Katherine M Newton

• PhD
• Managing Director at Kaiser Permanente Washington Health Research Institute

Background: Study to describe the degree of menopausal palpitation distress and its demographic, clinical, symptom, and quality-of-life (QOL) correlates. Analysis of existing, baseline, data from peri- and postmenopausal women, 42 to 62 years of age, who participated in the Menopause Strategies-Finding Lasting Answers for Symptoms and Health (MsFLA...

Objective: The Menopause Strategies: Finding Lasting Answers for Symptoms and Health network conducted three randomized clinical trials (RCTs) testing six interventions treating vasomotor symptoms (VMS), and also collected menopause-related quality of life (QOL) measures. A fourth RCT assessed an intervention for insomnia symptoms among women with...

Objective: The Menopause Strategies: Finding Lasting Answers for Symptoms and Health clinical trials network was funded by the National Institutes of Health to find new ways to alleviate the most common, bothersome menopausal symptoms by designing and conducting multiple concurrent clinical intervention studies, accommodating a wide scope of popul...

Background: Vulvovaginal symptoms, which include dryness, irritation, and pain with intercourse, are common among postmenopausal women and are associated with impaired sexual functioning and quality of life. Previous assessment of treatment strategies for these symptoms has been limited by a lack of sensitive patient-centered outcome measures that...

Importance To control spending, the Centers for Medicare & Medicaid Services reduced Medicare fee-for-service (FFS) payments for noninvasive cardiac tests (NCTs) performed in provider-based office settings (ambulatory offices not administratively affiliated with hospitals) starting in 2005. Contemporaneously, payments for hospital-based outpatient...

Background The MsFLASH (Menopause Strategies: Finding Lasting Answers for Symptoms and Health) Network recruited into five randomized clinical trials (n = 100–350) through mass mailings. The fifth trial tested two interventions for postmenopausal vulvovaginal symptoms (itching, pain, irritation, dryness, or pain with sex) and thus required a high l...

Objectives Women with prediabetes are identified from screening for overt diabetes in early pregnancy, but the clinical significance of prediabetes in pregnancy is unclear. We examined whether prediabetes in early pregnancy was associated with risks of adverse outcomes. Study Design We conducted a retrospective cohort study of pregnant women enroll...

Objective: To compare perinatal outcomes before and after a clinical guideline change from a two-step to a one-step approach to screening for gestational diabetes mellitus (GDM). Methods: We conducted a before-after cohort study of women with singleton live birth deliveries within Kaiser Permanente Washington, a mixed-model health plan in Washin...

Importance Nearly half of postmenopausal women report bothersome vulvovaginal symptoms, but few data support the efficacy of 2 commonly recommended treatments. Objective To compare the efficacy of a low-dose vaginal estradiol tablet and a vaginal moisturizer, each vs placebo, for treatment of moderate-to-severe postmenopausal vulvovaginal symptoms...

The mechanisms by which obesity increases cancer risk are unclear, but some lines of evidence suggest that gut microbial communities (GMC) may contribute to chronic inflammation in obese individuals through raised systemic levels of lipopolysaccharides (LPS). We evaluated associations of the GMC in stool with plasma LPS-binding protein (LBP, a meas...

Objective: The aim of the study was to identify associations between improvement in genitourinary symptoms of menopause (GSM) and vaginal microbiota, vaginal glycogen, and serum estrogen. Methods: Thirty postmenopausal women enrolled in a hot flash treatment trial (oral estradiol vs venlafaxine vs placebo) who reported GSM and provided vaginal s...

Study Objectives The Menopause Strategies: Finding Lasting Answers for Symptoms and Health network conducted three randomized clinical trials (RCT) testing six interventions treating vasomotor symptoms (VMS), and also collected self-reported sleep outcomes. A fourth RCT assessed an intervention for insomnia symptoms among women with VMS. We describ...

Objectives: To conduct psychometric analyses to condense the Hot Flash-Related Daily Interference Scale (HFRDIS) into a shorter form termed the Hot Flash Interference (HFI) scale; evaluate cut-points for both scales; and establish minimally important differences (MIDs) for both scales. Methods: We analyzed baseline and postrandomization patient-...

