Safety, timing, and outcomes of early post-operative cardiac catheterisation following congenital heart surgery.

OBJECTIVE: The safety of early post-operative cardiac catheterisation has been described following congenital heart surgery. Optimal timing of early post-operative cardiac catheterisation remains uncertain. The aim of this study was to describe the safety of early post-operative cardiac catheterisation and its impact on cardiac ICU and hospital length of stay, duration of mechanical ventilation, and extracorporeal support. METHODS: This single-centre retrospective cohort study compared clinical and outcome variables between "early" early post-operative cardiac catheterisation (less than 72 hours after surgery) and "late" early post-operative cardiac catheterisation (greater than 72 hours after surgery) groups using Chi-squared, Student's t, and log-rank test (or appropriate nonparametric test). RESULTS: In total, 132 patients were included, 22 (16.7%) "early" early post-operative cardiac catheterisation, and 110 (83.3%) "late" early post-operative cardiac catheterisation. Interventions were performed in 63 patients (51.5%), 7 (11.1%) early and 56 (88.9%) late. Complications of catheterisation occurred in seven (5.3%) patients, two early and five late. There were no major complications. Patients in the late group trended towards a longer stay in the cardiac ICU (19 days [7, 62] versus 11.5 days [7.2, 31.5], p = 0.6) and in the hospital (26 days [9.2, 68] versus 19 days [13.2, 41.8], p = 0.8) compared to the earlier group. CONCLUSION: "Early" early post-operative cardiac catheterisation was associated with an overall low rate of complications. Earlier catheterisations trended towards shorter cardiac ICU and hospital length of stays. Earlier catheterisations may lead to earlier recovery for patients not following an expected post-operative course.

Oxygenation index in the first three weeks of life is a predictor of bronchopulmonary dysplasia grade in very preterm infants.

BACKGROUND: The new bronchopulmonary dysplasia (BPD) grading system was developed based on its correlation with long-term respiratory and neurodevelopmental outcomes and may provide better personalized prognostication. Identifying early-life predictors for accurate BPD grade prediction may allow interventions to be tailored to individual needs. This study aimed to assess whether oxygenation index (OI) dynamics in the first three weeks of life are a predictor of BPD grade. METHODS: A single-center retrospective study was performed. Generalized additive mixed modeling was used to model OI trajectories for each BPD grade subgroup. A multinomial regression model was then developed to quantify the association between OI dynamics and BPD grade. RESULTS: Two hundred fifty-four infants were identified for inclusion in the trajectory modeling. A total of 6,243 OI data points were available for modeling. OI trajectory estimates showed distinct patterns in the three groups, most prominent during the third week of life. The average daily OI change was -0.33 ± 0.52 (n = 85) in the No-BPD group, -0.04 ± 0.75 (n = 82) in the Low-Grade BPD group, and 0.22 ± 0.65 (n = 75) in the High-Grade BPD group (p < 0.001). A multinomial regression analysis showed the initial OI value and the average daily OI change both independently correlated with BPD grade outcomes after adjusting for birth gestation, birth weight z-score, sex, and the duration of invasive ventilation. CONCLUSION: Early-life OI dynamics may be a useful independent marker for BPD grade prediction. Prospective studies may be warranted to further validate the findings.

Quantitative clinical outcomes of therapy for head and neck lymphedema.

PURPOSE: Head and neck surgery and radiation cause tissue fibrosis that leads to functional limitations and lymphedema. The objective of this study was to determine whether lymphedema therapy after surgery and radiation for head and neck cancer decreases neck circumference, increases cervical range of motion, and improves pain scores. METHODS AND MATERIALS: A retrospective review of all patients with squamous cell carcinoma of the oral cavity, oropharynx, or larynx who were treated with high-dose radiation therapy at a single center between 2011 and 2012 was performed. Patients received definitive or postoperative radiation for squamous cell carcinoma of the oral cavity, oropharynx, or larynx. Patients were referred to a single, certified, lymphedema therapist with specialty training in head and neck cancer after completion of radiation treatment and healing of acute toxicity (typically 1-3 months). Patients underwent at least 3 months of manual lymphatic decongestion and skilled fibrotic techniques. Circumferential neck measurements and cervical range of motion were measured clinically at 1, 3, 6, 9, and 12 months after completion of radiation therapy. Pain scores were also recorded. RESULTS: Thirty-four consecutive patients were eligible and underwent a median of 6 months of lymphedema therapy (Range, 3-12 months). Clinically measured total neck circumference decreased in all patients with 1 month of treatment. Cervical rotation increased by 30.2% on the left and 27.9% on the right at 1 month and continued to improve up to 44.6% and 55.3%, respectively, at 12 months. Patients undergoing therapy had improved pain scores from 4.3 at baseline to 2.0 after 1 month. CONCLUSIONS: Lymphedema therapy is associated with objective improvements in range of motion, neck circumference, and pain scores in the majority of patients.

