Modelo matemático optimizado para la predicción y planificación de la asistencia sanitaria por la COVID-19 / Mathematical model optimized for prediction and health care planning for COVID-19

Objetivo: La pandemia de la COVID-19 ha supuesto una amenaza de colapso de los servicios hospitalarios y de unidades de cuidado intensivo (UCI), así como una reducción de la dinámica asistencial de pacientes afectados por otras patologías. El objetivo fue desarrollar un modelo matemático diseñado para optimizar las predicciones relacionadas con las necesidades de hospitalización e ingresos en UCI por la COVID-19. Diseño: Estudio prospectivo. Ámbito: Provincia de Granada (España). Pacientes: Pacientes de COVID-19 hospitalizados, ingresados en UCI, recuperados y fallecidos desde el 15 de marzo hasta el 22 de septiembre del 2020. Intervenciones: Desarrollo de un modelo matemático tipo susceptible, expuesto, infectado y recuperado (SEIR) capaz de predecir la evolución de la pandemia, considerando las medidas de salud pública establecidas. Variables de interés: Número de pacientes infectados por SARS-CoV-2, hospitalizados e ingresados en UCI por la COVID-19.Resultados: A partir de los datos registrados, hemos podido desarrollar un modelo matemático que refleja el flujo de la población entre los diferentes grupos de interés en relación con la COVID-19. Esta herramienta permite analizar diferentes escenarios basados en medidas de restricción socio-sanitarias y pronosticar el número de infectados, hospitalizados e ingresados en UCI. Conclusiones: El modelo matemático es capaz de proporcionar predicciones sobre la evolución de la COVID-19 con suficiente antelación como para poder conjugar los picos de prevalencia y de necesidades de asistencia hospitalaria y de UCI, con la aparición de ventanas temporales que posibiliten la atención de enfermos no-COVID (AU)

Objective: The COVID-19 pandemic has threatened to collapse hospital and ICU services, and it has affected the care programs for non-COVID patients. The objective was to develop a mathematical model designed to optimize predictions related to the need for hospitalization and ICU admission by COVID-19 patients. Design: Prospective study. Setting: Province of Granada (Spain). Population: COVID-19 patients hospitalized, admitted to ICU, recovered and died from March 15 to September 22, 2020. Study variables: The number of patients infected with SARS-CoV-2 and hospitalized or admitted to ICU for COVID-19. Results: The data reported by hospitals was used to develop a mathematical model that reflects the flow of the population among the different interest groups in relation to COVID-19. This tool allows to analyse different scenarios based on socio-health restriction measures, and to forecast the number of people infected, hospitalized and admitted to the ICU. Conclusions:The mathematical model is capable of providing predictions on the evolution of the COVID-19 sufficiently in advance as to anticipate the peaks of prevalence and hospital and ICU care demands, and also the appearance of periods in which the care for non-COVID patients could be intensified (AU)

Mathematical model optimized for prediction and health care planning for COVID-19.

OBJECTIVE: The COVID-19 pandemic has threatened to collapse hospital and ICU services, and it has affected the care programs for non-COVID patients. The objective was to develop a mathematical model designed to optimize predictions related to the need for hospitalization and ICU admission by COVID-19 patients. DESIGN: Prospective study. SETTING: Province of Granada (Spain). POPULATION: COVID-19 patients hospitalized, admitted to ICU, recovered and died from March 15 to September 22, 2020. STUDY VARIABLES: The number of patients infected with SARS-CoV-2 and hospitalized or admitted to ICU for COVID-19. RESULTS: The data reported by hospitals was used to develop a mathematical model that reflects the flow of the population among the different interest groups in relation to COVID-19. This tool allows to analyse different scenarios based on socio-health restriction measures, and to forecast the number of people infected, hospitalized and admitted to the ICU. CONCLUSIONS: The mathematical model is capable of providing predictions on the evolution of the COVID-19 sufficiently in advance as to anticipate the peaks of prevalence and hospital and ICU care demands, and also the appearance of periods in which the care for non-COVID patients could be intensified.

Mathematical model optimized for prediction and health care planning for COVID-19. / Modelo matemático optimizado para la predicción y planificación de la asistencia sanitaria por la COVID-19.

