect would be substantial, given how common acetaminophen use seems to be.

Previous studies have looked at other exposures for pregnant women that might be linked to later ADHD. A 2012 study from New England showed that fish consumption was correlated with a lower risk, and industrial mercury exposure with a higher risk of later ADHD. This study, like the current one, could not prove that these influences were causal, or only associations. But they were statistically valid, and raise important questions about prenatal influences on later mental illness, school, and behavior problems.

If you’re pregnant, I’d think twice about taking any medication, including acetaminophen. While there are times when the risk: benefit ratio of a medicine is clearly justified, medicines should only be taken when there isn’t a more-safe option. Headaches could perhaps first be treated with massage and relaxation time (which I suspect every pregnant woman deserves anyway.) If medicines are used, patients should strive to use the lowest effective dose for the shortest amount of time.

And don’t forget to eat more fish—preferably the kind without any mercury.

Chikungunya fever: A new infection, coming your way soon

March 13, 2014

The Pediatric Insider

© 2014 Roy Benaroch, MD

I first heard about chikungunya about ten years ago, when outbreaks of this mosquito-borne illness were becoming common among travelers to India. It hasn’t taken long to spread to the Caribbean, and soon enough it’s likely to become widespread in the United States.

Sometimes called “Chikungunya Fever,” the illness causes fever and severe joint pain that can be debilitating, and can last for weeks. Fatalities are rare, and there is no specific treatment and no vaccine. Unlike West Nile Virus, the virus that causes Chikungunya triggers symptoms in almost everyone who is exposed.

The chikungunya virus is spread by the bite of one of two species of mosquitoes—species that are widespread in especially the southern USA. Those same mosquitoes can also transmit dengue, which has already started appearing in Florida and Texas.

We live in a big, interconnected world, with plenty of travelers and plenty of ways for new infections to cross continents and seas. In addition to new strains of influenza and the spread of resistant microorganisms, in the last ten years we’ve seen the emergence of new serious respiratory infections like MERS and SARS. Old infections, like tuberculosis, are back. And once-defeated vaccine-preventable diseases have returned to many communities, especially where vaccine uptake has fallen.

Germs have been around far longer than we have, and they will patiently wait for us to drop our defenses. We will not win this battle anytime soon. But we can still fight back:

  • Prevent mosquito-borne infections by preventing mosquito bites. Keep them off of your skin and out of your yard.
  • Continue to fund a strong public health infrastructure to track and identify health risks. We need to continue to pay attention, not just here, but throughout the world.
  • Advocate for universal vaccination of all children. It is always better to prevent infections than treat them. Vaccines need to be a public health priority, and no child should be denied vaccines because of financial reasons. Parents who are scared of vaccines because of misinformation need to hear the truth from friends, relatives, and their doctors.

When white noise is too noisy: Don’t crank that machine to eleven

March 10, 2014

The Pediatric Insider

© 2014 Roy Benaroch, MD

I like white noise to help babies sleep. It seems to mask other sounds, and when used routinely becomes a nice sleep-cue for newborns, infants, and older kids. White noise machines, or “generators”, are routinely sold at baby stores, and there’s (of course) even an app that will make your phone create that static-like, whooshing or raining noise.

Yup. An app. That makes your phone sound like a 1970’s clock radio tuned between stations. I knew I shouldn’t have let my mom throw that away.

Anyway: as with all things in life (except coffee), there can be too much of a good thing. So says a new study from Pediatrics, “Infant Sleep Machines and Hazardous Sound Pressure Levels”. Researchers from Canada tested 14 ordinary white noise generators that are marketed to parents as sleep helpers to see how loud they could be when cranked up to maximum volume. They re-created a crib sleeping environment, and tested sound levels with the devices right at the crib rail, or on a table next to the crib, or across the room.

Now, there really isn’t a single standard for white noise, but for hospital nursery equipment an accepted noise threshold is to keep volume under 50 dB (decibels) for one hour’s exposure. In real life, potential damage to hearing depends both on the intensity (volume) of the sound, its frequency, and its duration; other factors like ear shape and the overall health of the baby are probably important, too. But the 50 dB threshold is probably a fair approximation of a volume that shouldn’t be exceeded, at least not for more than an hour or so. 50 dB is about what the volume of a shower sound like when you’re standing in the bathroom—a little louder than ordinary speech, but you could talk over it by speaking up a bit.

