Archive for the ‘In the news’ category

Zika update!

April 4, 2016

The Pediatric Insider

© 2016 Roy Benaroch, MD

I last wrote about Zika in January*, and there’s a whole lot more we now know about this mosquito-borne virus. And still a lot we don’t know. Time for a Q&A-styled** update!

 

Give it to me straight, doc. Does Zika really cause birth defects?

Yes. As is typical for scientist-written press releases, early reports this winter were equivocal—you’d see phrases like “is associated with” or “likely caused by”. That’s because unlike pushers of GMO-free foods, real scientists try to respect the intelligence of their audience. Back then, it was clear that there was both a big spike in cases of Zika-associated illness during pregnancies (mostly in South America), and a big spike in cases of microcephaly and other neurologic birth defects. But did one cause the other?

More-recent reports have included evidence of Zika in the brain tissue of affected fetal brains, and also in the brain and nerve tissues of children and adults suffering from neurologic symptoms during Zika infections. It’s clear that Zika is a neurotropic virus – it likes to invade neurologic tissue.

We also know more about the structure of Zika. At the molecular level, we know it has a structure that interacts with brain cells. That is completely cool—we know exactly what the virus looks like and how its molecules are arranged. That’s one step away from designing a vaccine. All of this research was done in just a few months. Science!

 

Is Zika coming to America?

It’s already in America, dummy. South America, which (last time I looked) was part of America. Oh, you mean North America? Which includes Mexico? Which is also part of America? Maybe you should just start over.

 

Is Zika coming to the United States?

It’s already here. Zika-virus associated infections have been reported in almost every US State, though at least so far the only locally-acquired cases have been transmitted through sex. (No, not sex with mosquitoes, you sicko.)

 

OK, so that means as long as I don’t have sex with anyone who’s been traveling, I’m protected, right?

Maybe for now, but not for long. Over 300 cases of Zika have occurred in the continental US, and even more in our Caribbean territories. And the mosquitos that transmit ZIka, by mid-summer, will be found in a wide swath of the US, across the entire souther border, reaching up into Ohio and Missouri. It is only a matter of time before local mosquitos stare biting people with Zika infection, and then spreading it to other people.

 

 Yikes. I’m glad I’m not a pregnant woman!

So are we. We’ve seen the quality of your questions here, and frankly it would be better if you didn’t reproduce.

 

I meant I’m glad only pregnant women need to worry about infections. Right?

Nope. Pregnant women, and their unborn babies, are clearly at the highest risk. It looks like about 25% of the time, infection during pregnancy results in fetal damage—though that’s an estimate based on preliminary data.

We do know that most infections in otherwise-healthy children and adults result in no symptoms whatsoever. Probably only 1 in 4 or 5 people with Zika develop symptoms, which include fever, joint aches, and rash. But a small number of people also go on to develop serious complications, which can include brain inflammation or Guillain-Barre Syndrome. Though these conditions after Zika infection are rare, we really don’t know exactly what the risk is, or who’s likely to progress to serious Zika-related illness.

 

What should I do if I think I have a Zika virus infection?

Testing is available through public health agencies, and is routinely recommended for pregnant women living in or traveling to areas with active transmission. For the rest of us, health-care providers can help decide whether testing is needed. Go see your doctor.

 

What’s the best way to prevent infection?

Right now, there’s no vaccine, though one is actively being developed. The best way to prevent infection is to avoid mosquito bites and travel to areas with high rates of infection. You can find maps and other resources through the CDC Zika Prevention site.

The bottom line with mosquitoes: wear long sleeves and long pants, keep mosquitos out of homes with nets, screens, doors, and air conditioning, and use a mosquito repellant that actually works. Those typically contain the active ingredients DEET, picaridin, or “oil of lemon eucalyptus.” Of these, DEET is the standard—it’s been around since 1957, and it works, and as long as you don’t drink the stuff it’s safe.

 

*I wrote about it weeks before the story was picked up by the so-called “mainstream media.” Yet, still, no Pulitzer. Am I bitter? Of course not.

**Some “journalists” say slapping together a blog post in Q&A format shows laziness and a lack of creativity. Those people should go stick their journalistic heads in buckets of icy cold water. It’s Saturday morning, it’s beautiful outside, and you guys are getting get what you pay for. Srsly.

 

Coming to America

It’s time to rethink pertussis prevention

February 8, 2016

The Pediatric Insider

© 2016 Roy Benaroch, MD

A large, sobering study published in the March, 2016 edition of Pediatrics illustrates just how far we still need to go to effectively control pertussis.