Objective: To examine associations between the composition of the vaginal microbiota and genitourinary menopausal symptoms, serum estrogen, and vaginal glycogen. Methods: For this cross-sectional study, 88 women aged 40 to 62 years, enrolled in a hot flash treatment trial, provided vaginal swabs and a blood sample at enrollment. Bacterial commun...

Objective: Obesity can be a considerable health concern for peri- and post-menopausal women. Evidence suggests an association between the gut microbiome and obesity. The study objective was to evaluate the association between being overweight or obese and phenotypic markers of having an overall gut microbial environment not capable of metabolizing...

Aims: Seven-year surveillance study (2005-2011) to evaluate race/ethnic differences in the trends in rates of severe hypoglycemia (SH) in a population of insured, at-risk adults with diabetes. Methods: SH events were identified via any primary or principal diagnosis from emergency department or inpatient encounters among African American, Asian,...

The Female Sexual Function Index (FSFI) is a psychometrically sound and popular 19-item self-report measure, but its length may preclude its use in studies with multiple outcome measures, especially when sexual function is not a primary endpoint. Only one attempt has been made to create a shorter scale, resulting in the Italian FSFI-6, later transl...

Background: Monitoring trends in cardiovascular events can provide key insights into the effectiveness of prevention efforts. Leveraging data from electronic health records provides a unique opportunity to examine contemporary, community-based trends in acute myocardial infarction hospitalizations. Methods: We examined trends in hospitalized acu...

Study objectives: To determine effects of yoga and aerobic exercise compared with usual activity on objective assessments of sleep in midlife women. Methods: Secondary analyses of a randomized controlled trial in the Menopause Strategies: Finding Lasting Answers for Symptoms and Health (MsFLASH) network conducted among 186 late transition and po...

Importance Effective, practical, nonpharmacologic therapies are needed to treat menopause-related insomnia symptoms in primary and women’s specialty care settings. Objective To evaluate the efficacy of telephone-based cognitive behavioral therapy for insomnia (CBT-I) vs menopause education control (MEC). Design, Setting, and Participants A single-s...

Objectives: Heart rate variability (HRV) reflects the integration of the parasympathetic nervous system with the rest of the body. Studies on the effects of yoga and exercise on HRV have been mixed but suggest that exercise increases HRV. We conducted a secondary analysis of the effect of yoga and exercise on HRV based on a randomized clinical tri...

Objective: Research has suggested that the autonomic nervous system (ANS) is involved in the experience of vasomotor symptoms (VMS) during menopause. We examined the relationship of VMS intensity and heart rate variability (HRV), a measure of ANS function. Methods: Women (n = 282) were recruited from three American states for a clinical trial of...

Objective Diurnal salivary cortisol patterns in healthy adults are well established but have not been studied in midlife women with hot flashes. We hypothesized that frequent hot flashes areassociated with aberrant cortisol patterns similar to sleep-deficient individuals. DesignCross-sectional. ParticipantsA total of 306 women, ages 40-62, randomiz...

Objective: To describe self-reported menopausal symptom priorities and their association with demographics and other symptoms among participants in an intervention trial for vasomotor symptoms (VMS). Methods: Cross-sectional study embedded in the MsFLASH 02 trial, a three-by-two factorial design of yoga vs. exercise vs. usual activity and omega-...

Objective: To update and expand The North American Menopause Society's evidence-based position on nonhormonal management of menopause-Associated vasomotor symptoms (VMS), previously a portion of the position statement on the management of VMS. Methods: NAMS enlisted clinical and research experts in the field and a reference librarian to identify an...

Examining trends in cardiovascular events and mortality in US health systems can guide the design of targeted clinical and public health strategies to reduce cardiovascular events and mortality rates. We conducted an observational cohort study from 2005 to 2011 among 1.25 million diabetic subjects and 1.25 million nondiabetic subjects from 11 healt...

Among patients with diabetes, racial differences in cardiometabolic risk factor control are common. The extent to which differences in medication adherence contribute to such disparities is not known. We examined whether medication adherence, controlling for treatment intensification, could explain differences in risk factor control between black a...

