Incidence and clinical manifestations of giant cell arteritis in Spain: results of the ARTESER register.

OBJECTIVE: This study aimed to estimate the incidence of giant cell arteritis (GCA) in Spain and to analyse its clinical manifestations, and distribution by age group, sex, geographical area and season. METHODS: We included all patients diagnosed with GCA between 1 June 2013 and 29 March 2019 at 26 hospitals of the National Health System. They had to be aged ≥50 years and have at least one positive results in an objective diagnostic test (biopsy or imaging techniques), meet 3/5 of the 1990 American College of Rheumatology classification criteria or have a clinical diagnosis based on the expert opinion of the physician in charge. We calculated incidence rate using Poisson regression and assessed the influence of age, sex, geographical area and season. RESULTS: We identified 1675 cases of GCA with a mean age at diagnosis of 76.9±8.3 years. The annual incidence was estimated at 7.42 (95% CI 6.57 to 8.27) cases of GCA per 100 000 people ≥50 years with a peak for patients aged 80-84 years (23.06 (95% CI 20.89 to 25.4)). The incidence was greater in women (10.06 (95% CI 8.7 to 11.5)) than in men (4.83 (95% CI 3.8 to 5.9)). No significant differences were found between geographical distribution and incidence throughout the year (p=0.125). The phenotypes at diagnosis were cranial in 1091 patients, extracranial in 337 patients and mixed in 170 patients. CONCLUSIONS: This is the first study to estimate the incidence of GCA in Spain at a national level. We found a predominance among women and during the ninth decade of life with no clear variability according to geographical area or seasons of the year.

Utility of applying a diagnostic algorithm in giant cell arteritis based on the level of clinical suspicion. / Utilidad de la aplicación de un algoritmo diagnóstico en la arteritis de células gigantes en función del grado de sospecha clínica.

INTRODUCTION: To reach the diagnosis of giant cell arteritis (GCA), signs, symptoms, laboratory tests, imaging findings, and occasionally anatomopathological results from temporal artery biopsy are evaluated. This study describes the results of an algorithm analysis based on clinical and ultrasound evaluation of patients with suspected GCA, highlighting its diagnostic utility by contrasting its use in different clinical suspicion scenarios. METHOD: Prospective multicenter study evaluating patients referred with suspected GCA through a preferential circuit (fast track), grouping them according to low or high clinical suspicion of GCA. Each of these scenarios is evaluated by biopsy and ultrasound for all patients, resulting in positive, indeterminate, or negative outcomes, yielding six possible groups. Potential areas of improvement are explored, emphasizing that, following a negative or indeterminate ultrasound, 18-FDG-PET-CT could be recommended. We analyze the results and application of a diagnostic algorithm, confirming its efficiency and applicability based on whether there is high or low clinical suspicion. RESULTS: Sixty-nine patients (41 in the high suspicion group and 28 in the low suspicion group). There were 41 new diagnoses of GCA: 35 in the high suspicion group and 6 in the low suspicion group. Using ultrasound alone, the initial algorithm has an overall diagnostic efficiency of 72.5%, which improves to 80.5% when including 18F-FDG-PET/CT. The negative predictive value of ultrasound in patients with low clinical suspicion is 84.6%, and the positive predictive value of ultrasound in patients with high suspicion is 100%, improving sensitivity from 57.1% to 80.8% with 18F-FDG-PET/CT in this scenario. Temporal artery biopsy was performed on all patients, with no differences in sensitivity or specificity compared to ultrasound. In cases where all three tests - ultrasound, biopsy, and 18F-FDG-PET/CT - are performed, sensitivity increases to 92.3% in patients with high clinical suspicion. CONCLUSION: In situations of high clinical suspicion, the algorithm provides sufficient information for the diagnosis of GCA if ultrasound is positive. A negative ultrasound is sufficient to rule out the diagnosis in the context of low clinical suspicion. 18-FDG-PET-CT may be useful in patients with high suspicion and negative or indeterminate ultrasound results.

