Volume 18, Issue 3, Summer 2006
New Findings
Study finds significant link between obesity and depression
There is a strong link between obesity and mood and anxiety disorders, especially among Caucasian Americans and those with more education, according to an analysis conducted by researchers from Group Health Center for Health Studies.
The study, published in the July issue of the Archives of General Psychiatry, found that an obese person is about 25 percent more likely than a non-obese person to have a mood or anxiety disorder, such as depression. It also indicated that among Caucasian Americans and more educated people who are obese, that likelihood may be as high as 44 percent.
While the study did not show whether obesity leads to depression or vice versa, "it's almost certain that the association works in both directions," said Greg Simon, MD, MPH, a Group Health psychiatrist and the lead author of the study.
The researchers also found a negative association between obesity and substance abuse. That is, an obese person is 25 percent less likely than a non-obese person to have had a substance abuse disorder sometime in their lives.
"Understanding the connection between obesity and depression is an important public health issue because both of these conditions are so common and have a significant impact on our health care systems," Dr. Simon explained.
He pointed to the evidence that an average American has a 30 percent chance of being obese. This study shows that when a person is depressed, the odds of also becoming obese are as high as 40 percent.
About 20 percent of Americans are diagnosed sometime in their lives with depression. "Among those who are obese, that likelihood of depression jumps to 28 percent," said Dr. Simon.
The study is based on an in-person survey that the researchers from Harvard Medical School conducted among a nationally representative sample of 9,125 adult men and women. Obesity is defined in the study as having a body mass index (BMI) of 30 or more.
While previous studies have shown a connection between obesity and depression, this is the largest and most representative study of the two problems in U.S. population. Also, this study included a much more careful assessment of mental health problems than earlier research, according to Dr. Simon.
Unlike many previous studies that show a link between obesity and depression among women only, this study revealed a strong link in both genders. There were significant differences among social and cultural groups. In groups where obesity is more common—that is, among non-white and less educated groups—there is less depression among the people who are obese. But in groups where there is less obesity, it is accompanied by more depression.
This may indicate that stigma accounts for some of the relationship between obesity and depression, said Dr. Simon. "Perhaps in groups where obesity is less socially normative, it's less acceptable and that's why there's a greater association with depression," he suggested. "But in groups where it is less stigmatized, obesity doesn't seem to be as depressing."
Research currently underway Group Health may lead to a better understanding of the link between body weight and mental health, and how these problems might be moderated.
Dr. Simon and his team are now conducting studies to address questions such as: Do depressed people have more difficulty increasing physically activity? Are their diets different than the diets of non-depressed people? Are depressed people less likely to be successful with structured weight-loss programs? Can weight-loss programs designed specifically for depressed people make a difference?
Simon's article was co-authored by Michael Von Korff, ScD, Kathleen Saunders, JD, and Diana Miglioretti, PhD, of Group Health Center for Health Studies; Paul K. Crane, MD, and Gerald van Belle, PhD, of the University of Washington; and Ronald C. Kessler, PhD, of Harvard Medical School.
The research was supported by grants from the National Institute of Mental Health, with additional support from the National Institute of Drug Abuse, the Substance Abuse and Mental Health Services Administration, the Robert Wood Johnson Foundation, the John W. Alden Trust, the John D. and Catherine T. MacArthur Foundation, the Pfizer Foundation, the U.S. Public Health Service, the Pan American Health Organization, Eli Lilly and Company, and GlaxoSmithKline.
Good physical function linked to Alzheimer's delay
The first signs of dementia—including Alzheimer's disease—may be physical, rather than mental, according to a joint study between Group Health and the University of Washington reported in the May 22 Archives of Internal Medicine.
This study followed 2,288 Group Health members aged 65 and older for six years. At the start, none showed any signs of dementia or Alzheimer's disease. The researchers contacted the participants every two years, assessing physical and mental functioning. By six years, 319 participants had developed dementia, including 221 with Alzheimer's disease. The participants whose physical function was higher at the start of the study were three times less likely to develop dementia than were those whose physical function was lower.
"Everyone had expected the earliest signs of dementia would be subtle cognitive changes," said Eric B. Larson, MD, MPH, director of Group Health Center for Health Studies. "We were surprised to find that physical changes can precede declines in thinking." What is considered a brain disease may be intimately connected to physical fitness, he added.
