What is a Bone Age?

Bone age is helpful in assessing a child who is shorter or taller than predicted based on parent heights or if a child has early or late pubertal changes. It is simply an x-ray of the child's hand and wrist. It involves minimal radiation and does not hurt. The bone age can help us approximate how much longer a child will grow and the expected height, but does not tell us why a child is shorter or taller than expected or hitting puberty at an unexpected age.

A delayed bone age means that the bones think they are younger than the child actually is. This can mean catch up growth after peers have stopped growing. A delayed bone age can happen for many reasons, but a common one is due to late puberty and can run in families. A history, physical exam and possibly labs can help asses the reason for delayed bone age.

If a child has an advanced bone age it means the bones appear older than the child's actual age. With this we expect them to stop growing earlier than most kids. This means that even if they are tall for their age, they could end up shorter than average. This is often associated with early puberty and childhood obesity. An advanced bone age needs further evaluation to identify the cause.

If the bone age equals the actual age, you can estimate the final height to be about the same percentage as the current height.

We often repeat bone ages to see if they are changing at a different rate than the child grows.

Radiologists and endocrinologists use books with x-rays of standard bones of various age groups to assess which age the child's x-ray most closely resembles. Since there are different bones that can develop at different rates, it is possible that two doctors will assign a different bone age. It is not an exact science, but can give a good estimate of how much longer a child may grow. 

The photo above is from Amazon's bookstore. You can see how the bones of the youngest hand on the left are very different from those in the hand on the right. The radiologist or endocrinologist finds the image that is most like the child's x-ray and call it that bone age. 

In the boy growth charts pictured below, the top set of lines is the height (stature) for age chart. The bottom set is the weight chart. The ages that are used to plot a height at a given time are listed at the top and bottom. The heights are listed on the right and left of the graph. The middle line is 50%, which reflects a height of 50% (taller than half/shorter than half of boys of the same age). The other lines are also labeled for their respective height percentiles on the far right. Hopefully this looks familiar because you've seen a graph like this at your child's doctor. If you haven't, be sure to ask to see it next time you're there.

There are many "normal" heights, usually determined by genetics. Tall parents tend to have tall kids, short parents have short kids. There is no "correct" height or "best" height, the percentiles simply give us a way to follow the growth over time and estimate final adult height if a child hits puberty at a typical age (early puberty stops the growth early, late puberty allows for later growth).

In Figure 1, I filled in a fictitious child's heights with blue dots. You can see that from 3 to 5 years this boy was at the 50th percentile for height. That means he was taller than half the boys his age and shorter than half. The fact that he's in the middle doesn't make it "normal" it just means that if his parents are average height, he is growing as expected because it's consistent year to year and he is of average height like his parents. At 6 years, he dropped to the 25th percentile, and at 8 years he fell to the 10th percentile. This consistent drop in growth often triggers a physician to look for reasons of the drop. Maybe the parents are both very short. Maybe there is a medical problem. Or maybe there is a family history of people having late growth spurts (something called "constitutional growth delay"). Treatment (if needed) varies depending on the cause.

Figure 1

The red arrow on the right marks the actual height at 8 years (blue) at about 47 inches (120cm). For this fictitious child, the bone age is 7 years, and if you plot 47 inches (the actual height at the time) at 7 years (the bone age), you will see this white dot is at the 50th percentile and marked by the red arrow on the left. A delay in bone age often coincides with a late growth spurt. I finished out the growth plots, and this kiddo actually fell more (down to the 5th percentile) before he hit a late puberty and grew into late teens/early 20s to hit a final height at the 50th percentile.

In Figure 2 below a fictitious boy is tall for his age early on. At 6 years old his height (black dot) is at the 97th percentile (he is taller than 97 out of 100 of boys his age) at about 49.5 inches (125.5cm). His bone age at the time (red dot) is 8 years 6 months, which is at the 25th percentile for height. A year later he is off the height chart, taller than over 97% of boys his age, but the bone age is 10 years 9 months, again at the 25th percentile. This chart shows an early growth spurt (as he looks taller than his peers) but an early puberty and a slowed growth faster than other boys. His final height is only at the 25th percentile, much shorter than his early heights would have predicted.

Many parents are super excited when their children are tall and can't comprehend when I talk about the possibility that it might not last. (I typically discuss this if both parents are short but the child is tall, if I see signs of early puberty, or if the child is obese - especially if parents are not as tall as the child's height predicts.) The bone age does not give a reason for the altered growth rate, but can help identify a need for further evaluation and treatment if indicated.

Figure 2

Bone age is difficult to understand, and I hope this helps parents understand with some pictures. I completely made up these growth charts. They do not reflect any real patient or any real diagnosis. They are solely to illustrate how we estimate the bone age on the growth chart to help assess final predicted height. The reasons behind altered growth patterns are many and might require further evaluation.

