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Here’s an idea if your drug isn’t on Wal-Mart’s $4 generic list.

For many patients, Wal-Mart’s $4 generics program is a pretty good deal. And the plan to expand the program to most of the country means even more Americans will benefit. Still better: some stores are offering generic drugs for coughs and colds for free!

But there are some limitations. In addition to the caveats I’ve noted before, Wal-Mart’s list doesn’t come close to covering all available generics. In fact, for patients with a number of conditions – anxiety, depression, and high cholesterol — the Wal-Mart list is pretty thin. In addition, the Wal-Mart list excludes oral contraceptives.

What to do if you’re a patient with one of these conditions? Consider an alternative program, such as Rx Outreach. Patients who use Rx Outreach get a 90-day supply from a high-quality mail-order pharmacy located in the United States. (Express Scripts, the company behind Rx Outreach, also runs the prescription drug program used by the U.S. Department of Defense as well as several large U.S. employers.) Most drugs cost $20, including shipping and handling; some drugs are $30.

Although it sounds more expensive, it’s really not. A 90-day supply for $20 comes to a bit less than $7 for a 30-day supply. And the drugs are delivered to your door, so you don’t spend time and money driving to Wal-Mart (remember: you’ll have to make three round trips to Wal-Mart to get 90-days worth of medications) or buying things you might not need while you’re there.

More importantly, there are several drugs included in Rx Outreach that aren’t on the Wal-Mart list. Here are some of the highlights. (Brand names of the drugs are shown, with the generic name in parentheses.)

DRUGS NOT ON WAL-MART’S $4 GENERIC LIST BUT AVAILABLE THROUGH RX OUTREACH

Anxiety
Ativan (lorazepan)
Valium (diazepam)
Xanax (alprazolam)
BuSpar (buspirone tab) *

Depression
Celexa (citalopram) *
Paxil (paroxetine) *
Zoloft (sertraline)
Amitryptyline *
Pamelor (nortryptyline) *

Cholesterol
Mevacor (lovastatin) *
Gemfibrozil

Oral Contraceptives
Ortho-Cyclen
Ortho-Tri-Cyclen

* specific doses not on the Wal-Mart list but available through Rx Outreach

One wrinkle: Rx Outreach is available only to those patients whose income falls below a certain level (depending on family size). You’ll need to visit the Rx Outreach website to see whether you qualify.

Many of the hits I’m getting are from people looking for Wal-Mart’s “formulary” of $4 generic drugs.  Here’s the latest list I could find. 

Important things to keep in mind:

• The list has more than 300 entries, but they count each dose/form separately; it’s really more like 135 drugs (not including vitamins)
• You may not get a full 30-day supply — the number of pills is determined by “commonly prescribed doses”
• There are some big generics NOT on the list: simvastatin (generic Zocor), omeprazole (generic Prilosec), fexofenadine (generic Allegra) are all missing
• You have to get your drugs from the pharmacy in person (this requirement probably drives traffic and therefore sales of non-prescription goods)
• The program isn’t available everywhere, and the list is subject to change without notice

Remember — your greatest savings occur when you move from a brand to a generic, so ask your doctor whether any of the brand-name drugs you’re taking can be replaced with a generic alternative.  Look here for a list of possible generic alternatives to brand-name drugs.

UPDATE — November 16, 2006.  Wal-Mart’s list of $4 generics has expanded both in terms of the number of drugs on the list, and the number of states in the program.  See my blog entry for more details.

Opinions expressed are those of the author alone.

GOULASH OF GOODNESS

You Snooze, You Lose… Weight.  British researcher Shahad Taheri asserts that lack of sleep may increase the risk of obesity for children, teens and adults.  The mechanism may be multifaceted and might include an alteration appetite and metabolism mechanisms.  Taheri previously reported that shortened sleep times are associated with greater levels of ghrelin, hunger-signallnig hormone.

