Exercise-Induced Dose-Response Alterations in Adiponectin and Leptin Levels Are Dependent on Body Fat Changes in Women at Risk for Breast Cancer.

BACKGROUND: Dysregulation of adipokines, such as adiponectin and leptin, is associated with a variety of chronic diseases, including cancer. Physical activity protects against breast cancer and one of the mechanisms which may underlie this association is exercise-induced changes in adipokine levels. The WISER Sister Trial was a three-armed randomized controlled trial in premenopausal women (n = 137) with an elevated risk for breast cancer. METHODS: A 5-menstrual-cycle-long dosed aerobic exercise intervention compared low-dose exercise (150 min/wk; n = 44) or high-dose exercise (300 min/wk; n = 48) with a control group asked to maintain usual activity levels (n = 45). Exercise intensity progressed to and was maintained at 70% to 80% of age predicted heart rate max. Body composition and adipokine levels were measured at baseline and follow-up. RESULTS: We observed significant linear trends for increased fitness capacity (Δ%: -2.0% control, 10.1% low dose, 13.1% high dose), decreased fat tissue-to-total tissue mass (Δ%: 0.7% control, -2.9% low dose, -3.7% high dose), increased body fat adjusted adiponectin (Δ%: -0.6% control, 0.6% low dose, 0.9% high dose), and decreased body fat adjusted leptin (Δ%: 0.7% control, -8.2% low dose, -10.2% high dose). CONCLUSIONS: In this randomized clinical trial of premenopausal women at risk for breast cancer, we demonstrate a dose-response effect of exercise on adiponectin and leptin and that dose response is dependent on changes in body fat. IMPACT: Improved adipokine levels, achieved by aerobic exercise training-induced decreases in body fat, may decrease breast cancer risk for high-risk premenopausal women. Cancer Epidemiol Biomarkers Prev; 25(8); 1195-200. ©2016 AACR.

Women In Steady Exercise Research (WISER) Sister: study design and methods.

PURPOSE: Women at elevated risk for breast cancer are motivated to reduce their risk. Current approaches rely primarily on hormonal intervention. A preventive exercise intervention might address the same hormonal issues, yet have fewer serious side effects and less negative impact on quality of life as compared to prophylactic mastectomy. WISER Sister was a randomized controlled trial which examined effects of two doses of exercise training on endogenous sex hormone exposure, hormonally active breast tissue, and other breast cancer risk factors. METHODS: Subjects for this single site trial were recruited from across the U.S., in collaboration with organizations that serve women at elevated risk, via emails, flyers, and letters. Eligibility criteria included age ≥ 18, eumenorrheic, and at elevated risk for breast cancer (e.g. BRCA1 or BRCA2 mutation and/or ≥ 18% lifetime risk according to prediction models). A 1:1:1 randomization scheme was used to allocate participants into: control, low dose (150 min/week), or high dose (300 min/week) home based treadmill exercise. Participants provided first morning urine samples daily for two menstrual cycles at study beginning and end for calculation of endogenous hormone exposure. In addition, women completed breast dynamic contrast enhanced magnetic resonance imaging, a fasting blood draw, a treadmill exercise test, and surveys at baseline and follow-up. DISCUSSION: WISER Sister randomized 139 women, 122 of whom completed the study. The overall drop-out rate was 12%. Findings will be useful in understanding the potential for exercise to assist with reducing risk for breast cancer among women at elevated risk.

Risk-adjusted comparison of blood pressure and low-density lipoprotein (LDL) noncontrol in primary care offices.

OBJECTIVES: Population-level control of modifiable cardiovascular disease (CVD) risk factors is suboptimal. The objectives of this study were (1) to demonstrate the use of electronically downloaded electronic health record (EHR) data to assess guideline concordance in a large cohort of primary care patients, (2) to provide a contemporary assessment of blood pressure (BP) and low-density lipoprotein (LDL) noncontrol in primary care, and (3) to demonstrate the effect of risk adjustment of rates of noncontrol of BP and LDL for differences in patient mix on these clinic-level performance measures. METHODS: This was an observational comparative effectiveness study that included 232,172 adult patients ≥18 years old with ≥1 visit within 2 years in 33 primary care clinics with EHRs. The main measures were rates of BP and LDL noncontrol based on current guidelines and were calculated from electronically downloaded EHR data. Rates of noncontrol were risk-adjusted using multivariable models of patient-level variables. RESULTS: Overall, 16.0% of the 227,122 patients with known BP and 14.9% of the 136,771 patients with known LDL were uncontrolled. Clinic-level, risk-adjusted BP noncontrol ranged from 7.7% to 26.5%, whereas that for LDL ranged from 5.8% to 23.6%. Rates of noncontrol exceeded an achievable benchmark for 85% (n = 28) and 79% (n = 26) of the 33 clinics for BP and LDL, respectively. Risk adjustment significantly influences clinic rank order for rate of noncontrol. CONCLUSIONS: We demonstrated that the use of electronic collection of data from a large cohort of patients from fee-for-service primary care clinics is feasible for the audit of and feedback on BP and LDL noncontrol. Rates of noncontrol for most clinics are substantially higher than those achievable. Risk adjustment of noncontrol rates results in a rank-order of clinics very different from that achieved with nonadjusted data.

