A Cluster Randomized Trial of Primary Care Practice Redesign to Integrate Behavioral Health for Those Who Need It Most: Patients With Multiple Chronic Conditions.

PURPOSE: Patient outcomes can improve when primary care and behavioral health providers use a collaborative system of care, but integrating these services is difficult. We tested the effectiveness of a practice intervention for improving patient outcomes by enhancing integrated behavioral health (IBH) activities. METHODS: We conducted a pragmatic, cluster randomized controlled trial. The intervention combined practice redesign, quality improvement coaching, provider and staff education, and collaborative learning. At baseline and 2 years, staff at 42 primary care practices completed the Practice Integration Profile (PIP) as a measure of IBH. Adult patients with multiple chronic medical and behavioral conditions completed the Patient-Reported Outcomes Measurement Information System (PROMIS-29) survey. Primary outcomes were the change in 8 PROMIS-29 domain scores. Secondary outcomes included change in level of integration. RESULTS: Intervention assignment had no effect on change in outcomes reported by 2,426 patients who completed both baseline and 2-year surveys. Practices assigned to the intervention improved PIP workflow scores but not PIP total scores. Baseline PIP total score was significantly associated with patient-reported function, independent of intervention. Active practices that completed intervention workbooks (n = 13) improved patient-reported outcomes and practice integration (P ≤ .05) compared with other active practices (n = 7). CONCLUSION: Intervention assignment had no effect on change in patient outcomes; however, we did observe improved patient outcomes among practices that entered the study with greater IBH. We also observed more improvement of integration and patient outcomes among active practices that completed the intervention compared to active practices that did not. Additional research is needed to understand how implementation efforts to enhance IBH can best reach patients.

The impact of the implementation of medication for opioid use disorder and COVID-19 in a statewide correctional system on treatment engagement, postrelease continuation of care, and overdose.

BACKGROUND: People with opioid use disorder (OUD) are overrepresented in US correctional facilities and experience disproportionately high risk for overdose after release. Medications for OUD (MOUD) are highly efficacious but not available to most incarcerated individuals. In 2018, Vermont began providing MOUD for all incarcerated individuals with OUD statewide. In 2020, the COVID-19 state of emergency began. We assessed the impact of both events on MOUD utilization and treatment outcomes. METHODOLOGY: Analyses linked Vermont Department of Corrections administrative data and Medicaid claims data between 07/01/2017 and 03/31/2021. The study used logistic regression to analyze treatment engagement among all incarcerated individuals in Vermont. Multilevel modeling assessed change in clinical outcomes among release episodes that occurred among individuals with an OUD diagnosis Medicaid claim. RESULTS: Prescriptions for MOUD while incarcerated increased from 0.8% to 33.9% of the incarcerated population after MOUD implementation (OR = 67.4) and subsequently decreased with the onset of COVID-19 to 26.6% (OR = 0.7). After MOUD implementation, most prescriptions (63.1%) were to individuals who had not been receiving MOUD prior to incarceration, but this figure decreased to 53.9% with the onset of COVID-19 (OR = 0.7). Prescriptions for MOUD within 30 days after release increased from 33.9% of those with OUD before to 41.0% after MOUD implementation (OR = 1.4) but decreased to 35.6% with the onset of COVID-19 (OR = 0.8). Simultaneously, opioid-related nonfatal overdoses within 30 days after release decreased from 1.2% before to 0.8% after statewide MOUD implementation (OR = 0.3) but increased to 1.9% during COVID-19 (OR = 3.4). Fatal overdoses within 1 year after release decreased from 27 deaths before to ≤10 after statewide MOUD implementation and remained ≤10 during COVID-19. CONCLUSIONS: This longitudinal evaluation demonstrated increased treatment engagement and a decrease in opioid-related overdose following implementation of MOUD in a statewide correctional system. In contrast, these improvements were somewhat attenuated with the onset of COVID-19, which was associated with decreased treatment engagement and an increase in nonfatal overdoses. Considered together, these findings demonstrate the benefits of statewide MOUD for incarcerated individuals as well as the need to identify and address barriers to continuation of care following release from incarceration in the context of COVID-19.

Integrating behavioural health and primary care: qualitative findings on contextual factors that influence integration.