News Flash I: Mothers Don’t Get Enough Sleep. Braun Research reports that more than half of all moms in the US are sleep deprived.  The “no kidding” finding is only topped by this quote from sleep specialist Suzanne Griffin of Georgetown University Hospital: “Consistently not getting enough sleep and lying awake at night… could be a sign of insomnia.”

News Flash II: Happiness Lowers Blood Pressure. University of Texas researchers report an association between a positive outlook and lowered blood pressure.  I’ve never fainted from being ecstatic, but wouldn’t mind trying.

Diabetes Quackery… Times Two.  The FDA issued a warning about web sites hawking products that claim to cure diabetes.  Makes sense.  But according to German researcher Burt Richter, similar caution over the use of Actos, an antidiabetic drug made by Takeda, is warranted.  His analysis concludes that Actos works better than nothing, but not better than generic alternatives (e.g., metformin).  Actos may carry greater risks as well.

Better Late than Never.  Federal scientists report success in producing a vaccine effective against the flu virus — specifically, the 1918 flu virus.  Next up: a breakthrough technology for more efficient wig powdering.

An Aspirin a Day Means I Can Pee Like a Champ.  Folks at the Mayo Clinic report in the American Journal of Epidemiology that daily use of an NSAID (e.g., ibuprofen) can help reduce the risk of benign enlargement of the prostate.  Guys who used NSAIDs every day reduced that risk by 27%, and urinary symptoms overall by 35%.

Opinions expressed are those of the author alone.

DEPARTMENT OF RANTS

Wal-Mart announced its decision to expand its $4 generics program into 14 additional states. What looked like a savvy PR ploy to divert attention away from reductions in health benefits for some employees appears to be turning into an honest-to-goodness price war. (Do note that not all generics are available at that price, and that the $4 fee may not cover a full 30-days supply.)

As I’ve noted before, lower prices are a good thing. But the real savings for most Americans come not by moving from one pharmacy to another; the bonanza is moving from a brand to an equally good generic. Some examples:

Clarinex — typically used as a non-drowsy antihistamine. Ask your doctor whether fexofenadine (the generic version of Allegra) or over-the-counter Claritin will work for you.

Lipitor — cholesterol-lowering drug. Patients taking the lower doses of Lipitor will probably do just as well with simvastatin (generic Zocor) or lovastatin (generic Mevacor); ask your doctor.

Nexium, Prevacid, Aciphex, Protonix — typically used for heartburn and acid control. Ask your doctor whether omeprazole (generic Prilosec) will work for you.

Sonata — used to treat insomnia. The generic version of Ambien will be available next spring. Ask your doctor when it becomes available.

For more information about potential generic alternatives for a number of brand-name drugs, check out DrugDigest’s Check for Savings tool. Every time you use a generic instead of a comparable brand, you get significant savings… whether you shop at Wal-Mart or not.

Opinions expressed are those of the author alone.

DEPARTMENT OF RANTS

In a previous Economix column at the NY Times, David Leonhart got it mostly wrong.  In his latest column, however, he gets it mostly right.  Although others might tag him with a flip-flop on whether spending more for healthcare is a good thing (last time yes, this time no), I prefer to interpret the same two datapoints as a positive trend, a turn for the better.  (Matt Holt at The Health Care Blog differs so strongly you can almost hear him throwing a clot.)

Leonhart’s latest point is that we can’t effectively manage healthcare costs without recognizing that some interventions — even those that offer some benefit or some chance of a benefit — aren’t worth the cost.  And on this specific point, he’s on the side of the angels.

In a nutshell, when it comes to healthcare decisions today, we talk as though we’re scripting an ad for MasterCard:

• One month’s supply of cholesterol-lowering pills: $100
• Bypass surgery: $75,000
• Your health: priceless

Economists call this arrangement of preferences lexicographic: any improvement in health trumps cost, no matter how small the health increment or how great the cost.  But a much more reasonable — and honest — view is that when the price gets steep enough, even an effective health intervention just isn’t worth it.  Our health is prized, but it’s not priceless.