Randomized trial of vitamin D3 to prevent worsening of musculoskeletal symptoms in women with breast cancer receiving adjuvant letrozole. The VITAL trial.

PURPOSE: Aromatase inhibitor-associated musculoskeletal symptoms (AIMSS) frequently occur in women being treated for breast cancer. Prior studies suggest high prevalence of vitamin D deficiency in breast cancer patients with musculoskeletal (MS) pain. We conducted a randomized, placebo-controlled trial to determine if 30,000 IU vitamin D3 per week (VitD3) would prevent worsening of AIMSS in women starting adjuvant letrozole for breast cancer. METHODS: Women with stage I-III breast cancer starting adjuvant letrozole and 25(OH)D level ≤40 ng/ml were eligible. All subjects received standard daily supplement of 1200 mg calcium and 600 IU vitamin D3 and were randomized to 30,000 IU oral VitD3/week or placebo. Pain, disability, fatigue, quality of life, 25(OH)D levels, and hand grip strength were assessed at baseline, 12, and 24 weeks. The primary endpoint was incidence of an AIMSS event. RESULTS: Median age of the 160 subjects (80/arm) was 61. Median 25OHD (ng/ml) was 25 at baseline, 32 at 12 weeks, and 31 at 24 weeks in the placebo arm and 22, 53, and 57 in the VitD3 arm. There were no serious adverse events. At week 24, 51% of women assigned to placebo had a protocol defined AIMSS event (worsening of joint pain using a categorical pain intensity scale (CPIS), disability from joint pain using HAQ-II, or discontinuation of letrozole due to MS symptoms) vs. 37% of women assigned to VitD3 (p = 0.069). When the brief pain inventory (BPI) was used instead of CPIS, the difference was statistically significant: 56 vs. 39% (p = 0.024). CONCLUSIONS: Although 30,000 IU/week of oral vitamin D3 is safe and effective in achieving adequate vitamin D levels, it was not associated with a decrease in AIMSS events based on the primary endpoint. Post-hoc analysis using a different tool suggests potential benefit of vitamin D3 in reducing AIMSS.

All Nations Breath of Life: A Randomized Trial of Smoking Cessation for American Indians.

INTRODUCTION: American Indians have the highest cigarette smoking prevalence of any racial/ethnic group in the U.S. There is currently no effective empirically based smoking-cessation program for American Indians. The purpose of this study was to determine if a culturally tailored smoking-cessation program, All Nations Breath of Life (ANBL), is more effective than a non-tailored cessation program among American Indian smokers. DESIGN: A multisite RCT was conducted from September 2009 to July 2014; analysis was conducted in 2015. SETTING/PARTICIPANTS: Participants were rural or reservation-based American Indian smokers aged ≥18 years. INTERVENTION: Smokers were group randomized to either the culturally tailored ANBL or non-tailored current best practices (CBP) for a total enrolled sample size of 463 (ANBL, n=243; CBP, n=220). MAIN OUTCOME MEASURES: The primary outcome of interest was salivary cotinine-verified 7-day point prevalence smoking abstinence at 6 months. Results for both responder-only and intent-to-treat analyses for self-reported and cotinine-verified abstinence are presented. RESULTS: Intention-to-treat, imputing all non-responses as smokers, the self-reported point prevalence abstinence rates at 12 weeks were 27.9% in the ANBL arm and 17.4% in the CBP arm (p=0.028). There was a statistically significant difference in self-reported 6-month intent-to-treat point prevalence abstinence rates between ANBL (20.1%) and CBP (12.0%) arms (p=0.029). None of the cotinine-verified results were statistically significant. CONCLUSIONS: The culturally tailored smoking-cessation program ANBL may or may not be an effective program in promoting cessation at 12 weeks and 6 months. Participants in the culturally tailored ANBL program were approximately twice as likely to quit smoking at 6 months compared with the CBP program, using self-reported abstinence.

