Thursday, December 9, 2010

Deadly Medicine | Politics | Vanity Fair

You wouldn't think the cities had much in common. Ia┼či, with a population of 320,000, lies in the Moldavian region of Romania. Mégrine is a town of 24,000 in northern Tunisia, on the Mediterranean Sea. Tartu, Estonia, with a population of 100,000, is the oldest city in the Baltic States; it is sometimes called "the Athens on the Emajõgi." Shenyang, in northeastern China, is a major industrial center and transportation hub with a population of 7.2 million.

These places are not on anyone's Top 10 list of travel destinations. But the advance scouts of the pharmaceutical industry have visited all of them, and scores of similar cities and towns, large and small, in far-flung corners of the planet. They have gone there to find people willing to undergo clinical trials for new drugs, and thereby help persuade the U.S. Food and Drug Administration to declare the drugs safe and effective for Americans. It's the next big step in globalization, and there's good reason to wish that it weren't.

Once upon a time, the drugs Americans took to treat chronic diseases, clear up infections, improve their state of mind, and enhance their sexual vitality were tested primarily either in the United States (the vast majority of cases) or in Europe. No longer. As recently as 1990, according to the inspector general of the Department of Health and Human Services, a mere 271 trials were being conducted in foreign countries of drugs intended for American use. By 2008, the number had risen to 6,485—an increase of more than 2,000 percent. A database being compiled by the National Institutes of Health has identified 58,788 such trials in 173 countries outside the United States since 2000. In 2008 alone, according to the inspector general's report, 80 percent of the applications submitted to the F.D.A. for new drugs contained data from foreign clinical trials. Increasingly, companies are doing 100 percent of their testing offshore. The inspector general found that the 20 largest U.S.-based pharmaceutical companies now conducted "one-third of their clinical trials exclusively at foreign sites." All of this is taking place when more drugs than ever—some 2,900 different drugs for some 4,600 different conditions—are undergoing clinical testing and vying to come to market.

Some medical researchers question whether the results of clinical trials conducted in certain other countries are relevant to Americans in the first place. They point out that people in impoverished parts of the world, for a variety of reasons, may metabolize drugs differently from the way Americans do. They note that the prevailing diseases in other countries, such as malaria and tuberculosis, can skew the outcome of clinical trials. But from the point of view of the drug companies, it's easy to see why moving clinical trials overseas is so appealing. For one thing, it's cheaper to run trials in places where the local population survives on only a few dollars a day. It's also easier to recruit patients, who often believe they are being treated for a disease rather than, as may be the case, just getting a placebo as part of an experiment. And it's easier to find what the industry calls "drug-naïve" patients: people who are not being treated for any disease and are not currently taking any drugs, and indeed may never have taken any—the sort of people who will almost certainly yield better test results. (For some subjects overseas, participation in a clinical trial may be their first significant exposure to a doctor.) Regulations in many foreign countries are also less stringent, if there are any regulations at all. The risk of litigation is negligible, in some places nonexistent. Ethical concerns are a figure of speech. Finally—a significant plus for the drug companies—the F.D.A. does so little monitoring that the companies can pretty much do and say what they want.

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Tuesday, December 7, 2010

Human Behavior Blog > National Affairs

Every day, hundreds of thousands of scholars study human behavior. Every day, a few of their studies are bundled and distributed via e-mail by Kevin Lewis, who covers the social sciences for The Boston Globe and National Affairs. And every day, I file away these studies because I find them bizarrely interesting.

What the dying can teach us about living

Canadian hospice care workers say caring for the dying teaches them how to live, according to a new study that looks at how people are shaped by exposure to death.
After shadowing doctors, nurses, assistants, spiritual care workers and psychologists in palliative care centres in Toronto, Ottawa, Montreal, Calgary and Vancouver, researchers found health professionals reported a better understanding of the meaning of life, an increased awareness of spirituality and an acknowledgment of their own mortality.
Lead researcher Shane Sinclair, of Calgary's Tom Baker Cancer Centre, said many of respondents in his study admitted to rearranging priorities in their lives after learning from their dying patients that they wished they had spent more time with family or focused on enjoying life instead of working.
"No patients had ever said that if they could do one thing over, they would work harder. They always said that what they're most proud of is their memories with family and friends," Mr. Sinclair said.
"These thoughts helped health-care professionals realign themselves to live as meaningful a life as possible. Now they have this gift of time, unlike their patients who were looking back," he said.
Some workers heeded the advice they received by taking vacations, and promising themselves they wouldn't let money or their career paths interrupt family time. Making health-conscious choices was also "in the mix" as some workers watched their patients die of lung cancer or other painful illnesses.
"In incorporating these decisions, they were able to live more truly out of their own sense of meaning, value and purpose rather than being directed by an outside authority," Mr. Sinclair said.
Patty Power, who was interviewed in the study, has been a nurse caring for terminally ill patients for about 30 years.
She said examining the minute details when looking after her patients made her a better mother, spouse and friend.
"I used to think I know everything and it's important in palliative care to minimize and relieve any painful symptoms, but it's important to just sit back and listen first," she said.
She watches families patiently look after their sick relatives every day, which has also taught her "another level of devotion and sacrifice."
Mr. Sinclair hopes his study, published Monday in the Canadian Medication Association Journal, will help Canadians and doctors discuss death without hesitation because there are benefits involved.
"Here, death is partitioned off as a separate phase of life we don't talk about as often and we try to make it very neat and tidy. In other countries, people are exposed to the experience more through rituals or festivals," he said.
Canada ranked ninth in an international Quality of Death index released this summer that measured hospice and palliative care environments in 40 countries.
But the country is still unable to provide hospice care services to more than 70 per cent of dying Canadians, according to the nation's Hospice Palliative Care Association.

