Increasing confidence and changing behaviors in primary care providers engaged in genetic counselling.

BackgroundScreening and counseling for genetic conditions is an increasingly important part of primary care practice, particularly given the paucity of genetic counselors in the United States. However, primary care physicians (PCPs) often have an inadequate understanding of evidence-based screening; communication approaches that encourage shared decision-making; ethical, legal, and social implication (ELSI) issues related to screening for genetic mutations; and the basics of clinical genetics. This study explored whether an interactive, web-based genetics curriculum directed at PCPs in non-academic primary care settings was superior at changing practice knowledge, attitudes, and behaviors when compared to a traditional educational approach, particularly when discussing common genetic conditions.MethodsOne hundred twenty one PCPs in California and Pennsylvania physician practices were randomized to either an Intervention Group (IG) or Control Group (CG). IG physicians completed a 6 h interactive web-based curriculum covering communication skills, basics of genetic testing, risk assessment, ELSI issues and practice behaviors. CG physicians were provided with a traditional approach to Continuing Medical Education (CME) (clinical review articles) offering equivalent information.ResultsPCPs in the Intervention Group showed greater increases in knowledge compared to the Control Group. Intervention PCPs were also more satisfied with the educational materials, and more confident in their genetics knowledge and skills compared to those receiving traditional CME materials. Intervention PCPs felt that the web-based curriculum covered medical management, genetics, and ELSI issues significantly better than did the Control Group, and in comparison with traditional curricula. The Intervention Group felt the online tools offered several advantages, and engaged in better shared decision making with standardized patients, however, there was no difference in behavior change between groups with regard to increases in ELSI discussions between PCPs and patients.ConclusionWhile our intervention was deemed more enjoyable, demonstrated significant factual learning and retention, and increased shared decision making practices, there were few differences in behavior changes around ELSI discussions. Unfortunately, barriers to implementing behavior change in clinical genetics is not unique to our intervention. Perhaps the missing element is that busy physicians need systems-level support to engage in meaningful discussions around genetics issues. The next step in promoting active engagement between doctors and patients may be to put into place the tools needed for PCPs to easily access the materials they need at the point-of-care to engage in joint discussions around clinical genetics

Molecular and Electrophysiological Characterization of GFP-Expressing CA1 Interneurons in GAD65-GFP Mice

The use of transgenic mice in which subtypes of neurons are labeled with a fluorescent protein has greatly facilitated modern neuroscience research. GAD65-GFP mice, which have GABAergic interneurons labeled with GFP, are widely used in many research laboratories, although the properties of the labeled cells have not been studied in detail. Here we investigate these cells in the hippocampal area CA1 and show that they constitute ∼20% of interneurons in this area. The majority of them expresses either reelin (70±2%) or vasoactive intestinal peptide (VIP; 15±2%), while expression of parvalbumin and somatostatin is virtually absent. This strongly suggests they originate from the caudal, and not the medial, ganglionic eminence. GFP-labeled interneurons can be subdivided according to the (partially overlapping) expression of neuropeptide Y (42±3%), cholecystokinin (25±3%), calbindin (20±2%) or calretinin (20±2%). Most of these subtypes (with the exception of calretinin-expressing interneurons) target the dendrites of CA1 pyramidal cells. GFP-labeled interneurons mostly show delayed onset of firing around threshold, and regular firing with moderate frequency adaptation at more depolarized potentials

Biological characteristics and treatment outcomes of metastatic or recurrent neuroendocrine tumors: tumor grade and metastatic site are important for treatment strategy