In the study, the first indicators of future dementia appeared to be problems with walking and balance. A weak handgrip may be a later sign of the development of dementia in older people.
The National Institute on Aging supported this study. Coauthors are Li Wang, MS, of the Veterans Affairs Puget Sound Health Care System; and James D. Bowen, MD, and Gerald van Belle, PhD, of the University of Washington.
In a recent report, in the Annals of Internal Medicine in January 2006, some of these researchers found that when people exercised regularly, they were less likely to develop dementia, including Alzheimer's disease. The cause of this association was not clear, though. This newer study suggests a possible pathway: that regular exercise may help stave off dementia by improving and maintaining physical conditioning.
"These results suggest that in aging, there's a close link between the mind and body," said Larson. "Physical and mental performance may go hand in hand, and anything you can do to improve one is likely to improve the other." If people notice that they are starting to decline physically, he said, re-engaging in physical activity may help them to stop or slow this decline—and reduce their risk of early cognitive worsening.
On the other hand, he said, it is still possible for people who have physical constraints, even paralysis, to stay mentally alert and cognitively fit. Other studies have suggested that staying busy with nonphysical leisure activities and learning new things may also help delay the onset of dementia. Also, "healthy body, healthy mind" is probably only part of the story, he added. Other elements likely include social support and positive mood.
Intimate partner violence found widespread
Intimate partner violence (IPV), a.k.a. domestic violence, is common and damages women's physical and mental health significantly, according to a Group Health study reported in two papers in the June issue of the American Journal of Preventive Medicine.
In a random sample of more than 3,400 women members of Group Health, nearly half—44 percent—reported having experienced IPV during their adult lifetime.
Although extremely common, the problem "flies under the radar," said Robert S. Thompson, MD, senior investigator, Group Health Center for Health Studies, lead author of one paper. "That's because of the stigma and shame associated with it—as well as the fear that many health care providers have of opening what some call a ‘Pandora's Box' of difficult problems that they are unsure how to address."
This study is the first to find that the more recent a woman's IPV, and the longer it has gone on, the worse her physical and mental health and social network are likely to be.
"IPV harms women's physical and mental health even more than do other common conditions, such as back pain and even several forms of cancer," said Amy E. Bonomi, PhD, MPH, senior research associate, Group Health Center for Health Studies, lead author of the other paper. Compared to women with no IPV, women with recent physical IPV were four times as likely to report symptoms of severe depression, nearly three times as likely to report poor or fair health and more than one additional symptom. They also reported lower social functioning by several measures.
Previous estimates ranged from a quarter to a half of women experiencing IPV during their adult lifetimes, depending on how researchers defined IPV and whom they sampled, with young, low-income women reporting more IPV. Interestingly, this study (reporting a prevalence of nearly one half) involves health plan enrollees who tend to be older and have higher incomes and more education than average, making it clear that IPV is an equal-opportunity problem.
Bonomi and Thompson found the effects of physical abuse (slapping, hitting, kicking, or forced sex) to be stronger than those of nonphysical abuse (threats, chronic disparaging remarks, or controlling behavior) alone. But they also found that both physical and nonphysical IPV significantly damage women's health, and that physical abuse often accompanies nonphysical abuse.
IPV persisted for more than 20 years in 5 percent to 13 percent of the women, with more than one partner perpetrating IPV on 11 percent to 21 percent of them, with these ranges depending on the type of abuse. Prevalence was 15 percent in the last five years, and 8 percent in the last year, for any IPV.
"We are at a point with IPV that seems similar to where we were with cigarette smoking and alcoholism 20 years ago," said Bonomi. "To prevent IPV from starting and continuing, we need interventions that span individual, community, and social levels." She and Thompson suggest that these interventions should include inquiring routinely about IPV and linking those with positive responses to appropriate services.
The Agency for Health Research and Quality funded the study, which also surveyed men regarding their experience as victims of IVP. Results of that part of the survey are under review and will be submitted for publication.
The other authors of the papers about the study are Group Health Center for Health Studies affiliate scientific investigator Frederick P. Rivara, MD, MPH, of Harborview Injury Prevention and Research Center and the University of Washington; and Melissa Anderson, MS; Robert J. Reid, MD, PhD; Jane A. Dimer, MD; David Carrell, PhD, of Group Health—all in Seattle.
