Category Archives: Pediatrics

Sometimes more is not better

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‘More is not better’ may be the case with trimethoprim/sulfamethoxazole (TMP/SMX) Pneumocystis prophylaxis (PCP) (J Pediatr 2014; 164: 389-92).  This study indicates that a single-day course of TMP/SMX prophylaxis is as effective as other regimens.

Design: Prospective survey of 20 centers with newly diagnosed cancer between 2009-2011.  This included 1093 with solid tumors and 1373 with leukemia/lymphoma.  55.6% received 3-day/week prophylaxis, 16.5% received 2-day/week regimen, and 27.9% received 1-day/week regimen (5-10 mg/kg/day into 2 doses).

Key result:

  • Incidence of PCP at 3 years was 0.09% overall.  The two cases occurred in the 2-day regimen (though both had withdrawn from treatment)

The authors note the need for PCP prophylaxis has been questioned for solid tumor patients.  However, the lack of PCP among the 439  children with leukemia/lymphoma indicates that a single day per week regimen is effective.

Bottomline: In GI/liver patients who need TMP/SMX prophylaxis, 1-day per week regimen is likely effective (as it is in leukemia/lymphoma patients).  One-day/week is easier and should help with compliance, which is the key to preventing PCP.

Benefits of Rotavirus Vaccine and Intussception

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The latest information on rotavirus vaccines provide more information on the relative benefits (very high) compared to the risks (very low).

  • NEJM 2014; 370: 503-12
  • NEJM 2014; 370: 513-19
  • NEJM 2014; 370: 568-70 -editorial

While the initial marketing studies for Rotateq (Merck) and Rotarix (GlaxoSmithKiline) which each enrolled more than 60,000 infants did not show a significant risk of intussusception, these latest studies do indicate a very low risk for intussusception.

  • Risks of intussusception: “approximately 1 to 5 cases per 100,000 infants.” This equates to 45 to 213 cases of intussusception nationwide each year.
  • Benefits of these rotavirus vaccines in U.S.: “in the U.S. cohort of 4.5 million babies born each year, vaccination is estimated to prevent approximately 53,000 hospitalizations and 170,000 emergency department visits for diarrhea.”
  • In developing countries, the results for vaccination are even more impressive.  In Mexico which has implemented a vaccination program, there has been a 40% reduction in deaths due to diarrhea (NEJM 2010; 362: 299-305).

Related blog posts:

Why Doctors Don’t Want Unvaccinated Children in Their Practice

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This is a good read by Russell Sanders from The Daily Beast. Here’s the link along with an excerpt:

http://thebea.st/1lpV5Wl  (link from Atul Gawande’s twitter feed)

No contemporary phenomenon confounds and confuses me more than seemingly sensible people turning down one of the most unambiguously helpful interventions in the history of modern medicine.

There are few questions I can think of that have been asked and answered more thoroughly than the one about the safety and effectiveness of vaccines.

The measles-mumps-rubella vaccine does not cause autism.

The HPV vaccine is safe.

There is no threat to public health from thimerosal.

I often wonder why a parent who believes vaccines are harmful would want to bring their children to a medical doctor at all…

If vaccines caused the harms Jenny McCarthy and her ilk claim they do, then my persistence in giving them must say something horrifying about me. Why would you then want to bring your children to me when you’re worried about their illnesses? As a parent myself, I wouldn’t trust my children’s care to someone I secretly thought was a fool or a monster.

It’s not merely that I don’t want to have to worry that the two-week-old infant in my waiting room is getting exposed to a potentially-fatal case of pertussis if these parents bring their children in with a bad cough. It’s not just that I don’t want their kid to be the first case of epiglottitis I’ve ever seen in my career. Those are reasons enough, to be sure. But they’re not all.

What breaks the deal is that I would never truly believe that these parents trust me. Giving kids vaccines is the absolute, unambiguous standard of care, as easy an answer as I will ever be able to offer.

If they don’t trust me about that, how can I hope they would if the questions ever got harder?

Related blog entries:

Unrelated link: Medical app (from Kipp Ellsworth twitter feed): http://goo.gl/pV4vJC :BabyGrow App Enables Parents to Track Children’s CDC/WHO Growth Curves.

 

Do Probiotics Really Help Crying Infants?

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This is the question from a recent meta-analysis (JAMA Pediatr 2013; 167: 1150-57 -thanks to Ben Gold for this reference).

