Implantes cocleares: prioridad para niños con pérdida sensorial dual en Cuba / Cochlear implants: priority for children with dual sensory loss in Cuba

RESUMEN Fundamento: desde el año 2005 se crea el Programa Cubano de Implantes Cocleares para niños sordos y sordociegos, con prioridad para niños con pérdida sensorial dual. Objetivo: describir el comportamiento de la pérdida sensorial dual en niños del Programa Cubano de Implantes Cocleares. Métodos: se realizó un estudio observacional, descriptivo, retrospectivo de niños con pérdida sensorial dual que recibieron implante coclear entre febrero de 2005 y marzo de 2013 en Cuba. De las historias clínicas y la base de datos del programa fue obtenida la información que permitió elaborar el informe. Con antelación, se ilustran los primeros resultados sobre neuroplasticidad obtenidos con potencial evocado somatosensorial de nervio mediano realizado con parte del protocolo de estudio de investigación preimplante coclear en el Programa Cubano de Implantes Cocleares. Resultados: con el programa se han beneficiado 27 niños con pérdida sensorial dual con implantes cocleares, con cobertura a todas las provincias del país. Seis niños presentaron una enfermedad asociada, predominaron los factores pre/peri-natales y el síndrome de Usher como principales agentes causales de la sordoceguera. La pérdida auditiva fue prelocutiva en 24 niños, confirmada y caracterizada mediante electroaudiometría. Los estudios de imágenes de oídos no mostraron malformaciones. La implantación fue unilateral, sobre todo el oído derecho, sin complicaciones quirúrgicas en ninguno de los niños. Mientras que el estudio de neuroplasticidad evidencia reorganización cortical somestésica en niños con pérdida sensorial dual. Conclusiones: el Programa Cubano de Implantes Cocleares ha logrado un trabajo sostenido en la evaluación e implantación de niños con pérdida sensorial dual, distinguiéndose la investigación sobre neuroplasticidad, la cual ha dado evidencias de representación cortical somestésico preimplante coclear en estos niños. Ello será útil para evaluar la reorganización cortical post-implante coclear y correlacionarlo con el aprovechamiento del uso del implante coclear.

ABSTRACT Background : since 2005 the Cuban Cochlear Implant Program for deaf and deaf-blind children has been created, with priority for children with dual sensory loss. Objective: is to describe the work of the Cuban Cochlear Implant Program with children with dual sensory loss. Methods : a descriptive, retrospective study of children with dual sensory loss who received a cochlear implant between February 2005 and March 2013 in Cuba. The information to conform this descriptive report was obtained from the clinical histories and the database of the program; it also illustrates the first results on neuroplasticity obtained with the somatosensory evoked potential of the median nerve carried out with part of the pre-cochlear implant research study protocol in the Cuban Cochlear Implant Program. Results : the program has benefited 27 children with dual sensory loss with cochlear implants, covering all provinces of the country. Six children presented an associated pathology, with pre/peri-natal factors and Usher Syndrome as the main causal agents of deaf-blindness. Hearing loss was pre-lingual in 24 children, confirmed and characterized by electro-audiometry. No malformations were found in the ear images. The implantation was unilateral, mostly the right ear, without surgical complications in all the children. While the neuroplasticity study shows somesthetic cortical reorganization in children with dual sensory loss. Conclusions : the Cuban Cochlear Implant Program has achieved sustained work in the evaluation and implantation of children with dual sensory loss, a distinctive aspect being the research on neuroplasticity, which has provided evidence of somesthetic cortical representation pre-cochlear implantation in these children. This will be useful to assess cortical reorganization post- cochlear implant and correlate it with the use of the cochlear implant.

Calidad de vida en niños del Programa Cubano de Implantes Cocleares / Quality of life in children of the Cuban Cochlear Implant Program

RESUMEN Fundamento: los estudios publicados sobre los resultados del Programa Cubano de Implantes Cocleares hacen referencia a evaluaciones audiológicas y quirúrgicas, lo que carece de la dimensión que aportaría conocer, el impacto del programa en la calidad de vida de los niños implantados y familia. Objetivo: determinar el impacto del Programa Cubano de Implantes Cocleares en la calidad de vida de los niños implantados y su familia. Métodos: se realizó un estudio descriptivo, prospectivo, longitudinal (pre- y post-implante coclear) a partir de la aplicación del cuestionario de calidad de vida del proyecto internacional pediátrico Cochlear paediatric implanted recipient observational study y la prueba de categorías del rendimiento auditivo, mediante un análisis de varianza de medidas repetidas. Resultados: el estudio evidencia que los implantes cocleares impactan en la familia y la calidad de vida de los niños, con mejora significativa tan temprano como seis meses post-implante coclear y mayores beneficios al año de implantados, respaldado por los hallazgos en la prueba de categorías del rendimiento auditivo, mientras que las expectativas de los padres se ajustan según avanza la rehabilitación post-implante coclear. Conclusiones: los implantes cocleares impactan en la calidad de vida del niño y su familia en la medida que avanza el programa de rehabilitación post-implante, al ajustarse a las expectativas de los padres o tutores, los cuales reportan cambios positivos en el desarrollo de las actividades diarias del niño, efecto sostenido en el tiempo.

