Pain chronification : what should a non-pain medicine specialist know?

Objective: Pain is one of the most common reasons for an individual to consult their primary care physician, with most chronic pain being treated in the primary care setting. However, many primary care physicians/non-pain medicine specialists lack enough awareness, education and skills to manage pain patients appropriately, and there is currently no clear, common consensus/formal definition of pain chronification. Methods: This article, based on an international Change Pain Chronic Advisory Board meeting which was held in Wiesbaden, Germany, in October 2016, provides primary care physicians/non-pain medicine specialists with a narrative overview of pain chronification, including underlying physiological and psychosocial processes, predictive factors for pain chronification, a brief summary of preventive strategies, and the role of primary care physicians and non-pain medicine specialists in the holistic management of pain chronification. Results: Based on currently available evidence, we propose the following consensus-based definition of pain chronification which provides a common framework to raise awareness among non-pain medicine specialists: Pain chronification describes the process of transient pain progressing into persistent pain; pain processing changes as a result of an imbalance between pain amplification and pain inhibition; genetic, environmental and biopsychosocial factors determine the risk, the degree, and time-course of chronification. Conclusions: Early intervention plays an important role in preventing pain chronification and, as key influencers in the management of patients with acute pain, it is critical that primary care physicians are equipped with the necessary awareness, education and skills to manage pain patients appropriately.Peer reviewe

Make a CHANGE: optimising communication and pain management decisions

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Chromatin regulation by Histone H4 acetylation at Lysine 16 during cell death and differentiation in the myeloid compartment

Histone H4 acetylation at Lysine 16 (H4K16ac) is a key epigenetic mark involved in gene regulation, DNA repair and chromatin remodeling, and though it is known to be essential for embryonic development, its role during adult life is still poorly understood. Here we show that this lysine is massively hyperacetylated in peripheral neutrophils. Genome-wide mapping of H4K16ac in terminally differentiated blood cells, along with functional experiments, supported a role for this histone post-translational modification in the regulation of cell differentiation and apoptosis in the hematopoietic system. Furthermore, in neutrophils, H4K16ac was enriched at specific DNA repeats. These DNA regions presented an accessible chromatin conformation and were associated with the cleavage sites that generate the 50 kb DNA fragments during the first stages of programmed cell death. Our results thus suggest that H4K16ac plays a dual role in myeloid cells as it not only regulates differentiation and apoptosis, but it also exhibits a non-canonical structural role in poising chromatin for cleavage at an early stage of neutrophil cell death

Objetivos de desarrollo sostenible y Derechos Humanos: paz, justicia e instituciones sólidas / Derechos Humanos y empresas

Nota previa / Cástor Miguel Díaz Barrado (pp. 7-9). -- Unión Europea: Derechos Humanos y desarrollo sostenible / Araceli Mangas Martín (pp. 13 - 26). -- Paz, seguridad y gobernanza: el ODS 16 y la Agenda 2030 de desarrollo sostenible / José Antonio Sanahuja (pp. 27 - 54). -- La aplicación extraterritorial de los Derechos Humanos por acciones de empresas / Pablo Antonio Fernández Sánchez (pp. 57 - 60). -- Hacia un futuro tratado internacional sobre las empresas y los Derechos Humanos / Eugenia López-Jacoiste (pp. 61 - 73). -- La importancia del enfoque de los Derechos Humanos en los objetivos de desarrollo del sostenible / Diana M. Verdiales López (pp. 75 - 90). -- La perspectiva de género en la resolución de conflictos armados: las mujeres como agentes de paz / Cristina del Prado Higuera (pp. 93 - 106). -- La mutilación genital femenina desde una perspectiva integral y multidisciplinar / Cristina Hermida del Llano (pp. 107 - 120). -- Poner fin al maltrato, la explotación, la trata y todas las formas de violencia y tortura contra los niños: la trata de niños / María Ángeles Cano Linares (pp. 123 - 136). -- Participación juvenil en el fortalecimiento de las instituciones y el establecimiento de la paz: programas de participación juvenil del sistema de Naciones Unidas / Enrique Hernández Díez (pp. 137 - 160). -- Estado de la violencia criminal en la sociedad internacional: respuestas de la comunidad internacional para avanzar hacia el objetivo 16, Agenda 2030 / Sagrario Morán Blanco (pp. 163 - 178). -- Fortalecer la recuperación y devolución de bienes robados: justicia y reparación del daño causado a las víctimas y la sociedad como metas del objetivo 16 de los objetivos de desarrollo sostenible / Francisco Jiménez García (pp. 179 - 192). -- El derecho internacional, los ODS y la lucha contra el crimen transnacional / Juan Manuel Rodríguez Barrigón (pp. 193 - 216). -- El derecho internacional frente a la criminalidad financiera transnacional: la prevención y sanción del blanqueo de capitales / Jorge Urbaneja Cillán (pp. 217 - 232). -- Acceso a la justicia y objetivos del desarrollo sostenible / Florabel Quispe Remón (pp. 235 - 248). -- Paz y objetivos de desarrollo sostenible: la contribución del objetivo 16 / Elena C. Díaz Galán (pp. 249 - 262). -- Seguridad sanitaria y empresas / Ana Cristina Gallego Hernández (pp. 265 - 272). -- El acaparamiento de tierras por empresas multinacionales y la seguridad alimentaria / Adriana Fillol Mazo (pp. 273 - 288). -- Importancia y características de los planes nacionales de empresas y Derechos Humanos en relación con el desarrollo sostenible / Alberto Jiménez-Piernas García (pp. 289 - 301). -- Objetivo de desarrollo sostenible 16. Principios rectores y espacio iberoamericano: el caso Berta Cáceres / Ana Manero Salvador (pp. 305 - 315). -- Derechos de los pueblos indígenas: marcos de protección en la Agenda 2030 y en los principios rectores sobre empresas y Derechos Humanos / Juan Daniel Oliva Martínez y Adriana Sánchez Lizama (pp. 317 - 331

