Tracheostomy Patient Care Unit. An innovative Otorhinolaryngology solution of a transversal nature for the hospital.

BACKGROUND AND OBJECTIVE: The care of tracheostomized patients are high risk skills and low incidence. Strategies for improvement of health care in hospital wards and specialties other than otolaryngology based solely on training have not been able to offer an adequate solution. A tracheostomized patient unit is presented directed by the otolaryngology service to attend all tracheostomized hospitalised patients of all specialties. MATERIAL AND METHODS: Background: Third level public hospital with 876 hospitalisation beds and 30 ICU beds for 481,296 inhabitants. Unit model: Transversal unit for the hospital providing attention to all tracheostomized patients, adults, and children, of all specialties, with dedication of 50% of a ENT nurse of hospitalisation that moves to the hospitalisation bed of the specialty of each patient and 50% of another office ENT nurse for ambulatory patients care, with the consultancy of an ENT specialist and coordinated by the ENT supervisor. RESULTS: 572 patients between 2016 and 2021, 80% men, aged 63 ± 14 years, were attended in the Unit. 14.7 ± 2 tracheostomized patients daily and 96 ± 4 complication annual consultations were attended, rising up to 19 tracheostomized patients daily by 2020 and 141 ± 8.4 consultations by complications in 2020 and 2021, during the COVID-19 pandemic. The mean stay of the non-ENT specialties was reduced in 13 days, increasing the satisfaction of the ENT and non-ENT professionals and the satisfaction of the users. CONCLUSIONS: A Tracheostomized Patient Care Unit proactively directed from the Otorhinolaryngology Service to transversally care for all tracheostomized patients improves the quality of health care by reducing stay, complications, and emergencies. Improves the satisfaction of non-otolaryngological professionals by reducing the anxiety of facing care of patients who lack knowledge and experience and that of ENT specialists and nurses by reducing unplanned extemporaneous demands for care. Improves user satisfaction by perceiving adequate continuity of care. The Otorhinolaryngology Services provide their experience in the management of laryngectomized and tracheostomized patients and in teamwork with other specialists and professionals without the need to create new structures outside Otorhinolaryngology.

Myocardial infarction and viral triggers: what do we know by now?

Myocardial infarction (MI) is an acute clinical manifestation ischaemic heart disease, which is the leading cause of death worldwide. Infections also have an important burden worldwide, with lower respiratory infections being the worldwide leading cause of death due to communicable diseases. The relationship of MI with viral respiratory infections (including influenza and SARS-CoV-2) as a trigger has been well documented with significant associations. These infections can lead to Type 1 MI, where inflammation and vascular dysfunction, as well as the increased prothrombotic environment lead to atherothrombosis. Type 2 MI may also occur due to an imbalance of oxygen/blood supply and myocardial demand (hypoxaemia, fever, and tachycardia). The data from randomized controlled trials showing a potential benefit of influenza vaccination in coronary artery disease patients should not be ignored. This can be considered a further argument for the association of viral infections (influenza in particular) and MI.

Brief Research Report: Anti-SARS-CoV-2 Immunity in Long Lasting Responders to Cancer Immunotherapy Through mRNA-Based COVID-19 Vaccination.