Take home point: At every well visit your child should have a height and weight measured. If the yearly growth accelerates too fast or slows, talk to your doctor about possible reasons. If a bone age is done, you can use a growth chart to put the bone age in at your child's height (instead of actual age) and see how tall the final height estimate would be. It isn't a guarantee, but can be helpful.

Staying healthy as an athlete

Many people assume that kids who are active in sports are automatically healthy, but that can be far from the truth. Sports do provide exercise, but not all kids participate at the same intensity level, some sports are more inherently challenging, many kids don't eat the needed foods to provide optimal nutrition, and many kids fall far short of the sleep they need to maintain healthy body and mind. There needs to be a balance: eat right, sleep adequately, and exercise daily. Kids also need time to be kids with unstructured time in addition to school, homework, and activities.

Not a typical team sport, but my kids don't do typical sports. This is from an office Bubble Soccer game. 

Eat right

First and foremost with nutrition, we all need to maintain hydration. Many kids avoid drinking at school so they don't have to use the restroom. This is of course not healthy. Talk to your kids about the importance of drinking throughout the day and troubleshoot toileting issues. When kids exercise, be sure they stay hydrated. The large majority of athletes need nothing more than water to stay hydrated. Water is by far the preferred drink of sports nutrition experts unless there is intense exercise longer than 60 - 90 minutes. This does not mean a child playing a baseball game for more than 60 minutes because they are not maintaining the level of intense exercise for the entire game. If a child is running a marathon, added electrolytes might be needed, but short of that type of intensity/duration, water is fine. Sports drinks add far too much sugar and unneeded salts to the diet. Encourage kids to take a sip or two of water every 15-20 minutes of exercise (more or less depending on how hot it is and the intensity of exercise).

As for foods, not all are equal and not all that are marketed as healthy really are healthy. Get in the habit of reading labels. The longer the ingredient list, the less healthy it probably is unless the ingredients are all foods themselves (such as a trail mix with a number of dried fruits and nuts). I've previously addressed the issues of kids getting too many calories. Far too many of our kids are overweight or obese. Many of them are active in sports, but they take in more calories than they use.

• Carbohydrates give quick energy for activity. Examples of healthy carbs are bananas, berries, oats, pasta, rice, and whole grain breads. These are recommended before exercise for energy (but kids don't usually need to carb load unless they are doing an endurance sport), and after exercise with a protein. 
• Protein is important for building and maintaining muscle. I like kids to eat foods with protein and to avoid protein shakes and powders, which are expensive and could possibly lead to too much protein. Examples of good protein sources include nuts and nut butters, eggs, lean meats and fish, yogurt (look for a brand without added sugar) and other dairy products. About 5 -15 g of protein (or about 0.5 to 0.8 grams of protein for every pound of body weight) is all that's needed after a workout, depending on age, size, and workout intensity. Many Americans get far more daily protein than is needed.
• Fat is not as bad as many people make it out to be. It is an important energy source for our bodies and helps us absorb fat-soluble vitamins. Healthy fats come from nuts, avacados, meats, dairy products, and eggs. 

Sleep

Many athletes (and teens in general) fail to get sufficient sleep for good health. They are torn between the demands of school, sports, clubs, volunteering, and making the time for sleep. The spiral typically has them staying up late to catch up on homework, only to be more tired the following day, which leads to poor focus at school - then everything takes longer to do. This encourages them to stay up even later to finish homework, which reinforces the problem. It is not uncommon for me to hear teens report anywhere between 4 and 8 hours of sleep. None of this is enough. Kids who are chronically sleep deprived suffer from more injuries, falling grades, general irritability and depression. I see many teens who want me to find a reason for their fatigue with labs, but it commonly is simply due to sleep debt.

Try to get kids to get enough sleep so they are easy to wake in the morning, stay alert all day, and aren't irritable or hyper in the evenings. If they have trouble sleeping, talk with their doctor.

From the National Sleep Foundation

I see far too many kids who claim to be very active and eat healthy, yet they have problems keeping up with other kids running or have BMIs that seem too high for the reported habits (not due to muscle mass). This could be due to an underlying problem, such as asthma, or habits that aren't as healthy as you think. Bring your child in for a yearly physical to review eating, sleeping, and exercise habits in addition to other health related issues. With most insurance companies there is no co pay for well care, so make the most of your insurance dollars and schedule a well visit! If there are any concerns, you can work with your child's doctor to find help.

Fever Phobia

My partner went to the American Academy of Pediatrics National Conference last Fall and came home with all kinds of new information. Most of it was great. But she also told us about a new product that would be coming to market that is not so great. I personally feel that this new product will be dangerous. Not in the "it will hurt your baby directly" category, but in the "will increase parental anxiety and overtreatment" department.

What's this product?