ABSTRACT Background: the studies published on the results of the Cuban Cochlear Implants Program refer to audiological and surgical evaluations, lacking the dimension that knowing about the impact of cochlear implants on the quality of life of children and their family. Objective: to determine the impact in the Cuban Cochlear Implants Program on the quality of life of children and their family. Methods: it was carried out a descriptive, prospective, longitudinal study (pre- and post-cochlear implant) from the application of a quality of life questionnaire of the international pediatric project cochlear pediatric implanted recipient observational study and the categories auditory performance test, being applied an analysis of variance of repeated measures. Results: the study shows that cochlear implants impact on the quality of life of children and family, and improves significantly as early as six months post-cochlear implant, with greater benefits one year after implantation, supported by the findings of the categories auditory performance test. While parental expectations are adjusted as post-cochlear implant rehabilitation progresses. Conclusions: cochlear implants impact on the quality of life of the child and family with the post-implant rehabilitation program progresses, adjusting the expectations of the parents or child's guardian, who report positive changes in the development of their daily activities, a sustained effect in the time.

Autonomia e exercício de direitos na experiência da gestão autônoma da medicação / Autonomy and rights exercise in autonomous management of medication experience / Autonomía y ejercicio de derechos en la experiencia de la gestión autónoma de la medicación

Resumo O artigo investigou os efeitos de uso da versão brasileira do Guia da Gestão Autônoma da Medicação (GAM-BR) em grupos de intervenção em serviços públicos saúde mental. Objetiva-se analisar narrativas de usuários, psiquiatras e demais profissionais a partir da relação de cada um deles com a prescrição medicamentosa, mote do trabalho com o Guia. Participaram da pesquisa três CAPS do sul do país, integrantes da pesquisa multicêntrica GAM-BR. O áudio das falas produzidas nos grupos focais e nas entrevistas foi gravado, transcrito e transformado em narrativas por meio da extração dos núcleos argumentais. Os resultados apontam para a ampliação da concepção de autonomia e maior reconhecimento dos direitos dos usuários. Sugere, porém, dificuldades no exercício desses direitos, especialmente com relação ao tratamento medicamentoso, visto como condição para manutenção do vínculo com os serviços. Ressalta a importância de maior reflexão, tendo em vista a manutenção da lógica da escolha, privatizante e individualista, em detrimento da lógica do cuidado que valoriza o trabalho em rede e a corresponsabilização.

Abstract This article analyzed the effects of using the Brazilian version of the Autonomous Medication Management Guide (GAM-BR) in intervention groups in mental health services. Users, psychiatrists and other professionals' narratives were verified to check the relationship of each one with the prescription, the main principle of the guide. Three CAPS (mental health care services) from the south of the country have participated in this research, all members of the multicentric research GAM-BR. The material was audio-recorded, transcribed and transformed in narratives. The results show increase of the conception of autonomy and wider acknowledgment of users' rights. A broadening concept of users' autonomy and a greater recognition of their rights was observed. However, issues were found in the exercise of rights, especially regarding drug treatment, which was seen as a condition for their bond maintenance with services. Further reflection on this subject is emphasized, owing to maintaining the logic of choice, which focuses on privatization and individualism, instead of the care that enhances network and co-responsibility.

Resumen El artículo investiga los efectos de uso de la Guía de Gestión Autónoma de la Medicación (GAM-BR), versión brasileña, en grupos de intervención en servicios de salud mental. El objetivo fue analizar narrativas de usuarios, psiquiatras y otros profesionales a partir de su relación con la prescripción de medicamentos, principio del trabajo con la Guía. Participaron en la investigación tres CAPS (Centros de atención psicosocial) del Sur del país, todos miembros de la investigación multicéntrica acerca de la GAM. Todo el material de audio fue grabado, transcrito y transformado en narrativas por medio de la extracción de los núcleos de significación. Se señala la expansión de la noción de autonomía de los usuarios y un mayor reconocimiento de sus derechos. Se presentaron dificultades para avanzar en el ejercicio de esos derechos, especialmente en cuanto al tratamiento farmacológico, que todavía se ve como una condición a la manutención del vínculo con los servicios. Es necesaria una mayor reflexión acerca del tema, considerando la manutención de la lógica de la elección, privatizante e individualista, en lugar de una lógica del cuidado que valorice el trabajo en la red y la corresponsabilización.

Next generation sequencing of 11 HLA loci characterises a diverse UK cord blood bank.

