Multimorbidity as a predictor of health service utilization in primary care: a registry-based study of the Catalan population

Background: Multimorbidity is highly relevant for both service commissioning and clinical decision-making. Optimization of variables assessing multimorbidity in order to enhance chronic care management is an unmet need. To this end, we have explored the contribution of multimorbidity to predict use of healthcare resources at community level by comparing the predictive power of four different multimorbidity measures. Methods: A population health study including all citizens ≥18 years (n = 6,102,595) living in Catalonia (ES) on 31 December 2014 was done using registry data. Primary care service utilization during 2015 was evaluated through four outcome variables: A) Frequent attendants, B) Home care users, C) Social worker users, and, D) Polypharmacy. Prediction of the four outcome variables (A to D) was carried out with and without multimorbidity assessment. We compared the contributions to model fitting of the following multimorbidity measures: i) Charlson index; ii) Number of chronic diseases; iii) Clinical Risk Groups (CRG); and iv) Adjusted Morbidity Groups (GMA). Results: The discrimination of the models (AUC) increased by including multimorbidity as covariate into the models, namely: A) Frequent attendants (0.771 vs 0.853), B) Home care users (0.862 vs 0.890), C) Social worker users (0.809 vs 0.872), and, D) Polypharmacy (0.835 vs 0.912). GMA showed the highest predictive power for all outcomes except for polypharmacy where it was slightly below than CRG. Conclusions: We confirmed that multimorbidity assessment enhanced prediction of use of healthcare resources at community level. The Catalan population-based risk assessment tool based on GMA presented the best combination of predictive power and applicability

La memoria en la tradición cultural

Este artículo, fruto de la colaboración entre un estudioso de la folclorística y una psicóloga clínica, pretende hacer un repaso al pensamiento que se ha desarrollado en torno a la relación que existe entre recuerdo y cultura oral, poniendo especial atención en los trabajos realizados por folclorólogos y antropólogos por un lado y psicólogos y neurólogos por otro.This article is the result of the collaboration between people from two different fields, Folkloristics and Psychology; it tries to offer a survey of the scholarship developed around the relationship between memory and oral culture, with especial emphasis on works produced by folklorists and anthropologists on the one side, and psychologists and neurologists on the other

La memoria en la tradición cultural

Este artículo, fruto de la colaboración entre un estudioso de la folclorística y una psicóloga clínica, pretende hacer un repaso al pensamiento que se ha desarrollado en torno a la relación que existe entre recuerdo y cultura oral, poniendo especial atención en los trabajos realizados por folclorólogos y antropólogos por un lado y psicólogos y neurólogos por otro.This article is the result of the collaboration between people from two different fields, Folkloristics and Psychology; it tries to offer a survey of the scholarship developed around the relationship between memory and oral culture, with especial emphasis on works produced by folklorists and anthropologists on the one side, and psychologists and neurologists on the other

Evaluation of angiogenesis with the expression of VEGF and CD34 in human non-small cell lung cancer

Angiogenesis is an essential process in the progression of malignant tumors and the most potent angiogenic factor is the vascular endothelial growth factor (VEGF). On the other hand, the CD34 is an endothelial antigen that has been used to highlight the microvasculature vessel density (MVD) as a direct marker of the degree of neoangiogenesis. In the present study we report the VEGF expression and its relationship with MVD, measured by CD34, in two lineages of non-small cell lung cancer (NSCL): low differentiated adenocarcinomas and epidermoid carcinomas, in order to consider the possibility of using the correlation between both antibodies as a prognostic factor. Tumor sections were stained by immunohistochemistry for CD34 and VEGF. The results showed that the mean value of VEGF for adenocarcinoma was significantly higher than the one for epidermoid carcinoma (p < 0.001). However, the mean of MVD did not show significant differences between both types of tumors. The conventional factors taken into consideration (age over 60, sex, and presence of lymph nodes) was not significantly related to the angiogenic factors examined. In conclusion, we could affirm that CD34 is a better prognostic marker of neoangiogenesis in NSCLC, because both types of tumors have the same clinical prognosis, and so we expected the same behaviour from both markers.Facultad de Ciencias Médica

Evaluation of angiogenesis with the expression of VEGF and CD34 in human non-small cell lung cancer