Managing chronic pain in elderly patients requires a CHANGE of approach

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A promoter DNA demethylation landscape of human hematopoietic differentiation

Global mechanisms defining the gene expression programs specific for hematopoiesis are still not fully understood. Here, we show that promoter DNA demethylation is associated with the activation of hematopoietic-specific genes. Using genome-wide promoter methylation arrays, we identified 694 hematopoietic-specific genes repressed by promoter DNA methylation in human embryonic stem cells and whose loss of methylation in hematopoietic can be associated with gene expression. The association between promoter methylation and gene expression was studied for many hematopoietic-specific genes including CD45, CD34, CD28, CD19, the T cell receptor (TCR), the MHC class II gene HLA-DR, perforin 1 and the phosphoinositide 3-kinase (PI3K) and results indicated that DNA demethylation was not always sufficient for gene activation. Promoter demethylation occurred either early during embryonic development or later on during hematopoietic differentiation. Analysis of the genome-wide promoter methylation status of induced pluripotent stem cells (iPSCs) generated from somatic CD34+ HSPCs and differentiated derivatives from CD34+ HSPCs confirmed the role of DNA methylation in regulating the expression of genes of the hemato-immune system, and indicated that promoter methylation of these genes may be associated to stemness. Together, these data suggest that promoter DNA demethylation might play a role in the tissue/cell-specific genome-wide gene regulation within the hematopoietic compartment

Classification of follicular-patterned thyroid lesions using a minimal set of epigenetic biomarkers

[Objective]: The minimally invasive fine-needle aspiration cytology (FNAC) is the current gold standard for the diagnosis of thyroid nodule malignancy. However, the correct discrimination of follicular neoplasia often requires more invasive diagnostic techniques. The lack of suitable immunohistochemical markers to distinguish between follicular thyroid carcinoma and other types of follicular-derived lesions complicates diagnosis, and despite most of these tumours being surgically resected, only a small number will test positive for malignancy. As such, the development of new orthogonal diagnostic approaches may improve the accuracy of diagnosing thyroid nodules.[Design]: This study includes a retrospective, multi-centre training cohort including 54 fresh-frozen follicular-patterned thyroid samples and two independent, multi-centre validation cohorts of 103 snap-frozen biopsies and 33 FNAC samples, respectively.[Methods]: We performed a genome-wide genetic and epigenetic profiling of 54 fresh-frozen follicular-patterned thyroid samples using exome sequencing and the Illumina Human DNA Methylation EPIC platform. An extensive validation was performed using the bisulfite pyrosequencing technique.[Results]: Using a random forest approach, we developed a three-CpG marker-based diagnostic model that was subsequently validated using bisulfite pyrosequencing experiments. According to the validation cohort, this cost-effective method discriminates between benign and malignant nodules with a sensitivity and specificity of 97 and 88%, respectively (positive predictive value (PPV): 0.85, negative predictive value (NPV): 0.98).[Conclusions]: Our classification system based on a minimal set of epigenetic biomarkers can complement the potential of the diagnostic techniques currently available and would prioritize a considerable number of surgical interventions that are often performed due to uncertain cytology.[Significance statement]: In recent years, there has been a significant increase in the number of people diagnosed with thyroid nodules. The current challenge is their etiological diagnosis to discount malignancy without resorting to thyroidectomy. The method proposed here, based on DNA pyrosequencing assays, has high sensitivity (0.97) and specificity (0.88) for the identification of malignant thyroid nodules. This simple and cost-effective approach can complement expert pathologist evaluation to prioritize the classification of difficult-to-diagnose follicular-patterned thyroid lesions and track tumor evolution, including real-time monitoring of treatment efficacy, thereby stimulating adherence to health promotion programs.Peer reviewe

Pain in the cancer patient : different pain characteristics CHANGE pharmacological treatment requirements

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Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Resiliencia organizacional: predictor de calidad en los servicios sociales comunitarios.

El Sistema Público de Servicios Sociales plantea importantes dificultades en su escenario profesional que repercute de forma directa en el quehacer diario de las personas que desarrollan su labor en ese sistema. El estudio de la resiliencia organizacional en el Sistema público de Servicios Sociales se configura como predictor clave de un correcto funcionamiento y calidad en su prestación de servicios a la ciudadanía, teniendo en cuenta el nivel de satisfacción personal. En la presente comunicación se muestran los primeros resultados de una investigación llevada a cabo desde la Universidad de Málaga con el objetivo de evaluar la validez del concepto de Resiliencia Organizacional como predictor de calidad en los Servicios Sociales Comunitarios. Se han utilizado instrumentos validados de recogida de información: BRT 13 y Cuestionario SERVPERF. Con este estudio se aportan resultados que pretenden facilitar conocimiento sobre las competencias organizacionales necesarias para que se produzca un adecuado ajuste entre la respuesta organizacional y la demanda social en el sistema público de servicios sociales. Se concluye que el conocimiento sobre en qué medida los CSSC tienen una organización resiliente va a permitir aprender a anticiparse a las nuevas realidades y adaptar su estructura a las circunstancias sociales y culturales.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech