Economic Evaluation of Tirbanibulin for the Treatment of Actinic Keratosis in Scotland.

BACKGROUND: Tirbanibulin 1% ointment is a new treatment for actinic keratosis (AK) on the face or scalp. A health economic model was developed as part of a submission to the Scottish Medicines Consortium to evaluate the cost-effectiveness of tirbanibulin compared to the most frequently prescribed treatments. METHODS: A decision tree approach was used to calculate the costs and benefits of different treatment strategies for AK on the face or scalp over a one-year time horizon. Data on the relative efficacy of treatments, which were based on the probability of complete clearance of AK, were obtained from a network meta-analysis. Sensitivity and scenario analyses were performed to determine the robustness of the model results. RESULTS: Tirbanibulin is estimated to be cost saving versus diclofenac sodium 3%, imiquimod 5% and fluorouracil 5%. Tirbanibulin remains cost saving when inputs are varied in sensitivity and scenario analyses. While the complete clearance rates are deemed similar across comparators, tirbanibulin is associated with a lower rate of severe local skin reactions, and a shorter treatment duration, which may improve treatment adherence. CONCLUSIONS: Tirbanibulin is a cost saving intervention for the treatment of AK from the perspective of the Scottish Healthcare System.

Persistent symptoms after COVID-19 in children and adolescents from Argentina.

OBJECTIVES: Although long COVID-19 is widely recognized in adults, less information is available about this condition in children, especially in developing countries. Here, we studied the long-term symptoms of SARS-CoV-2 infection beyond 3 months and the associated risk factors in a pediatric population. METHODS: This observational study included 639 Argentinian children and adolescents with previously confirmed COVID-19 from June 2020-June 2021 and 577 children without previous COVID-19. Parents completed a survey about symptoms that their child had for >3 months after the diagnosis of SARS-CoV-2 infection. RESULTS: At least one persistent symptom was observed more frequently in children with previous COVID-19 than in the non-COVID-19 group (34% vs 13%, P <0.0001). SARS-CoV-2 infection increased the risk of headache, dizziness, loss of taste, dyspnea, cough, fatigue, muscle pain, and loss of weight by three- to seven-fold. The loss of smell was only reported in infected children. After controlling for the other variables, older age, symptomatic COVID-19, and comorbidities were independent predictors of long-term symptoms. CONCLUSIONS: One-third of children experienced persistent symptoms after COVID-19. Older age, symptomatic infection, and comorbidities were shown to be risk factors for long COVID-19. Pediatric long COVID-19 is a new condition that requires further investigation.

Antibody response against SARS-CoV-2 variants of concern in children infected with pre-Omicron variants: An observational cohort study.

BACKGROUND: Despite that pediatric COVID-19 is usually asymptomatic or mild, SARS-CoV-2 infection typically results in the development of an antibody response. Contradictory observations have been reported when the antibody response of children and adults were compared in terms of strength, specificity and perdurability. METHODS: This observational study includes three cohorts infected with SARS-CoV-2 between March 2020-July 2021: unvaccinated infected children (n=115), unvaccinated infected adults (n=62), and vaccinated infected children (n=76). Plasma anti-spike IgG antibodies and neutralising activity against Wuhan, Delta and Omicron variants after 7-17 months post-infection were analysed. FINDINGS: More than 95% of unvaccinated infected children and adults remained seropositive when evaluated at 382-491 and 386-420 days after infection, respectively. Anti-spike IgG titers and plasma neutralising activity against Wuhan, Delta and Omicron variants were higher in children compared to adults. No differences were found when unvaccinated infected children were stratified by age, gender or presence/absence of symptoms in the acute phase of SARS-CoV-2 infection, but a slight decrease in the antibody response was observed in those with comorbidities. Vaccination of previously infected children with two doses of the inactivated BBIBP-CorV or the mRNA vaccines, BNT162b2 and/or mRNA-1273, further increased anti-spike IgG titers and neutralising activity against Wuhan, Delta and Omicron variants. INTERPRETATION: Unvaccinated infected children mount a more potent and sustained antibody response compared with adults, which is significantly increased after vaccination. Further studies including not only the analysis of the immune response but also the effectiveness to prevent reinfections by the different Omicron lineages are required to optimise vaccination strategy in children. FUNDING: National Agency for Scientific and Technological Promotion from Argentina (PICTO-COVID-SECUELAS-00007 and PMO-BID-PICT2018-2548).