Objective: To describe the effects of six interventions for menopausal vasomotor symptoms relative to control in a pooled analysis, facilitating translation of the results for clinicians and symptomatic women. The Menopause Strategies: Finding Lasting Answers for Symptoms and Health network tested these interventions in three randomized clinical t...

Funding agencies and researchers increasingly recognize the importance of patient stakeholder engagement in research. Despite calls for greater patient engagement, few studies have engaged a broad-based online community of patient stakeholders in the early stages of the research development process. The objective of our study was to inform a resear...

Women, especially those with hot flashes, report poor sleep quality during various stages of the menopausal transition and postmenopause. Sleep measurements vary widely because of the copious instruments available. The Pittsburgh Sleep Quality Index (PSQI) is a frequently used questionnaire that produces a single score for sleep quality. This one-f...

Diabetes is a leading cause of chronic kidney disease (CKD). Different methods of CKD ascertainment may impact prevalence estimates. We used data from 11 integrated health systems in the United States to estimate CKD prevalence in adults with diabetes (2005-2011), and compare the effect of different ascertainment methods on prevalence estimates. We...

• Engaging stakeholders in the research process has the potential to improve quality of care and the patient care experience. • Online patient community surveys can elicit important topic areas for comparative effectiveness research. • Stakeholder meetings with substantial patient representation, as well as representation from health care delivery...

Introduction: The Female Sexual Distress Scale-Revised (FSDS-R) was created and validated to assess distress associated with impaired sexual function, but it is lengthy for use in clinical practice and research when assessing sexual function is not a primary objective. Aim: The study aims to evaluate whether a single item from the FSDS-R could b...

We appreciate the thoughtful comments from Blackberry et al. (1) on our article (2) and the insights they provide based on their efforts to improve medication adherence and timely treatment intensification in adults with diabetes (3). Although our study (2) and the study of Blackberry et al. (3) failed to improve medication adherence rates, another...

The objective of this study was to assess the incidence of major cardiovascular (CV) hospitalization events and all-cause deaths among adults with diabetes with or without CV disease (CVD) associated with inadequately controlled glycated hemoglobin (A1C), high LDL cholesterol (LDL-C), high blood pressure (BP), and current smoking. Study subjects in...

To characterize the time course, duration of improvement, and clinical predictors of placebo response in treatment of menopausal hot flashes. Data were pooled from two trials conducted in the Menopausal Strategies: Finding Lasting Answers to Symptoms and Health network, providing a combined placebo group (n = 247) and a combined active treatment gr...

After an initial episode of atrial fibrillation (AF), patients may develop long-standing persistent or permanent AF. We evaluated whether use of statins, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or β-blockers is associated with lower risk of long-standing persistent AF after an initial AF episode. We con...

Background: Lignans in plant foods are metabolized by gut bacteria to the enterolignans, enterodiol (END) and enterolactone (ENL). Enterolignans have biologic activities important to the prevention of cancer and chronic diseases. We examined the composition of the gut microbial community (GMC) as a contributor to human enterolignan exposure. Method...

An observational cohort analysis was conducted within the Surveillance, Prevention, and Management of Diabetes Mellitus (SUPREME-DM) DataLink, a consortium of 11 integrated health-care delivery systems with electronic health records in 10 US states. Among nearly 7 million adults aged 20 years or older, we estimated annual diabetes incidence per 1,0...

Thyroid stimulating hormone (TSH) hormone levels are normally tightly regulated within an individual; thus, relatively small variations may indicate thyroid disease. Genome-wide association studies (GWAS) have identified variants in PDE8B and FOXE1 that are associated with TSH levels. However, prior studies lacked racial/ethnic diversity, limiting...

This study aims to evaluate the effects of low-dose estradiol (E2) or venlafaxine on menopause-related quality of life and associated symptoms in healthy perimenopausal and postmenopausal women with hot flashes. A double-blind, placebo-controlled, randomized trial of low-dose oral 17β-E2 0.5 mg/day and venlafaxine XR 75 mg/day, versus identical pla...