Cancer patients (CPs) have been identified as particularly vulnerable to SARS-CoV-2 infection, and therefore are a priority group for receiving COVID-19 vaccination. From the patients with advanced solid tumors, about 20% respond very efficiently to immunotherapy with anti-PD1/PD-L1 antibodies and achieve long lasting cancer responses. It is unclear whether an efficient cancer-specific immune response may also correlate with an efficient response upon COVID-19 vaccination. Here, we explored the antiviral immune response to the mRNA-based COVID-19 vaccine BNT162b2 in a group of 11 long-lasting cancer immunotherapy responders. We analysed the development of SARS-CoV-2-specific IgG serum antibodies, virus neutralizing capacities and T cell responses. Control groups included patients treated with adjuvant cancer immunotherapy (IMT, cohort B), CPs not treated with immunotherapy (no-IMT, cohort C) and healthy controls (cohort A). The median ELISA IgG titers significantly increased after the prime-boost COVID vaccine regimen in all cohorts (Cohort A: pre-vaccine = 900 (100-2700), 3 weeks (w) post-boost = 24300 (2700-72900); Cohort B: pre-vaccine = 300 (100-2700), 3 w post-boost = 8100 (300-72900); Cohort C: pre-vaccine = 500 (100-2700), 3 w post-boost = 24300 (300-72900)). However, at the 3 w post-prime time-point, only the healthy control group showed a statistically significant increase in antibody levels (Cohort A = 8100 (900-8100); Cohort B = 900 (300-8100); Cohort C = 900 (300-8100)) (P < 0.05). Strikingly, while all healthy controls generated high-level antibody responses after the complete prime-boost regimen (Cohort A = 15/15 (100%), not all CPs behaved alike [Cohort B= 12/14 (84'6%); Cohort C= 5/6 (83%)]. Their responses, including those of the long-lasting immunotherapy responders, were more variable (Cohort A: 3 w post-boost (median nAb titers = 95.32 (84.09-96.93), median Spike-specific IFN-γ response = 64 (24-150); Cohort B: 3 w post-boost (median nAb titers = 85.62 (8.22-97.19), median Spike-specific IFN-γ response (28 (1-372); Cohort C: 3 w post-boost (median nAb titers = 95.87 (11.8-97.3), median Spike-specific IFN-γ response = 67 (20-84)). Two long-lasting cancer responders did not respond properly to the prime-boost vaccination and did not generate S-specific IgGs, neutralizing antibodies or virus-specific T cells, although their cancer immune control persisted for years. Thus, although mRNA-based vaccines can induce both antibody and T cell responses in CPs, the immune response to COVID vaccination is independent of the capacity to develop an efficient anti-cancer immune response to anti PD-1/PD-L1 antibodies.

Severe Acute Hepatitis of Unknown Origin in Children: What Do We Know Today?

In May 2022, the UK International Health Regulations National Focal Point notified World Health Organization of 176 cases of severe acute hepatitis of unknown etiology in children under 10 years of age. From that moment on, cases of severe acute hepatitis of unknown origin in children began to be reported in several countries. As of June 17, 2022, a total of 991 cases had been reported in 35 countries worldwide, 50 children needed a liver transplant and 28 patients died. According to information published by ECDC, 449 cases have been detected in 21 EU countries. The children were between 1 month and 16 years of age. Adenovirus was detected in 62.2% of the analyzed samples. So far, the cause of these cases is unknown and many hypotheses remain open, but hepatitis A-E viruses and COVID-19 vaccines have been ruled out. A possible hypothesis has been published to explain the cause of these cases of severe hepatitis, according to which it could be a consequence of adenovirus infection in the intestine in healthy children previously infected with SARS-CoV-2. No other clear epidemiological risk factors have been identified to date. Thus, at this time, the etiology of the current cases of hepatitis remains under active investigation.

Analysis of Prevalence and Predictive Factors of Long-Lasting Olfactory and Gustatory Dysfunction in COVID-19 Patients.

BACKGROUND: Although smell and taste disorders are highly prevalent symptoms of COVID-19 infection, the predictive factors leading to long-lasting chemosensory dysfunction are still poorly understood. METHODS: 102 out of 421 (24.2%) mildly symptomatic COVID-19 patients completed a second questionnaire about the evolution of their symptoms one year after the infection using visual analog scales (VAS). A subgroup of 69 patients also underwent psychophysical evaluation of olfactory function through UPSIT. RESULTS: The prevalence of chemosensory dysfunction decreased from 82.4% to 45.1% after 12 months, with 46.1% of patients reporting a complete recovery. Patients older than 40 years (OR = 0.20; 95% CI: [0.07, 0.56]) and with a duration of loss of smell longer than four weeks saw a lower odds ratio for recovery (OR = 0.27; 95% CI: [0.10, 0.76]). In addition, 28 patients (35.9%) reported suffering from parosmia, which was associated with moderate to severe taste dysfunction at the baseline (OR = 7.80; 95% CI: [1.70, 35.8]). Among the 69 subjects who underwent the UPSIT, 57 (82.6%) presented some degree of smell dysfunction, showing a moderate correlation with self-reported VAS (r = -0.36, p = 0.0027). CONCLUSION: A clinically relevant number of subjects reported persistent chemosensory dysfunction and parosmia one year after COVID-19 infection, with a moderate correlation with psychophysical olfactory tests.

