Research "Office Hour" with Ming Tai-Seale:
CYCORE Tests System for Comparing Effectiveness of Cancer Treatments
(San Diego and Houston, April 12, 2011) -- Researchers at the University of California, San Diego and clinicians at the MD Anderson Cancer Center in Houston have embarked on testing a new data system designed to determine which cancer treatments are most effective. The initial tests started this week, and they are designed to gauge how effective and easy-to-use the system is for physicians and patients enrolled in clinical trials of treatments for head-and-neck or colon cancer.
CYCORE researchers and clinicians. Pictured: (l-r): Stephanie Barrera, Susan Peterson, Celal Ziftci, Ingolf Krueger, Wendy Demark-Wahnefried, Alex Prokhorov, Chaitan Baru, Laura Wolszon, Kai Lin, Karen Basen-Engquist, Phil Rios and Kevin Patrick. Not shown: Fred Raab, Emilia Farcas, Viswanath Nandigam, Joshua Ng, Doug Palmer and others.
With funding from the National Cancer Institute (NCI), the one-year-old Cyberinfrastructure for Comparative Effectiveness Research (CYCORE) project is building hardware and software to help clinicians and researchers determine unequivocally which cancer treatments are most effective. "Currently there is no viable system for compiling the many kinds of medical data acquired during clinical trials," said Susan Peterson, CYCORE's lead principal investigator and an associate professor at the University of Texas MD Anderson Cancer Center (MDACC). "Until CYCORE, trying to compare the effectiveness of cancer treatments was complicated by differing data formats, privacy issues, and the need to incorporate novel types of data. Now we will be able to draw more complete comparisons, including evaluations of the patient's behavior and environment, which can influence treatment outcomes."
The project – a collaboration among the UC San Diego division of the California Institute for Telecommunications and Information Technology (Calit2), MDACC in Texas, and the University of Alabama at Birmingham – was awarded $4 million over two years through a Grand Opportunity American Recovery and Reinvestment Act (ARRA) 'stimulus' grant from NCI. The project employs and partially funds 29 researchers at the three institutions.
CYCORE recently unveiled a new website devoted to public education and accountability. The site provides tools for patients and for clinical researchers. It also offers more information on the project and its personnel, and features nano-scale images of cancer cells taken by U.S. scientists. To learn more about CYCORE, contact information can be found here.
California Smokers' Helpline
The California Smokers' Helpline -- a partnership between Dr. Shu-Hong Zhu (pictured), other investigators at the UC San Diego Moores Cancer Center and the California Department of Health -- offers telephone counseling assistance and a range of other free services, such as self help materials and opportunities to participate in ongoing research projects. Dr. Zhu studies and reports on the success of the Helpline, its rationale, methods, and operation.
Dr. John Pierce PhD
, an epidemiologist with a special focus on psychology and health communication, came to UCSD after having served as the founding chief of the Epidemiology Branch at the Office on Smoking and Health, Centers for Disease Control. At the time, this office was responsible to Surgeon-General C. Everett Koop for the development of the Surgeon-General's reports on smoking and health.
Dr. Pierce and his colleagues have defined the trends in smoking in the United States and much of the world's medical community. Their series of papers, published in JAMA in 1989, were the basis for the tobacco "Year 2000" goals for the nation. They documented the power of tobacco industry advertising and promotional activities to encourage young people to start smoking and to thwart Public Health efforts to convince adolescents not to smoke. Their research increased awareness of the dangers of second-hand smoke and demonstrated that restrictions on smoking, whether in the workplace or in the home, are associated with major declines in exposure to second-hand smoke and in smoking prevalence.
The group has developed a number of the key measures of smoking behavior and established the effectiveness of Statewide Tobacco Control Programs.
Center for Wireless and Population Health Systems
The Center for Wireless and Population Health Systems (formerly PACE) began in 1990 with a small contract from the US Centers for Disease Control and Prevention to develop tools to help primary care physicians counsel their patients on becoming more physically active. It has now grown to encompass a broad array of research aimed at developing tools that health care providers, health care systems and individuals can use to make initial and sustained improvements in physical activity, diet and other lifestyle behaviors.
CWPHS research is conducted by Drs. Kevin Patrick, MD, and Gregory J. Norman, PhD, and an interdisciplinary team of over 40 professionals with expertise in preventive medicine, health psychology, exercise sciences, behavioral medicine, nutrition, experimental psychology, computer sciences and engineering, media technology and graphic arts, health promotion, pediatrics, internal medicine and family medicine. In addition to the CDC, CWPHS research has been supported by other federal agencies (e.g. NIH, HRSA) and several entities in the private sector. The results of CWPHS-related research have been published in dozens of abstracts and peer-reviewed publications, and CWPHS has spawned research, development and dissemination efforts in several countries outside of the US, including Canada, Japan, The Czech Republic, Portugal, The Netherlands, Russia and Brazil.
