The Real-World Effectiveness, Persistence, Adherence, and Safety of Janus Kinase Inhibitor Baricitinib in Rheumatoid Arthritis: A Long-Term Study.

Background/Aim: Baricitinib (BAR) is the first oral selective Janus kinase inhibitor approved in Europe for rheumatoid arthritis (RA). Real-world data are still needed to clarify its long-term benefits/risk profile. This study aimed to evaluate the effectiveness, persistence, adherence, and safety of BAR in a real-world setting. Methods: An ambispective study was conducted between October 2017 and December 2021 in RA patients starting BAR. The effectiveness was evaluated, assessing changes from the baseline of the Disease Activity Score using 28-joint counts-C reactive protein (DAS28CRP), and the achievement of low disease activity/remission. Drug persistence was evaluated using Kaplan-Meier analysis. Adherence was estimated using the medication possession ratio (MPR) and the 5-item Compliance Questionnaire for Rheumatology. Safety was assessed determining global incidence proportion and adverse event adjusted incidence rates. Results: In total, 61/64 recruited patients were finally analyzed, 83.6% were female, 78.7% were seropositive, the mean age was 58.1 (15.4) years, and the disease duration was 13.9 (8.3) years. A total of 32.8% of patients were naïve to biologics and 16.4% received BAR as monotherapy. The median exposure to BAR was 12.4 (6.6-31.2) months (range 3.1-51.4). A significant change in DAS28CRP was observed after treatment (difference -1.2, p = 0.000). 70.5% and 60.7% of patients achieved low disease activity or remission, respectively, and 50.8% (31/61) remained on BAR throughout the follow-up, with a median persistence of 31.2 (9.3-53.1) months. The average MPR was 0.96 (0.08) and all patients exhibited "good adherence" according to the questionnaire. In total, 21.3% of patients discontinued baricitinib due to toxicity. Conclusions: In our real-world practice, BAR demonstrated effectiveness, large persistence, high adherence to treatment, and an acceptable safety profile.

Gram-negative anaerobes elicit a robust keratinocytes immune response with potential insights into HS pathogenesis.

Hidradenitis Suppurativa (HS) is a chronic autoinflammatory skin disease with activated keratinocytes, tunnel formation and a complex immune infiltrate in tissue. The HS microbiome is polymicrobial with an abundance of commensal gram-positive facultative (GPs) Staphylococcus species and gram-negative anaerobic (GNA) bacteria like Prevotella, Fusobacterium and Porphyromonas with increasing predominance of GNAs with disease severity. We sought to define the keratinocyte response to bacteria commonly isolated from HS lesions to probe pathogenic relationships between HS and the microbiome. Type strains of Prevotella nigrescens, Prevotella melaninogenica, Prevotella intermedia, Prevotella asaccharolytica, Fusobacterium nucleatum, as well as Staphylococcus aureus and the normal skin commensal Staphylococcus epidermidis were heat-killed and co-incubated with normal human keratinocytes. RNA was collected and analysed using RNAseq and RT-qPCR. The supernatant was collected from cell culture for protein quantification. Transcriptomic profiles between HS clinical samples and stimulated keratinocytes were compared. Co-staining of patient HS frozen sections was used to localize bacteria in lesions. A mouse intradermal injection model was used to investigate early immune recruitment. TLR4 and JAK inhibitors were used to investigate mechanistic avenues of bacterial response inhibition. GNAs, especially F. nucleatum, stimulated vastly higher CXCL8, IL17C, CCL20, IL6, TNF and IL36γ transcription in normal skin keratinocytes than the GPs S. epidermidis and S. aureus. Using RNAseq, we found that F. nucleatum (and Prevotella) strongly induced the IL-17 pathway in keratinocytes and overlapped with transcriptome profiles of HS patient clinical samples. Bacteria were juxtaposed to activated keratinocytes in vivo, and F. nucleatum strongly recruited murine neutrophil and macrophage migration. Both the TLR4 and pan-JAK inhibitors reduced cytokine production. Detailed transcriptomic profiling of healthy skin keratinocytes exposed to GNAs prevalent in HS revealed a potent, extensive inflammatory response vastly stronger than GPs. GNAs stimulated HS-relevant genes, including many genes in the IL-17 response pathway, and were significantly associated with HS tissue transcriptomes. The close association of activated keratinocytes with bacteria in HS lesions and innate infiltration in murine skin cemented GNA pathogenic potential. These novel mechanistic insights could drive future targeted therapies.

Effects of an Educational Intervention Program on Positional Cranial Deformity in Premature Infants.

