Small gene variations can increase risk of autism

An increased risk of autism spectrum disorders (ASD) could result from an accumulation of many small, common genetic variations rather than large-effect, rare changes in the genetic code, according to a multicenter team led by researchers at the School of Medicine. Their findings, published in Molecular Autism, provide new insights into the genetic factors that underlie the neurodevelopmental condition.

Scientists have debated about the genetic contributions that lead to ASD in families where only one individual is affected, called simplex, versus those that have multiple affected family members, called multiplex, said senior author Bernie Devlin, faculty member in the Department of Psychiatry.

“Our team compared simplex, multiplex and unaffected families using sophisticated quantitative genetic techniques,” he said. “In families where only one child has an ASD, 40 percent of the risk is inherited while in families with more than one affected child, the risk rises to 60 percent.”

In addition to reviewing nearly 1 million gene variations, called single nucleotide polymorphisms (SNPs), to look for inheritance patterns associated with ASD, the researchers also ran computer simulations to plot family trees using 1,000 SNPs that appear to impact the risk of ASD.

“These small gene changes can add up even though individually they do little harm,” Devlin said. “This might explain why parents who do not have autism traits can have children who do.”

Other research has shown that autism and related disorders also can arise from spontaneous variations in parental genes prior to conception as well as rare mutations of larger effect that are passed on, he noted. The multiple inheritance patterns could help explain the range of symptoms in the disorder.

The research was funded by the Simons Foundation and National Institutes of Health.

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Cooperation = better infection control rates

Methicillin-resistant staphylococcus aureus, or MRSA, infections are better prevented when hospitals cooperate and coordinate their infection control procedures, according to a multicenter study led by Pitt researchers. Hospitals working alone do not achieve the same level of infection control, according to the results of the computer simulation-based study published in Health Affairs.

Bruce Lee, director of Pitt’s public health and infectious diseases computational and operations research group and his colleagues obtained real-world data from all 29 hospitals in Orange County, Calif., and developed a computer simulation to assess a procedure called “contact isolation” to limit MRSA transmission. The procedure involves testing all patients for MRSA upon admission to a hospital. When a patient tests positive, hospital staff must wear gloves and gowns when entering that patient’s room or interacting with that person.

The simulation explored scenarios in which different combinations of hospitals implemented contact isolation to varying degrees.

“The more that hospitals work together and coordinate infection control efforts, the more they all benefit,” said Lee, also a faculty member in medicine, epidemiology and biomedical informatics at the School of Medicine and the Graduate School of Public Health. “For example, doubling the number of hospitals that adopt contact isolation can more than double their improvement in infection control.”

The simulation also found that requiring contact isolation at one hospital not only decreased MRSA at that hospital as expected, but also did so in other nearby hospitals that had not implemented the intervention.

When the simulation was run with all the hospitals in Orange County implementing contact isolation simultaneously with a 75 percent compliance rate, MRSA prevalence decreased an additional 3.85 percent over what the hospitals could have achieved on their own. Long-term acute care facilities fared even better, with a 12.13 percent additional decrease.

MRSA is widely prevalent in U.S. hospitals. In 2006, the MRSA colonization rate, or detection of the bacteria on a patient’s skin or soft tissue, was 12 per 1,000 inpatients. In 2010, the rate nearly quadrupled to 41 per 1,000 inpatients, despite an overall decrease in the rates of MRSA infection.

The researchers had shown previously that hospitals in Orange County are highly interconnected through patient transfers and readmission of patients to different hospitals after an intervening stay at home or elsewhere.

This study was supported by the National Institute of General Medical Sciences, the National Institute of Allergy and Infectious Diseases and the Pennsylvania Department of Health.

Pitt co-authors included Sarah M. Bartsch, medicine; Kim F. Wong and Levent Yilmaz, both of chemistry; Ashima Singh, epidemiology; Margaret A. Potter, health policy and management; Shawn T. Brown, biostatistics and the Pittsburgh Supercomputing Center, and Yeohan Song.

To access the report, go to http://content.healthaffairs.org/content/31/10/2295.abstract.

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City sees influx of educated young adults

Despite Pittsburgh’s mass exodus of young people in the 1980s, data from the University Center for Social and Urban Research (UCSUR) and PittsburghTODAY show that over the past five years Pittsburgh has seen a 7 percent influx of young people ages 20-34.

The Young Adults Report 2012 profiles the young men and women in a 32-county region around Pittsburgh. Findings are based on PittsburghTODAY’s reporting, as well as on a regional survey and focus groups conducted by UCSUR.

Douglas Heuck, director of PittsburghTODAY, said:  “Pittsburgh is attracting young adults, and those who are moving here are among the most educated in the nation.”

Among the report’s key findings:

• Migration: Nearly 70 percent of new Pittsburgh arrivals are ages 22-34, migrating from nearby cities such as Philadelphia, Washington, D.C., and New York.