Angiogenesis is an essential process in the progression of malignant tumors and the most potent angiogenic factor is the vascular endothelial growth factor (VEGF). On the other hand, the CD34 is an endothelial antigen that has been used to highlight the microvasculature vessel density (MVD) as a direct marker of the degree of neoangiogenesis. In the present study we report the VEGF expression and its relationship with MVD, measured by CD34, in two lineages of non-small cell lung cancer (NSCL): low differentiated adenocarcinomas and epidermoid carcinomas, in order to consider the possibility of using the correlation between both antibodies as a prognostic factor. Tumor sections were stained by immunohistochemistry for CD34 and VEGF. The results showed that the mean value of VEGF for adenocarcinoma was significantly higher than the one for epidermoid carcinoma (p < 0.001). However, the mean of MVD did not show significant differences between both types of tumors. The conventional factors taken into consideration (age over 60, sex, and presence of lymph nodes) was not significantly related to the angiogenic factors examined. In conclusion, we could affirm that CD34 is a better prognostic marker of neoangiogenesis in NSCLC, because both types of tumors have the same clinical prognosis, and so we expected the same behaviour from both markers.Facultad de Ciencias Médica

Evaluation of GenoFlow DR-MTB array test for detection of rifampin and isoniazid resistance in mycobacterium tuberculosis

The aim of this study was to evaluate the GenoFlow DR-MTB array test (DiagCor Bioscience, Hong Kong) on 70 cultured isolates and 50 sputum specimens. The GenoFlow array test showed good sensitivity and specificity compared to the phenotypic Bactec 460TB. This array accurately detected mutations in rpoB, katG, and inhA associated with resistance to rifampin and isoniazid

Psoriasis: from pathogenesis to pharmacological and nano-technological-based therapeutics

Research in the pathogenesis of inflammatory skin diseases, such as skin dermatitis and psoriasis, has experienced some relevant breakthroughs in recent years. The understanding of age-related factors, gender, and genetic predisposition of these multifactorial diseases has been instrumental for the development of new pharmacological and technological treatment approaches. In this review, we discuss the molecular mechanisms behind the pathological features of psoriasis, also addressing the currently available treatments and novel therapies that are under clinical trials. Innovative therapies developed over the last 10 years have been researched. In this area, advantages of nanotechnological approaches to provide an effective drug concentration in the disease site are highlighted, together with microneedles as innovative candidates for drug delivery systems in psoriasis and other inflammatory chronic skin diseases.This research was funded by the Portuguese Science and Technology Foundation (FCT/MCT) and European Funds (PRODER/COMPETE), under the project reference UIDB/04469/2020 (strategic fund), co-financed by FEDER, under the Partnership Agreement PT2020, granted to EBS.info:eu-repo/semantics/publishedVersio

First universal newborn screening program for severe combined immunodeficiency in Europe: two-years' experience in Catalonia (Spain)

Newborn screening; Severe combined immunodeficiency; T-cell receptor excision circlesCribratge de nadons; Immunodeficiència combinada greu; Cercles d'excisió de receptors de cèl·lules TCribado de recién nacidos; Inmunodeficiencia combinada grave; Círculos de escisión de receptores de células TSevere combined immunodeficiency (SCID), the most severe form of T-cell immunodeficiency, can be screened at birth by quantifying T-cell receptor excision circles (TRECs) in dried blood spot (DBS) samples. Early detection of this condition speeds up the establishment of appropriate treatment and increases the patient's life expectancy. Newborn screening for SCID started in January 2017 in Catalonia, the first Spanish and European region to universally include this testing. The results obtained in the first 2 years of experience are evaluated here. All babies born between January 2017 and December 2018 were screened. TREC quantification in DBS (1.5 mm diameter) was performed with the Enlite Neonatal TREC kit from PerkinElmer (Turku, Finland). In 2018, the retest cutoff in the detection algorithm was updated based on the experience gained in the first year, and changed from 34 to 24 copies/μL. This decreased the retest rate from 3.34 to 1.4% (global retest rate, 2.4%), with a requested second sample rate of 0.23% and a positive detection rate of 0.02%. Lymphocyte phenotype (T, B, NK populations), expression of CD45RA/RO isoforms, percentage and intensity of TCR αβ and TCR γδ, presence of HLA-DR+ T lymphocytes, and in vitro lymphocyte proliferation were studied in all patients by flow cytometry. Of 130,903 newborns screened, 30 tested positive, 15 of which were male. During the study period, one patient was diagnosed with SCID: incidence, 1 in 130,903 births in Catalonia. Thirteen patients had clinically significant T-cell lymphopenia (non-SCID) with an incidence of 1 in 10,069 newborns (43% of positive detections). Nine patients were considered false-positive cases because of an initially normal lymphocyte count with normalization of TRECs between 3 and 6 months of life, four infants had transient lymphopenia due to an initially low lymphocyte count with recovery in the following months, and three patients are still under study. The results obtained provide further evidence of the benefits of including this disease in newborn screening programs. Longer follow-up is needed to define the exact incidence of SCID in Catalonia