OBJECTIVE: The COVID-19 pandemic has threatened to collapse hospital and ICU services, and it has affected the care programs for non-COVID patients. The objective was to develop a mathematical model designed to optimize predictions related to the need for hospitalization and ICU admission by COVID-19 patients. DESIGN: Prospective study. SETTING: Province of Granada (Spain). POPULATION: COVID-19 patients hospitalized, admitted to ICU, recovered and died from March 15 to September 22, 2020. STUDY VARIABLES: The number of patients infected with SARS-CoV-2 and hospitalized or admitted to ICU for COVID-19. RESULTS: The data reported by hospitals was used to develop a mathematical model that reflects the flow of the population among the different interest groups in relation to COVID-19. This tool allows to analyse different scenarios based on socio-health restriction measures, and to forecast the number of people infected, hospitalized and admitted to the ICU. CONCLUSIONS: The mathematical model is capable of providing predictions on the evolution of the COVID-19 sufficiently in advance as to anticipate the peaks of prevalence and hospital and ICU care demands, and also the appearance of periods in which the care for non-COVID patients could be intensified.

Regulatory systems in bone marrow for hematopoietic stem/progenitor cells mobilization and homing.

Regulation of hematopoietic stem cell release, migration, and homing from the bone marrow (BM) and of the mobilization pathway involves a complex interaction among adhesion molecules, cytokines, proteolytic enzymes, stromal cells, and hematopoietic cells. The identification of new mechanisms that regulate the trafficking of hematopoietic stem/progenitor cells (HSPCs) cells has important implications, not only for hematopoietic transplantation but also for cell therapies in regenerative medicine for patients with acute myocardial infarction, spinal cord injury, and stroke, among others. This paper reviews the regulation mechanisms underlying the homing and mobilization of BM hematopoietic stem/progenitor cells, investigating the following issues: (a) the role of different factors, such as stromal cell derived factor-1 (SDF-1), granulocyte colony-stimulating factor (G-CSF), and vascular cell adhesion molecule-1 (VCAM-1), among other ligands; (b) the stem cell count in peripheral blood and BM and influential factors; (c) the therapeutic utilization of this phenomenon in lesions in different tissues, examining the agents involved in HSPCs mobilization, such as the different forms of G-CSF, plerixafor, and natalizumab; and (d) the effects of this mobilization on BM-derived stem/progenitor cells in clinical trials of patients with different diseases.

Colon cancer therapy: recent developments in nanomedicine to improve the efficacy of conventional chemotherapeutic drugs.

The number of patients with colorectal cancer, the third most frequently diagnosed malignancy in the world, has increased markedly over the past 20 years and will continue to increase in the future. Despite recent advances in chemotherapy, currently used anticancer molecules are unable to improve the prognosis of advanced or recurrent colorectal cancer, which remains incurable. The transport of classical drugs by nanoparticles has shown great promise in terms of improving drug distribution and bioavailability, increasing tissue half-life and concentrating anticancer molecules in the tumor mass, providing optimal drug delivery to tumor tissue, and minimizing drug toxicity, including those effects associated with pharmaceutical excipients. In addition, colon cancer targeting may be improved by incorporating ligands for tumor-specific surface receptors. Similarly, nanoparticles may interact with key drug-resistance molecules to prevent a reduction in intracellular drug levels drug. Recently published data have provided convincing pre-clinical evidence regarding the potential of active-targeted nanotherapeutics in colon cancer therapy, although, unfortunately, only a few of these therapies have been translated into early-phase clinical trials. As nanotechnology promises to be a new strategy for improving the prognosis of colon cancer patients, it would be very useful to analyze recent progress in this field of research. This review discusses the current status of nanoparticle-mediated cancer-drug delivery, the challenges restricting its application, and the potential implications of its use in colon cancer therapy.

How is gene transfection able to improve current chemotherapy? The role of combined therapy in cancer treatment.

