Expanded HILUS Trial: A Pooled Analysis of Risk Factors for Toxicity From Stereotactic Body Radiation Therapy of Central and Ultracentral Lung Tumors.

PURPOSE: Stereotactic body radiation therapy for tumors near the central airways implies high-grade toxic effects, as concluded from the HILUS trial. However, the small sample size and relatively few events limited the statistical power of the study. We therefore pooled data from the prospective HILUS trial with retrospective data from patients in the Nordic countries treated outside the prospective study to evaluate toxicity and risk factors for high-grade toxic effects. METHODS AND MATERIALS: All patients were treated with 56 Gy in 8 fractions. Tumors within 2 cm of the trachea, the mainstem bronchi, the intermediate bronchus, or the lobar bronchi were included. The primary endpoint was toxicity, and the secondary endpoints were local control and overall survival. Clinical and dosimetric risk factors were analyzed for treatment-related fatal toxicity in univariable and multivariable Cox regression analyses. RESULTS: Of 230 patients evaluated, grade 5 toxicity developed in 30 patients (13%), of whom 20 patients had fatal bronchopulmonary bleeding. The multivariable analysis revealed tumor compression of the tracheobronchial tree and maximum dose to the mainstem or intermediate bronchus as significant risk factors for grade 5 bleeding and grade 5 toxicity. The 3-year local control and overall survival rates were 84% (95% CI, 80%-90%) and 40% (95% CI, 34%-47%), respectively. CONCLUSIONS: Tumor compression of the tracheobronchial tree and high maximum dose to the mainstem or intermediate bronchus increase the risk of fatal toxicity after stereotactic body radiation therapy in 8 fractions for central lung tumors. Similar dose constraints should be applied to the intermediate bronchus as to the mainstem bronchi.

Predicting the benefit of stereotactic body radiotherapy of colorectal cancer metastases.

Aim: To evaluate Stereotactic body radiotherapy (SBRT) in metastatic colorectal cancer (mCRC) and identify the benefit of the treatment by using a predictive algorithm. Methods: 85 patients treated with SBRT for mCRC were retrospectively analyzed. The CLInical Categorical Algorithm (CLICAL©) was used to predict probability of relapse after SBRT. Variables pre-SBRT were tested for significance for time to relapse (TTR). The patients' CLICAL© score was the mean of sub-scores of each significant variable's effect on the endpoint. Patients with similar scores were grouped into four signatures dependent on level of benefit after SBRT. Results: Median age was 69 years (42-88), 63 % had a performance status 0 and 47 % were treated for a single metastasis. At the time of the analysis, 90 % had relapsed (95 % out-of-field). Median TTR was 7.3 months (4.6-8.5), and the 2-year relapse-free rate was 15 % (95 %CI = 7-22). The CLICAL© signature III-IV predicted a low risk of relapse if receiving high dose SBRT to all metastases or to lung metastases only. Signature I-II had a short TTR, why SBRT for these patients was judged non-beneficial. Conclusion: The benefit from SBRT varies among mCRC patients. CLICAL© may serve as a screening tool for SBRT referrals but needs to be validated.

Coordinating Centers as a Strategy for Accelerating Cancer Epidemiology Consortia: Best Practices.

Purposeof Review: This review highlights six "best practices" for cancer epidemiology coordinating centers to facilitate the success of a research consortium. Recent Findings: Evidence from emerging literature regarding the Science of Team Science suggests that coordinating centers can more effectively foster collaborative cancer epidemiology research in consortia by (1) establishing collaboration as a shared goal at the start, (2) providing scientific expertise complementary to the research sites that adapts over the course of the project, (3) enacting anti-racist and inclusive approaches in all consortium decisions and activities, (4) fostering early-stage investigator career development, (5) engaging stakeholders including cancer survivors as peers, and (6) delivering reliable logistical support and technology tools with planned process evaluation so that researchers can collaboratively focus on the science. Summary: By drawing on the Science of Team Science, coordinating centers can accelerate research progress and increase the impact of cancer epidemiology consortia.

The HILUS-Trial-a Prospective Nordic Multicenter Phase 2 Study of Ultracentral Lung Tumors Treated With Stereotactic Body Radiotherapy.