Two commentaries accompany the papers about the study: one by James S. Marks, MD, MPH, and Elaine F. Cassidy, PhD, of the Robert Wood Johnson Foundation, in Princeton, NJ; and the other by Ann L. Coker, PhD, of the University of Texas Health Science Center, in Houston.
Neither ibuprofen nor acetaminophen prevent reactions to last DTaP vaccine
A red splotch forms where most preschoolers get their fifth, and last, shot of the acellular diphtheria-tetanus-pertussis (DTaP) vaccine, and it can last a few days. Neither of two common over-the-counter drugs—ibuprofen (Advil) and acetaminophen (Tylenol)—help prevent this side effect, according to a Group Health study appearing in the March issue of Pediatrics.
In about one in five children, this "local reaction" measures at least four inches, spreading over the whole upper arm (or thigh) in about one in 100. But it is seldom serious and usually does not hurt.
"Often children don't notice they have it," said Lisa A. Jackson, MD, MPH, a senior investigator at Group Health's Center for Health Studies and the study's lead investigator. "But it can concern parents, leading to medical visits or even needless antibiotic treatment, so we'd like to make it rarer."
Jackson and Group Health colleagues observed 372 children from 4 to 6 years old who were due for their fifth DTaP dose after getting four doses of this vaccine since age 2 months. Four in 10 children were randomly assigned to receive ibuprofen; four in 10, acetaminophen; and two in 10, placebo (providers and families were "blind" to who got what).
The medication was given preventively three times: at two hours before, and six and 12 hours after, the vaccination. About a third of each group had local reactions at least two inches wide. The placebo and treatment groups did not differ significantly in their proportions of children whose reactions lasted at least three days or whose vaccinated limb swelled by about one inch or more.
Acetaminophen is commonly given to help prevent post-vaccine fever in babies, who are more likely than toddlers or preschoolers to have fever after vaccination.
"Acetaminophen is an effective anti-pyretic (fever reducer)," Jackson explained. "But it isn't an anti-inflammatory (inflammation reducer)." So even though acetaminophen is commonly given to older children for their later immunizations, Jackson was not surprised that her study showed it failed to prevent preschoolers' local reactions, which are likely caused by inflammation.
What Jackson did not expect is that the anti-inflammatory drug ibuprofen would prove similarly ineffective at preventing these local reactions. "We certainly thought that ibuprofen, through its anti-inflammatory effect, might make the local reactions less common or severe," she said. "We all want to decrease discomfort in children, so we were disappointed not to show a prevention effect for ibuprofen; but on the other hand we got a fairly definitive answer, and that's why we do research."
Possible explanations? Maybe a different kind of inflammation, which ibuprofen doesn't interrupt, causes the local reaction, Jackson said. Or perhaps taking any anti-inflammatory drug by mouth doesn't get enough active ingredients to the site of the vaccination—and reaction. Future approaches include evaluating more dilute DTaP vaccines. "These vaccines with a lower antigen content may be just as effective, but may be associated with fewer reactions, in 4 to 6 year olds," she said.
The acellular vaccine, licensed in 1997, contains only those parts of the diphtheria (whooping cough) bacteria that are critical to providing immunity. The previous version—whole cellular diphtheria-tetanus-pertussis (DTP) vaccine—contained whole bacteria. The older whole-cell pertussis vaccines also caused local reactions, but they happened less often with the later (fourth and fifth) doses than with the earlier ones; by contrast, the reaction risk from the newer acellular vaccine rises with the fourth dose and is highest with the fifth. The newer acellular shot results in less fever in 2- and 4-month-old babies than did the older whole-cell shot. This is significant because fever can lead to seizures—rare, but serious, adverse events associated with the DTP shot.
Sanofi-Aventis Group, which manufactures the Tripedia DTaP vaccine, funded the study. Other researchers contributing to the study were Maya Dunstan, RN; Patty Starkovich, RN; Onchee Yu, MS; Jennifer C. Nelson, PhD; Thom Rees, MHA; and Ann Zavitkovsky, MPH; and Group Health pediatrician John Dunn, MD, MPH. Nelson, like Jackson, has a joint appointment at the University of Washington.
