Characteristics of Walkable Built Environments and BMI z-Scores in Children: Evidence from a Large Electronic Health Record Database

Background: Childhood obesity remains a prominent public health problem. Walkable built environments may prevent excess weight gain. Objectives: We examined the association of walkable built environment characteristics with body mass index (BMI) z-score among a large sample of children and adolescents. Methods: We used geocoded residential address data from electronic health records of 49,770 children and adolescents 4 to < 19 years of age seen at the 14 pediatric practices of Harvard Vanguard Medical Associates from August 2011 through August 2012. We used eight geographic information system (GIS) variables to characterize walkable built environments. Outcomes were BMI z-score at the most recent visit and BMI z-score change from the earliest available (2008–2011) to the most recent (2011–2012) visit. Multivariable models were adjusted for child age, sex, race/ethnicity, and neighborhood median household income. Results: In multivariable cross-sectional models, living in closer proximity to recreational open space was associated with lower BMI z-score. For example, children who lived in closest proximity (quartile 1) to the nearest recreational open space had a lower BMI z-score (β = –0.06; 95% CI: –0.08, –0.03) compared with those living farthest away (quartile 4; reference). Living in neighborhoods with fewer recreational open spaces and less residential density, traffic density, sidewalk completeness, and intersection density were associated with higher cross-sectional BMI z-score and with an increase in BMI z-score over time. Conclusions: Overall, built environment characteristics that may increase walkability were associated with lower BMI z-scores in a large sample of children. Modifying existing built environments to make them more walkable may reduce childhood obesity. Citation: Duncan DT, Sharifi M, Melly SJ, Marshall R, Sequist TD, Rifas-Shiman SL, Taveras EM. 2014. Characteristics of walkable built environments and BMI z-scores in children: evidence from a large electronic health record database. Environ Health Perspect 122:1359–1365; http://dx.doi.org/10.1289/ehp.130770

Using the Teamlet Model to Improve Chronic Care in an Academic Primary Care Practice

Team care can improve management of chronic conditions, but implementing a team approach in an academic primary care clinic presents unique challenges. To implement and evaluate the Teamlet Model, which uses health coaches working with primary care physicians to improve care for patients with diabetes and/or hypertension in an academic practice. Process and outcome measures were compared before and during the intervention in patients seen with the Teamlet Model and in a comparison patient group. First year family medicine residents, medical assistants, health workers, and adult patients with either type 2 diabetes or hypertension in a large public health clinic. Health coaches, in coordination with resident primary care physicians, met with patients before and after clinic visits and called patients between visits. Measurement of body mass index, assessment of smoking status, and formulation of a self-management plan prior to and during the intervention period for patients in the Teamlet Model group. Testing for LDL and HbA1C and the proportion of patients at goal for blood pressure, LDL, and HbA1C in the Teamlet Model and comparison groups in the year prior to and during implementation. Teamlet patients showed improvement in all measures, though improvement was significant only for smoking, BMI, and self-management plan documentation and testing for LDL (p = 0.02), with a trend towards significance for LDL at goal (p = 0.07). Teamlet patients showed a greater, but non-significant, increase in the proportion of patients tested for HbA1C and proportion reaching goal for blood pressure, HgbA1C, and LDL compared to the comparison group patients. The difference for blood pressure was marginally significant (p = 0.06). In contrast, patients in the comparison group were significantly more likely to have had testing for LDL (P = 0.001). The Teamlet Model may improve chronic care in academic primary care practices

Aurora kinase A drives the evolution of resistance to third-generation EGFR inhibitors in lung cancer.

Although targeted therapies often elicit profound initial patient responses, these effects are transient due to residual disease leading to acquired resistance. How tumors transition between drug responsiveness, tolerance and resistance, especially in the absence of preexisting subclones, remains unclear. In epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma cells, we demonstrate that residual disease and acquired resistance in response to EGFR inhibitors requires Aurora kinase A (AURKA) activity. Nongenetic resistance through the activation of AURKA by its coactivator TPX2 emerges in response to chronic EGFR inhibition where it mitigates drug-induced apoptosis. Aurora kinase inhibitors suppress this adaptive survival program, increasing the magnitude and duration of EGFR inhibitor response in preclinical models. Treatment-induced activation of AURKA is associated with resistance to EGFR inhibitors in vitro, in vivo and in most individuals with EGFR-mutant lung adenocarcinoma. These findings delineate a molecular path whereby drug resistance emerges from drug-tolerant cells and unveils a synthetic lethal strategy for enhancing responses to EGFR inhibitors by suppressing AURKA-driven residual disease and acquired resistance