What the researchers found was that all of the devices exceeded 50 dB when turned up to maximum, as measured right nearby (as if the device was in or right near the crib.) Most of them exceeded 50 dB even when placed six feet away. Again, though, these were all tested at maximum output, with the dial turned up to 10 (or, perhaps, 11). The loudest of the devices came in at 93 dB, about as loud as a hand drill. For comparison, a rock concert is about 115 dB.

This study didn’t measure the effects of this level of noise on actual babies, and in fact there really isn’t any good data about just how loud/how long white noise needs to be to affect hearing development. Still, the study shows that these things can get pretty loud, and that may not be a good thing.

However, neither is a screaming, restless baby. Those get pretty loud, too—much louder than 50 dB. Mom and dad’s hearing (and sanity) are important, too.

The authors of the paper call on manufacturers to label their products informing parents of the danger of loud noise, and of limiting the devices’ sound output.

Let me also recommend some common sense: when you use these things, don’t turn them up to maximum and let them run all night. You can safely use a white noise machine reasonably, turned up half-way, or something like that. If it is hard to speak over the noise it’s making, it’s probably too loud. Junior might sleep better with some white noise, but I don’t think he’s quite ready for Crazy Train.

Start using fluoride-containing toothpaste as soon as baby teeth come in

February 27, 2014

The Pediatric Insider

© 2014 Roy Benaroch, MD

A new guideline from the American Dental Association suggests that parents start using fluoride toothpaste early to best protect teeth. (The guideline itself is behind a paywall, but you can read a summary here.)

The old advice was to wait until age two to use fluoride. The concern had been that babies can’t spit well (ironic—they seem to spit up just fine when they want to), and that early fluoride could lead to fluorosis, or a staining of teeth. But it turns out that the vast majority of children with fluorosis have minimal cosmetic changes that are only noticeable by a dental professional, and that mild fluorosis actually strengthens teeth. An appropriate amount of fluoride toothpaste, when used very young, will lead to fewer cavities and better dental health.

How much is the right amount? The ADA is suggesting just a smear, or a bit of toothpaste about the size of a single grain of rice. That’s not a lot. Even for older kids, past three, a pea-sized amount is plenty. (That’s what’s recommended for adults, too. The big blobby stripe of toothpaste shown in commercials is there just to trick you into using too much.)

Once teeth come in, brush them twice a day with a rice-sized bit of fluoride-containing toothpaste twice a day. Now, if we could also get them to floss….

Should pilots be replaced by lower-cost pilot assistants?

February 24, 2014

The Pediatric Insider

© 2014 Roy Benaroch, MD

As the Wall Street Journal reports, there’s a growing shortage of qualified pilots in the US, driven by both economic reality and federal policy.

Pilots typically start their professional careers at small, regional airlines—airlines that pay, approximately, fast-food wages. Less than that, really– for for the hours they work, many pilots make less than minimum wage.  After a few years, these pilots have enough flight time and experience to try to get jobs with the big carriers, for a substantial increase in salary. Once the promotion to “captain” of a commercial jet comes through, pilots can make $200,000 or more a year.

But the system is getting wobbly. The two-tiered payment system relies too heavily on a steady influx of new, fresh-faced pilots eager to fly at any income. And new federal regulations require that starting pilots have 1,500 hours of flying experience, up from 250 hours—meaning even more debt for young flyers.

In other words: long training for an eventually good salary isn’t likely to continue to attract enough talent. Does this remind you of any other industry?

It’s expensive to train a pilot, and it’s expensive to train a doctor. We typically spend 4 years as undergrads, 4 years in medical school, then at least 3 years at a less-than-minimum wage job (residency) just to qualify as “primary care providers” in internal medicine, pediatrics, or family medicine. If we want to make the big bucks, that’s another several years for fellowship or surgical training.

Meanwhile, there’s a push to get more people insured—more people who will want to see a doctor. As with pilots, a doctor shortage looms.

Some people are suggesting an expanded role for non-doctors—nurse practitioners, physician’s assistants, pharmacists, and others to take a larger role, perhaps to “lead the health care team.” It’s unclear what the effect of such a change will be on the quality of health care delivery, but that hasn’t stopped many health care systems from relying more on these lower-cost providers. Most of the time, with most patients, that works out fine.

I suppose we could also rely more on low-cost “pilot assistants” or “flying practitioners” as well. Most of the time, that would work out fine, too. But I don’t think most people would be happy to ride a plane piloted by a non-pilot. When people fly, they expect a real pilot to be in charge: someone with both the experience and the training not only to handle the routine stuff, but someone who can handle the rare emergencies or unexpected complications. Someone who can land any plane safely, even when things go wrong.