Birnbaum Lecture will feature Global Health expert Dr. William Foege
"With So Many Problems, Why Worry About Global Health?" is the title of the 7th Annual Birnbaum Lecture, which guest speaker William "Bill" H. Foege, MD, MPH, will deliver at the W Hotel in downtown Seattle on Thursday, October 5, 2006, at 11:30 a.m.
Foege has served as senior medical advisor to the Bill & Melinda Gates Foundation's Global Health Program, senior fellow in health policy at the Carter Center, and presidential distinguished professor at Emory University's Rollins School of Public Health in Atlanta. He also directed the Carter Center and the Centers for Disease Control and Prevention (CDC) after leading the CDC's Smallpox Eradication Program. In his talk, Foege will explore how health in other countries weaves throughout the U.S. health care system.
In keeping with Foege's work, the lecture and luncheon will include a celebration of the volunteer work that Group Health staff have done in other countries. Group Health staff who have served as health volunteers in other countries are cordially invited to attend the Birnbaum Lecture.
Watch for your invitation to the event in September.
Research Highlights
Although Americans spend an estimated $34.7 billion annually on weight loss programs and products, they're not getting their money's worth, according to an editorial by David Arterburn, MD, MPH, CHS assistant investigator. Published in the June 3 issue of the British Medical Journal, the piece accompanies a report on the BBC Diet Trials, a reality TV series on the British Broadcasting Corporation network. In this multi-center randomized controlled trial, four commercial weight loss programs all produced about the same loss of weight and body fat (about 6 percent and 3 percent, respectively) at six months. Arterburn called for evaluation of long-term health outcomes, cost-effectiveness, and new ways to promote adherence and maintenance.
Methods of measuring the use of electronic patient-provider messaging on MyGroupHealth (www.ghc.org), Group Health's Web portal for patients, was the topic of a paper that CHS Programmer David Carrell and CHS Investigator James Ralston, MD, MPH. Recently published in the annual symposium proceedings of the American Medical Informatics Association, the paper is intended to help advance analytic and monitoring techniques for health organizations worldwide.
The influence of the pharmaceutical industry on physician investigators' prescribing patterns is the subject of an editorial by CHS Senior Investigator Bruce Psaty, MD, PhD, in the June 21, 2006 issue of the Journal of the American Medical Association. "Agreeing to work as an investigator in industry-sponsored trials may represent a commitment to an effort that is more or less a scientific endeavor and, at the same time, a marketing initiative," writes Psaty. He also says public health would be better served "by conduct of fewer small short-term studies, and more well-designed large long-term trials."
More could be done to increase guideline-recommended chlamydia screening in young women according to two articles published by CHS researchers in recent weeks. A paper by Senior Investigator Delia Scholes, PhD—who, with Senior Investigator Robert S. Thompson, MD, led a randomized clinical trial of such screening within the Group Health delivery system—appeared in the June 16, 2006 online version of the journal Preventive Medicine. It found that implementation of several evidence-based clinic interventions improved chlamydia testing rates only among women making preventive care visits. "Additional organizational change and/or patient activation may improve plan-wide testing, particularly among asymptomatic women, " her team wrote.
In a related analysis of a provider survey, CHS Associate Investigator Jennifer McClure, PhD, concluded that routine chlamydia screening among asymptomatic, at-risk adolescent women could be enhanced through additional interventions targeting specific provider attitudes and beliefs. The findings suggest that providers be advised when to screen; that efforts be made to enhance providers' comfort recommending screening to sexually active adolescents; and that efforts be made to improve providers' confidence at discussing sexual issues with adolescents, at identifying those for whom screening is appropriate, and at choosing appropriate treatment. McClure's paper appears in the June 2006 issue of the Journal of Adolescent Health. Co-authors of the two studies include Lou Grothaus, MS, Rob Reid, MD, PhD, Paul Fishman, PhD, Cynthia Sisk, Beverly Green, MD, MPH, Jane Grafton, and Robert S. Thompson, MD.