Unidad de Atención al Paciente Traqueostomizado. Una solución innovadora desde Otorrinolaringología con carácter transversal para el hospital

Resumen Antecedentes y objetivo Los cuidados de los pacientes traqueostomizados son habilidades de alto riesgo y baja incidencia. Las estrategias de mejora de la atención sanitaria en plantas hospitalarias y en especialidades distintas a la Otorrinolaringología (ORL) basadas únicamente en la formación no han sido capaces de ofrecer una solución adecuada. Se presenta un modelo de Unidad de Atención al Paciente Traqueostomizado dirigida por el Servicio de Otorrinolaringología para atender a todos los pacientes traqueostomizados de un hospital en todas las especialidades. Material y métodos Ámbito: hospital universitario público de tercer nivel con 876 camas de hospitalización y 30 camas de UCI para 481.296 habitantes. Modelo de Unidad: unidad transversal para el hospital proporcionando atención a todos los pacientes traqueostomizados, adultos y niños, de todas las especialidades, con dedicación del 50% de una enfermera de ORL de hospitalización que se desplaza hasta la cama de hospitalización de la especialidad de cada paciente y el 50% de otra enfermera de ORL de consultas externas para los pacientes ambulatorios, con la consultoría de un especialista en ORL y coordinación de la supervisora de ORL. Resultados Se atendió en la unidad a 572 pacientes entre 2016 y 2021, el 80% varones, con una media de edad de 63±14 años. Se atendieron 14,7±2 pacientes traqueostomizados diarios y 96±4 consultas por complicaciones anuales, elevándose hasta 19 pacientes traqueostomizados diarios en 2020 y 141±8,4 consultas por complicaciones en los años 2020 y 2021, durante la pandemia por COVID-19. Se redujo la estancia media de las especialidades no ORL en 13 días a lo largo de los 6 años del estudio, aumentando la satisfacción de los profesionales de ORL y de no ORL, y la satisfacción de los usuarios. Conclusiones Una Unidad de Atención al Paciente Traqueostomizado dirigida proactivamente desde el Servicio de Otorrinolaringología para atender transversalmente a todos los pacientes traqueostomizados mejora la calidad de la atención sanitaria al reducir la estancia, complicaciones y urgencias. Este modelo de unidad ha resistido la pandemia COVID-19 manteniendo los estándares alcanzados de calidad y eficiencia. Se mejora la satisfacción de los profesionales no otorrinolaringológicos al reducir la incertidumbre de afrontar cuidados de pacientes sobre los que carecen de conocimientos y experiencia, y la de los especialistas y enfermeras de ORL al reducirse las demandas extemporáneas no planificadas de atención. Mejora la satisfacción de los usuarios al percibir una adecuada continuidad asistencial. Los Servicios de Otorrinolaringología aportan su experiencia en manejo de pacientes laringectomizados y traqueostomizados y en trabajo en equipo con otros especialistas y profesionales sin que el hospital tenga necesidad de crear nuevas estructuras al margen de Otorrinolaringología. Background and objective The care of tracheostomized patients are high risk skills and low incidence. Strategies for improvement of health care in hospital wards and specialties other than otolaryngology based solely on training have not been able to offer an adequate solution. A tracheostomized patient unit is presented directed by the otolaryngology service to attend all tracheostomized hospitalized patients of all specialties. Material and methods Background: Third level public hospital with 876 hospitalization beds and 30 ICU beds for 481,296 inhabitants. Unit model: Transversal unit for the hospital providing attention to all tracheostomized patients, adults, and children, of all specialties, with dedication of 50% of a ENT nurse of hospitalization that moves to the hospitalization bed of the specialty of each patient and 50% of another office ENT nurse for ambulatory patients care, with the consultancy of an ENT specialist and coordinated by the ENT supervisor. Results 572 patients between 2016 and 2021, 80% men, aged 63±14 years, were attended in the unit. 14.7±2 tracheostomized patients daily and 96±4 complication annual consultations were attended, rising up to 19 tracheostomized patients daily by 2020 and 141±8.4 consultations by complications in 2020 and 2021, during the COVID-19 pandemic. The mean stay of the non-ENT specialties was reduced in 13 days, increasing the satisfaction of the ENT and non-ENT professionals and the satisfaction of the users. Conclusions A Tracheostomized Patient Care Unit proactively directed from the Otorhinolaryngology Service to transversally care for all tracheostomized patients improves the quality of health care by reducing stay, complications, and emergencies. Improves the satisfaction of non-otolaryngological professionals by reducing the anxiety of facing care of patients who lack knowledge and experience and that of ENT specialists and nurses by reducing unplanned extemporaneous demands for care. Improves user satisfaction by perceiving adequate continuity of care. The Otorhinolaryngology Services provide their experience in the management of laryngectomized and tracheostomized patients and in teamwork with other specialists and professionals without the need to create new structures outside otorhinolaryngology.