Glycemic Challenge Is Associated with the Rapid Cellular Activation of the Locus Ceruleus and Nucleus of Solitary Tract: Circumscribed Spatial Analysis of Phosphorylated MAP Kinase Immunoreactivity.

Rodent studies indicate that impaired glucose utilization or hypoglycemia is associated with the cellular activation of neurons in the medulla (Winslow, 1733) (MY), believed to control feeding behavior and glucose counterregulation. However, such activation has been tracked primarily within hours of the challenge, rather than sooner, and has been poorly mapped within standardized brain atlases. Here, we report that, within 15 min of receiving 2-deoxy-d-glucose (2-DG; 250 mg/kg, i.v.), which can trigger glucoprivic feeding behavior, marked elevations were observed in the numbers of rhombic brain (His, 1893) (RB) neuronal cell profiles immunoreactive for the cellular activation marker(s), phosphorylated p44/42 MAP kinases (phospho-ERK1/2), and that some of these profiles were also catecholaminergic. We mapped their distributions within an open-access rat brain atlas and found that 2-DG-treated rats (compared to their saline-treated controls) displayed greater numbers of phospho-ERK1/2+ neurons in the locus ceruleus (Wenzel and Wenzel, 1812) (LC) and the nucleus of solitary tract (>1840) (NTS). Thus, the 2-DG-activation of certain RB neurons is more rapid than perhaps previously realized, engaging neurons that serve multiple functional systems and which are of varying cellular phenotypes. Mapping these populations within standardized brain atlas maps streamlines their targeting and/or comparable mapping in preclinical rodent models of disease.

Converting a face-to-face neuroanatomy course-based undergraduate research experience (CURE) to an online environment: lessons learned from remote teaching.

Previously, we described a course-based undergraduate research experience (CURE) for first-year students that featured a unique approach to brain mapping in a model organism (rat). In response to the COVID-19 pandemic, we adapted this course for an online learning environment, emphasizing image analysis (identifying immunoreactive signal in an immunohistochemical stain, making neuroanatomical distinctions in a cytoarchitectural stain) and translation of image data to the brain atlas. Using a quasiexperimental mixed methods approach, we evaluated aspects of student engagement and perceived gains in student confidence with respect to the nature and process of science and student science identity development. Additionally, we examined the dynamics of mentorship and student connectedness experienced in the online-only context. We found that the majority of students reported positive affective outcomes for the course in domains such as project ownership and project engagement in addition to positive responses toward perceived mentorship received during the course. Unsurprisingly, students expressed frustration in not being able to freely communicate with members of the course in an organic face-to-face environment. Furthermore, we found that students encountered greater difficulty in mastering image software skills causing a delay in producing consistent-quality data maps. From our analysis of the course, we have identified both useful approaches and areas for course improvement in any future iterations of the online research course.NEW & NOTEWORTHY Herein, we describe the process of converting a novel, face-to-face neuroanatomy course-based undergraduate research experience (CURE) to an online-only research setting. We document student affective and skill gains resultant from participating in this course and examine best practices for structuring online CUREs to maximize student learning and success.

Idoneidad de la punción guiada por ecografía de alta resolución en el diagnóstico de una tumoración de partes blandas infectada por Mycobacterium tuberculosis / Suitability of High-resolution Ultrasound-guided Puncture in the Diagnosis of a Soft Tissue Mass Infected With Mycobacterium tuberculosis

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PASE and EARP questionnaires for the identification of enthesitis, synovitis, and tenosynovitis in patients with psoriasis.