Health Measurement Research Group
Dr. Ted Ganiats is a senior investigator of the Health Measurement Research Group, a multi-institution program of research funded by the National Institute on Aging. The goals of the research group are to evaluate the use of widely used health-related quality of life measures, understand the strengths and limitations of each, and create a versatile "toolbox" of summary measures of health that can be used to track changes in the public’s health over time. Dr. Ganiats joins senior researchers from UCLA and the University of Wisconsin in conducting the studies funded under this program of research.
A number of research projects are being conducted. One study will evaluate the usefulness of self-administered, mailed surveys for tracking one- and six-month health-related quality of life outcomes among two cohorts of clinical patients – heart failure and cataract surgery patients. A corollary study will examine the extent to which measurement mode (e.g., self-administered mailed surveys vs. telephone interviews) makes a difference in assessments of health-related quality of life outcomes among these same clinical patients. Data collection for both of these projects will be conducted by the UCSD Health Services Research Center (HSRC).
Dr. Ganiats is also the Project Leader on a pilot study to examine the extent to which the duration of specific health conditions affects how individuals assess their health. This exploratory study will use focus groups and vignettes to learn more about how the length of time that a person has a particular condition may modify his or her assessments of their health.
The Smoker's Helpline
Integration of this body of knowledge has led to the 7-year success of the State's Smoking Helpline, which established the effectiveness of using telephone counseling as a strategy for providing assistance to smokers who want to quit. More than 100,000 smokers have participated in the program since it began in 1992. Its staff of 80 counselors provides smoking cessation counseling in at least five languages and to the hearing impaired. The Helpline expects to offer assistance to 30,000 smokers per year.
Dr. Shu-Hong Zhu reports that for those smokers requesting written materials but no counseling, the quit rate is about 15%. For those requesting one counseling session, the rate increases to about 20%. And for those participating in multiple counseling sessions, the rate shoots up to 27%.
Impressed by the efficacy of the program, some HMOs (most notably, Kaiser) and MediCal have certified the program and will provide free cessation patches and drugs to those patients who participate. In addition, Helpline personnel work with primary care physicians to get referrals allowing them to call pregnant women who smoke as a proactive intervention. Providing counseling to those who chew tobacco as well as smoke it makes the Helpline attractive to rural smokers who typically find it inconvenient to travel to health sites offering cessation classes. Ultimately, the individualized counseling and convenience of the service are its primary attraction for many smokers. Acknowledging the critical role in smoking cessation played by the Smokers Helpline, the State of California raised its annual funding of the Helpline.
Dr. Zhu also heads up research projects studying tobacco control policy and methods in China, where smoking is an enormous health problem. In a recent study, his team showed that despite the fact that China prohibits showing images of actual packs of cigarettes in tobacco ads, a significant number of college students at 12 universities reported having seen cigarette ads because the brand logo (e.g. "Marlboro Country") does appear in the ads. In fact, the study went on to show that the recognition of Marlboro brand ranked No. 1 among smokers and non-smokers. Other studies being conducted by Dr. Zhu in China focus on the effects of smoking on mood, and the effects of second-hand smoke on women, 95% of whom do not smoke; children; and male non-smokers.
Because epidemiological studies have shown a link between nutritional factors and risk for cervical cancer, clinical nutritionist Dr. Cheryl Rock is examining whether dietary change following an abnormal pap smear finding will result in a normal pap smear, thus avoiding the need to undergo surgery to treat the dysplasia. And because studies indicate that the amount of weight gain following a breast cancer diagnosis may be predictive of risk for recurrence, she is conducting research to identify effective methods of weight control for women in their middle years, who often have a long history of dieting.
Dr. Cheryl Rock and Dr. John Pierce collaborate in coordinating the multi-center, 8- year project known as the Women's Healthy Eating and Living Study (WHEL). Its objective is to find out whether a healthier diet in combination with lengthy, personalized follow-up phone counseling can improve breast cancer survival rates.
Dr. Donna Kritz-Silverstein conducts the Soy Health Effects Study (SHE) under a National Institutes of Health grant to study the potential benefits of a dietary supplement of soy on the health of postmenopausal women. Because many women prefer not to take standard forms of hormone replacement therapy, it is hoped that soy beans, which naturally contain high amounts of compounds known as phytoestrogens, may be an effective substitute. The study will examine the supplement's effects on heart disease risk factors, osteoporosis, menopausal symptoms, and quality of life.
Enabling Early Disease Detection
Dr. Matt Allison is a collaborating investigator with the LifeScore Clinic. In this capacity, Dr Allison has been examining the distribution of calcified atherosclerosis in multiple vascular beds and how the atherosclerosis in these areas is related to cardiovascular disease risk factors and events such as heart attack and stroke. The main study of this initiative is contacting prior clients of the LifeScore clinic in an effort to collect information on their health. The focus of this research is prevention utilizing technology with the hope that it may potentially enable early disease detection and therefore an earlier implementation of appropriate therapies.