Table 1 details the study designs, probiotic intervention, and outcomes.

Results: “Of the 12 eligible studies (1825 infants), 6 suggested that probiotics reduced crying and 6 did not…Meta-analysis of 3 small trials of breastfed infants with colic found that Lactobacillus reuteri markedly reduced crying time at 21 days…However, all trials had potential biases.”

In the three breastfed trials alluded to above, there were concerns regarding inadequate blinding of the intervention, unequal baseline characteristics, and use of non validated crying “diaries” which could be prone to recall bias.

More data are needed; fortunately there are several ongoing trials.

Bottomline (from the authors’ conclusion): “Although L reuteri may be effective as treatment for crying in exclusively breastfed infants with colic, there is still insufficient evidence to support probiotic use to manage colic, especially in formula-fed infants.”

Previous  related posts:

Cost of Email

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While email has been considered “cost-free,” a recent JAMA Peds letter titled “Metastasis of E-mail at an Academic Medical Center,” identifies a significant opportunity cost.  Think twice about sending that email to everybody! Here’s the link (from John Pohl’s twitter feed): http://dlvr.it/4lD22K 

“If 30 seconds were spent per e-mail, the annual cost per physician to read these mass distribution emails was $1641.”  If 90 seconds each, then $4923.

Tobacco 21 & ENDing Combustible Tobacco Use

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While “some 6 million [deaths] globally every year and 400,000 in the United States” are tobacco-related, the best way to reduce these statistics is unclear.  Currently, nearly 50 million Americans continue to use some form of tobacco. A couple important ideas are discussed in a few recent perspective articles:

  • NEJM 2014; 370: 293-4
  • NEJM 2014; 370: 295-7  bit.ly/P6LiF4 
  • NEJM 2014; 370: 297-9

In my view, the most promising idea is “Tobacco 21.”  Starting in May, in New York City, it will be illegal to sell tobacco products and electronic cigarettes to persons younger than 21 years of age.  While the FDA set a national minimum of age 18 years, states and localities can set a higher age.

Although there are those who decry the ‘nanny state’ interfering in adults who are capable of enlisting in the army, there are compelling arguments to ignore these nihilists.

  1. In 2005, Needham, Massachusetts became the first town with a Tobacco 21 statute.  What has happened?  Youth smoking rate has fallen by nearly half to 6.7% (previously 12.9%).  The surrounding communities have a rate of 12.4% (previously 14.9%). Thus, the rate of decline was nearly triple.  This counters the notion that most of these youths will purchase in adjacent areas.
  2. 80% of adult smokers began smoking daily before 20 years of age.  In addition, “90% of persons who purchase cigarettes for distribution to minors are under 21.”  Thus, Tobacco 21 could make a big dent in a minor’s ability to buy from other students/youths.  Furthermore, 90% of U.S. adults smokers have indicated that “if they had to it over again, they would not have started.”
  3. The “adolescent brain has a heightened susceptibility to the addictive qualities of nicotine.”  Also, adolescents are more impulsive and risk takers which increase the likelihood that they would discount the potential consequences of tobacco experimentation.
  4. Checking age of purchasers is already needed for anyone “who appears younger than 27.” Thus, this does not increase regulatory burdens significantly.

Even though Tobacco 21 is the most logical next step in reducing the dangers of tobacco, a much more visible and controversial measure has been ENDs or electronic nicotine delivery systems.  E-cigarettes have been widely advertised.  The opponents of e-cigarettes object because they have the potential to diminish the stigma of smoking and serve as a gateway product, leading to more smoking (JAMA 2013; 310: 685-6).

On the other hand, advocates suggest that “the majority of e-cigarette users treat them as cessation aides.” Ultimately, these products will improve health only if it helps reduce use of combustible products.

Bottomline: Tobacco 21 has the best potential to reduce the mortality and morbidity of smoking, but ongoing efforts with warning labels, tax increases, clean-indoor policies, cessation programs, and public-service campaigns need to continue.

From NEJM twitter feed: Listen now to audio interview w/ TobaccoFreeKids’ Matthew Myers on efforts to reduce, eliminate, prevent smoking. http://nej.md/LKTV7F 

Related blog posts:

Has Your Hospital Restricted Quarter-Normal Saline?