Pertussis, also known as ‘whooping cough’, is a serious illness. Older children and adults get to enjoy a horrible cough for about three months—a cough that sometimes makes people vomit, break ribs, or pass out. Seriously. You haven’t seen a “bad cough” until you’ve seen the cough of pertussis. Worse: in little babies pertussis can cause breathing problems, seizures, and death. Though its caused by a bacteria, antibiotics (unless given very early) are ineffective at reducing the length or severity of pertussis. Prevention, in this case, is worth far more than a pound of cure.

Up until the mid-1990s, infants and children routinely received the whole-cell DTP vaccine (DTP = diphtheria, tetanus, pertussis.) It worked at preventing all three of these diseases, but had a relatively high rate of side effects, mostly fevers. Many of the suspected more-serious side effects (like encephalopathy and seizures) are now known to have been caused by genetic conditions, not the vaccine, but nonetheless parents and doctors alike welcomed a newer vaccine, the acellular DTaP. This newer vaccine, which replaced DTP in the United States by around 1998, caused fewer fevers, and was thought to cause fewer serious reactions, too.

The problem is that it just doesn’t work as well. And as the first generation of infants to get an all-DTaP series starts to go through adolescence, we’re starting to see the unintended consequence of that vaccine change.

In the current study, researchers used a huge database of information from the Kaiser Permanente system of Northern California. We’re talking solid, big-data research, here, the kind of study that requires consistent and reliable data across a huge set of patients. In this case, about 3.5 million patients across 55 medical clinics and 20 hospitals, using centralized labs and an integrated medical records system. If health things happen to this population, Kaiser knows it.

In 2010 and again in 2014, California experienced large epidemics of pertussis. A total of 1207 cases were among Kaiser teenagers, all with complete records of their pertussis vaccination status. And the results aren’t anything to be happy about. In the first year after an adolescent pertussis (Tdap) booster, the vaccine was about 70% effective in protecting against pertussis. Not great, but not terrible, either – until you look a few days down the road. The vaccine effectiveness drops off dramatically, year after year, down to only about 9% by four years after receipt of the vaccine.

Why does Tdap seem to provide such poor protection—much worse than was seen in the original licensing studies? It’s a generational change, and it goes back to the shift from DTP to DTaP in the mid-1990s. By now, these teens in California are old enough to have received DTaP, not DTP, as infants. The authors looked at the specific ages of pertussis cases during the 2010 and 2014 outbreaks, and the trends support the conclusion that teens who received DTP as infants get good, lasting protection from Tdap; teens who got DTaP do not.

Now what? Clearly, we need a more-effective vaccine, perhaps even resuming the use of whole-cell pertussis vaccine, at least for the earlier doses. But in the meantime, we have to do the best we can with what we have. Vaccinating pregnant women with Tdap does effectively prevent pertussis in their babies, especially when they’re the youngest and most-vulnerable. And adults (who got DTP as children) should get Tdap boosters too, to protect the children around them. Another idea (floated by the study authors) is to use Tdap in teens not as a routine booster, but as a strategy to control local outbreaks, taking advantage of the higher effectiveness seen for the first year after vaccination.

I don’t have the answers. I’m not happy to see studies like these, but examining and re-examining vaccine safety and effectiveness is something we need to continue doing, with an open mind, relying on solid evidence. Bottom line: with pertussis, we need to do better.

Whooping crane

More water means slightly less weight in New York schools

February 1, 2016

The Pediatric Insider

© 2016 Roy Benaroch, MD

A simple, safe, and cheap intervention looks like a good way to help fight obesity in our schools. But not by very much.

A study published January 2016 in JAMA Pediatrics, “Effect of a school-cased water intervention on child body mass index and obesity”, looked at the effects of installing new water dispensers in New York City school cafeterias. 1227 schools, including 1 065  562 students,  participated in the observational study, which tracked student weights and BMIs, comparing trends before and after the new equipment was installed.

Those new dispensers are called “water jets” in the study, and I *think* they’re just those typical water cooler things that offices use, with a big jug of water on top and a little flappy valve to get cooled water into a cup below. The study description says they both chill and oxygenate the water “to keep it tasting fresh”, and cost about $1000 bucks each. Furthermore, they “are relatively easy to use” (pretty clever, those New York kids.) The authors pointed out that participants were weighed and measured by PE coaches, whose scale-using skills have “previously been found reliable” (pretty clever, those New York coaches.)

The results: after these water jets became available, there was a statistically significant drop in BMI of about 0.025 points (it was just a touch more effective in boys than girls), and the percentage of children in the schools who were overweight dropped by .6-.9%. (from about 39% to about 38%).

