Dolor, calidad de vida relacionada con la salud y utilización de servicios médicos asociados al herpes zoster en Argentina / Herpes zoster-associated pain, health-related quality of life, and healthcare utilization in Argentina

El herpes zoster (HZ) es causado por reactivación del virus varicela-zoster latente. Se caracteriza por exantema vesicular unilateral, neuri-tis aguda y neuralgia posherpética. Aún hay escasos datos sobre el do-lor asociado al HZ (DAZ), su repercusión en la calidad de vida (CdV) y la utilización de recursos sanitarios (URS) asociada en Argentina. En este estudio prospectivo, observacio-nal, de una cohorte, realizado en 3 centros argenti-nos se valuó la carga de morbilidad asociada al HZ en Argentina en contextos clínicos reales. Los pa-cientes fueron enrolados en diversos momentos du-rante un episodio herpético, y seguidos activamen-te los días 14, 21, 30, 60, 90, 120, 150 y 180. Hubo 96 enrolados(edad 70±10,7 años; tiempo desde el inicio del exantema 16±16,9 días[media±DE]). El puntaje del peor dolor (media±DE) disminuyó de 5,5±3,1 en el enrolamiento a 0,2±0,7 a los 180 días de seguimiento. El puntaje del cuestionario de cali-dad de vida EQ-5D (media±DE) disminuyó significa-tivamente de 0,8±0,1 antes del inicio del exantema a 0,6±0,2 tras su inicio (P<0,001), con mejoría gra-dual de la CdV durante 180 días (0,9±0,1), hasta un puntaje similar al previo al inicio del exantema. La URS más frecuente fueron visitas al consultorio mé-dico (96,9%). La gran mayoría de pacientes compró medicamentos recetados (95,8%) y de venta sin receta (83,3%) para los episodios herpéticos. El DAZ estuvo asociado a gran carga de morbili-dad, deterioro de CdV, aumento de URS y costos asociados en Argenti-na. Esto subraya la importancia de estrategias de intervención precoz o prevención para disminuir la carga de morbilidad asociada al HZ

Herpes zoster (HZ) is caused by re-activation of latent varicella zoster virus and is characterized by unilateral, vesicular cutaneous eruptions, acute neuritis, and post-herpetic neuralgia. To date, data on HZ associated pain (ZAP) and its impact on quality of life (QoL) and associated healthcare resource utilization use (HCRU) in Argentina is scarce. This study assessed the burden of illness associated with HZ in Argentina in a real-life clinical setting. This was a prospective, observational, single-cohort study conducted in 3 sites across Argentina. Patients were enrolled at various time points during the course of a zoster episode and were actively followed on days 14, 21, 30, 60, 90, 120, 150, and 180. There were 96 HZ patients enrolled with a mean±SD age and time since rash onset of 70±10. 7 years and 16±16. 9 days, respectively. Mean±SD worst pain score decreased from 5. 5±3. 1 at enrollment to 0. 2±0.7 at 180 days of follow-up. The mean±SD EQ-5D score significantly decreased from 0. 8±0. 1 before rash onset to 0. 6±0. 2 after rash onset (P <0.001) followed by gradual improvement in QoL over 180 days (0. 9±0.) reaching a similar score to that prior to rash onset. The most common HCRU was visits to the doctor's office with 96.9%. The vast majority of patients purchased prescription medications (95.8%) and over-the-counter medications (83.3%) for HZ episodes. ZAP was found to be associated with severe burden of illness, impaired QoL, increased HCRU, and associated cost in Argentina; highlighting the importance of early intervention or prevention strategies to reduce HZ-associated disease burden

Motivation, students' needs and learning outcomes: a hybrid game-based app for enhanced language learning.

