Expression of Elafin and CD200 as Immune Checkpoint Molecules Involved in Celiac Disease.

We comprehensively evaluated the expression of therapeutically targetable immune checkpoint molecules involved in celiac disease (CD). We have focused on the alteration of the CD200/CD200R pathway and Elafin expression in celiac disease and discussed their roles in regulating the immune response. There are limited data related to the expression or function of these molecules in celiac disease. This finding could significantly contribute to the understanding of the clinical manifestation of CD. CD200, CD200R and Elafin distributions were determined by ELISA and immunohistochemistry analyses in serum and biopsies of CD patients. Analyses of Th1 and Th17 cytokines were determined. PCR amplification of a fragment of the PI3 gene was carried out using genomic DNA isolated from whole blood samples of the study subjects. Different aliquots of the PCR reaction product were subjected to RFLP analysis for SNP genotyping and detection. We characterized the expression and function of the CD200-CD200R axis and PI3 in celiac disease. A significantly higher level of soluble CD200 and CD200R and lower expression of PI3 in serum of CD patients was observed compared to healthy controls. Consistent with our results, CD200 expression is regulated by IFN-gamma. Interaction of CD200/CD200R leads to production of type-Th1 and -Th17 cytokines. Regarding the PI3 genotype, the CT genotype proportion SNP rs1733103 and the GG genotype SNP rs41282752 were predominant in CD patients. SNP rs1733103 showed a significant association between the SNP variables and CD. In celiac disease the immune checkpoint is compromised or dysregulated, which can contribute to inflammation and the autoimmunity process. The study of these checkpoint points will lead to the development of targeted therapies aimed at restoring immunological balance in CD. Specific coding regions of the PI3 gene-splice variants predispose the Elafin protein, both at the transcriptional and post-translational levels, to modify its expression and function, resulting in reduced differential functional protein levels in patients with active celiac disease.

Effectiveness of Scalp Cooling to Prevent Chemotherapy-Induced Alopecia in Patients Undergoing Breast Cancer Treatment: A Systematic Review and Meta-analysis.

BACKGROUND: Chemotherapy-induced alopecia could cause significant psychological changes, affecting patients' quality of life and their capacity to cope with the disease. OBJECTIVES: The aims of this study was to analyze the effectiveness of scalp cooling (SC) to prevent chemotherapy-induced alopecia in patients with breast cancer and to compare the use of automated versus nonautomated therapy delivery devices. METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE (through PubMed), Scopus, Web of Science, and ClinicalTrials.gov from their inception to October 2022. A meta-analysis was performed to assess the effects of SC to prevent chemotherapy-induced alopecia in patients with breast cancer using fixed-effects models to calculate the pooled relative risk (RR) and corresponding 95% confidence interval (CI). RESULTS: The 8 included studies showed a 43% reduction in the risk of chemotherapy-induced alopecia (RR, 0.57; 95% CI, 0.50-0.64) after the use of SC. Moreover, the use of automated SC devices showed a 47% reduction (RR, 0.53; 95% CI, 0.45-0.60) in the risk of chemotherapy-induced alopecia versus a 43% reduction in the risk of chemotherapy-induced alopecia for nonautomated SC devices (RR, 0.57; 95% CI, 0.44-0.70). CONCLUSION: Our results showed that SC significantly reduced the risk of chemotherapy-induced alopecia. IMPLICATIONS FOR PRACTICE: Local cold application is a nonpharmacologic therapy that may provide a useful intervention to reduce hair loss and contribute to the psychological well-being of women. Scalp cooling contributes directly to reducing concern about altered body image and to reducing anxiety related to self-concept.

Efficacy of Different Types of Physical Activity Interventions on Exercise Capacity in Patients with Chronic Obstructive Pulmonary Disease (COPD): A Network Meta-Analysis.

