This month, Dr. Sydney Spiesel discusses early detection of lung cancer, a $1 pill that could save millions of women's lives, whether teeth whiteners work, nighttime calls to the doctor, and alleviating the pain of shots.
Detecting lung cancer early
New research: Lung cancer is the leading cause of death among cancer victims. Tobacco use contributes; so does the silent development of the disease in its early stages. By the time enough symptoms have developed for a likely diagnosis, the cancer generally has spread too widely to be treated successfully. What if lung cancer could be detected earlier? More than 65 physicians around the world have collaborated on a study of the value of screening for early diagnosis. Last week, they reported their results in the New England Journal of Medicine, with reason for optimism.
Results: Using a low-dose spiral CT scanner, researchers screened more than 30,000 people age 40 or older who were known to be at risk for developing lung cancer (they smoked, were exposed to secondhand smoke, or worked in an industry with a high incidence of lung cancer, like uranium mining). The subjects had no symptoms. As a result of screening, almost 500 cases of lung cancer were found. Eighty-five percent were diagnosed early (with clinical Stage 1 disease), and the majority of these cases (302 of 412) had surgery to remove the tumor within a month of diagnosis. Of this early-diagnosis and quick-treatment group, 92 percent have survived for 10 years or are projected to survive for at least that long. The patients whose treatment took longer to begin have done nearly as well, with a projected 80 percent 10-year survival rate. By contrast, the eight patients with Stage 1 disease who chose to have no treatment all died.
Caveat No. 1: These are impressive results, and there will be great pressure as a result of this study to dramatically expand lung cancer screening using this low-dose CT technology. Is this a good idea? Critics argue that this style of study—in which there is no comparison group of patients similarly at risk who were not given CT scans—can never tell us if the intervention will actually prevent lung cancer deaths. Perhaps, for example, some of the tumors discovered by CT scan and treated would have regressed on their own, since malignancies are not entirely predictable. The deaths of the eight patients diagnosed but not treated help address this weakness in the study, though. My back-of-the-envelope analysis of the data found only a minuscule probability (less than one in 10,000) that chance could account for their 100-percent death rate as compared with the 18-percent death rate in the patients who were diagnosed and treated.
Caveat No. 2: There's another critical question about CT scans for lung cancer: costs versus benefits. Cost for this study was estimated at about $200 per screening (a lot less than the $800 at my institution). For the experiment, 31,567 people were screened and 27,456 were screened twice. That comes to, let's see, somewhere between $24,400 and $97,600 per case of lung cancer diagnosed. In addition, the scans identified more than 5,600 patients whose lungs showed signs suspicious for cancer, all of whom had to be biopsied or required other expensive tests to identify the 484 patients who actually had lung cancer.
Caveat No. 3: Economic expense is not the only cost to consider. Even low-dose CT scanning exacts a radiation cost to the body, a cost that increases the risk of developing cancer in the future—and smokers and ex-smokers might be at a risk that's greater than average, as one researcher has pointed out. The key question is whether the benefit of early detection and treatment exceeds the increased risk of developing cancer.
Conclusion: The other side of the cost-benefit equation is that cancer diagnosed early and treated successfully greatly reduces misery and the cost of care, and pays dividends in increased productivity. If CT scanning can be shown to have a worthwhile cost-benefit ratio, the method has great promise for improving the outlook for people at increased risk of lung cancer.
An amazing postpartum pill
The problem: More than 1,400 women die every day worldwide as a result of complications of pregnancy or childbirth, virtually all of them in the developing world. The single most common cause is postpartum hemorrhage—uncontrolled, catastrophic bleeding following delivery. Usually this kind of bleeding occurs because the muscles of the uterus become lax after delivery and don't contract forcefully to squeeze blood vessels closed. In developed countries, doctors control heavy postpartum bleeding with intravenous medications that cause the muscles of the uterus to tighten. In developing countries, these kinds of treatment (and midwives skilled in their use) are often not available, and so the women die.
The miracle drug: A recently reported study (Lancet subscription required) by Richard Derman of the University of Missouri and colleagues shows that this need not be the case. The research team showed that a single pill costing $1, administered to women in poor communities in India, cut the rate of hemorrhage dramatically. The miracle drug, misoprostol, is well-known to American physicians, who use it here to prevent the stomach-damaging effects of many drugs used to treat arthritis. The drug has another use: It plays a role in the standard method of early-pregnancy medical abortions. (Though used alone, it is usually not effective to induce abortions and is terribly unsafe.)
Given after childbirth, misoprostol stimulates the muscles of the uterus to regain tone. It is not used after delivery in developed countries, where more-effective products (like oxytocin) are the norm. But those drugs must be administered intravenously, require refrigerated storage, and are far more expensive, and so aren't well-suited for the developing world.
The study: About 1,600 women in India were divided into two equal-sized groups. After delivery, midwives treated half with a tablet of misoprostol and half with a placebo tablet. Use of misoprostol led to a 50-percent reduction in postpartum hemorrhage generally and about an 80-percent reduction in severe hemorrhage—one case prevented for every 18 women treated. The only side effects found were brief episodes of shivering in some women. (And there was an unanticipated benefit: The study confirmed the value of a traditional method of estimating maternal blood loss.)
Further benefits: Postpartum misoprostol could have great benefits even beyond preventing hemorrhage and saving women's lives at delivery. These include 1) fewer orphaned children; 2) less postpartum anemia, which makes people weak, less able to take good care of themselves and their children, and more susceptible to infection; 3) many fewer blood transfusions for women—which have played a huge role in AIDS-HIV transmission in central Africa.