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In a previous post (What’s critical to you | gutsandgrowth), I’ve drawn attention to the problem of hyponatremia.  This particular hospital problem is often iatrogenic and often preventable.  Two recent studies provide more data to support limiting hypotonic fluids.

The first study that took place between 2009-2011, shows that this remains a common problem at Stanford’s pediatric hospital (J Pediatr 2013; 163: 1646-51).  This study was a retrospective study with data extracted from the hospital’s EMR.

From a cohort of 5498 patients receiving intravenous fluids (IVFs) on admission, 1048 were suitable for study due to the availability of serum sodium levels, not having several types of IVFs, and not being neonatal patients.  In addition, patients who had abnormal sodiums on admission (n=753) were excluded.

Hypotonic fluids included: D5W, one-quarter normal saline (1/4 NS), D5 1/4 NS, 1/2 NS, D5 1/2 NS, and total parenteral nutrition.  No patients received D5W as a maintenance fluid, but its use with medications contributed to total free water delivery.

Isotonic fluids were D5 NS, NS, and Lactated Ringer’s.

Results:

  • Hyponatremia (Na <135 mEq/L) developed in 260 of 674 (38.6%) who received hypotonic fluids and in 104 of 374 (27.8%) who received isotonic fluids. OR 1.63
  • The overall incidence of hyponatremia was 34.7% in this cohort.
  • Other factors associated with developing hyponatremia: surgical admission (adjusted OR 1.44), cardiac admitting diagnosis (aOR 2.08), and hematology/oncology admission (aOR 2.37)

The fact that hyponatremia occurred in a large number on isotonic fluids indicates that additional factors like total fluid volume and uncorrected volume deficits contribute as well. Preferential water retention can still occur in the setting of increased ADH levels. This study, like all retrospective studies, has several limitations.  However, the basic finding that hypotonic fluids increase the risk of hyponatremia remains solid.

The second study was a recent meta-analysis (Pediatrics 2014; 133: 105-113 -thanks to Seth Marcus for this reference) which included ten randomized controlled trials. It showed that hypotonic maintenance IV fluids were associated with a much higher risk of hyponatremia (RR 2.24) and severe hyponatremia (Na <130) (RR=5.29).

Bottomline from both studies: Isotonic fluids are safer than hypotonic fluids in hospitalized children for maintenance IV fluids in terms of decreasing the risk of hyponatremia.

 

“Because It Doesn’t Just Happen to Other People”

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While doctors and scientists extol the virtues of vaccination to prevent disease, the emotional arguments regarding vaccines are sometimes lost due to misleading anecdotal stories.  The stories of missed opportunities and suffering due to the lack of vaccination are underreported.

Here’s an excerpt from one that wasn’t:  Link from Eric Benchimol: fw.to/IiBDiOH 

He, our oldest, 5 1/2, who the day before had been jumping merrily on the trampoline at circus school. Monday morning he woke up, out of breath, complaining of a tummy ache…..He came downstairs to watch TV, sank into the sofa, wheezing as if he had just run a marathon…

Everything was not okay. At noon, our big boy was in the pediatric intensive-care unit of the Centre hospitalier de l’Université Laval; he was plugged in everywhere, an oxygen mask covering his whole face, making him look like an astronaut. The respirator was whirring beside him, the oxygen desperately seeking its path, but not finding it…

The doctor said it was time to intubate, “to give him a chance…”

I marvelled at the work of the nurses, the doctors, in a constant death-defying dance. They put in long days and nights, 12 hours at a stretch and more. They obsessed, they never forgot, always determined to make the right decision at the right time.

Thursday morning, they decided to wake up our big boy, to remove the breathing tube, the IVs, trading them for a simple oxygen mask. Friday morning, the mask gave way to two little prongs in his nostrils. His battered lungs still needed some help. But his heart was beating normally again….

Each time I sat down in that blue leather chair, I wondered: “Where did that pneumonia come from? How did he get hit so hard, so fast?”…

The definitive diagnosis came Wednesday night: H1N1.

“Your son wasn’t vaccinated?”

We lowered our heads. Guilty as charged…

So why am I telling you all this? Why would I annoy you with this little story which, after all, happens to countless others every day during flu season?

Because it doesn’t just happen to other people.