Positional cranial deformities are associated with prematurity evolving during the first 2 years of life due to the malleable characteristics of the skull, the first year being the main/primary therapeutic window for intervention. The objectives were (a) to describe health characteristics, peri- and postnatal pathologies, and positional cranial deformities in infants enrolled in an early intervention program and (b) to analyze the effects of a parent education-based intervention program on positional cranial deformity in premature infants. A quantitative, analytical, longitudinal study was conducted. It included 103 premature infants enrolled in an early intervention program (EIP) during the year 2017, all under 4 months of corrected age, to whom a parent education-based intervention program was applied. Cranial circumference, cranial width, diagonals, and anteroposterior diameter were measured, and the cranial asymmetry index (CAI) and cephalic index (CI) were calculated at baseline and during two subsequent evaluations separated by a 3-month period. The main results showed that 75.7% of the infants belonged to a very premature gestational age category, and 57.3% had an adequate weight for gestational age. The most frequent pathologies were premature jaundice, premature anemia, and hyaline membrane disease. The most frequent positional cranial deformity was plagiocephaly. The parent education-based intervention program resulted in (1) a significant decrease in the CAI and a significant increase in the IC, (2) plagiocephalies: an increase in the mild category and a decrease in the moderate + severe categories, (3) brachycephalies: a decrease in the absence category and an increase in the moderate + severe category, and (4) dolichocephalies: an increase in the absence category and a decrease in the mild category. In conclusion, the recommended first line of intervention was not enough for this population, and future studies should support the development of national clinical guidelines, where education is complemented with other therapeutic measures.

Anti-interleukin-17 therapies for moderate/severe psoriasis in clinical practice: effectiveness, safety and association with clinical patient factors.

OBJECTIVES: Interleukin-17 (IL-17) contributes to the pathogenesis of psoriasis. Secukinumab, ixekizumab, and brodalumab are monoclonal antibodies anti-IL-17 antibodies, approved for the treatment of moderate/severe plaque psoriasis.The aim of the study was to describe the effectiveness and safety of anti-IL-17 agents in moderate/severe plaque psoriasis in clinical practice. We also analysed anti-IL-17 therapies' survival, dose adjustment, and clinical patients' factors associated with their effectiveness and safety. METHODS: A retrospective, longitudinal study was conducted at a tertiary hospital. We included patients with moderate/severe psoriasis treated with anti-IL-17 agents. The effectiveness was evaluated with Psoriasis Area and Severity Index (PASI) score and safety through the adverse drug reactions (ADRs) collected. RESULTS: 38 patients were studied (median age=47.4 years, 71.0% male). The mean number of biological therapies that patients received was 2.6, and anti-IL-17 therapy was the first biological therapy for 36.8% of patients. The median years in treatment were 2.5 (95% CI 1.95 to 2.98) for secukinumab, 1.2 (95% CI 0.36 to 1.47) for ixekizumab, and 0.7 (IQR 0.71) for brodalumab. The median PASI score after 6 months of treatment was 0 (IQR 0) and 85.3% of patients achieved a PASI of 90 (84.0% with secukinumab, 87.5% with ixekizumab, and 100% with brodalumab). Dose adjustment was associated with the line of treatment (p=0.034 for naïve patients), age (p=0.044 for younger patients), and concomitant pathologies (p=0.015 without more diseases).24 patients suffered from ADRs, mainly infections of the upper respiratory tract, and there were no statistically significant differences between the three therapies. CONCLUSIONS: Anti-IL-17 agents constitute an effective treatment for patients with moderate/severe plaque psoriasis and for longer. Dose reductions were associated with fewer lines of treatment, younger patients and absence of concomitant pathologies. ADR were minor and similar among the anti-IL-17.

Damage to Sorubim cuspicaudus Sperm Cryopreserved with Ethylene Glycol.