Objective: This study aims to evaluate the associations of vasomotor symptom (VMS) frequency, bother, and severity with equol producer status and dietary daidzein intake. Methods: This is an observational study. This study included women aged 45 to 55 years, in postmenopause or in the menopausal transition, who had soy food intake of three or mo...

Study objectives: Determine effects of low-dose estradiol and low-dose venlafaxine on self-reported sleep measures in menopausal women with hot flashes. Design: 3-arm double-blind randomized trial. Participants assigned in a 2:2:3 ratio to 17β estradiol 0.5 mg/day (n = 97), venlafaxine XR 75 mg/day (n = 96), or placebo (n = 146) for 8 weeks. Se...

Objective: Medication nonadherence is a major obstacle to better control of glucose, blood pressure (BP), and LDL cholesterol in adults with diabetes. Inexpensive effective strategies to increase medication adherence are needed. Research design and methods: In a pragmatic randomized trial, we randomly assigned 2,378 adults with diabetes mellitus...

Background/Aims To analyze the incidence of major cardiovascular disease(CVD) hospitalization events and all-cause mortality among adults with diabetes with or without cardiovascular disease; and to estimate the proportion of preventable events due to uncontrolled lipids, glucose, blood pressure, and to active smoking.

Background/Aims A major goal of diabetes care is the prevention of major cardiovascular events (CVE). Its success can be measured by quantifying trends over time in major CVE in adults with and without diabetes. To quantify trends in occurrence of major CVE in adults with and without diabetes who received care at 11 U.S. managed care organizations...

Objective: To evaluate sexual function in midlife women taking low-dose oral estradiol or venlafaxine for hot flushes. Methods: In an 8-week randomized controlled trial among women aged 40-62 years, sexual function was compared between 0.5 mg oral estradiol per day or 75 mg venlafaxine per day (both compared with a placebo). Measures included co...

Antihyperglycemic medication intensification practices among patients with incident diabetes are incompletely understood. We characterized the first intensification the year after oral antihyperglycemic medication initiation among incident diabetes patients. This retrospective cohort study across 11 US health systems included adults identified with...

Background: Comparative effectiveness studies using electronic health records (EHRs) often define chronic kidney disease (CKD) outcomes using laboratory-based definitions. Recommendations for defining CKD require multiple longitudinal measurements. The implications of applying these definitions to EHR data are poorly understood. Methods: Using a...

Estrogen exposure plays a role in breast cancer (BC) development. A novel estrogen biomarker, the estrogen DNA adduct (EDA) ratio, was shown to be elevated in women at high-risk of BC and among BC cases. Modifiable factors may impact the EDA ratio, with studies demonstrating that resveratrol reduces EDA ratio in vitro. We sought to examine the hypo...

Importance: Estrogen therapy is the gold standard treatment for hot flashes and night sweats, but some women are unable or unwilling to use it because of associated risks. The serotonin-norepinephrine reuptake inhibitor venlafaxine hydrochloride is used widely as a nonhormonal treatment. While the clinical impression is that serotonin-norepinephri...

Background: Careful management of symptoms, particularly sleep and mood disturbances, may assist women in discontinuing hormone therapy (HT). We sought to describe characteristics associated with successful HT cessation in women who attempted to discontinue estrogen pills/patches with or without progestin. Methods: We invited 2,328 women, aged 4...

Determine efficacy of three non-hormonal therapies for improving menopause-related quality of life (QOL) in women with vasomotor symptoms (VMS). 12-week 3x2 randomized, controlled, factorial design trial. Peri- and postmenopausal women, ages 40-62 years, were randomized to yoga (n=107), exercise (n=106), or usual activity (n=142), and also randomiz...

Among adults with incident diabetes, data are lacking about first antihyperglycemic initiation and whether medication choice aligns with recommendations. To identify predictors of initiating any antihyperglycemic, and specifically sulfonylurea versus metformin. This retrospective cohort study included 241 327 patients from 11 US health systems, 200...

This study aims to determine the efficacy of yoga in alleviating vasomotor symptoms (VMS) frequency and bother. This study was a three-by-two factorial, randomized controlled trial. Eligible women were randomized to yoga (n = 107), exercise (n = 106), or usual activity (n = 142), and were simultaneously randomized to a double-blind comparison of ω-...