Conclusion: I'm sure there are worries that easy availability of misoprostol will lead to its diversion for abortions. But that shouldn't stop its use after delivery: It has pretty amazing potential for a $1 pill.
White teeth: Can they be yours?
New research: The drugstore aisle promises a dazzling smile. But are tooth whiteners safe and effective? Hana Hasson and associates at the University of Michigan examined the question by finding 25 academic papers that compared home-use teeth-bleaching products with a placebo or with each other. Results were measured after two weeks of use with an electronic instrument (a colorimeter) or by visually comparing teeth with a standard set of toothlike color tabs. The products evaluated included gels, paint-on films, and whitening strips. The active bleaching ingredient was either hydrogen peroxide or carbamide peroxide.
Findings: The authors were appropriately critical of the 25 studies, noting that all of them were sponsored by the manufacturer of a whitening product. Nevertheless, the results were a little encouraging for those of us with movie-star fantasies. Teeth whiteners work, at least in the short term. In general the gels worked best, the tooth-whitening strips came in second, and the paint-on products were third. Not surprisingly, the more concentrated the active ingredient, the more effective the whitening. Some of the studies compared immediate results with effects measured three or six months out and found improvement maintained over the longer period.
Side effects: Both hydrogen peroxide and carbamide peroxide cause bleaching by releasing oxygen. The short-term effects, especially of the gels, include tooth sensitivity and gum irritation. I was surprised to learn that both active ingredients penetrate through the tooth's enamel and dentin, and into the pulp, minutes after application. Whether that harms these structures in the long run is unknown.
Bottom line: So, these products are pretty good at whitening teeth, but poorly studied for long-term risks. Would I do it? Hmmm … let me go smile at the mirror and commune with my vanity.
The nighttime call: The other night I was awakened at 3 a.m. by a medical phone call. The patient's question seemed trivial. I thought about it for a minute, answered, hung up, mused for a bit about the meaning behind the call, turned off the light, and went back to sleep.
New research: Many doctors feel angry and resentful when they get a call like this, but I don't. Partly that's because I almost never have trouble going back to sleep. But it's also that I think these middle-of-the-night calls serve a function. Now I am vindicated by a paper in the most recent issue of the Journal of the American Board of Family Medicine by David Hildebrandt of the University of Minnesota and colleagues. These researchers studied after-hours phone calls received by a family-practice training program. An operator asked callers whether the call was an emergency. If they answered yes, their calls were forwarded to a doctor; otherwise, a written message was faxed to the office for review and response in the morning.
Findings: Ninety percent of the night callers said it was an emergency and spoke to the covering practitioner. Of the remaining 10 percent—288 nonemergency calls—more than half couldn't be reached, so only 119 were evaluated. Hildebrandt found that one-quarter of these calls came from patients with pain or discomfort that, though not directly harmful or health-threatening, should have been addressed at the time of the call. Three percent of the deferred callers suffered clinical harm, and 8 percent needed to visit the emergency room or another major intervention, which they had to arrange themselves. By pure good luck, no patients in this sample suffered serious harm or died—particularly fortunate was a man who complained of chest pain traveling down his left arm, went to the ER, and turned out to have gastroenteritis rather than an impending heart attack.
Conclusion: The authors of this paper argue—and I agree—that all after-hours clinical calls to primary-care physicians (and why not specialists, too?) should be forwarded directly to the on-call physician. I learned years ago that if patients know you can be reached, even in the middle of the night, they are more likely to call you about a serious problem and less likely to call about a minor one. And if the call does turn out to be trivial, there is always the fun of trying to divine its hidden meaning.
The problem: I can't tell you the number of older children who fondly describe the time they forced me to chase them around the examining table with a dripping syringe as they did their best to avoid the needle. I refrain from pointing out that I am almost never inclined to run, and that one end of my examining table has always been pressed up against the wall. I do give my own shots, never try to trick children, and offer a straight warning. This pays off in patient trust, which lessens the fear and decreases the pain. But no matter how much I'd like to, I can't make shots pain-free. And for children who are exceptionally anxious or exquisitely sensitive, immunizations or blood drawings can really be a nightmare.
New research: So, I really looked forward to reading a recent review by Lindsay Uman at Dalhousie University in Nova Scotia and her colleagues on psychological interventions for children going through medical procedures that use needles. The authors examined 28 studies involving almost 2,000 children in total. In each study, the children (aged 2 and up) were randomly assigned to treatment (for example, distraction, breathing exercises, desensitization, hypnosis) before the shot or to no treatment. After the procedure, the pain of the two groups was compared.
Because the 28 studies included disparate methods to help prevent pain and distress (not to mention disparate methods to evaluate the results), it is hard to draw firm conclusions that I can take back to my examining room. Except these: Hypnosis was the most effective method, and distraction also had some value. Some of the other methods were vaguely described (what are "combined cognitive-behavioral intervention," "virtual reality distraction," and "memory alteration?"). And most didn't seem to be useful anyway.
At least until I learn the tricks of hypnosis, I guess I'm back to muddling along. I talk fast and hard, which amounts to distraction, I suppose. I give tips to minimize pain ("Jell-O arm"). And for the really hard cases, I have a secret stash of a special sticker that's no longer for sale. It says "I pitched a fit," and it is clearly worn with great pride.