In the context of European Higher Education students face an increasing focus on independent, individual learning-at the expense of face-to-face interaction. Hence learners are, all too often, not provided with enough opportunities to negotiate in the target language. The current case study aims to address this reality by going beyond conventional approaches to provide students with a hybrid game-based app, combining individual and collaborative learning opportunities. The 4-week study was carried out with 104 German language students (A1.2 CEFR) who had previously been enrolled in a first-semester A1.1 level course at a Spanish university. The VocabTrainerA1 app-designed specifically for this study-harnesses the synergy of combining individual learning tasks and a collaborative murder mystery game in a hybrid level-based architecture. By doing so, the app provides learners with opportunities to apply their language skills to real-life-like communication. The purpose of the study was twofold: on one hand we aimed to measure learner motivation, perceived usefulness and added value of hybrid game-based apps; on the other, we sought to determine their impact on language learning. To this end, we conducted focus group interviews and an anonymous Technology Acceptance Model survey (TAM). In addition, students took a pre-test and a post-test. Scores from both tests were compared with the results obtained in first-semester conventional writing tasks, with a view to measure learning outcomes. The study provides qualitative and quantitative data supporting our initial hypotheses. Our findings suggest that hybrid game-based apps like VocabTrainerA1-which seamlessly combine individual and collaborative learning tasks-motivate learners, stimulate perceived usefulness and added value, and better meet the language learning needs of today's digital natives. In terms of acceptance, outcomes and sustainability, the data indicate that hybrid game-based apps significantly improve proficiency, hence are indeed, effective tools for enhanced language learning.

Non-random aneuploidy specifies subgroups of pilocytic astrocytoma and correlates with older age.

Pilocytic astrocytoma (PA) is the most common brain tumor in children but is rare in adults, and hence poorly studied in this age group. We investigated 222 PA and report increased aneuploidy in older patients. Aneuploid genomes were identified in 45% of adult compared with 17% of pediatric PA. Gains were non-random, favoring chromosomes 5, 7, 6 and 11 in order of frequency, and preferentially affecting non-cerebellar PA and tumors with BRAF V600E mutations and not with KIAA1549-BRAF fusions or FGFR1 mutations. Aneuploid PA differentially expressed genes involved in CNS development, the unfolded protein response, and regulators of genomic stability and the cell cycle (MDM2, PLK2),whose correlated programs were overexpressed specifically in aneuploid PA compared to other glial tumors. Thus, convergence of pathways affecting the cell cycle and genomic stability may favor aneuploidy in PA, possibly representing an additional molecular driver in older patients with this brain tumor.

En 2010, la Consejería de Salud de Andalucía... [editorial] / No disponible

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Análisis causal del dolor postartroplastia. Propuesta de un algoritmo diagnóstico-terapéutico / causal analysis of painful arthroplasty. Proposal of a diagnostic and therapeutic algorithm

Objetivo del trabajo: Determinar la incidencia de artroplastia dolorosa de rodilla, realizar un análisis causal exhaustivo del dolor postartroplastia y evaluar los resultados funcionales de los pacientes tratados en nuestro centro. Material y Métodos: Estudio observacional prospectivo en el que se evaluaron 540 pacientes sometidos a ATR primaria cementada durante dos años y se seleccionaron los que sufrían un dolor postartroplastia intenso. Todos los pacientes fueron sometidos a diferentes pruebas complementarias con el fin de determinar la causa más probable de dolor. De igual forma, para cada paciente se instauró un tratamiento quirúrgico específico que pretendía resolver la causa de dolor. Resultados: De las 541 artroplastias primarias practicadas, 63 pacientes presentaron un dolor postartroplastia intenso. La incidencia acumulada de dolor intenso ostartroplastia en nuestro centro durante los dos años de seguimiento fue de un 11,64 %. Las causas mecánicas intraarticulares fueron las más frecuentes, justificando el 52,4 % del dolor postartroplastia severo, seguidas por las causas biológicas intraarticulares que constituyeron el 34,9%. En el 11,1 % de los casos no se pudo determinar ninguna causa específica del dolor postartroplastia, considerando, por tanto el origen del dolor desconocido. Por último, las causas extraarticulares, que constituyeron sólo el 1,6% del dolor postartroplastia. Conclusiones: El dolor postartroplastia es una complicación frecuente de la artroplastia de rodilla que puede padecer uno de cada diez pacientes que se somete a una cirugía de sustitución articular. El dolor protésico tiene un origen multifactorial, por lo el diagnóstico causal es complicado y tedioso. Existen determinados factores, como padecer alteraciones psiquiátricas, la obesidad, y una demanda analgésica elevada antes de la intervención se asocian a una mayor probabilidad de dolor postartroplastia

