Posts Tagged ‘drugs’

New recommendations for the treatment of bronchiolitis: we should do less because it doesn’t help

December 2, 2014  |  General  |  No Comments

Every fall I write about bronchiolitis because it is one of the most common respiratory ailments affecting infants and children under about two years of age. It is the most common reason infants end up in the hospital during the winter and early spring months. Every year we get severe cases in the PICU. Pediatricians have struggled for decades to figure out how to treat bronchiolitis but we don’t have any specific therapies that work very well. (We have some promising treatments on the horizon, though, as I wrote about here.) Recognizing this, the American Academy of Pediatrics has significantly revised its recommendations of what we should and should not do for children with bronchiolitis. Before I describe these new recommendations, however, I should review what bronchiolitis is and why it can make small children, particularly infants, so sick.

Bronchiolitis is caused by a viral infection of the small airways, the bronchioles. By far the most common virus to do this is one we call respiratory syncytial virus, or RSV. To scientists, RSV is a fascinating virus with several unique properties. One of these is its behavior in the population. When it’s present, RSV is everywhere. Then it suddenly vanishes. There are exceptions to everything in medicine — I have seen sporadic cases during the off-months — but generally RSV arrives with a bang in mid-winter and then leaves suddenly in the spring. It’s the only virus that consistently and reliably causes an epidemic every year, although it often alternates more severe with milder visitations. RSV epidemics often have some regional variability. For example, often one city will have a much more severe epidemic than do others in other regions of the country.

Another aspect of RSV that interests medical scientists is how poor a job our immune systems do in fighting it off. Virtually all children are infected with RSV during the first few years of life. Not only that, all of us are reinfected multiple times during our lives. Attempts at devising a vaccine for RSV have all been unsuccessful. In fact, early versions of an experimental vaccine seemed to make the disease worse in some infants, raising the possibility that some aspect of our immune response to the virus actually contributes to the symptoms.

RSV has a high attack rate — the term scientists use for the chances that a susceptible person will get the infection if exposed to it. That, plus our generally poor defenses against it, explain the frequent epidemics. Every year a new crop of susceptible infants enters the population.

So what is bronchiolitis? What does it look like? In medical terminology, adding the ending “itis” to a word means that whatever comes before is inflamed. Thus tonsillitis is an inflammation of the tonsils and appendicitis means an inflamed appendix. So bronchiolitis is an inflammation of the bronchioles, the final part of the system of air-conducting tubes that connect the lungs with the outside world. Beyond the bronchioles are the aveoli, the grape-like clusters of air sacs where the business of the lungs — getting oxygen into our bodies and carbon dioxide out — takes place.

Bronchiolitis is a disorder of blocked small airways. This prevents air from getting in and out normally, primarily out.  The principal source of the blockage is that the bronchiole tubes are blocked from swelling of the walls and from debris caused by the RSV infection — bits of broken airway cells and mucous plugs. This picture shows what it looks like:

Infants are the ones who have the most trouble breathing with bronchiolitis. There are several reasons for this, but a key one is the construction of an infant’s chest. When small airways get blocked, we use our chest muscles — tightening them — to force air in and out of our lungs. We are helped in doing this by the fact that our lungs are encased in a fairly rigid rib cage; when we use our muscles to squeeze or expand our chest the system works like a bellows. Infants can’t do this well because the ribs across the entire front half of their chest are not yet solid bone — they are still soft cartilage.  So when a small infant tries to move air against anything that is restricting airflow, like clogged bronchioles, his chest tends to sink inwards, causing what we call retractions. These are easiest to see just below the last ribs. They especially have trouble forcing air out, so their chests become hyperexpanded with air, making it look as if their chests are puffed out a little. The other reason infants have so much trouble handling debris in their bronchioles is that these tubes are already much smaller to start with, so they get more easily clogged up than do the larger airways of older children.

How does a child with bronchiolitis look? Typically they are breathing faster than the normal respiratory rate of 25-35; often they are puffing along at 60-70 breaths per minute. They also will show those chest retractions and have a cough. Fever is uncommon. They may look a bit dusky from not having enough oxygen in the blood. They often have trouble feeding because they are breathing so fast. The fast breathing, along with the poor feeding, often makes them become dehydrated. Our breath is completely humidified, so when we breathe fast we lose more water.

What can we do to treat bronchiolitis? You read above that we have no specific medicine that will kill the virus. What we have to offer is what we call supportive care: treating the symptoms until the infection clears. Some of that supportive care has been based on how we treat asthma, another condition where air has trouble getting into and out of the lungs. Some years ago we learned that these asthma treatments, such as albuterol breathing treatments and steroids, helped very few children. Even though we knew that fact, a common thing was to try the asthma drugs and see if they helped an individual child, then continue them if it appeared they did.

The new recommendations come down strongly on the side of not even trying these asthma drugs because compelling research argues against it. More than that, the new recommendations say not to take a chest x-ray because it doesn’t help the child and may cause more risk; taking a chest x-ray often leads to physicians over-diagnosing pneumonia and giving antibiotics when they aren’t called for. The new recommendations even suggest we stop testing for the RSV virus, which has been commonly done, because it doesn’t affect anything we do. One thing the recommendations continue from the past is providing good hydration, as well as oxygen if the child needs it — some do, but many do not.

One important point to make, especially for me as a pediatric intensivist, is that these recommendations only apply to children with milder disease. Some children with bronchiolitis become extremely ill and require help with their breathing, either with soft plastic prongs in their nose that deliver oxygen and air pressure or with a mechanical breathing machine. For those children we do what it takes to keep their blood oxygen levels in the safe range.

Old ways die hard, and it will be interesting to see if physicians follow these new recommendations. My guess is that, over time, we will. More and more we are learning that therapies that add risk and cost, without adding any benefit, are not the way to go.

Finally, an effective treatment for respiratory syncytial virus (RSV)?

September 22, 2014  |  General  |  1 Comment

Respiratory syncytial virus infection, aka RSV, is a common infection in children. A key aspect of RSV is how poor a job our immune systems do in fighting it off. Virtually all children are infected with RSV during the first few years of life. Not only that, all of us are reinfected multiple times during our lives. Attempts at devising a vaccine for RSV have all been unsuccessful. In fact, early versions of an experimental vaccine seemed to make the disease worse in some infants, raising the possibility that some aspect of our immune response to the virus actually contributes to the symptoms.

RSV has a high attack rate — the term scientists use for the chances that a susceptible person will get the infection if exposed to it. That, plus our generally poor defenses against it, explain the frequent epidemics. Every year a new crop of susceptible infants enters the population.

The most common form of RSV infection is called bronchiolitis. In medical terminology, adding the ending “itis” to a word means that whatever comes before is inflamed. Thus tonsillitis is an inflammation of the tonsils and appendicitis means an inflamed appendix. So bronchiolitis is an inflammation of the bronchioles, the final part of the system of air-conducting tubes that connect the lungs with the outside world. Beyond the bronchioles are the aveoli, the grape-like clusters of air sacs where the business of the lungs — getting oxygen into our bodies and carbon dioxide out — takes place.