AIM: A network meta-analysis (NMA) was performed to determine the effects on the exercise capacity, measured by the 6 MWT, of patients with COPD of (i) different physical activity interventions and (ii) supervised or unsupervised programs. METHODS: A literature search was carried out from inception to April 2022. Randomized controlled trials of the effectiveness of physical activity on exercise capacity in patients with COPD were included. The risk of bias was assessed using the Cochrane Risk of Bias (RoB 2.0) tool, and the Grading of Recommendations, Assessment, Development, and Evaluation tool (GRADE) was used to assess the quality of the evidence. A pairwise meta-analysis for direct and indirect effects was carried out. RESULTS: A total of 41 studies were included in this NMA. The highest effects were for urban training pulmonary rehabilitation (PR) programs (ES, 1.50; 95% CI: 0.46 and 2.55) versus the control group. For supervised and unsupervised PR and home-based PR programs, the highest effects were found for supervised PR (ES, 0.85; 95% CI: 0.46 to 1.23) versus the control group. CONCLUSIONS: PR implemented with urban circuit training should be considered the most effective strategy to improve exercise capacity in patients with COPD. Supervision of the programs improves exercise capacity.

TIC en actividad física y parámetros cardiovasculares en mayores: una revisión / Health technology tools used to increase physical activity and improve cardiovascular parameters in older adults: A review

Introducción: El envejecimiento es una etapa de cambios físicos y psicológicos. La inactividad es uno de los grandes problemas que la generación de adultos mayores presenta, aumentando el riesgo de sarcopenia y de enfermedades crónicas. En los últimos años se ha producido un incremento en el uso de la tecnología, apareciendo las herramientas TIC (acrónimo de tecnología de la información y la comunicación) como intervención para aumentar la actividad física y mejorar los problemas de salud asociados. Objetivo: En esta revisión se evalúa la efectividad de las herramientas TIC para aumentar la actividad física y mejorar los parámetros cardiovasculares en adultos mayores. Metodología: Se incluyeron estudios que usaran herramientas TIC para aumentar los niveles de actividad física en adultos mayores y que evaluaran el efecto de ese aumento en los parámetros cardiovasculares realizando la búsqueda en las principales bases de datos. Resultados: en esta revisión se incluyeron 11 estudios que reportan el uso de una gran variedad de herramientas TIC. A pesar de estas diferencias, se ha demostrado la efectividad de estas intervenciones en el aumento de la actividad física y la reducción de los parámetros cardiovasculares. Discusión: La falta de adhesión de la generación de adultos mayores a la tecnología sería una desventaja, pero se ha demostrado que los adultos mayores jóvenes están más familiarizados con estas y el número de los que las usan va creciendo con el tiempo. Conclusión: Las herramientas TIC muestran efectividad en el aumento de la actividad física en los adultos mayores y en la mejora de los parámetros cardiovasculares.(AU)

Introduction: Ageing is a period of physical and psychological changes. Inactivity is one of the biggest problems among the older adult population increasing the risk of sarcopenia and chronic diseases. Physical activity is an effective intervention to improve health outcomes. In recent years, there has been an increase in the use of technology, with health technology tools (ICT) appearing as an intervention to increase physical activity and improve associated health problems. Objective: In this review, we evaluated the effectiveness of health technology to increase physical activity and to improve cardiovascular parameters in older adults. Methodology: Studies with a great variety of health technology tools to increase physical activity levels, and that evaluated the effect of that increase on cardiovascular parameters were included by searching the main databases. Results: Eleven studies reporting the use of a variety of ICT tools were included in this review. Despite these differences, the effectiveness of health technology tool interventions has been demonstrated in increasing physical activity and reducing cardiovascular parameters. Discussion: The lack of adherence of older adults to health technology would be a disadvantage, but it has been shown that younger older adults are more familiar with health technology tools and the number using them is increasing. Conclusion: Health technology tools show effectiveness in increasing physical activity in older adults and improving cardiovascular parameters.(AU)

Health technology tools used to increase physical activity and improve cardiovascular parameters in older adults: A review.

INTRODUCTION: Ageing is a period of physical and psychological changes. Inactivity is one of the biggest problems among the older adult population increasing the risk of sarcopenia and chronic diseases. Physical activity is an effective intervention to improve health outcomes. In recent years, there has been an increase in the use of technology, with health technology tools (ICT) appearing as an intervention to increase physical activity and improve associated health problems. OBJECTIVE: In this review, we evaluated the effectiveness of health technology to increase physical activity and to improve cardiovascular parameters in older adults. METHODOLOGY: Studies with a great variety of health technology tools to increase physical activity levels, and that evaluated the effect of that increase on cardiovascular parameters were included by searching the main databases. RESULTS: Eleven studies reporting the use of a variety of ICT tools were included in this review. Despite these differences, the effectiveness of health technology tool interventions has been demonstrated in increasing physical activity and reducing cardiovascular parameters. DISCUSSION: The lack of adherence of older adults to health technology would be a disadvantage, but it has been shown that younger older adults are more familiar with health technology tools and the number using them is increasing. CONCLUSION: Health technology tools show effectiveness in increasing physical activity in older adults and improving cardiovascular parameters.