It's called FeverFrida. It has a sticker that goes under a baby's armpit that measures a baby's temperature every 4 seconds and sends information by bluetooth to the parent so the parent can know all the temperatures. It sends an alert if the temperature is over 99F.

Can you say anxiety inducing???

Fever is our friend, people! It helps fight infection. If we get a virus or bacteria, our body elevates the temperature to kill the infectious agent. I know a lot of people worry when their kids have a fever. I wrote about that in Fever is... because it is a very common fear. But we shouldn't feed that fear. This device will feed the fear with alerts for non-fevers and a reading every 4 seconds. That's 15 readings every minute. That means 21,600 readings in 24 hours. And they encourage you to bring all those readings to your pediatrician. Please don't. I won't even humor you by looking at them. That will encourage the fear. I can't do that.

Pediatricians don't usually consider a temperature a fever until it is at least 100.4F rectally (99F under the arm), so why this gizmo alerts you right at 99F is beyond me. The American Academy of Pediatrics doesn't recommend treating a temperature under 102F unless there is significant pain. (Note: This does not apply to babies less than 2 months, underimmunized kids, and those with immune problems.) In other words, you treat the pain, not the temperature in most kids. Let the fever do it's job! So what is the benefit of having a temperature taken every 4 seconds?

The FeverFrida is from a company that I have recommended for years because they make a wonderful product called Nosefrida. The Nosefrida can get mucus out of babies and helps them get through upper respiratory infections. I do love this product despite how gross it seems to suck the snot out of baby's nose. (We do a lot of gross things as parents if they help!)

I'm disappointed that the company is trying to play on parental fears with the fever monitor. Save your money and watch your baby for symptoms and treat based on these tips.

Travelling around the world? Stay safe and healthy!

Spring Break is around the corner, which means many of my patients will be travelling to various areas of the world for vacation or mission trips. Many of these areas require vaccines prior to travel, so plan ahead and schedule a travel appointment with your doctor (if they do them) or at a travel clinic. Many insurance companies do not cover the cost of travel medicine visits, medications, or vaccines, but they are important and are a small cost in comparison to getting sick when on your trip.

Vaccinate when you can!

Immunization records will need to be reviewed, so if you are going to a travel clinic outside your medical home (doctor's office) be sure to bring the records with you. Vaccines work best when they are given in advance, so do not schedule the pre-travel visit the week you leave! Some vaccines that are recommended are easily available at your medical office but others are not commonly given so might require a trip to a local health department, large medical center, or travel clinic. Check with your insurance company to see if the cost of the vaccine will be covered or not so you can include your cost in your travel budget if needed.

Watch the food and drinks

Many diseases are spread through eating and drinking contaminated foods. If in doubt: do not eat! Cooked foods are generally safer. Any fresh fruits or vegetables should be washed in clean water before eating. Be sure all dairy products are pasteurized. Avoid street vendors, undercooked foods (especially eggs, meats, and fish), salads and salsas made from fresh ingredients, unpeeled fruits, and wild game. Drink bottled water or water that has been boiled, filtered or treated in a way that is known to be reliable. Use the same water to brush teeth. Do not use ice unless you know it is from safe water because freezing does not kill the germs that cause illness. As always, wash hands often, use sanitizer as needed when washing is not available, and avoid touching the "T" zone of your face (eyes, nose, and mouth). Do not share utensils or foods. Avoid people who are obviously ill.

From: http://wwwnc.cdc.gov/travel/page/infographic-food-water-whats-safer

Many companies that schedule international travel recommend bringing antibiotics for prevention or treatment of diarrhea. This is not recommended by many experts due to the rise of "superbugs" with the use of unnecessary antibiotics. In general, the use of antibiotic prophylaxis is recommended only for high-risk travelers, and then only for short periods. The average duration of illness when untreated will be 4 to 5 days, with the worst of the symptoms usually lasting less than a day. Antibiotics might lead to yeast infections, allergic reactions, or even a chronic carrier state (colonization) or irritable bowel syndrome. Antibiotics should be reserved for the treatment of more serious illnesses that include fever and significant associated symptoms such as severe abdominal pain, bloody stools, cramping, and vomiting. Bismuth subsalicylate is available over the counter for adults and can reduce traveler’s diarrhea rates by approximately 65% if taken four times daily. Risks of bismuth products are that it can turn the tongue and stool black and they contain salicylate. Salicylate carries a theoretical risk of Reye syndrome in children, so should be avoided in children. Probiotics and prebiotics have been shown to help prevent and treat diarrheal illnesses safely in most people with intact immune systems.

Mosquitos...

Many diseases are spread by mosquitos. Contact with mosquitoes can be reduced by using mosquito netting and screens (preferably insecticide-treated nets), using an effective insecticide spray in living and sleeping areas during evening and nighttime hours, and wearing clothes that cover most of the body. Everyone at risk for mosquito bites should apply mosquito repellant.