The study aimed to evaluate cryo-injury during the cryopreservation in Sorubim cuspicaudus sperm with ethylene glycol (EG) at different rates (6, 8, 10%). Fresh, prefrozen, and post-thawed sperm quality as motility total, velocities, mitochondria damage (Mit-d), membrane damage (Mem-d), and DNA fragmentation (DNA-f), were examined. The Mit-d, Mem-d, and DNA-f were evaluated through flow cytometry. High motility (>95%) and a low percentage of Mem-d (1.0 ± 0.5%), Mit-d (1.4 ± 0.9%), and DNA-f (2.4 ± 0.8%) were recorded for fresh semen. Prefrozen semen increases in Mit-d and DNA-f were observed compared to fresh semen (p < 0.05). In thawed semen, increased Mit-d (2.6 to 3-fold), Mem-d (6 to 1-fold), and DNA-f (3.3 to 6.6-fold) compared to prefrozen was observed. Thawed semen showed Mit-d (34 to 37-fold), Mem-d (24.5 to 26.6-fold) and DNA-f (13 to 18.5-fold) increased high. In conclusion, the present study demonstrated that mitochondria, membrane, and DNA integrity undergo significant damage during both pre-freezing and freezing/thawing with EG inclusion percentages from 6 to 10% that affect its fertilizing capacity, which is reduced to half of that obtained with fresh semen. It is suggested that a cryoprotective solution composed of 6% EG, 6% glucose, and 5% skimmed milk powder is a useful protocol for the cryopreservation of S. cuspicaudus semen.

Real-world outcomes of abiraterone and enzalutamide in first-line treatment of metastatic castration-resistant prostate cancer: which patients benefit most?

OBJECTIVES: Abiraterone and enzalutamide are two oral novel androgen receptor axis-targeted agents approved for the treatment of castration-resistant prostate cancer (mCRPC). Despite the availability of multiple treatments, there is a need to improve the knowledge and management of these drugs in the real-world setting, especially in patient groups under-represented in clinical trials. Our aim was to review the outcome of patients with chemotherapy-naïve mCRPC treated with abiraterone or enzalutamide in routine clinical practice in order to identify factors that are predictive for response. METHODS: This observational retrospective study was performed in a Spanish tertiary hospital and included men with chemotherapy-naïve mCPRC who started treatment with abiraterone or enzalutamide between September 2012 and November 2018. The study end date was 30 October 2020. RESULTS: Ninety patients with mCRPC were included, 57 with abiraterone and 33 with enzalutamide. Median overall survival (OS) was 26.87 months (95% CI 19.68 to 34.05), with no difference found between the two treatment groups. Nine variables were related to increased OS in the univariate analysis: Eastern Cooperative Oncology Group (ECOG) performance status (0-1 vs 2), pain (need of opioids for cancer pain), visceral disease, ≥3 bone lesions, exclusively lymph node metastases, baseline prostate specific antigen (PSA) (<50 vs ≥50 ng/dL and <20 vs ≥20 ng/dL), haemoglobin (<12 vs ≥12 g/dL) and alkaline phosphatase (≤116 vs >116 IU/L). A PSA response >50% was observed in 65 patients (76.5%). In the multivariate analysis, ECOG performance status, pain, visceral disease and alkaline phosphatase provided independent prognostic information. Median OS by Kaplan-Meier analysis was significantly longer for patients with a PSA response (32.1 vs 17.9 months; HR 0.46, 95% CI 0.27 to 0.78; p=0.003). CONCLUSIONS: This study assessed the efficacy of abiraterone and enzalutamide in a real-world setting, including patients under-represented in pivotal studies. Some clinical factors were correlated with improved OS in chemotherapy-naïve men with mCPRC treated with these drugs.

Empathy, psychometrics, cut-off points in nursing students from Latin America.

BACKGROUND: Currently, there are no cut-off points for levels of empathy, making it difficult to assess the change experienced in its development or as a result of its intervention. It is an unsolved problem. INTRODUCTION: Empathy is a cognitive-affective attribute that enables nursing staff to maintain a professional relationship that entails various benefits for the patient. Its strengthening and development during university education is desirable. Empathy studies in Latin American nursing students are based on the direct scores obtained on an empathy test, based on which the variable is described and groups are compared. Statistical comparisons are not enough to discriminate substantive changes since two statistical values can show differences without implying that the post-intervention levels may correspond to a higher category in relation to those of pre-intervention or that two compared groups are qualitatively different. The above applies to empathic behaviour and is valid for students and professionals of health. This study aimed to establish cut-off points that allow defining ordinal categories in empathy. METHODS: In this multicenter and cross-sectional study, 3712 students from 11 Latin American nursing schools participated. The Jefferson Empathy Scale (JES) was applied; the psychometric properties were confirmed by Factor Analysis Confirmatory and Invariance. RESULTS: The JSE empathy scale is a measure with adequate reliability and construct validity. Examined cut-offs determined a structure of five empathy intervals that allowed them to be classified as empathy values in very high, high, medium, low and very low. DISCUSSION: The sequence of statistical tests carried out allowed us to determine ranges of categorical values in the empathy levels of groups of students. However, the determined categories may constitute a specific characteristic of them. It is not possible to extrapolate these results to regions other than those of Latin America. CONCLUSION: The estimated rankings allow comparing levels of empathy between groups of nursing students and the real effect of empathic interventions. IMPLICATIONS FOR NURSING: To contribute with strategies to evaluate changes in the empathic skills of nursing students, resulting in a well-valued skill in health services. IMPLICATIONS FOR NURSING POLICY: The cut-off points define evaluative categories (very low, low, medium, high and very high) that allow objective classification of levels of empathy achieved after (for example) an empathic intervention. This allows assessment of substantive changes experienced by nursing students (and professionals).