A poor and delayed anti-SARS-CoV2 IgG response is associated to severe COVID-19 in children.

BACKGROUND: Most children and youth develop mild or asymptomatic disease during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, a very small number of patients suffer severe Coronavirus induced disease 2019 (COVID-19). The reasons underlying these different outcomes remain unknown. METHODS: We analyzed three different cohorts: children with acute infection (n=550), convalescent children (n=138), and MIS-C (multisystem inflammatory syndrome in children, n=42). IgG and IgM antibodies to the spike protein of SARS-CoV-2, serum-neutralizing activity, plasma cytokine levels, and the frequency of circulating Follicular T helper cells (cTfh) and plasmablasts were analyzed by conventional methods. FINDINGS: Fifty-eight percent of the children in the acute phase of infection had no detectable antibodies at the time of sampling while a seronegative status was found in 25% and 12% of convalescent and MIS-C children, respectively. When children in the acute phase of the infection were stratified according disease severity, we found that contrasting with the response of children with asymptomatic, mild and moderate disease, children with severe COVID-19 did not develop any detectable response. A defective antibody response was also observed in the convalescent cohort for children with severe disease at the time of admission. This poor antibody response was associated to both, a low frequency of cTfh and a high plasma concentration of inflammatory cytokines. INTERPRETATION: A weak and delayed kinetic of antibody response to SARS-CoV-2 together with a systemic pro-inflammatory profile characterize pediatric severe COVID-19. Because comorbidities are highly prevalent in children with severe COVID-19, further studies are needed to clarify their contribution in the weak antibody response observed in severe disease. FUNDING: National Agency for Scientific and Technological Promotion from Argentina (IP-COVID-19-0277 and PMO-BID-PICT2018-2548).

Collaborative Working Architecture for IoT-Based Applications.

The new sensing applications need enhanced computing capabilities to handle the requirements of complex and huge data processing. The Internet of Things (IoT) concept brings processing and communication features to devices. In addition, the Cloud Computing paradigm provides resources and infrastructures for performing the computations and outsourcing the work from the IoT devices. This scenario opens new opportunities for designing advanced IoT-based applications, however, there is still much research to be done to properly gear all the systems for working together. This work proposes a collaborative model and an architecture to take advantage of the available computing resources. The resulting architecture involves a novel network design with different levels which combines sensing and processing capabilities based on the Mobile Cloud Computing (MCC) paradigm. An experiment is included to demonstrate that this approach can be used in diverse real applications. The results show the flexibility of the architecture to perform complex computational tasks of advanced applications.

Hydrogel doped with nanoparticles for local sustained release of siRNA in breast cancer.

Of all the much hyped and pricy cancer drugs, the benefits from the promising siRNA small molecule drugs are limited. Lack of efficient delivery vehicles that would release the drug locally, protect it from degradation, and ensure high transfection efficiency, precludes it from fulfilling its full potential. This work presents a novel platform for local and sustained delivery of siRNA with high transfection efficiencies both in vitro and in vivo in a breast cancer mice model. siRNA protection and high transfection efficiency are enabled by their encapsulation in oligopeptide-terminated poly(ß-aminoester) (pBAE) nanoparticles. Sustained delivery of the siRNA is achieved by the enhanced stability of the nanoparticles when embedded in a hydrogel scaffold based on polyamidoamine (PAMAM) dendrimer cross-linked with dextran aldehyde. The combination of oligopeptide-terminated pBAE polymers and biodegradable hydrogels shows improved transfection efficiency in vivo even when compared with the most potent commercially available transfection reagents. These results highlight the advantage of using composite materials for successful delivery of these highly promising small molecules to combat cancer.

[Identification of risk times for dissemination of methicillin-resistant Staphylococcus aureus in an intensive care unit]. / Identificación de los tiempos de riesgo de diseminación de Staphylococcus aureus resistente a meticilina en una unidad de medicina intensiva.