INTRODUCTION: Stereotactic body radiation therapy of thoracic tumors close to the central airways implies risk of severe toxicity. We report a prospective multicenter phase 2 trial for tumors located less than or equal to 1 cm from the proximal bronchial tree with primary end point of local control and secondary end point of toxicity. METHODS: Stereotactic body radiation therapy with 7 Gy × 8 was prescribed to the 67% isodose encompassing the planning target volume. The patients were stratified to group A (tumors ≤ 1 cm from the main bronchi and trachea) or group B (all other tumors). Risk factors for treatment-related death were tested in univariate analysis, and a logistic regression model was developed for fatal bronchopulmonary bleeding versus dose to the main bronchi and trachea. RESULTS: A total of 65 patients (group A/group B, n = 39/26) were evaluated. The median distance between the tumor and the proximal bronchial tree was 0 mm (0-10 mm). The 2-year local control was 83%. Grade 3 to 5 toxicity was noted in 22 patients, including 10 cases of treatment-related death (bronchopulmonary hemorrhage, n = 8; pneumonitis, n = 1; fistula, n = 1). Dose to the combined structure main bronchi and trachea and tumor distance to the main bronchi were important risk factors. Dose modeling revealed minimum dose to the "hottest" 0.2 cc to the structure main bronchi and trachea as the strongest predictor for lethal bronchopulmonary hemorrhage. CONCLUSIONS: On the basis of the presented data, 7 Gy × 8, prescribed to the planning target volume-encompassing isodose, should not be used for tumors located within 1 cm from the main bronchi and trachea. Group B-type tumors may be considered for the treatment on the basis of an individual risk-benefit assessment and a maximum dose to the main bronchi and trachea in the order of 70 to 80 Gy (equivalent dose in 2 Gy fractions).

The Impact of a Community Resource Navigator Program on Patient Trust.

BACKGROUND: Addressing patients' nonmedical needs has become a focal point in primary care research and practice. Programs such as the Center for Patient Partnerships' Community Resource Navigator Program address social determinants of health by connecting participants to community-based resources in an effort to ameliorate unmet social needs. METHODS: Twenty-six interviews were conducted with program participants to assess improvements in social needs and trust with the health care system as a result of the program. RESULTS: Program participants reported increased trust in their provider or health system, improved health, and confidence in self-advocacy. DISCUSSION: Findings suggest that in addition to providing crucial support to address participants' unmet social needs, navigation programs have the added benefit of enhancing their relationship with the clinic and health system.

Incidence, prevalence, and outcome of primary biliary cholangitis in a nationwide Swedish population-based cohort.

Available epidemiological data on primary biliary cholangitis (PBC) in Sweden originate from regional studies in the 1980s and may not reflect modern day PBC. We aimed to estimate incidence and prevalence, survival and death causes, and gender differences in PBC. We used international classification of disease (ICD) codes to identify patients with PBC in inpatient and outpatient registries 1987-2014 who were then linked to the Swedish cause of death, cancer and prescribed drug registries. Each PBC patient was matched with 10 reference individuals from the general population. In sensitivity analyses, we examined PBC patients identified through clinical patient records from Karolinska, Sahlgrenska and Örebro University Hospitals. We identified 5,350 adults with PBC. Prevalence of PBC increased steadily from 5.0 (1987) to 34.6 (2014) per 100,000 inhabitants whereas the yearly incidence rate was relatively constant with a median of 2.6 per 100,000 person-years, with a female:male gender ratio of 4:1. Compared to reference individuals, PBC individuals aged 15-39 years at diagnosis had a substantially higher risk of death (Hazard Ratio [HR] 12.7, 95% Confidence Interval [CI] 8.3-19.5) than those diagnosed between 40-59 (HR 4.1, 95% CI 3.7-4.5) and >60 (HR 3.7, 95% CI 3.5-3.9) years of age. Relative risks of mortality were highest in men. In conclusion, we found that recorded prevalence of PBC in Sweden has increased substantially during the last 30 years although incidence has been stable. Patients diagnosed in young adulthood were at a 12.7-fold increased risk of death, and male PBC patients had worse prognosis.