Expression profiling of in vivo ductal carcinoma in situ progression models identified B cell lymphoma-9 as a molecular driver of breast cancer invasion.

INTRODUCTION: There are an estimated 60,000 new cases of ductal carcinoma in situ (DCIS) each year. A lack of understanding in DCIS pathobiology has led to overtreatment of more than half of patients. We profiled the temporal molecular changes during DCIS transition to invasive ductal carcinoma (IDC) using in vivo DCIS progression models. These studies identified B cell lymphoma-9 (BCL9) as a potential molecular driver of early invasion. BCL9 is a newly found co-activator of Wnt-stimulated ß-catenin-mediated transcription. BCL9 has been shown to promote progression of multiple myeloma and colon carcinoma. However BCL9 role in breast cancer had not been previously recognized. METHODS: Microarray and RNA sequencing were utilized to characterize the sequential changes in mRNA expression during DCIS invasive transition. BCL9-shRNA knockdown was performed to assess the role of BCL9 in in vivo invasion, epithelial-mesenchymal transition (EMT) and canonical Wnt-signaling. Immunofluorescence of 28 patient samples was used to assess a correlation between the expression of BCL9 and biomarkers of high risk DCIS. The cancer genome atlas data were analyzed to assess the status of BCL9 gene alterations in breast cancers. RESULTS: Analysis of BCL9, by RNA and protein showed BCL9 up-regulation to be associated with DCIS transition to IDC. Analysis of patient DCIS revealed a significant correlation between high nuclear BCL9 and pathologic characteristics associated with DCIS recurrence: Estrogen receptor (ER) and progesterone receptor (PR) negative, high nuclear grade, and high human epidermal growth factor receptor2 (HER2). In vivo silencing of BCL9 resulted in the inhibition of DCIS invasion and reversal of EMT. Analysis of the TCGA data showed BCL9 to be altered in 26 % of breast cancers. This is a significant alteration when compared to HER2 (ERBB2) gene (19 %) and estrogen receptor (ESR1) gene (8 %). A significantly higher proportion of basal like invasive breast cancers compared to luminal breast cancers showed BCL9 amplification. CONCLUSION: BCL9 is a molecular driver of DCIS invasive progression and may predispose to the development of basal like invasive breast cancers. As such, BCL9 has the potential to serve as a biomarker of high risk DCIS and as a therapeutic target for prevention of IDC.

Resting-state brain connectivity after surgical and behavioral weight loss.

OBJECTIVE: Changes in food-cue neural reactivity associated with behavioral and surgical weight loss interventions have been reported. Resting functional connectivity represents tonic neural activity that may contribute to weight loss success. This study explores whether intervention type is associated with differences in functional connectivity after weight loss. METHODS: Fifteen participants with obesity were recruited prior to adjustable gastric banding surgery. Thirteen demographically matched participants with obesity were selected from a separate behavioral diet intervention. Resting-state functional magnetic resonance imaging was collected 3 months after surgery/behavioral intervention. ANOVA was used to examine post-weight loss differences between the two groups in connectivity to seed regions previously identified as showing differential cue-reactivity after weight loss. RESULTS: Following weight loss, behavioral dieters exhibited increased connectivity between left precuneus/superior parietal lobule (SPL) and bilateral insula pre- to postmeal and bariatric patients exhibited decreased connectivity between these regions pre- to postmeal (P(corrected) <0.05). CONCLUSIONS: Behavioral dieters showed increased connectivity pre- to postmeal between a region associated with processing of self-referent information (precuneus/SPL) and a region associated with interoception (insula) whereas bariatric patients showed decreased connectivity between these regions. This may reflect increased attention to hunger signals following surgical procedures and increased attention to satiety signals following behavioral diet interventions.

