How Reliable Are Those Test Results?

When you go to your doctor with one complaint or another, the most common response is, “Let’s run some tests.” You and your physician both expect that with those results in hand, you’ll have a better idea of what’s going on and can work toward a solution.

Of course, anyone who’s seen an episode of House knows it’s not always that simple. But even when your symptoms aren’t due to some obscure condition, there’s a complicating factor: the test results may not give the right answer.

How Things Can Go Wrong

We need to get into statistics again, if only briefly. There are four possible outcomes of a test:

  1. You have the condition, and the test says that you do. This is known as the sensitivity of the test.
  2. You have the condition, but the test says that you don’t. This is called a false negative (in statistics lingo a “Type 2” error).
  3. You don’t have the condition, but the test says that you do. This is a false positive (a “Type 1” error).
  4. You don’t have the condition, and the test says you don’t. This is the specificity of the test.

A Type 2 error leads to not getting treated for something you have, while a Type 1 error leads to unnecessary treatment for a condition you don’t have—or, more importantly, instead of the condition you do have. (If you’d like to wander into the weeds of statistical methods, here’s a good explanation of the errors from Mark Liberman, a professor at the University of Pennsylvania.)

Tests can go wrong for any number of reasons. They can be misread or misinterpreted, for example on an x-ray or sonogram. Or they can be based on uncertain data, as in PSA testing. What caught my eye was some recent news about kidney damage.

Good Tests Can Lead to Bad Treatments

Many medications can cause damage to your kidneys—pain relievers, antibiotics, and drugs for heartburn among them. Certain health conditions can injure your kidneys as well, chiefly high blood pressure and diabetes. Kidney injury is usually diagnosed by measuring levels of a protein called creatinine; more particularly, changes in the level of creatinine.

A study published in last week’s Clinical Journal of the American Society of Nephrology showed that blood tests for levels of creatinine can result in a false diagnosis of kidney damage (specifically, acute kidney injury) an average of 8% of the time. That may not sound like much of an error, but in people with higher levels of creatinine to begin with, the error rate rose to 30%.

The implication is that your physician may be making treatment decisions based on these test results. The most drastic decision is to begin dialysis, but he/she may also withhold an effective treatment because of known effects on the kidneys, such as the pain relievers I mentioned earlier.

For you, here’s what this means. Whenever you see test results that are out of the normal range, dig further. Before beginning any treatment based on those results, ask your doc what the error rate is and how that rate affects the decision. (They may be surprised to hear that question, and in fact may not even know.) It’s part of being a smart consumer.

OTC to Rx Seems Like the Wrong Direction

It keeps happening. A common substance (two actually), available on drug store shelves everywhere, has been turned into a prescription drug. The current culprit is a drug called Diclegis, prescribed for morning sickness in pregnancy. You may recall that the drug has gained some notoriety because a famous person was shown on her Instagram account holding a bottle of the product and exclaiming over its benefits.

It turns out that Diclegis is nothing more than a combination of an antihistamine and a vitamin. A 30-day prescription runs around $350, while a 30-day supply of doxylamine succinate (aka Unisom) and pyridoxine hydrochloride (vitamin B6) will cost you about $25. Not only is it made from common ingredients, it’s a repeat of a drug that was on the market more than 30 years ago. The drug Bendectin was the only FDA-approved remedy for morning sickness. Many women had filed lawsuits claiming that the drug had caused birth defects in their babies. It wasn’t true, but the cost of defending the suits led the maker to pull the drug from the market in 1983. The only real side effect from Bendectin/Diclegis is sleepiness—not surprising considering that the main ingredient is an antihistamine.

There’s Gold In Them There Pills

As I mentioned in an earlier post, when a drug goes off patent protection the manufacturer often looks to take it to over-the-counter (OTC) status. But every now and then someone with a deep pocketed research grant sees a way to go the other direction. Another example of this transfer is a prescription fish oil. Lovaza contains 840 mg of omega-3 oils from fish, in 1 gram total of fish oil. The maker has run plenty of clinical trials showing that Lovaza provides benefits for your heart and brain. The claim is that Lovaza is better than ordinary off-the-shelf fish oil because it’s more concentrated, or because it’s standardized, or some such. I don’t believe a word of it. If your doctor recommends Lovaza, look for a good high-potency fish oil at your local grocery instead.

