ALDRESS: A Retrospective Pilot Study to Develop a Pharmacological Causality Algorithm for Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).

Background: The drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome represents a severe form of drug hypersensitivity reaction characterized by significant morbidity, mortality, and long-term sequelae, coupled with limited therapeutic avenues. Accurate identification of the causative drug(s) is paramount for acute management, exploration of safe therapeutic alternatives, and prevention of future occurrences. However, the absence of a standardized diagnostic test and a specific causality algorithm tailored to DRESS poses a significant challenge in its clinical management. Methods: We conducted a retrospective case-control study involving 37 DRESS patients to validate a novel causality algorithm, the ALDRESS, designed explicitly for this syndrome, comparing it against the current standard algorithm, SEFV. Results: The ALDRESS algorithm showcased superior performance, exhibiting an 85.7% sensitivity and 93% specificity with comparable negative predictive values (80.6% vs. 97%). Notably, the ALDRESS algorithm yielded a substantially higher positive predictive value (75%) compared to SEFV (51.40%), achieving an overall accuracy rate of 92%. Conclusions: Our findings underscore the efficacy of the ALDRESS algorithm in accurately attributing causality to drugs implicated in DRESS syndrome. However, further validation studies involving larger, diverse cohorts are warranted to consolidate its clinical utility and broaden its applicability. This study lays the groundwork for a refined causality assessment tool, promising advancements in the diagnosis and management of DRESS syndrome.

Amygdala-liver signaling orchestrates rapid glycemic responses to stress and drives stress-induced metabolic dysfunction.

Behavioral adaptations to environmental threats are crucial for survival and necessitate rapid deployment of energy reserves. The amygdala coordinates behavioral adaptations to threats, but little is known about its involvement in underpinning metabolic adaptations. Here, we show that acute stress activates medial amygdala (MeA) neurons that innervate the ventromedial hypothalamus (MeAVMH neurons), which precipitates hyperglycemia and hypophagia. The glycemic actions of MeAVMH neurons occur independent of adrenal or pancreatic glucoregulatory hormones. Instead, using whole-body virus tracing, we identify a polysynaptic connection from MeA to the liver, which promotes the rapid synthesis of glucose by hepatic gluconeogenesis. Repeated stress exposure disrupts MeA control of blood glucose and appetite, resulting in diabetes-like dysregulation of glucose homeostasis and weight gain. Our findings reveal a novel amygdala-liver axis that regulates rapid glycemic adaptations to stress and links recurrent stress to metabolic dysfunction.

Myocarditis and pericarditis risk with mRNA COVID-19 vaccination compared to unvaccinated individuals: A retrospective cohort study in a Spanish Tertiary Hospital.

OBJECTIVE: This study compared the incidence of pericarditis and myocarditis in patients exposed to mRNA COVID-19 vaccines to the incidence in those who were not vaccinated, considering the incidence of these conditions resulting from COVID-19 infection. METHODS: This was a retrospective cohort study of individuals assigned to health area of La Paz University Hospital in Spain. The exposure factor was vaccination with mRNA COVID-19 vaccines between December 27th, 2020 and January 9th, 2022 with a minimum follow-up of one month. The outcome was the incidence of pericarditis or myocarditis in these individuals. RESULTS: The incidence of pericarditis and myocarditis in the total population exposed to at least one dose of mRNA COVID-19 vaccines was 5/100,000 (CI95%:3 to 8 per 100,000), compared to 70/100,000 (CI95%: 66 to 92 per 100,000) in those who were not vaccinated. In the adolescent population (aged 12-17), the incidence was 10/100,000 in vaccinated population (CI95%: 5 to 45 per 100,000) compared to 20/100,000 in unvaccinated (CI95%: 6 to 79 per 100,000). The incidence of pericarditis or myocarditis in patients with COVID-19 infection was 200/100,000 people (CI95%: 114 to 306 per 100,000). The most common cause of pericarditis and myocarditis in the cohort was idiopathic/infectious (74 cases). Cases of myocarditis attributed to COVID-19 infection were more severe and had higher mortality rates compared to cases with other causes. CONCLUSION: The incidence of pericarditis and myocarditis in patients exposed to mRNA COVID-19 vaccines was lower than in those who were not vaccinated, especially in adults.The most common cause of pericarditis and myocarditis was idiopathic/infectious, but the most frequent cause in adolescent patients was mRNA COVID-19 vaccination. Cases of myocarditis due to COVID-19 infection were more severe and had greater mortality.