Cathelicidin Antimicrobial Peptide LL37 Induces Toll-Like Receptor 8 and Amplifies IL-36γ and IL-17C in Human Keratinocytes.

LL37 is produced by skin injury and bacterial infection and plays an important role in the early stages of psoriasis. In particular, the intracellular receptors toll-like receptors (TLR)3, TLR7, TLR8, and TLR9 are thought to be involved in the pathogenesis of psoriasis in conjunction with LL37, but the interaction between TLR7/8 and LL37 in keratinocytes (KCs) remains unclear. This study aimed to clarify the relationship between LL37 and TLR7/8 in KCs and their involvement in the pathogenetic pathways seen in psoriasis using cultured KCs and skin samples of patients with psoriasis. TLR7/8 was induced by LL37 in KCs. TLR8 but not TLR7 functionally induced many psoriasis-related molecules, whereas IL-17C was not altered by the blockade of TLR7/8. Although costimulation of LL37 with self-RNA/DNA did not show any interaction, LL37 itself would promote psoriasis-related genes. IL-36 receptor antagonistic antibody suppressed IL-17C induced by LL37. In psoriatic epidermis, LL37, TLRs, IL-17C, and IL-36γ expressions were increased and coexpressed with each other. Thus, we concluded that LL37 activates TLR8 in KCs and induces IL-17C through the induction of IL-36γ. Regulation of TLR8 or LL37 in KCs could be a potential therapeutic strategy for psoriatic inflammation.

Development of a telematic pharmaceutical care app (Haemoassist) for multidisciplinary follow-up of patients with congenital coagulopathies.

BACKGROUND: Guidelines for congenital coagulopathies recommend that patients record treatment administrations and bleeding episodes to help healthcare professionals monitor the disease. RESEARCH DESIGN AND METHODS: We studied over two years which patient profiles (age, treatment regimen, treatment compliance) were most likely to accept the use of an app to collect this information. We validated the quality of patient-reported data by comparing it with data obtained from hospital electronic records, pharmacy dispensing records and patient interview, collected in an access database used as a reference. Patient and professional opinions were solicited through open-ended interviews. RESULTS: The app was used by 52% of 315 patients studied. Younger patients were the most frequent users. Patients with better treatment compliance used the app more, although data collection was incomplete for most patients. The best rated by patients were the reminders of days of administration and the minimum stock alerts at home. Healthcare professionals rated the app positively. CONCLUSIONS: Healthcare professionals valued the app as useful for managing treatment of congenital coagulopathies. Patients need support and time to use the app and improve the quality of the data entered. Patients who used the app rated it positively. The treatment compliance improved.

Comparison of the Inflammatory Circuits in Psoriasis Vulgaris, Non‒Pustular Palmoplantar Psoriasis, and Palmoplantar Pustular Psoriasis.

Palmoplantar pustular psoriasis (PPPP) and non‒pustular palmoplantar psoriasis (NPPP) are localized, debilitating forms of psoriasis. The inflammatory circuits involved in PPPP and NPPP are not well-understood. To compare the cellular and immunological features that differentiate PPPP and NPPP, skin biopsies were collected from a total of 30 participants with PPPP, NPPP, and psoriasis vulgaris (PV) and from 10 healthy participants. A subset consented to a second biopsy after 3 additional weeks off medication. Histologic staining of lesional and nonlesional skin showed higher neutrophil counts in PPPP than in NPPP and PV and higher CD8+ T-cell counts in NPPP. RNA sequencing and transcriptional analysis of skin biopsies showed enhanced IFN-γ pathway activation in NPPP lesions but stronger signatures of IL-17 pathway and neutrophil-related genes (e.g., IL36A) in PPPP lesional skin. Serum analysis on the Olink platform detected higher concentrations of T helper type 1, IFN-γ‒inducible chemokines in NPPP, and higher neutrophil-associated cytokines in PPPP. Taken together, this evidence suggests more pronounced T helper 1‒mediated inflammation in NPPP than in PV and PPPP and stronger neutrophil-associated activity in PPPP than in NPPP and PV. These data support targeting inflammatory pathways associated with neutrophilic inflammation (e.g., IL-36 signaling) for therapeutic development in PPPP.