In fact, we make tradeoffs every day that reveal that our preferences about health aren’t lexicographic at all.  We speed to get home in time for a ballgame (health vs. entertainment); we smoke and we drink and we eat more than we should (health vs. pleasure); and we generally don’t buy the safest car available (health vs. money). 

But there more to it than simply coming clean about our willingness to trade health and money.  We need to open our eyes to the fact that every dollar we waste (i.e., spend on something that provides less than a dollar’s worth of benefit) is a dollar we can’t spend on something else that could.  The fact that we can’t pay for everything means we must not pay for something…  and better that the something we don’t pay for offers as little benefit as possible.  It’s not health vs. money — it’s more health vs. less health.

Most of us get our health coverage through our employers.  Each time one of our fellow employees spends a dollar foolishly, there’s one less dollar for us to spend on something that matters.  This kind of waste ought to infuriate us as much or more as the guy who orders the most expensive thing on the menu because he knows we’re splitting the check.

The solution to overspending in healthcare is to accept a fair set of rules — a set of rules that is designed to assure that there’s enough money for the things we know work, and work the best.  That’s precisely the reasoning behind programs that mandate the use of generic drugs when clinically approriate. 

We should never have to go without such interventions when money is being spent on things that don’t matter much, or might not matter at all.   As Leonhardt notes, how can we claim that health is more important than money when 47 million of fellow citizens have no healthcare coverage?

Opinions expressed are those of the author alone.

GENES IN CHARGE

Many pregnant women — especially those in their mid-thirties and older — grapple with the difficult decision of prenatal testing.  Diagnostic tests are available, but they impose a risk of miscarriage to the fetus.  Non-invasive tests are also available, but aren’t accurate enough to fully assure the mom about the status of her fetus.

For childless women approaching menopause, the decision is particularly difficult.  Bypassing the test exposes her to the possiblity that her only child will be affected by Down Syndrome, a condition that would likely require significant caregiving for the rest of the woman’s life; diagnostic testing could rule out this option but imposes a risk of causing a miscarriage to a healthy fetus. 

Women in this situation often ponder the question, which is worse: a baby with Down Syndrome, or no baby at all?

From the perspective of the genes, however, the answer is more clear.  People with Down Syndrome are typically fertile, so better to have some chance of survival than none at all.  Skip the diagnostic test, and hope for the best.

This “Hail Mary” strategy is exactly what German researchers reported in Naturwissenschaften.  Conventional thinking is that the mother possesses a quality-control mechanism that increases the likelihood of spontaneous abortion of abnormal fetuses.  Such a mechanism nakes sense: having a baby is an enormous investment for a woman, and as long as there is a possibility of another pregnancy, better to terminate one that is suboptimal.

Neuhauser and Krackow hypothesized the existence of a more sophisticated filtering mechanism, in which the likelihood of abortion varied depending on the context.  Specifically, they reasoned an adaptive filtering approach would account for how close the mom is to infertility (i.e., age), how well she’s done in the past in terms of spreading her genes (i.e., current number of offspring), and the cost/benefit of raising an additional child (i.e., age of the next youngest child).

To test their hypothesis, they needed to 1) focus on data for which therapeutic abortion was not available, and 2) thoroughly adjust for effects of maternal age (women with more children tend to be older, as do women with bigger age gaps between the youngest child and the pregancy in question).  They did a good job on both counts, limiting their analysis to data collected before abortion was widely available, and doing an impressive simulation of the association between age and other variables.

The results were exactly as expected: rates of DS birth rose with age, dropped with family size, and were higher for families in which there was a bigger gap between the next youngest child and the pregnancy in question.  The authors also note that the existence of an adaptive filtering mechanism might explain observed associations between maternal age and other defects (trisomy 18, trisomy 13, and hypospadias).

Sometimes what’s good for the genes feels good to us too; cooperation among non-kin is the hallmark of the human species, and offers significant evolutionary advantages as well as lots of warm fuzzies.  But when they’re at the end of their evolutionary rope, the genes look out for themselves.  Hopefully more research in this area will identify ways to manipulate the adaptive filter to improve our happiness… even if it comes at the expense of the genes.

