Behavioral Health and Aging

Dementia Risk Factors: High blood pressure in mid-adulthood is linked to dementia risk in women, but not in men, according to research published in Neurology by Rachel Whitmer, PhD, Paola Gilsanz, ScD, and colleagues. At a July Alzheimer’s conference, Whitmer and Gilsanz presented additional research showing that early life adversity and birthplace contribute to racial disparities in dementia rates that persist even among the oldest of the elderly. Another study in JAMA Neurology linked being born in the United States. “Stroke Belt” with increased dementia risk in people who eventually lived elsewhere.
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Marijuana Use During Pregnancy: Data on marijuana use during pregnancy is limited, hampering efforts to identify potential risks. Kelly C. Young-Wolff, PhD, MPH, Nancy Goler, MD, and colleagues addressed this gap using data from almost 300,000 pregnant women treated at Kaiser Permanente Northern California. As reported in the Journal of the American Medical Association, they found that maternal prenatal marijuana use increased from 4 to 7 percent from 2009 to 2016. Now that marijuana can be bought legally in California, “it will be important to monitor whether prenatal marijuana use escalates further,” Young-Wolff said.
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Genetics and Glaucoma: Analysis of DNA from nearly 70,000 Kaiser Permanente Northern California patients uncovered 47 specific positions, or loci, in the genome that are associated with variations in pressure inside the eye. The findings, which could help clarify how elevated eye pressure leads to glaucoma, were published in Nature Communications by Eric Jorgenson, PhD, Hélène Choquet, PhD, and colleagues. “Knowing which genes are involved, and how, could suggest new avenues for development of novel treatments,” said co-author Ronald Melles, MD.
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Cognitive Health in the Oldest-Old: The oldest-old – people aged 90 and older – are the fastest-growing segment of the elderly population in the United States. The National Institute on Aging has awarded the Division of Research a six-year grant to investigate cognitive health in this population. Led by senior research scientist Rachel Whitmer, PhD, the study aims to determine if in the oldest-old there are ethnoracial differences in the incidence of mild cognitive impairment and dementia, to quantify mid- and late-life risk and protective factors for these conditions, and to understand the burden of cerebral and brain pathologies in this group.
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Interventions for Alcohol Use, Depression: Short counseling sessions, or “brief interventions,” for unhealthy alcohol use may also help improve blood pressure control in patients with hypertension. Senior author Stacy Sterling, DrPH, MSW, MPH, and Division of Research colleagues published the findings in the Journal of Substance Abuse Treatment. Funded by the National Institute of Alcohol Abuse and Alcoholism, Sterling is currently leading research into the effects of system-wide implementation of screening, brief intervention, and referral to treatment (SBIRT) for alcohol use among adults within Kaiser Permanente Northern California. Sterling is also lead author of a Journal of Adolescent Health study showing that referral to behavioral clinicians trained in delivering SBIRT for substance use could benefit adolescents with depression symptoms.
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Biostatistics Core

Large data set reveals waning effectiveness of shingles vaccine: A study published in the American Journal of Epidemiology by biostatistician Bruce H. Fireman, MA, and colleagues (including posthumous author Roger Paul Baxter, MD, FACP) analyzed data from nearly 400,000 adults in Kaiser Permanente Northern California who received the live attenuated zoster vaccine between 2007 and 2014. They found that the vaccine was about 68 percent effective initially against shingles, but its effectiveness waned over time. Kaiser Permanente’s large population of members receiving the vaccine at age 65 and older, electronic records for a long follow-up period, and innovative statistical methods yielded precise estimates of the trajectory of waning vaccine effectiveness for 8 years after vaccination.
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Research Consultations: Under the direction of Mary Anne Armstrong, MA, in 2017 the Biostatistical Consulting Unit provided support for 166 resident and fellow research projects, 27 miscellaneous funded projects, and 14 miscellaneous unfunded consultations (via funding from the Clinical Trials Program); and helped clinical partners develop 62 Community Benefit grant proposals. The unit also provided intensive consultations on 24 Community Benefit projects that were funded in 2017. Throughout the year, unit staff contributed to 27 publications and 42 conference presentations for their clients. 
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Statisticians Join Core: Two statisticians have joined the Biostatistics Core. Catherine Lee, PhD, received a PhD in mathematics from University of California, Los Angeles, and a PhD in biostatistics from Harvard University. Lee’s current research includes the development of methods for joint risk prediction using semi-competing risks data. Stacey E. Alexeeff, PhD, earned her MSc in Statistics at Carnegie Mellon University and her PhD in biostatistics from Harvard University. Alexeeff’s projects include studies of genetic and environmental risk factors for disease, intervention studies, and diagnostic prediction modeling.
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Cancer