BACKGROUND: Integrating behavioural health care into primary care practices may increase patients' access to behavioural health services and improve health outcomes. However, few studies have explored factors that influence integration processes. OBJECTIVE: We sought to better understand contextual factors that support or impede behavioural health integration in primary care practices. METHODS: We conducted 71 semi-structured interviews with providers, staff, and leaders from eight primary care practices in the United States with integrated behavioural health services, which were participating in a randomized control, pragmatic trial: Integrating Behavioural Health and Primary Care. Practices were selected for diversity on geographic location, size, ownership, and experience with integration. We conducted a thematic analysis of the qualitative data derived from the interviews. RESULTS: We identified four categories of contextual factors influencing behavioural health integration: leadership commitment to integration, financial considerations, workflow and communication systems, and providers' perspectives on integration and team-based healthcare. Supportive factors included leaders' commitment to integration, adequate staffing, customized communication and workflow systems, collaborative practice culture, and healthy working relationships amongst providers. Impediments included staffing issues and payment models that do not reimburse for activities required to support integrated care. CONCLUSION: Interviewees described various benefits of integration, including providers feeling better equipped to address patients' needs due to collaboration between medical and behavioural providers and resulting interdisciplinary learning. Given concerns about provider burnout, this finding warrants further study.

This study examines the integration of behavioural health services, such as mental health counselling, into primary care practices. We conducted interviews with representatives from eight primary care practices with integrated behavioural health services. The participating practices are located in diverse geographic locations across the United States, and all were engaged in a large, national project entitled Integrating Behavioural Health and Primary Care. A total of 71 healthcare providers, staff, and practice leaders were interviewed and asked to discuss the factors that influenced efforts to integrate behavioural healthcare in their primary care practice. We analysed the interview transcripts and identified factors that supported or impeded behavioural health integration. Supportive factors included practice leaders' commitment to integration, adequate staffing, customized communication and workflow systems within the practice, a collaborative practice culture, and healthy working relationships amongst the medical and behavioural health providers. Impediments included staffing issues and a lack of reimbursement from insurance companies and government payers for the time and effort that practice staff needs to devote in order to provide integrated care. Interviewees described various benefits of behavioural health integration, including providers feeling better equipped to address patients' needs due to collaboration between medical and behavioural providers.

Econometric evaluation of implementing a behavioral health integration intervention in primary care settings.

Integrated behavioral health (IBH) is an approach to patient care that brings medical and behavioral health providers (BHPs) together to address both behavioral and medical needs within primary care settings. A large, pragmatic, national study aimed to test the effectiveness and measure the implementation costs of an intervention to improve IBH integration within primary care practices (IBH-PC). Assess the time and cost to practices of implementing a comprehensive practice-level intervention designed from the perspective of clinic owners to move behavioral service integration from co-location toward full integration as part of the IBH-PC study. IBH-PC program implementation costs were estimated in a representative sample of 8 practices using standard micro-econometric evaluation of activities outlined in the implementation workbook, including program implementation tasks, remote quality improvement coaching services, educational curricula, and learning community activities, over a 24-month period. The total median cost of implementing the IBH-PC program across all stages was $20,726 (range: $12,381 - $60,427). The median cost of the Planning Stage was $10,258 (range: $4,625 - $14,840), while the median cost of the Implementation Stage was $9,208 (range: $6,017 - 49,993). There were no statistically significant differences in practice or patient characteristics between the 8 selected practices and the larger IBH-PC practice sample (N=34). This study aimed to quantify the relative costs associated with integrating behavioral health into primary care. Although the cost assessment approach did not include all costs (fixed, variable, operational, and opportunity costs), the study aimed to develop a replicable and pragmatic measurement process with flexibility to adapt to emerging developments in each practice environment, providing a reasonable ballpark estimate of costs associated with implementation to help guide future executive decisions.

This study estimated the cost of implementing a program that helped 8 primary care practices transition from a co-located behavioral health services model to greater integration. Our study was part of a larger study across the United States. The authors found that the per-practice program implementation cost ranged between $12,381 and $60,427 and the median cost was $20,726. Leaders of healthcare organizations that participated in this study thought that these costs represented the work of program implementation and that they were reasonable and acceptable.

Intraclass Correlation and Variance in the Characteristics of Primary Care Patients Managing Chronic Medical and Behavioral Conditions.

