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Drug offers hope for a brighter start for premature babies
Prematurely born babies score lower on intelligence tests than their healthy, full-term siblings and frequently require special educational services and other assistance. One suspected cause of the problems they face later in life is bleeding into tissues of the brain, which often occurs during premature births. Giving them an anti-inflammatory drug that reduces the bleeding at birth, however, has raised hope that fewer prematurely born children will suffer significant long-term intellectual and emotional problems.
Investigators in a multi-center study directed by Yale pediatric neurologist Laura R. Ment, M.D., administered the non-steroidal drug indomethacin, which is generally used for treating adults with arthritis, to 431 very-low-birth-weight premature babies shortly after birth. In follow-up ultrasound studies, the infants who had been treated with the drug bled less and had less brain atrophy than babies treated with a placebo. In assessments at 6 and 8 years of age, they appeared to have suffered fewer long-term intellectual deficits and required significantly fewer special services than those children who had been given the placebo. Almost three times the number of children who received the placebo required speech and language therapy when compared to those who received the medication. The placebo group also scored lower on intelligence tests and tests of communication skills and emotional status.
The findings of the study were presented at the joint meeting of the Pediatric Academic Societies and the American Academy of Pediatrics in May. Ment said, “Almost all other studies of protective agents in the newborn period do not have long-lasting effects. This drug does, in fact, appear to protect the developing brain.”
According to Ment, approximately 25 percent of neonatal intensive care units in the country use indomethacin as the standard of care for very-low-birth-weight preterm infants.
She hopes to see that percentage increase so that all premature babies can benefit from the drug.
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Combination therapy,
acupuncture shown effective
in curbing cocaine cravings
Many heroin addicts also abuse cocaine and continue taking the drug even after they stop using heroin. Currently available medications that help them stop using heroin do little to reduce their appetite for cocaine. Yale investigators have found that combining a drug used to treat alcoholism with an experimental drug to treat heroin addiction can help users abstain from using cocaine as well. Another study showed that acupuncture in combination with a heroin drug treatment regimen may also effectively diminish the desire for cocaine.
Past studies had shown that buprenorphine, an experimental alternative to methadone for treating opiate addiction, is effective in reducing heroin use, but no currently used medication treatment is effective in reducing an addict’s concurrent cocaine use. When buprenorphine was combined with disulfiram—a drug for treating alcoholism marketed as Antabuse—the combination worked better than buprenorphine alone in promoting three weeks of abstinence from cocaine use in persons with dual heroin and cocaine addictions. The early-stage study of 20 addicts appeared in the Spring 2000 issue of Biological Psychiatry. Tony P. George, M.D., assistant professor of psychiatry and an investigator for the study, said, “Addiction to heroin along with cocaine abuse is a horrible problem. Disulfiram can actually reduce cocaine use in these patients.”
Principal investigator Richard S. Schottenfeld, M.D. ’76, a professor of psychiatry, is now directing a trial of the drugs with a larger group of subjects and other studies of the combination treatment. He and colleagues are also working to correlate the medications’ mechanism of action with the genetics of drug addiction. “Even if disulfiram proves effective, it’s not an ideal treatment,” he said. “It has all sorts of associated problems. By finding its mechanism of action, we’ll be able to design a new drug that refines its effect.”
The acupuncture study tested 82 subjects in three groups. Among those who had needles inserted in acupuncture regions of the outer ear five times a week—a protocol already widely used in addiction treatment facilities—54.8 percent tested free of cocaine at the end of the eight-week study. The second group of subjects received treatment with acupuncture needles that were inserted into four points in the ear not thought to have a therapeutic effect. Among this group, 23.5 percent of the subjects managed to remain free of cocaine during the study. Only 9 percent of the third group, who watched relaxation videos, abstained for the eight-week period. Arthur Margolin, Ph.D., a research scientist in psychiatry and director of the study, said, “This was one of the most stringent tests of acupuncture to date, insofar as it compared the experimental treatment to two relatively ‘active’ control groups. However, further research is needed to replicate these findings, as well as to understand the mechanism of acupuncture in this application.” The study was published in the August issue of Archives of Internal Medicine.
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New clue to cocaine addiction
“A lot of people try drugs, but only some of them become addicted,” says David Self, M.D., an assistant professor of psychiatry at Yale. He and his colleagues have set out to discover why this is so, and their most recent study points to a possible red flag for cocaine addiction. Unlike other users who experiment and then move on, prospective addicts tend to increase the amount of the drug sharply in the early stages of use.
The team provided a group of rats with an unlimited supply of cocaine for 10 days, allowing them to “self-administer” by pressing a lever. When the supply was cut off, the rats that had shown the greatest escalation of cocaine use in the early part of the study continued to press the lever with a persistence and intensity that signaled extreme cravings—a hallmark of addiction.
The next step in this investigation, says Self, is to locate this predisposition within the animal’s genes, a prospect that could lead to new ideas for early intervention and more effective treatment. The study was published in the June issue of Neuropsychopharmacology.
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Stress testing may hold older persons back from healthy exercise
The standard recommendation to get a stress test before starting to exercise may hinder efforts to keep older people active. According to a Yale study, a simple physical examination may be sufficient. After weighing the potential benefits and risks of exercise among persons age 75 years and older, researchers concluded that current guidelines for exercise stress testing are not applicable for the vast majority of older persons interested in starting an exercise program and may instead hold them back.