Radiation-induced brachial plexus toxicity after SBRT of apically located lung lesions.

Purpose: To evaluate the rate and dose response of brachial plexus toxicity post stereotactic body radiation therapy (SBRT) of apically situated lung lesions. Material/methods: We retrospectively identified all patients with apically located tumors, defined by the epicenter of the tumor being located superiorly to the aortic arch, and treated with SBRT between 2008 and 2013. Patients with a shorter follow-up than 6 months were excluded. Primary aim was to evaluate radiation-induced brachial plexopathy (RIBP). Dose to the plexus was assessed by a retrospective delineation of the brachial plexus on the CT used for treatment planning. Then, Dmax, D0.1cc, D1cc and D3.0cc of the brachial plexus were collected from the dose-volume histograms (DVH) and recalculated to the biologically effective dose (BED) using α/ß = 3 Gy. A normal tissue complication probability (NTCP) model, based on four different dose-volume parameters (BED3,max, BED3,0.1cc, BED3,1.0cc, BED3,3.0cc) was fitted to the data. Results: Fifty-two patients with 56 apically located tumors were identified. Median prescription dose per fraction was 15 Gy (range 6-17) and median number of fractions was 3 (3-10). With a median follow-up of 30 months (6.1-72) seven patients experienced maximum grade 2 (scored 3 times) or 3 (scored 4 times) RIBP after a median of 8.7 months (range 4.0-31). Three patients had combined symptoms with pain, sensory and motor affection and four patients had isolated pain. Median BED3,max for the patients experiencing RIBP was 381 Gy (range 30-524) versus BED3,max of 34 Gy (range 0.10-483) for the patients without RIBP. The NTCP models showed a very high predictive ability (area under the receiver operating characteristic curve (AUC) 0.80-0.88). Conclusion: SBRT of apically located lung lesions may cause severe neurological symptoms; for a three-fraction treatment, we suggest that the maximum dose to the plexus should be kept ≤30 Gy (130 Gy BED3).

Integrating Medical-Dental Care for Diabetic Patients: Qualitative Assessment of Provider Perspectives.

Globally, periodontal disease and diabetes have achieved epidemic proportions and have become a top health care priority. Mutual bidirectional exacerbation of these conditions is promoting creation of cross-disciplinary integrated care delivery (ICD) models that bridge the traditionally siloed health care domains of dentistry and medicine. By engaging focus groups inclusive of both medical and dental providers and one-on-one interviews, this qualitative study investigated provider knowledgeability, receptiveness, and readiness to engage ICD and sought input from the medical-dental primary care practitioner participants on perceived opportunities, benefits, and challenges to achieving ICD models for patients with diabetes/prediabetes. Statewide regional representation and inclusivity of diverse practice settings were emphasized in soliciting participants. Thematic analysis of focus group and interview transcripts was undertaken to establish current state of the art, gauge receptivity to alternative ICD models, and seek insights from practitioners surrounding opportunities and barriers to ICD achievement. Forty providers participated, and thematic analyses achieved saturation. Providers were well informed regarding disease interaction; were receptive to ICD, including implementation of better screening and referral processes; and favored improving interdisciplinary communication inclusive of access to integrated electronic health records. Perceived barriers and opportunities communicated by participants for advancing ICD were documented.

Effect of a Best Practice Alert on Gestational Weight Gain, Health Services, and Pregnancy Outcomes.

Objective To examine whether an electronic medical record "best practice alert" previously shown to improve antenatal gestational weight gain patient education resulted in downstream effects on service delivery or patient health outcomes. Methods This study involved secondary analysis of data from an intervention to improve provider behavior surrounding gestational weight gain patient education. Data were from retrospective chart reviews of patients who received care either before (N = 333) or after (N = 268) implementation of the intervention. Pre-post comparisons and multivariable logistic regression were used to analyze downstream effects of the intervention on health outcomes and obesity-related health services while controlling for potential confounders. Results The intervention was associated with an increase in the proportion of prenatal patients who gained weight within Institute of Medicine guidelines, from 28 to 35 % (p < .05). Mean total gestational weight gain did not change, but variability decreased such that post-intervention women had weight gains closer to their gestational weight gain targets. The intervention was associated with a 94 g decrease in mean infant birth weight (p = .03), and an increase in the proportion of overweight and obese women screened for undiagnosed Type 2 diabetes before 20 weeks gestation, from 13 to 25 % (p = .01). Conclusions for Practice The electronic medical record can be leveraged to promote healthy gestational weight gain and early screening for undiagnosed Type 2 diabetes. Yet most patients still need additional support to achieve gestational weight gain within Institute of Medicine guidelines.

The Obesity Prevention Initiative: A Statewide Effort to Improve Child Health in Wisconsin.

BACKGROUND/SIGNIFICANCE: Obesity rates have increased dramatically, especially among children and disadvantaged populations. Obesity is a complex issue, creating a compelling need for prevention efforts in communities to move from single isolated programs to comprehensive multisystem interventions. To address these issues, we have established a childhood Obesity Prevention Initiative (Initiative) for Wisconsin. This Initiative seeks to test community change frameworks that can support multisystem interventions and provide data for local action as a means for influencing policies, systems, and environments that support individuals' healthy eating and physical activity. APPROACHES/AIMS: The Initiative is comprised of three components: (1) infrastructure to support a statewide obesity prevention and health promotion network with state- and local-level public messaging and dissemination of evidence-based solutions (healthTIDE); (2) piloting a local, multisetting community-led intervention study in 2 Wisconsin counties; and (3) developing a geocoded statewide childhood obesity and fitness surveillance system. RELEVANCE: This Initiative is using a new model that involves both coalition action and community organizing to align resources to achieve health improvement at local and state levels. We expect that it will help lead to the implementation of cohesive and sustainable policy, system, and environment health promotion and obesity prevention strategies in communities statewide, and it has the potential to help Wisconsin become a national model for multisetting community interventions to address obesity. Addressing individual-level health through population-level changes ultimately will result in reductions in the prevalence of childhood obesity, current and future health care costs, and chronic disease mortality.

Development of an Obesity Prevention Dashboard for Wisconsin.

IMPORTANCE: A comprehensive obesity surveillance system monitors obesity rates along with causes and related health policies, which are valuable for tracking and identifying problems needing intervention. METHODS: A statewide obesity dashboard was created using the County Health Rankings model. Indicators were obtained through publicly available secondary data sources and used to rank Wisconsin amongst other states on obesity rates, health factors, and policies. RESULTS: Wisconsin consistently ranks in the middle of states for a majority of indicators and has not implemented any of the evidence-based health policies. CONCLUSIONS AND RELEVANCE: This state of obesity report shows Wisconsin has marked room for improvement regarding obesity prevention, especially with obesity-related health policies. Physicians and health care systems can play a pivotal role in making progress on obesity prevention.

Prevalence of Pre-pregnancy Obesity, 2011-2014.

IMPORTANCE: Obesity before and during pregnancy increases risk among mothers for poor health outcomes, such as diabetes, high blood pressure, and cardiovascular disease. OBJECTIVE: To describe trends in pre-pregnancy obesity rates among women in Wisconsin. METHODS: Cross-sectional data from Wisconsin birth certificates were analyzed. Prevalence of pre-pregnancy obesity (defined as body mass index ≥ 30) among Wisconsin women who gave birth from 2011 through 2014 was compared across demographic and geographic dimensions. RESULTS: Overall, 27.8% of Wisconsin women who gave birth during 2011-2014 were obese. Obesity rates were highest among 40- to 44-year-old women (31.8%), women with a high school/ GED diploma (32.8 %), American Indian/Alaska Native women (43.9%), and women with 5 or more pregnancies (35.4%). Obesity rates varied by county of residence (highest in Forest County, 45.2%) and city of residence (highest in the city of Racine, 34.8%). CONCLUSIONS: There are significant socioeconomic, racial, and geographic disparities in pre-pregnancy obesity among women who give birth in Wisconsin.

Prevalence and Predictors of Unhealthy Weight Gain in Pregnancy.