Background To avoid statistical errors, researchers who recruit patients from selected medical practices and analyze them at the individual level need to account for the clustered nature of their sample. This is most often done using the intraclass correlation coefficients (ICCs), a measure of how strongly subjects recruited from the same cluster (in this case patients from a clinic) resemble each other. Aims The aim is to support the design of cluster-randomized studies by supplying estimates of variance and ICC of various measures using a population of patients from multiple primary care clinics. Materials and methods ICCs were extracted from a large cluster-randomized pragmatic clinical trial of adult primary care patients managing multiple chronic conditions, the Integrating Behavioral Health and Primary Care study (IBH-PC). IBH-PC collected demographics and patient-reported health outcomes on over 3,000 adults from 44 primary care practices in 13 states across the US. We present estimates of the standard deviation and ICC for gender, race, ethnicity, marital status, employment, income, education, social determinants of health, PROMIS-29 functional status, Duke Activity Status Index (DASI), nine-item Patient Health Questionnaire (PHQ-9) depression score, Generalized Anxiety Disorder (GAD-7) anxiety score, Asthma Symptom Utility Index, restricted activity days, medication adherence, health care visits in the past month, emergency room visits in the past year, hospital days in the past year, perception of quality and patient-centeredness of care, alcoholic drinks per month, and the GAIN substance use disorder screener. Results ICCs varied broadly with the highest values found for race and income and the lowest for short-term estimates of the GAIN. Conclusions These values can be used to inform the design, especially power estimates and sample size requirements, of future studies.

Payment strategies for behavioral health integration in hospital-affiliated and non-hospital-affiliated primary care practices.

Recent value-based payment reforms in the U.S. called for empirical data on how primary care practices of varying characteristics fund their integrated behavioral health services. To describe payment strategies used by U.S. primary care practices to fund behavioral health integration and compare strategies between practices with and without hospital affiliation.Baseline data were used and collected from 44 practices participating in a cluster-randomized, pragmatic trial of behavioral health integration. Data included practice characteristics and payment strategies-fee-for-service payment, pay-for-performance incentives, grants, and graduate medical education funds. Descriptive and comparative analyses using Fisher's exact tests and independent T-tests were conducted. The sample had 26 (59.1%) hospital-affiliated (hospital/health system-owned, academic medical centers and hospital-affiliated practices) and 18 (40.9%) non-hospital-affiliated practices (community health centers/federally qualified health centers and privately-owned practices). Most practices (88.6%) received payments through fee-for-service; 63.6% received pay-for-performance incentives; 31.8% received grant funds. Collaborative Care Management billing (CPT) codes were used in six (13.6%) practices. Over half (53.8%) of hospital-affiliated practices funded their behavioral health services through fee-for-service and pay-for-performance incentives only, as opposed to two-thirds (66.7%) of non-hospital-affiliated practices required additional support from grants and/or general medical education funds. Primary care practices support behavioral health integration through diverse payment strategies. More hospital-affiliated practices compared to non-hospital-affiliated practices funded integrated behavioral health services through fee-for-service and pay-for-performance incentives. Practices without hospital affiliation relied on multiple funding streams including grants and/or general medical education funds, suggesting their approach to financial sustainment may be more precarious or challenging, compared to hospital-affiliated practices.

Development and validation of the patient centeredness index for primary care.

AIMS AND OBJECTIVES: To describe the development of the Patient Centeredness Index (PCI), evaluate its psychometric characteristics and evaluate the relationships between scores on the PCI and an established measure of empathy. BACKGROUND: Patient centeredness helps patients manage multiple chronic conditions with their providers, nurses and other team members. However, no instrument exists for evaluating patient centeredness within primary care practices treating this population. DESIGN: Multi-site instrument development and validation. STROBE reporting guidelines were followed. METHODS: To identify themes, we consulted literature on patient centeredness and engaged stakeholders who had or were caring for people with multiple chronic conditions (n = 7). We composed and refined items to represent those themes with input from clinicians and researchers. To evaluate reliability and convergent validity, we administered surveys to participants (n = 3622) with chronic conditions recruited from 44 primary care practices for a large-scale cluster randomised clinical trial of the effects of a practice-level intervention on patient and practice-level outcomes. Participants chose to complete the 16-item survey online, on paper or by phone. Surveys assessed demographics, number of chronic conditions and ratings of provider empathy. We conducted exploratory factor analysis to model the interrelationships among items. RESULTS: A single factor explained 93% of total variance. Factor loadings ranged from 0.55-0.85, and item-test correlations were ≥.67. Cronbach's alpha was .93. A moderate, linear correlation with ratings of provider's empathy (r = .65) supports convergent validity. CONCLUSIONS: The PCI is a new tool for obtaining patient perceptions of the patient centeredness of their primary care practice. The PCI shows acceptable reliability and evidence of convergent validity among patients managing chronic conditions. RELEVANCE TO CLINICAL PRACTICE: The PCI rapidly identifies patients' perspectives on patient centeredness of their practice, making it ideal for administration in busy primary care settings that aim to efficiently address patient-identified needs. TRIAL REGISTRATION: Clinicaltrials.org Protocol ID: WLPS-1409-24372. TITLE: Integrating Behavioural Health and Primary Care for Comorbid Behavioural and Medical Problems (IBHPC).