Bronchiolitis is a disorder of blocked small airways. This prevents air from getting in and out normally, primarily out. In bronchiolitis, the main problem is that the bronchiole tubes are blocked from swelling of the walls and from debris caused by the RSV infection — bits of broken airway cells and mucous plugs. It looks like this, with the arrows showing air movement.

Infants are the ones who have the most trouble breathing with bronchiolitis. There are several reasons for this, but a key one is the construction of an infant’s chest. When small airways get blocked, we use our chest muscles — tightening them — to force air in and out of our lungs. We are helped in doing this by the fact that our lungs are encased in a fairly rigid rib cage; when we use our muscles to squeeze or expand our chest the system works like a bellows. Infants can’t do this well because the ribs across the entire front half of their chest are not yet solid bone — they are still soft cartilage.  So when a small infant tries to suck air in against anything that is restricting airflow, like clogged bronchioles, his chest tends to sink inwards, causing what we call retractions. These are easiest to see just below the last ribs. They also have trouble forcing air out, so their chests become hyperexpanded with air, making it look as if their chests are puffed out a little. The other reason infants have so much trouble handling debris in their bronchioles is that these tubes are already much smaller to start with, so they get more easily clogged up than do the larger airways of older children.

We have never had any specific treatment that works for RSV bronchiolitis. All we can do is what we call supportive care — oxygen, some breathing treatments (which usually don’t help much), IV fluids if the child is too sick to eat, and a few things we can do to help with mucus clearance. But now that may be changing. A recent study looked at a new drug to kill the RSV virus directly, something we’ve never had before.

The drug, which can be given orally, was tested on adults, not children — yet. The results were very encouraging. One of the issues with other anti-viral drugs has been that they only work well if they are given very early in the course of the illness or even before symptoms start. This new anti-RSV drug works even after people are sick with the virus. It greatly reduced the amount of virus in respiratory mucus, where we usually find the virus. Perhaps more importantly for sick infants, it also caused rapid improvement in symptoms.

Dr. Peter Wright, an RSV expert, is excited about the possibilities of the drug. Dr. Wright has worked on RSV for many, many years — so many that he was one of my teachers at Vanderbilt Hospital way back in 1978. I can recall that he does not get excited easily. I’m excited, too, because severe RSV bronchiolitis is a real scourge we see frequently in the PICU. Some infants even die from it. I was also pleased to read that Dr. Wright is still on the RSV case after all these years.

Is the ADHD fad finally going to break?

Is the ADHD fad finally going to break?

May 6, 2014  |  General  |  No Comments

Few pediatricians doubt that ADHD — attention deficit hyperactivity disorder — is a real thing than can be quite disabling to some children. Further, few pediatricians question that stimulant medications like Adderall and Concerta can be very helpful for these children. But any reasonable person should be skeptical that 11% of all children and 20% of teenage boys have ADHD requiring medication. Those are the recent numbers reported by the Centers for Disease Control. The person most responsible for identifying ADHD and researching for 30 years how to treat it is Dr. Keith Conners, emeritus professor of psychology at Duke University. In a recent interview he had this to say about this apparent epidemic:

“The numbers make it look like an epidemic. Well, it’s not. It’s preposterous,” . . . “This is a concoction to justify the giving out of medication at unprecedented and unjustifiable levels.”

There is big money to be made in ADHD. As you can see from the graph above, sales of stimulants have risen 500% since 2002. ADHD is also just the kind of disorder the drug companies love — a chronic condition that requires daily medication for many years. They are far less interested in developing drugs that cure things because the market goes away. Drug companies market ADHD. They sponsor a large number of conferences for physicians and mental health workers encouraging them to diagnose it and, of course, to treat it. Patient advocacy groups for ADHD are helpful. But they also get a huge chunk of their funding from the drug industry, something few people know. And now a whole new frontier for Big Pharma has opened up with the identification that some adults have ADHD and respond to stimulant therapy. For those who suffer from ADHD the therapy helps significantly. But you can see the temptation to over-diagnosis it in adults, too. With all these prescriptions you can also see the ease with which they can be diverted to the illicit drug market. That happens frequently.

Is there any hope of moderating this trend, of getting the prescription numbers back down out of the stratosphere? A recent editorial in Psychiatric Times by Allen Frances sees some hope. That hope is based in the common sense of people pushing back. Here is what he has to say about that:

The percentage of kids being diagnosed (11% overall and 20% of teenage boys) is so absurdly high that reasonable people can no longer accept that the label is being applied with anything approaching sufficient care and caution.

I hope he’s correct. The principal problem with diagnosing ADHD is that there is no specific test for it, no blood test or scan that doctors can use to decide who has it. The diagnosis is made by ticking off items on a checklist, a checklist that was devised by committees of experts, committees which periodically change their minds and modify the diagnostic criteria. Inevitably the diagnosis has a fair amount of subjectivity built into it. Dr. Frances also reminds us that psychiatry has always wrestled with the subjective nature of mental illness, a situation that is ripe for diagnostic fads and fashions:

The history of psychiatry is littered with the periodic recurrence of fad diagnoses that suddenly achieve prominence and then just as suddenly fade away. Human distress is always hard to explain and sometimes hard to tolerate. Diagnostic labels, even false ones, can gain great and undeserved popularity because they seem to explain the otherwise unexplainable and provide hope that describing a problem will lead to improving it. And once you have a diagnostic hammer, everything begins looking like a nail.

I think that is quite perceptive.

Vaccines and parents’ selective worries about medical risks

February 23, 2014  |  General  |  No Comments

I’ve been involved in several boisterous Twitter debates about vaccines, at least to the extent that one can debate using snippets of 140 characters or less. I’ve also been a Super Moderator at a very large Internet message board (AbsoluteWrite) for many years and have seen my share of passionate vaccine debates there. I’ve been a pediatrician for over 30 years and trained in the subspecialty of pediatric infectious diseases before I went into critical care. So I think a lot about vaccines and have watched controversies about them come and go for a very long time. It’s been interesting. One very interesting aspect for me is trying to understand how parents think about the relative risk of medical treatments and procedures for their children. It’s different from how physicians think of risk, and I think this difference is key to understanding the continuing ferment over vaccinations. I’ve previously written about the risk of a vaccine injury (about 1 in a million at worst) compared to the risks of everyday life, but there is another aspect to the issue: in my experience parents are uniquely worried about vaccine risk in ways they are not about other medical procedures and treatments. A few examples illustrate my point.

Stevens-Johnson syndrome is a severe skin reaction to something, most commonly a medication. It varies in severity but can progress to a very bad condition known as toxic epidermal necrolysis. This is a life-threatening condition and often requires a prolonged stay in the intensive care unit. I have seen several life-threatening cases over the years. The drugs that can cause it are quite common ones. Many are antibiotics; sulfa drugs, for example,  are well-known offenders. How common is this condition? There are about 300 cases per year in the USA. This makes it much more common than vaccine injury, yet nearly all parents think of antibiotics as safe drugs. On balance, they are — but they are not risk free.