Non-Infectious Risks

Vehicle safety risks vary around the world. Know local travel options and risks. Only use authorized forms of public transportation. For general information, see this International Road Safety page.

Learn local laws prior to travelling.

Be sure to talk with your teens about drug and alcohol safety prior to travel. Many countries have laws that vary significantly from the United States, and some teens will be tempted to take advantage of the legal nature of a drug or alcohol.

Remind everyone to stay in groups and to not venture out alone.

Dress appropriately for the area. Some clothing common in the United States is inappropriate in other parts of the world. Americans are also at risk of getting robbed, so do not wear things that will make others presume you are a good target.

Wear sunscreen! It doesn't matter if you're on the beach or on the slopes, you need to wear sunscreen every time you're outside. Don't ruin a vacation with a sunburn.

For more safety tips, see this helpful brochure.

Keep records

It is a great idea to take pictures of everyone each morning in case someone gets separated from the group. Not only will you have a current picture for authorities to see what they look like, but you will also know what they were wearing at the time they were lost.

Take pictures of your passport, vaccine record, medicines, and other important items to use if the originals are lost. Store the images so you have access to them from any computer in addition to your phone in case your phone is lost.

Have everyone, including young children, carry a form of identification that includes emergency contact information.

Create a medical history form that includes the following information for every member of your family that is travelling. Save a copy so you can easily find it on any computer in case of emergency.

• your name, address, and phone number
• emergency contact name(s) and phone number(s)
• immunization record
• your doctor's name, address, and office and emergency phone numbers
• the name, address, and phone number of your health insurance carrier, including your policy number
• a list of any known health problems or recent illnesses
• a list of current medications and supplements you are taking and pharmacy name and phone number
• a list of allergies to medications, food, insects, and animals
• a prescription for glasses or contact lenses

Specific Diseases to Prevent

Risks of illness vary depending on where you will be travelling and what time of year it will be. I refer to the CDC's travel pages and the Yellow Book for information on recommendations. Some of the most common issues to address are discussed below in alphabetical order.

Dengue Fever

Dengue is a mosquito-borne viral illness. It is seen in parts of the Caribbean, Central and South America, Western Pacific Islands, Australia, Southeast Asia, and Africa. There is no vaccine or specific treatment. Mosquito bite prevention measures are important.

Hepatitis

Infants should begin vaccinations against Hepatitis B starting at birth and against Hepatitis A starting at a year of age. Be sure these vaccines are up to date. Hepatitis A is spread through food and water, so be sure to follow the above precautions even if vaccinated.

Malaria 

Malaria transmission occurs in large areas of Africa, Latin America, parts of the Caribbean, Asia (including South Asia, Southeast Asia, and the Middle East), Eastern Europe, and the South Pacific. Depending on the level of risk (location, time of year, availability of air conditioning, etc) no specific interventions, mosquito avoidance measures only, or mosquito avoidance measures plus prescription medication for prophylaxis might be recommended.

Prevention medications might be recommended, depending on when and where you will be travelling. The medicines must begin before travel starts, continue during the duration of the travel, and continue once you return home. There is a lot of resistance to various drugs, so area resistance patterns will need to be evaluated before choosing a medication.

• Atovaquone-proguanil should begin 1–2 days before travel, daily during travel, and 7 days after leaving the areas. Atovaquone-proguanil is well tolerated, and side effects are rare but include abdominal pain, nausea, vomiting, and headache. Atovaquone-proguanil is not recommended for prophylaxis in children weighing <5 kg (11 lb).
• Mefloquine prophylaxis should begin at least 2 weeks before travel. It should be continued once a week, on the same day of the week, during travel and for 4 weeks upon return. Mefloquine has been associated with rare but serious adverse reactions (such as psychoses or seizures) at prophylactic doses but are more frequent with the higher doses used for treatment. It should be used with caution in people with psychiatric disturbances or a history of depression. 
• Primaquine should be taken 1–2 days before travel, daily during travel, and daily for 7 days after leaving the areas. The most common side effect is gastrointestinal upset if primaquine is taken on an empty stomach. This problem is minimized if primaquine is taken with food. In G6PD-deficient people, primaquine can cause hemolysis that can be fatal. Before primaquine is used, G6PD deficiency MUST be ruled out by laboratory testing.
• Doxycycline prophylaxis should begin 1–2 days before travel to malarious areas. It should be continued once a day, at the same time each day, during travel in malarious areas and daily for 4 weeks after the traveler leaves such areas. Doxycycline can cause photosensitivity so sun protection is required.  It also is associated with an increased frequency of vaginal yeast infections. Gastrointestinal side effects (nausea or vomiting) may be minimized by taking the drug with a meal and it should be swallowed with a large amount of fluid and should not be taken before bed. Doxycycline is not used in children under 8 years. Vaccination with the oral typhoid vaccine should be delayed for 24 hours after taking a dose of doxycycline.
• Chloroquine phosphate or hydroxychloroquine sulfate can be used for prevention of malaria only in destinations where chloroquine resistance is not present. Prophylaxis should begin 1–2 weeks before travel to malarious areas. It should be continued by taking the drug once a week during travel and for 4 weeks after a traveler leaves these areas. Side effects include gastrointestinal disturbance, headache, dizziness, blurred vision, insomnia, and itching, but generally these effects do not require that the drug be discontinued.  