Integrating behavioral health & primary care for multiple chronic diseases: Clinical trial of a practice redesign toolkit.

Context: Most patients in need of behavioral health (BH) care are seen in primary care, which often has difficulty responding. Some practices integrate behavioral health care (IBH), with medical and BH providers at the same location, working as a team. However, it is difficult to achieve high levels of integration. Objective: Test the effectiveness of a practice intervention designed to increase BH integration. Study Design: Pragmatic, cluster-randomized controlled trial. Setting: 43 primary care practices with on-site BH services in 13 states. Population: 2,460 adults with multiple chronic medical and behavioral conditions. Intervention: 24-month practice change process including an online curriculum, a practice redesign and implementation workbook, remote quality improvement coaching services, and an online learning community. Outcomes: Primary outcomes were changes in the 8 Patient-Reported Outcomes Measurement Information System (PROMIS-29) domain scores. Secondary outcomes were changes in medication adherence, self-reported healthcare utilization, time lost due to disability, cardiovascular capacity, patient centeredness, provider empathy, and several condition-specific measures. A sample of practice staff completed the Practice Integration Profile at each time point to estimate the degree of BH integration in that site. Practice-level case studies estimated the typical costs of implementing the intervention. Results: The intervention had no significant effect on any of the primary or secondary outcomes. Subgroup analyses showed no convincing patterns of effect in any populations. COVID-19 was apparently not a moderating influence of the effect of the intervention on outcomes. The intervention had a modest effect on the degree of practice integration, reaching statistical significance in the Workflow domain. The median cost of the intervention was $18,204 per practice. In post-hoc analysis, level of BH integration was associated with improved patient outcomes independent of the intervention, both at baseline and longitudinally. Conclusions: The specific intervention tested in this study was inexpensive, but had only a small impact on the degree of BH integration, and none on patient outcomes. However, practices that had more integration at baseline had better patient outcomes, independent of the intervention. Although this particular intervention was ineffective, IBH remains an attractive strategy for improving patient outcomes.

Differences in Occupational Burnout Among Primary Care Professionals.

BACKGROUND: Occupational burnout is a major concern for personal well-being and patient care. We examined burnout among primary care providers (PCPs), medical residents, behavioral health providers (BHPs), nurses, and other clinical and nonclinical primary care team members. METHODS: This was a cross-sectional study, nested within a larger randomized trial. Participants completed a validated 9-item burnout measure with 3 domains: depersonalization, emotional exhaustion, and personal accomplishment. Multivariable multilevel linear regression with a random intercept for each practice was used to determine mean differences in burnout across professional roles. RESULTS: Overall burnout rates varied by professional role: PCPs 70%, medical residents 89%, BHPs 59%, nurses 66%, other clinicians 68%, and nonclinical professionals 70%. Compared with nonclinical professionals, residents experienced more burnout in more domains, followed by PCPs. PCPs, residents, and nurses reported significantly worse depersonalization and exhaustion scores. Nonclinical professionals had worse accomplishment scores than all clinical professionals except for residents. This study revealed moderate-to-high levels of burnout among primary care professionals. DISCUSSION: Clinicians may be experiencing aspects of burnout more intensely than their nonclinical colleagues, and this may be most true for residents and PCPs. Based on these variations, interventions to mitigate burnout may need to be tailored by professional role.