Despite advances in cancer treatment, a large number of patients eventually develop metastatic disease that is generally incurable. Systemic chemotherapy remains the standard treatment for these patients. Several chemotherapeutic combinations have proven effective in the management of cancer. Paradoxically, although the purpose of polychemotherapy is to improve the prognosis and prolong the survival of patients, it often carries considerable toxicity that causes substantial adverse symptoms. For this reason, a major goal of cancer research is to improve the effectiveness of these cytotoxic agents and reduce their adverse effects. Gene transfer has been proposed as a new strategy to enhance the efficacy of anti-tumor drugs in the treatment of intractable or metastatic cancers. In fact, the association of gene therapy and drugs (combined therapy) has been reported to increase the anti-proliferative effect of classical treatments in lung, bladder, pancreatic, colorectal and breast cancers, among others. Various especially promising therapies have been proposed in this context, including the use of suicide genes, antisense oligonucleotides, ribozymes and RNA interference. In this chapter, we review recent progress in the development of novel anti-cancer strategies that associate cytotoxic agents with gene transfer to enhance their antitumor effect.

El futuro de los ensayos clínicos: Caiber / The future of clinical trials: Caiber

La directiva 2001/20/EC, traspuesta a nuestro ordenamiento jurídico en el Real Decreto 223/2004 de 6 de febrero 1, por el que se regulan los ensayos clínicos con medicamentos, exige a los promotores de un ensayo unas responsabilidades que han hecho pensar que sólo las multinacionales farmacéuticas pueden asumir, poniendo en riesgo la investigación sin interés comercial. Investigadores independientes europeos presentaron el proyecto ECRIN (European Clinical Research Infraestructures Network for clinical trial and biotherapy) en la Comisión Europea (6º Programa Marco). Esta red de ensayos clínicos no comerciales pretende dar soporte a dichos investigadores europeos. La denominación de la red española en ECRIN es CAIBER. La existencia de estas redes se basa en la creencia de que la directiva provoca un detrimento en el número de ensayos no comerciales, por lo que, es interesante estudiar si es real y cuantificar este perjuicio. Se analizaron los ensayos clínicos que se abrieron durante diez años en un hospital de tercer nivel como el Hospital Universitario Virgen de las Nieves de Granada, respecto al número ensayos de promotores independientes. A partir de 2004 los ensayos clínicos no comerciales casi han desaparecido, incluso habiendo aumentado el número de ensayos totales en el último lustro. No podemos responder a preguntas sobre si funcionarán estas redes, pero resulta evidente por los resultados, que los investigadores que pretendan poner en marcha un ensayo clínico no comercial, hoy día, se encuentran desamparados. Lo que justificaría la puesta en marcha este mango proyecto(AU)

The 2001/20/EC European Directive was transposed to our legal system in the Royal Decree 223/2004 February the 6th 1, which regulates clinical drug trials. This requires the Sponsor responsibilities are ashard to follow that only multinational pharmaceutical companies can take, jeopardizing the investigation without commercial interest. Independent European researchers presented ECRIN project (European Clinical Research Infrastructures Network and biotherapy for clinical trial) to the European Commission (6th Marco Program). This network of non-commercial clinical trials intended to support European researchers. The name of the Spanish network in ECRIN is CAIBER.The creation of these networks is based on the belief that the Directive causes a detrimental effect on the number of non-commercial trials. It has been analyzed how many independent sponsor clinical trials have had out of ten years of clinical trials in a third level hospital, like Hospital Universitario Virgen de las Nieves of Granada. From 2004, non-commercial clinical trials have almost disappeared, even the amount of clinical trials have been increased in the last five years. We have no answer whether these networks are going to be helpful to the investigator, but it looks clear that investigator have more problems after the Directive than before to start a non-commercial clinical trial. European Commission in order to solve these problems investigators are involved with, they create those networks(AU)

Tumour malignancy loss and cell differentiation are associated with induction of gef gene in human melanoma cells.