Seric IgG anti-SARS-CoV-2 pre- and post- Covid-19 pandemic from Mexican asymptomatic subjects.

OBJECTIVE: To detect serum IgG anti-SARS-CoV-2 in pre-and post- Covid-19 pandemic in Mexican asymptomatic subjects in order to know the degree of viral dispersion. MATERIALS AND METHODS: Association of serum IgG antibodies (determined by ELISA) to sociodemographic and clinical data or contact with Covid-19 cases in three groups of subjects: 1) Covid-19 pre-pandemic blood donors (n= 538); 2) Covid-19 post-pandemic blood donors (n= 243); 3) Covid-19 post-pandemic neurological patients (n= 312). None of the subjects studied had been vaccinated. RESULTS: The positive rate of IgG anti-SARS-CoV-2 was notably higher in participants recruited during the pandemic (donors, 29.6%; neurological patients, 15.7%) than in those recruited pre-pan-demic (donors 0.6%) (p <0.001). Other conditions associated to antibody positivity were being a worker in sales or services, or having had previous contact with people with Covid-19, for donnors and neurological patients, and having diabetes mellitus, for neurological patients. Higher positivity levels of anti-SARS-CoV-2 IgG were found in females than in males. The highest proportion of subjects with anti-SARS-CoV-2 antibodies was found in central Mexico. CONCLUSIONS: The dispersion of SARS-CoV-2 in asymptomatic, unvaccinated subjects (donors and neurological patients) recruited in a Mexican health institution, who work in sales or services or had previously had contact with Covid-19 patients is 16 to 30%. The level of positivity for anti-SARS-CoV-2 IgG is higher in females than in males. SARS-CoV-2 antibody seropreva-lence follow-up studies must be favored among the general population, being mandatory for donors.

Seric IgG anti-SARS-CoV-2 pre- and post- Covid-19 pandemic from Mexican asymptomatic subjects / IgG sérica anti-SARS-CoV-2 pre y post pandemia de Covid-19 en mexicanos asintomáticos

Abstract: Objective: To detect serum IgG anti-SARS-CoV-2 in pre- and post- Covid-19 pandemic in Mexican asymptomatic subjects in order to know the degree of viral dispersion. Materials and methods: Association of serum IgG antibodies (determined by ELISA) to sociodemographic and clinical data or contact with Covid-19 cases in three groups of subjects: 1) Covid-19 pre-pandemic blood donors (n= 538); 2) Covid-19 post-pandemic blood donors (n= 243); 3) Covid-19 post-pandemic neurological patients (n= 312). None of the subjects studied had been vaccinated. Results: The positive rate of IgG anti-SARS-CoV-2 was notably higher in participants recruited during the pandemic (donors, 29.6%; neurological patients, 15.7%) than in those recruited pre-pandemic (donors 0.6%) (p <0.001). Other conditions associated to antibody positivity were being a worker in sales or services, or having had previous contact with people with Covid-19, for donnors and neurological patients, and having diabetes mellitus, for neurological patients. Higher positivity levels of anti-SARS-CoV-2 IgG were found in females than in males. The highest proportion of subjects with anti-SARS-CoV-2 antibodies was found in central Mexico. Conclusions: The dispersion of SARS-CoV-2 in asymptomatic, unvaccinated subjects (donors and neurological patients) recruited in a Mexican health institution, who work in sales or services or had previously had contact with Covid-19 patients is 16 to 30%. The level of positivity for anti-SARS-CoV-2 IgG is higher in females than in males. SARS-CoV-2 antibody seroprevalence follow-up studies must be favored among the general population, being mandatory for donors.

