Good News and Bad From a Heart Study

Medical experts say the results, presented Sunday at the American Heart Association meeting, show there is a lesson to be learned about the effectiveness of small studies over all.

The drug, nesiritide, brand name Natrecor, was approved after small studies in carefully selected patients. It seemed to soothe a terrible heart-failure symptom — patients’ lungs fill with fluid and they feel as if they are drowning.

But the large study, with real-world patients, found no significant effect on that symptom.

A few years after its approval, nesiritide fell out of use because small studies seemed to indicate an increased risk of kidney problems and an increased death rate.

The large study showed those risks, too, were wrong.

“Once again, small studies give us the wrong answers,” said Dr. Robert M. Califf, a Duke cardiologist who directed the large study. “There was no safety issue at all.”

“To me, the really important message is that the drug got very widely used for reasons that are incorrect, and then it got bashed for reasons that are incorrect,” Dr. Califf said. “Unless we do these kinds of large clinical trials we are engaged in a comedy of errors,” he added.

The question of how to evaluate rare side effects that seem to arise in small studies plagues medical researchers. Most drug studies are not designed to assess rare effects, but as more drugs are sold to huge numbers of people who often take them for years, the question has become increasingly pressing.

Treatment of Head and challenges of the patient needs to be done

WASHINGTON — No patient gets closer medical attention than the president of the United States. Wherever he goes, a doctor, nurse or paramedic trails a few footsteps behind, ready for any medical need. It is the ultimate in concierge medicine.

A medical staff member stays overnight in the White House. When the president travels, the doctor rides in a limousine near the head of the motorcade. Jet lag and stress make the job one of near-constant fatigue, shadowed by dread of assassination attempts.

Now a recent holder of the job, Dr. Connie Mariano, has written an account of her nine-year tenure under three presidents, Bill Clinton and both George Bushes. The book, “The White House Doctor: My Patients Were Presidents — a Memoir” (Thomas Dunne Books), is one of just a handful of autobiographical accounts by presidential physicians.

Dr. Mariano’s story is an inspiring one. The daughter of a Navy steward, she was the first Filipino-American of either sex to rise to rear admiral, and the first woman in the military to become the White House physician. But her account gives scant attention to some important points and passes over others.

For example, the 25th Amendment deals with succession when a president becomes disabled or incapacitated. Dr. Mariano does mention that to avoid invoking the amendment, Mr. Clinton received spinal rather than general anesthesia when he needed surgery to repair a torn quadriceps tendon. But she has little more to say about the amendment, which is central to any serious discussion of presidential health.

Asked about that in an interview, Dr. Mariano replied: “There was a lot I didn’t put in the book because the publisher said it wasn’t of interest to the general public. They said this isn’t a scholarly thing — it’s a memoir.”

Not Just for Women?

For men, the potential consequences of infection by the human papillomavirus are nasty, like genital warts, and even life-threatening, as penile and anal cancers. But these complications are quite rare. For the average guy, the virus lies silent, doesn't cause problems, and clears in a year or two.

Still, HPV is the most common sexually transmitted disease in the United States, and the federal Advisory Committee on Immunization Practices is deliberating whether to issue a public recommendation that boys and men be vaccinated with Gardasil, the only HPV vaccine approved for that group, just as it's recommended for women. There is no easy answer. Experts must weigh the cost of immunizing against the benefits, which could include fewer cases of HPV-related cervical cancer in female partners but most of the time is just about staving off a few relatively harmless warts. They also want to wait and see whether the U.S. Food and Drug Administration will allow Gardasil maker Merck to market the vaccine for the prevention of anal cancer; currently it is approved for preventing cervical cancer in females between the ages of 9 and 26 and genital warts in males and females in that same age group. The FDA is expected to make a decision by the end of the year. ACIP officials will consider the FDA's action in making their recommendation, which could come as soon as February, says Lauri Markowitz, leader of ACIP's HPV working group. For now, though, men and parents of boys are on their own. They can request the three-shot series, and doctors are free to provide it.

So far, however, demand has been underwhelming. "Let's just say they're not knocking down the doors asking for it," says Michael Rich, an associate professor of pediatrics at Children's Hospital Boston. And from a professional perspective, he says, "it's not a standard protocol for your average 11-year-old boy, you know, troopin' in for his physical." But it's still something some parents will ponder.

Want to Be Happier? Keep Your Focus

Nearly half the time we're awake, our thoughts drift to topics unrelated to whatever we're doing. We think about the fight we had with our spouse when we're driving or replay events from a friend's wild party while brushing our teeth in the morning. We text incessantly while watching TV and phone mom during laundry-folding time. And all the while our minds are wandering—even when we're having pleasant daydreams—we're not very happy, according to a new study published today in the journalScience. "How often peoples' minds wander is definitely a big predictor of who's happy and who's not happy," says study author Matthew Killingsworth, a doctoral candidate in psychology at Harvard University, because the more often they take themselves out of the present moment, the less happy they are.


Most of the daydreams were about unpleasant or neutral topics, like mental to-do lists. But even pleasurable mental fantasies left participants no happier than when they were focused on whatever activity they were doing: weaving through traffic, tying their shoes, writing out a check. How the heck can this be? "When the mind wanders to a happy memory, it tends to eventually turn back to things that aren't quite as positive," says health psychologist Kelly McGonigal, who teaches a class on the science of willpower at Stanford University. Reminiscing about, say, that romantic Paris honeymoon might land you thinking about the snotty bellhop at the overpriced hotel where you stayed. This is the brain returning to what brain researchers refer to as its "default mode," a state of contemplating the past to learn from it, the future to prepare for it, or things in the present to see what needs to be fixed, explains Killingsworth. This default mode probably gave us an evolutionary advantage by making us alert to dangers while we were hunting and gathering. "We maximized our survival chances even if we didn't maximize our happiness," says McGonigal. "Evolution doesn't give a damn about happiness."