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June 26, 2008

RESEARCH NOTES

Teen substance abusers risk dying young

A study of American adolescents by Pitt researchers has found that teens who abuse alcohol or drugs are more likely to die in early adulthood. The work, published in the current issue of the Journal of Adolescent Health, found that substance abuse disorders (SUDs) in adolescents were linked to specific high-risk behaviors including intoxicated driving and drug trafficking.

“The fact that these were, to an extent, predictable deaths raises additional concerns about the hazards of alcohol and drug problems in teens and young adults,” said Duncan B. Clark, associate professor of psychiatry and pharmaceutical sciences at the School of Medicine and director of the Pittsburgh Adolescent Alcohol Research Center at Western Psychiatric Institute and Clinic.

Researchers followed 870 white and African-American adolescents ages 12-18 for up to eight years, starting in 1990. They noted 21 deaths, or about 2 percent of the group, at an average age of nearly 25 years.

Fourteen of those deaths occurred in males with SUDs, or more than 10 percent of that group. Among African-American males with SUDs, 23 percent had died by the age of 25. Males with SUDs in this study group had a mortality rate far in excess of the rate of 137 per 100,000 reported for young adult males in the U.S. general population. Socioeconomic status was not a significant predictor of survival time. Causes of death for the young adults in the study ranged from homicide and suicide to drug overdose and motor vehicle accidents.

Clark said the results need to be confirmed in a larger, nationally representative sample over a longer period of time. Still, he said, “The adolescent characteristics predicting death in young adulthood can be readily identified in clinical evaluations.”

Adolescents may not be oblivious to the risks their behaviors pose. Previous studies have shown that many teenagers who engage in alcohol and drug use and other high-risk behavior believed they would die within two years. “Unfortunately, this insight on the part of some teens apparently does not eliminate these problem behaviors,” said Clark. “Effective interventions need to be developed to prevent these predictable deaths in our young adults.”

Co-authors of the study included Christopher S. Martin of psychiatry and psychology and Jack R. Cornelius of psychiatry and pharmaceutical sciences.

Clark was supported by funding from the National Institute on Alcohol Abuse and Alcoholism and the National Institute on Drug Abuse.

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Parkinson’s research funded

Pitt researchers have received four American Parkinson Disease Association (APDA) research grants.

The University is an APDA Center for Advanced Research, one of nine APDA-supported centers in major academic and research institutions across the United States.

Neurology professor David Hinkle received a Dr. George C. Cotzias Fellowship, awarded to assist promising neurologists in establishing careers in research, teaching and clinical services relevant to the problems, causes, prevention, diagnosis and treatment of Parkinson’s disease. The award carries a three-year, $80,000 annual award based upon favorable progress.

Jianhui Zhu, a research assistant professor in the School of Medicine’s Department of Pathology, was awarded a one-year, $50,000 research grant and Jason Cannon and Robert Drolet each received a one-year, $35,000 postdoctoral fellowship.

APDA’s Scientific Advisory Board, a panel of 15 experts in Parkinson disease specialties, reviews and recommends all research funding.

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Anti-HIV gels tested in pregnant women

In a new clinical trial, researchers from the Microbicide Trials Network (MTN) and the University will study the use of anti-HIV vaginal microbicides in pregnant women.

The trial will enroll 16 healthy HIV-negative women who are scheduled for Caesarean delivery at Magee-Womens Hospital.

The women will have a single dose of tenofovir topical gel applied inside the vagina about two hours before giving birth. The gel incorporates an antiretroviral drug normally used to treat people with HIV and is among a newer class of candidate microbicides that differ from early types because it has specific activity against HIV.

Researchers hope to understand the extent that pregnancy affects how the body absorbs the active drug in the gel and whether the drug can be transferred to the fetus.

The National Institute of Allergy and Infectious Diseases and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, both components of the National Institutes of Health, are funding the study.

Depending on the study results, larger trials that will assess repeated tenofovir gel use over longer periods during pregnancy may be conducted.

A recent Institute of Medicine report on the methodological challenges in HIV prevention trials highlighted the need to evaluate the potential effects products may have on pregnant women and their fetuses. One argument for such studies is that if a microbicide were to become widely available, pregnant women will be among those using the product. Evaluating safety in this population before any product is marketed is important to ensure that microbicides are used by as many women as can safely benefit. Studies could also indicate if using microbicides during pregnancy — a time when women may be at even greater risk for acquiring HIV through sexual intercourse — could also help prevent mother-to-child HIV transmission.

Richard Beigi, an assistant professor of obstetrics, gynecology and reproductive sciences at the School of Medicine, who is leading the MTN study, said: “The study of drugs during pregnancy continues to be one of the most neglected areas of biomedical research. As for microbicides, when the very population at risk for HIV is the same population of women most likely to become pregnant, we have a clinical and ethical obligation to pursue studies involving the use and safety of microbicides in pregnancy.”

Women in clinical trials of microbicides typically are between the ages of 18 and 40 and required to use effective methods of contraception, in addition to male condoms, for a study’s duration. Still, pregnancies are not uncommon, occurring in at least 5-10 percent of participants. Because the risks to both women and their babies are not known, women who are found to be pregnant are told to stop using the study product immediately.