Measles

We routinely give the first vaccine against measles (MMR or MMRV) at 12-15 months of age, but the MMR can be given to infants at least 6 months of age if they are considered high risk due to travel or outbreaks. Under 6 months of age, an infant is considered protected from his mother's antibodies. These antibodies leave the baby between 6 and 12 months. The antibodies prevent the vaccine from properly working, which is why we generally start the vaccine after the first birthday. Any vaccine dose given before the first birthday does not count toward the two doses required after the first birthday, but might help protect against exposure if the immunity from the mother is waning. It is safe for a child to get extra doses of the vaccine if needed for travel between 6 and 12 months.

Meningitis

Meningococcal disease can refer to any illness that is caused by the type of bacteria called Neisseria meningitidis. Within this family, there are several serotypes, such as A, B, C, W, X, and Y. This bacteria causes serious illness and often death, even in the United States. In the US there is a vaccine against meningitis types A, C, W, and Y recommended at 11 and 16 years of age but can be given as young as 9 months of age. MenACWY-CRM is newly approved for children 2 months and older. 

There is a vaccine for meningitis B prevention recommended for high risks groups in the US but is not specifically recommended for travel. 

Meningitis vaccines should be given at least 7-10 days prior to potential exposure.

Travellers to the meningitis belt in Africa or the Hajj pilgrimage in Saudi Arabia are considered high risk and should be vaccinated. Serogroup A predominates in the meningitis belt, although serogroups C, X, and W are also found. There is no vaccine against meningitis X, but if one gets the standard one that protects against ACWY, they will be protected against the majority of exposures. The vaccine is available for children 9 months and older in my office and a newer vaccine is approved for 2 months and up. Boosters for people travelling to these areas are recommended every 5 years. 

Tuberculosis

Tuberculosis (TB) occurs worldwide, but travelers who go to areas of sub-Saharan Africa, Asia, and parts of Central and South America are at greatest risk. Travelers should avoid exposure to TB in crowded and enclosed environments and avoid eating or drinking unpasteurized dairy products. The vaccine against TB (bacillus Calmette-Guérin (BCG) vaccine) is given at birth in most developing countries but has variable effectiveness and is not routinely recommended for use in the United States. Those who receive BCG vaccination must still follow all recommended TB infection control precautions and participate in post-travel testing for TB exposure. It is recommended to test for exposure in healthy appearing people after travel. It is possible to have a positive test but no symptoms. This is called latent disease. One can remain in this stage for decades without any symptoms. If TB remains untreated in the body, it may activate at any time. Typically this happens when the body's immune system is compromised, as with old age or another illness. Appropriately treating the TB before it causes active disease is beneficial for the long term.

Typhoid

Typhoid fever is caused by a bacteria found in contaminated food and water. It is common in most parts of the world except in industrialized regions (United States, Canada, western Europe, Australia, and Japan) so travelers to the developing world should consider taking precautions. There are two vaccines to prevent typhoid.

• Children over 2 years of age can be vaccinated with the injectable form. It must be given at least 2 weeks prior to travel and lasts 2 years. 
• The oral vaccine for children over 5 years and adults is given in 4 doses over a week's time and should be completed at least a week prior to travel. The oral vaccine lasts 5 years. 
• Neither vaccine is 100 % effective so even immunized people must be careful what they eat and drink in areas of risk.

Yellow Fever

Yellow fever is another mosquito-borne infection that is found in sub-Saharan Africa and tropical South America. There is no treatment for the illness, but there is a vaccine to help prevent infection. Some areas of the world require vaccination against yellow fever prior to admittance. Yellow fever vaccine is recommended for people over 9 months who are traveling to or living in areas with risk for YFV transmission in South America and Africa.

Zika Virus

At this time it is advised that pregnant women and women who might become pregnant avoid areas in which the zika virus is found. For up to date travel advisories due to this virus, see the CDC's Zika page.