Enhancing electronic health record measurement of depression severity and suicide ideation: a Distributed Ambulatory Research in Therapeutics Network (DARTNet) study.

BACKGROUND: Depression is a leading cause of morbidity worldwide. The majority of treatment for depression occurs in primary care, but effective care remains elusive. Clinical decision making and comparative studies of real-world antidepressant effectiveness are limited by the absence of clinical measures of severity of illness and suicidality. METHODS: The Distributed Ambulatory Research in Therapeutics Network (DARTNet) was engaged to systematically collect data using the 9-item Patient Health Questionnaire (PHQ-9) at the point of care. We used electronic health records (EHRs) and the PHQ-9 to capture, describe, and compare data on both baseline severity of illness and suicidality and response and suicidality after diagnosis for depressed patients in participating DARTNet practices. RESULTS: EHR data were obtained for 81,028 episodes of depression (61,464 patients) from 14 clinical organizations. Over 9 months, data for 4900 PHQ-9s were collected from 2969 patients in DARTNet practices (this included 1892 PHQ-9s for 1019 adults and adolescents who had at least one depression diagnosis). Only 8.3% of episodes identified in our depression cohort had severity of illness information available in the EHR. For these episodes, considerable variation existed in both severity of illness (32.05% with no depression, 26.89% with minimal, 19.54% with mild, 12.04% with moderate, and 9.47% with severe depression) and suicidality (69.43% with a score of 0, 22.58% with a score of 1, 4.97% with a score of 2, and 3.02% with a score of 3 on item 9 of the PHQ-9). Patients with an EHR diagnosis of depression and a PHQ-9 (n = 1019) had similar severity but slightly higher suicidality levels compared with all patients for which PHQ-9 data were available. The PHQ-9 showed higher sensitivity for identifying depression response and emergent (after diagnosis) severity and suicidality; 25% to 30% of subjects had some degree of suicidal thought at some point in time according to the PHQ-9. CONCLUSIONS: This study demonstrated the value of adding PHQ-9 data and prescription fulfillment data to EHRs to improve diagnosis and management of depression in primary care and to enable more robust comparative effectiveness research on antidepressants.

Weight lifting for women at risk for breast cancer-related lymphedema: a randomized trial.

CONTEXT: Clinical guidelines for breast cancer survivors without lymphedema advise against upper body exercise, preventing them from obtaining established health benefits of weight lifting. OBJECTIVE: To evaluate lymphedema onset after a 1-year weight lifting intervention vs no exercise (control) among survivors at risk for breast cancer-related lymphedema (BCRL). DESIGN, SETTING, AND PARTICIPANTS: A randomized controlled equivalence trial (Physical Activity and Lymphedema trial) in the Philadelphia metropolitan area of 154 breast cancer survivors 1 to 5 years postunilateral breast cancer, with at least 2 lymph nodes removed and without clinical signs of BCRL at study entry. Participants were recruited between October 1, 2005, and February 2007, with data collection ending in August 2008. INTERVENTION: Weight lifting intervention included a gym membership and 13 weeks of supervised instruction, with the remaining 9 months unsupervised, vs no exercise. MAIN OUTCOME MEASURES: Incident BCRL determined by increased arm swelling during 12 months (≥5% increase in interlimb difference). Clinician-defined BCRL onset was also evaluated. Equivalence margin was defined as doubling of lymphedema incidence. RESULTS: A total of 134 participants completed follow-up measures at 1 year. The proportion of women who experienced incident BCRL onset was 11% (8 of 72) in the weight lifting intervention group and 17% (13 of 75) in the control group (cumulative incidence difference [CID], -6.0%; 95% confidence interval [CI], -17.2% to 5.2%; P for equivalence = .04). Among women with 5 or more lymph nodes removed, the proportion who experienced incident BCRL onset was 7% (3 of 45) in the weight lifting intervention group and 22% (11 of 49) in the control group (CID, -15.0%; 95% CI, -18.6% to -11.4%; P for equivalence = .003). Clinician-defined BCRL onset occurred in 1 woman in the weight lifting intervention group and 3 women in the control group (1.5% vs 4.4%, P for equivalence = .12). CONCLUSION: In breast cancer survivors at risk for lymphedema, a program of slowly progressive weight lifting compared with no exercise did not result in increased incidence of lymphedema. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00194363.