A Descriptive analysis of urine drug screen results in patients with opioid use disorder managed in a primary care setting.

BACKGROUND: Urine drug screening (UDS) is commonly used as part of treatment for opioid use disorder (OUD), including treatment with buprenorphine-naloxone for OUD in a primary care setting. Very little is known about the value of UDS, the optimum screening frequency in general, or its specific use for buprenorphine treatment in primary care. To address this question, we thought that in a stable population receiving buprenorphine-naloxone in the primary care setting it would be useful to know how often UDS yielded expected and unexpected results. METHODS: We present a descriptive analysis of UDS results in patients treated with buprenorphine-naloxone for OUD in a primary care setting over a two-year period. An unexpected test result is: 1. A negative test for buprenorphine and/or 2. A positive test for opioids, methadone, cocaine and/or heroin. RESULTS: A total of 161 patients received care during the study period and a total of 2588 test results were analyzed from this population. We found that 64.4% of the patient population (n = 104 patients) demonstrated both treatment adherence (as measured by buprenorphine positive test results) and no apparent unexpected test findings, as defined by negative tests for opioids, methadone, cocaine and heroin. Of the 161 patients, 20 results were positive for opioids, 5 for methadone, 39 for heroin and 2 for cocaine. Analysis at the UDS level demonstrated that, of the 2588 test results, 38 (1.5%) results did not have buprenorphine. Of the 2588, 28 (1.1%) test results were positive for opioids, 8 (0.3%) were positive for methadone, 39 (1.5%) for cocaine and 2 (0.1%) for heroin. CONCLUSION: Given that the majority of patients in our study had expected urine results, it may be reasonable for less frequent urine testing in certain patients.

The Relationship Between Social Determinants of Health and Functional Capacity in Adult Primary Care Patients With Multiple Chronic Conditions.

PURPOSE: Social determinants of health (SDoH) including insecure access to food, housing, and financial resources are critical threats to overall health. We sought to examine this relationship among adult primary care patients with multiple chronic conditions. METHODS: We obtained cross-sectional data on 2763 adults with chronic medical and behavioral conditions or greater than 2 chronic medical conditions from a survey of participants in Integrating Behavioral Health and Primary Care, a multicenter randomized trial. RESULTS: The prevalence of 1 or more insecurities was reported in 29% of participants, including food (13%), housing (3%), or financial (25%). Functional capacity ranged from 2.74 to 9.89 metabolic equivalents (METs) (median, 6.05). The distribution of functional capacity was significantly lower for those with any 1 or more SDoH than for those without. Each insecurity independently affected the functional capacity in multivariable analysis. CONCLUSIONS: Among primary care patients with chronic conditions, SDoH are associated with poorer functional capacity, independent of other social and demographic factors. Primary care offers a promising, if underused, opportunity to intervene in SDoH. There is a need for future studies to explore the role of screening and intervention by primary care providers to mitigate or prevent SDoH.

Integrating Behavioral Health and Primary Care (IBH-PC) to improve patient-centered outcomes in adults with multiple chronic medical and behavioral health conditions: study protocol for a pragmatic cluster-randomized control trial.

BACKGROUND: Chronic diseases that drive morbidity, mortality, and health care costs are largely influenced by human behavior. Behavioral health conditions such as anxiety, depression, and substance use disorders can often be effectively managed. The majority of patients in need of behavioral health care are seen in primary care, which often has difficulty responding. Some primary care practices are providing integrated behavioral health care (IBH), where primary care and behavioral health providers work together, in one location, using a team-based approach. Research suggests there may be an association between IBH and improved patient outcomes. However, it is often difficult for practices to achieve high levels of integration. The Integrating Behavioral Health and Primary Care study responds to this need by testing the effectiveness of a comprehensive practice-level intervention designed to improve outcomes in patients with multiple chronic medical and behavioral health conditions by increasing the practice's degree of behavioral health integration. METHODS: Forty-five primary care practices, with existing onsite behavioral health care, will be recruited for this study. Forty-three practices will be randomized to the intervention or usual care arm, while 2 practices will be considered "Vanguard" (pilot) practices for developing the intervention. The intervention is a 24-month supported practice change process including an online curriculum, a practice redesign and implementation workbook, remote quality improvement coaching services, and an online learning community. Each practice's degree of behavioral health integration will be measured using the Practice Integration Profile. Approximately 75 patients with both chronic medical and behavioral health conditions from each practice will be asked to complete a series of surveys to measure patient-centered outcomes. Change in practice degree of behavioral health integration and patient-centered outcomes will be compared between the two groups. Practice-level case studies will be conducted to better understand the contextual factors influencing integration. DISCUSSION: As primary care practices are encouraged to provide IBH services, evidence-based interventions to increase practice integration will be needed. This study will demonstrate the effectiveness of one such intervention in a pragmatic, real-world setting. TRIAL REGISTRATION: ClinicalTrials.gov NCT02868983 . Registered on August 16, 2016.