Objective: The aim of this study was to determine the incidence of painful knee arthroplasty and performance a causal analysis of painful arthroplastyin our center. Material and Methods: A prospective observational study in which 540 patients undergoing primary cemented arthroplasty for two years. Were selected those suffering intense pain postarthroplasty. All patients were subjected to various tests in order to determine the most likely cause of pain. Similarly, for each patient a specific surgical treatment intended to address the cause of pain was realized. Results: Of the 541 primary arthroplasties performed, 63 patients suffered severe pain. The cumulative incidence of severe pain postartroplastia in our center during the two years of follow-up was 11.64 %. Mechanical causes were the most frequent justifying 52.4% of the cases, followed by intraarticular biological causes which constituted 34.9% In 11.1% of cases could not determine any specific cause of painful arthroplasty considering therefore an unknown pain. Finally, extra-articular causes, which constituted only 1.6% of painful arthroplasty. Conclusions: The painful arthroplasty is a common complication of knee arthroplasty can have one in ten patients undergoing joint replacement surgery. The prosthetic pain has a multifactorial etiology, so the causal diagnosis is difficult and tedious. Certain factors, such as having psychiatric disorders , obesity , high demand and analgesic before surgery are associated with a greater likelihood of painful arthroplasty

Fusion of TTYH1 with the C19MC microRNA cluster drives expression of a brain-specific DNMT3B isoform in the embryonal brain tumor ETMR.

Embryonal tumors with multilayered rosettes (ETMRs) are rare, deadly pediatric brain tumors characterized by high-level amplification of the microRNA cluster C19MC. We performed integrated genetic and epigenetic analyses of 12 ETMR samples and identified, in all cases, C19MC fusions to TTYH1 driving expression of the microRNAs. ETMR tumors, cell lines and xenografts showed a specific DNA methylation pattern distinct from those of other tumors and normal tissues. We detected extreme overexpression of a previously uncharacterized isoform of DNMT3B originating at an alternative promoter that is active only in the first weeks of neural tube development. Transcriptional and immunohistochemical analyses suggest that C19MC-dependent DNMT3B deregulation is mediated by RBL2, a known repressor of DNMT3B. Transfection with individual C19MC microRNAs resulted in DNMT3B upregulation and RBL2 downregulation in cultured cells. Our data suggest a potential oncogenic re-engagement of an early developmental program in ETMR via epigenetic alteration mediated by an embryonic, brain-specific DNMT3B isoform.

Hypothalamic hamartomas. Part 1. Clinical, neuroimaging, and neurophysiological characteristics.

Hypothalamic hamartomas are uncommon but well-recognized developmental malformations that are classically associated with gelastic seizures and other refractory seizure types. The clinical course is often progressive and, in addition to the catastrophic epileptic syndrome, patients commonly exhibit debilitating cognitive, behavioral, and psychiatric disturbances. Over the past decade, investigators have gained considerable knowledge into the pathobiological and neurophysiological properties of these rare lesions. In this review, the authors examine the causes and molecular biology of hypothalamic hamartomas as well as the principal clinical features, neuroimaging findings, and electrophysiological characteristics. The diverse surgical modalities and strategies used to manage these difficult lesions are outlined in the second article of this 2-part review.

Hypothalamic hamartomas. Part 2. Surgical considerations and outcome.

Hypothalamic hamartomas are uncommon developmental heterotopic masses composed of an intermixed array of neurons, glia, and myelinated fibers closely associated with the mammillary bodies. Gelastic seizures, the hallmark feature of hypothalamic hamartomas, commonly present in early childhood. However, patients usually also display a disabling clinical syndrome, which may include various other types of refractory seizures with secondary generalization together with progressive cognitive, behavioral, and psychiatric dysfunction. The hamartoma itself has been unequivocally shown to be intrinsically epileptogenic. Over the past 2 decades there has been considerable effort to develop neurosurgical techniques to treat the epileptic syndrome effectively as well as to improve the neurocognitive and behavioral outcome.

Registro de artroplastias de Andalucía / Andalusia Arthroplasty register

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Recambios en un solo tiempo de prótesis de cadera y rodilla sobre terreno contaminado: nuestra experiencia / Combined replacement of hip and knee prostheses in a contaminated field: our experience

Objetivo del trabajo: Evaluar resultados obtenidos en recambios en un tiempo de artroplastia séptica o segundo tiempo de recambio séptico (implantación de prótesis sobre terreno contaminado). Material y métodos: Serie de 17 casos, con edad media de 66.8 años y seguimiento medio de 49 meses. Los criterios de exclusión fueron inmunodepresión grave y germen desconocido o no sensible al menos a tres antibióticos. Tras la intervención se administraron antibióticos correspondientes entre 6 semanas y 3 meses. Se estableció la curación como la normalización de las variables indicadoras de infección como mínimo a los 9 meses del recambio. Resultados:14 pacientes evolucionaron hacia la curación completa (seguimiento mínimo 9 meses y máximo 84 meses). 3 casos presentaron recidiva, los tres, portadores de Stafilococcus epidermidis ( a 1, 3 y 7 meses de seguimiento respectivamente). El porcentaje de éxito es de 82.41% (seguimiento medio de 49 meses). Conclusiones: El recambio en un tiempo es una opción atractiva sobre todo en pacientes pluripatológicos, por ofrecer una sola cirugía, menor morbilidad, retorno rápido a las actividades para restaurar una función normal, y un menor coste asociado (AU)

Objective: Evaluate the results obtained in the simultaneous replacement of a septic arthroplasty or a second septic replacement (implanting the prosthesis in a contaminated field). Material and method: Series of 17 cases, with a mean age of 66.8 years and average follow-up of 49 months. The exclusion criteria were serious immunological depression and unknown germ or not sensitive to at least three antibiotics. After the intervention, the corresponding antibiotics were administered between six weeks and three months. Recovery was established as the normality for infection indicator variables at least nine months after the replacement. Results: 14 patients developed towards total recovery (follow-up at least 9 months and maximum 84 months). 3 cases presented relapse, all three carriers of Staphylococcus epidermidis (at 1, 3 and 7 months of follow-up respectively). The success percentage is 82.41% (average follow-up of 49 months). Conclusions: Simultaneous replacements is an interesting option for patients with plural pathologies as it offers a single operation, less morbidity, quicker return to activities to restore normal function and less associated costs (AU)

Body mass index as predictor of health-related quality-of-life changes after total hip arthroplasty: a cross-over study.

The objective of this study was to examine the contribution of patient weight and other preoperative variables to improvements in the general physical health of patients undergoing total hip arthroplasty (THA). Data were prospectively collected on 63 THA patients (28 males and 35 females). The primary outcome measure was the improvement in general health (Short Form-12 Health Survey questionnaire) at three months post-THA. Patients with body mass index >28kg/m(2) showed greater improvements in function and in the physical component of general health after THA. Stepwise regression analyses revealed that the BMI and WOMAC general index were independent and significant predictors of physical function and together explained 34.2% of the variance in physical function scores. These findings suggest that the body mass index before surgery and improvements in hip function are relevant contributors to post-THA improvements in general health.

Genetic aberrations leading to MAPK pathway activation mediate oncogene-induced senescence in sporadic pilocytic astrocytomas.

PURPOSE: Oncogenic BRAF/Ras or NF1 loss can potentially trigger oncogene-induced senescence (OIS) through activation of the mitogen-activated protein kinase (MAPK) pathway. Somatic genetic abnormalities affecting this pathway occur in the majority of pilocytic astrocytomas (PA), the most prevalent brain neoplasm in children. We investigated whether OIS is induced in PA. EXPERIMENTAL DESIGN: We tested expression of established senescence markers in three independent cohorts of sporadic PA. We also assessed for OIS in vitro, using forced expression of wild-type and V600E-mutant BRAF in two astrocytic cell lines: human telomerase reverse transcriptase (hTERT)-immortalized astrocytes and fetal astrocytes. RESULTS: Our results indicate that PAs are senescent as evidenced by marked senescence-associated acidic ß-galactosidase activity, low KI-67 index, and induction of p16(INK4a) but not p53 in the majority of 52 PA samples (46 of 52; 88.5%). Overexpression of a number of senescence-associated genes [CDKN2A (p16), CDKN1A (p21), CEBPB, GADD45A, and IGFBP7] was shown at the mRNA level in two independent PA tumor series. In vitro, sustained activation of wild-type or mutant BRAF induced OIS in both astrocytic cell lines. Loss of p16(INK4a) in immortalized astrocytes abrogated OIS, indicative of the role of this pathway in mediating this phenomenon in astrocytes. OIS is a mechanism of tumor suppression that restricts the progression of benign tumors. We show that it is triggered in PAs through p16(INK4a) pathway induction following aberrant MAPK activation. CONCLUSIONS: OIS may account for the slow growth pattern in PA, the lack of progression to higher-grade astrocytomas, and the high overall survival of affected patients.

Percutaneous treatment of bone tumors by radiofrequency thermal ablation.

We present our experience of the treatment of bone tumors with radiofrequency thermal ablation (RFTA). Over the past 4 years, we have treated 26 cases (22 benign and 4 malignant) using CT-guided RFTA. RFTA was the sole treatment in 19 cases and was combined with percutaneous cementation during the same session in the remaining seven cases. Our approach to the tumors was simplified, using a single point of entrance for both RFTA and percutaneous osteoplasty. In the benign cases, clinical success was defined as resolution of pain within 1 month of the procedure and no recurrence during the follow-up period. It was achieved in 19 out of the 21 patients in which curative treatment was attempted. The two non-resolved cases were a patient with osteoid osteoma who developed a symptomatic bone infarct after a symptom-free period of 2 months and another with femoral diaphysis osteoblastoma who suffered a pathological fracture after 8 months without symptoms. The procedure was considered clinically successful in the five cases (4 malign and 1 benign) in which palliative treatment was attempted, because there was a mean (±SD) reduction in visual analogue scale (VAS) pain score from 9.0±0.4 before the procedure to <4 during the follow-up period.

Treatment of bone tumours by radiofrequency thermal ablation.

Radiofrequency thermal ablation (RFTA) is considered the treatment of choice for osteoid osteomas, in which it has long been safely used. Other benign conditions (chondroblastoma, osteoblastoma, giant cell tumour, etc.) can also be treated by this technique, which is less invasive than traditional surgical procedures. RFTA ablation is also an option for the palliation of localized, painful osteolytic metastatic and myeloma lesions. The reduction in pain improves the quality of life of patients with cancer, who often have multiple morbidities and a limited life expectancy. In some cases, these patients are treated with RFTA because conventional therapies (surgery, radiotherapy, chemotherapy, etc.) have been exhausted. In other cases, it is combined with conventional therapies or other percutaneous treatments, e.g., cementoplasty, offering faster pain relief and bone strengthening. A multidisciplinary approach to the management of these patients is recommended to select the optimal treatment, including orthopaedic surgeons, neurosurgeons, medical and radiation oncologists and interventional radiologists.

Coordinación sanitaria en España. La coordinación hoy / Health care coordination in Spain. Coordination today

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Endosonografía del esfínter rectal / Ano-rectal endosonography

Objetivo: Describir la técnica e indicaciones de la valoración del canal anorrectal mediante endosonografía, en el estudio de hallazgos normales y lesiones benignas observadas. Materiales y métodos: Experiencia en 234 pacientes entre el 2004 y el 2007. Técnica: Se describen y se registran los hallazgos de las diferentes capas anatómicas observadas durante el estudio endosonográfico. En caso de sospechar una fístula, se inyectó de 1 ml-2 ml de peróxido de hidrógeno al 5 por el orificio fistuloso, al tiempo que se mueve el transductor, hasta evaluar su trayecto. Se describen los tipos de fístulas, relación anatómica circundante, estado de esfínteres y otros hallazgos. Todos los exámenes fueron realizadospor un proctólogo y un radiólogo. Resultados: El 60% hombres y el 40% mujeres. De los 234 pacientes, 2 desistieron de realizarse el estudio completo por molestias. Encontramos 14% normales y 86% patológicos. El motivo de envío más frecuente fue sospecha clínica de fístulas, seguido de incontinencia fecal. La distribución de los hallazgos patológicos fue: fístulas transesfinterianas, 59%; sección esfintérica, 22%; fístulas con sección esfintérica, 4,5%, y otros, 13,6%, que corresponden a zonas fibróticas sin otra lesión asociada. Las alteraciones esfinterianas fueron clasificadas, y se encontró compromiso mixto (tanto en el interno como en el externo) en el 80% de todas las secciones esfinterianas. Conclusión: las imágenes obtenidas mediante rotación del transductor 360º durante la endosonografia anorrectal son de gran utilidad en la valoración de la localización, extensión y compromiso anatómico de los trastornos esfinterianos de manera rápida.