Comparative effectiveness research in DARTNet primary care practices: point of care data collection on hypoglycemia and over-the-counter and herbal use among patients diagnosed with diabetes.

BACKGROUND: The Distributed Ambulatory Research in Therapeutics Network (DARTNet) is a federated network of electronic health record (EHR) data, designed as a platform for next-generation comparative effectiveness research in real-world settings. DARTNet links information from nonintegrated primary care clinics that use EHRs to deliver ambulatory care to overcome limitations with traditional observational research. OBJECTIVE: Test the ability to conduct a remote, electronic point of care study in DARTNet practices by prompting clinic staff to obtain specific information during a patient encounter. RESEARCH DESIGN: Prospective survey of patients identified through queries of clinical data repositories in federated network organizations. On patient visit, survey is triggered and data are relinked to the EHR, de-identified, and copied for evaluation. SUBJECTS: Adult patients diagnosed with diabetes mellitus that scheduled a clinic visit for any reason in a 2-week period in DARTNet primary care practices. MEASURES: Survey on hypoglycemic events (past month) and over-the-counter and herbal supplement use. RESULTS: DARTNet facilitated point of care data collection triggered by an electronic prompt for additional information at a patient visit. More than one-third of respondents (33% response rate) reported either mild (45%) or severe hypoglycemic events (5%) in the month before the survey; only 3 of those were also coded using the ICD-9 (a significant difference in detection rates 37% vs. 1%). Nearly one-quarter of patients reported taking an OTC/herbal, 4% specifically for the treatment of symptoms of diabetes. CONCLUSIONS: Prospective data collection is feasible in DARTNet and can enable comparative effectiveness and safety research.

Weight lifting in women with breast-cancer-related lymphedema.

BACKGROUND: Weight lifting has generally been proscribed for women with breast-cancer-related lymphedema, preventing them from obtaining the well-established health benefits of weight lifting, including increases in bone density. METHODS: We performed a randomized, controlled trial of twice-weekly progressive weight lifting involving 141 breast-cancer survivors with stable lymphedema of the arm. The primary outcome was the change in arm and hand swelling at 1 year, as measured through displaced water volume of the affected and unaffected limbs. Secondary outcomes included the incidence of exacerbations of lymphedema, number and severity of lymphedema symptoms, and muscle strength. Participants were required to wear a well-fitted compression garment while weight lifting. RESULTS: The proportion of women who had an increase of 5% or more in limb swelling was similar in the weight-lifting group (11%) and the control group (12%) (cumulative incidence ratio, 1.00; 95% confidence interval, 0.88 to 1.13). As compared with the control group, the weight-lifting group had greater improvements in self-reported severity of lymphedema symptoms (P=0.03) and upper- and lower-body strength (P<0.001 for both comparisons) and a lower incidence of lymphedema exacerbations as assessed by a certified lymphedema specialist (14% vs. 29%, P=0.04). There were no serious adverse events related to the intervention. CONCLUSIONS: In breast-cancer survivors with lymphedema, slowly progressive weight lifting had no significant effect on limb swelling and resulted in a decreased incidence of exacerbations of lymphedema, reduced symptoms, and increased strength. (ClinicalTrials.gov number, NCT00194363.)

Physical Activity and Lymphedema (the PAL trial): assessing the safety of progressive strength training in breast cancer survivors.

