Formación continuada en un equipo de atención primaria: análisis de las sesiones docentes 1996-1998

ObjetivoDescribir las sesiones docentes de un equipo de atención primaria en el trienio 1996-1998. Identificar los profesionales que las realizaron, así como estudiar las áreas del conocimiento abordadas.DiseñoEstudio descriptivo transversal, retrospectivo.EmplazamientoCentro de salud docente perteneciente a una zona de salud rural.ParticipantesTotal de sesiones docentes realizadas durante el trienio estudiado (n = 249).IntervencionesDe la hoja de registro mensual del programa de formación continuada de nuestra gerencia, se extrajeron las siguientes variables: fecha actividad, duración, número de asistentes, tipo de sesión, profesional docente y contenido de actividad (clasificada por patología según órganos y sistemas para sesión bibliográfica, clínica y con experto; cartera servicios de atención primaria-INSALUD 1996 para sesión sobre programa; informática).Mediciones y resultados principalesSesiones por mes: media 6,9 (DE, 4,8). Media asistentes: 9,3 (DE, 3,01). Duración media: 36,5 minutos (DE, 11,0). Tipo de sesión: bibliográfica, 65,2%; sobre programa, 18; sesión con experto, 7,2; informática, 5,6; clínica, 4. Responsables docentes: médico residente, 39,4%; médico de familia tutor, 34,9; médico de familia no tutor, 7,2; ATS, 6,4; médico hospitalario, 4; médico de familia sustituto, 3,6; farmacéutico, 2,8; pediatra, 1,2; fisioterapeuta, 0,4. Contenido actividades más frecuentes: patología general inespecífica, 16,1%; enfermedades de la piel, 8,8, y enfermedades del sistema endocrino, 7,6%.ConclusionesBaja frecuencia de sesiones clínicas. Los responsables docentes fueron mayoritariamente médicos de familia tutores y médicos residentes, siendo escasa la participación del resto de personal.ObjectivesTo describe the teaching sessions of a primary care team in the three-year period 1996-1998. To identify the professionals who ran them and study the areas of knowledge tackled. Design. A retrospective, cross-over, descriptive study.SettingTeaching health centre belonging to a rural health district.ParticipantsAll the teaching sessions that took place during the three-year period (n = 249). Interventions. The following variables were extracted from the monthly register sheet of the ongoing training programme of our management: date of activity, duration, number attending, type of session, teaching professional and contents of activity (classified by pathology according to organs and systems for bibliographic, clinical and expert sessions; portfolio of 1996 Primary Care- INSALUD services for session on programme; computer studies).Measurements and main resultsMean sessions per month: 6.9 (SD: 4.8). Mean attendance: 9.3 persons (SD: 3.01). Mean length: 36.5 minutes (SD: 11.0). Type of session: bibliographic 65.2%, on programme 18%, session with expert 7.2%, computer studies 5.6%, clinical 4%. Responsible for teaching: intern 39.4%; family doctor tutor 34.9%; family doctor not a tutor 7.2%; nurse 6.4%; hospital doctor 4%; locum family doctor 3.6%; pharmacist 2.8%; paediatrician 1.2%; physiotherapist 0.4%. Most common contents: non-specific general pathology (16.1%), skin diseases (8.8%), diseases of the endocrine system (7.6%).ConclusionsLow frequency of clinical sessions. The teachers in charge were mainly family doctor tutors and interns, with the rest of the staff participating little

Implementation of at-line capillary zone electrophoresis for fast and reliable determination of adenovirus concentrations in vaccine manufacturing

A CZE method was validated and implemented for fast and accurate in-process determination of adenovirus concentrations of downstream process samples obtained during manufacturing of adenovirus vector-based vaccines. An analytical-quality-by-design approach was embraced for method development, method implementation, and method maintenance. CZE provided separation of adenovirus particles from sample matrix components, such as cell debris, residual DNA and proteins. The intermediate precision of the virus particle concentration was 6.9% RSD and the relative bias was 2.3%. In comparison, the CZE method is intended to replace a quantitative polymerase chain reaction method which requires three replicates in three analytical runs to achieve an intermediate precision of 8.1% RSD. Given that, in addition, the time from sampling till reporting results of the CZE method was less than 2 h, whereas quantitative polymerase chain reaction requires 3 days, it follows that the CZE method enables faster processing times in downstream processing

Hepatic disease as the first manifestation of progressive myoclonus epilepsy of Lafora