Investigating and predicting early lumbar spine surgery outcomes.

OBJECTIVE: To examine short-term changes in patients' clinical status following lumbar spine surgery (LSS) and to explore presurgical variables that predict surgical outcomes. METHODS: Prospective cohort study. A total of 46 patients underwent LSS. Patients completed the following questionnaires 1 week before LSS and 2 weeks after discharge from the hospital: back and leg visual pain analogue scale, Ronald Morris questionnaire (RMQ), Modified Somatic Perception questionnaire (MSPQ), SF-36, Fear-Avoidance Beliefs Questionnaire, Beck's Depression Inventory, EuroQol questionnaire, and patient-perception of improvement. Regression models were constructed to examine predictors of pain, function, quality of life, and patient-perception of improvement at 2 weeks postsurgery. RESULTS: Patients demonstrated significant improvement in back and leg pain and function. MSPQ and symptom duration were significant predictors of back pain, while type of diagnosis and use of opioids were significant predictors of leg pain. Preoperative MSPQ and RMQ were significant predictors of postoperative RMQ. MSPQ, gender, and back pain were significant predictors of quality of life. Back pain, leg pain, depression, smoking, and worker's compensation were significantly associated with patient-perception of improvement. CONCLUSIONS: This preliminary study could be viewed as a directory to identify potential risk factors for unfavorable outcomes at early stages following LSS.

Structural equation model analysis of the length-of-hospital stay after lumbar spine surgery.

BACKGROUND CONTEXT: Length-of-hospital stay (LOS) after lumbar spine surgery (LSS) can be affected by many factors. However, few studies have evaluated predictors of LOS, and all have used limited number of variables as predictors. PURPOSE: The purpose of the study was to identify presurgical, surgical, and postsurgical predictors of LOS after LSS. STUDY DESIGN/SETTING: Retrospective review of consecutive patients who had LSS at the University of Kansas Hospital from October 2008 to April, 2012. PATIENT SAMPLE: Five hundred ninety-three patients underwent LSS consisting of laminotomy, laminectomy, or arthrodesis. DEPENDENT VARIABLE: LOS. Multiple presurgical, surgical, and postsurgical variables were extracted from the patients' medical records and considered as possible predictors (independent variables) of LOS. METHODS: Potential predictors that were significantly correlated with LOS were used as indicators to construct three latent factors presurgical, surgical, and postsurgical, which were in turn used to predict LOS in a structural equation model. RESULTS: The average LOS was 4.01±2.73 days. The presurgical factor was indicated by age (61.97±14.49 years), previous level of function (60.5% were totally independent), previous hemoglobin level (13.70±1.36 mg/dL), and use of assistive devices (60% were assistive device users). The surgical factor was indicated by severity of illness (50.2% had minor disease severity), presence of complications (1.9%), and stay in an intensive care unit (4.0%). The postsurgical factor was indicated by postsurgical walking distance (166.43±175.75 ft), level of assistance during walking (5.18±0.81 out of 7 points), balance scores (6.18±1.82 out of 10 points), and bed mobility and transfer dependency scores (9.81±1.99 out of 14 points). These three latent factors explained 47% of variation in LOS. CONCLUSIONS: Postsurgical factors predicted the highest variation in LOS in comparison with presurgical and surgical factors and should be taken into consideration for discharge planning. Postsurgical factors are related to the patient's function, modifiable with rehabilitation, and can be improved to shorten LOS. Inclusion of more reliable and standardized presurgical variables could improve the predictability of the model.

Implementation intentions and colorectal screening: a randomized trial in safety-net clinics.

