138 research outputs found

    The Role of State Health Departments in Supporting Community-based Obesity Prevention

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    Background: Recent national attention to obesity prevention has highlighted the importance of community-based initiatives. State health departments are in a unique position to offer resources and support for local obesity prevention efforts. Community Context: In North Carolina, one-third of children are overweight or obese. North Carolina's Division of Public Health supports community-based obesity prevention by awarding annual grants to local health departments, providing ongoing training and technical assistance, and engaging state-level partners and resources to support local efforts. Methods: The North Carolina Division of Public Health administered grants to 5 counties to implement the Childhood Obesity Prevention Demonstration Project; counties simultaneously carried out interventions in the community, health care organizations, worksites, schools, child care centers, and faith communities. Outcome: The North Carolina Division of Public Health worked with 5 local health departments to implement community-wide policy and environmental changes that support healthful eating and physical activity. The state health department supported this effort by working with state partners to provide technical assistance, additional funding, and evaluation. Interpretation: State health departments are well positioned to coordinate technical assistance and leverage additional support to increase the strength of community-based obesity prevention efforts

    Evolution of non-thyroidal illness syndrome in acute decompensation of liver cirrhosis and acute-on-chronic liver failure

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    Background and aimsNon-thyroidal illness syndrome (NTIS) is frequent in critically ill patients and associated with adverse outcomes. We aimed to characterize the evolution of NTIS in patients with acute decompensation (AD) of cirrhosis and acute-on-chronic liver failure (ACLF), since NTIS is not well described in these newly defined syndromes.MethodsThyroid hormones (TH) were quantified at baseline in consecutive patients with cirrhosis. In addition, 76 inflammatory mediators were quantified by proximity extension analysis assay in a subgroup of patients. Associations between TH, cirrhosis stage, mortality and inflammation were assessed.ResultsOverall, 437 patients were included, of whom 165 (37.8%), 211 (48.3%), and 61 (14%) had compensated cirrhosis (CC), AD, and ACLF. FT3 concentrations were lower in AD versus CC, and further decreased in ACLF. Importantly, NTIS was present in 83 (39.3%) patients with AD and in 44 (72.1%) patients with ACLF (P<0.001). Yet, TSH and TSH-based indexes (TSH/FT3-ratio, thyroid index) showed an U-shaped evolution during progression of cirrhosis, suggesting a partially preserved responsiveness of the hypothalamus and pituitary in AD. Infections were associated with lower FT3 concentrations in AD, but not in ACLF. Low FT3 concentrations correlated significantly with 90-day mortality. Both, AD/ACLF and NTIS, were associated with signatures of inflammatory mediators, which were partially non-overlapping.ConclusionNTIS is frequent already in AD and therefore precedes critically illness in a subgroup of patients with decompensated cirrhosis. This might constitute a new paradigm of TH signaling in cirrhosis, offering opportunities to explore preventive effects of TH in AD

    EUPRON: nurses’ practice in interprofessional pharmaceutical care in Europe. A cross-sectional survey in 17 countries

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    Abstract Objectives Safe pharmaceutical care (PC) requires an interprofessional team approach, involving physicians, nurses and pharmacists. Nurses’ roles however, are not always explicit and clear, complicating interprofessional collaboration. The aim of this study is to describe nurses’ practice and interprofessional collaboration in PC, from the viewpoint of nurses, physicians and pharmacists. Design A cross-sectional survey. Setting The study was conducted in 17 European countries, each with their own health systems. Participants Pharmacists, physicians and nurses with an active role in PC were surveyed. Main outcome measures Nurses’ involvement in PC, experiences of interprofessional collaboration and communication and views on nurses’ competences. Results A total of 4888 nurses, 974 physicians and 857 pharmacists from 17 European countries responded. Providing patient education and information (PEI), monitoring medicines adherence (MMA), monitoring adverse/therapeutic effects (ME) and prescribing medicines were considered integral to nursing practice by 78%, 73%, 69% and 15% of nurses, respectively. Most respondents were convinced that quality of PC would be improved by increasing nurses’ involvement in ME (95%), MMA (95%), PEI (91%) and prescribing (53%). Mean scores for the reported quality of collaboration between nurses and physicians, collaboration between nurses and pharmacists and interprofessional communication were respectively <7/10, ≤4/10, <6/10 for all four aspects of PC. Conclusions ME, MMA, PEI and prescribing are part of nurses’ activities, and most healthcare professionals felt their involvement should be extended. Collaboration between nurses and physicians on PC is limited and between nurses and pharmacists even more

    A Sequential Targeting Strategy Interrupts AKT-Driven Subclone-Mediated Progression in Glioblastoma

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    Purpose: Therapy resistance and fatal disease progression in glioblastoma are thought to result from the dynamics of intra-tumor heterogeneity. This study aimed at identifying and molecularly targeting tumor cells that can survive, adapt, and subclonally expand under primary therapy. Experimental design: To identify candidate markers and to experimentally access dynamics of subclonal progression in glioblastoma, we established a discovery cohort of paired vital cell samples obtained before and after primary therapy. We further used two independent validation cohorts of paired clinical tissues to test our findings. Follow-up preclinical treatment strategies were evaluated in patient-derived xenografts. Results: We describe, in clinical samples, an archetype of rare ALDH1A1+ tumor cells that enrich and acquire AKT-mediated drug resistance in response to standard-of-care temozolomide (TMZ). Importantly, we observe that drug resistance of ALDH1A1+ cells is not intrinsic, but rather an adaptive mechanism emerging exclusively after TMZ treatment. In patient cells and xenograft models of disease, we recapitulate the enrichment of ALDH1A1+ cells under the influence of TMZ. We demonstrate that their subclonal progression is AKT-driven and can be interfered with by well-timed sequential rather than simultaneous antitumor combination strategy. Conclusions: Drug-resistant ALDH1A1+/pAKT+ subclones accumulate in patient tissues upon adaptation to TMZ therapy. These subclones may therefore represent a dynamic target in glioblastoma. Our study proposes the combination of TMZ and AKT inhibitors in a sequential treatment schedule as a rationale for future clinical investigation

    Profiling Critical Cancer Gene Mutations in Clinical Tumor Samples

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    Background: Detection of critical cancer gene mutations in clinical tumor specimens may predict patient outcomes and inform treatment options; however, high-throughput mutation profiling remains underdeveloped as a diagnostic approach. We report the implementation of a genotyping and validation algorithm that enables robust tumor mutation profiling in the clinical setting. Methodology: We developed and implemented an optimized mutation profiling platform (“OncoMap”) to interrogate ∼400 mutations in 33 known oncogenes and tumor suppressors, many of which are known to predict response or resistance to targeted therapies. The performance of OncoMap was analyzed using DNA derived from both frozen and FFPE clinical material in a diverse set of cancer types. A subsequent in-depth analysis was conducted on histologically and clinically annotated pediatric gliomas. The sensitivity and specificity of OncoMap were 93.8% and 100% in fresh frozen tissue; and 89.3% and 99.4% in FFPE-derived DNA. We detected known mutations at the expected frequencies in common cancers, as well as novel mutations in adult and pediatric cancers that are likely to predict heightened response or resistance to existing or developmental cancer therapies. OncoMap profiles also support a new molecular stratification of pediatric low-grade gliomas based on BRAF mutations that may have immediate clinical impact. Conclusions: Our results demonstrate the clinical feasibility of high-throughput mutation profiling to query a large panel of “actionable” cancer gene mutations. In the future, this type of approach may be incorporated into both cancer epidemiologic studies and clinical decision making to specify the use of many targeted anticancer agents
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