BACKGROUND: Gene therapy is a new method used to induce cancer cell differentiation. Our group previously showed that transfection of the gef gene from Escherichia coli, related to cell-killing functions, may be a novel candidate for cancer gene therapy. Its expression leads to cell cycle arrest unrelated to the triggering of apoptosis in MS-36 melanoma cells. OBJECTIVES: To determine the basis of the antiproliferative effect of the gef gene in this cell line. METHODS: Transmission electron microscopy, apoptosis analysis by confocal microscopy, flow cytometry and immunocytochemical analysis were used. RESULTS: Ultrastructural analysis showed a strikingly different morphology after treatment with dexamethasone and expression of the gef gene, with large accumulations of pigment throughout the cell cytoplasm and presence of melanosomes in different stages of development. High mitochondrial turnover and myeloid bodies, characteristics of neurone cells, were also observed. In addition, both immunocytochemical and indirect immunofluorescence analysis demonstrated a significant decrease in HMB-45, Ki-67 and CD44 antigen expression and an increase in S100 and p53 expression in gef gene-transfected MS-36 melanoma cells that were correlated with the duration of dexamethasone treatment. In the present work, we report that gef gene not only reduces cell proliferation in transfected melanoma MS-36TG cell line but also induces morphological changes clearly indicative of melanoma cell differentiation and a reduction in tumour malignancy. CONCLUSIONS: These findings support the hypothesis that the gef gene offers a new approach to differentiation therapy in melanoma.

Methodology in the European higher education area for the Anatomy learning in the Health Sciences

Development of the European Higher Education Area is linked to the adoption of a new educational model. Thus, in the Health Sciences, basic science knowledge must be integrated with the clinical skills that students will require in their professional activity. The Anatomy and Embryology Teaching Investigation Group at our university (UGR-N-40-UCUA) designed a specific questionnaire to analyse specific items that affect Anatomy learning. It also developed a teaching methodology for the acquisition of anatomic knowledge, integrating theory and practice, including individual and collective tasks for students and leading to future self-learning. Analyses were performed in different groups of first-year students at the School of Medicine of Granada University, School of Nursing of Almería University and School of Physiotherapy of Jaén University. It was found that application of this teaching methodology achieved an improvement in two areas considered essential by these students, i.e. a better understanding of several aspects of the study subject, and greater satisfaction with their acquisition of anatomic and embryologic knowledge (AU)

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Role of the organization of subjects and the educational resources used in their teaching in the Anatomy education-learning process

Within the three-year nursing degree course in Spain, the way in which anatomy teaching is organised shows distinct differences between different universities. At the University of Jaén, first-year students have human anatomy (HA) as a separate subject, whereas at the University of Almeria, anatomy is included within a larger module called the structure and function of the human body (SFHB). The aim of this study was to analyze the reaction of students to the organization of their anatomy courses, the resources used in their teaching, their contents, and the tutoring and evaluation system. For this purpose, a 35-item questionnaire was designed to address aspects related to these objectives and administered at the end of the 2005-6 academic year to 82 students of taking human anatomy at the University of Jaén and 52 students taking structure and function of human body at the University of Almeria. Results obtained showed differences in the evaluation of the educational organization of these subjects at the two universities. The approval rating of Jaen students for the relationship between their theoretical and practical education/training was 25% lower than that of Almeria students. This difference appears to be related to the different distributions of credits between the two subjects in the courses surveyed. Students appeared more highly to value the resources that were most frequently used during the course, suggesting that students may value most highly those resources employed most frequently within a course. There were some similarities between the students at the different universities in the importance they assigned to the different thematic units of the respective subjects. Finally, both groups revealed a preference for face-to-face tutorial sessions and for evaluation by written examinations (AU)

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Anatomy teaching to physiotherapy students: Preliminary study in the European higher education area setting

The integration of the Spanish university system within the European Higher Education Area implies a change in the current educational model towards a more flexible system that establishes the equivalence of degrees and encourages greater competition among courses. In this system, students will be expected to make a greater contribution to real learning in order for it to be more useful in their future professional activity. These changes will involve new student-teacher relationships, new methodologies, new teaching strategies and different evaluation systems. The success of this project will depend on a thorough knowledge of the present state of the courses that we teach. This is the first study to address the current state of human anatomy and embryology learning in the physiotherapy degree course. The analysis was performed in first-year students and focussed on the subject designated the structure and function of the human body, skeletal and muscle system anatomy at the Universities of Almería and Jaén. Student opinions were sought on the appropriateness of these subjects to their degree, on the methods used in practice and theory classes and on the evaluation and tutorial systems. Results obtained were similar between the two universities included in this study and indicated that: 1) students have a good opinion of the usefulness of the subject contents in human anatomy and embryology, 2) students prefer the new technologies to traditional educational systems, and 3) students have a positive appreciation of written examination versus oral examination or continuous continuous assessment. These findings will assist teachers of anatomy and embryology to establish approaches to improve the quality of learning in the setting of the European Higher Education Area (AU)