I know, not very impressive. The statistics are solid—whether the authors looked at trends over entire schools, or at trends among individual students before and after water jet availability, these weight parameters did drop. And the drop is, technically, statistically valid and real. That’s how it’s been reported in the media. The New York Daily News said “Water machines available in schools can help kids lose weight.”

But the drop really wasn’t very much. Going from 39% to 38% overweight is good, but I think we ought to try to do better. You can lead a student to water, but studies like this show it’s hard to make them actually lose weight.

What should we do with all of this yellow paint?

New Zika travel alerts especially for pregnant women

January 18, 2016

The Pediatric Insider

© 2016 Roy Benaroch, MD

What animal kills more people, year to year, than any other on the planet? The lowly, annoying mosquito. They fly around poking their snouts (I think) into person after person, spreading infections like malaria, yellow fever, and dengue. And new infections, too—like West Nile virus, which first appeared in Uganda in 1937. Infections don’t seem to recognize the borders of countries and continents, and West Nile has now become the most common mosquito-borne encephalitis in the US.

Now, the CDC is warning travelers against an even newer virus named “Zika”. Like West Nile, Zika was first found in Uganda, in a research station in the Zika rainforest (Zika means “overgrown” in the local language.) It remained an uncommon cause of human infection until the mid-2000’s, when the virus was first spotted outside of Africa and Southeast Asia. Since then, it has spread worldwide, throughout the warmer areas of the globe, leading to a large outbreak in Brazil that may have started with visitors to the 2014 Soccer World Cup. Brazil has probably had 500,000-1.5 million cases of Zika virus infection in the last few years.

Zika had been thought to cause only mild disease, with fever, rash, and joint pains. But at around the same time as the cases spiked in Brazil, health authorities there noted an alarming increase in health problems in newborns, especially a failure of brain growth called “microcephaly.” It’s since been shown that an unborn fetus can catch Zika virus across the placenta, and it’s very likely that the Zika virus infection is causing problems in the developing baby. We don’t know exactly how that’s happening, or when, or exactly when pregnant moms and babies are vulnerable.

What we do know is that like malaria, dengue, West Nile, and Chikungunya, Zika virus is spread by mosquitoes, and the best way to prevent transmission is to prevent mosquito bites. Stay inside at dusk, wear protective clothing, and use a chemical mosquito repellant containing DEET or picaridin.

The CDC has also now issued a “Level 2 Travel Alert” for areas with active Zika transmission, including Brazil, Puerto Rico, Mexico, and most of the rest of Central and South America. That means “practice enhanced precautions”, and applies especially to pregnant women.

Meanwhile, in the US, the first reported case of Zika virus infection occurred in Texas in November, 2015, in a woman who had recently traveled to El Salvador. And a resident of Puerto Rico recently developed Zika with no history of travel off the island—meaning that Zika is probably being transmitted by local mosquitos, now. It is only a matter of time for mosquitos in the rest of the warmer parts of the US to start spreading it around here.

It’s a big world, and the health problems of Africa are our health problems, too. New infections will continue to emerge. We’d better keep paying attention, and keep an eye on those mosquitoes.

Ew, Zima

Contraceptives don’t cause birth defects

January 11, 2016

The Pediatric Insider

© 2016 Roy Benaroch, MD

A huge, well-designed Danish study should finally put one concern about oral contraceptive pills to rest. They do not increase the risk of birth defects.

Wait a minute, you might say—birth defects? Those pills are supposed to prevent pregnancy—and if you don’t get pregnant, who cares about birth defects? It turns out that though oral contraceptive pills (OCPs) are about 99% effective in preventing pregnancy in medical studies, in real-world use they fail about 10% of the time over a year of use (that is, about 10% of women relying on OCPs become pregnant during a year of use.) This happens because people sometimes skip pills, or experience drug-drug interactions. So it’s common that women taking OCPs (or who recently stopped OCPs) become pregnant.

There have been several previous studies that have shown mixed results, though those studies were much smaller and often relied on self-reporting of OCPs use and birth defects. In the new study, published in January 2016 in BMJ, researchers evaluated all live births in Denmark from 1997-2011. Pharmacy records were used to see which women had pilled prescriptions for oral contraceptives. They ended up with almost 900,000 births with complete records. The rates of birth defects were essentially identical among all of the groups:

  • Never used OCPs: 25.1 birth defects per 1,000 births
  • Used OCPs more than 3 months before pregnancy: 25.0
  • OCP use 0-3 months before pregnancy: 24.9
  • OCP use during early pregnancy: 24.8

Striking, isn’t it? All of those numbers were statistically identical (that is, within the expected margin of error.) OCP use whether immediately before or during pregnancy did not increase the risk of birth defects.