CONTEXT: Low-income and racial/ethnic minority populations experience disproportionate colorectal cancer (CRC) burden and poorer survival. Novel behavioral strategies are needed to improve screening rates in these groups. BACKGROUND: The study aimed to test a theoretically based "implementation intentions" intervention for improving CRC screening among unscreened adults in urban safety-net clinics. DESIGN: Randomized controlled trial. SETTING/PARTICIPANTS: Adults (N=470) aged ≥50 years, due for CRC screening, from urban safety-net clinics were recruited. INTERVENTION: The intervention (conducted in 2009-2011) was delivered via touchscreen computers that tailored informational messages to decisional stage and screening barriers. The computer then randomized participants to generic health information on diet and exercise (Comparison group) or "implementation intentions" questions and planning (Experimental group) specific to the CRC screening test chosen (fecal immunochemical test or colonoscopy). MAIN OUTCOME MEASURES: The primary study outcome was completion of CRC screening at 26 weeks based on test reports (analysis conducted in 2012-2013). RESULTS: The study population had a mean age of 57 years and was 42% non-Hispanic African American, 28% non-Hispanic white, and 27% Hispanic. Those receiving the implementation intentions-based intervention had higher odds (AOR=1.83, 95% CI=1.23, 2.73) of completing CRC screening than the Comparison group. Those with higher self-efficacy for screening (AOR=1.57, 95% CI=1.03, 2.39), history of asthma (AOR=2.20, 95% CI=1.26, 3.84), no history of diabetes (AOR=1.86, 95% CI=1.21, 2.86), and reporting they had never heard that "cutting on cancer" makes it spread (AOR=1.78, 95% CI=1.16, 2.72) were more likely to complete CRC screening. CONCLUSIONS: The results of this study suggest that programs incorporating an implementation intentions approach can contribute to successful completion of CRC screening even among very low-income and diverse primary care populations. Future initiatives to reduce CRC incidence and mortality disparities may be able to employ implementation intentions in large-scale efforts to encourage screening and prevention behaviors.

Sorting it Out: Pile Sorting as a Mixed Methodology for Exploring Barriers to Cancer Screening.

We discuss a mixed methodology for analyzing pile sorting data. We created a list of 14 barriers to colon cancer screening and recruited 18, 13, and 14 participants from three American Indian (AI) communities to perform pile sorting. Quantitative data were analyzed by cluster analysis and multidimensional scaling. Differences across sites were compared using permutation bootstrapping. Qualitative data collected during sorting were compiled by AI staff members who determined names for the clusters found in quantitative analysis. Results showed 5 clusters of barriers in each site although barriers in the clusters varied slightly across sites. Simulation demonstrated type I error rates around the nominal 0.05 level whereas power depended on the numbers of clusters, and between and within cluster variability.

Favorable modulation of benign breast tissue and serum risk biomarkers is associated with > 10 % weight loss in postmenopausal women.

We conducted a phase II feasibility study of a 6-month behavioral weight loss intervention in postmenopausal overweight and obese women at increased risk for breast cancer and the effects of weight loss on anthropomorphic, blood, and benign breast tissue biomarkers. 67 women were screened by random peri-areolar fine-needle aspiration, 27 were registered and 24 participated in the interventional phase. The 24 biomarker evaluable women had a median baseline BMI of 34.2 kg/m(2) and lost a median of 11 % of their initial weight. Significant tissue biomarker modulation after the 6-month intervention was noted for Ki-67 (if restricted to the 15 women with any Ki-67 at baseline, p = 0.041), adiponectin to leptin ratio (p = 0.003); and cyclin B1 (p = 0.001), phosphorylated retinoblastoma (p = 0.005), and ribosomal S6 (p = 0.004) proteins. Favorable modulation for serum markers was observed for sex hormone-binding globulin (p < 0.001), bioavailable estradiol (p < 0.001), bioavailable testosterone (p = 0.033), insulin (p = 0.018), adiponectin (p = 0.001), leptin (p < 0.001), the adiponectin to leptin ratio (p < 0.001), C-reactive protein (p = 0.002), and hepatocyte growth factor (p = 0.011). When subdivided by <10 or >10 % weight loss, change in percent total body and android (visceral) fat, physical activity, and the majority of the serum and tissue biomarkers were significantly modulated only for women with >10 % weight loss from baseline. Some factors such as serum PAI-1 and breast tissue pS2 (estrogen-inducible gene) mRNA were not significantly modulated overall but were when considering only those with >10 % weight loss. In conclusion, a median weight loss of 11 % over 6 months resulted in favorable modulation of a number of anthropomorphic, breast tissue and serum risk and mechanistic markers. Weight loss of 10 % or more should likely be the goal for breast cancer risk reduction studies in obese women.