Adverse events reported after administration of BNT162b2 and mRNA-1273 COVID-19 vaccines among hospital workers: a cross-sectional survey-based study in a Spanish hospital.

BACKGROUND: The World Health Organization declared COVID-19 a pandemic in March 2020. The first vaccine became available in December, with practically no post-marketing data. METHODS: An analytical cross-sectional survey-based study was conducted in a third-level hospital in Spain between March and April 2021 to describe the difference in adverse events with the BNT162b2 and mRNA-1273 COVID-19 vaccines. The participants were hospital workers who completed a survey voluntarily at least 14 days after the last vaccine. The STROBE checklist was followed. RESULTS: One thousand two hundred and forty-nine respondents completed the survey; 48% (599) received mRNA-1273 and 52% (650) BNT162b2. Fourteen thousand four hundred and two adverse reactions were recorded, 6896 local (3939 with mRNA-1273 and 2957 with BNT162b2 (6.6 vs 4.4 reactions per patient)) and 7506 systemic (4460 with mRNA-1273 and 3046 with BNT162b2 (7.4 vs 4.7 per patient)). Local reactions were more frequent after the first dose, while systemic reactions were higher after the second, for both vaccines and in a higher percentage with mRNA-1273 compared to BNT162b2 (p-value<0.05). CONCLUSIONS: Licensed mRNA vaccines were highly safe when administered under post-marketing conditions among working-age adults. The main adverse events were mild, although they occurred in most patients, especially after the mRNA-1273 vaccine.

Adecuación de la prescripción en pacientes mayores polimedicados en atención primaria. Ensayo clínico controlado aleatorizado por grupos PHARM-PC / Prescription appropriateness in elderly patients with polypharmacy in primary care: Cluster-randomized controlled trial PHARM-PC

Objetivos: Evaluar la efectividad de la revisión sistemática de medicación realizada por farmacéutico sobre medicaciones potencialmente inapropiadas (MPI), resultados en salud y costes. Diseño: Ensayo clínico prospectivo, abierto, controlado y aleatorizado por clústeres. Emplazamiento: Seis centros de atención primaria de las Islas Baleares. Participantes: Se incluyeron 42 clústeres (21 por grupo), y 549 pacientes de ≥ 65 años y ≥ 5 medicamentos crónicos, de los cuales 277 se asignaron al Grupo Intervención (GI) y 272 al Grupo Control (GC). Se excluyeron pacientes: institucionalizados, desplazados, atendidos habitualmente por la sanidad privada, o en atención domiciliaria. Intervención: Detección de MPI por parte del farmacéutico mediante combinación de métodos explícitos e implícitos y comunicación de las alternativas terapéuticas más apropiadas al médico prescriptor. Mediciones: Se evaluaron la proporción de pacientes con MPI y número medio de MPI/paciente (variables principales); así como morbilidad, mortalidad, y costes (variables secundarias). Análisis estadístico: Siguiendo el principio de intención de tratar, se compararon las variables cuantitativas y cualitativas mediante las pruebas t Student y X2, respectivamente. Los resultados se expresaron como diferencia de proporciones para variables cualitativas y diferencia de medias para cuantitativas, con los correspondientes intervalos de confianza 95% (IC 95%). Resultados: Después de la intervención, la proporción de pacientes con MPI disminuyó un 13,7% (IC 95%: 9,3; 18,2) más en GI que GC. El número medio de MPI/paciente y coste medio de MPI/paciente disminuyeron en 0,43 (IC 95%: 0,32; 0,54) y 72,11€ (IC 95%: 26,15; 118,06) más en GI que GC, respectivamente. Sin embargo, no se observaron diferencias estadísticamente significativas en morbilidad, mortalidad ni en costes de episodios asistenciales.(AU)