Colonoscopy Urgency:If a fecal immunochemical test (FIT) detects a small amount of blood in a patient’s stool, they receive a colonoscopy to find and possibly remove any cancerous or pre-cancerous polyps. A large study led by Douglas A. Corley, MD, PhD, and Theodore R. Levin, MD, found that the risk of colorectal cancer increased significantly when colonoscopy was delayed by more than nine months following a positive fecal screening test. The findings appear in the Journal of the American Medical Association.
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Breast Cancer Survivorship: Women with more vitamin D in their blood after a breast cancer diagnosis had significantly better long-term outcomes, according to a JAMA Oncology study that used data from Pathways, an ongoing project led by Lawrence H. Kushi, ScD. A second study led by Candyce H. Kroenke, ScD, MPH, and published in Cancer showed that invasive breast cancer patients with more social ties had lower risks of recurrence and mortality, providing support for the peer navigation program at the Kaiser Permanente Oakland Breast Care Center.
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Understanding Disparities: Urban American-Indian and Alaskan Native patients had lower survival rates than non-Hispanic white patients following a diagnosis of invasive prostate or breast cancer, according to research performed by Laurel A. Habel, PhD, and colleagues. The study, published in Cancer Research, helps fill a gap in understanding of the cancer experience for American-Indian and Alaskan Native patients living in urban settings.
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New Bladder Cancer Study: The Be-Well Study, the largest and most comprehensive study of bladder cancer survivorship, was launched in 2017. By gathering information about diet and lifestyle, Marilyn L. Kwan, PhD, Lawrence H. Kushi, ScD, and colleagues at Kaiser Permanente Southern California and at Roswell Park Cancer Institute in Buffalo, N.Y., aim to find out whether lifestyle choices have any effect on disease recurrence and health after bladder cancer diagnosis.
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Treating HER2-Low Breast Cancer: Adding trastuzumab (Herceptin) to standard adjuvant chemotherapy can improve outcomes for HER2-positive breast cancer patients. However, in a randomized, phase III clinical trial, this treatment did not improve invasive disease–free survival for patients with early-stage breast cancer who have low HER2 protein levels or few HER2 gene copies. Louis Fehrenbacher, MD, presented these findings at the 2017 San Antonio Breast Cancer Symposium.
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Molecular Testing for Prostate Cancer: A patient’s Genomic Prostate Score relies on molecular testing of 17 genes and can help determine how aggressively his cancer should be treated. New research conducted by Stephen K. Van Den Eeden, PhD, Joseph Presti, MD, and colleagues showed that the Genomic Prostate Score can strongly predict long-term risks of metastasis and death after radical prostatectomy in men with low- and intermediate-risk prostate cancer. The findings, published in European Urology, support the use of the score when deciding on a patient’s best course of treatment.
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Cardiovascular and Metabolic Conditions

Stroke Risk in Atrial Fibrillation: Clinical trials show that the drugs warfarin and dabigatran can reduce the risk of ischemic stroke in people with atrial fibrillation. A new study led by Alan Go, MD, director of the Clinical Trials Program within the Kaiser Permanente Division of Research, has now found that outcomes for typical patients with atrial fibrillation who receive these medications are consistent with clinical trial results, as reported in Annals of Internal Medicine.
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Outstanding Work on Heart Disease: Senior research scientist Stephen Sidney, MD, MPH, was honored at the annual meeting of the National Forum for Heart Disease and Stroke Preventionfor his “exceptional contributions” and his work on understanding national trends in cardiovascular disease. At the event, Sidney presented his new National Forum report, which draws attention to a recent slowing of the rate of decline in deaths from heart disease and stroke in the United States.
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Heart Failure Deaths Rising in United States: A long-term, nationwide decline in deaths from heart disease reversed in 2015, but death rates for different heart disease subgroups followed different trends, according to research published in BMC Cardiovascular Disorders by Stephen Sidney, MD, MPH, Jamal S. Rana, MD, Alan Go, MD, and colleagues. Ischemic heart disease mortality continued to drop from 2011 to 2015, but deaths from heart failure and all other heart diseases rose. The authors called for “urgent attention” to address these trends.
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Public Health Education Partnership: Residents at Kaiser Permanente Oakland Medical Center can enhance their medical training with formal public health education through an innovative collaboration with the University of California Berkeley School of Public Health. A paper and video published in Advances in Medical Education and Practice by Joan C Lo, MD, and colleagues showed how the combined residency–Masters in Public Health program successfully trains future physician leaders in public health.
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Record-Breaking Stroke Drug Delivery: Kaiser Permanente hospitals in Northern California are delivering the clot-busting medication alteplase to new stroke patients more than twice as fast as the national average, thanks to regionwide adoption of an integrated telemedicine program. “Door to needle times” average just 34 minutes at all 21 Northern California hospitals, as reported by leader author Mai Nguyen-Huynh, MD, MAS, senior author Alexander Flint, MD, and colleagues in the journal Stroke.
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World’s Highest-Impact Researchers: Cardiovascular research scientist Alan Go, MD, and Kaiser Permanente Northern California oncologist Louis Fehrenbacher, MD, are among the less than 400 people in the world named as Highly Cited Researchers in clinical medicine for 2017 by Clarivate Analytics. The annual list recognizes investigators whose research ranks in the top 1 percent most cited works in their field, indicating exceptional scientific impact. “This is a remarkable achievement,” said Philip Madvig, MD, associate executive director of The Permanente Medical Group.
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Healthcare Policy and Delivery