Medications like antibiotics can cause other kinds of allergic reactions, which can be severe or life-threatening. A very conservative estimate is that about 0.01-0.05 % of all people — about 1-5 per 10,000 individuals — will have such a serious drug reaction in their lifetime. Yet parents accept prescriptions without worrying about that.

Another example is anesthesia. As part of my practice I anesthetize many children for procedures, such as MRI scans. The risk of doing this is low, but it is well above zero. The actual risk of death from an anesthetic is around 1 in 250-300,000 — about 3 times the risk of a serious vaccine reaction. There also may be neuro-developmental risks to young children who receive anesthetics. That risk is very low, too (there are many studies ongoing to define it), but it is not zero. Of course if a child needs emergency surgery the balance of risk versus benefit overwhelmingly favors using the anesthetic, but there are many other situations that are not so clear-cut. Yet virtually all parents willingly allow me anesthetize their child.

My point is that vaccine risk, compared with the risks of other medical interventions, causes particular concern among parents, and I am not sure why that is. However, it is not new. Since the introduction of the very first vaccine, Edward Jenner’s use of smallpox vaccine, people have been particularly suspicious of vaccines. (The name “vaccine” itself is derived from Jenner’s use of the vaccinia virus, the cowpox virus, as a protection against smallpox.) As noted in the essay linked above:

Although the time periods have changed, the emotions and deep-rooted beliefs—whether philosophical, political, or spiritual—that underlie vaccine opposition have remained relatively consistent since Edward Jenner introduced vaccination.

I suppose the notion of putting a foreign substance into a child’s body with the intention of provoking the body to react to it is philosophically distinct from giving a child a medication that is not intended to do that. But I would be very interested in what other people think makes vaccines unique.


On brain death and the Jahi McMath story

January 21, 2014  |  General  |  44 Comments

The recent and unfolding tragedy of Jahi McMath, the 13-year-old girl who died following complications of tonsillectomy and adenoidectomy, has focused many people on the question of brain death. Although I have no more details about this case than anyone else reading the news, I am quite familiar with the sort of things that happened to this unfortunate child. As many of you know, her family does not believe she is dead, although multiple physicians have documented she is and the county medical examiner’s office (the coroner) has issued a death certificate. The latest news is that she has been transferred from Oakland to a facility in New York.

So what is brain death? It means no function at the level of the brain stem or above. Function stops where the spinal cord joins the base of the brain. How do we know somebody is brain dead? There are a series of standard and relatively low-tech bedside tests to determine that. We first make sure the patient has a normal body temperature and has no sedating drugs in their system. There should be no purposeful response to any stimuli. The muscles are flaccid. Then we test for brain stem reflexes. One of these is response of the pupils to light — there should be none. There needs to be absence of normal movement of the eyes to motion of the head (called doll’s eyes) or no movement when we put cold water on the ear drum (called cold calorics); both of these measure the same reflex. There should be no blink reflex, called the corneal reflex, when a wisp of cotton is brushed on the eyeball. There should be no gag reflex when we stimulate the back of the throat with a wooden tongue depressor. Finally, the last test of brain stem function is the apnea test: we allow the blood carbon dioxide level to rise and look for any effort to take a breath. Rising blood carbon dioxide level is a strong trigger to the normal brain to breathe, and failure to do so means this ability is lost.

What happens after the bedside brain death determination varies a little from hospital to hospital. Many hospitals require 2 tests 24 hours apart; if both show no brainstem function, the patient is legally dead at the conclusion of the second test. As an alternative, we can do the bedside test followed by a simple scan to determine of there is any blood flowing to the brain. These two tests together give us an immediate answer, and many hospitals require the flow study for children. If the bedside examination shows no brainstem function and the flow study shows no blood flow to the brain, the patient is legally dead. I write the time of death on the death certificate as the time of the scan.

When I do these things I always want the family with me and watching what I do as I explain what is happening.

That all seems straightforward. As with this case, sometimes it’s not. For one thing, not all cultural traditions recognize brain death as real if the heart is still beating. I’ve been in that situation. For another, sometimes there are reflexes at the spinal cord level that look as if the patient is alive. That’s a difficult thing to watch.

The upshot is that I have continued support — mechanical ventilation, often medicines to support heart and other organ function — on a brain-dead patient for some time. Usually this is because the family wants some time to cope with things, or else there is a family member traveling to the hospital. I’m always OK with that, up to a point. A key principle here is that a family cannot force me to behave unethically, and continuing organ support of a dead person is disrespectful of the dead — mutilating to the body. Many ethical traditions, including my own, refuse to do that.

The longest I have ever continued organ support on a dead person was 6 weeks. We had a huge court battle similar to this case, with the court ultimately allowing us to withdraw support. A family member then attempted to enter the hospital with a gun. It was ugly.

The bottom line is that, with the exception of the one case above, I have always been able to mediate the situation by listening to families, being frank about my own duties (both legal and ethical), and allowing them time to grieve. I have always regarded caring for dying people and participating in their death as an honor granted me by the family.

I think there is more going on in this case than we know. Why this case became so adversarial is probably a complicated issue, and these complexities do not translate well to the evening news. At the very least, clearly the hospital and doctors failed to establish a relationship of trust with the family.

Regarding the child’s cause of death, I’d lay odds she had sudden bleeding from the tonsilar bed, the tissues under where the tonsils were. This is a well-known complication after tonsillectomy if the clots fall off. After that I think she probably lost her airway, either from obstruction from blood clots or some other reason. She was a large girl undergoing the procedure because of sleep apnea. Such people often have difficult upper airways to access and control with a breathing tube in a hurry, and that was what she probably needed. The back of the throat is also quite inflamed immediately after this kind of surgery and a rebleeding tonsil site can obscure everything with a large quantity of blood. I know this from experience. It’s a difficult situation to manage. I assume she went 4-5 minutes without an adequate airway, leading to brain damage and subsequent brain death. This is a common progression after anoxic brain injury — lack of oxygen — from any cause.

There are some directly antagonistic ethical issues in play here. Patients, and their families, are in charge of medical decision making. But they don’t have the right to demand whatever they want. This can be as simple as requesting a test that is not medically indicated or as complicated as this case. Futile care is unethical, particularly if it causes pain to the patient. Of course in this case the patient is already dead, so one could argue that there is no harm in persisting. But there is ethical harm, I think.

I have been in the situation of requesting, on behalf of a family, transfer of their brain dead child to another facility when we have reached an impasse. That is my obligation to them. But no facility I have ever dealt with would accept transfer of a dead person; I wouldn’t, and I am surprised the family was able to locate one.

One other thing I’m occasionally asked: Has anyone who was declared brain dead ever been found later not to be dead? I am unaware of any cases of this. If you hear of such things you need to understand that a patient in a deep coma, totally unresponsive to the world, is not dead. They still have the reflexes I described above intact. Once in a while such a person awakens.

At any rate, nature has a way of deciding these things no matter what we puny humans do.

Good news for parents with children born by assisted conception

December 22, 2013  |  General  |  No Comments

In vitro fertilization was first done in 1978. Since then, the number of children born of pregnancies that were the results of various kinds of assisted conception has dramatically increased — there are 5 million persons alive today who wouldn’t be here without it. It’s expensive, and doesn’t always work, but for some families it’s a choice available to try for a baby. It’s not all gravy. For a hard-headed and moving description of what the process can be like, I highly recommend Miriam Zoll’s recent memoir about the process, Cracked Open. You can read some excerpts here.