Brief Research Report: Anti-SARS-CoV-2 Immunity in Long Lasting Responders to Cancer Immunotherapy Through mRNA-Based COVID-19 Vaccination

Cancer patients (CPs) have been identified as particularly vulnerable to SARS-CoV-2 infection, and therefore are a priority group for receiving COVID-19 vaccination. From the patients with advanced solid tumors, about 20% respond very efficiently to immunotherapy with anti-PD1/PD-L1 antibodies and achieve long lasting cancer responses. It is unclear whether an efficient cancer-specific immune response may also correlate with an efficient response upon COVID-19 vaccination. Here, we explored the antiviral immune response to the mRNA-based COVID-19 vaccine BNT162b2 in a group of 11 long-lasting cancer immunotherapy responders. We analysed the development of SARS-CoV-2-specific IgG serum antibodies, virus neutralizing capacities and T cell responses. Control groups included patients treated with adjuvant cancer immunotherapy (IMT, cohort B), CPs not treated with immunotherapy (no-IMT, cohort C) and healthy controls (cohort A). The median ELISA IgG titers significantly increased after the prime-boost COVID vaccine regimen in all cohorts (Cohort A: pre-vaccine = 900 (100-2700), 3 weeks (w) post-boost = 24300 (2700-72900);Cohort B: pre-vaccine = 300 (100-2700), 3 w post-boost = 8100 (300-72900);Cohort C: pre-vaccine = 500 (100-2700), 3 w post-boost = 24300 (300-72900)). However, at the 3 w post-prime time-point, only the healthy control group showed a statistically significant increase in antibody levels (Cohort A = 8100 (900-8100);Cohort B = 900 (300-8100);Cohort C = 900 (300-8100)) (P < 0.05). Strikingly, while all healthy controls generated high-level antibody responses after the complete prime-boost regimen (Cohort A = 15/15 (100%), not all CPs behaved alike [Cohort B= 12/14 (84'6%);Cohort C= 5/6 (83%)]. Their responses, including those of the long-lasting immunotherapy responders, were more variable (Cohort A: 3 w post-boost (median nAb titers = 95.32 (84.09-96.93), median Spike-specific IFN-γ response = 64 (24-150);Cohort B: 3 w post-boost (median nAb titers = 85.62 (8.22-97.19), median Spike-specific IFN-γ response (28 (1-372);Cohort C: 3 w post-boost (median nAb titers = 95.87 (11.8-97.3), median Spike-specific IFN-γ response = 67 (20-84)). Two long-lasting cancer responders did not respond properly to the prime-boost vaccination and did not generate S-specific IgGs, neutralizing antibodies or virus-specific T cells, although their cancer immune control persisted for years. Thus, although mRNA-based vaccines can induce both antibody and T cell responses in CPs, the immune response to COVID vaccination is independent of the capacity to develop an efficient anti-cancer immune response to anti PD-1/PD-L1 antibodies.

Virtual Combinatorial Chemistry and Pharmacological Screening: A Short Guide to Drug Design.