Resumen: Objetivo: Detectar IgG sérica anti-SARS-CoV-2 antes y después de la pandemia de Covid-19 en sujetos mexicanos asintomáticos, con la intención de conocer el grado de dispersión viral. Material y métodos: Se analizó la asociación de anticuerpos IgG séricos (determinados por ELISA), datos sociodemográficos y clínicos y contacto con casos de Covid-19 en tres grupos de sujetos: 1) donadores de sangre reclutados antes de la pandemia de Covid-19 (n= 538); 2) donadores (n= 243) y 3) pacientes neurológicos (n= 312) reclutados durante la pandemia de Covid-19. Ninguno de los sujetos estudiados había sido vacunado. Resultados: La tasa de positividad de IgG anti-SARS-CoV-2 fue notablemente mayor en los participantes reclutados durante la pandemia (donadores, 29.6%; pacientes neurológicos, 15.7%) que en los reclutados prepandemia (donadores 0.6%). Otras condiciones asociadas con positividad de anticuerpos fueron trabajar en ventas o servicios, o haber tenido contacto previo con pacientes Covid-19, en donadores y pacientes neurológicos, y haber tenido diabetes mellitus, en pacientes neurológicos. Se encontraron mayores niveles de positividad de IgG anti-SARS-CoV-2 en mujeres que en hombres. La mayor proporción de sujetos con anticuerpos anti-SARS-CoV-2 procedía del centro de México. Conclusiones: La dispersión del SARS-CoV-2 en sujetos asintomáticos, no vacunados (donadores y pacientes neurológicos), reclutados en una institución de salud mexicana, que trabajan en ventas o servicios, o tienen contacto previo con pacientes Covid-19 es de 16 a 30%. El nivel de positividad de IgG anti-SARS-CoV-2 es más alto en mujeres que en hombres. Los estudios de seguimiento de la seroprevalencia del SARS-CoV-2 deben favorecerse en la población general, siendo obligatorios en los donadores.

Factores socio demográficos y de estilos de vida asociados a un bajo nivel de actividad física durante el confinamiento producto del COVID-19 en adultos latinoamericanos / Factors associated with inactivity during COVID-19 confinement among Latin American adults

BACKGROUND: The confinement caused by the COVID-19 pandemic changed the lifestyles of the population affecting their levels of physical activity. AIM: To determine the factors associated with a low level of physical activity in adults during confinement during the COVID-19 pandemic. MATERIAL AND METHODS: Adults from Chile, Colombia, México and Perú were invited through social networks to answer an online survey. Questions about sociodemographic, health status and lifestyle variables were included. The level of physical activity and sedentary behavior were determined through the short version of the International Physical Activity Questionnaire (IPAQ). Results: The survey was answered by 3,362 adults aged between 18 and 60 years. Respondents more likely to be inactive were women, those with less than eight years of education, those with overweight or obesity, those who smoked at least one cigarette a day, consumed alcohol four or more times a week, slept less than six hours per day and spent more than 6 hours per day in sedentary behaviors. CONCLUSIONS: These findings provide a sociodemographic and lifestyle profile associated with physical inactivity during the period of confinement in Latin American adults. The results confirm the need to promote healthy lifestyles in the population during periods of confinement.

Ustekinumab reduces serum protein levels associated with cardiovascular risk in psoriasis vulgaris.

Psoriasis increases the risk of cardiovascular disease (CVD). Biomarkers for cardiovascular (CV) risk stratification in psoriasis are lacking, and the effects of psoriasis biologics on CV risk reduction remain unclear. The goal of this study was to identify biomarkers of CV risk in psoriasis blood that are reduced by ustekinumab. We quantified 276 inflammatory and CV-related serum proteins with Olink's multiplex assay in 10 psoriasis patients (vs. 18 healthy controls) and after 12 weeks of ustekinumab treatment. For each protein down-regulated after treatment, the literature was reviewed for studies assessing the protein's association with CVD. Data were collected from each study to calculate CV risk thresholds for each protein, which were compared with protein levels in psoriasis patients before and after treatment. Our results showed that 43 out of 276 proteins were down-regulated after treatment, 25 of which were initially up-regulated at baseline (vs. controls, all p-values ≤0.1). 8 down-regulated proteins were initially elevated above thresholds associated with enhanced CV risk in the literature (myeloperoxidase, C-X-C motif chemokine 10, E-selectin, interleukin-6, cystatin B, von Willebrand factor, tumor necrosis factor receptor 1 and N-terminal prohormone brain natriuretic peptide). Treatment lowered these proteins to below their risk thresholds, except for IL-6, which was lowered but remained at its risk threshold despite successful psoriasis skin treatment. In summary, 12 weeks of ustekinumab treatment reduced serum proteins present at levels associated with CV risk in psoriasis patients. Further studies can evaluate these proteins as potential ustekinumab-modulated biomarkers of CV risk in psoriasis and the impact of ustekinumab on CV risk reduction.

Interleukin-17RA blockade by brodalumab decreases inflammatory pathways in hidradenitis suppurativa skin and serum.