The introduction of next generation sequencing (NGS) for stem cell donor registry typing has contributed to faster identification of compatible stem cell donors. However, the successful search for a matched unrelated donor for some patient groups is still affected by their ethnicity. In this study, DNA samples from 714 National Health Service (NHS) Cord Blood Bank donors were typed for HLA-A, -B, -C, -DRB1, -DRB345, -DQA1, -DQB1, -DPA1 and -DPB1 by NGS. Analysis of the ethnic diversity showed a high level of diversity, with the cohort comprising of 62.3% European and 37.7% of either multi-ethnic or non-European donors, of which 12.3% were multi-ethnic. The HLA diversity was further confirmed using PyPop analysis, 405 distinct alleles were observed in the overall NHS-CBB cohort, of which 37 alleles are non-CWD, including A*31:14N, B*35:68:02, C*14:23 and DQA1*05:10. Furthermore, HLA-DQA1 and HLA-DPA1 analysis showed 12% and 10%, respectively, of the alleles currently submitted to IMGT, confirming further diversity of the NHS-CBB cohort. The application of 11 HLA loci resolution by NGS revealed a high level of diversity in the NHS-CBB cohort. The incorporation of this data coupled with ethnicity data could lead to improved donor selection, contributing to better clinical outcomes for patients.

Analysis of Anti-RNA Polymerase III Antibody-positive Systemic Sclerosis and Altered GPATCH2L and CTNND2 Expression in Scleroderma Renal Crisis.

OBJECTIVE: Scleroderma renal crisis (SRC) is a life-threatening complication of systemic sclerosis (SSc) strongly associated with anti-RNA polymerase III antibody (ARA) autoantibodies. We investigated genetic susceptibility and altered protein expression in renal biopsy specimens in ARA-positive patients with SRC. METHODS: ARA-positive patients (n = 99) with at least 5 years' follow-up (49% with a history of SRC) were selected from a well characterized SSc cohort (n = 2254). Cases were genotyped using the Illumina Human Omni-express chip. Based on initial regression analysis, 9 single-nucleotide polymorphisms (SNP) were chosen for validation in a separate cohort of 256 ARA-positive patients (40 with SRC). Immunostaining of tissue sections from SRC or control kidney was used to quantify expression of candidate proteins based upon genetic analysis of the discovery cohort. RESULTS: Analysis of 641,489 SNP suggested association of POU2F1 (rs2093658; P = 1.98 × 10-5), CTNND2 (rs1859082; P = 5.58 × 10-5), HECW2 (rs16849716; P = 1.2 × 10-4), and GPATCH2L (rs935332; P = 4.92 × 10-5) with SRC. Further, the validation cohort showed an association between rs935332 within the GPATCH2L region, with SRC (P = 0.025). Immunostaining of renal biopsy sections showed increased tubular expression of GPATCH2L (P = 0.026) and glomerular expression of CTNND2 (P = 0.026) in SRC samples (n = 8) compared with normal human kidney controls (n = 8), despite absence of any genetic replication for the associated SNP. CONCLUSION: Increased expression of 2 candidate proteins, GPATCH2L and CTNND2, in SRC compared with control kidney suggests a potential role in pathogenesis of SRC. For GPATCH2L, this may reflect genetic susceptibility in ARA-positive patients with SSc based upon 2 independent cohorts.

Next-generation HLA typing of 382 International Histocompatibility Working Group reference B-lymphoblastoid cell lines: Report from the 17th International HLA and Immunogenetics Workshop.

Extended molecular characterization of HLA genes in the IHWG reference B-lymphoblastoid cell lines (B-LCLs) was one of the major goals for the 17th International HLA and Immunogenetics Workshop (IHIW). Although reference B-LCLs have been examined extensively in previous workshops complete high-resolution typing was not completed for all the classical class I and class II HLA genes. To address this, we conducted a single-blind study where select panels of B-LCL genomic DNA samples were distributed to multiple laboratories for HLA genotyping by next-generation sequencing methods. Identical cell panels comprised of 24 and 346 samples were distributed and typed by at least four laboratories in order to derive accurate consensus HLA genotypes. Overall concordance rates calculated at both 2- and 4-field allele-level resolutions ranged from 90.4% to 100%. Concordance for the class I genes ranged from 91.7 to 100%, whereas concordance for class II genes was variable; the lowest observed at HLA-DRB3 (84.2%). At the maximum allele-resolution 78 B-LCLs were defined as homozygous for all 11 loci. We identified 11 novel exon polymorphisms in the entire cell panel. A comparison of the B-LCLs NGS HLA genotypes with the HLA genotypes catalogued in the IPD-IMGT/HLA Database Cell Repository, revealed an overall allele match at 68.4%. Typing discrepancies between the two datasets were mostly due to the lower-resolution historical typing methods resulting in incomplete HLA genotypes for some samples listed in the IPD-IMGT/HLA Database Cell Repository. Our approach of multiple-laboratory NGS HLA typing of the B-LCLs has provided accurate genotyping data. The data generated by the tremendous collaborative efforts of the 17th IHIW participants is useful for updating the current cell and sequence databases and will be a valuable resource for future studies.