Medical News: Psychotherapy Used Less in Depression - in Psychiatry, Depression from MedPage Today

More patients were being treated for depression in 2007 than a decade earlier, but fewer were receiving psychotherapy, researchers said.

Comparing 1998 with 2007, the percentage of those receiving psychotherapy fell from 53.6% to 43.1%, a downward trend that continued from the decade prior, Mark Olfson, MD, MPH, of Columbia University, and colleagues reported in the Archives of General Psychiatry.

For some patients, "depression care may be becoming more narrowly focused on pharmacotherapy," they wrote.

Due to the growth of selective serotonin reuptake inhibitors (SSRIs) and newer medications, the rate of outpatient depression treatment increased markedly in the U.S. between 1987 and 1997. But it was not known whether the trend has continued, the researchers said.

So they looked at data from the Medical Expenditure Panel Surveys from 1998 and 2007.

They found that those earlier rapid increases in depression treatment were followed by more modest increases: the rate of outpatient treatment for depression increased from 2.37 per 100 persons in 1998 to 2.88 per 100 in 2007 (OR 1.18, 95% CI 1.03 to 1.35).

That corresponds to an increase from about 6.5 million to 8.7 million patients, they said.

Treatment with antidepressants remained about the same, rising only slightly from 73.8% in 1998 to 75.3% in 2007, and the researchers said this trend was significant for those ages 50 to 64 and for uninsured patients.

Yet the percentage of those receiving psychotherapy fell from 53.6% to 43.1% (OR 0.71, 95% CI 0.53 to 0.95), following a drop between 1987 and 1997 (71.1% to 60.2%).

That's "despite progress by academic researchers in demonstrating the efficacy of several specific forms of psychotherapy for depression," the researchers wrote.

"It is not possible to determine whether declining use of psychotherapy reflects patient preferences for antidepressant medications or difficulties with access to psychotherapy related to a scarcity of local psychotherapists, financial or insurance coverage considerations, or other barriers," they said.

Those who did have psychotherapy had a decline in the mean number of visits and in the expenses for those visits.

A trend toward declining use of any psychotherapy was significant for patients ages 35 to 49, Hispanics, those with less than 12 years of education, Medicaid beneficiaries, and unemployed adults.

National expenditures for outpatient treatment of depression increased from $10.05 billion to $12.45 billion over the study period, although this was not a statistically significant increase.

However, there was a significant increase in Medicare expenditures for depression treatment, from $0.52 billion to $2.25 billion (P<0.001).

The researchers noted that despite the fact that more Americans are being treated for depression, it's "likely that a substantial number of patients with depression remain untreated."

They concluded that it will be important to "develop clinical policies that promote access to effective treatments for depression."

Sunday, December 5, 2010

A Heart Loses Its Way -

The 59-year-old woman struggled to her feet. Even with her husband at her side, it was tricky getting out of the car. At least it was now. She stood for a moment, unsure of her legs. Then all her strength seemed to evaporate; her legs felt like Jell-O, and despite her husband's arm around her, she sank to the ground. "Can you stand if I help you?" he asked. She shook her head — tears of frustration filled her eyes. "I'll be right back," he assured her, then he sprinted the few steps to the doctor's office, returning moments later with a wheelchair and a couple of nurses.

An ambulance rushed her to the hospital. It was her blood pressure, again. The patient had considered herself pretty healthy, at least until recently. Sure, she had high blood pressure and diabetes, but she never let them slow her down. And then she had a heart attack — almost a month ago — and ever since, nothing had been right.

The patient's husband felt overwhelmed and angered by his inability to help his wife of 36 years. She had yet another doctor's appointment that afternoon — this time with her internist — but she didn't feel well enough to go. She was just too weak. She was scared, and as much as her husband tried to hide it, so was he.