Results of phase 2 randomized multi-center study to evaluate the safety and efficacy of infusion of memory T cells as adoptive therapy in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia and/or lymphopenia (RELEASE NCT04578210).

BACKGROUND AIMS: There are currently no effective anti-viral treatments for coronavirus disease 2019 (COVID-19)-hospitalized patients with hypoxemia. Lymphopenia is a biomarker of disease severity usually present in patients who are hospitalized. Approaches to increasing lymphocytes exerting an anti-viral effect must be considered to treat these patients. Following our phase 1 study, we performed a phase 2 randomized multicenter clinical trial in which we evaluated the efficacy of the infusion of allogeneic off-the-shelf CD45RA- memory T cells containing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells from convalescent donors plus the standard of care (SoC) versus just the SoC treatment. METHODS: Eighty-four patients were enrolled in three Spanish centers. The patients were randomized into the infusion of 1 × 106/kg CD45RA- memory T cells or the SoC. We selected four unvaccinated donors based on the expression of interferon gamma SARS-CoV-2-specific response within the CD45RA- memory T cells and the most frequent human leukocyte antigen typing in the Spanish population. RESULTS: We analyzed data from 81 patients. The primary outcome for recovery, defined as the proportion of participants in each group with normalization of fever, oxygen saturation sustained for at least 24 hours and lymphopenia recovery through day 14 or at discharge, was met for the experimental arm. We also observed faster lymphocyte recovery in the experimental group. We did not observe any treatment-related adverse events. CONCLUSIONS: Adoptive cell therapy with off-the-shelf CD45RA- memory T cells containing SAR-CoV-2-specific T cells is safe, effective and accelerates lymphocyte recovery of patients with COVID-19 pneumonia and/or lymphopenia. TRIAL REGISTRATION: NCT04578210.

A Comparison of the Efficacy of Treatment With Fidaxomicin Versus Vancomycin in Clostridioides difficile Infection.

Background Clostridioides difficile infection (CDI) is a major cause of diarrhea in hospitalized adult patients. This study aims to evaluate the clinical characteristics, clinical cure, recurrence and mortality in patients with CDI treated with either fidaxomicin or vancomycin. Methods A retrospective case-control study was conducted on patients with CDI treated with either fidaxomicin or vancomycin at a hospital from January 2019 to March 2022. Results We assessed 140 patients with CDI episodes, 70 patients treated with fidaxomicin and 70 with vancomycin. Seventy (50%) were male. Median age was 70 years old (IQR: 56-81). Fidaxomicin group had more recurrent CDI episodes within six months (59% vs 11%, p ≤ 0.001), more severity (43% vs 16%, p ≤ 0.001) and less treatment response (84% vs 100%, p ≤ 0.002) compared with vancomycin group. Recurrence and mortality rates in the follow-up period did not differ in both groups. Conclusions Our study found fidaxomicin treatment had worse outcomes due to restricted usage, potentially impacting its effectiveness in CDI. This finding is especially significant for patients with severe or recurrent CDI, as prescribing of the drug was limited until May 2022 in Spain with the lifting of this restriction, further research is necessary to better understand the potential benefits of fidaxomicin in treating CDI.

[Procalcitonin as sepsis predictor in cardiovascular surgery with cardiopulmonary bypass]. / Procalcitonina como predictor de sepsis en cirugía cardiovascular con circulación extracorpórea.

Background: Cardiopulmonary bypass generates an exacerbated response that may lead to sepsis. Objective: To describe the association between procalcitonin levels and sepsis diagnosis in cardiovascular surgery subjects with cardiopulmonary bypass. Methods: A case-series study was conducted in 142 patients. Serum procalcitonin levels were measured at 24 hours and at 72 hours after surgery using a point of care testing based on quantitative immunochromatographic method. To assess association between procalcitonin levels and sepsis status, we calculated area under the curve (AUC) and sensitivity, specificity, and predictive values for the best cut-off point. Results: From 142 patients studied, 7 developed sepsis after surgery (4.9%). For 24-hours procalcitonin levels AUC was 0.921 and best cut-off point was 3.8 ng/mL (sensitivity 0.857 and specificity 0.904). In the case of 72-hours procalcitonin levels, we observed a value of 0.868 for AUC and best cut-off point was 8.4 ng/mL (sensitivity 0.86 and specificity 0.97). Conclusions: Procalcitonin levels at 24 and 72 hours after cardiovascular surgery with cardiopulmonary bypass are associated with sepsis presence at cut-off points of 3.8 and 8.4 ng/mL respectively.