Tamiflu

During flu season we have many requests for Tamiflu (oseltamivir) because of flu exposure or disease. I have rarely complied with these requests, though in recent years more often due to the powers that set the guidelines recommending it more. It is more common in my experience to hear negative feedback about side effects than it is to see patients get better faster. (Note: this is a very biased view, since those who are better would not call, but since so many call with side effects it seems fair to say I don't like the drug.)

photo source: Shutterstock

I am not alone in my dislike of Tamiflu. I follow a listserv of pediatricians around the country and many share my views. A recent topic thread on treatment of flu has peaked my interest. One doctor suggested watching a TED Talk by Dr. Ben Goldacre: What doctor's don't know about the drugs they prescribe.  Dr. Goldacre starts talking about Tamiflu specifically about 10:10, but the entire lecture is done in an entertaining and informative manner if you have the time.

I feel deceived. When I practice medicine, I follow standard recommendations and guidelines that are based on peer reviewed articles and data. The question is, what important data is left out? There is a movement to solve this problem of unpublished studies. You can see updates at the Tamiflu Campaign of the British Medical Journal.

Back to influenza treatment...

First, current influenza treatment guidelines regarding the use of antivirals: 

The current guidelines basically say every child should be considered a candidate for an antiviral treatment. I understand the reasoning behind the first two conditions of antiviral use (except that studies don't really support even those indications), but I am very confused about the third highlighted below.

(from http://aapnews.aappublications.org/content/early/2013/09/02/aapnews.20130902-1)

ANTIVIRALS CONTINUE TO BE IMPORTANT IN THE CONTROL OF INFLUENZA.

Treatment should be offered for:

• any child hospitalized with presumed influenza or with severe, complicated or progressive illness attributable to influenza, regardless of influenza immunization status; and
• influenza infection of any severity in children at high risk of complications of influenza.

Treatment should be considered for:

• any otherwise healthy child with influenza infection for whom a decrease in duration of clinical symptoms is felt to be warranted by his or her pediatrician; the greatest impact on outcome will occur if treatment can be initiated within 48 hours of illness onset.

Then look at what a search for "unpublished tamiflu trials" shows.

For those of you unfamiliar with the Cochrane group, I need to take a quick sideline. They are a well respected group that reviews all the studies within certain parameters on one topic to evaluate the overall findings of several independent studies. 

From the Cochrane Group: A review of unpublished regulatory information from trials of neuraminidase inhibitors (Tamiflu - oseltamivir and Relenza - zanamivir) for influenza. These results are from a review of published and unpublished studies that they could find. From the abstract: "The authors have been unable to obtain the full set of clinical study reports or obtain verification of data from the manufacturer of oseltamivir (Roche) despite five requests between June 2010 and February 2011. No substantial comments were made by Roche on the protocol of our Cochrane Review which has been publicly available since December 2010. 

They found several problems with Tamiflu from the studies they were able to review:

• Drug manufacturers sponsored the trials, leading to publication and reporting biases. One of the authors reported that 60% of the data was never published. This is over half of the research, and I suspect it didn't support use of the medicine (remember the company that benefits from selling the medicine was doing the trials...)
• There was no decrease in hospitalization rate for influenza in people treated with Tamiflu.
• There was not enough evidence of prevention of complications from influenza. Design of the trials (again by the people who make the drug) did not report the prevention of complications from influenza, such as secondary infections.
• There is not evidence in the trials to support that Tamiflu reduces spread of the virus. One of the main reasons people request the medication is after exposure to prevent illness! (Note: this might have changed because the indications on the package insert now say it can be used to prevent illness in those over 1 year of age and they were previously not allowed to mention prophylaxis.) 
• Tamiflu reduced symptoms by 21 hours. Yep. Less than one day of fewer symptoms. For the cost of the drug and the potential side effects, is feeling sick for 1 day less really worth it? 
• There was a decreased rate of being diagnosed with influenza in those randomized to get Tamiflu, probably due to an altered antibody response. The authors suspect a body becomes less able to make its own antibodies against influenza when taking Tamiflu. 
• Side effects were not well documented.

A review study done in children exclusively Neuraminidase inhibitors for treatment and prophylaxis of influenza in children: systematic review and meta-analysis of randomised controlled trials focused on treatment of disease and prevention of illness after exposure. Findings included:

• Symptom duration decreased between 0.5 and 1.5 days, but only significantly reduced symptoms in 2 of 4 trials. That means in 2 of 4 trials there was no significant reduction in symptoms.
• Prophylaxis after exposure decreased incidence by 8% of symptomatic influenza. This means for every 13 people given Tamiflu to prevent disease, one case will be prevented. Not great odds.
• Treatment was not associated with an overall decrease in antibiotic use, suggesting it did not alter the complication of bacterial secondary infections.
• Tamiflu was associated with in increased risk of vomiting. About 1 in 20 children treated with Tamiflu had an increased risk of vomiting over the baseline vomiting due to influenza.
• There was little effect on the number of asthma exacerbations or ear infections by treating influenza with Tamiflu.