We’ve got to hand it to the Danes. Their robust national health database and meticulous record-keeping has allowed us to look at huge populations, to find even small markers of risk. A classic 2002 study from the NEJM showed that in a cohort of half a million Danish children, MMR vaccine did not increase the risk of autism. Studies that large are a great way to uncover evidence of even tiny risks. It’s very reassuring that OCPs (and the MMR vaccine) are not things parents need to worry are hurting their babies.

OCPs

The murky connection between maternal antidepressants and autism

December 15, 2015

The Pediatric Insider

© 2015 Roy Benaroch, MD

A new study of almost 150,000 Canadian children is sure to further worry parents. Does taking antidepressants during pregnancy really increase the risk of your baby developing autism by 87%? As usual, the details matter. And the truth is never quite as clear-cut as the press release.

First: what we already know. Autism is a complex disorder of social behaviors and language. It’s unlikely that we’ll ever know “The Cause” of autism, because (like cancer and obesity and many other things) there’s probably not just One Cause. Certainly, genetics plays a huge role—siblings and other relatives of people with autism are at an increased risk for autism spectrum disorders. And we know that many prenatal factors (like premature delivery or maternal health problems) increase the risk, too. Some children with autism have a known genetic variant or marker, and the proportion of those kids seems to rise every year as our testing gets better. Still, there’s a whole lot we don’t know about other influences on how the brain develops, and on what other factors might contribute.

Previous studies on antidepressants taken during pregnancy have had mixed results—some gave shown an increased risk of autism, and others have not. One of the difficulties in doing such a study is that we know maternal depression, itself, is a risk factor for autism. So is it the antidepressant medicines that cause the risk, or the depression itself, or some other factor? For instance, depressed moms may get less sleep, or are perhaps more likely to drink alcohol, or may just feel more stressed—any of these, or any combination of these, could be what really confers the risk to the unborn baby.

In the current study, the authors tried to control for these effects by looking at multiple covariates. There’s some heavy-duty math behind these statistical techniques, but the idea is to isolate one independent variable (taking antidepressants) from every other variable, so you only “see” the effect of what you’re looking for. Of course, you have to know all of those other variables beforehand, and how to measure them, and how they might contribute to your end-point—and that’s why it’s tricky, and that’s why it’s easier to write about a press release than it is to read an actual study and muck your way through the details. In this study, the authors “controlled” for maternal health and mental health issues (though not specifically for maternal autism), substance abuse, income, education level, whether the family received welfare, and many other variables.

The authors used registries of births along with child and maternal health records from Quebec, looking at all babies born in 1998-2009. They excluded premature babies and twins (because these are already known predictors of autism), along with babies with other health problems. Then they looked at the child and maternal health records. To see if mom took antidepressants during pregnancy, pharmacy records were reviewed for filled prescriptions.

The numbers, themselves, are interesting. Of 145,456 live-born babies eligible, 1054 (.7%) were diagnosed with autism during the study period (typically within the first 6 years of life). Of those 145,456 babies, 2532 had moms who took antidepressants during the 2nd or 3rd trimester, including 31 who developed autism. When all of the math was done and covariates accounted for, the proportion of autism worked out to be 87% higher among the moms who took antidepressants after the 1st trimester (there was no increased risk during the 1st trimester, only during the 2nd and 3rd, or the last 6 months of pregnancy.)

That 87% increased risk—that pops, and that’s what you’ll see in the headline. But there are some other things to notice about the study that are more subtle, but just as important. Of the babies whose moms took antidepressants, 1.2% developed autism—and 98.8% did not. The relative increase in risk looks high, but the absolute, actual risk is still quite low. And the whole conclusion of the study rests on those 31 of the 150,000 babies who developed autism after exposure to antidepressants. That’s not a very big number.

I also wonder about controlling for known maternal risks. Perhaps more-severe depression itself confers a higher risk of autism than mild depression—and if more severely depressed moms were more likely than mildly depressed moms to take medication, that would explain the different observed rates. And maternal autism, itself—a friend of mine pointed out that the authors didn’t control for that, and didn’t even try to measure it. But if a higher proportion of moms with autism were depressed (which, logically, makes sense), that would also explain this association, without implicating the antidepressant medication itself.