Suddenly, he knew what he had to do. He picked up the phone and called the Fairfield, Conn., office of Dr. Deborah Mayer, his wife's internist. "My wife has an appointment this afternoon, but she's not well enough to come in," he told the receptionist. He wanted to come instead, to talk with the doctor about his wife. They simply couldn't go on this way.

The patient first saw Mayer six years earlier, the husband reminded the internist later that afternoon. He referred to the notes that his wife had kept since then. At that first visit, her blood pressure was a little high, and so was her weight. So the doctor advised her to lose a few pounds and start exercising. She was supposed to come back in a month or two, but life got busy, and she didn't make her way back to Mayer's office for another four years. At that point her blood pressure was really high, and Mayer started her on a blood-pressure medicine. When that wasn't enough, Mayer added a second. Her blood pressure remained high. The doctor fiddled with the medicines, increasing the doses, adding a third. Her blood pressure still remained high. Mayer instructed the patient to buy a blood-pressure cuff to use at home to make certain she didn't have "white-coat hypertension": blood pressure that goes up just because you're at the doctor's office. The home readings were all over the place: sometimes very high, sometimes very low. Her blood pressure was never normal — not in the office, not at home.

Then she had a heart attack. She was in the hospital for four days. They finally sent her home with a bunch of new pills, but she'd been a mess ever since. "Something has to be done," the husband told the doctor. "We can't go on this way."

Mayer reviewed the patient's chart. Her last appointment was a couple of weeks ago, just after she left the hospital following her heart attack. At that time, her blood pressure was a little high when she was sitting, but when she stood up it plummeted.

This kind of position-related drop in blood pressure — a condition known as orthostatic hypotension — is pretty common and is usually linked to dehydration or overmedication. After that last visit, Mayer lowered the medication dosages and advised drinking plenty of fluids.

But the patient sounded as if she was feeling no better and maybe even a little worse.

As the husband went through his wife's story, Mayer paged through her chart. She was shocked to note that there wasn't a single normal blood pressure recorded. Not one. Each visit had triggered yet another effort to control the patient's blood pressure. None of it worked.

Getting high blood pressure under control is a process — it can take weeks, even months. A patient starts on a medicine and then returns in a couple of weeks to see if the dose needs to be increased or another medicine added. It's a crude process of trial and error, but usually it works.

It hadn't worked here.

"I think maybe we are focusing on the wrong thing," Mayer said, pronouncing each word slowly and carefully as she thought through the problem. At each visit the patient had an abnormal blood pressure — usually too high, but not always. And at each visit Mayer had adjusted the medications. She hadn't really stepped back to look at the big picture. Until now. It was clear that this wasn't a case of blood pressure that wasn't being controlled; it was a case of blood pressure that couldn't be controlled, and that was a very different kind of problem.

Usually when blood pressure stays high despite treatment, it's because the patient either isn't taking her medications or isn't taking them correctly. Studies show than nearly half of all patients with high blood pressure don't take their medications as prescribed by their doctors. But Mayer didn't believe that this patient wasn't taking her medicines. She was too sick and too worried not to take them.

Certain blood-pressure medications — most commonly diuretics, which can make the patient dehydrated — can cause orthostatic hypotension. This patient had been on a diuretic, but Mayer stopped it at that last visit, and that hadn't helped.

No, it wasn't going to be one of the usual suspects. What else could cause these episodes of wildly fluctuating blood pressure — hypertension alternating with orthostatic hypotension? Then it struck her. Could this combination of symptoms be caused by too much adrenaline? There are rare tumors — pheochromocytomas — that secrete high levels of adrenaline, and such tumors can cause this combination of high blood pressure and orthostatic hypotension. It's a really rare disease. In a sample of 100,000 patients with high blood pressure, maybe only 5 of them will end up having this kind of tumor as the cause. But if the patient did have a "pheo" (as it's called), that could explain why her symptoms became so much worse after her heart attack. A class of medicines known as beta blockers is regularly used in patients with heart disease, and when taken by a patient with an excess of adrenaline, these drugs can cause erratic fluctuations in heart rate and blood pressure. This patient was on a whopping dose of a beta blocker. Mayer was certain she had a pheo.

She quickly explained her thinking to the husband and ordered an abdominal ultrasound for his wife. A pheo is usually a large tumor, and it would be easy to spot. And indeed, the ultrasoundrevealed a mass the size of a plum on top of her left kidney. A blood test revealed that she had more than 100 times the normal amount of adrenaline in her system. She was referred to a surgeon at Yale for removal of the tumor. That was six months ago. After the operation, the patient's blood pressure was controlled with only one medication. And she feels great.

In medical school, I was often told that if you listen, the patient will tell you what she has. It turns out that sometimes the patient's husband will, too.

Lisa Sanders is the author of "Every Patient Tells a Story: Medical Mysteries and the Art of Diagnosis."