5 páginas, 2 figuras -- PAGS nros. 1369-1373Background: Lafora disease (LD; progressive myoclonus epilepsy type 2; EPM2) is an autosomal recessive disorder caused by mutations in the EPM2A and EPM2B genes. LD is characterized by the presence of strongly PAS-positive intracellular inclusions (Lafora bodies) in several tissues. Glycogen storage disease type IV (GSD-IV; Andersen disease) is an autosomal recessive disorder characterized by cirrhosis leading to severe liver failure. GSD-IV has been associated with mutations in the glycogen branching enzyme gene (GBE). Histopathologic changes of the liver in both diseases show an identical appearance, although cirrhosis has never been described in patients with LD. We report a LD family in which the proband presented severe liver failure at onset of the disease. Methods: Clinical histories, physical and neurologic examination, laboratory tests, EEGs, MRI of the brain, and liver or axillary skin biopsies were performed in the two affected siblings. The diagnosis was confirmed by molecular genetic analysis of the EPM2A, EPM2B, and GBE genes and loci. Results: During the first decade of life, abnormalities in liver function tests were detected in the two affected siblings. The proband's liver dysfunction was severe enough to require liver transplantation. Subsequently, both sibs developed LD. Mutation analysis of EPM2A revealed a homozygous Arg241stop mutation in both patients. Conclusions: This is the first description of severe hepatic dysfunction as the initial clinical manifestation of LD. The phenotypic differences between the two affected siblings suggest that modifier genes must condition clinical expression of the disease outside the CNSPeer reviewe

Drp1 overexpression induces desmin disassembling and drives kinesin-1 activation promoting mitochondrial trafficking in skeletal muscle

Mitochondria change distribution across cells following a variety of pathophysiological stimuli. The mechanisms presiding over this redistribution are yet undefined. In a murine model overexpressing Drp1 specifically in skeletal muscle, we find marked mitochondria repositioning in muscle fibres and we demonstrate that Drp1 is involved in this process. Drp1 binds KLC1 and enhances microtubule-dependent transport of mitochondria. Drp1-KLC1 coupling triggers the displacement of KIF5B from kinesin-1 complex increasing its binding to microtubule tracks and mitochondrial transport. High levels of Drp1 exacerbate this mechanism leading to the repositioning of mitochondria closer to nuclei. The reduction of Drp1 levels decreases kinesin-1 activation and induces the partial recovery of mitochondrial distribution. Drp1 overexpression is also associated with higher cyclin-dependent kinase-1 (Cdk-1) activation that promotes the persistent phosphorylation of desmin at Ser-31 and its disassembling. Fission inhibition has a positive effect on desmin Ser-31 phosphorylation, regardless of Cdk-1 activation, suggesting that induction of both fission and Cdk-1 are required for desmin collapse. This altered desmin architecture impairs mechanotransduction and compromises mitochondrial network stability priming mitochondria transport through microtubule-dependent trafficking with a mechanism that involves the Drp1-dependent regulation of kinesin-1 complex

Unjamming overcomes kinetic and proliferation arrest in terminally differentiated cells and promotes collective motility of carcinoma

During wound repair, branching morphogenesis and carcinoma dissemination, cellular rearrangements are fostered by a solid-to-liquid transition, known as unjamming. The biomolecular machinery behind unjamming and its pathophysiological relevance remain, however, unclear. Here, we study unjamming in a variety of normal and tumorigenic epithelial two-dimensional (2D) and 3D collectives. Biologically, the increased level of the small GTPase RAB5A sparks unjamming by promoting non-clathrin-dependent internalization of epidermal growth factor receptor that leads to hyperactivation of the kinase ERK1/2 and phosphorylation of the actin nucleator WAVE2. This cascade triggers collective motility effects with striking biophysical consequences. Specifically, unjamming in tumour spheroids is accompanied by persistent and coordinated rotations that progressively remodel the extracellular matrix, while simultaneously fluidizing cells at the periphery. This concurrent action results in collective invasion, supporting the concept that the endo-ERK1/2 pathway is a physicochemical switch to initiate collective invasion and dissemination of otherwise jammed carcinoma

La dispensación como punto clave en la detección de necesidades farmacoterapeuticas de los pacientes

Es durante el proceso de la dispensación donde el farmacéutico tiene una gran oportunidad para poder detectar las necesidades farmacoterapéuticas de los pacientes que acuden a la Oficina de Farmacia y por ello este servicio profesional es de una importancia muy relevante en la Atención Farmacéutica; ya que tras la dispensación y siempre que el paciente así lo quiera, se dará paso al proceso de optimización de la farmacoterapia, para tratar de asegurar que cada medicamento que precisa nuestro paciente alcanza el objetivo terapéutico para el que fue prescrito sin producir efectos adversos

La dispensación como punto clave en la detección de necesidades farmacoterapeuticas de los pacientes