What should parents do about this? Maternal depression can be debilitating, and needs to be treated—but perhaps non-medical therapy should be the best, first option, especially in the last 2/3rds of pregnancy. But if medication is needed to help mom, I think it’s still a reasonable option, given the small risks that could be implied by this study. It’s also clear from this study that antidepressants in the beginning of pregnancy, through the first trimester, are not associated with increased risks. Women on antidepressants probably don’t need to stop taking them while trying to become pregnant, or early on in the pregnancy.

If your child was exposed to these kinds of medications prior to birth, it would also be sensible to keep tabs on Junior’s development, and refer early on if there’s a concern of autism. Early therapy can be very effective.

People want a clear answer –“This” causes autism. It’s not that simple. This study supports the idea that early influences during pregnancy (such as maternal depression, or maternal medications) can be at least one risk factor. But there’s a whole lot more to learn.

 

Note: after I wrote this, someone sent me this link to NPR’s review of the same study – they did a good job, and provided links to previous research. They also made the point that the lead author of this study has worked with plaintiff’s attorneys who are suing antidepressant manufacturers. Should that color how we look at results like these? You decide.

 

Leo Kanner

Keeping the world safe from antibiotics

December 8, 2015

The Pediatric Insider

© 2015 Roy Benaroch, MD

Intellectually, we know it’s true. Antibiotics are becoming less able to protect us from infections, and it’s our fault. Exposing microorganisms to antibiotics “selects out” the ones best able to survive. Over generations of life the germs that are left become craftier and hardier – and they can even share their genetic material with other unrelated microorganisms, giving nearby pathogens a protective power boost.

This is no surprise. We’ve known this since the first early antibiotics started to lose their power in the 1950’s. But the hope had been that we would keep inventing new antibiotics, so we’d stay ahead of the evolutionary learning curve. We think we’re clever. But we’re now losing the war. The pipeline of genuinely new antibiotics has been running dry, and those persistent and patient bugs are quickly catching up.

To make matters worse, we continue to shoot ourselves in the foot with policies and attitudes that seem designed to make sure the bacteria win:

 

#1: We pump farm animals full of antibiotics they don’t even need

In the US, 80% of the total antibiotics sold go into farm animals, literally about 32.2 million pounds each year. The vast majority of this, about 94%, is added to animal feed or water to be given to healthy, non-infected animals. We’re not talking about animals that are sick with infections, examined by a vet, and prescribed a therapeutic course of medication to help them get healthy—we’re talking about tons of antibiotics, sold legally without a prescription or a veterinarian’s input, directly to farming companies to give to all of their animals. This is entirely legal, and is thought to promote faster growth of animals or allow them to be raised with less feed.

Antibiotics given to animals unquestionably changes the resistance pattern of bacteria on farms, in consumed meat, and in people. And active antimicrobial agents can be found in runoff and wastewater from farms, and in groundwater nearby. These are often the same antibiotics used to treat people with infections.

This problem has a relatively simple fix: we should ban the use of non-therapeutic antimicrobials for agricultural use. Antibiotics should only be given to animals who have infections, under the supervision of a veterinarian, similar to how antibiotics are used in people in the USA. Though, even then there’s still far too much antibiotic overuse, in part because….

 

#2: We expect antibiotics for viral infections

Ask any practicing physician—it’s a daily struggle. Our sloppy prescribing has led to an expectation from many patients that an antibiotic be given for almost any ailment. People think “bronchitis” needs antibiotics, and sore throats, and fevers, and upper respiratory infections. It’s quicker to just write a prescription than to fight about it. And if we don’t give them antibiotics, our “satisfaction scores” will suffer. (Which often means we’ll lose our bonus, or even lose our jobs.)

The fix, this time, has to come from a few different angles:

  • Patient and physician education should stress when antibiotics are and are not helpful.
  • Physicians need to be protected from patient complaints when their recommendations are appropriate.
  • At the same time, physicians need to have the time to evaluate and explain and develop rapport. If we’re expected to prescribe fewer antibiotics, we need the time to explain why.
  • Patients should speak up, too. Physicians often assume that patients “want” antibiotics—but, in truth, many really just want a good careful exam and recommendations. Start your visit with “Doc, I don’t really want antibiotics unless you really think they’re help.” Watch how that statement changes the tone of the encounter. Make yourself an ally in the decisions about your own medical care.

I don’t think these fixes are very difficult, but they’re both going to take some changes in the minds of regulators, doctors, and patients. We can do this, together, but time’s running short. We can still beat the bugs, but it’s not going to be quite as easy as we expected.

 

Alexander Fleming


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