Objectives: To assess the effectiveness of a pharmacist-led systematic review of medications on: potentially inappropriate medications (PIM), health outcomes and costs. Design: Prospective, open, controlled and cluster-randomized clinical trial. Setting: Six primary care clinics from Balearic Islands. Participants: Forty-two clusters (21 per group), and 549 patients aged ≥65 years and ≥5 chronic medications were included; of which 277 were allocated to Intervention Group (IG) and 272 to Control Group (CG). Patients were excluded if they were: institutionalized, temporarily displaced, routinely monitored under private healthcare, or home care. Intervention: PIM detection by the pharmacist using a combination of explicit and implicit methods; and communication of the most appropriate therapeutic strategies to the physician. Measurements: Proportion of patients with PIM and mean number of PIM/patient (main outcomes); and morbidity, mortality, and costs (secondary outcomes) were assessed. Statistical plan: Following an intention-to-treat approach, quantitative and qualitative outcomes variables were compared by T-Student and Chi-square tests, respectively. Results were providing as difference in proportions for qualitative outcomes and difference in means for quantitative outcomes with respective 95% confidence intervals (95% CI). Results: After intervention, proportion of patients with PIM decreased by 13.7% (95% CI: 9.3; 18.2) more in IG than CG. Mean number of PIM/patient and mean cost of PIM/patient decreased by 0.43 (95% CI: 0.32; 0.54) and 72.11€ (95% CI: 26.15; 118.06) more in IG than CG, respectively. However, no statistically significant differences were observed in morbidity, mortality or costs of healthcare resources.(AU)

[Suicide related factors in the elderly: A systematic review.] / Factores relacionados con el suicidio en personas mayores: una revisión sistemática.

BACKGROUND: Depression is a disease prevalent in most older people and is negatively associated with suicidal ideation and behaviour in the elderly. The objective of this systematic review was to study the relationship between suicidal behaviour and the associated risk factors that lead older people to commit it. METHODS: We searched systematically in the PubMed, Web of Science, SciELO and CUIDEN database, in addition, we used a search engine, Google Scholar, including studies when they were observational, with population of 60 years or more, whose patients had made any suicide attempt and instead were excluded when the participants were children or adolescents, reported cases of homicide or only reported the methods used in the suicide. The search was not delimited based on filters or time periods. The data is presented based on Odds Ratio, Relative Risk and percentage (%). RESULTS: Eighteen studies were included in this systematic review. Various factors associated with the appearance of suicidal behaviour in the elderly were reported, the following are the most relevant: serious mental disorders (mean OR/RR value of 157.80); depression (mean OR/RR value of 16.53); and previous suicide attempts (average OR/RR value of 12.33). CONCLUSIONS: Pathological, sociodemographic and psychosocial factors related to the ideation and appearance of suicidal behaviour in the elderly have been differentiated.

OBJETIVO: La depresión es una patología prevalente en la mayoría de las personas mayores y que está asociada negativamente con la ideación y la conducta suicida en la tercera edad. El objetivo de esta revisión sistemática fue estudiar la relación entre la conducta suicida y los factores de riesgo asociados que llevan a las personas mayores a cometerlo. METODOS: Se buscó sistemáticamente en las bases de datos PubMed, Web of Science, SciELO y CUIDEN, además, se empleó un buscador, Google Académico, incluyendo los estudios cuando eran observacionales, con población de 60 años o más, cuyos pacientes hubieran realizado algún intento suicida y por el contrario se excluyeron cuando los participantes eran niños o adolescentes, reportaran casos de homicidios o solo reportaran los métodos empleados en el suicidio. No se delimitó la búsqueda en base a filtros ni a periodos de tiempo. Los datos se presentan en base a Odds Ratio, Riesgo Relativo y porcentaje (%). RESULTADOS: Se incluyeron 18 estudios en esta revisión sistemática. Se reportaron diversos factores asociados con la aparición de la conducta suicida en las personas mayores, siendo los siguientes los más relevantes: trastornos mentales graves (valor medio OR/RR de 157,80); depresión (valor medio OR/RR de 16,53); e intentos de suicidio previo (valor medio OR/RR de 12,33). CONCLUSIONES: Se han diferenciado factores patológicos, sociodemográficos y psicosociales relacionados con la ideación y la aparición de la conducta suicida en las personas mayores.

[Prescription appropriateness in elderly patients with polypharmacy in primary care: Cluster-randomized controlled trial PHARM-PC]. / Adecuación de la prescripción en pacientes mayores polimedicados en atención primaria. Ensayo clínico controlado aleatorizado por grupos PHARM-PC.