Molecular profiling identifies prognostic subgroups of pediatric glioblastoma and shows increased YB-1 expression in tumors.

PURPOSE: Pediatric glioblastoma (pGBM) is a rare, but devastating brain tumor. In contrast to GBM in adults (aGBM), little is known about the mechanisms underlying its development. Our aim is to gain insight into the molecular pathways of pGBM. MATERIALS AND METHODS: Thirty-two pGBM and seven aGBM samples were investigated using biochemical and transcriptional profiling. Ras and Akt pathway activation was assessed through the phosphorylation of downstream effectors, and gene expression profiles were generated using the University Health Network Human 19K cDNA arrays. Results were validated using real-time polymerase chain reaction and immunohistochemistry and compared with existing data sets on aGBM. RESULTS: There are at least two subsets of pGBM. One subset, associated with Ras and Akt pathway activation, has very poor prognosis and exhibits increased expression of genes related to proliferation and to a neural stem-cell phenotype, similar to findings in aggressive aGBM. This subset was still molecularly distinguishable from aGBM after unsupervised and supervised analysis of expression profiles. A second subset, with better prognosis, is not associated with activation of Akt and Ras pathways, may originate from astroglial progenitors, and does not express gene signatures and markers shown to be associated with long-term survival in aGBM. Both subsets of pGBM show overexpression of Y-box-protein-1 that may help drive oncogenesis in this tumor. CONCLUSION: Our work, the first study of gene expression profiles in pGBM, provides valuable insight into active pathways and targets in a cancer with minimal survival, and suggests that these tumors cannot be understood exclusively through studies of aGBM.

Disconnective hemispherectomy for hemispheric dysplasia.

Twelve patients suffering from intractable epilepsy and presenting with radiological evidence of diffuse hemispheric involvement of a dysplastic process, were treated by disconnective hemispherectomy, either functional hemispherectomy or peri-insular hemispherotomy. The median age at surgery was 4.5 years old and the interval between seizure onset and surgery, 3 years. All patients underwent a presurgical evaluation that led to the suggestion of disconnective hemispherectomy. Over 70% of patients have remained in Engel's seizure outcome class I since surgery and another 18% have had a satisfactory seizure outcome. There was one unexplained death and one case of early hydrocephalus. Hemispherectomy offers the possibility to improve seizure control in the majority of patients undergoing surgery for extensive dysplastic pathology of the hemisphere. Disconnective techniques reduce the rate of complications in this specific pathology.

Ophthalmic complications of slit-ventricle syndrome in children.

OBJECTIVE: To present the ophthalmic features and visual prognosis of patients with slit-ventricle syndrome (SVS). DESIGN: Observational case series. PARTICIPANTS: Six patients diagnosed and treated with SVS at the Montreal Children's Hospital between 1985 and 1999. METHODS: Patients were included in this study if they had an appropriate ophthalmologic follow-up and if they fulfilled the criteria for the diagnosis of SVS based on intracranial pressure monitoring and neuroimaging studies. MAIN OUTCOME MEASURES: Features studied included patients' baseline ophthalmologic evaluation, visual outcome, and neurosurgical characteristics. RESULTS: The follow-up ranged from 1 to 14 years. The average number of shunting procedures was 3.7. Ocular examination performed on the initial visit revealed a normal visual acuity in four patients, esotropia in three of six patients, and nystagmus in two of six patients. Cycloplegic refraction was normal in all the subjects. Initial funduscopic evaluation revealed optic atrophy in a 4-month-old infant, whereas two children developed optic atrophy later in the course of the disease. One child developed severe visual field defects. The two children with optic atrophy had moderate to severe loss of visual acuity associated with SVS. CONCLUSIONS: A prompt recognition of patients with SVS is crucial, because these individuals are at an increased risk for significant visual loss.