Evaluation of Ion Torrent sequencing technology for rapid clinical human leucocyte antigen typing.

The development of techniques to define the human leucocyte antigen (HLA) region has proven to be challenging due to its high level of polymorphism. Within a clinical laboratory, a technique for high-resolution HLA typing, which is rapid and cost effective is essential. NGS has provided a rapid, high-resolution HLA typing solution, which has reduced the number of HLA ambiguities seen with other typing methods. In this study, the One Lambda NXType NGS kit was tested on the Ion Torrent PGM platform. A total of 362 registry donors from four ethnic populations (Europeans, South Asians, Africans and Chinese) were NGS HLA typed across 9-loci (HLA-A, -B, -C, -DRB1,-DRB345 -DQB1 and -DPB1). Concordance rates of 91%-98% were obtained (for HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1) when compared to historical PCR-SSO HLA types, and the identification of uncommon alleles such as A*24:07:01 and C*04:82 were observed. A turnaround time of four days was achieved for typing 44 samples. However, some limitations were observed; primer locations did not allow all ambiguities to be resolved for HLA Class II where Exon I and IV amplification are needed (HLA-DRB1*04:07:01/04:92, HLA-DRB1*09:01:02/*09:21 and HLA-DRB1*12:01:01/*12:10). This study has demonstrated high-resolution typing by NGS can be achieved in an acceptable turnaround time for a clinical laboratory; however, the Ion Torrent workflow has some technical limitations that should be addressed.

Molecular Basis for Dysregulated Activation of NKX2-5 in the Vascular Remodeling of Systemic Sclerosis.

OBJECTIVE: NKX2-5 is a homeobox transcription factor that is required for the formation of the heart and vessels during development, with significant postnatal down-regulation and reactivation in disease states, characterized by vascular remodeling. The purpose of this study was to investigate mechanisms that activate NKX2-5 expression in diseased vessels, such as systemic sclerosis (scleroderma; SSc)-associated pulmonary hypertension (PH), and to identify genetic variability that potentially underlies susceptibility to specific vascular complications. METHODS: We explored NKX2-5 expression in biopsy samples from patients with SSc-associated PH and in pulmonary artery smooth muscle cells (PASMCs) from patients with scleroderma. Disease-associated putative functional single-nucleotide polymorphisms (SNPs) at the NKX2-5 locus were cloned and studied in reporter gene assays. SNP function was further examined through protein-DNA binding assays, chromatin immunoprecipitation assays, and RNA silencing analyses. RESULTS: Increased NKX2-5 expression in biopsy samples from patients with SSc-associated PH was localized to remodeled vessels and PASMCs. Meta-analysis of 2 independent scleroderma cohorts revealed an association of rs3131917 with scleroderma (P = 0.029). We demonstrated that disease-associated SNPs are located in a novel functional enhancer, which increases NKX2-5 transcriptional activity through the binding of GATA-6, c-Jun, and myocyte-specific enhancer factor 2C. We also characterized an activator/coactivator transcription-enhancer factor domain 1 (TEAD1)/Yes-associated protein 1 (YAP1) complex, which was bound at rs3095870, another functional SNP, with TEAD1 binding the risk allele and activating the transcription of NKX2-5. CONCLUSION: NKX2-5 is genetically associated with scleroderma, pulmonary hypertension, and fibrosis. Functional evidence revealed a regulatory mechanism that results in NKX2-5 transcriptional activation in PASMCs through the interaction of an upstream promoter and a novel downstream enhancer. This mechanism can act as a model for NKX2-5 activation in cardiovascular disease characterized by vascular remodeling.

Influence of TYK2 in systemic sclerosis susceptibility: a new locus in the IL-12 pathway.

OBJECTIVES: TYK2 is a common genetic risk factor for several autoimmune diseases. This gene encodes a protein kinase involved in interleukin 12 (IL-12) pathway, which is a well-known player in the pathogenesis of systemic sclerosis (SSc). Therefore, we aimed to assess the possible role of this locus in SSc. METHODS: This study comprised a total of 7103 patients with SSc and 12 220 healthy controls of European ancestry from Spain, USA, Germany, the Netherlands, Italy and the UK. Four TYK2 single-nucleotide polymorphisms (V362F (rs2304256), P1104A (rs34536443), I684S (rs12720356) and A928V (rs35018800)) were selected for follow-up based on the results of an Immunochip screening phase of the locus. Association and dependence analyses were performed by the means of logistic regression and conditional logistic regression. Meta-analyses were performed using the inverse variance method. RESULTS: Genome-wide significance level was reached for TYK2 V362F common variant in our pooled analysis (p=3.08×10(-13), OR=0.83), while the association of P1104A, A928V and I684S rare and low-frequency missense variants remained significant with nominal signals (p=2.28×10(-3), OR=0.80; p=1.27×10(-3), OR=0.59; p=2.63×10(-5), OR=0.83, respectively). Interestingly, dependence and allelic combination analyses showed that the strong association observed for V362F with SSc, corresponded to a synthetic association dependent on the effect of the three previously mentioned TYK2 missense variants. CONCLUSIONS: We report for the first time the association of TYK2 with SSc and reinforce the relevance of the IL-12 pathway in SSc pathophysiology.