IMPORTANCE: Weight gain during pregnancy affects obesity risk in offspring. OBJECTIVE: To assess weight gain among UW Health prenatal patients and to identify predictors of unhealthy gestational weight gain. METHODS: Retrospective cohort study of women delivering at UW Health during 2007-2012. Data are from the UW eHealth Public Health Information Exchange (PHINEX) project. The proportion of women with excess and insufficient (ie, unhealthy) gestational weight gain was computed based on 2009 Institute of Medicine guidelines. Multivariable logistic regression was used to identify risk factors associated with excess and insufficient gestational weight gain. RESULTS: Gestational weight gain of 7,385 women was analyzed. Fewer than 30% of prenatal patients gained weight in accordance with Institute of Medicine guidelines. Over 50% of women gained excess weight and 20% gained insufficient weight during pregnancy. Pre-pregnancy weight and smoking status predicted excess weight gain. Maternal age, race/ethnicity, smoking status, and having Medicaid insurance predicted insufficient weight gain. CONCLUSIONS AND RELEVANCE: Unhealthy weight gain during pregnancy is the norm for Wisconsin women. Clinical and community interventions that promote healthy weight gain during pregnancy will not only improve the health of mothers, but also will reduce the risk of obesity in the next generation.

Excess Gestational Weight Gain in Low-Income Overweight and Obese Women: A Qualitative Study.

OBJECTIVE: Examine factors implicated in gestational weight gain (GWG) in low-income overweight and obese women. DESIGN: Qualitative study. SETTING: Community-based perinatal center. PARTICIPANTS: Eight focus groups with women (black = 48%, white non-Hispanic = 41%, and Hispanic = 10%) in the first half (n = 12) and last half of pregnancy (n = 10) or postpartum (n = 7), 2 with obstetrician-gynecologists (n = 9). PHENOMENON OF INTEREST: Barriers and facilitators to healthy eating and GWG within different levels of the Social Ecological Model: for example, intrapersonal, interpersonal, and organizational. ANALYSIS: Coding guide was based on the Social Ecological Model. Transcripts were coded by 3 researchers for common themes. Thematic saturation was reached. RESULTS: At an intrapersonal level, knowledge/skills and cravings were the most common barriers. At an interpersonal level, family and friends were most influential. At an organizational level, the Special Supplemental Nutrition Program for Women, Infants, and Children and clinics were influential. At the community level, lack of transportation was most frequently discussed. At a policy level, complex policies and social stigma surrounding the Special Supplemental Nutrition Program for Women, Infants, and Children were barriers. There was consensus that ideal intervention approaches would include peer-facilitated support groups with information from experts. Obstetrician-gynecologists felt uncomfortable counseling patients about GWG because of time constraints, other priorities, and lack of training. CONCLUSIONS AND IMPLICATIONS: There are multilevel public health opportunities to promote healthy GWG. Better communication between nutrition specialists and obstetrician-gynecologists is needed.

Improving gestational weight gain counseling through meaningful use of an electronic medical record.

The purpose of this study was to test the effectiveness of an intervention to improve the consistency and accuracy of antenatal gestational weight gain counseling through introduction of a "best practice alert" into an electronic medical record (EMR) system. A best practice alert was designed and implemented in the EMR. Based on each patient's pre-gravid body mass index (BMI), fetal number, and 2009 Institute of Medicine (IOM) guidelines, the alert provides an individualized total gestational weight gain goal, the weight gain goal per week of gestation, a template for scripted provider counseling and documentation, and a patient handout containing personalized gestational weight gain information. Retrospective chart reviews of 388 pre-intervention patients and 345 post-intervention patients were used to evaluate effectiveness. Introduction of a gestational weight gain best practice alert into the EMR improved the rate of antenatal gestational weight gain counseling that was consistent with current IOM guidelines (p < 0.001). Improvement in IOM-consistent gestational weight gain counseling was seen across all provider types, including obstetricians, family practice physicians, and certified nurse midwives. The intervention also resulted in significant improvement in documentation of pre-gravid weights and BMIs within the EMR. The EMR is an effective tool for improving the consistency and accuracy of antenatal gestational weight gain counseling in accord with 2009 IOM guidelines.

Individuation or Identification? Self-Objectification and the Mother-Adolescent Relationship.