Another example is Niaspan. This is simply a time-release formulation of niacin, vitamin B3. A 90-day supply of 500-mg Niaspan will cost nearly $200, while the same amount of ordinary niacin is less than $10 at the grocery. (Or you can do what I do, and buy niacin as bulk powder from online sources such as www.PureBulk.com.) Not to mention that time-release formulas of niacin carry a higher risk of liver damage than the ordinary type.

Be a smart consumer. When your doctor recommends a prescription type of something ordinary, ask why the preference.

FDA vs. FTC Over Homeopathy

This past week our Federal Trade Commission (FTC) commented on the FDA’s regulation of homeopathic medicines. While this might seem like all a bureaucratic fuss over not much, it points up the unique position homeopathy holds in the health care universe.

The 411 on Homeopathy

Homeopathy is based on the principle that “like cures like.” For example, a dose of something that makes your skin itch will help health skin that’s itchy from another cause. Mainstream medicine, though, claims that homeopathy is the height of quackery. Their claim is based on both the way homeopathic remedies are made and how they’re used.

Individual remedies are made by successive dilution of an original substance, such as sulfur or poison ivy. The label of a remedy will tell you how far it’s been diluted: 6X means it’s been diluted 10-to-1 6 times (“X” = 10 in Roman numerals), and 30C means it’s been diluted 100-to-1 30 times (“C” = 100). As you can imagine, it doesn’t take very many dilutions before the original substance is barely detectable in the final product. In fact, once you get to 30X or 15C dilution, there might not be any of the original substance available. (Google Avogadro’s number for an explanation of why.) And homeopathic theory holds that a greater dilution is often more effective.

Enter the Regulators…

The FDA is charged with ensuring that all medical items, whether drugs or devices, are both safe and effective. The FTC monitors advertising claims for truthfulness. Somehow, homeopathic remedies got grandfathered in under the FDA’s current structure in 1938, so for FDA approval they only have to show that they’re safe. And given the argument that they might not contain anything other than sugar, it’s hard to claim that the remedies might be dangerous. So as far as the FDA is concerned, homeopathic remedies are just fine for self-limiting conditions that aren’t chronic. You’ll see Oscillococcinum for flu, Zicam for colds, and SinuFix decongestant nasal spray in CVS and Walgreens, and many other more specialized remedies in your local health food store.

The FTC wants more, however—they want proof of effectiveness to back up any health claims on the label. There have been very few clinical trials run on homeopathy, though, for several reasons:

  • “Respected” researchers don’t believe it’s plausible, so why waste money on the research?
  • Treatments are very individualized, which makes it difficult to standardize results. Two people with high blood pressure will receive different treatments if one has headaches and the other doesn’t.
  • Very few homeopathic physicians are also MDs. Being outside the system reduces the incentive to publish.

My take is that anything that works in animals—and homeopathy most certainly does work there—should work in humans as well.

…and Exit the Regulators

For now it appears to be a standoff between the two agencies. Back in 1972, the FDA said it was cracking down on advertising claims. In the more than 40 years since, though, nothing has been done regarding homeopathy. The FTC would like to change that, but there seems to be no movement at the FDA on the issue.

In the meantime, homeopathy continues on its merry way. If you decide that you want to try this therapy, work with a homeopathic practitioner to identify the best remedies and strengths for you.

A New Drug of Choice?

My local paper carried an article this morning about the latest series of deaths from an overdose of heroin. It seems like that’s become the drug of choice for people of all stripes. It used to be that heroin was for the junkies, the losers, the lowest of the low. No more. Now it’s the go-to option for people looking to replace prescription opioid painkillers such as oxycodone.

All the opioids—drugs that act like opium, such morphine—are excellent at relieving mild-to-moderate pain for most people. But they also all create physical addiction and mental dependence in regular users. This creates a dilemma for physicians and for society: How do you provide access to these drugs for people who truly need them, while keeping them out of the hands of those who abuse the drug? And how do you tell the difference for sure? (One of my new favorite bloggers, Jen Gunter, has an excellent article about the dilemma physicians face.)

The term diversion refers to any use of a drug outside its purpose intended by the prescribing physician. (This definition may seem a little convoluted, and it is. But diversion has a very specific meaning.) In the case of opioids, they can be diverted by theft, by black-market sales to other people, or by what’s known as doctor-shopping—going from doctor to doctor looking to get a prescription without the others being aware.