The aim of this study was to assess the diagnostic value of the Psoriatic Arthritis Screening Evaluation (PASE) and Early Psoriatic Arthritis Screening Questionnaire (EARP) questionnaires in the ultrasonographic detection of enthesitis, synovitis, and tenosynovitis. A cross-sectional study was done in a total of 96 consecutive patients. Double blind clinical examination and echographic assessment were performed. A receiver-operating characteristic (ROC) model analysis for the questionnaires was established using echographic findings as reference variable. The optimal diagnostic point was determined following a Youden analysis model from the obtained data, calculating sensitivity and specificity along with predictive values, likelihood ratio, and diagnostic odds ratio. A logistic regression analysis was used to determine possible predictor variables of enthesitis, synovitis, and tenosynovitis. When enthesitis, synovitis, and tenosynovitis were considered as one outcome for the diagnostic study of the PASE or EARP questionnaire, there were no statistically significant differences among the score of the study groups and the rest of patients. The PASE and EARP tests had a diagnostic performance for enthesitis, synovitis, and tenosynovitis that followed the expected pattern when the prevalence of findings is low. In these cases, the tests increase their negative predictive value, being particularly interesting in ruling out the disease.

[Impact of the Pharmaceutical Copayment Reform on the Use of Antidiabetics, Antithrombotics and for Chronic Obstructive Airway Disease Agents, Spain]. / Impacto de la reforma del copago farmaceútico sobre la utilización de medicamentos antidiabéticos, antitrombóticos y para la obstrucción crónica del flujo aéreo.

OBJECTIVE: In 2012 it changed the Spanish legislation regulating the pharmaceutical copayment by the National Health System (NHS). The objective was to know if the Spanish pharmaceutical copayment reform in 2012 has affected drugs consumptions for chronic diseases such as antidiabetics, antithrombotics and agents against obstructive conditions of the respiratory tract. METHODS: Retrospective longitudinal observational study, using general segmented linear regression models for interrupted time series. The variables analyzed were the number of defined daily doses (DDDs) and the amount corresponding to public funding and not public funding from the (NHS) since September 2010 to August 2015 (T=60). RESULTS: The estimated variation rate of DDDs is negative but decreasing for the three therapeutic subgroups at 6, 12, 24 and 38 months after the intervention: -0.1% for antidiabetics after 6 months and 0.3% after 38 months; -3.7% for antithrombotics after 6 months and -4.6% after 38 months; -2.7% for asthma and COPD drugs after 6 months and -1.3% after 38 months. A sustained and significant reduction in expenditure was estimated only in the subgroup of asthma and COPD drugs: -5.2% after 6 months, -7.0% after 12 months and after 24 months, and -6.2% after 38 months. CONCLUSIONS: The pharmaceutical copayment reform of 2012 led to an immediate and significant reduction in the number of DDDs of all three therapeutic subgroups selected in this study. This level effect is not permanent, as it is accompanied by a change in the growth trend in the post-intervention months, which has partly offset the effect on the level.

OBJETIVO: En 2012 cambió la legislación española que regulaba el copago farmaceútico de la prestación farmaceútica del Sistema Nacional de Salud (SNS).El objetivo fue conocer si la reforma del copago farmacéutico español en 2012 ha afectado al consumo de los medicamentos para enfermedades crónicas, tales como antidiabéticos, antitrombóticos y fármacos contra padecimientos obstructivos de las vías respiratorias. METODOS: Estudio observacional longitudinal retrospectivo. Se utilizaron modelos de regresión lineal segmentada general para series de tiempo interrumpido. Las variables analizadas fueron el número de dosis diarias definidas (DDDs) y el importe de la facturación de las dispensaciones financiadas y no financiadas por el SNS desde septiembre de 2010 hasta agosto de 2015 (T=60). RESULTADOS: La tasa de variación estimada de las DDDs fue negativa pero decreciente para los 3 subgrupos terapéuticos a los 6, 12, 24 y 38 meses de la intervención: -0,1% para antidiabéticos a los 6 meses y 0,3% a los 38 meses; -3,7% para antitrombóticos a los 6 meses y -4,6% a los 38 meses; -2,7% a los 6 meses para anti-asma y EPOC y -1,3% a los 38 meses. Se estimó una reducción mantenida y significativa del gasto únicamente en el subgrupo para asma y EPOC: -5,2% a los 6 meses, -7,0% a los 12 meses y a los 24 meses y -6,2% a los 38 meses. CONCLUSIONES: La reforma del copago farmacéutico de 2012 ocasiona una reducción inmediata y significativa en el número de dosis diarias definidas de los tres grupos terapéuticos estudiados. Este efecto nivel no es permanente ya que se acompaña de un cambio en la tendencia de crecimiento en los meses post-intervención que, en parte, compensa el efecto sobre el nivel.