Opinions expressed are those of the author alone.

NEWS FLASH

Reuters UK reported today that a Japanese woman gave birth to her own grandchild. The birth was produced using an egg from her daughter and sperm from her son-in-law, in a procedure overseen by obstetrician Yahiro Netsu.

It was only five years ago that the first surrogate birth occurred in Japan. The obstetrician in charge? The same Dr. Netsu.

Opinions expressed are those of the author alone.

BUYING TIME

On Friday, the FDA approved Genentech’s Avastin for use in patients with advanced non-small cell carcinoma of the lung.  The approval was based on E4599, a Phase III clinical trial which showed that adding Avastin to platinum-based chemotherapy increased median survival by about 2 months (median survival with Avastin: 12.3 months; without Avastin: 10.3 months). 

Is the bang worth the buck?  Probably not.  Health economists generally measure the efficiency of an intervention by calculating the incremental cost-effectiveness ratio.  In a nutshell, they estimate how much society has to spend to obtain an additional year of life in reasonably good quality.  Although they don’t set the break point, health economists tend to use numbers in the $75,000 to $100,000 per year of life range as the target.  Interventions that cost more than $100,000 per additional year of life gained are typically deemed as inefficient.

We can get a very rough estimate of that number for Avastin.  Based on current pricing, the added cost for treating a typical lung cancer patient will be about $56,000.  (Genentech recently announced a cap on Avastin costs for selected patients, but conveniently that cap is at $55,000.)  Let’s assume the incremental cost of Avastin is $55,000, and the incremental gain in life expectancy is the 2 months observed in the E4599 trial.  Leaving out additional costs to administer the drug, as well as possible side effects (about 1 Avastin patient in 40 had a bleed into their lungs), we get an incremental cost-effectiveness ratio of about $330,000 per year of life gained ($55,000 / 2 months).

To some of us, that may seem like a reasonable deal.  If you’re footing the bill, more power to you.  But for employers, spending money on these types of interventions — spending a lot but not getting a lot — leads to a tough decision down stream.  As the costs of health care rise, employers must decide whether to even cover health care for their employees.  For every employer, there’s a limit to how much money can be devoted to health care.  And the sad fact is that by committing to very expensive therapies that don’t offer commensurate gains in health, we are eventually condemning some workers to loss of health coverage altogether.

Opinions expressed are those of the author alone.

WE ARE NOT ALONE

Imagine if alien invaders had the power to turn our women into spendthrift hussies and our men into unkempt scofflaws. That they had the ability to decrease our reaction times, and increase the rate at which we are injured in accidents. That they could cause birth defects and mental retardation among newborns. That they could even cause the fraction of male births to rise above 70%.

Such an alien not only lives among us, it lives in us… and a lot of us. The toxoplasma gondii (or t. gondii) parasite infects 20% to 80% of the world’s population, and there’s reasonably good evidence – most of it flowing out of a single group in Prague – that t. gondii exhibits these effects among its human hosts. [1]

The latest study from Dr. Flegr and colleagues published this week in the journal “Naturwissenschaften” shows a clear association between the concentration of t. gondii antibodies and the fraction of male births: the stronger the woman’s immune system’s response (indicating prior infection), the more likely she is to give birth to a boy.

Although infection with t. gondii can cause some flu-like symptoms (that’s your immune system kicking in), those symptoms generally disappear pretty quickly. But instead of being eradicated, t. gondii settles quietly into your muscle and nerve tissue – including your brain – in tiny cysts, waiting silently as you go about with your life.

But how does this dormant parasite alter the rate of male births?

Believe it or not, at the earliest stages of pregnancy, the deck is strongly stacked in favor of males. In humans the implantation success rate is far higher for male zygotes than female, and at 5 – 7 weeks, about 62% of embryos are male. This imbalance early on is crucial to achieving sex balance at birth because the maternal immune system because, as Legr notes:

“The maternal immunological reaction against male-specific H-Y antigens is an important cause of selective mortality of the Y-chromosome-bearing embryos, and, consequently, of the secondary sex ratio adjustment.”