So what do I recommend during the cold and flu season?

1. Get vaccinated! The influenza vaccines have been shown to help prevent influenza and are very well tolerated with few side effects. If you or your children are due for other vaccines, be sure to get caught up.
2. If you get sick, stay home until you're fever free without the use of a fever reducer for at least 24 hours! Don't spread the illness to others by going to work or school. The influenza virus is spread for several days, starting the day before your symptoms start until 5-7 days after symptoms start-- kids may be contagious for even longer. You are most contagious the days you have a fever.
3. Wash hands well and frequently. If you can't use soap and water, use hand sanitizer.
4. Cover your cough and sneeze with your elbow or a tissue.
5. Avoid close contact with people who are sick. But remember that people spread the virus before they feel the first symptoms, so anyone is a potential culprit!
6. Don't share food, drinks, or towels (such as after brushing teeth to wipe your mouth) with others. 
7. Don't touch your eyes, nose, and mouth -- these are the portals for germs to get into your body. 
8. Keep infants away from large crowds during the sick season.
9. Frequently clean objects that get a lot of touches, such as keyboards, phones, doorknobs, refrigerator handle, etc.
10. Avoid smoke. It irritates the airway and makes it easier to get sick.
11. Remember that many germs make us sick during the flu season. Just because you've been sick once doesn't mean you won't catch the next bug that comes around. Use precautions all year long!

Because the guidelines recommend Tamiflu as above, I will probably be forced to prescribe it by worried parents who hope that their kids will feel better. (You've heard of defensive medicine, right?) 

Influenza is a miserable illness. The key is prevention. I've had my vaccine, how about you? 

Further Reading:

Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children: A link is available to the full text of the study by T Jefferson, MA Jones, P Doshi, CB Del Mar, CJ Heneghan, R Hama, and MJ Thompson.

Update 2016:

The CDC continues to recommend Tamiflu (oseltamivir) and other anti-viral medications. I continue to wonder why.

There continues to be a lot of confusion about unpublished studies. Investigators have documented their discussions with the maker of Tamiflu on Tamiflu correspondence with Roche.

Recent studies have tried to compile all that is known about how oseltamivir works:

• Oseltamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments. 

Results from this study include:

• In the treatment of adults, oseltamivir reduced the time to first alleviation of symptoms by 16.7 hours, 29 hours in children.
• There was no difference in rates of admission to hospital between treatment groups in both adults and children.
• Oseltamivir relieves symptoms in otherwise healthy children but has no effect on children with asthma who have influenza-like illness.
• Oseltamivir had no significant effect on admissions to the hospital.
• Oseltamivir causes gastrointestinal disturbances in both prophylaxis and treatment roles. In prophylaxis, it caused headaches, renal events (especially decreased creatinine clearance), and psychiatric effects. 

Antibiotic Allergy or Just a Rash?

During the winter months more people get sick, so more people are treated with antibiotics. While antibiotics can help treat bacterial infections, they do carry risks. One of those risks is an allergic reaction. This is one of the reasons pediatricians avoid using antibiotics liberally. Most of the time our bodies can fight off the germs that cause illness and antibiotics don't help treat viruses at all.

When someone is on a medicine and they develop a rash it can sometimes be hard to sort out if symptoms are part of the illness, a non-allergic drug reaction, or an allergic reaction. There are many people who had a rash while taking an antibiotic as a child and were told that they are allergic to that antibiotic, but really aren't. Unfortunately this can lead to more expensive and broader-range antibiotics being used inappropriately and unnecessarily.

About 2% of prescription medications (not just antibiotics) cause a "drug rash". The rash usually begins after being on the medicine for over a week (earlier if there was previous exposure to the medicine), and sometimes even after stopping the medicine. It can look different in different people. Some get pink splotchy areas that whiten (blanch) with touch. Others get target-like spots, called Erythema Multiforme. Often the rash seems to worsen before it improves, whether or not the medicine is stopped. Skin can peel in later stages. It can itch but doesn't have to. Some people have mild fever with these symptoms. In adults this type of rash is often a sign of allergic reaction, but in kids a rash is most often a viral rash - meaning they have a virus that causes a rash but they happen to be on an antibiotic (or other medicine). This is why diagnosing allergy versus drug reaction is tricky. These symptoms can mean allergy to the drug, but (especially in kids) is often just a symptom of a virus (or some bacteria, such as Strep or Mycoplasma).

Up to 10% of children taking a penicillin antibiotic (which includes the commonly used amoxicillin and augmentin) develop a rash starting on day 7 of the treatment. (It can be earlier in people who have had the antibiotic previously.) This rash tends to start on the trunk, looks like pink splotches that can grow and darken before fading. It does not involve difficulty breathing, swelling of the face or airway, or severe itching. Because of this reaction many people live their life thinking they have an allergy to penicillin, even though many of them don't. 