OBJECTIVES: To assess the effectiveness of a pharmacist-led systematic review of medications on: potentially inappropriate medications (PIM), health outcomes and costs. DESIGN: Prospective, open, controlled and cluster-randomized clinical trial. SETTING: Six primary care clinics from Balearic Islands. PARTICIPANTS: Forty-two clusters (21 per group), and 549 patients aged ≥65 years and ≥5 chronic medications were included; of which 277 were allocated to Intervention Group (IG) and 272 to Control Group (CG). Patients were excluded if they were: institutionalized, temporarily displaced, routinely monitored under private healthcare, or home care. INTERVENTION: PIM detection by the pharmacist using a combination of explicit and implicit methods; and communication of the most appropriate therapeutic strategies to the physician. MEASUREMENTS: Proportion of patients with PIM and mean number of PIM/patient (main outcomes); and morbidity, mortality, and costs (secondary outcomes) were assessed. STATISTICAL PLAN: Following an intention-to-treat approach, quantitative and qualitative outcomes variables were compared by T-Student and Chi-square tests, respectively. Results were providing as difference in proportions for qualitative outcomes and difference in means for quantitative outcomes with respective 95% confidence intervals (95% CI). RESULTS: After intervention, proportion of patients with PIM decreased by 13.7% (95% CI: 9.3; 18.2) more in IG than CG. Mean number of PIM/patient and mean cost of PIM/patient decreased by 0.43 (95% CI: 0.32; 0.54) and 72.11€ (95% CI: 26.15; 118.06) more in IG than CG, respectively. However, no statistically significant differences were observed in morbidity, mortality or costs of healthcare resources. CONCLUSIONS: PIM detection and recommendations provided by pharmacist could contribute to reduce significantly PIM and drug expenditure; but without reaching statistically significant differences in morbidity, mortality, and healthcare resources costs.

Early use of tocilizumab in patients with severe pneumonia secondary to severe acute respiratory syndrome coronavirus 2 infection and poor prognostic criteria: Impact on mortality rate and intensive care unit admission.

ABSTRACT: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2, keeps spreading globally. Evidence suggests that a subgroup of patients with severe symptomatology might have cytokine storms, which increases mortality. The use of interleukin-6 (IL-6) inhibitors may help in controlling the pathological immune response to the virus. Tocilizumab, a monoclonal antibody against IL-6, stands as an optional treatment for COVID-19 patients presenting this inflammatory hyper-response.We conducted a retrospective, observational, cohort study including 50 patients affected by COVID-19 with severe pneumonia and poor prognosis criteria, who have also undergone standard treatment; 36 of these patients additionally received tocilizumab in an early stage. The need for intensive care unit (ICU) admission, mortality, recovery of respiratory function, and improvement of biochemical and hematological parameters were compared between cohorts.Most patients were men, non-smokers and the most frequently reported comorbidities were hypertension and diabetes. Recurrent symptoms were fever, cough, and dyspnoea. 54.8% of patients from the tocilizumab group needed intubation, while in the control group 85.7% needed it. Treatment with tocilizumab significatively increased IL-6 levels, (554.45; CI 95% 186.69, 1032.93; P < .05) while C-reactive protein mean levels were reduced (-108.19; CI 95% -140.15, -75.33; P < .05), but no significant difference was found between cohorts. In comparison with the controls, tocilizumab reduced mortality (25.0% vs 42.9%, P = .021) and the number of ICU admissions (63.9% vs 100.0%, P = .021). 44.1% of patients treated with tocilizumab showed favorable radiological evolution, when compared with 15.4% of patients from the control group.Tocilizumab may improve clinical symptoms and mitigate deterioration observed in severe COVID-19 patients, and could be considered as an effective therapeutic option in subjects experiencing a significant inflammatory response to the disease.