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Pedagogic evaluation of anatomical teaching for a medical and surgical degree at the University of Granada

Anatomy has been classically considered as a basic foundation for the teaching of medicine, developing a decisive role in medical education and for future professional activity. But, in common with other scientific disciplines, it has grown simultaneously with technology and communication sciences and in a much prescribed manner. The purpose of our study was to estimate different parameters related to the quality of the anatomical teaching at the University of Granada. In trying to achieve this, we have focused on the Human Anatomy I and II courses (given in the first and second years of the medical degree respectively). Once the examinations in these courses were completed, a questionnaire was filled by the students in which they had to estimate, in a one to five range, the adaptation and the adjustment of different aspects related to the development of the course. The results indicated that the students were in favour of practical classes compared to theoretical tuition. On the other hand, the pedagogical organisation of the courses was highly valued by the students, particularly in relation to the adaptation of programme objectives and to the recommended bibliography (both for textbooks and atlases). The best estimated didactic resource for the practical aspect of the subject was the use of human anatomical specimens, and the most favoured procedure in the theoretical classes was the use of the blackboard. For the examinations and assessments, no special preference for any evaluation method was found, but the use of complementary papers (e.g. use of monographs, oral expositions) was considered by the students to be of very little importance (AU)

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Induction of drug resistance in embryonal rhabdomyosarcoma treated with conventional chemotherapy is associated with HLA class I increase.

Effectiveness of conventional cytotoxic treatment of rhabdomyosarcoma (RMS) may be limited by the development of multidrug resistance (MDR) mediated by mdr1 gene. This gene codes for P-glycoprotein (P-gp) which has been related to a immunoregulatory function. Modulation of HLA expression by P-gp has been described in different types of tumor cells including RMS. However, very little is known about biological implications of the P-gp expression in RMS patients treated with conventional chemotherapy. In order to study the problem, we used embryonal RMS tissue samples from treated patients. Our results indicated that positive RMS samples to mdr1 show higher HLA class I expression than those which were negative to mdr1 PCR, what indicates a significant correlation between the expression of both molecules. In addition, we developed two resistant RMS cell lines (A-204-1 and 2) using similar concentrations of actinomycin D as are plasma levels in clinical situation. Both resistant cell lines showed mdr1 expression and an increase of HLA class I expression which was dose-dependent. These results demonstrated that conventional chemotherapy of embryonal RMS is able to induce resistance which can modulate HLA class I expression and suggest that immunological studies of these tumors may be necessary to the design new specific therapeutic strategies.

Release of alpha-actin into serum after skeletal muscle damage.

OBJECTIVE: The skeletal muscle protein alpha-actin was investigated in the serum of subjects with severe skeletal muscle damage to assess its utility as a reliable and predictive marker of muscle damage. METHODS: Serum samples were obtained from 33 healthy controls and 33 patients with severe skeletal muscle damage, defined by a total creatine kinase value of >500 IU/l (Rosalki method). Troponin I, troponin T, and myoglobin concentrations were determined by immunoassay and alpha-actin concentrations by Western blot and densitometry. RESULTS: The mean serum concentration of alpha-actin in controls and patients with skeletal muscle damage was 600.9 and 1968.51 ng/ml, respectively, a statistically significant difference. Sera of patients with muscle damage showed higher levels of alpha-actin than of troponin or myoglobin. No significant difference in troponin I levels was observed between the groups. CONCLUSIONS: According to these results, alpha-actin was the most significant skeletal muscle damage marker analysed and may be an ideal candidate for the identification of all types of myofibre injury, including sports injuries. Our findings support the use of alpha-actin as a marker alongside other currently used biological proteins.

Does Silybum marianum play a role in the treatment of chronic hepatitis C?