Physician extenders and other mid-levels can safely and effectively handle most medical questions. But the trick is knowing which patients really would do better with a physician. We don’t necessarily know ahead of time (just like we don’t know which flights will have emergencies.) Co-pilots and navigators and other assistants can be a valuable part of the cockpit team, but who will you turn to when something goes wrong?

Fixing peanut allergy by eating peanuts

February 20, 2014

The Pediatric Insider

© 2014 Roy Benaroch, MD

Peanut allergy can be a big deal. And most children who are allergic to peanuts will not outgrow their allergies. Avoidance has been the main way to treat peanut-allergic people, but that doesn’t always work. Peanuts can sneak into foods, especially with young children who may not be able to monitor their intake closely. What if there were an easy way to “cure” peanut allergy?

Researchers in the UK published a study last week looking at the safety and effectiveness of oral desensitization. They enrolled 99 children from age 7-16, all of whom with documented real peanut allergy by prior oral challenge (ie, they had all had serious, immediate reactions to peanut under controlled conditions in the past.) They were randomized into two groups. The control group was told to continue avoiding peanuts. The kids in the intervention group were given a daily dose of oral peanut flour, starting with a tiny dose of 2 mg, and working up every two weeks to a maximum dose of about 5 peanuts worth of protein.  Of the 49 children randomized into the intervention group, 6 withdrew from the study—four of whom because of reactions to the peanut. One child required one dose of epinephrine during the study because of a serious reaction. After the study period, all of the remaining participants in both groups had a double-blind, placebo controlled peanut ingestion to see if an ordinary dose of about 10 peanuts could be safely tolerated without a reaction.

Of the children in the control group, who had been told to just continue to avoid eating peanuts, none could then tolerate a peanut ingestion (46 of the 46 who were still participating at that time reacted.) In the exposure arm, about 85% of the participants who completed the oral desensitization scheme were able to tolerate eating peanuts. After the study period, most of the children who had been randomized into the control arm were offered oral desensitization, and they ended up doing about as well.

Though oral desensitization worked most of the time, some questions remain. It’s not known how long these children will remain desensitized—they may need to continue oral exposures daily to prevent relapse back into clinical allergy. And about 20% of the original intervention group didn’t complete the study for a variety of reasons, some of whom because they couldn’t tolerate the treatment itself. But for most of the children who could complete the therapy, oral desensitization seems very promising.

It makes sense, too—we know that early oral exposures to foods seems to prevent at least some kinds of allergies, and that policies that encouraged delaying foods (especially past six months of age) probably led to increased allergy.

However: this is still an area of active research. Please do NOT try this on your own. The research groups had specific protocols using purified proteins, and though it’s likely that widespread use of this technique will lead to a simple, home-based regimen, we’re not quite there yet. If your child has peanut allergy and you’re interested in pursuing oral desensitization, speak with a board-certified allergist about enrolling in a trial or learning more about this before you give your child any peanut.

edit 2/21/2014 — fixed broken link to study

There are no safe shortcuts to weight training

February 13, 2014

The Pediatric Insider

© 2014 Roy Benaroch, MD

You or one of your children want to bulk up? Maybe get stronger, improve your tone, posture, and endurance? Weight training can be a great, healthful hobby for kids of (almost) any age.

But, as happens so often, some people try to push things too hard. Many people think they can get ahead faster with supplements and special powders, pills, and energy bars. Nope. All of that stuff is for suckers. And worse: some of it might kill you.

23-year old Andrew Mabry of Atlanta was found dead in his Atlanta apartment in 2013. He lived alone, and spent a lot of time working out, hoping to join a local minor-league football team. Investigators found boxes of supplements in his home, including N.O.-Xplode, Amplified Wheybolic Extreme 60, and GNC Beyond Raw Ravage. They also found that he had a damaged heart, and toxic blood levels of a chemical called DMAA. That “supplement” has caused at least 10 known deaths, but since the reporting of adverse effects from supplements is voluntary, that’s probably an understatement. Worse, the FDA has no way of knowing which supplements even contain this ingredient. The FDA has been trying to ban DMAA, but it’s still widely available on the internet.

More after the break -

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The safest place to have a baby is in a hospital

February 10, 2014

The Pediatric Insider

© 2014 Roy Benaroch, MD

Two big studies have been published in the last few weeks, both of which have confirmed previous data: home birth is not as safe as hospital birth. These studies show that having a baby at home increases the risk of your baby dying by about 4 times. That really is a big increased risk—especially considering that most home births are supposedly low-risk pregnancies. Those babies should be less likely to die.