From Savior to Satan In One Easy Step

Oxycodone had been available for many years as the brands Percodan (when combined with aspirin) and Percocet (with acetaminophen [Tylenol]). But these formulations called for taking the drug every 4–6 hours to maintain effectiveness—which played hell with the sleep pattern of someone in pain. When the time-release formulation Oxycontin was approved in 1995, it was seen as a godsend for people who suffer chronic pain. Now they could take the drug only twice a day for longer-lasting pain relief.

Oxycontin packs twice as much oxycodone into a single tablet, released over time. But if you crush the tablet the time-release mechanism is defeated and all the drug is available at once. This is what made Oxycontin so attractive to addicts. For a period in the late 1990s and early 2000s, pharmacy break-ins seemed like the crime du jour. Eventually pharmacists got smart and held only enough Oxycontin in stock for that day’s needs. Now the primary source of diversion is patients, who sell what they don’t use for up to $50 per pill.

Yes, Heroin Kills

As the supply of Oxycontin has dried up, people have been turning toward heroin instead. It’s relatively cheap and easily available (so I’m told), and increasingly socially acceptable. Except when it kills.

Street heroin is cut with anything from powdered milk to kitchen cleanser, and the user can’t tell the difference. Who knows what else they’re putting in their arm, or foot, or neck, or wherever else they can pop out a vein. And the cutting leaves the drug at an uncertain strength, which is how most overdose deaths happen—the user gets an unexpectedly potent dose. Not that I’m recommending the abuse of prescription drugs, but at least with Oxycontin you know what you’re getting.

Convenient Isn’t Always Best

It seems like everywhere you look these days you see ads for anticoagulant drugs. These meds, Pradaxa, Xarelto, and Eliquis, are being promoted to reduce the risk of stroke due to the heart condition atrial fibrillation (aFib). They’re intended to replace the older warfarin (Coumadin), and are supposed to be better because they’re more convenient. But once you know the facts you’ll see that “convenient” may not be right for you.

No Salad for You Today

Warfarin reduces blood’s ability to clot by blocking the action of vitamin K—a factor in what’s known as the clotting cascade. The drug has been around since the 1950s, and works very well at thinning the blood. It has a bad reputation among patients, though, for two reasons. The first has to do with what’s known as the therapeutic index. This is the range of dosage that walks the line between too little to be effective and so much that it’s dangerous. The balance is so delicate that the brand-name drug was alone in the marketplace for more than 40 years before makers of generics could show that their warfarin was as stable as the branded medication.

Patients on warfarin need regular testing of their blood’s clotting ability, with a test called the INR (international normalized ratio, what used to be known as PT/prothrombin time). When beginning a regimen of warfarin, it can takes weeks of constant testing and adjustment to get just the right dosage. And any change in your other medications or your lifestyle can drag you back into the test/adjust phase.

This leads to the second reason. Warfarin works through the vitamin K system, so you have to keep your dietary intake of vitamin K steady. That is, if you have a salad for dinner, you have to have one pretty much every day, with the same kind of greens. (Leafy greens such as lettuce and kale are the main source of dietary vitamin K.) For just about everyone, the only way to keep your intake constant is to make that intake zero. And, um, leafy greens are good for you.

There’s So Much Blood

The risk of any blood thinner is that of excess bleeding. If you’re going in for surgery you need to stop the medication some time beforehand to avoid excessive bleeding during the procedure. And any injury poses a higher risk. I once watched a friend taking warfarin bleed almost all day from a simple shaving cut. Bumps and falls carry a higher risk of bruising. Serious injuries like those from an auto accident can cause death by bleeding out. The highest risk, though, comes from undetected bleeding such as from an ulcer.

Fortunately, for someone who’s taking warfarin there’s an antidote: vitamin K. But the newer drugs work differently, and there’s no antidote. The results are about what you’d expect. Between 2010 and 2014, there were about 9,000 anti-coagulant-related deaths reported to the FDA. Of those, only 700 were related to warfarin, even though up to 10 times as many patients are taking warfarin as are on these newer drugs. Curiously, studies on the new drugs show a lower risk of stroke compared to warfarin. But the real world doesn’t always agree with results from clinical studies.