Traditionally, drug development involved the individual synthesis and biological evaluation of hundreds to thousands of compounds with the intention of highlighting their biological activity, selectivity, and bioavailability, as well as their low toxicity. On average, this process of new drug development involved, in addition to high economic costs, a period of several years before hopefully finding a drug with suitable characteristics to drive its commercialization. Therefore, the chemical synthesis of new compounds became the limiting step in the process of searching for or optimizing leads for new drug development. This need for large chemical libraries led to the birth of high-throughput synthesis methods and combinatorial chemistry. Virtual combinatorial chemistry is based on the same principle as real chemistry-many different compounds can be generated from a few building blocks at once. The difference lies in its speed, as millions of compounds can be produced in a few seconds. On the other hand, many virtual screening methods, such as QSAR (Quantitative Sturcture-Activity Relationship), pharmacophore models, and molecular docking, have been developed to study these libraries. These models allow for the selection of molecules to be synthesized and tested with a high probability of success. The virtual combinatorial chemistry-virtual screening tandem has become a fundamental tool in the process of searching for and developing a drug, as it allows the process to be accelerated with extraordinary economic savings.

Drug-drug interactions between COVID-19 treatments and antidepressants, mood stabilizers/anticonvulsants, and benzodiazepines: Integrated evidence from 3 databases

Introduction: The SARS-CoV-2 pandemic with psychiatric comorbidities leads to a scenario in which the use of psychotropic drugs may be required. This requires the support of evidence-based medicine to take into account possible interactions between antidepressants, mood stabilizers, benzodiazepines, and coronavirus infection treatments. Methods: Three databases were consulted: (a) Lexicomp Drug Interactions, (b) Micromedex Solutions Drugs Interactions, (c) Liverpool Drug Interaction Group for COVID-19 therapies. The CredibleMeds QTDrugs List was also queried. Hydroxychloroquine, chloroquine, azithromycin, lopinavir-ritonavir, remdesivir, favipiravir, tocilizumab, baricitinib, anakinra, and dexamethasone - drugs used for SARS-CoV-2-were analyzed, and consensus recommendations are made. Results: The potential interactions of agomelatine, desvenlafaxine, duloxetine, milnacipran, and vortioxetine with COVID-19 treatments shall be considered less risky. Antidepressant interactions with hydroxychloroquine, chloroquine, and azithromycin enhance the risk of QT prolongation, and ECG monitoring is advised for most antidepressants. Antidepressants with lopinavir/ ritonavir involve multiple CYP enzyme interactions (except with milnacipran). Gabapentin, oxcarbazepine, pregabalin, topiramate, and zonisamide are safe treatment options that have no significant interactions with COVID-19 treatments. Lithium is contraindicated with hydroxychloroquine, chloroquine, and azithromycin. Precaution should be taken in using valproic acid with lopinavir-ritonavir. The use of benzodiazepines does not present a risk of drug interaction with COVID-19 treatments, except lopinavir/ritonavir. Conclusions: Clinicians prescribing antidepressants, mood stabilizers/anticonvulsants, and benzodiazepines, should be aware of the probable risk of drug-drug interaction with COVID- 19 medications and may benefit from heeding these recommendations for use to ensure patient safety. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

Vitamin D-related polymorphisms and vitamin D levels as risk biomarkers of COVID-19 disease severity.

Vitamin D is a fundamental regulator of host defences by activating genes related to innate and adaptive immunity. Previous research shows a correlation between the levels of vitamin D in patients infected with SARS-CoV-2 and the degree of disease severity. This work investigates the impact of the genetic background related to vitamin D pathways on COVID-19 severity. For the first time, the Portuguese population was characterized regarding the prevalence of high impact variants in genes associated with the vitamin D pathways. This study enrolled 517 patients admitted to two tertiary Portuguese hospitals. The serum concentration of 25 (OH)D, was measured in the hospital at the time of patient admission. Genetic variants, 18 variants, in the genes AMDHD1, CYP2R1, CYP24A1, DHCR7, GC, SEC23A, and VDR were analysed. The results show that polymorphisms in the vitamin D binding protein encoded by the GC gene are related to the infection severity (p = 0.005). There is an association between vitamin D polygenic risk score and the serum concentration of 25 (OH)D (p = 0.04). There is an association between 25 (OH)D levels and the survival and fatal outcomes (p = 1.5e-4). The Portuguese population has a higher prevalence of the DHCR7 RS12785878 variant when compared with its prevalence in the European population (19% versus 10%). This study shows a genetic susceptibility for vitamin D deficiency that might explain higher severity degrees in COVID-19 patients. These results reinforce the relevance of personalized strategies in the context of viral diseases.Trial registration: NCT04370808.