In other words, it may be a man’s world, baby, but the womb is a completely different story. Just because you’re paranoid doesn’t mean someone’s not out to get you, and in many cases that someone is your mom.

No one really knows why t. gondii infection might alter the reaction of the maternal immune system to male-specific antigens, but we do know that with toxoplasmosis comes production of interleukin-10 and transforming growth beta factor, both of which can cause immunosuppression. Furthermore, we know that women acutely affected with t. gondii during pregnancy are at significantly increased risk of giving birth to infants with developmental defects. Surprisingly, another Czech researcher [2] reported way back in 1957 that the prevalence of toxoplasmosis in 94 mothers of Down Syndrome children was 84%; the prevalence in a control population matched on age and other factors associated with Down Syndrome was only 32%

What this all adds up to is that infection with t. gondii relaxes the quality control mechanism that’s applied during gestation. In short, the rate of spontaneous abortion probably drops as a result of t. gondii.

If you put it all together, you get more boys. The sex ratio is stacked in favor of males at implantation as a means to balance out the selective mortality rate for male embryos. Toxoplasmosis turns down that rejection process, the ratio is held more or less constant, and presto – you end up with more male births.

What’s really interesting is whether the increased rate of male births is simply an accident or the beautifully sneaky result of millions of years of evolution. T. gondii, for example, cannot complete its life cycle in humans. For completion of the circle of life from the perspective of t. gondii, you need a cat. Only in a cat can the t. gondii parasite complete all five stages of its existence, which concludes with the dispersal of “eggs” in feline feces (i.e., kitty poop). [3]

But trying to get from one cat’s droppings into the innards of another cat is not easily accomplished, especially given the fastidious habits of cats. (It’s not unlikely, by the way, that cats developed such habits as a defense to t. gondii – in the presence of the parasite, cats that practiced better potty habits were more likely to survive and procreate than those who did not.)

No, if you want to get back into a cat, you’ll need something else: a rat, for example. And indeed, t. gandii infects rodents very effectively.

Okay, now you’ve successfully made your way into a rat. You need to find your way back into a cat, which is not a remote possibility. A cat catches your rat host, eats it up (without cooking or freezing it), and you’re all set.

But if you really wanted to increase your chances of getting into a cat, better that your host have as many encounters with cats as possible. It turns out that male rodents are more exploratory, have a larger home range, and are more migratory than female rodents.

Getting the picture? If you’re a crafty t. gondii, you’ll do everything you can to make sure you get yourself into a male rodent – including increasing the birth rate of male offspring among mother rats from whom you will transmit yourself vertically. And while you’re at it, you’d might as well make the male rat you now call home more aggressive and less nimble – all the better to get eaten by that cat.

This constellation of actions is known as the parasites manipulation activities. Such activities alter the behavior of the intermediate host (here, the rat) to increase the chance of transmission to the definitive host (here, the cat).

Saber-toothed tigers aside, there’s not not much of an opportunity for humans to be manipulated in a manner that helps t. gondii make its way back into their favored cats. In short, these changes in our behavior and sex ratio at birth are simply collateral damage in the war between cats, rats and t. gondii.

For some very interesting commentaries on manipulation and the possible effects of toxoplasmosis in humans, check an online copy of a presentation given by Dr. Flegr, a commentary by Carl Zimmer (author of Parasite Rex), a 2003 Future Pundit blog, and a thorough review of the evidence at Signal Plus Noise.

1. You’ll find Flegr’s manuscripts on his website.

2. Hostomska et al. The role of toxoplasmosis in the mother in the development of mongolism in the child. Ceskoslov Pediatr 12:713-723, 1957

3. Hence the warnings to pregnant women to avoid cat litter boxes.

Opinions expressed are those of the author alone.