“Absent any data, the wisest course of action has been the one we have adopted. But asking women to stop a product is not an approach that would be feasible in a real-world setting, and surely, in the short term, we would do better to have data with which we could inform women in clinical trials,” added Beigi.

Beigi also will lead an MTN registry of women who become pregnant while participating in microbicide or oral antiretroviral drug trials to help determine the effects early exposure to these products may have on fetal and/or neonatal development.

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TB’s growth, drug resistance studied

A team led by Pitt researchers has discovered that the primary bacteria behind tuberculosis (TB) can grow on surfaces and that drug-tolerant strains flourish in these bacterial communities. Their findings, recently reported in Molecular Microbiology, suggest a possible reason why human TB requires months of intensive antibiotic treatment and indicate a potential cause for the relapses that can occur.

Senior author Graham Hatfull, chair and Eberly Family Professor of Biological Sciences in the School of Arts and Sciences, explained that the research is the first to show that Mycobacterium tuberculosis can grow in surface-level bacteria clusters known as biofilms that are common in nature but never before shown for TB bacteria. Hatfull collaborated and co-authored the paper with William Jacobs Jr. of the Albert Einstein College of Medicine.

The team found that the biofilm bacteria are physiologically and genetically different from TB bacteria harvested in a lab — the type used in developing antibiotics. These variations result in a population of the bacteria that are “drug-tolerant and harbor persistent cells that survive high concentrations of anti-tuberculosis antibiotics,” the team reported.

Jacobs said, “The nature of persisting M. tuberculosis cells has been an enigma for the entire field. Clearly M. tuberculosis cells in biofilms represent at least one class of persistent cells, and we are testing their biological relevance.”

It is not yet known whether the biofilm actually factors into human TB infections, Hatfull said. “While our data does not show conclusively that biofilm formation in people gives rise to a drug-tolerant population, the fact that biofilms do so in the lab makes this an interesting and testable hypothesis,” he said.

Pitt postdoctoral researcher Anil Ojha also collaborated on the project. The full paper can be viewed at www.blackwell-synergy.com/doi/full/10.1111/j.1365-2958.2008.06274.x.

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Fewer helmets, more head injuries for motorcyclists

Pennsylvania motorcyclists suffered large increases in head injury deaths and hospitalizations in the two years following the repeal of its motorcycle helmet law, according to a Pitt study published in the June issue of the American Journal of Public Health. Even after accounting for increases in motorcycle registrations that occurred during this period, study authors noted a 32 percent increase in head injury deaths and a 42 percent increase in head injury-related hospitalizations, raising concerns about motorcyclists’ safety and the impact of this trend on health care costs.

Pennsylvania repealed its universal motorcycle helmet law in 2003. Under the current law, only motorcyclists under 21 and riders with less than two years’ experience who have not taken a safety course are required to wear helmets. Nationwide, only 20 states now have laws that require all riders to wear helmets.

Study authors analyzed data from Pennsylvania’s health and transportation departments during the years 2001-2002 and 2004-2005. They found helmet use by motorcyclists involved in reported crashes decreased from 82 percent to 58 percent in the two years after the helmet law was repealed. The authors also looked at data from head injury and non-head injury deaths to determine specifically how many deaths were caused by not wearing helmets. They found the registration-adjusted head injury death rate increased by 32 percent, whereas the non-head injury death rate did not change.

“Our study shows that since the repeal of Pennsylvania’s motorcycle helmet law, helmet use has gone down, while head injuries from motorcycle crashes have gone up, even after increased motorcycle registration,” said study lead author Kristen Mertz, an assistant professor in the Graduate School of Public Heath’s Department of Epidemiology. “We looked at both head injuries and non-head injuries to get a clearer picture of the impact of the helmet law repeal. The relatively large increase in head injury deaths and hospitalizations after the repeal suggests that the law was protecting riders.”

The study authors looked at hospitalizations per 10,000 registrations from motorcycle crashes by examining discharge data compiled from all acute care hospitals in the state. They found an increase of 42 percent in the head injury hospitalization rate and a 2 percent increase in the non-head injury hospitalization rate. The number of head-injured, hospitalized motorcyclists requiring further care at facilities specializing in rehabilitation and long-term care increased 87 percent after the repeal, and increased 16 percent for non-head injured motorcyclists.

Total acute care hospital charges stemming from motorcycle-related head injuries increased 132 percent in the two years following repeal compared to 69 percent for non-head injuries.

“Our findings strengthen the argument for more comprehensive helmet laws that help protect riders and lower the cost of health care,” said study co-author Hank Weiss, an associate professor in the Department of Neurological Surgery, Center for Injury Research and Control.

“Serious head injuries, causing anything from short-term memory loss, inability to concentrate, to coma and death, can severely impact quality of life and affect not just those injured, but their families as well. Until a universal helmet law is reinstated, Pennsylvania needs effective voluntary strategies to increase helmet use.”

The study was supported in part by the Centers for Disease Control and Prevention, National Center for Injury Prevention and Control.

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