Es durante el proceso de la dispensación donde el farmacéutico tiene una gran oportunidad para poder detectar las necesidades farmacoterapéuticas de los pacientes que acuden a la Oficina de Farmacia y por ello este servicio profesional es de una importancia muy relevante en la Atención Farmacéutica; ya que tras la dispensación y siempre que el paciente así lo quiera, se dará paso al proceso de optimización de la farmacoterapia, para tratar de asegurar que cada medicamento que precisa nuestro paciente alcanza el objetivo terapéutico para el que fue prescrito sin producir efectos adversos

Phase 2 Study of Pomalidomide (CC-4047) Monotherapy for Children and Young Adults With Recurrent or Progressive Primary Brain Tumors

INTRODUCTION: Treatment of recurrent primary pediatric brain tumors remains a major challenge, with most children succumbing to their disease. We conducted a prospective phase 2 study investigating the safety and efficacy of pomalidomide (POM) in children and young adults with recurrent and progressive primary brain tumors. BACKGROUND: METHODS: Patients with recurrent and progressive high-grade glioma (HGG), diffuse intrinsic pontine glioma (DIPG), ependymoma, or medulloblastoma received POM 2.6 mg/m2/day (the recommended phase 2 dose [RP2D]) on days 1-21 of a 28-day cycle. A Simon’s Optimal 2-stage design was used to determine efficacy. Primary endpoints included objective response (OR) and long-term stable disease (LTSD) rates. Secondary endpoints included duration of response, progression-free survival (PFS), overall survival (OS), and safety. RESULTS: 46 patients were evaluable for response (HGG, n = 19; DIPG, ependymoma, and medulloblastoma, n = 9 each). Two patients with HGG achieved OR or LTSD (10.5% [95% CI, 1.3%-33.1%]; 1 partial response and 1 LTSD) and 1 patient with ependymoma had LTSD (11.1% [95% CI, 0.3%-48.2%]). There were no ORs or LTSD in the DIPG or medulloblastoma cohorts. The median PFS for patients with HGG, DIPG, ependymoma, and medulloblastoma was 7.86, 11.29, 8.43, and 8.43 weeks, respectively. Median OS was 5.06, 3.78, 12.02, and 11.60 months, respectively. Neutropenia was the most common grade 3/4 adverse event. CONCLUSIONS: Treatment with POM monotherapy did not meet the primary measure of success in any cohort. Future studies are needed to evaluate if POM would show efficacy in tumors with specific molecular signatures or in combination with other anticancer agents. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT03257631; EudraCT, identifier 2016-002903-25

Accuracy and limitations of the growth hormone (GH) releasing hormone-arginine retesting in young adults with childhood-onset GH deficiency

Background: Re-testing for GH secretion is needed to confirm the diagnosis of GH deficiency (GHD) after adult height achievement in childhood-onset GHD (COGHD). Aim: To define the cut-off of GH peak after retesting with GH-releasing hormone plus arginine (GHRHarg) in the diagnosis of permanent GHD in COGHD of different etiology. Patients and methods: Eighty-eight COGHD (median age 17.2 y), 29 idiopathic GHD (IGHD), 44 cancer survivors (TGHD) and 15 congenital GHD (CGHD) were enrolled in the study; 54 had isolated GHD (iGHD) and 34 had multiple pituitary hormone deficiencies (MPHD). All were tested with insulin tolerance test (ITT) and GHRHarg. IGHD with a GH response to ITT 656\ub5g/L were considered true negatives and served as the control group, and patients with a GH response <6\ub5g/L as true positives. Baseline IGF-I was also measured. The diagnostic accuracy of GHRHarg testing and of IGF-I SDS in patients with GHD of different etiologies was evaluated by ROC analysis. Results: Forty-six subjects with a GH peak to ITT 656\ub5g/L and 42 with GH peak <6 \ub5g/L showed a GH peak after GHRHarg between 8.8\u2013124\ub5g/L and 0.3\u201326.3\ub5g/L, respectively; 29 IGHD were true negatives, 42 were true positives and 17 with a high likelihood GHD showed a GH peak to ITT 656\ub5g/L. ROC analysis based on the etiology indicated the best diagnostic accuracy for peak GH cutoffs after GHRHarg of 25.3 \ub5g/L in CGHD, 15.7 in TGHD, and 13.8 in MPHD, and for IGF-1 SDS at 122.1 in CGHD, 121.5 in TGHD, and 121.9 in MPHD. Conclusions: Our findings indicate that the best cut-off for GH peak after retesting with GHRHarg changes according to the etiology of GHD during the transition age. Based on these results the diagnostic accuracy of GHRHarg remains questionable

Genome-wide association meta-analysis for early age-related macular degeneration highlights novel loci and insights for advanced disease

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