A Bayesian model for censored positive count data in evaluating breast cancer progression.

Basic science researchers transplant human cancer tissues from patients with ductal carcinoma in situ (DCIS) to animals and observe the progression of the disease. Successful transplants show invasion of human tissues across mammary ducts in animal fat pads and cause DCIS-like lesions in one or more ducts. In this work, we consider data from a recent publication of breast cancer research where positive counts of affected ducts may be subject to censoring. We fit the data with zero-truncated Poisson (ZTP) models with an informative prior of gamma. Due to the zero-truncation and right censoring, posterior distributions may not be conventional gamma and are estimated through Markov chain Monte Carlo and grid approximation. For each of the two cell lines, we fit a model with group-specific parameters for DCIS subtypes classified by the cell surface biomarkers, and another model with a homogeneous parameter across groups. Models are compared by the Deviance Information Criterion (DIC). For the chosen prior parameter values, Bayes estimates are comparative to the maximum likelihood estimates, and the DIC favors the simpler model in both cell lines.

The Zero-truncated Poisson with Right Censoring: an Application to Translational Breast Cancer Research.

We propose to analyze positive count data with right censoring from Behbod et al. (2009) using the censored zero-truncated Poisson model (CZTP). The comparison in truncated means across subgroups in each cell line is carried out through a log-linear model that links the un-truncated Poisson parameter and regression covariates. We also perform simulation to evaluate the performance of the CZTP model in finite and large sample sizes. In general, the CZTP model provides accurate and precise estimates. However, for data with small means and small sample sizes, it may be more proper to make inference based on the mean counts rather than on the regression coefficients. For small sample sizes and moderate means, the likelihood ratio test is more reliable than the Wald test. We also demonstrate how power analysis can be used to justify and/or guide the choice of censoring thresholds in study design. A SAS macro is provided in Appendix for readers' reference.

Simultaneous evaluation of abstinence and relapse using a Markov chain model in smokers enrolled in a two-year randomized trial.

BACKGROUND: GEE and mixed models are powerful tools to compare treatment effects in longitudinal smoking cessation trials. However, they are not capable of assessing the relapse (from abstinent back to smoking) simultaneously with cessation, which can be studied by transition models. METHODS: We apply a first-order Markov chain model to analyze the transition of smoking status measured every 6 months in a 2-year randomized smoking cessation trial, and to identify what factors are associated with the transition from smoking to abstinent and from abstinent to smoking. Missing values due to non-response are assumed non-ignorable and handled by the selection modeling approach. RESULTS: Smokers receiving high-intensity disease management (HDM), of male gender, lower daily cigarette consumption, higher motivation and confidence to quit, and having serious attempts to quit were more likely to become abstinent (OR = 1.48, 1.66, 1.03, 1.15, 1.09 and 1.34, respectively) in the next 6 months. Among those who were abstinent, lower income and stronger nicotine dependence (OR = 1.72 for ≤ vs. > 40 K and OR = 1.75 for first cigarette ≤ vs. > 5 min) were more likely to have relapse in the next 6 months. CONCLUSIONS: Markov chain models allow investigation of dynamic smoking-abstinence behavior and suggest that relapse is influenced by different factors than cessation. The knowledge of treatments and covariates in transitions in both directions may provide guidance for designing more effective interventions on smoking cessation and relapse prevention.

Effects of acute and chronic hyperglycemia on the neurochemical profiles in the rat brain with streptozotocin-induced diabetes detected using in vivo ¹H MR spectroscopy at 9.4 T.

Chronic hyperglycemia could lead to cerebral metabolic alterations and CNS injury. However, findings of metabolic alterations in poorly managed diabetes in humans and animal models are rather inconsistent. We have characterized the cerebral metabolic consequences of untreated hyperglycemia from the onset to the chronic stage in a streptozotocin-induced rat model of diabetes. In vivo ¹H magnetic resonance spectroscopy was used to measure over 20 neurochemicals longitudinally. Upon the onset of hyperglycemia (acute state), increases in brain glucose levels were accompanied by increases in osmolytes and ketone bodies, all of which remained consistently high through the chronic state of over 10 weeks of hyperglycemia. Only after over 4 weeks of hyperglycemia, the levels of other neurochemicals including N-acetylaspartate and glutathione were significantly reduced and these alterations persisted into the chronic stage. However, glucose transport was not altered in chronic hyperglycemia of over 10 weeks. When glucose levels were acutely restored to euglycemia, some neurochemical changes were irreversible, indicating the impact of prolonged uncontrolled hyperglycemia on the CNS. Furthermore, progressive changes in neurochemical levels from control to acute and chronic conditions demonstrated the utility of ¹H magnetic resonance spectroscopy as a non-invasive tool in monitoring the disease progression in diabetes.