Fighting cancer together: Development and implementation of shared medical appointments to standardize and improve chemotherapy education.

OBJECTIVE: Shared medical appointments offer a novel approach to improve efficiency and quality of care consistent with the goals of the Institute of Medicine. Our objective was to develop and implement a shared medical appointment for gynecologic cancer patients initiating chemotherapy. METHODS: We first assessed the level of interest in shared medical appointments among our patients and providers through qualitative interviews. Both patients and providers identified pre-chemotherapy as an optimal area to pilot shared medical appointments. We subsequently created a multidisciplinary team comprised of physicians, advanced practice providers, nurses, pharmacists, administrators, health education specialists and members of the Quality Improvement Department to establish a Shared Medical Appointment and Readiness Teaching (SMART) program for all gynecologic oncology patients initiating chemotherapy with platinum- and/or taxane-based regimens. We developed a standardized chemotherapy education presentation and provided patients with a tool kit that consisted of chemotherapy drug education, a guide to managing side effects, advance directives, and center contact information. RESULTS: From May 9, 2014 to June 26, 2015, 144 patients participated in 51 SMART visits. The majority of patients had ovarian cancer and were treated with carboplatin/paclitaxel. Surveyed patients reported being highly satisfied with the group visit and would recommend shared medical appointments to other patients. CONCLUSIONS: This model of care provides patient education within a framework of social support that empowers patients. Shared medical appointments for oncology patients initiating chemotherapy are both feasible and well accepted.

Evaluación del efecto antitumoral del nimotuzumab combinado con radioquimioterapia en tumores de esófago / Non-described adverse reactions in pregnant women in Cuba

Introducción: el cáncer de esófago en Cuba es una de las cinco primeras causas de muerte por tumores. El tratamiento incluye quimioterapia, radioterapia y cirugía, así como el descubrimiento de nuevos blancos potenciales para la inmunoterapia, entre los que se encuentra el receptor del Factor de Crecimiento Epidérmico. El anticuerpo monoclonal cubano AcM HR3 (nimotuzumab) se estudia actualmente a nivel mundial. Objetivo: evaluar la eficacia y seguridad del nimotuzumab combinado con radioquimioterapia en tumores de esófago inoperable en comparación con el tratamiento habitual en los pacientes atendidos por esta enfermedad en el Hospital Hermanos Ameijeiras, durante los meses de diciembre de 2005 a junio 2010. Método: se diseñó un estudio clínico controlado, aleatorizado, abierto con dos grupos de tratamiento, uno con Radioquimioterapia más Bioterapia y otro con Radioquimioterapia. La variable principal fue la respuesta clínica, con que clasifica la reducción del tumor, de acuerdo al criterio RECIST, en: remisión completa, remisión parcial, estabilización de la enfermedad y progresión. La toxicidad evaluó los eventos adversos que presentaron los pacientes en cada uno de los grupos de tratamiento. Resultados: en relación a la respuesta objetiva se obtuvo una mayor proporción en el grupo de nimotuzumab (88,9 por ciento) contra el grupo control (22,2 por ciento), con una diferencia estadísticamente significativa entre ambos grupos de 66,7 por ciento. Fueron frecuentes los eventos tos, insomnio, síntomas gastrointestinales y dolor retroesternal en el grupo tratado, mientras que en el grupo control las molestias gastrointestinales y la astenia fueron las de mayor aparición. Conclusiones: los pacientes tratados con nimotuzumab presentaron un mejor índice de respuesta objetiva y de control de la enfermedad y su administración fue segura al combinarse con la terapia establecida para el tratamiento del cáncer de esófago inoperable según las normas terapéuticas cubanas(AU)

Introduction: esophageal cancer in Cuba is one of the first five causes of death from tumors. The treatment includes chemotherapy, radiotherapy and surgery as well as the discovery of new potential targets for immunotherapy such as the epidermal growth factor receptor. The Cuban monoclonal antibody AcM HR3 (nimotuzumab) is studied at present internationally. Objective: to evaluate the efficacy and safety of nimotuzumab combined with radiochemotherapy in inoperable esophageal tumors and to compare it with the ordinary treatment given to patients seen at Hermanos Ameijeiras hospital from December 2005 to June 2010. Method: open, controlled, randomized clinical study was designed for two groups of patients, one with radiochemotherapy plus biotherapy and the other one with radiochemotherapy. The main variable was the clinical response with which the tumor reduction is classified in accordance with the RECIST criteria: complete remission, partial remission, disease stabilization and progression. Toxicity tests evaluated the adverse events that occurred in patients of each of the groups. Results: regarding the objective response, a higher proportion was reached in the group with nimotuzumab (88,9 percent) against the control group (22,2 percent), with statistically significant difference between both groups of patients equal to 66,7 percent. Cough, insomnia, gastrointestinal problems and retrosternal pain were frequent in the treatment group whereas the control group suffered gastrointestinal disturbances and asthenia more frequently. Conclusions: the patients treated with nimotuzumab presented better index of objective response and of disease control and its administration was safe when combined with the set therapy for treatment of inoperable esophageal cancer in line with the Cuban therapeutic standards(AU)