The effect of feedback to general practitioners on quality of care for people with type 2 diabetes. A systematic review of the literature

<p>Abstract</p> <p>Background</p> <p>There have been numerous efforts to improve and assure the quality of treatment and follow-up of people with Type 2 diabetes (PT2D) in general practice. Facilitated by the increasing usability and validity of guidelines, indicators and databases, feedback on diabetes care is a promising tool in this aspect. Our goal was to assess the effect of feedback to general practitioners (GPs) on the quality of care for PT2D based on the available literature.</p> <p>Methods</p> <p>Systematic review searches were conducted using October 2008 updates of Medline (Pubmed), Cochrane library and Embase databases. Additional searches in reference lists and related articles were conducted. Papers were included if published in English, performed as randomized controlled trials, studying diabetes, having general practice as setting and using feedback to GPs on diabetes care. The papers were assessed according to predefined criteria.</p> <p>Results</p> <p>Ten studies complied with the inclusion criteria. Feedback improved the care for PT2D, particularly process outcomes such as foot exams, eye exams and Hba1c measurements. Clinical outcomes like lowering of blood pressure, Hba1c and cholesterol levels were seen in few studies. Many process and outcome measures did not improve, while none deteriorated. Meta analysis was unfeasible due to heterogeneity of the studies included. Two studies used electronic feedback.</p> <p>Conclusion</p> <p>Based on this review, feedback seems a promising tool for quality improvement in diabetes care, but more research is needed, especially of electronic feedback.</p

Clinical implications of novel activating EGFR mutations in malignant peritoneal mesothelioma

<p>Abstract</p> <p>Background</p> <p>There is a paucity of information about the molecular perturbations involved in MPM tumor formation. We previously reported that EGFR-TK mutations in MPM were predictive of achieving optimal surgical cytoreduction, but the status of EGFR pathway activation potential of these mutations was not known. Here we present the mutant EGFR activating potential and the matured survival data of the EGFR mutant(mut+) relative to wild type EGFR(mut-) mesothelioma.</p> <p>Methods</p> <p>Twenty-nine patients were evaluated and their tumors were probed for mutations in the catalytic TK-domain. Twenty-five patients were treated with cytoreductive surgery and complete clinical data was available for comparison of the mut+ and mut- groups. A COS-7 cell expression model was used to determine mutation activating profiles and response to erlotinib.</p> <p>Results</p> <p>Functional mutations were found in 31%(9/29) of patients; 7 of these mutations were novel and another was the L858R mutation. All missense mutations were found to be activating mutations and responsive to erlotinib. Of the 25 patients managed surgically, there were 7 mut+ and 18 mut-. Two of 7 (29%) mut+ developed progressive disease and died with a median follow-up time of 22 months; while 13/18 (72%) mut- developed progressive disease and 10/18 (56%) died with median TTP of 12 months and median survival of 14 months.</p> <p>Conclusions</p> <p>The novel EGFR mutations identified are activating mutations responsive to erlotinib. The mut+ subset have a 'relative' improved outcome. Erlotinib may have a role in MPM and exploration for mutations in a larger patient cohort is warranted.</p

Rethinking Research Ethics for Latinos: The Policy Paradox of Health Reform and the Role of Social Justice

http://dx.doi.org/10.1080/10508422.2012.72999

Carcinoma of an unknown primary: are EGF receptor, Her-2/neu, and c-Kit tyrosine kinases potential targets for therapy?

Carcinomas of an unknown primary site (CUP) are heterogeneous tumours with a median survival of only 8 months. Tyrosine kinase inhibitors are promising new drugs. The aim of this study was to determine the expression of EGF-receptor, Her-2/neu, and c-Kit tyrosine kinases in CUP. Paraffin-embedded specimens were obtained from 54 patients with a CUP who were included in the GEFCAPI 01 randomised phase II trial. Immunohistochemistry was performed using the Dako autostainer with antibodies directed against HER-2/neu protein, EGFR protein, and c-Kit protein (CD117). EGFR expression was found in 36 out of 54 samples (66%). In contrast, Her-2/neu overexpression and c-Kit positivity were only detected in 4 and 10% of patients, respectively. No significant association was found between the expression of the tyrosine kinase receptors and prognosis. EGFR expression was significantly associated with response to cisplatin-based chemotherapy: the response rates were 50 and 22% in patients with EGFR-positive tumours and EGFR-negative tumours, respectively (P<0.05). This study shows that EGFR is frequently expressed in CUP. This finding may prompt clinical trials investigating EGFR inhibitors in this setting. In contrast, c-Kit expression and Her-2/neu overexpression occur infrequently in CUP. EGFR expression was correlated to tumour chemosensitivity