Intervención del farmacéutico en la prescripción potencialmente inapropiada en pacientes polimedicados: Protocolo ensayo clínico PHARM-PC / Pharmacist-led intervention on potentially inappropriate prescription in patients with polypharmacy: PHARM-PC clinical trial protocol

Objetivo: La polimedicación y la medicación potencialmente inapropiada (que presenta balance beneficio-riesgo desfavorable) son importantes preocupaciones respecto a los pacientes mayores en atención primaria,ya que pueden incrementar el riesgo de morbimortalidad y los costes sanitarios. Diversos estudios han evaluado el impacto de la revisión sistemáticade la medicación conducida por el farmacéutico sobre variables de adecuación, recursos sanitarios y/o costes. Sin embargo, no se han encontradoensayos controlados aleatorizados por clúster que evalúen globalmentetodas estas variables. El objetivo de este estudio es determinar el impactode una revisión sistemática de medicación conducida por el farmacéuticopara reducir el número medio y la proporción de pacientes con medicaciónpotencialmente inapropiada (objetivo principal), así como para reducir lamorbimortalidad y los costes (objetivos secundarios).Método: Se realizará un ensayo clínico abierto, controlado y aleatorizado por clústeres, donde los médicos de atención primaria, en representación de sus respectivos cupos de pacientes, serán aleatorizadosa recibir recomendaciones del farmacéutico para retirar medicacionespotencialmente inapropiadas detectadas mediante combinación de métodos implícitos y explícitos (grupo intervención) o no recibirlas (grupo control). Las variables primarias serán la proporción de pacientes y el númeromedio de medicaciones potencialmente inapropiadas por paciente. Lasvariables secundarias serán los recursos asistenciales frecuentados, proporción de pacientes fallecidos y días de supervivencia; y costes de medicamentos y de recursos asistenciales. (AU)

Objective: Polypharmacy and potentially inappropriate medications(that is, those associated with an unfavorable risk-benefit ratio) are common concerns in the context of elderly patients treated in primary care asthey may increase the risk of morbidity and mortality, as well as healthcare costs. Several studies have assessed the impact of pharmacist-ledsystematic reviews with respect to prescription appropriateness, healthoutcomes and/or costs. However, no cluster-randomized controlled trialhas been identified that provides an overall assessment of these variables.The objective is to determine the effectiveness of a pharmacist-led systematic medication review in reducing the mean number and proportion ofpatients on potentially inappropriate medications (primary goal); as wellas in decreasing morbidity and mortality and the cost of medications andthe use of healthcare resources (secondary goals).Method: An open-label, cluster-randomized controlled trial will beconducted; where primary care physicians will be randomized either toreceive (intervention group) or not to receive pharmacist recommendationsto withdraw potentially inappropriate medications detected through thecombined use of explicit and implicit criteria (control group). Primary endpoints will be the proportion of patients on potentially inappropriate medications and the mean number of such medications per patient. Secondaryendpoints will be healthcare resources used, the proportion of patientswho die and the mean number of days survived, as well as the cost ofmedications and cost of healthcare resources used. (AU)

Pharmacist-led intervention on potentially inappropriate prescription in patients with polypharmacy: PHARM-PC clinical trial protocol.

OBJECTIVE: Polypharmacy and potentially inappropriate medications (that  is, those associated with an unfavorable risk-benefit ratio) are common concerns in the context of elderly patients treated in primary care as they may increase the risk of morbidity and mortality, as well as  healthcare costs. Several studies have assessed the impact of pharmacist- led systematic reviews with respect to prescription appropriateness, health outcomes and/or costs. However, no cluster-randomized controlled  trial has been identified that provides an overall assessment of these  variables. The objective is to determine the effectiveness of a pharmacist- led systematic medication review in reducing the mean number and proportion of patients on potentially inappropriate medications (primary  goal); as well as in decreasing morbidity and mortality and the cost of  medications and the use of healthcare resources (secondary goals). METHOD: An open-label, cluster-randomized controlled trial will be conducted; where primary care physicians will be randomized either to receive (intervention group) or not to receive pharmacist  recommendations to withdraw potentially inappropriate medications  detected through the combined use of explicit and implicit criteria (control  group). Primary end-points will be the proportion of patients on potentially inappropriate medications and the mean number of such medications per  patient. Secondary endpoints will be healthcare resources used, the  proportion of patients who die and the mean number of days survived, as  well as the cost of medications and cost of healthcare resources used. CONCLUSIONS: In line with similar reports and based on our study´s design, we hope to obtain statistically significant reductions in the use  of potentially inappropriate medications and in medication costs overall.  We do not however expect to obtain significant reductions in  morbimortality or the cost of health resources employed.