BACKGROUND: Hidradenitis suppurativa (HS) is an inflammatory skin disease with dysregulation of the interleukin (IL)-17 axis. Recently, we reported the clinical benefit of brodalumab, a human anti-IL-17 receptor A (IL-17RA) monoclonal antibody, in moderate-to-severe HS. OBJECTIVES: To characterize the molecular response to brodalumab in HS skin and serum, and to identify biomarkers of treatment response. METHODS: Ten participants, who received brodalumab 210 mg /1·5 mL subcutaneously at weeks 0, 1, 2, 4 and every 2 weeks thereafter, were included in this molecular profiling study (NCT03960268). RNA sequencing and immunohistochemistry of nonlesional, perilesional and lesional HS skin biopsies, and Olink high-throughput proteomics of serum at baseline, weeks 4 and 12 were assessed. RESULTS: At week 12, brodalumab led to a decrease of overall inflammation, and improvement of psoriasis-, keratinocyte- and neutrophil-related pathways. Despite perilesional and lesional skin exhibiting no differentially expressed genes at baseline, treatment response was best assessed in perilesional skin. In serum, brodalumab treatment decreased pathways involved in neutrophil inflammation. Patients with higher baseline expression of neutrophil-associated lipocalin-2 (LCN2) in the skin or IL-17A in the serum demonstrated greater decreases of HS-related inflammatory cytokines as measured in skin biopsies at week 12. CONCLUSIONS: IL-17RA inhibition by brodalumab decreases several pathogenic inflammatory axes in HS. Perilesional skin provides a valid and robust assessment of treatment response. Expression of LCN2 in skin or IL-17A in serum may be used as biomarkers to stratify patients that may have a superior molecular response to brodalumab.

Intervention by a clinical pharmacist carried out at discharge of elderly patients admitted to the internal medicine department: influence on readmissions and costs.

BACKGROUND: Patient education on pharmacological treatment could reduce readmissions. Our objective was to carry out a pharmacist intervention focused on providing information about high-risk medications to chronic patients and to analyse its influence on readmissions and costs. METHODS: A single-centre study with an intervention group and a retrospective control group was conducted. The intervention was carried out in all polymedicated patients ≥ 65 years who were admitted to internal medicine and signed the informed consent between June 2017 and February 2018. Patients discharged to nursing homes or long-term hospitals were excluded. The control group were all the patients who were admitted during the same months of 2014 who met the same inclusion criteria. The patients were classified according to the HOSPITAL score as having a low, intermediate, or high risk of potentially avoidable readmission. Outcome measures were 30-day readmission and cost data. To analyse the effect of the intervention on readmission, a logistic regression was performed. RESULTS: The study included 589 patients (286 intervention group; 303 control group). The readmission rate decreased from 20.13% to 16.43% in the intervention group [OR = 0.760 95% CI (0.495-1.166); p = 0.209)]. The incremental cost for the intervention to prevent one readmission was €3,091.19, and the net cost saving was €1,301.26. In the intermediate- and high-risk groups, readmissions were reduced 10.91% and 10.00%, and the net cost savings were €3,3143.15 and €3,248.71, respectively. CONCLUSIONS: The pharmacist intervention achieved savings in the number of readmissions, and the net cost savings were greater in patients with intermediate and high risks of potentially avoidable readmission according to the HOSPITAL score.

[Factors associated with inactivity during COVID-19 confinement among Latin American adults]. / Factores socio demográficos y de estilos de vida asociados a un bajo nivel de actividad física durante el confinamiento producto del COVID-19 en adultos latinoamericanos.

BACKGROUND: The confinement caused by the COVID-19 pandemic changed the lifestyles of the population affecting their levels of physical activity. AIM: To determine the factors associated with a low level of physical activity in adults during confinement during the COVID-19 pandemic. MATERIAL AND METHODS: Adults from Chile, Colombia, México and Perú were invited through social networks to answer an online survey. Questions about sociodemographic, health status and lifestyle variables were included. The level of physical activity and sedentary behavior were determined through the short version of the International Physical Activity Questionnaire (IPAQ). RESULTS: The survey was answered by 3,362 adults aged between 18 and 60 years. Respondents more likely to be inactive were women, those with less than eight years of education, those with overweight or obesity, those who smoked at least one cigarette a day, consumed alcohol four or more times a week, slept less than six hours per day and spent more than 6 hours per day in sedentary behaviors. CONCLUSIONS: These findings provide a sociodemographic and lifestyle profile associated with physical inactivity during the period of confinement in Latin American adults. The results confirm the need to promote healthy lifestyles in the population during periods of confinement.