Amoxicillin rash after 17th dose (about the 8th day). Photo source: By Skoch3 (Own work) [GFDL (http://www.gnu.org/copyleft/fdl.html) or CC BY-SA 4.0-3.0-2.5-2.0-1.0 (http://creativecommons.org/licenses/by-sa/4.0-3.0-2.5-2.0-1.0)], via Wikimedia Commons

Same child, 8 hours after the above photo. Photo source: By Skoch3 (Own work) [GFDL (http://www.gnu.org/copyleft/fdl.html) or CC BY-SA 4.0-3.0-2.5-2.0-1.0 (http://creativecommons.org/licenses/by-sa/4.0-3.0-2.5-2.0-1.0)], via Wikimedia Commons

Why does this happen? We don't know for sure. But it can cause a very significant rash, especially with the virus that causes mono.

Up to 80 -90 % of people who have mono develop a rash if they are treated with a penicillin antibiotic (like amoxicillin). This is common since symptoms of Strep throat and mono are very similar, and penicillins are the drug of choice for Strep throat. Some people with mono have a false positive test for Strep throat, meaning they do not have Strep but the test is positive. This is why it is very important for the medical clinician to take a careful history of symptoms and do an exam, even with "classic" Strep symptoms. (If I had a dollar for every parent who says the symptoms are just like all her kids when they get Strep, can't I just call it in...) Always be sure to get a Strep test and full exam to evaluate if it is really Strep or possibly mono. Blood tests for mono can be ordered if clinically indicated. Never treat a sore throat without a full evaluation.

Amoxicillin rash that developed several days after starting amoxicillin with mono. Image from Ónodi-Nagy et al. Allergy, Asthma & Clinical Immunology 2015 11:1   doi:10.1186/1710-1492-11-1

How do we know if it's a real allergy? 

Doctors will take a careful history of all symptoms of the illness, the timing of when the rash developed during the illness and when the medicine was given. If it is a classic viral rash, nothing further needs to be done. If there are symptoms (see below) that help identify a true allergy and make a clear diagnosis, then avoidance of that medication should be done. Be sure all your doctors and pharmacists know of this allergy. If it is not clear then further evaluation can be done. Allergists can do skin testing to see if there is a penicillin allergy, but most antibiotics do not have testing available so an oral challenge (in a controlled setting) is used if there were no clear allergy symptoms with a rash.

Mild to moderate allergic reactions can have the following symptoms:

• Hives (raised, extremely itchy spots that come and go over a period of hours)
• Tissue swelling under the skin, often around the face (also known as angioedema)
• Trouble breathing, coughing, and wheezing

Anaphylaxis is a more serious allergic reaction and can include:

• Difficulty breathing or wheezing
• Swelling of the face, tongue, throat, lips, and airway
• Dizziness
• Loss of consciousness
• Shock
• Death

Final Take Away

As you can see, rashes that develop while on medications can be quite a conundrum. If one develops, be sure to get in touch with your doctor. We usually cannot diagnose rashes over the phone, so an appointment may be necessary.

Thank you to Kressly Pediatrics for posting a comment on Twitter (@KresslyPeds) about drug reactions to give me the idea for this blog!

How To Keep Your Family Healthy This Winter

This blog is short and sweet about avoiding illness this sick season, but has links to dig deeper as desired.

It's not a big secret. We know the best ways to stay healthy, but it takes everyone to participate to make it work.

Practice the following routinely and help stop the spread of illness!

1. Wash hands or use hand sanitizer (sanitizer is not helpful at eliminating all germs - see the link for more information on how and when it is appropriate) 
2. Eat healthy and drink water (infants under 6 months should drink breast milk or formula)
3. Sleep
4. Get vaccinated
5. Don't touch your face - this is where germs enter our bodies!
6. Probiotics might help (recent meta analysis)
7. Wipe down objects regularly: learn the difference between cleaning, disinfecting, and sanitizing.
8. Safely prepare and serve food 
9. Cover your cough and sneeze with your elbow.
10. Avoid sick people
11. Stay home when sick

Things that haven't been shown to help:

1. Mega doses of vitamins
2. Cough and cold medicines have limited benefits, if any at all
3. Homeopathic medications
4. Essential oils
5. Antibiotics for viral illnesses (most cold and coughs)
6. Using an improper medication dosing device

Related blogs:

How Long Will a Cough or Cold Last?

Cough Medicine: Which one's best?

My Child's Cough Sounds Like...

But the snot is green...

Sick, sick, and more sick

Holidays and family spoiled by illness... It's that time of year!

To Tamiflu or Not to Tamiflu?

Tamiflu: Guest Blogger Dr. Mark Helm

Adenovirus Infections

Evolution of Illness

Fever Is...

New High Risk Child RSV Prevention Guidelines