Impacto de la reforma del copago farmacéutico sobre la utilización de medicamentos antidiabéticos, antitrombóticos y para la obstrucción crónica del flujo aéreo / Impact of the pharmaceutical copayment reform on the use of antidiabetics, antithrombostics and drugs for chronic airflow obstructions. Spain

Fundamentos: En 2012 cambió la legislación española que regulaba el copago farmacéutico de la prestación farmacéutica del Sistema Nacional de Salud (SNS). El objetivo fue conocer si este cambio afecta al consumo de los medicamentos para enfermedades crónicas, tales como antidiabéticos, antitrombóticos y fármacos contra padecimientos obstructivos de las vías respiratorias. Método: Estudio observacional longitudinal retrospectivo. Se utilizaron modelos de regresión lineal segmentada general para series de tiempo interrumpido. Las variables analizadas fueron el número de dosis diarias definidas (DDDs) y el importe de la facturación de las dispensaciones financiadas y no financiadas por el SNS desde septiembre de 2010 hasta agosto de 2015 (T=60). Resultados: La tasa de variación estimada de las DDDs fue negativa pero decreciente para los 3 subgrupos terapéuticos a los 6, 12, 24 y 38 meses de la intervención: -0,1% para antidiabéticos a los 6 meses y 0,3% a los 38 meses; -3,7% para antitrombóticos a los 6 meses y -4,6% a los 38 meses; -2,7% a los 6 meses para anti-asma y EPOC y -1,3% a los 38 meses. Se estimó una reducción mantenida y significativa del gasto únicamente en el subgrupo para asma y EPOC: -5,2% a los 6 meses, -7,0% a los 12 meses y a los 24 meses y -6,2% a los 38 meses. Conclusiones: La reforma del copago farmacéutico de 2012 ocasionó una reducción inmediata y significativa en el número de dosis diarias definidas de los tres grupos terapéuticos estudiados. Este efecto nivel no fue permanente ya que se acompañó de un cambio en la tendencia de crecimiento en los meses post-intervención que, en parte, compensó el efecto sobre el nivel (AU)

Background: In 2012 it changed the Spanish legislation regulating the pharmaceutical copayment by the National Health System (NHS). The objective was to know if the Spanish pharmaceutical copayment reform in 2012 has affected drugs consumptions for chronic diseases such as antidiabetics, antithrombotics and agents against obstructive conditions of the respiratory tract. Methods: Retrospective longitudinal observational study, using general segmented linear regression models for interrupted time series. The variables analyzed were the number of defined daily doses (DDDs) and the amount corresponding to public funding and not public funding from the NHS since September 2010 to August 2015 (T=60). Results: The estimated variation rate of DDDs is negative but decreasing for the three therapeutic subgroups at 6, 12, 24 and 38 months after the intervention: The estimated variation rate of DDDs is negative but decreasing for the most part of the three therapeutic subgroups at 6, 12, 24 and 38 months after the intervention: -0.1% for antidiabetics after 6 months and 0.3% after 38 months; -3.7% for antithrombotics after 6 months and -4.6% after 38 months; -2.7% for asthma and COPD drugs after 6 months and -1.3% after 38 months. A sustained and significant reduction in expenditure was estimated only in the subgroup of asthma and COPD drugs: -5.2% after 6 months, -7.0% after 12 months and after 24 months, and -6.2% after 38 months. Conclusions: The pharmaceutical copayment reform of 2012 led to an immediate and significant reduction in the number of DDDs of all three therapeutic subgroups selected in this study. This level effect is not permanent, as it is accompanied by a change in the growth trend in the post-intervention months, which has partly offset the effect on the level (AU)