Lymphedema is a chronic and progressive long-term adverse effect of breast cancer treatment commonly defined by swelling of the affected arm. Current clinical guidelines indicate that women with and at risk for lymphedema should protect the affected arm from overuse. In clinical practice, this often translates into risk aversive guidance to avoid using the arm. This could lead to a disuse pattern that may increase the likelihood of injury from common activities of daily living. Further, such guidance poses an additional barrier to staying physically active, potentially translating to weight gain, which has been shown to be associated with worse clinical course for women with lymphedema. We hypothesize that a program of slowly progressive strength training with no upper limit on the amount of weight that may be lifted would gradually increase the physiologic capacity of the arm so that common activities represent a decreasing percentage of maximal capacity. Theoretically, this increased capacity should decrease the risk that daily activities put stress on the lymphatic system of the affected side. The Physical Activity and Lymphedema (PAL) Trial is a recently completed randomized controlled exercise intervention trial that recruited 295 breast cancer survivors (141 with lymphedema at study entry, 154 at risk for lymphedema at study entry). The purpose of this report is to provide detail regarding the study design, statistical design, and protocol of the PAL trial.

The use and effectiveness of electronic clinical decision support tools in the ambulatory/primary care setting: a systematic review of the literature.

BACKGROUND: The 1999 Institute of Medicine (IOM) report To Err is Human alerted the healthcare industry and the public to the lack of consistency in the delivery of quality care to the US population. Clinical decision support systems (CDSS) have become a leading response to this report, and to the growing demand for the promotion of standards-based care delivery. The objective of this paper is to evaluate the recent literature for both the types and effectiveness of electronic CDSS in the primary care setting. METHODS: An electronic search of the literature was conducted utilising MEDLINE (1996-2006), CINAHL (1982-2006) and all EBM Reviews--Cochrane DSR, ACP Journal Club, DARE and CCTR. The search included various combinations of the MeSH search terms 'clinical decision support systems', 'primary health care', 'ambulatory care' and 'practice guidelines' and was limited to articles published from 2000 to 2006. Studies were selected for review if they involved either non-randomised observational or randomised controlled trials (RCTs) utilising CDSS as a single intervention, were performed in an ambulatory primary care setting and included quantifiable outcome measures. RESULTS: Seventeen studies were included in the review, including five non-randomised observational studies and 12 RCTs. Thirteen studies (76%) found either positive or variable outcomes related to CDSS intervention with four studies (24%) showing no significant effect. CONCLUSION: Although there is validation that CDSS has the potential to produce statistically significant improvement in outcomes, there is much variability among the types and methods of CDSS implementation and resulting effectiveness. As CDSS will likely continue to be at the forefront of the march toward effective standards-based care, more work needs to be done to determine effective implementation strategies for the use of CDSS across multiple settings and patient populations.

Provider and policy response to reverse the consequences of low health literacy.

The 2004 Institute of Medicine publication, Health Literacy: A Prescription to End Confusion, is the first comprehensive report about low health literacy and its consequences. Although affecting more than 50 percent of the adult population in the United States, low health literacy is a pervasive issue that has received little attention among policymakers and healthcare executives. Yet, strategies to increase the health literacy of patient communities are relatively inexpensive and easy to implement. Furthermore, such strategies have the potential to significantly reduce costs and improve outcomes by arming the population with information on self-management and prevention of disease. This article presents an overview of the issues surrounding low health literacy, highlights its impact on the delivery system, and discusses practical steps that healthcare providers and executives can implement to enable health literate communities.

Strength training and adiposity in premenopausal women: strong, healthy, and empowered study.

BACKGROUND: American women aged 25-44 y gain 0.5-1 kg yearly, most of which is fat. Because few midlife women participate in strength training, this mode of activity may be a novel intervention for preventing age-associated fat increases in this population. OBJECTIVES: The primary aim was to assess the efficacy of twice-weekly strength training to avoid increases in percentage body fat and intraabdominal fat. DESIGN: A randomized controlled trial was conducted in an ethnically diverse sample of 164 overweight and obese [body mass index (in kg/m2): 25-35] women aged 25-44 y. The treatment group did twice-weekly strength training for 2 y. The standard care comparison group was given brochures recommending aerobic exercise. Assessments at baseline, 1, and 2 y included intraabdominal fat by computed tomography scan and body fat and fat-free mass by dual-energy X-ray absorptiometry. RESULTS: During 2 y, percentage body fat changes were -3.68 +/- 0.99% for the treatment group and -0.14 +/- 1.04% for the control group, P = 0.01. Two-year intraabdominal fat changes were 7.05 +/- 5.07% for the treatment group and 21.36 +/- 5.34% for the control group, P = 0.05. CONCLUSION: This study suggests that strength training is an efficacious intervention for preventing percentage body fat increases and attenuating intraabdominal fat increases in overweight and obese premenopausal women. This is relevant to public health efforts for obesity prevention because most weight gain can be assumed to be fat, including abdominal fat.