Assisted conception has real risks that have been known for some time —  prematurity, low birth weight, and fetal malformations. Multiple birth is also common. In the background there has long been the fear that children born this way might also be at an increased risk for cancer. This makes theoretical sense because many of the drugs used to enhance fertility affect cellular growth, and cancer is fundamentally a disorder of deranged, out of control growth of body cells. Now we have some information about that.

A British study examined the records of all children born there between 1992 and 2008 as a result of some variety of assisted conception. Since cancer develops years after exposure to any cancer-causing agent, it was important to follow these children for a long time. This study did pretty well in that department, with a median followup of 7 years. (The median is different from the average, and is more useful in this situation.)

The researchers studied 106,013 children born with assisted conception and compared their rates of childhood cancer to the known rates of childhood cancer in Britain. They found 108 cancers in the assisted fertilization group; the number predicted from previous population studies was 110, virtually the same number. (This also tells you that the background risk for any child to get cancer is about 1 in 1,000.)

Bottom line: assisted conception carries no increased risk for childhood cancer.

What is asthma and how do we treat it?

November 11, 2013  |  General  |  No Comments

Asthma is a common problem in children — nearly 10% now have it — and the number is increasing. Researchers are not sure of the reasons for this steady increase (more here), but decreased air quality, lower activity levels among children, and an increase childhood obesity have all been implicated. Whatever the cause, it means that millions of American children take medicine for asthma. A significant number of these children end up in the PICU for a severe asthma attack. As I speak to their parents, it is clear that more than a few parents have only vague ideas of how the different types of asthma medicines we use work in their child’s body. This is an important subject, since using the medicines correctly is the best way to keep your child out of breathing trouble, and to use them correctly it very much helps to understand how they work.

The first thing to understand is what is taking place inside the lung during an asthma attack. Once you know that, you can see how the different asthma medicines relieve the symptoms. Here is a schematic drawing of what a normal lung looks like:

You can think of the lungs as being composed of two parts. The first is a system of conducting tubes that begin at the nose and mouth, move through the trachea (windpipe), split into ever smaller tubes, called bronchi, and end with tiny tubes called bronchioles. The job of this system is to get the air to the business portion of the lungs, which are the alveolar sacs. This second part of the lung brings the air right next to tiny blood vessels, or lung capillaries. Entering capillary blood is depleted in oxygen and loaded with carbon dioxide, one of the waste products of the body’s metabolism. What happens next is gas exchange: as the blood moves through the capillaries, oxygen from the air we breathe in goes into the blood, and carbon dioxide leaves the blood and goes into the air we breathe out. The newly recharged blood then leaves the lungs in an ever enlarging system of pulmonary veins and then goes out to the body.

The main problem in asthma is that the conducting airway system gets blocked in several ways, so the oxygen can’t get in and the carbon dioxide can’t leave. Although both are a problem in a severe asthma attack, getting the air out is usually a bigger issue than getting it in because it is easier for us to generate more force sucking in air than blowing it out. So the hallmark of asthma is not getting the air out — called air trapping. Why does this happen? There are two principal reasons: for one, the small airways, the bronchioles, constrict, get smaller; for another, the walls of the airways swell and the airways themselves fill with excess mucous, blocking air flow. Here’s another schematic drawing of what that looks like.

Thus during an asthma attack these things happen, all of which act together to narrow the airways and reduce air flow:

  1. The smooth muscle bands around the tiny airways tighten
  2. The linings of the airways get inflamed and swell
  3. The mucous glands in the airways release too much mucous, filling the airways

The medicines that we use to treat asthma work by reducing (or even preventing) one or more of these things. But before we get to them, an obvious question is why are our lungs are constructed in this way, especially if it can cause trouble? Why are those smooth muscle bands there? Why does there need to be mucous in our airways?

The smooth muscle bands are there for a good reason. The lungs need a way to direct the air we breathe in to the best spots, which are those regions of the lung with the best blood flow, and that changes from minute to minute from such things as changes in our position — lying down to standing up, for example. Those muscle bands function like the head gates of an irrigation system, opening and closing to direct air to the best places. The mucous is important because it is one of the chief defenses our lungs have against harmful or irritating things we breathe in. The mucous traps debris and steadily moves it up and out of our lungs. In asthma, both of these natural systems become deranged. The so-called triggers for this derangement vary from person to person, but the results are similar. The medicines we use are similar, too, no matter what started the asthma attack.

One of the mainstays of asthma treatment is a member of a class of medicines we call selective beta agonists. The generic name for the one we use most commonly is albuterol. Common brand names for albuterol are Ventolin and Proventil. Albuterol comes as a liquid, which we blow into a mist either with a device called a nebulizer or with what’s called a metered dose inhaler (“puffer”). The second of these is more convenient to carry around, but it can be more difficult to use with small children, although adding a special chamber to the device can help. The patient inhales the mist of albuterol. It works by soaking into the smooth muscle bands, making them relax, and in that way making the airway tubes bigger to allow more air flow. (There is also an oral form of albuterol, but for a variety of reasons it is not a good choice for children with asthma.) For many patients with asthma, inhaled albuterol alone is adequate treatment for their symptoms. A key thing to know about albuterol is that it goes to work right away, generally within minutes, so it is a good medicine for an acute asthma attack.

Another class of medicines long used in the treatment of asthma is corticosteroids, or steroids for short. These medicines work by being powerful blockers of inflammation. If you have ever had a poison ivy rash, for example, you are familiar with inflammation: redness, swelling, and seepage of fluid from the tissue (we can use steroids to treat poison ivy, too). A similar inflammation around the small airways is characteristic of asthma. It makes the linings of the airways swell, weep fluid, and increase mucous production. For a severe attack, we give steroids by mouth or intravenously (IV, directly into the bloodstream). They are very effective when given that way. But they do not go to work right away — several hours are needed at least. So although we may start them during an acute attack, we don’t expect them to help for a while.

Steroids are powerful drugs. When you take them by mouth they affect your entire body, not just your asthma, and that can cause problems. This is why we only use systemic steroids — those by vein or by mouth — for as short a time as possible, typically five days or so. We have other forms of steroids that are inhaled. This allows them to work directly on the airways without affecting the entire body. Common brand names of inhaled steroids are Pulmicort and Flovent. The inhaled steroids, like the systemic ones, don’t go to work right away. So they are intended primarily as a medicine to maintain control of the asthma. It is a common mistake for parents to give their child multiple doses of inhaled steroids when they have worsening breathing troubles — steroids are not intended to be used that way. The proper so-called “rescue medication” for worsening symptoms is albuterol or drugs like it.

These days we have hybrid medications that combine a long-acting albuterol type drug with an inhaled steroid. This combination is intended as something to be taken for chronic control of patients with moderate or worse asthma, and these agents are quite effective at doing that. Common brand names are Advair and Symbicort.