Introducción: la circulación extracorpórea durante la cirugía cardiovascular genera una respuesta exacerbada que puede asociarse con sepsis. Objetivo: describir la asociación entre los niveles de procalcitonina y el diagnóstico de sepsis en sujetos de cirugía cardiovascular con circulación extracorpórea. Material y métodos: se realizó un estudio de serie de casos en 142 pacientes. Los niveles de procalcitonina fueron medidos a las 24 horas y a las 72 horas después de la cirugía. Para evaluar la asociación entre los niveles de procalcitonina y la identificación de sepsis, se calculó el área bajo la curva (AUC) y la sensibilidad y especificidad identificando el mejor punto de corte. Resultados: de un total de 142 pacientes estudiados, 7 desarrollaron sepsis (4.9%). En los niveles de procalcitonina en las 24 horas, el AUC fue de 0.921 y el mejor punto de corte fue 3.8 ng/mL (sensibilidad de 0.857 y especificidad de 0.904). En el caso de los niveles de procalcitonina a las 72 horas, observamos un AUC de 0.868 y el mejor punto de corte fue 8.4 ng/mL (sensibilidad de 0.86 y especificidad de 0.97). Conclusiones: los niveles de procalcitonina a las 24 y 72 horas de la cirugía cardiovascular con circulación extracorpórea se asociaron con la presencia de sepsis con los puntos de corte de 3.8 ng/mL y 8.4 ng/mL respectivamente.

Magnetogenetic cell activation using endogenous ferritin.

The ability to precisely control the activity of defined cell populations enables studies of their physiological roles and may provide therapeutic applications. While prior studies have shown that magnetic activation of ferritin-tagged ion channels allows cell-specific modulation of cellular activity, the large size of the constructs made the use of adeno-associated virus, AAV, the vector of choice for gene therapy, impractical. In addition, simple means for generating magnetic fields of sufficient strength have been lacking. Toward these ends, we first generated a novel anti-ferritin nanobody that when fused to transient receptor potential cation channel subfamily V member 1, TRPV1, enables direct binding of the channel to endogenous ferritin in mouse and human cells. This smaller construct can be delivered in a single AAV and we validated that it robustly enables magnetically induced cell activation in vitro . In parallel, we developed a simple benchtop electromagnet capable of gating the nanobody-tagged channel in vivo . Finally, we showed that delivering these new constructs by AAV to pancreatic beta cells in combination with the benchtop magnetic field delivery stimulates glucose-stimulated insulin release to improve glucose tolerance in mice in vivo . Together, the novel anti-ferritin nanobody, nanobody-TRPV1 construct and new hardware advance the utility of magnetogenetics in animals and potentially humans.

Identifying biomarkers of treatment response to ciclosporin in atopic dermatitis through multiomic predictive modelling: DERMATOMICS study protocol.

INTRODUCTION: There is a need to optimise the management of atopic dermatitis (AD), improving the efficacy of treatments and reducing the toxicity associated with them. Although the efficacy of ciclosporine (CsA) in the treatment of AD has been thoroughly documented in the literature, the optimal dose has not been yet established. The use of multiomic predictive models of treatment response could optimise CsA therapy in AD. METHODS AND ANALYSIS: The study is a low-intervention phase 4 trial to optimise the treatment of patients with moderate-severe AD requiring systemic treatment. The primary objectives are to identify biomarkers that could allow for the selection of responders and non-responders to first-line treatment with CsA and to develop a response prediction model to optimise the CsA dose and treatment regimen in responding patients based on these biomarkers. The study is divided into two cohorts: the first comprised of patients starting treatment with CsA (cohort 1), and the second, of patients already receiving or who have received CsA therapy (cohort 2). ETHICS AND DISSEMINATION: The study activities began following authorisation by the Spanish Regulatory Agency (AEMPS) and the Clinical Research Ethics Committee of La Paz University Hospital approval. Trial results will be submitted for publication in an open access peer-reviewed medical speciality-specific publication.Trial registration of this study can be located at the EU Clinical Trials Register, available from https://euclinicaltrials.eu/search-for-clinical-trials/?lang=en. Our clinical trial was registered in the website before the enrolment of the first patient complying with European regulations. EU Clinical Trials Register is a primary registry according the WHO. Once our trial was included in a primary and official registry, in order to extend the accessibility to our research, we also registered it retrospectively in clinicaltrials.gov; however, this is not mandatory as per our regulation. TRIAL REGISTRATION NUMBER: NCT05692843.