Having a family history of breast cancer was more strongly associated with mammographic breast density when the affected relatives were more genetically similar, according to a study of Group Health members published last month in the June 2006 issue of Cancer Causes and Control. This suggests that there may be common, yet undiscovered genetic elements that affect breast cancer and mammographic breast density, the authors conclude. CHS researchers on the study were Erin Aiello, PhD, Melissa Anderson, PhD, and Diana Buist, PhD, MPH. The lead author was Anthony B. Crest, PhD, of UW's Institute for Public Health Genetics.
Use of statins was found to have no influence on breast density in general in a study by CHS Assistant Investigator Denise M. Boudreau, PhD, Associate Investigator Carolyn M. Rutter, PhD, and Associate Investigator Diana S. Buist, PhD, MPH. Their cohort study of women aged 50 to 80, with two mammography screenings, included women who were—and were not—taking hormone therapy. The results, published in Cancer Epidemiology, Markers, & Prevention, suggest that use of statins (3-hydroxy-3-methylglutaryl CoA reductase inhibitors) may be associated with increases in breast density among women who do not use hormone therapy. Increased density makes it more difficult to interpret mammograms to detect breast cancer. Another recently published study, coauthored by CHS Senior Investigator Andrea Z. LaCroix, PhD, and other members of the Women's Health Initiative and published in the Journal of the National Cancer Institute, found that overall statin use was not associated with incidence of invasive breast cancer.
Population-based systematic care programs can make manic episodes rarer and milder in bipolar disorder, according to a study published in the Archives of General Psychiatry and written by CHS Senior Investigator Greg E. Simon, MD, MPH, Senior Research Associate Evette J. Ludman, PhD, Research Project Manager Belinda Operskalski, Affiliate Scientific Investigator Jürgen Unützer, MD, MPH, of the University of Washington, and MS Bauer. They found the cost increases associated with these care programs to be modest considering the clinical gains. They suggest that to reduce depression symptoms significantly in people with bipolar disorder, it may be necessary to incorporate more specific cognitive and behavioral content or more effective medication regimens into the programs.
Inadequate use of screening mammography may help explain why African American women are more likely to be diagnosed with advanced-stage breast cancer than are members of other ethnic groups, according to a study by Rebecca Smith-Bindman, MD, of the University of California, San Francisco. Other authors include Group Health Center for Health Studies Associate Investigator Diana L. Miglioretti, PhD; Biostatistician Linn Abraham, MS; and Senior Investigator William E. Barlow, PhD. An article in the April 18 issue of the Annals of Internal Medicine reports the six-year study analyzing data from mammograms of 1 million women aged 40 and older. The researchers linked data from mammography and tumor registries from facilities (including Group Health) that form the Breast Cancer Surveillance Consortium, funded by the National Cancer Institute. The data showed that African American and Hispanic women have longer intervals between mammograms and are more likely to have advanced-stage tumors at diagnosis and to die of breast cancer than white women. Most of the African American women were from sites other than Group Health; and the racial discrepancies were less marked at Group Health than at the other sites.
No link was found between antibiotic use and breast tumor features in a study published in the April issue of Cancer Causes & Control. The study explored the relationship between breast tumor characteristics and antibiotic use prior to diagnosis. The researchers included former CHS Research Associate Christine Velicer, PhD (now at the University of Washington), CHS Affiliate Investigator Susan Heckbert, MD, PhD, of the University of Washington's Cardiovascular Health Research Unit, and CHS Associate Investigator Carolyn M. Rutter, PhD. For at least one year, they followed more than 2,000 women who were enrolled at Group Health and had been diagnosed with primary, invasive breast cancer. The patients' case status, tumor features, and patient characteristics came from the Surveillance, Epidemiology, and End Results (SEER) cancer registry and Group Health electronic files. Their prescription information came from electronic pharmacy records. After controlling for age and length of enrollment, the study found no association between antibiotic use before diagnosis with breast cancer and the following: a less favorable tumor profile (as measured by cancer stage, grade, and size); estrogen receptor-negative tumors; or lobular histology. However, while not achieving statistical significance, the results suggest that antibiotic use may be associated with less favorable breast tumor features. Although these results seem to refute a previous paper by some of the same researchers, which associated use of antibiotics with increased risk of incident and fatal breast cancer, they write that the results are consistent with the possibility that antibiotic use may raise the risk of less favorable tumors and that larger studies are needed to investigate this hypothesis further.