Culturally-tailored smoking cessation for American Indians: study protocol for a randomized controlled trial.

BACKGROUND: Cigarette smoking is the number one cause of preventable death among American Indian and Alaska Natives, AI/ANs. Two out of every five AI/AN will die from tobacco-related diseases if the current smoking rates of AI/ANs (40.8%) persist. Currently, there is no proven, effective culturally-tailored smoking cessation program designed specifically for a heterogeneous population of AI.The primary aim of this group randomized clinical trial is to test the efficacy of "All Nations Breath of Life" (ANBL) program compared to a non-tailored "Current Best Practices" smoking cessation program among AI smokers. METHODS: We will randomize 56 groups (8 smokers per group) to the tailored program or non-tailored program for a total sample size of 448 American Indian smokers. All participants in the proposed study will be offered pharmacotherapy, regardless of group assignment. This study is the first controlled trial to examine the efficacy of a culturally-tailored smoking cessation program for American Indians. If the intervention is successful, the potential health impact is significant because the prevalence of smoking is the highest in this population. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01106456.

A randomized controlled trial of breastfeeding support and education for adolescent mothers.

Despite substantial evidence of maternal and infant benefits of breastfeeding, adolescent mothers initiate breastfeeding less often and maintain breastfeeding for shorter durations when compared to their adult counterparts. A randomized controlled trial drawing on the theory of planned behavior and developmental theory was conducted to determine if an education and counseling intervention provided by a lactation consultant-peer counselor team increased breastfeeding initiation and duration up to 6 months postpartum among adolescent mothers. Study participants ( N = 289) enrolled from multiple prenatal clinic and school settings, were 15 to 18 years old, and predominately African American, single, and primiparous. The intervention, which started in the second trimester of pregnancy and extended through 4 weeks postpartum, positively influenced breastfeeding duration (p < .001) within the experimental group, but not breastfeeding initiation or exclusive breastfeeding rates. This education/support intervention was partially effective in enhancing breastfeeding outcomes. Implications for research and practice are described.

Reduction in Ki-67 in benign breast tissue of high-risk women with the lignan secoisolariciresinol diglycoside.

Preclinical and correlative studies suggest reduced breast cancer with higher lignan intake or blood levels. We conducted a pilot study of modulation of risk biomarkers for breast cancer in premenopausal women after administration of the plant lignan secoisolariciresinol given as the diglycoside (SDG). Eligibility criteria included regular menstrual cycles, no oral contraceptives, a >3-fold increase in 5-year risk, and baseline Ki-67 of ≥2% in areas of hyperplasia in breast tissue sampled by random periareolar fine-needle aspiration (RPFNA) during the follicular phase of the menstrual cycle. SDG (50 mg/d) was given for 12 months, followed by repeat RPFNA. The primary end point was change in Ki-67. Secondary end points included change in cytomorphology, mammographic breast density, serum bioavailable estradiol and testosterone insulin-like growth factor-I and IGF-binding protein-3, and plasma lignan levels. Forty-five of 49 eligible women completed the study with excellent compliance (median = 96%) and few serious side effects (4% grade 3). Median plasma enterolactone increased ∼9-fold, and total lignans increased 16-fold. Thirty-six (80%) of the 45 evaluable subjects showed a decrease in Ki-67, from a median of 4% (range, 2-16.8%) to 2% (range, 0-15.2%; P < 0.001, Wilcoxon signed rank test). A decrease from baseline in the proportion of women with atypical cytology (P = 0.035) was also observed. Based on favorable risk biomarker modulation and lack of adverse events, we are initiating a randomized trial of SDG versus placebo in premenopausal women.