Role of the blood-brain barrier in multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system associated with demyelination and axonal loss eventually leading to neurodegeneration. MS exhibits many of the hallmarks of an inflammatory autoimmune disorder including breakdown of the blood-brain barrier (BBB). The BBB is a complex organization of cerebral endothelial cells, pericytes and their basal lamina, which are surrounded and supported by astrocytes and perivascular macrophages. In pathological conditions, lymphocytes activated in the periphery infiltrate the central nervous system to trigger a local immune response that ultimately damages myelin and axons. Cytotoxic factors including pro-inflammatory cytokines, proteases, and reactive oxygen and nitrogen species accumulate and may contribute to myelin destruction. Dysregulation of the BBB and transendothelial migration of activated leukocytes are among the earliest cerebrovascular abnormalities seen in MS brains and parallel the release of inflammatory cytokines. In this review we establish the importance of the role of the BBB in MS. Improvements in our understanding of molecular mechanism of BBB functioning in physiological and pathological conditions could lead to improvement in the quality of life of MS patients.

Analysis of surface properties of human cancer cells using derivatized beads.

Standard histochemical analysis of cells and tissues generally involves procedures that utilize a relatively small number of probes such as dyes, and generally requires hours or days to process. Our laboratory has developed a novel method for histochemical surveys of cell surface properties that utilizes a large number of probes (derivatized agarose beads) and takes seconds or minutes to accomplish. In this study, 4 human cell lines (CCL-255 (LS123) human colon cancer cells that are non-tumorigenic in nude mice; CRL-1459 (CCD-18CO) human colon endothelial cells that are non-malignant; CCL-220 (COLO 320DM) human colon cancer cells that are tumorigenic in nude mice; and HTB-171 (NCI H446) human lung carcinoma cells) were tested for their ability to bind to agarose beads derivatized with 51 different molecules. There were statistically significant differences in binding of the 4 cell types to all of the 51 types of beads, but 15 types of beads showed dramatic differences in binding to one or more of the 4 cell types. For example, only HTB-171 (NCI H446) bound to p-aminophenyl-beta-D-glucopyranoside-derivatized beads and only CCL-220 (COLO 320DM) bound to L-tyrosine-derivatized beads. The specificity of cell-bead binding was examined by performing assays in the presence or absence of exogenously added compounds in hapten-type of inhibition experiments. This assay, that utilizes large numbers of novel probes, may help in the development of new libraries of surface properties of specific cell types, with differing degrees of malignancy, that at this time could not be developed by using other available technologies.

Analysis of surface properties of fixed and live cells using derivatized agarose beads.

A novel assay has been developed for the histochemical characterization of surface properties of cells based on their adhesion to agarose beads derivatized with more than 100 types of molecules, including sugars, lectins and other proteins, and amino acids. The assay simply involves mixing small quantities of washed cells and beads in droplets on glass microscope slides and determining to which beads various cell types adhere. Distilled water was found to be the best medium for this assay because added ions or molecules in other media inhibit adhesion in some cases. Many cells, however, cannot tolerate distilled water. Here we show that cells fixed with either of two fixatives (1% formaldehyde or Prefer fixative) displayed similar bead-binding properties as did live cells. Specificity of cell-bead binding was tested by including specific free molecules in the test suspensions in hapten-type inhibition experiments. If a hapten compound inhibited live-cell adhesion to a specific bead, it also inhibited fixed-cell adhesion to a specific bead. The results of these experiments suggest that fixed cells display authentic surface properties, opening the door for the use of this assay with many cell types that cannot tolerate distilled water.