High prevalence of injection drug use and blood-borne viral infections among patients in an urban emergency department.

BACKGROUND: The opioid epidemic has led to an increase in the number of persons who inject drugs, and this population accounts for 12% of new human immunodeficiency virus (HIV) and 60% of new hepatitis C virus (HCV) infections in the United States annually. While persons who inject drugs disproportionately utilize the emergency department (ED), accurate data is lacking on the prevalence and patterns of injection drug use, and prevalence of co-occurring HIV and HCV infections among ED patients. OBJECTIVE: The primary outcome was to assess the prevalence of injection drug use and co-occurring HIV and HCV infection among patients presenting to an urban ED. METHODS: This was a cross sectional study conducted at an urban ED, with an annual census of 65,000 visits. A closed-response questionnaire was developed based on publicly available validated surveys to assess patterns of injection drug use and HIV and HCV infection status, and administered by trained research assistants to all registered adult patients during 4-hour blocks of time. RESULTS: Of the 2,319 eligible patients, 2,200 (94.9%) consented and completed the survey. 241 (11.0%) had ever used injection drugs, 103 (4.7%) currently used injection drugs, and 138 (6.3%) formerly used injection drugs. White patients age 25 to 34 years and white patients age 55 to 64 years had the highest prevalence of current (25.6%) and former (27.1%) injection drug use, respectively. Persons who use injection drugs had a higher prevalence of HCV infection (52.7% vs. 3.4%) and HIV infection (6.2% vs. 1.8%) than the rest of the population. CONCLUSION: A high prevalence of ED patients report injection drug use, and this population self-reports a high prevalence of HIV and HCV infection. Emergency departments are in a unique position to engage with this population with regards to substance use treatment and linkage to care for HIV and HCV infection.

The Association between Serum Magnesium Levels and Depression in an Adult Primary Care Population.

Depression is common, places a large burden on the patient, their family and community, and is often difficult to treat. Magnesium supplementation is associated with improved depressive symptoms, but because the mechanism is unknown, it is unclear whether serum magnesium levels act as a biological predictor of the treatment outcome. Therefore, we sought to describe the relationship between serum magnesium and the Patient Health Questionnaire (PHQ, a measure of depression) scores. A cross-sectional analysis of medical records from 3604 adults (mean age 62 years; 42% men) seen in primary care clinics between 2015 and 2018, with at least one completed PHQ were included. The relationship between serum magnesium and depression using univariate analyses showed a significant effect when measured by the PHQ-2 (-0.19 points/mg/dL; 95% CI -0.31, -0.07; P = 0.001) and the PHQ-9 (-0.93 points/mg/dL; 95% CI -1.81, -0.06; P = 0.037). This relationship was strengthened after adjusting for covariates (age, gender, race, time between serum magnesium and PHQ tests, and presence of diabetes and chronic kidney disease) (PHQ-2: -0.25 points/mg/dL; 95% CI -3.33, -0.09; P < 0.001 and PHQ-9: -1.09 95% CI -1.96 -0.21; P = 0.015). For adults seen in primary care, lower serum magnesium levels are associated with depressive symptoms, supporting the use of supplemental magnesium as therapy. Serum magnesium may help identify the biological mechanism of depressive symptoms and identify patients likely to respond to magnesium supplementation.

Adiposity, but not Obesity, Is Associated With Arterial Stiffness in Young Nulliparous Women.

Subclinical vascular dysfunction is increasingly recognized as an independent risk factor for cardiovascular events and adverse pregnancy outcomes. The evidence linking indices of obesity and vascular dysfunction is mixed. As an example, some data suggest that adiposity may be a better predictor of endothelial dysfunction than body mass index (BMI). The aim of the current study is to compare the association of obesity, as evaluated by BMI, and a direct measure of body fat to biophysical parameters of vascular function including flow-mediated vasodilation and pulse wave velocity (PWV) in healthy nulliparous reproductive-age women. This is a secondary analysis of data collected as a prospective study of prepregnancy physiology in healthy, nulliparous women. Body mass index was calculated as weight (kg)/height (m2). Total and android body fat were calculated by dual-energy X-ray absorptiometry. Brachial PWV and flow-mediated vasodilation were assessed ultrasonographically. Seventy-nine women were evaluated. Mean BMI was 24.4 (5.4) kg/m2, and 15% of women were obese (BMI ≥ 30 kg/m2). In contrast, 39% were considered to have excess adiposity, with ≥39% android body fat. Brachial PWV was associated with increased adiposity, but not obesity. We found no differences in flow-mediated dilation associated with either BMI or body fat. Adiposity may be superior to BMI in identifying women with vascular dysfunction at increased risk of adverse pregnancy outcome and cardiovascular disease. Proper identification may allow implementation of prevention strategies to improve perinatal outcomes and maternal health.

Racial Differences in 20-Year Cardiovascular Mortality Risk Among Childhood and Young Adult Cancer Survivors.

PURPOSE: Whether cardiovascular disease (CVD) risk differs according to race and cancer type among survivors of childhood or young adulthood cancers is unknown. METHODS: Data from the years 1973-2011 were analyzed using the Surveillance, Epidemiology, and End Results (SEER) registries. Cases were categorized by ICD-0-3/WHO 2008 Adolescent and Young Adult classification. CVD death was determined by ICD-10 codes for diseases of the heart, atherosclerosis, cerebrovascular diseases, or other diseases of the arteries. Cox proportional hazards models were fitted to evaluate the hazard ratio (HR) and 95% confidence intervals (CIs) for the effects of race on time-to-event outcomes. RESULTS: A total of 164,316 cases of childhood and young adult primary cancers were identified. There were 43,335 total and 1466 CVD deaths among Black and White survivors. Black survivors had higher risks of all-cause mortality (HR: 1.75, 95% CI: 1.70-1.7) and CVD mortality (HR: 2.13, 95% CI: 1.85-2.46) compared to White survivors. The increased risk of CVD for Black survivors compared to White survivors persisted at 5-years (HR: 2.38, 95% CI: 1.83-3.10), 10-years (HR: 2.59, 95% CI: 2.09-3.21), and 20-years (HR: 2.31, 95% CI: 1.95-2.74) postdiagnosis, and varied by cancer type, with the highest HRs for melanoma (HR: 8.16, 95% CI: 1.99-33.45) and thyroid cancer (HR: 3.43, 95% CI: 1.75-6.73). CONCLUSIONS: Black survivors of childhood or young adulthood cancers have a higher risk of CVD mortality compared to Whites that varies by cancer type. Knowledge of at-risk populations is important to guide surveillance recommendations and behavioral interventions. Further study is needed to understand the etiology of racial differences in CVD mortality in this population.

The Effect of Atorvastatin on Breast Cancer Biomarkers in High-Risk Women.

Statins have the potential to reduce breast cancer incidence and recurrence as shown in both epidemiologic and laboratory studies. The purpose of this study was to evaluate the effect of a lipophilic statin, atorvastatin, on breast cancer biomarkers of risk [mammographic density (MD) and insulin growth factor 1 (IGF-1)] in high-risk premenopausal women.Premenopausal women at increased risk for breast cancer received either 40 mg of atorvastatin or placebo for 1 year. Biomarker assessment was performed prior to initiation and at completion of study medication. MD was determined using both Breast Imaging Reporting and Data System and the visual analogue scale. Serum IGF-1 was determined by ELISA assay at the end of the study.Sixty-three women were enrolled between December 2005 and May 2010. Sixteen (25%) women withdrew. The mean age of participants was 43 (range, 35-50), 100% were white, and the average body mass index (BMI) was 26.4. The statin group demonstrated a significant decrease in cholesterol and low-density lipoprotein (LDL), suggesting compliance with study medication. After accounting for BMI, there was no difference in change in MD between groups. There was a significant increase in serum IGF-1 in the statin group.In this multi-institutional randomized prospective clinical trial of premenopausal women at increased risk for breast cancer, we did not see an effect of atorvastatin on MD. Further investigation of statins may be warranted; however, design of prior trials and potential mechanism of action of the agent need to be considered in the design of future trials. Cancer Prev Res; 9(5); 379-84. ©2016 AACR.

Methadone and buprenorphine for opioid dependence during pregnancy: a retrospective cohort study.

OBJECTIVES: To compare maternal characteristics, prenatal care, and newborn outcomes in a cohort of opioid-dependent pregnant women treated with methadone versus buprenorphine. METHODS: In a retrospective cohort study, 609 pregnant, opioid-dependent women were treated with methadone (n = 248) or buprenorphine (n = 361) between 2000 and 2012 at a single institution. RESULTS: Mothers treated with buprenorphine were more likely to start medication before or earlier in pregnancy, had longer gestation, and gave birth to larger infants. Newborns of buprenorphine- versus methadone-maintained mothers required treatment for neonatal abstinence significantly less often and for a shorter duration. CONCLUSIONS: These data suggest pregnancy outcomes with buprenorphine to treat opioid dependence during pregnancy in clinical practice are as good and often better than outcomes with methadone. These results are consistent with efficacy data from randomized clinical trials and further support the use of buprenorphine for the treatment of opioid dependence during pregnancy.

Ductal lavage of cancerous and unaffected breasts: procedure success rate and cancer detection.

OBJECTIVE: To evaluate ductal lavage (DL) performance in women with known breast cancer and to assess cell yield from contralateral high-risk breasts. STUDY DESIGN: Women with newly diagnosed breast cancer were offered study participation. They underwent bilateral nipple aspiration, followed by DL of those ducts demonstrating nipple aspiration fluid (NAF) production. The procedures were conducted in the operating room prior to definitive surgery. Samples were interpreted masked as to which breast was malignant, and the interpretation used a 5-category scheme: insufficient, benign, mildly atypical, markedly atypical or malignant. RESULTS: A total of 23 women with 24 cancers were enrolled, ranging in age from 32 to 76. One had ductal carcinoma in situ; there were 13 T1, 6 T2 and 4 T3 lesions. NAF was identified in 72% of breasts, more commonly in cancerous than unaffected breasts. DL was performed on 33 breasts; of these, 55% were adequate. Only 16.6% of samples from malignant breasts contained abnormality, marked atypia in 1 and malignancy in 3. No samples from unaffected breasts demonstrated cellular abnormalities. CONCLUSION: The low sensitivity of DL performed on malignant breasts to identify abnormal cells adds to the growing body of evidence that this is not an effective tool in identifying existing breast cancer. Numbers are small, but the ability of DL to identify atypia in unaffected high-risk breasts may also be suboptimal. Future efforts should focus on molecular markers of risk and on alternate means of cell or tissue retrieval.

Molecular signatures suggest a major role for stromal cells in development of invasive breast cancer.

BACKGROUND: Breast cancer invasion and metastasis involves both epithelial and stromal changes. Our objective was to delineate the pivotal role stroma plays in invasion by comparing transcriptomes among stromal and epithelial cells in normal tissue and invasive breast cancer. METHODS: Total RNA was isolated from epithelial and stromal cells that were laser captured from normal breast tissue (n = 5) and invasive breast cancer (n = 28). Gene expression was measured using Affymetrix U133A 2.0 GeneChips. Differential gene expression was evaluated and compared within a model that accounted for cell type (epithelial [E] versus stromal [S]), diagnosis (cancer [C] versus normal [N]) as well as cell type-diagnosis interactions. RESULTS: Compared to NE, the CE transcriptome was highly enriched with genes in proliferative, motility and ECM ontologies. Differences in CS and NS transcriptomes suggested that the ECM was being remodeled in invasive breast cancer, as genes were over-represented in ECM and proteolytic ontologies. Genes more highly expressed in CS compared to CE were primarily ECM components or were involved in the remodeling of ECM, suggesting that ECM biosynthesis and remodeling were initiated in the tumor stroma. CONCLUSION: Based on identified molecular cross-talk between the two contiguous cell populations, a mechanistic model that spurs invasion is proposed, that shows breast cancer invasion proceeds through the acquisition of a motile phenotype in tumor epithelial cells and a reactive phenotype in cancer associated fibroblasts.