Ads for these newer anticoagulants show people leading carefree lives, I suppose because they’re no longer burdened with all the testing. Somehow the family sitting around after a funeral doesn’t make it into those ads.

Oh, and by the way, a 90-day script of generic warfarin costs about $10, while the new guys are $500–$1,000. So much for controlling health care costs.

Nobody’s Breathing Easier Around Here

I was scrolling through statistics on drug sales recently, looking up information for another post. I found something that shocked me right down to my socks. For as long as I’ve been following this information—more than 20 years now—the number-one selling drug in terms of prescriptions written has been a painkiller. Most recently this has been the opiate hydrocodone plus acetaminophen, the popular Vicodin.

Now 38 million scripts a year is a lot of prescriptions, but I do understand how this could happen. The trend makes sense to me because so many people experience distracting pain at some point during a year. I’ve taken one or another of these drugs for dental issues and for a broken rib. But pain relief has taken a back seat to drugs for breathing difficulty.

A Breath of Fresh Air? Hardly

In 2013 (the latest year available) the number-one selling drug in this country was generic budesonide, a drug used to treat asthma. The shocking part for me is that budesonide is joined by 3 more breathing drugs in the top 10, and another 5 among the top 75 sellers. That’s more than 120 million prescriptions all told in 2013. Some of these later 8 are also used to treat COPD—chronic obstructive pulmonary disorder, a catch-all phrase that includes emphysema and chronic bronchitis.

As a child I had allergy-related asthma. I eventually mostly grew out of the allergies, and a damp summer night is about the only thing that bothers me now. I still have a prescription inhaler around for occasional use (but I think it’s about 10 years old by now—maybe time for a replacement). Allergies in general seem much more prevalent now overall, so I suppose the increase in respiratory drugs is related to that. And when you look at sales statistics, the asthma drugs are very seasonal—peaking during the winter—while those primarily for COPD have a much more level sales trend.

Maybe this is all related to people living longer. Or maybe it’s the long tail of the tobacco use dragon. It could be related to lung damage from other prescription meds. Or the allergy piece. Whichever, there are many, many people out there on meds for lung health.

Don’t Be Scared by (or of) Statistics

A study came out recently showing that having a joint replaced increases the risk of having a heart attack by at least a factor of three in the month after surgery. Gah! What’s a person to do, then, if you’re barely able to walk because your knee or your hip is causing you so much pain? The first thing to do is look at the actual numbers behind those statistics.

How Large Is Large?

Researchers in Great Britain reviewed records of patients through the Health Improvement Network, which captures information about more than 10 million people. They found that during the period 2000–2012, nearly 14,000 people in that database had a total knee replacement, and more than 6,000 had a total hip replacement. When compared to similar patients who had not had a joint replaced, those who had a new knee were more than 8 times as likely to have a heart attack in the following month, and those with a new hip were more than 4 times as likely to experience a heart attack.

Those figures sound dreadful, but the raw numbers were so low that the change in absolute risk is negligible. And over the longer term, the risk of heart attack evened out between the two groups. In the 4 years following surgery, there were 306 heart attacks in the replacement knee group and 286 in the born-with knee group. For the hip folks the numbers were 128 and 138 (yes, fewer in the replacement group). For the knee group those 20 extra heart attacks sent the total risk zooming from 2.0% without replacement all the way up to 2.2% with joint replacement. Hardly a cause for excitement. And in a group that was older (average age 71) and heavier (BMI of 28—not obese but still overweight) to begin with, it’s not surprising that there were heart attacks.

What, Me Worry?

Other recent studies had shown a reduced risk of heart attack long-term in those who have had a joint replaced. Research in Toronto showed that over a followup period averaging 7 years, joint replacement reduced a person’s risk of heart attack, stroke, or other cardiovascular events by about 12%. Other research, conducted in Taiwan, showed a 7% reduction in CV risk over 5 years.

There could be many reasons for this health improvement. It could come from a change in diet after surgery, or less for NSAID pain medication, or increased physical activity. Regardless, the benefit is there.

The press release from the publisher of this current study was titled, “Knee and Hip Replacements May Be Bad for the Heart.” This seems like a title aimed at getting noticed rather than one that tells the truth. Now that you’ve seen how statistics get cherry-picked to make a point, you can be a smarter consumer of information.