OBJECTIVES: The recent boom in patient education on chronic hepatitis C has resulted in a worldwide increase in the diagnosis of this condition. Available treatment is expensive and associated with significant side effects; therefore, many patients seek for alternative medicine. Silybum marianum is a natural herb known to mankind for over 2,000 years that has been used as a liver-protecting agent due to its antioxidant properties. The objective of this study is to evaluate the safety profile and the effects of this herb, using a commercially available extract; in the liver chemistry and viral load of hepatitis C in chronically infected patients. METHODS: Patients aged 21-65 years old with a diagnosis of chronic hepatitis C who were not using antiviral therapy were asked to participate. Patients were randomized to treatment with S. marianum 160 mg orally three times a week for four weeks or to no-treatment (control). Blood tests for viral load and liver enzymes (ALT and AST) were done at randomization and at the end of treatment. Paired-t test was used to measure differences between baseline and week 4 values for ALT, AST and viral load. The percent change for ALT, AST and viral load of both groups was analyzed using the Mann Whitney statistical test. RESULTS: 34 patients were enrolled. Men and women were equally distributed. Mean age was 50 years old. Mean baseline measurements of AST, ALT and viral load in the treatment group were 85 +/- 12.41 IU/ml, 120 +/- 20.57 IU/ml and 8.77 +/- 4.12 copies x 10(6)/ml while for the no-treatment group were 71 +/- 9.46 IU/ml, 97 +/- 15.35 IU/ ml and 1.8 +/- 0.62 copies x 10(6)/ml respectively. For treated subjects the mean values of AST, ALT and viral load demonstrated a decrease from baseline values, but this difference was not statistically significant. For control patients the values of ALT (p= .049), AST (p = .005) and viral load (p = .005) showed a statistically significant increase at week 4. Week 4 measurement chang...

[Health examination of children from the Democratic Sahara Republic (North West Africa) on vacation in Spain]. / Examen de salud de niños de la República Arabe Saharaui Democrática (noroeste de Africa) de vacaciones en España.

OBJECTIVE: We present results of a global health evaluation of groups of children from the Democratic Sahara Republic who came to Spain for vacation. PATIENTS AND METHODS: Clinical and analytical tests of 242 Sahara children from refugee camps in Tindouf (Algeria) that were adopted temporarily by Spanish families between July 1993 and July 1997 are reported. We have used standard groups graphics from the World Health Organization. RESULTS: The results were as follows: sex, 53% girls; mean age, 11.1 +/- 1.6 years and age range, 7-16 years (mode 11). Sixty percent of the children had a weight lower than the 10th percentile and 28% less than the 3rd percentile. Fifty-one percent of the children had a height lower than the 10th percentile and 32% less than the 3rd percentile. The corporal mass was lower than the 10th percentile in 19% and less than the 3rd percentile in 8%. The mean hemoglobin was 12.7 +/- 1.2 gr/dl (17% Hb < 12), iron 66 +/- 32 micrograms/dl (23% Fe < 40), and ferritin 28 +/- 24 ngr/ml (26% Fe < 12). Between 1 and 3 intestinal parasites were found in 75% of the children. Isolated were: Entamoeba coli (38%), Blastocystis hominis (22%), Lamblia (18%), Endolimax nana (17%), Hymenolepis nana (11%), and Oxiuros (5%). Sixteen percent of the children had dental caries and 54% dental malocclusion. Ophthalmological problems were found in 28%, generally myopia. Mantoux > 9 mm was found in 5%. Other pathologies included: 5 kyphoscoliosis, 2 cardiopathies, 2 poliomyelitis sequels, 1 gastric ulcer, 1 epilepsy, 1 spherocytosis and 1 euthyroid goiter. Those with weight in p < 3 and/or functional murmur had Hb < 12 in 61% of the cases and Fe < 40 in 48%. CONCLUSIONS: Anamnesis is difficult because of ignorance of the pathological antecedents and date of birth. For physical exploration and collection of parasites they were extremely modest. Feeding and conditions of life would explain low weight and height percentiles, ferropenic anemia and intestinal parasite rates. It would be better to give anti-parasite drugs and systematic ferroprofilaxis as routine and perform blood tests only in those with weight p < 3.