A COVID-19 Drug Repurposing Strategy through Quantitative Homological Similarities Using a Topological Data Analysis-Based Framework.

Since its emergence in March 2020, the SARS-CoV-2 global pandemic has produced more than 116 million cases and 2.5 million deaths worldwide. Despite the enormous efforts carried out by the scientific community, no effective treatments have been developed to date. We applied a novel computational pipeline aimed to accelerate the process of identifying drug repurposing candidates which allows us to compare three-dimensional protein structures. Its use in conjunction with two in silico validation strategies (molecular docking and transcriptomic analyses) allowed us to identify a set of potential drug repurposing candidates targeting three viral proteins (3CL viral protease, NSP15 endoribonuclease, and NSP12 RNA-dependent RNA polymerase), which included rutin, dexamethasone, and vemurafenib. This is the first time that a topological data analysis (TDA)-based strategy has been used to compare a massive number of protein structures with the final objective of performing drug repurposing to treat SARS-CoV-2 infection.

Anatomy of digital contact tracing: Role of age, transmission setting, adoption, and case detection.

The efficacy of digital contact tracing against coronavirus disease 2019 (COVID-19) epidemic is debated: Smartphone penetration is limited in many countries, with low coverage among the elderly, the most vulnerable to COVID-19. We developed an agent-based model to precise the impact of digital contact tracing and household isolation on COVID-19 transmission. The model, calibrated on French population, integrates demographic, contact and epidemiological information to describe exposure and transmission of COVID-19. We explored realistic levels of case detection, app adoption, population immunity, and transmissibility. Assuming a reproductive ratio R = 2.6 and 50% detection of clinical cases, a ~20% app adoption reduces peak incidence by ~35%. With R = 1.7, >30% app adoption lowers the epidemic to manageable levels. Higher coverage among adults, playing a central role in COVID-19 transmission, yields an indirect benefit for the elderly. These results may inform the inclusion of digital contact tracing within a COVID-19 response plan.

Drug-drug interactions between COVID-19 treatments and antipsychotics drugs: integrated evidence from 4 databases and a systematic review.

RATIONALE: Management of anxiety, delirium, and agitation cannot be neglected in coronavirus disease (COVID-19). Antipsychotics are usually used for the pharmacological management of delirium, and confusion and behavioral disturbances. The concurrent use of treatments for COVID-19 and antipsychotics should consider eventual drug-drug interactions OBJECTIVE: To systematically review evidence-based available on drug-drug interactions between COVID-19 treatments and antipsychotics. EVIDENCE REVIEW: Three databases were consulted: Lexicomp® Drug Interactions, Micromedex® Solutions Drugs Interactions, and Liverpool© Drug Interaction Group for COVID-19 therapies. To acquire more information on QT prolongation and Torsade de Pointes (TdP), the CredibleMeds® QTDrugs List was searched. The authors made a recommendation agreed to by consensus. Additionally, a systematic review of drug-drug interactions between antipsychotics and COVID-19 treatment was conducted. RESULTS: The main interactions between COVID-19 drugs and antipsychotics are the risk of QT-prolongation and TdP, and cytochromes P450 interactions. Remdesivir, baricinitib, and anakinra can be used concomitantly with antipsychotics without risk of drug-drug interaction (except for hematological risk with clozapine and baricinitib). Favipiravir only needs caution with chlorpromazine and quetiapine. Tocilizumab is rather safe to use in combination with antipsychotics. The most demanding COVID-19 treatments for coadministration with antipsychotics are chloroquine, hydroxychloroquine, azithromycin, and lopinavir/ritonavir because of the risk of QT prolongation and TdP and cytochromes interactions. The systematic review provides highly probable drug interaction between lopinavir/ritonavir plus quetiapine and ritonavir/indinavir plus risperidone. CONCLUSIONS: Clinicians prescribing antipsychotics should be aware of the likely risk of drug-drug interaction with COVID-19 medication and may benefit from taking into account present recommendations of use to preserve patient safety.