Disparities in Cancer Care: Devon Check, PhD, a second-year Delivery Science Fellow, led an analysis of data from the Pathways study, finding that cancer patients who were racial/ethnic minorities were more likely than white patients to report a high burden of side effects during treatment. Check reported these findings at the 2017 Palliative and Supportive Care in Oncology Symposium in San Diego, Calif., supported by a Merit Award from the Conquer Cancer Foundation of the American Society of Clinical Oncology (ASCO).
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Patient Portal Helps Families: Kaiser Permanente offers its members an online patient portal that allows them to access health care information and engage with clinicians. A new survey study — designed with the direct assistance of Kaiser Permanente members — found that more than a quarter (27.5 percent) of 1,392 members with chronic conditions who were registered to use kp.org also used it to help a family member. Research scientist Mary E. Reed, DrPH, and colleagues published their findings in JAMA Internal Medicine.
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Low Blood Sugar Emergencies: A multi-institutional team led by senior research scientist Andrew J Karter, PhD, used machine learning techniques to develop and validate a practical tool for identifying diabetes patients who are at the highest risk for ending up in an emergency department or hospital due to very low blood sugar. The team, supported by funding from the U.S. Food and Drug Administration, reported the success of their innovative tool in JAMA Internal Medicine. The paper received the Division of Research’s Gary D. Friedman Outstanding Paper Award for 2017.
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Improving Surgical Outcomes: A comprehensive Enhanced Recovery After Surgery program implemented at Kaiser Permanente’s 20 Northern California medical centers involved nearly 9,000 surgical patients and resulted in a one-third relative reduction in postoperative complication rates and a 21 percent reduction in opioid prescribing rates, according to a study published in JAMA Surgery. The program aims “to reduce the stress of surgery, reduce complications, and maximize the potential for recovery,” said study leader Vincent Liu, MD.
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Weight Coaching by Telephone: Kaiser Permanente offers voluntary wellness coaching by phone to all its members nationwide for no additional fee. A new study led by Julie A. Schmittdiel, PhD, and published in the journal Obesity found that members who voluntarily participated in individual wellness coaching by telephone for weight management lost an average of 10 pounds each and changed their weight trajectories from upward to downward.
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2017-18 Member Health Survey Underway: The confidential Kaiser Permanente Member Health Survey is conducted every three years by Nancy Gordon, ScD, since 1993. All results for the 2014-15 Member Health Survey cycle are now available, and results of a small survey of Spanish-speaking members was posted in early 2018. Data collection for the 2017 Member Health Survey will be completed in early 2018 and results will be available in 2019.
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Dropping Caps on Drug Coverage: Alyce Adams, PhD, and colleagues investigated changes in non-cancer medication use among dual Medicare/Medicaid patients with cancer, after the 2006 Medicare Modernization Act shifted their prescription coverage to Medicare Part D plans that do not cap drug coverage. Dropping drug coverage caps was associated with increased medication use and reduced racial gaps in medication use. The findings appeared in Value in Health, the official journal of the International Society for Pharmacoeconomics and Outcomes Research.
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Infectious Diseases