Breast Health and Other Women's Issues
Professor Deborah Wingard has presented more than 100 papers and published over 100 articles on gender differences related to disease and lifestyle behaviors, generally, and on women's health issues including the effects of hormone use on weight, mood, and cognitive function, specifically. Her special interests include examining the long term effects of exposure to diethylstilbestrol (DES), a drug used in pregnancy, and exploring the possible behavioral or biological reasons why women live longer than men.
Dr. Hillary S. Klonoff-Cohen is looking at whether breast cancer surgical procedures conducted during particular phases of the menstrual cycle have an impact on recurrence or death among different racial groups, since evidence suggests that there may be decreased survival among certain women during the first phase of the cycle. Klonoff-Cohen also conducts studies on the effects of passive smoking on Sudden Infant Death Syndrome (SIDS), the role of passive smoke on sperm, ICSI & in vitro fertilizations, and the effect of smoking on success rates of in vitro fertilization.
The increasing cultural diversity of the population of the State of California dictates that physicians and educators require a better understanding of the health care needs of that population--some level of cultural competency in caring for patients that goes beyond merely speaking the same language. Issues ranging from emerging infectious illnesses, the epidemiologic transition from infectious to chronic disease, physical and psychological trauma experienced by refugees, malnutrition, high fertility and rapid population growth, and limited resources for effective health care service delivery all must be addressed. In addition, all residents living in the region are tied to the fact that they reside along a border with Mexico. This reality has important implications for health care delivery, including the prevention and control of infectious diseases that originate from south of the border, issues related to occupational and environmental health associated with rapid and oftentimes unregulated economic development along both sides of the border, and issues related to health care delivery to an increasingly uninsured population. And finally, there is a need to prepare professionals from the U.S. and abroad to assume major positions of leadership and responsibility for the health care needs of populations living on the Pacific Rim as well as other culturally diverse and medically underserved populations.
The Rancho Bernardo Study
Beginning in 1972 and continuing through 1974, 6,339 individuals, representing 82% of all people living in Rancho Bernardo, CA, at that time, were enrolled in a study of heart disease risk factors. In the years since, world-renowned epidemiologist and former Chair of the Department of Family Medicine and Public Health Dr. Elizabeth Barrett-Connor (pictured) has followed the health of these individuals both with mailed questionnaires and with clinical evaluations. The studies conducted with the Rancho Bernardo cohort have led to discoveries about cancer, strokes, heart disease, osteoporosis, depression, diabetes, dementia, blood pressure, hormone replacement therapy, exercise, diet, aging, behavior change, and gender differences. Many of these discoveries address topics of fundamental Public Health importance.
The guidelines from the American Diabetes Association recommend the use of fasting glycemia as a screening test for diabetes. However, a Rancho Bernardo study found many older adults who have a high risk of cardiovascular disease may be overlooked if physicians rely solely on the fasting glucose test. Another study explored whether weight loss associated with Alzheimer's Disease (AD) precedes or follows dementia. Results indicated that both men and women who were later diagnosed with AD had a significant decrease in weight after the baseline visit, but there was no significant weight loss in men and women who remained cognitively intact. Data collected from the Rancho Bernardo cohort has also demonstrated that cholesterol and lipoproteins decrease with age in both men and women. The decrease in older ages may explain why previous studies conducted in the elderly did not find an association between high cholesterol levels and the risk of CVD.
Other Studies of Heart Disease
Research in cardiovascular disease as it relates to an aging population, hormone use, diabetes, hypertension, smoking cessation, and alcohol consumption has earned international praise for Professor of Epidemiology and Vice Chair of the Family Medicine and Public Health Department, Dr. Michael Criqui.
His paper, "Mortality over a period of 10 years in patients with peripheral arterial disease (PAD)," published in the New England Journal of Medicine in 1992, was the basis for the 1993 addition to the National Cholesterol Education Program Adult Treatment Panel guidelines that patients with PAD should be treated as secondary rather than primary prevention patients. This paper has had a major impact on the way patients are evaluated for CVD and how patients with evidence of PAD are treated.
"Plasma triglyceride level and mortality from coronary heart disease," a 1993 paper Criqui published in the New England Journal of Medicine showed that although overall triglyceride was a weak risk factor for CHD mortality, within subgroups characterized by low HDL cholesterol and/or younger ages that triglyceride was a strong risk factor. This paper has had a major impact on the evaluation and treatment of patients with elevated triglycerides.
"Does diet or alcohol explain the French paradox?," an article published in Lancet in 1994 revealed findings that wine consumption was associated with lower CHD death rates but not total mortality, thus providing a clear focus on the hazards as well as benefits of alcohol. This article has stimulated much comment and has been extensively quoted.