This study aims to determine the efficacy and tolerability of omega-3 fatty acids in reducing vasomotor symptoms (VMS) frequency and bother in perimenopausal and postmenopausal women. This study was a 12-week, three-by-two factorial, randomized controlled trial. Eligible women were randomized to a double-blind comparison of omega-3 (n = 177) or pla...

This study aims to determine the efficacy of exercise training for alleviating vasomotor and other menopausal symptoms. Late perimenopausal and postmenopausal sedentary women with frequent vasomotor symptoms (VMS) participated in a randomized controlled trial conducted in three sites: 106 women randomized to exercise and 142 women randomized to usu...

Objective: This report describes the Menopausal Strategies: Finding Lasting Answers to Symptoms and Health network and methodological issues addressed in designing and implementing vasomotor symptom trials. Methods: Established in response to a National Institutes of Health request for applications, the network was charged with conducting rapid...

Objective: The prevalence of vasomotor symptoms (VMS) among women aged 45 years or older who report regular menses has not been described well. Variability by race/ethnicity is expected. Methods: A cross-sectional analysis of Group Health enrollees was performed among women ages 45-56 y with regular and no skipped menses, and not taking hormones...

The feasibility of using imperfectly phenotyped "silver standard" samples identified from electronic medical record diagnoses is considered in genetic association studies when these samples might be combined with an existing set of samples phenotyped with a gold standard technique. An analytic expression is derived for the power of a chi-square tes...

Bias in point estimates of odds ratio for various φ and γca with k = .01, R = 4, m = .3, RRAA = 3 and a multiplicative disease risk model. (EPS)

P-values from null models in simulation are approximately uniformly distributed. (EPS)

ICD-9 Codes and Medications defining silver standard cases from EMR. (XLS)

Objectives: Evaluate the association of self-reported vasomotor symptom (VMS) frequency with race/ethnicity among a diverse midlife US population and explore menopause symptom differences by dietary soy isoflavone (genistein+daidzein) consumption. Study design: Cross-sectional population-based study of peri- and postmenopausal women, ages 45-58....

Background Genetic studies require precise phenotype definitions, but electronic medical record (EMR) phenotype data are recorded inconsistently and in a variety of formats. Objective To present lessons learned about validation of EMR-based phenotypes from the Electronic Medical Records and Genomics (eMERGE) studies. Materials and methods The eMERG...

Chromosomal abnormalities provide clinical utility in the diagnosis and treatment of hematologic malignancies, and may be predictive of malignant transformation in individuals without apparent clinical presentation of a hematologic cancer. In an effort to confirm previous reports of an association between clonal mosaicism and incident hematologic c...

Percent of individuals with a mosaic anomaly across 5-year age bins. (TIF)

Distribution of age at baseline across studies. The red dotted line represents the median age of the study. (TIF)

Distribution of size of mosaic anomaly versus age of specimen collection (or intake surrogate) by estimated copy change from disomic state (red = loss, dark blue = gain, orange = copy neutral loss of heterozygosity). (TIF)

Supplementary tables. (DOCX)

Background: Behavioral strategies are recommended for menopausal symptoms, but little evidence exists regarding efficacy. Purpose: Describe design and methodology of a randomized controlled 3 by 2 factorial trial of yoga, exercise and omega-3 fatty acids. Methods: Women from three geographic areas with a weekly average of ≥14 hot flashes/night...

With white blood cell count (WBC) emerging as an important risk factor for chronic inflammatory diseases, genetic associations of differential leukocyte types, specifically monocyte count, are providing novel candidate genes and pathways to further investigate. Circulating monocytes play a critical role in vascular diseases, such as in the formatio...

Background: An expansive body of evidence implicates estrogen in the development of breast cancer (BC). Recently, a novel estrogen biomarker, the genotoxoic estrogen ratio (GER), was shown to be associated with BC. In addition, an elevated GER was observed in women at high-risk of BC, and furthermore, high GER has been shown to be reversible. Becau...