Transition to the Role of Family Caregiver of Older Adults After a Stroke: A Specific Theory / Transición del rol cuidador familiar de la persona adulta mayor post accidente cerebrovascular (ACV): teoría específica / Transição ao papel de cuidador familiar no idoso após acidente vascular cerebral (AVC): teoria específica

Introduction: Nursing professionals develop situation-specific theories to describe, explain, and provide comprehensive care during a family member's transition to the caregiver role. Objective: To develop a situation-specific theory about the transition to the role of family caregiver of older adults after a stroke. Methodology: The integrating approach by Meleis and Im was applied, which consists of five stages: 1) Description of the context and target population, 2) Verification of assumptions regarding the philosophical stance, 3) Exploration of multiple sources, 4) Theorization of concepts, and 5) Proposal of empirical indicators for validation and verification. Results: The prescriptive theory was developed in the light of Afaf Meleis' Theory of Transitions and was supported by an exhaustive literature review, with four underlying concepts: Situational transition to the family caregiver role, Care-related knowledge and skills, Self-confidence and coping in adopting the caregiver role, and Nursing therapeutic education. The following assumption emerges from these concepts: a healthy transition to the family caregiver role is directly dependent on the care-related knowledge and skills provided by Nursing therapeutic education to develop self-confidence and coping in adopting the caregiver role. Conclusions: The proposal provides a conceptual framework that identifies the transition challenges and needs faced by family caregivers to adopt the role of caregivers of older adults after a stroke.

Introducción: los profesionales de enfermería desarrollan teorías de situación específica para describir, explicar y proporcionar cuidados integrales durante la transición del familiar al rol cuidador. Objetivo: desarrollar una propuesta de teoría de situación específica sobre la transición al rol cuidador familiar de la persona adulta mayor post accidente cerebrovascular. Metodología: se aplicó el enfoque integrador de Meleis e Im, que consta de cinco etapas: 1) descripción del contexto y población blanco; 2) comprobación de suposiciones en relación con la postura filosófica; 3) exploración de múltiples fuentes; 4) teorización de conceptos; y 5) propuesta de indicadores empíricos para la validación y comprobación. Resultados: la teoría prescriptiva fue desarrollada a la luz de la teoría de las transiciones de Afaf Meleis y se apoyó en una revisión exhaustiva de literatura, con cuatro conceptos subyacentes: transición situacional del rol cuidador familiar, conocimiento y habilidad del cuidado, confianza y afrontamiento en la adopción del rol cuidador, y educación terapéutica de enfermería. A partir de estos, surge la siguiente proposición: la transición saludable al rol cuidador familiar depende directamente de los conocimientos y habilidades de cuidado que brinda la terapéutica de enfermería para el desarrollo de confianza y afrontamiento en la adopción del rol cuidador. Conclusiones: la propuesta proporciona un marco conceptual que identifica los desafíos y necesidades de transición de los cuidadores familiares para la adopción del rol cuidador de la persona adulta mayor post accidente cerebrovascular.

Introdução: os profissionais de enfermagem desenvolvem teorias específicas para descrever, explicar e prestar cuidados holísticos durante a transição do familiar para o papel de cuidador. Objetivo: desenvolver uma proposta de teoria específica sobre a transição para o papel de cuidador familiar do idoso pós-AVC. Metodologia: foi aplicada a abordagem integrativa de Meleis e Im, composta por cinco etapas: 1) descrição do contexto e da população-alvo; 2) teste de hipóteses em relação à postura filosófica; 3) exploração de múltiplas fontes; 4) teorização de conceitos; e 5) proposta de indicadores empíricos para validação e teste. Resultados: a teoria prescritiva foi desenvolvida à luz da teoria das transições de Afaf Meleis e com o suporte de uma revisão exaustiva da literatura, com quatro conceitos subjacentes: transição situacional do papel de cuidador familiar, conhecimentos e competências de cuidado, confiança e enfrentamento na adoção do papel de cuidador e educação terapêutica em enfermagem. Destes conceitos emerge a seguinte proposição: a transição saudável para o papel de cuidador familiar depende diretamente do conhecimento e das competências de cuidado proporcionadas pela enfermagem terapêutica para o desenvolvimento de confiança e capacidade de enfrentamento na adoção do papel de cuidador. Conclusões: A proposta fornece um quadro conceitual que identifica os desafios e as necessidades de transição dos cuidadores familiares na adoção do papel de cuidador do idoso após acidente vascular cerebral (AVC).