From the January, 2014 issue of the American Journal of Obstetrics and Gynecology comes a study of over 10 million babies born in 2007-2009. This study looked only at term deliveries, excluding small babies and twins and babies with congenital anomalies (that’s now the preferred term. We don’t really say “birth defects” any more.) The babies were then divided into groups by the setting of their delivery: in a hospital, in a free-standing birth center, or at home. The results are stark. The neonatal mortality among babies delivered by a midwife in a hospital was 3.1 per 10,000 births. For midwives delivering at home, the death rate was 13.2 per 10,000 (about four times the hospital risk.) There were far more babies born in the hospital than at home, but plenty of home births were analyzed, including over 48,000 by midwives. This was a large study with a reliable data set cross referenced from CDC data, and if anything it underestimates home birth mortality because babies transferred to the hospital because of complications during home birth counted as hospital babies.

The second January, 2014 study came out in the Journal of Midwifery and Women’s Health. This study did not have a built-in comparison group—it collected data only from women intending to have a home delivery by midwife from 2004 to 2009. The authors looked at many outcomes, including whether the babies successfully delivered at home, Apgar scores, and their use of medical interventions. The overall intrapartum death rate was 13 out of 10,000—and that includes only deaths during labor itself (not including babies who died shortly after birth.) Note that the death rate, 13 out of 10,000, just about matches the death rate for home midwife births from the ACOG study, which was 13.2 per 10,000. Though this study had no built-in comparison group, the rate is much higher than the hospital death rate from the ACOG study. And, again, the four-fold increased death rate is very likely an underestimate—this number does not include babies who barely survived delivery and died shortly afterwards. Also, data submission was entirely voluntary, capturing only 20-30% of home births. I’m thinking that midwives who delivered dead babies may have been somewhat less motivated to submit their data.

Though the total number of deaths was not large—the vast majority of deliveries in either setting were successful—a four-fold or more increase in death risk is not something I think most families would consider acceptable. The fact of the matter is that obstetric complications are not always predictable, and that hospitals are the place where medical interventions can be done quickly. These studies concerned deaths, but keep in mind that for every dead baby, there are many more that suffer brain damage with lasting handicaps.

Based on these and other good, large studies, a hospital birth dramatically improves the safety of delivery compared to having a baby at home. Further studies could improve the safety of home births—by developing stricter criteria to limit home births to the lowest risk pregnancies, and by making sure that home birth midwives are qualified to handle complications. But even in an optimal home birth situation, with a very competent midwife, some mothers and babies will suffer complications like massive bleeding or strokes or placental separations or umbilical cord catastrophies that will require near-instant hospital assistance to help mom and baby survive. Sometimes, there just isn’t time to wait for an ambulance. If you want the safest choice for your delivery, choose a hospital. And then bring your healthy baby home.

Yet more evidence for the safety and effectiveness of vaccines

November 4, 2013

The Pediatric Insider

© 2013 Roy Benaroch, MD

Item #1: A study of about a million (!) girls in Sweden and Denmark showed no serious side effects, none at all, after administration of the HPV vaccine.

Item #2: Another study, looking at children vaccinated against influenza from 2010-2012, showed a 77% reduction in life threatening flu illness.

Item #3: From JAMA Pediatrics, a study showing that among children 3-36 months of age, those who hadn’t received their routine vaccines had 18 times the risk of pertussis compared to fully vaccinated children.

What do these studies have in common? They’ve all been published within the last few weeks, and they’re good, solid science. They’ll also be ignored by the hardcore anti-vaccine crowd, for whom no amount of evidence matters one bit. They’ve made up their minds, and they have no interest in what scientists or doctors or anyone else has to say—unless you already agree with them.

Jonathan Swift said, “It is useless to attempt to reason a man out of a thing he was never reasoned into.” People who have come to their antivaccine views out of hysteria and fear have not used reason. And I don’t think there is much hope to convince them of anything.

But the vast majority of vaccine-questioning parents aren’t like that. They want good, reliable information to help them make their decisions. Studies like these continue to be published, hundreds of them a year. As more evidence accumulates, the safety and effectiveness of vaccines continues to be reinforced. We’re learning more and more about the immune system and how to protect ourselves, and newer vaccines have been very effective. That’s great news for those of us who want to do what’s best to protect our children, or families, and our communities.


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