Evaluación del efecto antitumoral del nimotuzumab combinado con radioquimioterapia en tumores de esófago / Evaluation of the antitumor effect of nimotuzumab combined with radiochemotherapy in treatment of esophageal tumors

Introducción: el cáncer de esófago en Cuba es una de las cinco primeras causas de muerte por tumores. El tratamiento incluye quimioterapia, radioterapia y cirugía, así como el descubrimiento de nuevos blancos potenciales para la inmunoterapia, entre los que se encuentra el receptor del Factor de Crecimiento Epidérmico. El anticuerpo monoclonal cubano AcM HR3 (nimotuzumab) se estudia actualmente a nivel mundial. Objetivo: evaluar la eficacia y seguridad del nimotuzumab combinado con radioquimioterapia en tumores de esófago inoperable en comparación con el tratamiento habitual en los pacientes atendidos por esta enfermedad en el Hospital Hermanos Ameijeiras, durante los meses de diciembre de 2005 a junio 2010. Método: se diseñó un estudio clínico controlado, aleatorizado, abierto con dos grupos de tratamiento, uno con Radioquimioterapia más Bioterapia y otro con Radioquimioterapia. La variable principal fue la respuesta clínica, con que clasifica la reducción del tumor, de acuerdo al criterio RECIST, en: remisión completa, remisión parcial, estabilización de la enfermedad y progresión. La toxicidad evaluó los eventos adversos que presentaron los pacientes en cada uno de los grupos de tratamiento. Resultados: en relación a la respuesta objetiva se obtuvo una mayor proporción en el grupo de nimotuzumab (88,9 por ciento) contra el grupo control (22,2 por ciento), con una diferencia estadísticamente significativa entre ambos grupos de 66,7 por ciento. Fueron frecuentes los eventos tos, insomnio, síntomas gastrointestinales y dolor retroesternal en el grupo tratado, mientras que en el grupo control las molestias gastrointestinales y la astenia fueron las de mayor aparición. Conclusiones: los pacientes tratados con nimotuzumab presentaron un mejor índice de respuesta objetiva y de control de la enfermedad y su administración fue segura al combinarse con la terapia establecida para el tratamiento del cáncer de esófago inoperable según las normas terapéuticas cubanas(AU)

Introduction: esophageal cancer in Cuba is one of the first five causes of death from tumors. The treatment includes chemotherapy, radiotherapy and surgery as well as the discovery of new potential targets for immunotherapy such as the epidermal growth factor receptor. The Cuban monoclonal antibody AcM HR3 (nimotuzumab) is studied at present internationally. Objective: to evaluate the efficacy and safety of nimotuzumab combined with radiochemotherapy in inoperable esophageal tumors and to compare it with the ordinary treatment given to patients seen at Hermanos Ameijeiras hospital from December 2005 to June 2010. Method: open, controlled, randomized clinical study was designed for two groups of patients, one with radiochemotherapy plus biotherapy and the other one with radiochemotherapy. The main variable was the clinical response with which the tumor reduction is classified in accordance with the RECIST criteria: complete remission, partial remission, disease stabilization and progression. Toxicity tests evaluated the adverse events that occurred in patients of each of the groups. Results: regarding the objective response, a higher proportion was reached in the group with nimotuzumab (88,9 percent) against the control group (22,2 percent), with statistically significant difference between both groups of patients equal to 66,7 percent. Cough, insomnia, gastrointestinal problems and retrosternal pain were frequent in the treatment group whereas the control group suffered gastrointestinal disturbances and asthenia more frequently. Conclusions: the patients treated with nimotuzumab presented better index of objective response and of disease control and its administration was safe when combined with the set therapy for treatment of inoperable esophageal cancer in line with the Cuban therapeutic standards(AU)

Costes de la anticoncepción hormonal combinada en España: ¿hay algún método más coste-efectivo? / Cost-effectiveness of combined hormonal contraception in Spain: Which is the most cost-effective method?