Objective: To evaluate the effects of escitalopram 10-20 mg/day on menopause-related quality of life and pain in healthy menopausal women with hot flashes. Study design: A double-blind, placebo-controlled randomized trial of escitalopram 10-20mg/day vs. identical placebo was conducted among 205 women ages 40-62 years with an average of ≥4 daily...

Background: After an initial episode of atrial fibrillation (AF), AF may recur and become permanent. AF progression is associated with higher morbidity and mortality. Understanding the risk factors for permanent AF could help identify people who would benefit most from interventions. Objective: To determine whether body mass index (BMI), diabete...

The Health Maintenance Organization Research Network (HMORN), a consortium of 19 health care delivery systems with integrated research centers, held their 18th annual conference in Seattle, Washington from April 29 to May 2, 2012. Group Health Research Institute hosted the conference, "Learning health care systems: Leading through research". The 20...

Background/Aims Programs to translate the Diabetes Prevention Program (DPP) into effective real-life interventions are needed. In the Call-2-Health pilot study we designed and tested a telephone-based intervention modeled on the DPP. Here we present the impact of Call-2-Health on participants' report of support from friends and family for diet chan...

Background: Bone density has been suggested as a marker of cumulative hormone exposure. Small studies also suggest that patterns of daidzein metabolism may be related to hormone concentrations. To our knowledge, no studies in premenopausal women have compared bone density by daidzein-metabolizing phenotypes in the absence of a soy intervention. O...

Background About one-third of adults with diabetes have severe oral complications. However, limited previous research has investigated dental care utilization associated with diabetes. This project had two purposes: to develop a methodology to estimate dental care utilization using claims data and to use this methodology to compare utilization of d...

Appendices [[21,27]].

We sought to identify biomarkers associated with progestin therapy resistance and persistence/progression of endometrial hyperplasia. We performed a nested case-control study among women with complex (n = 73) and atypical (n = 41) hyperplasia treated with oral progestin, followed up 2-6 months for persistence/progression. We evaluated index endomet...

The aim of this study was to determine the effect of escitalopram on insomnia symptoms and subjective sleep quality in healthy perimenopausal and postmenopausal women with hot flashes. A randomized, blinded, multicenter, placebo-controlled parallel-group 8-week trial with 205 women (95 African American, 102 white, 8 other) was conducted between Jul...

Objective. We sought to determine among people whose initial atrial fibrillation (AF) terminated whether use of statins, beta-blockers, and ACE inhibitors or ARBs was associated with lower risk of recurrent AF or progression to permanent AF. Methods. In Group Health, an integrated health care system, we identified an inception cohort of people aged...

Immunohistochemical markers to assist in the diagnosis and classification of hyperplastic endometrial epithelial proliferations would be of diagnostic use. To examine the possible use of PAX2 as a marker of hyperplastic endometrium, cases of normal endometrium, simple and complex hyperplasia without atypia, atypical hyperplasia, and International F...

Urinary concentrations of 2:16-hydroxyestrone (2:16-OHE1) approximate concentrations of 2-OHE1 and 16α -OHE1 in breast tissue. As estrogens are purported to be involved in breast cancer development, the 2:16-OHE1 ratio can provide an indication of estrogen metabolite exposure in the breast. With prior studies observing associations between urinary...

The availability of automated administrative databases in medical and dental healthcare, combined with modern computing power, allows sophisticated multi-layered analyses of the causes and consequences of care delivered to large populations. These automated databases are now also commonly linked to data extracted from electronic medical records, an...

The aim of this study was to evaluate monitors for assessing vasomotor symptoms (VMS) in laboratory and ambulatory settings before use in the Menopause Strategies Finding Lasting Answers for Symptoms and Health network clinical trials testing VMS therapies. This was a three-phase study. Phase 1 included laboratory testing of the Freedman and protot...

Genome-wide association studies (GWAS) require high specificity and large numbers of subjects to identify genotype-phenotype correlations accurately. The aim of this study was to identify type 2 diabetes (T2D) cases and controls for a GWAS, using data captured through routine clinical care across five institutions using different electronic medical...