• Education: Those moving in are better-educated young adults in pursuit of job opportunities. Pittsburgh ranks fifth in the nation for workers ages 25-34 with at least a bachelor’s degree and is one of only three regions where more than 20 percent of young workers hold advanced degrees.

• Jobs: Nearly half of local young adults earn at least $50,000 annually, and 22 percent report earnings of $75,000 or more.

• Transportation: Young adults are the most likely age group to frequently use public transportation, and public transit issues were identified in every focus group session as a regional weakness, with complaints ranging from the cost of fares to unreliable service, recent service cuts and outdated payment procedures.

• Voting: Young adults here have the lowest rates of voter participation in any age group. One in four reports never voting, even in presidential elections.

Christopher Briem, UCSUR regional economist, and Sabina Deitrick, director of Pitt’s urban and regional analysis program, were involved in creating the survey. Laurel Person Mecca, UCSUR program assistant director, administered the focus group sessions.

The report can be accessed at www.pittsburghtoday.org/special_reports.html.

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Medicare recipients overpay for drug plans

Medicare beneficiaries are overpaying by hundreds of dollars annually because of difficulties in selecting their ideal prescription drug plan, Graduate School of Public Health researchers found.

Only 5.2 percent of beneficiaries chose the least-expensive Medicare prescription drug benefit (Part D) plan that satisfied their medical needs in 2009, overspending on Part D premiums and prescription drugs by an average of $368 a year. The evaluation, published in Health Affairs, takes a national look at how well beneficiaries were making plan choices in the fourth year of the Medicare Part D program.

Lead author Chao Zhou, a post-doctoral associate, said: “Educational programs that help people navigate the dozens of plans available would make it easier to select plans that best meet their health care needs without overspending.”

Coauthor Yuting Zhang, faculty member in health economics, said: “In particular, government officials could recommend the three most appropriate Part D plans for each person, based on their medication history. Alternatively, they could assign beneficiaries to the best plan for them based on their medication needs, while offering them the option to choose another plan.”

The results of this study could be useful in designing health insurance exchanges, which are state-regulated organizations created under health care reform to offer standardized health care plans.

“In designing health insurance exchanges, models with more active assistance would be more helpful than models with large numbers of plans and information,” Zhang said. “For example, health insurance exchanges could actively screen plans on quality and negotiate premiums to reduce the number of plans.”

Implemented in 2006, Part D cost the federal government $65.8 billion in 2011, according to the Congressional Budget Office.

Researchers looked at the difference in a patient’s total spending, including the plan premium and out-of-pocket payment for the prescriptions filled, between the plan the patient chose and the cheapest alternative option that would satisfy the patient’s medication needs. The study looked at data for 412,712 people.

Beneficiaries tend to overprotect themselves by purchasing plans with more generous features, such as generic drug coverage in the coverage gap.

A few other trends emerged: As beneficiaries aged, they increasingly chose more expensive plans, with people older than 85 overspending by $30 more than people 65-69 years old. Blacks, Hispanics and Native Americans chose less expensive plans than whites.

People with common medical conditions, such as diabetes and chronic heart failure, were not significantly more likely to choose more expensive plans. People with cognitive deficits or mental health issues, such as Alzheimer’s disease, tended to choose less expensive plans, spending an average of $10 less than those without such conditions. The researchers could not determine if those people had assistance from caregivers.

As the number of local plan options increased, the amount of overspending increased by $3.20 for every additional plan available.

“A previous study showed that in 2006, beneficiaries could have saved nearly 31 percent of their total drug spending by switching to the lowest-cost plan,” Zhou said. “Since our results are similar, this suggests people are not learning to reduce overspending.”

One possible explanation is the impact of inertia and bias toward maintaining the status quo, she noted.

To access the report, go to http://content.healthaffairs.org/content/31/10/2259.abstract.

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Award to fund pancreatic cancer research

The Alliance for Cancer Gene Therapy (ACGT) has named UPMC surgical oncologist Herbert Zeh III, a faculty member in the Department of Surgery, the 2012 ACGT Investigator. The award includes a $500,000 grant that will allow Zeh to continue his research focused on gene therapy for pancreatic cancer. Zeh’s team will use a modified virus to produce hormones that attract a tumor-fighting T-cell that not only kills cancer but also protects the patient against potential recurrence.

This approach, also used to treat patients with brain tumors, has proven toxic to cancer cells and also holds greater potential for long-term survival.

Zeh is chief of the Division of Gastrointestinal (GI) Surgical Oncology at UPMC Cancer Center and codirects the UPMC Pancreatic Cancer Center and the UPCI GI oncology program.

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The University Times Research Notes column reports on funding awarded to Pitt researchers as well as findings arising from University research.

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