Objetivo: Evaluar el coste-efectividad de diferentes métodos anticonceptivos hormonales combinados. Material y método: Estudio de farmacoeconomía utilizando un modelo de Markov sobre los costes de 3 métodos anticonceptivos hormonales combinados: un anticonceptivo oral financiado, un parche transdérmico y un anillo vaginal. Resultados: El coste total para el Sistema Nacional de Salud, teniendo en cuenta todas las mujeres en edad fértil que utilizan anticoncepción hormonal combinada, sería de 410.122.928 euros en el caso del anticonceptivo oral financiado, de 296.961.568 euros en el caso del parche y de 295.380.316 euros en el caso del anillo vaginal. Para las mujeres los costes serían de 106.164.890 euros, 521.386.383 y 534.474.699 euros respectivamente. Conclusión: Desde la perspectiva del Sistema Nacional de Salud el método de anticoncepción hormonal combinada más coste-efectivo es el anillo vaginal. Desde la perspectiva de las mujeres el uso del anillo vaginal les cuesta más dinero, pero se exponen menos al riesgo de un embarazo no deseado (AU)

Objective: To assess the cost-effectiveness of different combined hormonal contraceptive (CHC) methods. Material and method: A pharmacoeconomic study was conducted using a Markov model of three CHC methods: a reimbursed oral contraceptive, a contraceptive patch, and a vaginal ring. Results: The total cost to the National Health Service would be Euros 410,122,928 if all women of fertile age who employed CHC used a financed oral contraceptive, Euros 296,961,568 if they used the transdermal patch, and Euros 295,380,316 if they used the vaginal ring. For women, these costs would be Euros 106,164,890, Euros 521,386,383, and Euros 534,474,699, respectively. Conclusion: From an National Health Service perspective, the most cost-effective CHC method is the vaginal ring. For women, the vaginal ring is most expensive method, but the excess price could be balanced by a greater protection against unwanted pregnancies (AU)

Multiplex cytokine analysis of dermal interstitial blister fluid defines local disease mechanisms in systemic sclerosis.

INTRODUCTION: Clinical diversity in systemic sclerosis (SSc) reflects multifaceted pathogenesis and the effect of key growth factors or cytokines operating within a disease-specific microenvironment. Dermal interstitial fluid sampling offers the potential to examine local mechanisms and identify proteins expressed within lesional tissue. We used multiplex cytokine analysis to profile the inflammatory and immune activity in the lesions of SSc patients. METHODS: Dermal interstitial fluid sample from the involved forearm skin, and synchronous plasma samples were collected from SSc patients (n = 26, diffuse cutaneous SSc (DcSSc) n = 20, limited cutaneous SSc (LcSSc) n = 6), and healthy controls (HC) (n = 10) and profiled by Luminex® array for inflammatory cytokines, chemokines, and growth factors. RESULTS: Luminex® profiling of the dermal blister fluid showed increased inflammatory cytokines (median interleukin ( IL)-6 in SSc 39.78 pg/ml, HC 5.51 pg/ml, p = 0.01, median IL-15 in SSc 6.27 pg/ml, HC 4.38 pg/ml, p = 0.03), chemokines (monocyte chemotactic protein (MCP)-3 9.81 pg/ml in SSc, 7.18 pg/ml HC, p = 0.04), and profibrotic growth factors (platelet derived growth factor (PDGF)-AA 10.38 pg/ml versus 6.94 pg/ml in HC, p = 0.03). In general dermal fluid and plasma cytokine levels did not correlate, consistent with predominantly local production of these factors within the dermal lesions, rather than leakage from the serum. In hierarchical clustering and network analysis IL-6 emerged as a key central mediator. CONCLUSIONS: Our data confirm that an immuno-inflammatory environment and aberrant vascular repair are intimately linked to fibroblast activation in lesional skin in SSc. This non-invasive method could be used to profile disease activity in the clinic, and identifies key inflammatory or pro-fibrotic proteins that might be targeted therapeutically. Distinct subgroups of SSc may be defined that show innate or adaptive immune cytokine signatures.

Sitios clínicos, eslabón fundamental en la calidad de un ensayo clínico / Clinical sites, a fundamental pillar for the quality of a clinical assay

Introducción: el Centro Nacional Coordinador de Ensayos Clínicos (CENCEC) tiene como función fundamental la realización de ensayos clínicos a nuevos productos de la Industria Biotecnológica y Farmacéutica cubana. Desde el año 2008 tiene implementado un Sistema de Gestión de la Calidad que trabaja basado en la mejora continua de sus procesos. Un factor de suma importancia para el buen desarrollo y garantía de los resultados de sus investigaciones, es el trabajo que brindan los sitios clínicos. Objetivo: determinar las principales dificultades detectadas en los monitoreos realizados en los sitios clínicos. Métodos: la evaluación de la calidad del trabajo de los sitios clínicos en el primer semestre del año 2011, se realizó teniendo en cuenta el cumplimiento o no de los requisitos planteados en la Guía de Buena Práctica Clínica para la investigación clínica. Resultados: las principales dificultades se enmarcaron en los acápites de la institución, en los requisitos correspondientes a los recursos necesarios, a aspectos vinculados con el Comité Ética Institucional y en lo referido a las calificaciones y acuerdos con el investigador; aspectos estos que inciden en el cumplimiento de las Buenas Prácticas Clínicas por parte de los sitios clínicos, lo cual repercute en la calidad del servicio brindado por el CENCEC. Conclusiones: este trabajo sirve como punto de partida para la mejora continua del Sistema de Gestión de Calidad de la organización a fin de encaminar los esfuerzos a la total aplicación del principio de las relaciones mutuamente beneficiosas con los proveedores(AU)