Systematic care for elderly patients with depression benefits their health over the long haul, according to study published in the February 4 issue of the British Medical Journal. The study described the long-term outcomes of the IMPACT (Improving Mood Promoting Access to Collaborative Care Treatment) randomized trial for depressed elderly patients in primary care. The authors included CHS affiliate scientific investigators Elizabeth Lin, MD, MPH (of the Group Health medical staff), Wayne Katon, MD, and Jürgen Unützer, MD, MPH (of the University of Washington), along with colleagues from Duke University, Kaiser Permanente, SCAN Health Plan, Regenstrief Institute, GlaxoSmithKline, and the University of California at Los Angeles and at San Francisco. After two years of follow-up, the patients who had one year of systematic, primary-care intervention for depression remained significantly less depressed and had better physical functioning and enhanced quality of life than did those who received usual care. CHS Senior Investigator Greg E. Simon, MD, MPH, wrote an accompanying editorial.
Most women with cancer in one breast who decide to have the unaffected breast removed along with the diseased breast do not regret the decision and have a quality of life equal to patients who did not have a preventive mastectomy, according to a survey of breast cancer survivors. The 15-minute survey was designed to measure contentment with quality of life, body image, sexual satisfaction, breast cancer concern, depression, and health perception. The study involved 519 women with cancer in one breast who chose to have preventive mastectomy in addition to regular cancer treatment and 61 breast cancer survivors who had only the affected breast treated. Most of the women (86.5 percent) who had the procedure were satisfied with their decision. Of all of the women, most (75 percent) reported "very much" or "quite a bit" of contentment with quality of life, whether or not they had the preventive mastectomy. Previous studies have shown that women with cancer in one breast have about four times more risk of developing cancer in the other breast than women without breast cancer—and that preventive removal of the unaffected breast reduces the risk of cancer and may improve survival. This new study, reported in the Journal of Clinical Oncology, was conducted by six health care systems, including Group Health, which participate in the National Cancer Institute-funded Cancer Research Network. Its authors included CHS Research Associate Sarah M. Greene, MPH, and CHS Affiliate Investigator Joann Elmore, MD, MPH, of the University of Washington.
Staff News
Theresa Shea has been appointed CHS' new Manager of Clinical Research. In addition to directing the research-related activities of CHS Research Clinics at Metropolitan Park East and Group Health's Eastside Campus, Theresa will serve as a resource to CHS and Group Health delivery system staff in the design, development, and implementation of clinical research. Theresa comes to CHS most recently from the Fred Hutchinson Cancer Research Center where she provided oversight of safety data in multinational Phase I, II, and III clinical trials in HIV vaccines and prevention. Prior to her tenure at the Hutch, she managed the UW Center for AIDS Research and Primary Infection Clinic. A licensed physician's assistant with a master's degree in medical science, Theresa will join the Center on July 19.
CHS recently welcomed two Harkness fellows to study at Group Health over the next year. One is Richard Hamblin, head of analytic support for the United Kingdom Healthcare Commission, in Kent, England. The other fellow is Shirley Bowen, executive director of population health and ambulatory care for Western Australia. Both will be studying various aspects of chronic disease management. Harkness Fellows are sponsored by The Commonwealth Fund, allowing mid-career health professionals from Commonwealth countries and Germany to study health policy in the United States.
Andrea J. Cook, PhD, joined CHS as an assistant investigator on May 1. A biostatistician trained at Harvard School of Public Health, Andrea's statistical research focuses on methods to handle correlated outcomes arising from longitudinal, spatial, and multi-level data. Her work has also dealt with incorporating nonparametric and survival methods within this correlated data framework. Her areas of application include breast cancer screening, alternative approaches to healing, and using system approaches to improve the care of high blood pressure. Her interests in biostatistics methodology include hierarchical modeling, longitudinal data analysis, nonparametrics, survival analysis, and spatial statistics. She studied math as an undergraduate at the University of Washington and is happy to be back in Seattle again.
CHS Senior Investigator Lisa Jackson, MD, MPH, has been appointed to the Food and Drug Association's Vaccine and Related Biological Products Advisory Committee. She will serve a four-year term on the group, which reviews recommendations regarding licensure.