Microorganisms isolated in patients with post-cardiac surgery mediastinitis at a cardiology hospital of Mexico City.

INTRODUCTION: Mediastinitis after cardiovascular surgery gives rise to prolonged hospital stay and increased medical care costs, and is associated with high in-hospital mortality. OBJECTIVE: To describe the clinical characteristics of patients with post-surgical mediastinitis, including the isolated microorganisms, resistance profile, and in-hospital survival. METHODS: Cross-sectional study of patients with bacteriologically-confirmed post-surgical mediastinitis cared for at a cardiology hospital in Mexico City between January 2017 and March 2019. RESULTS: Fifty-eight cases of mediastinitis were included. Median age was 67 years. Most subjects were males who underwent myocardial revascularization. During in-hospital follow-up, all-cause and mediastinitis-related mortality were 27.6% and 20.7%, respectively. Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli were the most commonly isolated microorganisms. High resistance to methicillin was found in coagulase-negative staphylococci, as well as high expression of extended-spectrum beta-lactamases in Escherichia coli and Klebsiella pneumoniae strains. CONCLUSIONS: High mortality and significant antimicrobial resistance were found in patients with post-cardiac surgery mediastinitis.

INTRODUCCIÓN: La mediastinitis posterior a cirugía cardiovascular deriva en estancia hospitalaria prolongada e incremento de los costos de la atención médica, y se asocia a elevada letalidad hospitalaria. OBJETIVO: Describir las características clínicas de los pacientes con mediastinitis posquirúrgica, incluyendo los microorganismos aislados, perfil de resistencia y supervivencia hospitalaria. MÉTODOS: Estudio transversal de pacientes con mediastinitis posquirúrgica bacteriológicamente confirmada, atendidos en un hospital de cardiología de la Ciudad de México entre enero de 2017 y marzo de 2019. RESULTADOS: Se incluyeron 58 casos de mediastinitis. La mediana de edad fue de 67 años. La mayoría de los sujetos fueron varones sometidos a revascularización miocárdica. Durante el seguimiento hospitalario, la letalidad por todas las causas y la secundaria a la mediastinitis fueron de 27.6 y 20.7 %, respectivamente. Los microorganismos más frecuentemente aislados fueron Staphylococcus aureus, Staphylococcus epidermidis y Escherichia coli. Se encontró alta resistencia a meticilina en los estafilococos coagulasa negativos y alta expresión de betalactamasas de espectro extendido en cepas de Escherichia coli y Klebsiella pneumoniae. CONCLUSIONES: En los pacientes con mediastinitis posquirúrgica analizados se observó alta letalidad e importante resistencia antimicrobiana.

Microorganismos aislados en pacientes con mediastinitis poscirugía cardiaca en un hospital de cardiología de la Ciudad de México / Microorganisms isolated in patients with post-cardiac surgery mediastinitis at a cardiology hospital of Mexico City

Resumen Introducción: La mediastinitis posterior a cirugía cardiovascular deriva en estancia hospitalaria prolongada e incremento de los costos de la atención médica, y se asocia a elevada letalidad hospitalaria. Objetivo: Describir las características clínicas de los pacientes con mediastinitis posquirúrgica, incluyendo los microorganismos aislados, perfil de resistencia y supervivencia hospitalaria. Métodos: Estudio transversal de pacientes con mediastinitis posquirúrgica bacteriológicamente confirmada, atendidos en un hospital de cardiología de la Ciudad de México entre enero de 2017 y marzo de 2019. Resultados: Se incluyeron 58 casos de mediastinitis. La mediana de edad fue de 67 años. La mayoría de los sujetos fueron varones sometidos a revascularización miocárdica. Durante el seguimiento hospitalario, la letalidad por todas las causas y la secundaria a la mediastinitis fueron de 27.6 y 20.7 %, respectivamente. Los microorganismos más frecuentemente aislados fueron Staphylococcus aureus, Staphylococcus epidermidis y Escherichia coli. Se encontró alta resistencia a meticilina en los estafilococos coagulasa negativos y alta expresión de betalactamasas de espectro extendido en cepas de Escherichia coli y Klebsiella pneumoniae. Conclusiones: En los pacientes con mediastinitis posquirúrgica analizados se observó alta letalidad e importante resistencia antimicrobiana.