Introduction: the National Coordinating Center of Clinical Assays (CENCEC in Spanish) has the fundamental function of performing clinical assays in new products from the Cuban biotechnological and drug industry. Since 2008, the Center has the quality management system in place to continuously improve its processes. A key factor for good development and assurance of the results of its research is the work of the clinical sites. Objective: to find out the main difficulties in the monitoring of the clinical sites. Methods: the evaluation of the work quality of the clinical sites in the first semester of 2011 took into consideration the fulfillment or non-fulfillment of the requirements set in the Good Clinical Practice Guide for the clinical research. Results: the main difficulties are found in the sections of the institutions, in the requirements for necessary resources, in issues linked to the institutional ethics committee and in qualifications and agreements with the researcher; these are aspects having an impact on the fulfillment of Good Clinical Practices by the clinical sites, which also affects the quality of service rendered by CENCEC. Conclusions: this paper may serve as a starting point for ongoing improvement of the quality management system of the organization in order to direct our efforts to the total implementation of the principle of mutually beneficial relationships with the suppliers(AU)

Sitios clínicos, eslabón fundamental en la calidad de un ensayo clínico / Clinical sites, a fundamental pillar for the quality of a clinical assay

INTRODUCCIÓN: estudios realizados acerca de la prevalencia de la hipertensión arterial en Cuba, muestran valores entre un 20 y un 40 por ciento de la población adulta. En la actualidad se dispone de un amplio arsenal terapéutico para el tratamiento de esta afección y se conocen los criterios higiénico-sanitarios que permiten mantener los niveles arteriales dentro de la normalidad. La falta de adherencia a la pauta terapéutica es común en las enfermedades crónicas. En el caso de la hipertensión arterial, las cifras de no cumplidores alcanzan límites realmente preocupantes, cerca del 40 por ciento para el tratamiento farmacológico y entre el 60-90 por ciento en las medidas higiénico-dietéticas. El incumplimiento hace ineficaz el tratamiento prescripto, lo que ocasiona un aumento de la morbilidad y mortalidad. OBJETIVO: evaluar la adherencia al tratamiento con antipertensivos en una muestra de pacientes hipertensos. MÉTODOS: se realizó un estudio observacional y descriptivo. La muestra estuvo constituida por pacientes de un área de salud del municipio San Miguel del Padrón en La Habana, Cuba. La adherencia se midió empleando el testde Morinsky-Green-Levine, la frecuencia de adquisición del medicamento en farmacia y el control de la presión arterial. Las variables estudiadas fueron edad, sexo, tipo de terapia y adherencia. RESULTADOS: predominaron los pacientes hipertensos del género femenino, del grupo correspondiente a las edades de 70 a 79 años, que emplean la politerapia principalmente. Resultaron adherentes y controlados solo el 30,4 por ciento de los casos estudiados. CONCLUSIONES: se evidencia la necesidad de continuar la labor educativa del paciente hipertenso en esta comunidad, principalmente acerca de la importancia de la adherencia al tratamiento en la hipertensión arterial(AU)

INTRODUCTION: studies on the prevalence of hypertension in Cuba show figures ranging 20 to 40 percent of the adult population. At present, there is a wide therapeutic arsenal for the treatment of hypertension whereas health and hygiene criteria to maintain blood pressure levels within the normal range are known. The non-adherence to the therapeutic regimen is common in chronic diseases. As to blood hypertension, the numbers of noncompliant patients is a real concern since about 40 percent do not follow drug treatment and 60-90 percent of them do not comply with the hygiene and food requirements. Non-compliance makes the prescribed treatment ineffective leading to increased morbidity and mortality. OBJECTIVE: to evaluate the adherence to antihypertensive treatment in a sample of hypertensive patients. METHODS: observational and descriptive study of a sample of patients from a health area of San Miguel del Padrón in Havana, Cuba, for which the test Morinsky-Green-Levine test, how frequent the drug is purchased at the drugstore and the blood pressure control were used to measure adherence to treatment. The study variables were age, sex, type of therapy and adherence. RESULTS: female hypertensive patients aged 70 to 79 years-old and using polytherapy in the main predominated. Just 30.4 percent of the studied cases adhered to their treatment and were under control. CONCLUSIONS: there is a real need of continuous educational work aimed at the hypertensive patient at the study community, mainly on the importance of adherence to treatment in hypertension(AU)