So albuterol (and beta-agonists like it) and steroids are mainstay medicines for treating asthma. In combination they make a good team because they attack the asthma via two different modes of action. We have some other medications that work by still other mechanisms. Montelukast (brand name Singulair) blocks airway inflammation by another mechanism than do steroids. Unlike systemic steroids, the action of montelukast is more selective and this medication is safe to take for prolonged periods. For some patients, montelukast and an occasional puff of albuterol is sufficient to keep them out of trouble. Finally, an inhaled drug called ipratropium (brand name Atrovent) blocks excessive mucous production by another method than blocking inflammation; it is often helpful as an adjunct to the other medicines. A couple of medications (brand names Combivent and DuoNeb) combine ipratropium and albuterol together so they can be inhaled at the same time.

So how do doctors decide what asthma medicines to use? One obvious principle is that it makes little sense to use more than one medication of the same category: combinations ought to work in different ways so they can work together. But beyond that obvious principle, how do we decide? The usual approach is to classify patients with asthma according to their severity and then add medicines in a logical, step-wise way until we get control of the symptoms. There are guidelines to help us do this. A good, recent summary is here, published by the National Institutes of Health. If you or your child has asthma it is a good place to find information. It is also useful to look at the actual decision tree doctors use to decide what medicines to use and in what order. You can find it here. One key principle is that we divide medicines into maintenance medications — those the child takes every day — and “rescue” medications, ones the child takes for worsening symptoms.

Asthma is common and is getting more common every year. Certainly speak with your child’s doctor about doing some good detective work to figure out what your child’s asthma triggers are. Then take steps to modify exposure to them or avoid them. Common sense tells us that if we can reduce symptoms by reducing exposure to common triggers, such as tobacco smoke, we should do everything we can to reduce the need for asthma medications. But for many children, this will not be enough; their parents should understand how these medicines work in order to make the best use of them.

About all those kids on anti-reflux medications: what’s the best practice evidence?

August 3, 2013  |  General  |  No Comments

Gastroesophageal reflux (GERD) is when stomach contents slosh backwards from the stomach up into the esophagus, the swallowing tube that runs from the mouth to the stomach. The spot where the esophagus enters the stomach is called, unsurprisingly, the gastroesphageal junction. At the junction there is a kind of one-way valve, called the lower esophageal sphincter. Its job is to allow through what we swallow and keep stomach contents from going back up the wrong way. It has to be a pretty smart valve, because there are times when we want stomach contents to be able to go backwards — when we vomit, for example.

The lining of the esophagus is also different from that of the stomach. The stomach lining cells secrete hydrochloric acid, which helps digest our food. If the acid stays in the stomach, it causes no harm and does some good; but if the stomach contents go up the wrong way, the acid burns the lower reaches of the esophagus. Hence the other common term for GERD — acid reflux disease. Occasional GERD we call heartburn. Long-term GERD can cause serious problems. Here’s what the system looks like:

We have several ways to treat GERD. The most common is to use drugs to block acid production in the stomach. This doesn’t stop the reflux, but it treats the pain and inflammation caused by stomach acid. We have two main categories of drugs to do that: so-called H2 blockers, which indirectly reduce acid production; and the more powerful proton pump inhibitors, which directly block acid secretion. The most commonly used H2 blocker is ranitidine (Zantac); common proton pump inhibitors are omeprazole (Prilosec) and lansoprazole (Prevacid). When they first came out these drugs were prescription only, but now you can get them over-the-counter at least in pill form. (Making them into a liquid for small children often requires a pharmacist.) Severe GERD can be treated with surgery to snug up the lower esophageal sphincter. This is called a Nissen fundoplication.

Anti-acid drugs are very commonly used. If you are a parent with a child under one year of age, he may be on (or have been on) one of these drugs. If not, if you poll your friends you will find many children taking them. Is that a good thing? What do we know about reflux in children?

To help answer these questions you can look at a recent policy statement from the American Academy of Pediatrics called, “Gastroesophageal Reflux: Management Guidance for the Pediatrician.” Most of the article is behind a paywall and it’s a bit heavy going for nonphysicians, but it has some useful summary concepts. The biggest take-home is that many, even most infants reflux from time to time. Any parent, especially one with several children, knows that babies spit up a lot. They’re not vomiting — that’s reflux.

  • A key distinction is between GER and GERD. That is, between simple reflux (GER) and reflux that causes disease — symptoms (GERD).
  • Half of 4-month-old infants reflux; this drops to 5-10% by age one year.
  • GERD as a cause of wheezing is rare. (We used to think it was more common from stomach contents getting down into the lungs.)
  • Diagnosis of both GER and GERD is largely a clinical one; that means a conversation between parents and the doctor. As the linked article states:  “The strategy of using diagnostic testing to diagnose GERD may also be fraught with complexity, because there is no single test that can rule it in or out. Instead, diagnostic tests must be used in a thoughtful and serial manner to document the presence of reflux of gastric contents in the esophagus, to detect complications, to establish a causal relationship between reflux and symptoms, to evaluate the efficacy of therapies, and to exclude other conditions.”
  • Lifestyle changes are the first-line treatment of GERD among children. These changes may include using smaller, more frequent feedings for infants and thickening the feedings with rice cereal. Keeping the child more upright after feedings also often helps.
  • Don’t use anti-acid medications if there are no symptoms, such as apparent pain with feeding and feeding avoidance. This is because these medications don’t stop reflux; they relieve the symptoms associated with it.
  • Only consider surgery for reflux if the symptoms don’t respond to medications or if they are severe, such as failure to gain weight or respiratory problems from feedings getting into the airway.

These are all pretty common sense things. Yet I see quite a few children who are on anti-acid medications simply for spitting up a lot. The spitting up is normal for many children, and it will improve with age.

Do probiotic supplements reduce antibiotic-associated diarrhea in children?

Do probiotic supplements reduce antibiotic-associated diarrhea in children?

July 22, 2013  |  General  |  No Comments

The intestines, particularly the large intestine, are teeming with bacteria. They are piled on each other as dense as the above photomicrograph shows. The huge majority of them are what we call friendly bacteria: they live inside us, feeding off the rich stew of food we eat, but cause no disease. In fact, their presence is important to our health because they crowd out bacteria that cause disease — the good guys take all the food.

This balanced ecosystem is disrupted when we take antibiotics. A large number of the friendly bacteria are killed off by the antibiotic. Some of the less friendly ones are resistant to the action of the antibiotic, and they take the opportunity to multiply and become a much larger proportion of the population. That can cause problems, typically diarrhea. It doesn’t happen all the time, but frequently enough to be a well-known phenomenon. Most of the time the friendly bacteria repopulate the intestines quite quickly after the antibiotic course is finished, but not always. Diarrhea or other symptoms can persist.

One of the most serious bad bacteria that can cause trouble is one called Clostridium difficile, or C. difficile (or just C. diff) for short. That particular bacterium releases a toxin that can cause quite severe inflammation of the large intestine, called colitis. Bloody diarrhea is often the result, and severe illness occasionally happens along with it. C. Difficile can also be quite difficult to eradicate once established, sometimes requiring long courses of quite expensive drugs.