Abstract Introduction: Mediastinitis after cardiovascular surgery gives rise to prolonged hospital stay and increased medical care costs, and is associated with high in-hospital mortality. Objective: To describe the clinical characteristics of patients with post-surgical mediastinitis, including the isolated microorganisms, resistance profile, and in-hospital survival. Methods: Cross-sectional study of patients with bacteriologically-confirmed post-surgical mediastinitis cared for at a cardiology hospital in Mexico City between January 2017 and March 2019. Results: Fifty-eight cases of mediastinitis were included. Median age was 67 years. Most subjects were males who underwent myocardial revascularization. During in-hospital follow-up, all-cause and mediastinitis-related mortality were 27.6% and 20.7%, respectively. Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli were the most commonly isolated microorganisms. High resistance to methicillin was found in coagulase-negative staphylococci, as well as high expression of extended-spectrum beta-lactamases in Escherichia coli and Klebsiella pneumoniae strains. Conclusions: High mortality and significant antimicrobial resistance were found in patients with post-cardiac surgery mediastinitis.

Effect of HIV infection and antiretroviral therapy initiation on genome-wide DNA methylation patterns.

BACKGROUND: Previous epigenome-wide association studies have shown that HIV infection can disrupt the host DNA methylation landscape. However, it remains unclear how antiretroviral therapy (ART) affects the HIV-induced epigenetic modifications. METHODS: 184 individuals with HIV from the NEAT001/ANRS143 clinical trial (with pre-ART and post-ART samples [96 weeks of follow-up]) and 44 age-and-sex matched individuals without HIV were included. We compared genome-wide DNA methylation profiles in whole blood between groups adjusting for age, sex, batch effects, and DNA methylation-based estimates of leucocyte composition. FINDINGS: We identified 430 differentially methylated positions (DMPs) between HIV+ pre-ART individuals and HIV-uninfected controls. In participants with HIV, ART initiation modified the DNA methylation levels at 845 CpG positions and restored 49.3% of the changes found between HIV+ pre-ART and HIV-uninfected individuals. We only found 15 DMPs when comparing DNA methylation profiles between HIV+ post-ART individuals and participants without HIV. The Gene Ontology enrichment analysis of DMPs associated with untreated HIV infection revealed an enrichment in biological processes regulating the immune system and antiviral responses. In participants with untreated HIV infection, DNA methylation levels at top HIV-related DMPs were associated with CD4/CD8 ratios and viral loads. Changes in DNA methylation levels after ART initiation were weakly correlated with changes in CD4+ cell counts and the CD4/CD8 ratio. INTERPRETATION: Control of HIV viraemia after 96 weeks of ART initiation partly restores the host DNA methylation changes that occurred before antiretroviral treatment of HIV infection. FUNDING: NEAT-ID Foundation and Instituto de Salud Carlos III, co-funded by European Union.

Tenofovir Disoproxil Fumarate/Emtricitabine and Baricitinib for Patients at High Risk of Severe Coronavirus Disease 2019: The PANCOVID Randomized Clinical Trial.

BACKGROUND: This study was designed to evaluate if patients with high risk for severe coronavirus disease 2019 (COVID-19) would benefit from treatment with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) followed by baricitinib in case of hypoxemia and systemic inflammation. METHODS: PANCOVID is an open-label, double-randomized, phase 3 pragmatic clinical trial including adults with symptomatic COVID-19 with ≥2 comorbidities or aged ≥60 years and was conducted between 10 October 2020 and 23 September 2021. In the first randomization, patients received TDF/FTC or no TDF/FTC. In the second randomization, patients with room air oxygen saturation <95% and at least 1 increased inflammatory biomarker received baricitinib plus dexamethasone or dexamethasone alone. The primary endpoint was 28-day mortality. Main secondary endpoint was 28-day disease progression or critical care unit admission or mortality. The trial was stopped before reaching planned sample size due to the decrease in the number of cases and a mortality rate substantially lower than expected. RESULTS: Of the 355 included participants, 97% were hospitalized at baseline. Overall, 28-day mortality was 3.1%. The 28-day mortality relative risk (RR) for participants treated with TDF/FTC was 1.76 (95% confidence interval [CI], .52-5.91; P = .379); it was 0.42 (95% CI, .11-1.59; P = .201) for those treated with baricitinib. The 28-day RR for the main secondary combined endpoint for participants treated with TDF/FTC was 0.95 (95% CI, .66-1.40; P = .774); it was 0.90 (95% CI, .61-1.33; P = .687) for those treated with baricitinib. CONCLUSIONS: Our results do not suggest a beneficial effect of TDF/FTC; nevertheless, they are compatible with the beneficial effect of baricitinib already established by other clinical trials. CLINICAL TRIALS REGISTRATION: EudraCT: 2020-001156-18.