Objetivo: La polimedicación y la medicación potencialmente inapropiada (que presenta balance beneficio-riesgo desfavorable) son  importantes preocupaciones respecto a los pacientes mayores en atención  primaria, ya que pueden incrementar el riesgo de morbimortalidad y los  costes sanitarios. Diversos estudios han evaluado el impacto de la revisión  sistemática de la medicación conducida por el farmacéutico sobre variables de adecuación, recursos sanitarios y/o costes. Sin embargo, no se han  encontrado ensayos controlados aleatorizados por clúster que evalúen  globalmente todas estas variables. El objetivo de este estudio es  determinar el impacto de una revisión sistemática de medicación  conducida por el farmacéutico para reducir el número medio y la  proporción de pacientes con medicación potencialmente inapropiada  (objetivo principal), así como para reducir la morbimortalidad y los costes  (objetivos secundarios).Método: Se realizará un ensayo clínico abierto, controlado y aleatorizado por clústeres, donde los médicos de atención primaria, en  representación de sus respectivos cupos de pacientes, serán aleatorizados a recibir recomendaciones del farmacéutico para retirar  medicaciones potencialmente inapropiadas detectadas mediante  combinación de métodos implícitos y explícitos (grupo intervención) o no  recibirlas (grupo control). Las variables primarias serán la proporción de  pacientes y el número medio de medicaciones potencialmente  inapropiadas por paciente. Las variables secundarias serán los recursos  asistenciales frecuentados, proporción de pacientes fallecidos y días de  supervivencia; y costes de medicamentos y de recursos asistenciales.Conclusiones: Análogamente a estudios similares, y en base al diseño de  nuestro estudio, esperamos obtener reducción estadísticamente  ignificativa para medicaciones potencialmente inapropiadas y costes de medicamentos. Sin embargo, no esperamos diferencias significativas en morbimortalidad ni en costes de recursos asistenciales.

Significance of PD1 Alternative Splicing in Celiac Disease as a Novel Source for Diagnostic and Therapeutic Target.

Background: We have focused on the alteration of the PD-1/PD-L1 pathway in celiac disease and discussed the roles of the PD1 pathway in regulating the immune response. We explored the idea that the altered mRNA splicing process in key regulatory proteins could represent a novel source to identify diagnostic, prognostic, and therapeutic targets in celiac disease. Methods: We characterized the PD1 mRNA variants' profile in CD patients and in response to gluten peptides' incubation after in vitro experiments. Total RNA from whole blood was isolated, and the coding region of the human PD-1 mRNA was amplified by cDNA PCR. Results: PCR amplification of the human PD-1 coding sequence revealed an association between the over-expression of the sPD-1 protein and the PD-1Δex3 transcript in celiac disease. Thus, we have found three novel alternative spliced isoforms, two of which result in a truncated protein and the other isoform with a loss of 14 aa of exon 2 and complete exon 3 (Δ3) which could encode a new soluble form of PD1 (sPD-1). Conclusions: Our study provides evidence that dietary gluten can modulate processes required for cell homeostasis through the splicing of pre-mRNAs encoding key regulatory proteins, which represents an adaptive mechanism in response to different nutritional conditions.

Effect of Sex Differences on Computed Tomography Findings in Adults With Cystic Fibrosis: A Multicenter Study.

BACKGROUND: The survival of women with cystic fibrosis (CF) is lower than that of men by approximately 5 years. While various factors have been put forward to account for this discrepancy, no specific reasons have been established. Our hypothesis was that anatomical-structural involvement is more pronounced in women with CF than in men and that this is reflected in thoracic HRCT findings. MATERIAL AND METHODS: We performed a prospective multicentre study, in which adult patients were consecutively included over 18 months. Chest HRCT was performed, and findings were scored by 2 thoracic radiologists using the modified Bhalla system. We also studied respiratory function, applied the CFQR 14+ questionnaire, and collected clinical variables. RESULTS: Of the 360 patients followed up in the participating units, 160 were eventually included. Mean age was 28 years, and 47.5% were women. The mean±SD global score on the modified Bhalla score was 13.7±3.8 in women and 15.2±3.8 in men (p=0.024). The highest scores were observed for sacculations, bronchial generations, and air trapping in women. Women had lower BMI, %FEV1, %FVC, and %DLCO. Similarly, the results for the respiratory domain in CFQR 14+ were worse in women, who also had more annual exacerbations. CONCLUSIONS: This is the first study to provide evidence of the implication of sex differences in HRCT findings in patients with CF. Women with CF present a more severe form of the disease that results in more frequent exacerbations, poorer functional and nutritional outcomes, deterioration of quality of life, and greater structural damage.