All this has been known for a long time. An obvious approach to preventing it would be to preserve the population of friendly bacteria by giving the patient doses of them to replace those killed off by the antibiotic. There are several species of bacteria that are potential helpers, which together are called probiotics. Many brands of yogurt, as well as some other products you can find in the dairy section, contain one of them, called lactobacilli. Other probiotic microorganisms include bifidobacteria and saccharomyces. Many over-the-counter products contain mixtures of these. Such products are also heavily touted as treatments for a wide variety of other intestinal complaints besides diarrhea. That’s another topic, but what do we know about their ability to prevent antibiotic-induced diarrhea — do they work?

The Cochrane Collaboration is an organization devoted to collecting the best data for evidence-based medicine. The group of investigators (all volunteers) carefully reviews a treatment and examines all the research reports to determine what we know and what we don’t. It’s a good site to browse just for interest, and it does have some information about probiotics. You might also check out this article from the Journal of Pediatric Gastroenterology entitled “Clinical efficacy of probiotics: review of the evidence with focus on children.” It’s written for doctors, but much of it is understandable to non-physicians.

One recent Cochrane review found clear evidence that probiotics significantly reduce (by about 65%) the risk of C. difficile infection. For my practice in the PICU, where C. difficile is a big problem in children already sick from other things, I’m convinced — I administer a probiotic when I use powerful antibiotics.

But what about other, milder forms of antibiotic-induced diarrhea, such as the diarrhea your child might get while taking amoxicillin for an ear infection — do probiotics help then? Another Cochrane review was equivocal about that: they may help, and they certainly don’t do any harm. The article linked above from the Journal of Pediatric Gastroenterology also talks about that issue, and points out that there may be some differences in the beneficial effects depending upon which probiotic organism is given. This is why most products are mixtures of several of them.

The bottom line for me is that probiotics help many children avoid antibiotic-associated diarrhea, particularly the severe C. difficile colitis, and the risk of using them appears tiny to nonexistent in otherwise normal children. If you want to use them, I would check with your child’s healthcare provider to see if he or she has a specific recommendation about which of the many products to use.

In vitro fertilization and the business of making babies: hype vs. hope

July 17, 2013  |  General  |  No Comments

(Guest Post: What follows is a fascinating and enlightening essay and book review by Maggie Mahar, who blogs on healthcare policy issues at her excellent blog Healthbeat, posted here with her permission.)

Miriam Zoll’s  Cracked Open:  Liberty, Fertility and the Pursuit of High Tech Babies is in part a moving memoir, in part a troubling expose of yet another unregulated corner of our healthcare system. In this case it is an industry that offers women everything from in-vitro fertilization (IVF) to another women’s eggs-for-sale.

Zoll titles her first chapter “One Egg, Please and Make it Easy.” If only it were that simple. She begins by acknowledging how naïve she was:

“I am an official member of the Late Boomer Generation. We grew up . . . . in the 1970s and ‘80s, watching with wide eyes while millions of American women—some with children and some not—infiltrated formerly closed-to-females professions like medicine, law, and politics. This exodus from the kitchen into the boardroom created a thrilling, radical shift in home and office politics, in the economy, and in relations between the sexes. ‘Shoot for the stars,’ some of the more thoughtful women advised us, ‘but don’t forget about the kids.’”

Zoll herself became one of the trailblazers. She is the founding co-producer of the original “Take Our Daughters to Work” Day, and on the board of “Our Bodies Ourselves.” In 2005, she became a Research Fellow at MIT’s Center for International Studies. There, her widely –published research addressed gender inequity and poverty in HIV/AIDS-affected households in sub-Saharan Africa.

At 35, Zoll married. At 40 she reports, she looked in the mirror, and decided: “It’s time to have a baby.” Finally, she felt confident that she would be a good mother. It didn’t occur to her that she might have trouble conceiving.

“We are the generation that . . . came of age at a time of burgeoning reproductive technologies,” she explains. “We grew up with dazzling front-page stories heralding the marvels of test-tube babies, frozen sperm, surrogates and egg donors; stories that helped paint the illusion that we could forget about our biological clocks and have a happy family life after—not necessarily before or during—the workplace promotions.”

Zoll goes on to chronicle her own long trek through our multi-billion-dollar fertility industry. At the beginning, she and he husband were as innocent as most couples who believe what the media had told them: “Science and technology have finally outsmarted Mother Nature. Just because you’re over 40, this does not mean that you can’t conceive.”

That final line is absolutely true. Each year in-vitro fertilization and other forms of Assisted Reproductive Technology (ART) produce miracles. The extraordinary joy that parents who thought that they could never have a child feel when holding their baby should never be discounted. When the right patient receives the right therapy at the right time, these technologies can heal broken hearts.

ART is still a medical experiment. Or, as Zoll puts it: “ART is a crap shoot.” In many cases, physicians don’t know why some couples succeed and others do not. No one keeps tabs on who wins and who loses. We have a National Joint Replacement Registry, a database of information that surgeons can consult as they learn why certain procedures work for certain patients while others go awry. But there is no official registry for in vitro fertilization—despite the fact it is an infant science shot through with uncertainties.

As Minnesota law professor Michele Goodwin and Judy Norsigian, Executive Director of Our Bodies Ourselves, warn in the Foreword to Cracked Open: “While the ‘better’ fertility centers now claim live birth rates of 50 percent or more, the national average remains at about one-third. It is easy to misinterpret pregnancy rates—which are high but often end in miscarriage—as live birth rates, which are much lower in comparison.”

Here are the facts: The most recent data from the CDC reveal IVF failure rates as high as 68 to 78% in women ages 35 to 40, and 88 to 95% among women 40-44. Meanwhile the “baby business” is a for-profit business. The industry’s mission statement is also a marketing statement: “It just takes one good egg.” Little wonder that so many would-be parents are seduced. They want to believe that their doctor is a fairy-godfather/mother who has just one desire: to make sure that they become parents.

“As a business, what makes the fertility industry unique is the combination of supply-side virtuousness and demand-side desperation,” writes Michael Cook, editor of Mercatornet. “The doctors and scientists who run the clinics can do no wrong. The women who want the babies will pay them whatever they charge.” But fertility clinics are run by human beings. Some are more truthful than others. Zoll describes her first visit to one.

“Michael and I were nervous and excited. The clinic literature cited studies claiming that well over two-thirds of all couples seeking treatment for fertility-related problems become parents. It didn’t occur to us then to ask if this statistic meant that two-thirds of parents birthed their own babies or a donor egg or embryo baby, or if they became parents through adoption or surrogacy. We were as green as could be about what to expect and what to ask, and we were eager to hear how the doctors thought they might help us.”

“That first day, my husband and I met with two health care professionals, one who examined my female interior and another who walked us through the ins and outs of the medical aspects of fertility treatments. A marble egg sat on a little pedestal on both staff members’ desks, and at one point during our meetings they each held it between their thumb and index fingers. . . .They smiled and said, verbatim: ‘Like we say here at the clinic, it only takes one good egg to make a baby.’ It was obviously the clinic’s mission statement.”