Criqui's 1996 paper published in Vascular Medicine, "The correlation between symptoms and non-invasive test results in patients referred for peripheral arterial disease testing," led to the development of the San Diego Claudication Questionnaire, which was published as an Appendix to this paper. The questionnaire is now used in several studies of PAD, including three major new initiatives in the U.S.
Professor Cedric Garland, Dr. P.H., F.A.C.E, was an early contributor to scientific research in vitamins and mineral supplementation as they impact cancers. His report in 1985 that calcium is associated with reduced incidence of colon cancer or its precursors was recently confirmed by the Dartmouth group. His 1989 report that Vitamin D intake or serum level of 25-(OH)-vitamin D is associated with reduced incidence of colon cancer has been confirmed in 9 studies since its original publication. And his 1990 hypothesis that ultraviolet A and unsafe sunscreens are a causal factor in melanoma was recently confirmed in Europe.
Osteoporosis is often considered a woman's disease, and certainly departmental programs in women's health devote a great deal of attention to osteoporosis. Less well known is its impact on men. Dr. Barrett-Connor is P.I. on an NIH-funded observational study which will examine and follow 6,000 men aged 65 and older to evaluate bone density and covariates. As an incentive for the men to participate, the study will also provide free bone density measurements for female partners; these data will provide further insight into spouse concordance for bone density and covariates.
The Department has a long-standing track record in the field of women's studies covering a broad span of health issues including breast cancer, heart disease, osteoporosis, and quality of life. Two landmark studies under the direction of Dr. Elizabeth Barrett-Connor led to the current generation of studies of postmenopausal health: the postmenopausal Estrogen-Progestin Intervention (PEPI) study and the Heart and Estrogen-Progestin Study (HERS). PEPI found that estrogen-based hormone replacement therapy improved HDL and LDL cholesterol levels and fibrinogen (a blood clotting factor) without affecting blood pressure. These results suggest mechanisms through which hormone replacement could protect women from heart attacks. Following on the heels of the PEPI trial, HERS results indicated that estrogen use showed no reduced risk of coronary heart disease. Both studies proved that postmenopausal women are strong supporters of clinical research.
In 1993, the Department was awarded funding for the National Institutes of Health landmark Women's Health Initiative (WHI), the largest (160,000 women), longest (12 years), nationwide (45 sites) study of postmenopausal women in history--designed to answer key questions about cancer, cardiovascular disease, and osteoporosis. Women enroll in the observational study or one or more of 3 clinical trial components: hormone replacement, low fat diet, and calcium/vitamin D supplementation.
The UCSD site was chosen as one of 16 Vanguard Clinical Centers and one of four of those centers designated a "minority clinic" with a mission to recruit a high percentage of women from special populations. Finishing recruitment ahead of schedule, the local study enrolled more than 5,500 women, exceeding the site's goal, and enrolling nearly 30% of the cohort from the African-American, Asian/Pacific Islander, and primarily Latina populations. Conclusive results of the study will be published sometime after 2005, with some preliminary reports to be published over the next few years. Co-investigators are Dr. Michael Criqui, Dr. Cedric Garland, and Dr. Gregory Talavera.
The Women's Health Initiative Memory Study (WHIMS) will examine the relationship between hormone replacement therapy and cognitive functioning. And another study will conduct a comprehensive evaluation of a series of thrombotic, inflammatory, and genetic markers for myocardial infarction among 90,000 postmenopausal women.
The MORE study, under the direction of Dr. Barrett-Connor, found that raloxifene (a selective estrogen receptor modulator) reduced bone loss and the risk of new vertebral fractures in women with osteoporosis, whether or not they had vertebral fractures at baseline. The MORE study also identified a 75% reduction in invasive breast cancer-with all of the protection observed in estrogen receptor modulators. A new study called CORE, under Dr. Barrett-Connor's leadership, is evaluating the effect of longer-term raloxifene on bone loss and whether the breast cancer protection persists. Yet another study, called RUTH, is examining whether raloxifene has protective effects for women with heart disease, or high risk of heart disease. Dr. Barrett-Connor is overall P.I. for the RUTH study which is recruiting 10,000 women in 23 countries.
The FIT study, also under the leadership of Dr. Barrett-Connor, found that alendronate significantly reduced vertebral and hip fractures in older women who had prior fractures or osteoporosis by bone densitometry. This study (now called FLEX) has been extended for three more years to determine what happens to bone density in women who continue or stop alendronate after four years.
In NORA, Dr. Barrett-Connor is one of five P.I.s developing a large national database (200,000 women) to examine fracture risk by various baseline characteristics including bone density of the heel and radius. The very large database will allow dissection of the effect of colinear exposures such as estrogen duration and recency of use. NORA includes the largest number of minority women in a US bone density study.