First records of Anopheles (Anopheles) plumbeus Stephens, 1828 and Culex (Culex) torrentium Martini, 1925 (Diptera: Culicidae) in Galicia (NW Spain).

We present the first records of Anopheles (Anopheles) plumbeus Stephens, 1828 and Culex (Culex) torrentium Martini, 1925 in the autonomous region of Galicia (NW Spain), obtained through the Rede Galega de Vixilancia de Vectores (ReGaViVec). This entomological surveillance network, which was initiated in 2017 by the Xunta de Galicia in collaboration with the University of Vigo and the University of Santiago de Compostela, aims to detect the arrival of invasive vectors as well as to improve the knowledge about mosquito populations (Diptera: Culicidae) in the Galician territory. This study shows the first findings of these species in Galicia, which have been reported in six different locations throughout the region: five in the province of Pontevedra and one in the province of Lugo. The 51 captured specimens were collected at different stages of development between July and September, 2018 and 2019 by using specialized traps arranged in favorable regions for the settlement and development of culicids.

Infección urinaria por Acinetobacter dijkshoorniae y buena respuesta clínica al tratamiento / Urinary tract infection by Acinetobacter dijkshoorniae and good clinical response to treatment

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Complex Evolutionary History of Mboumar, a Mariner Element Widely Represented in Ant Genomes.

Mboumar-9 is an active mariner-transposable element previously isolated in the ant Messor bouvieri. In this work, a mariner-like element, Mboumar, isolated from 22 species of ants, is analyzed. These species belong to nine different subfamilies, including Leptanillinae, the most primitive ant subfamily, and Myrmicinae and Formicidae, the most derived ones. Consequently, Mboumar-like elements seem to be well-represented in ant genomes. The phylogenetic tree drawn for mariner elements is highly inconsistent with the phylogeny of host ants, with almost identical elements found in clearly distant species and, on the contrary, more variable elements in closely related species. The inconsistency between the two phylogenetic trees indicates that these transposable elements have evolved independently from the speciation events of the ants that host them. Besides, we found closer genetic relationships among elements than among their host ants. We also found potential coding copies with an uninterrupted open reading frame of 345 aa in 11 species. The putative transposase codified by them showed a high sequence identity with the active Mboumar-9 transposase. The results of selection tests suggest the intervention of purifying selection in the evolution of these elements. Overall, our study suggests a complex evolutionary history of the Mboumar-like mariner in ants, with important participation of horizontal transfer events. We also suggest that the evolutionary dynamics of Mboumar-like elements can be influenced by the genetic system of their host ants, which are eusocial insects with a haplodiploid genetic system.

La farmacia hospitalaria en tiempos de COVID-19 / Hospital pharmacy in COVID-19

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Stimulatory Response of Celiac Disease Peripheral Blood Mononuclear Cells Induced by RNAi Wheat Lines Differing in Grain Protein Composition.

Wheat gluten proteins are responsible for the bread-making properties of the dough but also for triggering important gastrointestinal disorders. Celiac disease (CD) affects approximately 1% of the population in Western countries. The only treatment available is the strict avoidance of gluten in the diet. Interference RNA (RNAi) is an excellent approach for the down-regulation of genes coding for immunogenic proteins related to celiac disease, providing an alternative for the development of cereals suitable for CD patients. In the present work, we report a comparative study of the stimulatory capacity of seven low-gluten RNAi lines differing in grain gluten and non-gluten protein composition, relevant for CD and other gluten pathologies. Peripheral blood mononuclear cells (PBMCs) of 35 patients with active CD were included in this study to assess the stimulatory response induced by protein extracts from the RNAi lines. Analysis of the proliferative response and interferon-gamma (INF-γ) release of PBMCs demonstrated impaired stimulation in response to all RNAi lines. The lower response was provided by lines with a very low content of α- and γ-gliadins, and low or almost devoid of DQ2.5 and p31-43 α-gliadin epitopes. The non-gluten protein seems not to play a key role in PBMC stimulation.