“I immediately thought that, if all we had to do was find one good egg, we were certainly the right candidates for the job. How hard could that be, really? . . . . I was in great mental and physical health. I exercised and practiced yoga regularly. I ate well. What more could a doctor ask from a patient? Little did I know that the process of finding one good egg would be a bit like panning for gold in a mine that had already been stripped of much of its bullion.”                  

A few weeks later, Zoll and her husband met with a veteran physician she would dub the “Silver Fox.” After reading the couple’s medical records, he looked Zoll straight in the eye: “‘The first thing I want to say is that you’re old.’”

“I winced as his words cut through me like a razor-sharp sword,” she remembers, “and then within a split second I found myself in a serious state of denial, fighting back the urge to tell him that he was the one with the white hair, not me. He was the old geezer in the room, not me. No sir, not me. All my life I had to convince people that I wasn’t as young as I appeared. I knew I was teetering on the brink of officially entering middle age, but I didn’t think I was there—yet. ‘Women your age have a harder time conceiving, especially if they have endometriosis, like you,’ he continued. ‘You should have come to see me when you were thirty.’ This veteran fertility specialist was horribly blunt. But he was right.”

Endometriosis is an often painful disorder involving tissue that normally lines the uterus growing outside the uterus. While it can be treated, endometriosis can lower a woman’s chances of conceiving. The first doctor should have told her this. This doesn’t mean that a woman diagnosed with endometriosis shouldn’t try ART. That is a personal decision. But a woman needs to know the truth about her chances so that she can make an informed choice.

When Zoll saw the Silver Fox, she harbored high hopes. “I was confident that, since my mother had birthed me later in life, I would have no trouble doing the same thing. During that first meeting with the Silver Fox, I proudly told him that my mother had been thirty-nine years old when I was born. ‘Just because your mother did it doesn’t mean you will too,’ he replied. ‘Do you think there’s a gene for birthing in middle age that your mother passed onto you?'”

“In response to that question, I distinctly remember that I blinked three times,” she writes. “Um, yes, think me an idiot, but actually I did believe that since mom had done it I could do it. Why would I think otherwise? For decades, the Sunday New York Times and People magazine had reported that it was possible to birth a baby later in life, and American pop culture is loaded with messages telling women that they can become pregnant when they are older. In the movie Parenthood, Mary Steenburgen and Dianne Wiest both play the role of older women who have no trouble birthing babies, and in Father of the Bride, a middle-aged Diane Keaton delivers a baby on the same day her 21-year-old daughter does. . . .Year after year, the headlines and cultural messages screamed out: ‘Relax and sit back. You’ve got science on your side.”

“But now this doctor was telling me that I might not have science on my side, after all. He was telling me that I had deluded myself with misinformation and false hopes about my own biology—and, according to global research, I am not alone . . . . In a survey of undergraduates in the United States conducted in 2012, two-thirds of women and 81 percent of men believed that female fertility did not markedly decline until after the age of 40. One-third of women and nearly half of men believed this marked decline occurred after the age of 44—an age at which IVF is least effective. A full 64 percent of men and 53 percent of women surveyed overestimated the chances of couples conceiving a child following only one IVF treatment. The study concluded: “The discrepancy between participant’s perceived knowledge and what is known regarding the science of reproduction is alarming and could lead to involuntary childlessness.”

Ultimately, Zoll would meet a doctor who advised: “In a situation like yours, where your hormones are not stimulating the kind of egg production needed for pregnancy, we like to recommend that couples think about egg donation or adoption.” This was honest advice.

Reluctantly, Zoll explored the idea of finding a donor: “I first entertained the possibility of working with a donor egg agency after the second IVF cycle failed. The very idea of Michael’s sperm fertilizing a stranger’s eggs and then having those embryos inserted into my uterus made me wince. But, given what the doctors had told us about the quality of my eggs early on, I wanted to be open to the idea of a donor—just in case. While some of the literature said there was great success with older women using younger women’s eggs, other data suggested just the opposite. Once again, it was a crapshoot: you either win or you lose, but the big question was, do you want to play the game?”                        

Zoll confides that “The first donor egg website I happened to stumble upon was a California agency where the majority of potential donors looked like contestants for the Miss California pageant. They were all slender, blonde, and buxom and their price tags were high, ranging from $8,000 to $10,000. Why did they call them donors, I wondered? I spent only five minutes on the site before I hastily clicked off.”

I felt like an eggless sociopath for even considering asking one of these young women to risk her health so that I might purchase her eggs.

“The vast majority of donors on this site and elsewhere in the United Staes were in their twenties. How and why do they decide to sell their eggs to someone like me? How do the donor agencies and these young women determine that their eggs are worth $8,000 while someone else’s eggs are worth only $5,000? Were blonde, blue-eyed donors always more expensive than brown-eyed, overweight donors? . . . . We were told on more than one occasion that it is not unheard of for infertile Ivy League alums to post a classified ad in campus publications offering up to $100,000 for an egg donor with high SAT scores, 36-24-36 body measurements, and a penchant for Mozart.”

Capitalism sets a price for eggs, depending upon a woman’s bloodline.

“One thing this boom in fertility medicine has done is to help us apply an economic value to women’s reproductive labor,” Zoll writes. “This may or may not be a good thing, depending on how you look at it. In today’s U.S. marketplace, a woman’s egg is valued at anywhere between $5,000 to $100,000 or more, depending on her bloodline. On average, though, let’s say an egg is worth between $5,000 and $10,000. Some people think it is immoral to put a price tag on genetic material and women’s reproductive hardware and capabilities. But, considering that the global fertility industry generates billions of dollars a year, why not calculate women’s economic contributions, too?”

Zoll makes a reasonable point. Pharmaceutical companies are paid a fortune for fertility drugs. Why shouldn’t the women who donate their eggs cash in too? Like Zoll, I, personally, am appalled by the idea of commerce that traffic in womens’ eggs. But men regularly sell their sperm. Shouldn’t women be able peddle their eggs? Here’s the difference: when men donate sperm they take no risk. By contrast harvesting eggs from a woman’s body is an invasive procedure and can affect her health. The drugs the donor must take are potent. Particularly when researchers are paying for the eggs, poor women may be exploited.                         

After Miriam’s second IVF cycle failed, she and Michael bravely advanced to a third. And finally, she became pregnant. Then the silver fox gave her the news: “The heartbeat is weak. . . You’ll miscarry within a week, most likely.’’ He told her this as he was leaving the office.

Inconsolable, Miriam and Michael embarked on a fourth IVF cycle, using “new super-drugs.” This time, they chose a young fertility doctor who leveled with them, explaining that “a female baby is born with millions of egg follicles that dwindle to about 400,000 by the time she reaches puberty.” But by the time she is 40, “’what remains are the eggs that were never very healthy in the first place. ‘The strong ones leave the roost early,’ he explained. “The robust eggs want to move out. They want to meet the sperm. The weaker ones stay behind.” Nevertheless, Zoll writes, “he was unable to resist the temptation of his clinic’s mantra.” And so he continued: ” Of course, that’s not to say that you don’t have some good eggs left.”