Do adolescents model their mothers' self-objectification? We measured self-objectification (body surveillance and body shame), body mass index (BMI), body esteem, and quality of the mother-adolescent relationship in 179 female and 162 male adolescents at age 15, as well as self-objectification in their mothers. Initial analyses indicated no improvement in model fit if paths were allowed to differ for females and males; therefore a single model was tested for the combined sample. Findings revealed that mothers' body surveillance negatively predicted adolescents' body surveillance. Mothers' body shame was unrelated to adolescents' body shame, but positively predicted adolescents' body surveillance. Results for the relationship between mothers' and adolescents' self-objectification suggest that adolescents engaged in more individuation than modeling. A more positive mother-adolescent relationship predicted lower body shame and higher body esteem in adolescents, suggesting that the quality of the relationship with the mother may be a protective factor for adolescents' body image. Mother-adolescent relationship quality did not moderate the association between mothers' and adolescents' self-objectification. These findings contribute to our understanding about the sociocultural role of parents in adolescents' body image and inform interventions addressing negative body image in this age group. The quality of the mother-adolescent relationship is a clear point of entry for such interventions. Therapists should work with adolescents and their mothers toward a more positive relationship quality, which could then positively impact adolescents' body image.

Early predictors of obesity and cardiovascular risk among American Indian children.

American Indian (AI) children have the highest rates of obesity among ethnic groups in the United States, and rates continue to increase. This study was designed to examine the effects of prenatal and early postnatal factors on AI children's body mass index (BMI) trajectories, adiposity, and cardiovascular risk markers during early childhood. We screened 471 AI children (ages 5-8) from three Wisconsin tribes. Screenings included anthropometric and body fat measures and non-fasting lipid and glucose via fingerstick blood samples. Tribal records from Women Infants and Children (WIC) programs and clinic charts provided data on children's BMI trajectories, maternal prenatal factors, and the early postnatal feeding environment. Forty-seven percent of children were overweight or obese. Analysis of growth trajectories showed that children's BMI category was largely determined within the 1 year of life. Significant predictors of children's BMI category at age 1 included macrosomia (OR 4.38), excess gestational weight gain (OR 1.64) and early termination of breastfeeding (OR 1.66). Children who were overweight/obese at age 1 had greater odds of being overweight (OR 3.42) or obese (OR 3.36), and having unhealthy levels of body fat (OR 2.95) and LDL cholesterol (OR 1.64) at ages 5-8. Children's BMI category is determined in the early post-natal environment, within the 1 year of life, by factors including excess gestational weight gain and early termination of breastfeeding. In turn, children's BMI category at age 1 predicts the emergence of cardiovascular risk markers in early childhood.

New trends in gender and mathematics performance: a meta-analysis.

In this article, we use meta-analysis to analyze gender differences in recent studies of mathematics performance. First, we meta-analyzed data from 242 studies published between 1990 and 2007, representing the testing of 1,286,350 people. Overall, d = 0.05, indicating no gender difference, and variance ratio = 1.08, indicating nearly equal male and female variances. Second, we analyzed data from large data sets based on probability sampling of U.S. adolescents over the past 20 years: the National Longitudinal Surveys of Youth, the National Education Longitudinal Study of 1988, the Longitudinal Study of American Youth, and the National Assessment of Educational Progress. Effect sizes for the gender difference ranged between -0.15 and +0.22. Variance ratios ranged from 0.88 to 1.34. Taken together, these findings support the view that males and females perform similarly in mathematics.

Adolescent gender-role identity and mental health: gender intensification revisited.

Gender intensification, an increased pressure for adolescents to conform to culturally sanctioned gender roles, has been posited as an explanation for the emergence of the gender difference in depression. This longitudinal study assessed whether 410 individuals became more stereotypical in their gender-role identity across adolescence and whether such patterns predicted depressive symptoms. Girls reported higher femininity than boys at ages 11, 13, and 15, but girls and boys did not differ in masculinity. Contrary to prevailing views, there was not evidence of intensification in femininity or masculinity. Positive trajectories in masculinity for both girls and boys predicted fewer depressive symptoms, particularly at moderate levels of stress. Findings suggest a need to reconceptualize gender intensification in ways that characterize contemporary adolescence.