Caracterización de habilidades comunicativas en estudiantes de Medicina / Characterization of communicative skills in medical students

RESUMEN Fundamento: la comunicación médica efectiva durante la promoción y prevención en salud constituye un reto profesional que enfrenta la educación médica superior en Cuba. Objetivo: caracterizar el desarrollo de habilidades comunicativas en estudiantes de Medicina de la Filial de Ciencias Médicas del municipio Palma Soriano, provincia Santiago de Cuba. Métodos: se realizó una investigación descriptiva, durante el curso 2018-2019. Se emplearon métodos teóricos: análisis-síntesis e inductivo-deductivo, y empíricos: observación, entrevista a profundidad para profesores y estudiantes y grupo focal; se realizó la triangulación de fuentes y metodológica y todo se sustentó en el enfoque dialéctico- materialista. Resultados: se identificaron dificultades en el desempeño comunicativo de los estudiantes, se aprecia que poseen dominio teórico sobre las habilidades comunicativas, pero las relegan a un segundo plano respecto a las habilidades clínicas y técnicas. Se considera que los profesores están insatisfechos con la preparación que muestran los estudiantes en su desempeño comunicativo comunitario y reconocen que es insuficiente el tratamiento didáctico en favor de las habilidades comunicativas. También se constató que en opinión de los estudiantes las habilidades comunicativas serán adquiridas y desarrolladas durante la práctica médica cotidiana del posgrado, y no realizaban un esfuerzo activo y consciente para su perfeccionamiento. Conclusiones: se caracterizaron las habilidades comunicativas de los estudiantes, insuficientes aún para la comunicación efectiva en la relación médico-comunidad; existe un insuficiente tratamiento didáctico y teórico-práctico de estas habilidades.

ABSTRACT Background: effective medical communication during health promotion and prevention is a professional challenge faced by higher medical education in Cuba. Objective: to characterize the development of communication skills in Medicine students of the Medical Sciences Branch of Palma Soriano municipality, Santiago de Cuba province. Methods: a descriptive research was carried out during the 2018-2019 academic year. Theoretical methods were used: analysis-synthesis and inductive-deductive, and empirical ones: observation, in-depth interviews with teachers and students, and focal group; the comparison of sources and methodology was carried out and everything was based on the dialectical-materialist approach. Results: difficulties were identified in the communicative performance of the students, it is appreciated that they have theoretical mastery over communicative skills, but relegate them to the background with respect to clinical and technical skills. It is considered that the professors are dissatisfied with the preparation that the students show in their community communicative performance and recognize that the didactic treatment in favor of communicative skills is insufficient. It was also found that, in the opinion of the students, communication skills will be acquired and developed during the daily postgraduate medical practice, and they did not make an active and conscious effort to improve them. Conclusions: the communication skills of the students were characterized, still insufficient for effective communication in the doctor-community relationship; there is insufficient didactic and theoretical-practical treatment of these skills.

Narrativa de enfermería: visión y patrones de conocimiento en la experiencia de cuidado de una persona con colostomía. Reporte de caso / A Nursing Narrative: Vision and Patterns of Knowledge in the Care Experience of a Patient with Colostomy. A case report

RESUMEN La narrativa de las situaciones de enfermería resalta las vivencias y significados de la persona objeto de cuidado con un proceso de enfermedad y da cuenta de la relación de cuidado enfermero-paciente como aspecto clave para la recuperación de la salud física, mental y espiritual, teniendo como base el proceso de atención de enfermería. Se presenta la situación de enfermería de una persona mayor de 74 años de edad, posquirúrgica de laparotomía exploratoria más resección de masa en colon sigmoide, que derivó en una colostomía. Se resaltan situaciones relacionadas con la ansiedad y preocupación de parte de una de sus hijas por el estado de salud de su madre. Con base en la narrativa se analizaron los patrones de conocimiento personal, empírico, ético y estético, la visión del mundo de enfermería integrativa-interactiva, así como la aplicación de la teoría de rango medio de las transiciones; los supuestos de las propiedades de la transición de Afaf Meleis.

ABSTRACT The narrative of nursing situations highlights the experiences and meanings of the person object of care with a disease process, and accounts for the caring relationship between the nurse and the patient in need of nursing care as a key aspect for the recovery of physical, mental, and spiritual health, based on the nursing care process. The nursing situation of a 74-year-old woman after a laparotomy surgery plus resection of a mass in the sigmoid colon, that led to a colostomy, is presented. Situations related to anxiety and concern of one of her daughters about the state of health of her mother are highlighted. Based on the narrative, we analyzed the fundamental patterns of personal, empirical, ethical, and aesthetic knowledge; and also the Interactive-Integrative Nursing Worldview, as well as the application of Afaf Meleis' Transitions mid-range Theory and its assumptions of the transition properties.