Whooping Cough Protection: Among infants whose mothers received the Tdap pertussis booster vaccine during pregnancy, the risk of contracting pertussis, or whooping cough, decreased by about 91 percent during the first two months of life — the critical period before they can receive their first childhood pertussis vaccine. Reported in Pediatrics, these findings from the Kaiser Permanente Vaccine Study Center “demonstrate that maternal Tdap administered during pregnancy provides the best protection against pertussis,” said senior author Nicola P. Klein, MD, PhD. The paper received the Division of Research’s Gary D. Friedman Outstanding Paper Award for 2017.
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Vaccination During Pregnancy: Postdoctoral researcher Ousseny Zerbo, PhD, was lead author on two studies that found no association between influenza vaccination during pregnancy and increased risk of autism spectrum disorder in children, nor with birth outcomes such as preterm birth, need for mechanical ventilation, and low birth weight. The authors do not recommend any policy or practice changes, but noted that the findings suggest a need for more research. The autism findings appeared in JAMA Pediatrics and the birth outcome results in Vaccine.
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HIV and Alcohol Use: With support from the National Institute on Alcohol Abuse and Alcoholism, Kaiser Permanente and the University of Bristol are joining the Veterans Healthcare System to participate in COMpAAAS: the Consortium to improve OutcoMes in HIV/Aids, Alcohol, Aging & multi-Substance. The partnership will enable evaluation of the risk of alcohol and tobacco exposure on mortality, hospitalizations, comorbidities, and physiologic frailty for people living with HIV. Division of Research scientist Michael J. Silverberg, PhD, MPH, and psychologist Derek Satre, PhD, are co-principal investigators on the project.
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Women's and Children's Health

Fewer Antibiotics for Newborns: A study published in JAMA Pediatrics, led by research scientist Michael Kuzniewicz, MD, MPH, showed that the development and implementation of a neonatal sepsis risk calculator safely reduced antibiotic use by nearly 50 percent in newborns in Kaiser Permanente’s Northern California region. “By dramatically reducing the use of antibiotics, the risk calculator allows mothers and babies to stay together in the days after birth,” said co-author Allen Fischer, MD, director of neonatology for Kaiser Permanente Northern California. The study demonstrates how predictive analytics can aid in the development of tools that lead to direct improvements in patient care. The paper received the Division of Research’s Gary D. Friedman Outstanding Paper Award for 2017.
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Minimally Invasive Hysterectomy: The rate of minimally invasive surgery for routine hysterectomy increased from 40 percent to 93 percent in Kaiser Permanente’s Northern California region between 2008 and 2015, with significantly reduced post-operative complications and hospital stays, according to a study published in Obstetrics & Gynecology by senior author Tina Raine-Bennett, MD, MPH, research director of the Kaiser Permanente Women’s Health Institute, and lead author Eve Zaritsky, MD. “Women who have hysterectomies with minimally invasive surgery have shorter recoveries, less pain, and smaller scars,” Zaritsky said.
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Environmental Influences on Child Health: The Division of Research has launched a new 7-year, $24 million study, funded by the National Institutes of Health, on how exposures to environmental chemicals during pregnancy may influence the risk of obesity and neurodevelopmental disorders in children. Division of Research associate director Assiamira Ferrara, MD, PhD, is principal investigator, along with co-principal investigator Lisa A. Croen, PhD, director of the Autism Research Program. The study is part of NIH’s $144 million Environmental Influences on Child Health Outcomes (ECHO) program, which is investigating how exposure to a range of environmental factors from conception through early childhood influences the health of children and adolescents.
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Magnetic Fields and Miscarriage: A study of real-world exposure to non-ionizing radiation from magnetic fields, led by research scientist De-Kun Li, MD, PhD, and published in Scientific Reports, found that high exposure was associated with a significantly higher rate of miscarriage, providing new evidence regarding their potential health risks. Objective magnetic field measurements and pregnancy outcomes were obtained for 913 pregnant women; miscarriage occurred in 10.4 percent of the women with the lowest measured exposure level on a typical day, and in 24.2 percent of the women with the higher measured exposure levels, a nearly three times higher relative risk.
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Best Environmental Research Paper: Lisa A. Croen, PhD, director of the Autism Research Program, was a co-author of the best paper of the year (2016) in the journal Environmental Research. The paper, “Presence of an epigenetic signature of prenatal cigarette smoke exposure in childhood,” by Ladd-Acosta et al., found that an epigenetic signature of prenatal exposure to cigarette smoke, originally discovered in other studies of cord blood at birth, is detectable in childhood blood samples at ages 3 to 5, providing evidence that prenatal exposure to tobacco smoke has lifelong health consequences.
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