Long-term Evaluation of Residual Viremia in a Clinical Trial of Dolutegravir Plus Lamivudine as Maintenance Treatment for Participants With and Without Prior Lamivudine Resistance.

In this pilot clinical trial, we evaluated rates of residual replication in persons without lamivudine resistance-associated mutations in proviral DNA population sequencing who switched to dolutegravir plus lamivudine. After 144 weeks, there was no signal of changes in residual viremia based on qualitative detection methods, irrespective of past lamivudine resistance. Clinical Trials Registration. NCT03539224.

Sociodemography and epidemiology of the population attended in a psychological care center in Mexico / Sociodemografía y epidemiología de la población atendida en un centro de atención psicológica en México

Abstract: Objective: It was to analyze the sociodemographic and diagnostic characteristics of the population attending psychotherapy. Materials and Method: Design was quantitative, descriptive, retrospective and longitudinal of 322 files. Results: It was found that the majority is male (60%), young (33%), Catholic (81%) and with basic school (26%). Females present more anxiety disorders (56%), related to trauma and stressors (71.4%), personality (75%), primary support group (65%), child neglect (80%), abuse (71.4%) and others related to social environment (62.5%). Males had neurodevelopmental (100%), impulse control/behavioral (70%) and family upbringing (54.4%) problems. Most frequent problems are the parent-child relationship (14.6%), conflicts with the partner (8.9%) and life phase (6.1%). Conclusions: Instead of individual problems, most of population (especially women) attended derive from difficulties in their environment (insecurity, poverty) or from the lack of social skills to manage their interpersonal relationships in an assertive manner (parenting styles, resolution of couple problems). Aggressive masculinity is present in many situations, even when patients did not realize it when attending the service.

Resumen: Objetivo: Fue analizar las características sociodemográficas y diagnósticas de la población en psicoterapia. Materiales y Método: Diseño cuantitativo, descriptivo, retrospectivo y longitudinal de 322 expedientes. Resultados: La mayoría es masculina (60%), joven (33%), católica (81%) y con secundaria (26%). Las mujeres presentan más trastornos de ansiedad (56%), relacionados con traumas y estresores (71,4%), personalidad (75%), grupo de apoyo primario (65%), abandono infantil (80%), abuso (71,4%) y otros relacionados con el entorno social (62,5%). Los varones tenían problemas de neurodesarrollo (100%), control de impulsos/conducta (70%) y educación familiar (54,4%). Los problemas más frecuentes son la relación padre-hijo (14,6%), los conflictos con la pareja (8,9%) y la fase vital (6,1%). Conclusiones: En lugar de tratarse de problemáticas individuales, la mayoría de los problemas (especialmente para las mujeres) se derivan de las dificultades de su entorno (inseguridad, pobreza) o de la falta de habilidades sociales para manejar sus relaciones interpersonales de manera asertiva (estilos de crianza, resolución de problemas de pareja). La masculinidad agresiva se encuentra presente en muchas de las situaciones atendidas, aún cuando los pacientes no habían tomado conciencia de ello al llegar al servicio.

Urinary Tract Infections in Hospitalized COVID-19 Patients, What's Up, Doc?

The SARS-CoV-2 pandemic might have increased the risks of healthcare-associated infections (HAIs); however, several studies of HAI such as urinary tract infections (UTIs) and catheter-associated urinary tract infections (CAUTIs) have shown contradictory results. The aim of this study is to assess the clinical features of UTIs and bacterial isolates from urine samples of hospitalized COVID-19 patients. We conducted a retrospective observational study including 87 COVID-19 patients with UTIs admitted to our centre. Bacterial UTIs presented were 87: 9 (10.3%) community-acquired UTIs (coinfection group) and 78 (89.6%) hospital-acquired UTIs (superinfection group). In the coinfection group, the most frequent type was non-CAUTI with 5 (55.5%) patients; however, the most frequent UTI in the superinfection group was CAUTI, with 53 (67.9%) patients. The median number of days of hospitalization in coinfected patients was lower than superinfection patients: 13 (IQR 11, 23) vs. 34 days (IQR 23, 47) p < 0.006. All UTI patients admitted to ICU, 38 (43.7%), belonged to the superinfection group. The mortality rate was 26.4% (23/87), 22/23 in the superinfection group. The most common microorganisms were E. coli 27 (28.4%), E. faecalis 25 (26.3%) and E. faecium 20 (21.1%). There was an increased incidence of E. faecalis and E. faecium in UTIs as well as hospital-acquired UTIs. This can be related to urethral catheterization during hospitalization, UCI admissions and the number of days of hospitalization.