<p>Abstract</p> <p>Background</p> <p>Studies about the biology, treatment pattern, and treatment outcome of metastatic/recurrent neuroendocrine tumor (NET) have been few.</p> <p>Methods</p> <p>We enrolled patients with metastatic/recurrent NET diagnosed between January 1996 and July 2007 and retrospectively analyzed.</p> <p>Results</p> <p>A total of 103 patients were evaluated. Twenty-six patients (25.2%) had pancreatic NET, 27 (26.2%) had gastrointestinal NET, 2 (1.9%) had lung NET, 28 (27.2%) had NET from other sites, and 20 (19.4%) had NET from unknown origin. The liver was the most common metastatic site (68.9%). Thirty-four patients had grade 1 disease, 1 (1.0%) had grade 2 disease, 15 (14.6%) had grade 3 disease, 9 (8.7%) had large cell disease, and 7 (6.8%) had small cell disease.</p> <p>Sixty-six patients received systemic treatment (interferon, somatostatin analogues or chemotherapy), 64 patients received local treatment (TACE, radiofrequency ablation, metastasectomy, etc.). Thirty-six patients received both systemic and local treatments.</p> <p>Median overall survival (OS) was 29.0 months (95% confidence interval, 25.0-33.0) in the103 patients. OS was significantly influenced by grade (<it>p </it>= .001). OS was 43.0, 23.0, and 29.0 months in patients who received local treatment only, systemic treatment only, and both treatments, respectively (<it>p </it>= .245). The median time-to-progression (TTP) was 6.0 months. Overall response rate was 34.0% and disease-control rate was 64.2%. TTP was influenced by the presence of liver metastasis (<it>p </it>= .011).</p> <p>Conclusions</p> <p>OS of metastatic/recurrent NET was different according to tumor grade. TTP was different according to metastasis site. Therefore, development of optimal treatment strategy based on the characteristics of NET is warranted.</p

The coral core microbiome identifies rare bacterial taxa as ubiquitous endosymbionts

© 2015 International Society for Microbial Ecology All rights reserved. Despite being one of the simplest metazoans, corals harbor some of the most highly diverse and abundant microbial communities. Differentiating core, symbiotic bacteria from this diverse hostassociated consortium is essential for characterizing the functional contributions of bacteria but has not been possible yet. Here we characterize the coral core microbiome and demonstrate clear phylogenetic and functional divisions between the micro-scale, niche habitats within the coral host. In doing so, we discover seven distinct bacterial phylotypes that are universal to the core microbiome of coral species, separated by thousands of kilometres of oceans. The two most abundant phylotypes are co-localized specifically with the corals' endosymbiotic algae and symbiont-containing host cells. These bacterial symbioses likely facilitate the success of the dinoflagellate endosymbiosis with corals in diverse environmental regimes

Errores de medicación en pediatría

Concerns regarding patient safety affect healthcare, and medication errors are the most frequent category of medical errors and linked with severe consequences. This study discusses epidemiologic characteristics of medication errors in pediatric patients and points out prevention strategies. Approximately 8% of the studies on the subject of medication errors identified in different national and international databases are distinctively related to the pediatric population. Children are vulnerable to medication errors due to intrinsic factors, such as proper anatomic and physiological characteristics; and due to extrinsic factors, with emphasis on the lack of public health politics and changes in the pharmaceutical industry to attend children's needs. The available evidences indicate, as imperative, the implementation of strategies to prevent medication errors, contributing to promote patient safety.La seguridad del paciente es un problema de salud pública y los errores con medicamentos son los más frecuentes y más graves. Este artículo describe características epidemiológicas de errores de medicación en áreas de atención pediátrica y algunas estrategias de prevención. Aproximadamente 8% de las investigaciones sobre errores de medicación identificadas en las bases de datos nacionales e internacionales se refieren específicamente a niños. Los niños tienen mayor vulnerabilidad a la ocurrencia de errores debidos a factores intrínsecos, con destaque para características anatómicas y fisiológicas, e extrínsecos, en particular con respecto a falta de políticas sanitarias y de la industria farmacéutica orientada a la atención de tales características. Evidencias muestran la necesidad de aplicar estrategias para prevenir errores de medicación, promoviendo la seguridad del paciente.A segurança do paciente constitui problema de saúde pública, e erros com medicamentos são os mais freqüentes e graves. O artigo apresenta características epidemiológicas dos erros de medicação em diferentes áreas de atendimento pediátrico, e aponta estratégias de prevenção. Aproximadamente 8% das pesquisas sobre erros de medicação identificadas em bases de dados nacionais e internacionais referem-se à população pediátrica. Crianças apresentam maior vulnerabilidade à ocorrência de erros devido a fatores intrínsecos, destacando-se características anatômicas e fisiológicas; e extrínsecos, relativos à falta de políticas de saúde e da indústria farmacêutica voltadas ao atendimento de tais especificidades. As evidências apontam para a necessidade de implementação de estratégias de prevenção de erros de medicação, contribuindo para promover a segurança do paciente.Universidade Federal de São Paulo (UNIFESP) Departamento de EnfermagemUNIFESP, Depto. de EnfermagemSciEL

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.