Cell-Mediated Immune Responses to in vivo -Expressed and Stage-Specific Mycobacterium tuberculosis Antigens in Latent and Active Tuberculosis Across Different Age Groups

A quarter of the global human population is estimated to be latently infected by Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB). TB remains the global leading cause of death by a single pathogen and ranks among the top-10 causes of overall global mortality. Current immunodiagnostic tests cannot discriminate between latent, active and past TB, nor predict progression of latent infection to active disease. The only registered TB vaccine, Bacillus Calmette-Guérin (BCG), does not adequately prevent pulmonary TB in adolescents and adults, thus permitting continued TB-transmission. Several Mtb proteins, mostly discovered through IFN-γ centered approaches, have been proposed as targets for new TB-diagnostic tests or -vaccines. Recently, however, we identified novel Mtb antigens capable of eliciting multiple cytokines, including antigens that did not induce IFN-γ but several other cytokines. These antigens had been selected based on high Mtb gene-expression in the lung in vivo, and have been termed in vivo expressed (IVE-TB) antigens. Here, we extend and validate our previous findings in an independent Southern European cohort, consisting of adults and adolescents with either LTBI or TB. Our results confirm that responses to IVE-TB antigens, and also DosR-regulon and Rpf stage-specific Mtb antigens are marked by multiple cytokines, including strong responses, such as for TNF-α, in the absence of detectable IFN-γ production. Except for TNF-α, the magnitude of those responses were significantly higher in LTBI subjects. Additional unbiased analyses of high dimensional flow-cytometry data revealed that TNF-α+ cells responding to Mtb antigens comprised 17 highly heterogeneous cell types. Among these 17 TNF-α+ cells clusters identified, those with CD8+TEMRA or CD8+CD4+ phenotypes, defined by the expression of multiple intracellular markers, were the most prominent in adult LTBI, while CD14+ TNF-α+ myeloid-like clusters were mostly abundant in adolescent LTBI. Our findings, although limited to a small cohort, stress the importance of assessing broader immune responses than IFN-γ alone in Mtb antigen discovery as well as the importance of screening individuals of different age groups. In addition, our results provide proof of concept showing how unbiased multidimensional multiparametric cell subset analysis can identify unanticipated blood cell subsets that could play a role in the immune response against Mtb

Transcriptional Profile Associated with Clinical Outcomes in Metastatic Hormone-Sensitive Prostate Cancer Treated with Androgen Deprivation and Docetaxel

(1) Background: Androgen deprivation therapy (ADT) and docetaxel (DX) combination is a standard therapy for metastatic hormone-sensitive prostate cancer (mHSPC) patients. (2) Methods: We investigate if tumor transcriptomic analysis predicts mHSPC evolution in a multicenter retrospective biomarker study. A customized panel of 184 genes was tested in mRNA from tumor samples by the nCounter platform in 125 mHSPC patients treated with ADT+DX. Gene expression was correlated with castration-resistant prostate cancer-free survival (CRPC-FS) and overall survival (OS). (3) Results: High expression of androgen receptor (AR) signature was independently associated with longer CRPC-FS (hazard ratio (HR) 0.6, 95% confidence interval (CI) 0.3-0.9; p = 0.015), high expression of estrogen receptor (ESR) signature with longer CRPC-FS (HR 0.6, 95% CI 0.4-0.9; p = 0.019) and OS (HR 0.5, 95% CI 0.2-0.9, p = 0.024), and lower expression of tumor suppressor genes (TSG) (RB1, PTEN and TP53) with shorter OS (HR 2, 95% CI 1-3.8; p = 0.044). ARV7 expression was independently associated with shorter CRPC-FS (HR 1.5, 95% CI 1.1-2.1, p = 0.008) and OS (HR 1.8, 95% CI 1.2-2.6, p = 0.004), high ESR2 was associated with longer OS (HR 0.5, 95% CI 0.2-1, p = 0.048) and low expression of RB1 was independently associated with shorter OS (HR 1.9, 95% CI 1.1-3.2, p = 0.014). (4) Conclusions: AR, ESR, and TSG expression signatures, as well as ARV7, RB1, and ESR2 expression, have a prognostic value in mHSPC patients treated with ADT+DX