After 10 days of shots, vitamins and suppositories, Miriam went for her first ultrasound appointment. She remembers what the technicians said as she greased the probe and slid it into her vagina: “Well let’s see what’s happening in there.” The examination didn’t take long: “Okay, that’s it.”

“That was fast,” Zoll said as she stood up.

“There’s nothing there,” she said. “The doctor will call you.”

Finally, Zoll overcame her reservations and decided to look for an egg donor. She and Michael picked two. When doctors screened the first one, it turned out that she was infertile. That cost Miriam and Michael $4,000. Then the clinic explained that it couldn’t screen the second donor until it received another $4,000.

“But that’s ridiculous,” Zoll told the nurse. “The second donor just completed a cycle at a reputable hospital clinic that produced a pregnancy. Why can’t you use their tests?”

“Well, we have to run our own tests,” the nurse replied. Finally, she explained “you have to realize that we have to make money somehow. These tests can’t be free.”

Because Zoll put up a fight, the clinic eventually waived the fee. The donor was screened, and the doctor retrieved 12 eggs that were fertilized with Michael’s sperm.

Then they got the news that crushed them, once again. None of the 12 eggs fertilized.

Zoll recalls her conversation with the doctor: “’It’s really quite shocking to us,’ he said in that tone we had heard before. It was the tone that implied that the clinic was not responsible for the outcome, and I suppose that in many ways, they weren’t. Doctors could try to control nature, but they couldn’t manipulate it completely. Still, the clinic has approved the donor. Now, the doctor was saying ‘there is likely something wrong with the donor’s eggs. . . . . . I do hope you will try another donor cycle, but I don’t recommend that you use this woman again .. . Given the drugs she was taking, she should have produced many more eggs than she did.’”

“I didn’t say a word, I just sat there listening,” Zoll recalls. “Our donor had helped another couple become pregnant only a few months earlier. Maybe she should have taken more time off between cycles before working with us. Why hadn’t the doctors flagged the possibility that her reproductive system was oversaturated with drugs that were likely wreaking havoc on her ovaries?”

At this point Zoll realizes that “We had spent thousands of dollars on IVF and even more on the donor egg process, and through it all, no one was accountable for the outcomes. The clnics were not accountable. The pharmaceutical companies that made the drugs the donor and I ingested were not accountable. . . . . Thousands of dollars earlier this same doctor had told us that Donor #2 was a fine candidate . . . . Now. . . he was encouraging us to spend more money and select a different donor, perhaps a younger donor, or a donor with purple eyes and blue hair , who might give us a better yield. What kind of wishy-washy medicine was this?”

Still, Zoll admits: “We had willingly and under no duress paid ridiculous amounts of money for access to medical technologies that we were sure would work and did not. We paid for the chance to hope. We paid for the chance to try.

We were the only ones who are accountable.

Of course, Zoll is right. But still, the question of accountability haunts medicine. When a patient submits to medical treatment, there are no guarantees and no warrantees. If he is unhappy with the results of an operation, he cannot return it. If the patient dies, the surgeon and the hospital still must be paid. This is because most of medicine is still such an uncertain science, fraught with unknowns. If hospitals and physicians were paid only when they were successful many, if not most, would only take the easiest cases. But this is all the more reason why patients need to be fully informed about risks and the odds of success before they choose a course of treatment.

Instead, silence reinforces the fairy-tales

When treatments fail, Zoll writes, “most couples never want to talk about it. And who could blame them.”

There was a cultural taboo — reinforced by the clinics themselves, that we shouldn’t talk about our infertility or our miscarriages or the inability of science to solve our reproductive health challenges. It was that absence of truth-telling that made the success stories sensationalized in the media so dangerously misleading.

It is terribly important that couples tell the truth about their experiences. At the end of her book, Zoll explains: “By sharing my experience, I’m hoping that others will begin to speak out and share theirs, whether treatments were successful or not. For those still recovering, I invite you to cast off your silence and contribute to expanding an open and honest consumer-driven discussion about these life-altering technologies. Men and women contemplating fertility treatments need to hear your perspective . . . By sharing your experiences you can help create a more balanced perspective.”

Best of all, Zoll points readers to a place where “if you would like to share information about your experience, please visit the voluntary registry at Dartmouth-Hitchcock Medical Center.” (I am far from suprised that Dartmouth has taken on this task. It remains one of the most patient-centered institutions in the nation.)

How Does the Story End?  A Postscript

I won’t disclose whether a child ever found Miriam and Michael. It is their story, and I don’t want to spoil the ending. Cracked Open is available in paperback and it’s an excellent read.

If you pick up the book, you will find out, among other things, how they met, and, perhaps most importantly, why they didn’t marry in their 20s.

Here, I would like to add a postscript.

Cracked Open is meant as a cautionary tale for women who may think that they should first become successful in their careers, then plan to have a child when they turn 40. Both media and market hype have convinced many that they can plan a pregnancy when they choose. The CDC’s numbers reveal that his just isn’t true.

I should add that the story of Michael and Miriam’s roller-coaster relationship when they were in their 20s convinces me that if they had married then, they would have divorced within a few years.

Miriam acknowledges that she wasn’t ready for marriage: “This kind of ‘push-me-pull-me’ love eventually ended our relationship and helped motivate me to begin therapy. Difficulties from childhood were now spilling over into my life. I needed to make sense of it all. This was an excellent reason to delay marriage and children. A great many twenty-somethings—women as well as men—are not ready for marriage and parenthood.”

When writing about Cracked Open, I worried that this tale could send a 33-year-old single woman (or her mother) into a panic –though I know this is not Zoll’s intention. Cracked Open is not urging women to let the “tick-tock” of their biological clocks rush them into marriage.

Delaying motherhood because you’re caught on a fast-track and just don’t know how to get off is one thing. Postponing children until you and the right person find each other at the right time is another.

Not everyone would agree with me. Zoll reports that “an article published a few years ago in the British Medical Journal, advised women to start having children before they turn 30: ‘Surveys of older mothers show that half say they delayed because they had not yet met a suitable partner. Maybe instead of waiting for Mr. Right they ought to wait for Mr. Good-Enough, if they want children.’ If Mr. Good-Enough means ‘he doesn’t earn as much as my sister’s husband– but we have such a good time together, and I know he’ll be a great father,’ that’s fine. But if it means that when you think about spending 30 or 40 years with him, you sigh . . . all I can say is “don’t do it.”

I have known so many women who found the right husband after 35. Out of nowhere, he appears. When that happens, it’s not a difficult decision. You recognize each other.

At that point, women have many options including in vitro fertilization, finding an egg donor, and adoption. Not long ago, a friend who met her husband in her late 30s told me: “When I turned 40, I realized I could take $20,000 and go to a fertility clinic. Or I could take the same $20,000, go to Russia and adopt a child.” She has never regretted her decision.

Those are not a woman’s only options. Some will decide that rather than struggling to become the perfect 40-something mother, they would prefer to become the perfect aunt. It’s a personal choice, not a medical decision.

(Thanks, Maggie — and thanks Ms. Zoll for writing this excellent and heartfelt book.)