Also, a link from the New England Journal of Medicine: nej.md/1hLXqWt 

An excerpt: “Influenza activity has been surging in the United States, and there are reports of critical illness and death in young and middle-aged adults. The predominant virus so far this season is influenza A(H1N1)pdm09, the cause of the 2009 H1N1 pandemic. Despite many challenges, there is much that the public, patients, the public health community, and clinicians can do now to reduce influenza’s impact…”

“Annual influenza vaccination is recommended for everyone 6 months of age or older in the United States..” It is not too late!

Related blog entries:

How to Understand Scientific Studies

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From John Pohl’s Twitter Feed:

Twenty tips for interpreting scientific claims http://bit.ly/1hY3nD5. Referenced article: Nature 503, 335–337 (21 November 2013) doi:10.1038/503335a

An excerpt:

we suggest 20 concepts that should be part of the education of civil servants, politicians, policy advisers and journalists — and anyone else who may have to interact with science or scientists. Politicians with a healthy scepticism of scientific advocates might simply prefer to arm themselves with this critical set of knowledge…

Differences and chance cause variation…

No measurement is exact. Practically all measurements have some error…Results should be presented with a precision that is appropriate for the associated error, to avoid implying an unjustified degree of accuracy…

Bias is rife. Experimental design or measuring devices may produce atypical results in a given direction….

Bigger is usually better for sample size…

Correlation does not imply causation. It is tempting to assume that one pattern causes another. However, the correlation might be coincidental, or it might be a result of both patterns being caused by a third factor — a ‘confounding’ or ‘lurking’ variable…

Regression to the mean can mislead. Extreme patterns in data are likely to be, at least in part, anomalies attributable to chance or error…

Extrapolating beyond the data is risky. Patterns found within a given range do not necessarily apply outside that range…

Beware the base-rate fallacy. The ability of an imperfect test to identify a condition depends upon the likelihood of that condition occurring (the base rate). For example, a person might have a blood test that is ‘99% accurate’ for a rare disease and test positive, yet they might be unlikely to have the disease. If 10,001 people have the test, of whom just one has the disease, that person will almost certainly have a positive test, but so too will a further 100 people (1%) even though they do not have the disease.

Controls are important. A control group is dealt with in exactly the same way as the experimental group, except that the treatment is not applied. Without a control, it is difficult to determine whether a given treatment really had an effect…

Randomization avoids bias. Experiments should, wherever possible, allocate individuals or groups to interventions randomly…

Seek replication, not pseudoreplication. Results consistent across many studies, replicated on independent populations, are more likely to be solid…

Scientists are human. Scientists have a vested interest in promoting their work, often for status and further research funding, although sometimes for direct financial gain. This can lead to selective reporting of results and occasionally, exaggeration. Peer review is not infallible: journal editors might favour positive findings and newsworthiness. Multiple, independent sources of evidence and replication are much more convincing.

Significance is significant. Expressed as P, statistical significance is a measure of how likely a result is to occur by chance. Thus P = 0.01 means there is a 1-in-100 probability that what looks like an effect of the treatment could have occurred randomly, and in truth there was no effect at all. Typically, scientists report results as significant when the P-value of the test is less than 0.05 (1 in 20).

Separate no effect from non-significance. The lack of a statistically significant result (say a P-value > 0.05) does not mean that there was no underlying effect: it means that no effect was detected. A small study may not have the power to detect a real difference…

Effect size matters. Small responses are less likely to be detected…

Study relevance limits generalizations. The relevance of a study depends on how much the conditions under which it is done resemble the conditions of the issue under consideration…

Feelings influence risk perception. Broadly, risk can be thought of as the likelihood of an event occurring in some time frame, multiplied by the consequences should the event occur…

Dependencies change the risks. It is possible to calculate the consequences of individual events, such as an extreme tide, heavy rainfall and key workers being absent. However, if the events are interrelated, (for example a storm causes a high tide, or heavy rain prevents workers from accessing the site) then the probability of their co-occurrence is much higher than might be expected…

Data can be dredged or cherry picked. Evidence can be arranged to support one point of view…

Extreme measurements may mislead…

Comment: This is a really good reference to provide context for understanding scientific studies and sources of error.

Science That Matters -Especially for Teenage Drivers

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Animated overview of distracted driving study narrated by Editor-in-Chief Jeffrey Drazen. http://nej.md/1hVzO1t (2:43 video from NEJM)

More explanation of this study from NY Times: http://nyti.ms/1dX4lcp 

“An inexperienced driver who reaches for a cellphone increases the risk for a crash by more than 700 percent, a new study found.”