Unravelling innervation of pancreatic islets.

The central and peripheral nervous systems play critical roles in regulating pancreatic islet function and glucose metabolism. Over the last century, in vitro and in vivo studies along with examination of human pancreas samples have revealed the structure of islet innervation, investigated the contribution of sympathetic, parasympathetic and sensory neural pathways to glucose control, and begun to determine how the structure and function of pancreatic nerves are disrupted in metabolic disease. Now, state-of-the art techniques such as 3D imaging of pancreatic innervation and targeted in vivo neuromodulation provide further insights into the anatomy and physiological roles of islet innervation. Here, we provide a summary of the published work on the anatomy of pancreatic islet innervation, its roles, and evidence for disordered islet innervation in metabolic disease. Finally, we discuss the possibilities offered by new technologies to increase our knowledge of islet innervation and its contributions to metabolic regulation.

Melatonin in the Prophylaxis of SARS-CoV-2 Infection in Healthcare Workers (MeCOVID): A Randomised Clinical Trial.

We evaluated in this randomised, double-blind clinical trial the efficacy of melatonin as a prophylactic treatment for prevention of SARS-CoV-2 infection among healthcare workers at high risk of SARS-CoV-2 exposure. Healthcare workers fulfilling inclusion criteria were recruited in five hospitals in Spain and were randomised 1:1 to receive melatonin 2 mg administered orally for 12 weeks or placebo. The main outcome was the number of SARS-CoV-2 infections. A total of 344 volunteers were screened, and 314 were randomised: 151 to placebo and 163 to melatonin; 308 received the study treatment (148 placebo; 160 melatonin). We detected 13 SARS-CoV-2 infections, 2.6% in the placebo arm and 5.5% in the melatonin arm (p = 0.200). A total of 294 adverse events were detected in 127 participants (139 in placebo; 155 in melatonin). We found a statistically significant difference in the incidence of adverse events related to treatment: 43 in the placebo arm and 67 in the melatonin arm (p = 0.040), and in the number of participants suffering from somnolence related to treatment: 8.8% (n = 14) in the melatonin versus 1.4% (n = 2) in the placebo arm (p = 0.008). No severe adverse events related to treatment were reported. We cannot confirm our hypothesis that administration of melatonin prevents the development of SARS-CoV-2 infection in healthcare workers.

A Case-Control of Patients with COVID-19 to Explore the Association of Previous Hospitalisation Use of Medication on the Mortality of COVID-19 Disease: A Propensity Score Matching Analysis.

Data from several cohorts of coronavirus disease 2019 (COVID-19) suggest that the most common comorbidities for severe COVID-19 disease are the elderly, high blood pressure, and diabetes; however, it is not currently known whether the previous use of certain drugs help or hinder recovery. This study aims to explore the association of previous hospitalisation use of medication on the mortality of COVID-19 disease. A retrospective case-control from two hospitals in Madrid, Spain, included all patients aged 18 years or above hospitalised with a diagnosis of COVID-19. A Propensity Score matching (PSM) analysis was performed. Confounding variables were considered to be age, sex, and the number of comorbidities. Finally, 3712 patients were included. Of these, 687 (18.5%) patients died (cases). The 22,446 medicine trademarks used previous to admission were classified according to the ATC, obtaining 689 final drugs; all of them were included in PSM analysis. Eleven drugs displayed a reduction in mortality: azithromycin, bemiparine, budesonide-formoterol fumarate, cefuroxime, colchicine, enoxaparin, ipratropium bromide, loratadine, mepyramine theophylline acetate, oral rehydration salts, and salbutamol sulphate. Eight final drugs displayed an increase in mortality: acetylsalicylic acid, digoxin, folic acid, mirtazapine, linagliptin, enalapril, atorvastatin, and allopurinol. Medication associated with survival (anticoagulants, antihistamines, azithromycin, bronchodilators, cefuroxime, colchicine, and inhaled corticosteroids) may be candidates for future clinical trials. Drugs associated with mortality show an interaction with the underlying conditions.