Thomas M. Gill, M.D., an associate professor of internal medicine and geriatrics, and his collaborators reported in the July 19 issue of The Journal of the American Medical Association that, “Based on a rigorous review of the available evidence, we found that the risk of myocardial infarction (MI) related to exercise among older persons may be overstated.” Current guidelines from the American Heart Association and American College of Sports Medicine recommend that older people undergo a stress test before beginning a moderately intense exercise program. The purpose of testing is to detect asymptomatic blockages to the heart’s arteries that could lead to MI. “The problem with a stress test,” said Gill, “is that most older people can’t complete it, so you have to go to more expensive, chemical tests to detect asymptomatic blockages to arteries.” Gill found no evidence that detecting these asymptomatic blockages is beneficial. “The risk of MI from exercise is very low.”
Instead, Gill and his colleagues recommend that older persons starting an exercise program skip the stress test and undergo a complete physical examination including a health history to identify potential risks of exercise. And all previously sedentary older persons without symptomatic cardiovascular disease should start with a low-intensity exercise program such as balance exercises, tai chi, self-paced walking and lower-extremity muscle strengthening.
The Yale researchers are following up on their study to learn more about the safest ways to get older adults into exercise programs. “We need more research on exercise and aging,” said Gill, “particularly now that the large baby boom population, who started the exercise movement, is growing older.”
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When it comes to diet, parents weigh in heavily with their children
A Yale study has found that children’s perceptions of their parents’ attitudes toward eating and weight have a big impact on them. According to the study, college-age women are particularly sensitive to perceived criticism from their mothers in forming their own attitudes and behaviors regarding food and weight. Similarly, male college students adopt attitudes toward eating and weight that are associated with their perception of their fathers’ attitudes and behaviors, the study shows.
The study, published last summer in Health Psychology was based on research conducted by Christina Baker, then a graduate student in psychology at Yale, and Kelly D. Brownell, Ph.D., professor of psychology and epidemiology and director of the Yale Center for Eating and Weight Disorders. They compared what the parents reported about their own attitudes and behaviors related to eating and weight with what their children perceived about their parents’ attitudes and behaviors. The investigators found some evidence that a discrepancy between the two might be a predictor of eating concerns.
Baker said one problem with previously available data is that much of it is based solely upon parents’ reports of their own attitudes and behaviors, which they might skew for fear of looking as if they passed along unhealthy eating and weight-loss habits. “A lot of people are concerned about blame being placed on parents,” said Baker. “This study points out that children’s perceptions are more important. The results really highlight the importance of good parent-child communication.”
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Screening for alcohol abuse with a few key questions
There are a variety of screening methods available for detecting alcohol problems. According to a review by Yale investigators, however, asking a few carefully worded questions during routine medical appointments is the best way of spotting alcohol problems before they get out of hand.
The study, led by David A. Fiellin, M.D., assistant professor of medicine, reviewed 38 previous studies of screening methods for alcohol problems in primary care physicians’ practices. It showed that the four so-called CAGE questions and the Alcohol Use Disorders Identification Test (AUDIT) were the most effective in identifying patients with alcohol abuse and dependence problems and at-risk, hazardous or harmful drinking. Patrick G. O’Connor, M.D., M.P.H., professor of medicine and senior author of the study published in August in the Archives of Internal Medicine, said, “This is the first study to examine the evidence in the literature for the effectiveness of these instruments, which focuses specifically on their use in primary care settings. This is important because primary care physicians have been urged to screen their patients for alcohol problems but may often neglect to do so.”
The four CAGE questions are: Have you ever tried to Cut down on your drinking? Have people Annoyed you by criticizing your drinking? Have you ever felt bad or Guilty about your drinking? Have you ever taken a drink first thing in the morning, an Eye opener, to steady your nerves or get rid of a hangover?
The first three questions of the 10-question AUDIT instrument address the quantity and frequency of alcohol consumption. These questions were found to be the most effective in showing more recent drinking behavior and problems.
O’Connor said blood tests are not good indicators of alcohol problems because they generally only reveal markers of advanced alcohol abuse, such as liver problems. “There are many people with drinking problems who are missing work and getting arrested for driving while intoxicated who might not show any physical problems on a blood test,” O’Connor said. “You want to try to get them before they appear in an emergency room or hospital. At that point, they are often far advanced.”
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An odd silver lining
in unhappy marriages
“Freud said that ambivalent, conflicted relationships would predispose the survivor to pathological grief,” said Holly G. Prigerson, Ph.D., an associate professor of psychiatry. According to a study she directed, Freud was wrong. “We found that losing a partner in a harmonious marriage puts you at greater risk of health problems. Your health care costs are lower if you are widowed in a discordant marriage.”
For the study, which was published in the June issue of The Gerontologist, the researchers interviewed 694 people who were part of a longitudinal study on successful aging and who remained married between the initial survey and the follow-up. The investigators then compared the health care costs of the married people to those of the widowed people. They also looked at the health costs of widows and widowers from happy and unhappy marriages, as characterized by answers to questions posed to the couples before one spouse died.
The researchers found that annual health care costs were $2,384 for widowed persons compared with $1,498 for those who were married. Health care costs for the surviving partners in happy marriages were $2,766 compared with $2,100 for survivors of unhappy marriages.
Prigerson said the sense of loss for the survivor in a happy marriage is often so profound it can be defined as “traumatic grief syndrome,” which can cause an array of health disorders. “Doctors should realize that older widowed people are at increased risk,” Prigerson said. “Many widowed persons in the study needed mental health care, but few were receiving it.”
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