BACKGROUND AND OBJECTIVE: The dissemination of methicillin-resistant Staphylococcus aureus (MRSA) in patients admitted to an Intensive Care Unit (ICU) depends, among other reasons, on the time interval between obtention of the first positive sample and the establishment of measures for contact isolation. The objective of this study was to identify the risk intervals for the spread of MRSA in ICU patients and to assess the relationship between these periods and the development of new cases of MRSA acquired in the ICU. MATERIAL AND METHOD: Observational and prospective study, which was carried out in a 18-bed polyvalent ICU during a 49-month period (October 1998-October 2002). The exposure risk period was defined as the time elapsed between obtention of the first positive sample and contact isolation of the index case, and the window period as the time elapsed between recovery of the last negative sample to the first positive sample. Infection sources of MRSA were classified into community-acquired and hospital-acquired (nosocomial extra-ICU and nosocomial intra-ICU infections). RESULTS: MRSA was isolated in 69 (2.73%) of 2,531 patients admitted to the ICU during the study period and in all patients measures of contact isolation were indicated. Community-acquired MRSA was diagnosed in 9 (13%) cases, nosocomial intra-ICU in 29 (42%), and nosocomial extra-ICU in 31 (44.9%). The mean duration of the exposure risk period was 3.1 (SD 2.2) (median 3, range 0-9) days and the window period 2.9 (SD 4.6) (median 1, range 0-28) days. In 18 of the 29 cases of intra-ICU-acquired MRSA (62.1%; 95% CI, 42.3-79.3), the infection was acquired within the exposure risk and/or window periods of other patients with MRSA. CONCLUSIONS: The exposure risk periods and the window periods showed a strong relationship between detection of new cases of intra-ICU colonization and/or infection by MRSA.

[Effectiveness of contact isolation in the control of multiresistant bacteria in an intensive care service]. / Efectividad del aislamiento de contacto en el control de bacterias multirresistentes en un servicio de medicina intensiva.

AIM: To describe the frequency, characteristics and progression of critically ill patients admitted to the ICU, for whom isolation is indicated due to detection of multiresistant pathogenic bacteria, and to study the effectiveness of precautionary measures to avoid dissemination of these microorganisms. PATIENTS AND METHODS: Prospective, observational, cohort study performed by a specially created working group of four nurses and an ICU specialist. The study included 55 patients in whom contact isolation was indicated (isolation rate, 15.2 per 100 patients), collected over a 16-month period. RESULTS: The multiresistant bacteria responsible for isolation of the patients were: Pseudomonas aeruginosa (17 cases), Staphylococcus aureus (17 cases), Stenotrophomonas maltophilia (15 cases), Acinetobacter baumannii (4 cases) and extended-spectrum beta-lactamase (ESBL)- producing Enterobacteria (2 cases). Vancomycin-resistant Enterococcus spp. was not identified in any case. The mean duration of ICU isolation was 17.6 6 5.1 days (range 1-75). Multiresistant bacteria were classified as intra-ICU nosocomial in 39 cases (70.9%), extra-ICU nosocomial in 10 cases (18.2%) and community-acquired in 6 (10.9%). During the study period, no epidemic outbreak due to any of the controlled bacteria was detected. The multiresistant bacteria presented in the form of colonization in 41 cases (74.5%). The reasons for discontinuing isolation were death of the patient in 18 cases, transferal to a hospital ward (discharge from the ICU) in 19 cases, and eradication of the bacteria in 18 cases. Of the 55 patients with multiresistant bacteria, 35 (63.6%) died during hospitalization, and 23 of these (41.8%) during their stay in the ICU. CONCLUSIONS: The implementation of a working team for early detection of multiresistant pathogenic bacteria resulted in application of contact isolation in 15.2% of patients admitted. Surveillance to fulfill isolation precautions in a medical-surgical ICU achieved an absence of epidemic outbreaks due to these bacteria during the study period.

Efectividad del aislamiento de contacto en el control de bacterias multirresistentes en un servicio de medicina intensiva / Effectiveness of contact isolation in the control of multiresistant bacteria in an intensive care service

FUNDAMENTO. Describir la frecuencia, características y evolución de pacientes críticos, ingresados en UCI, con indicación de aislamiento de contacto por identificación de bacterias patógenas multirresistentes (BPMR) y demostrar la efectividad de las medidas aplicadas para evitar su diseminación. PACIENTES Y MÉTODO. Estudio de cohortes, prospectivo y observacional. Para realizar el estudio se formó un grupo de trabajo compuesto por 4 enfermeras y un médico de UCI. Se han incluido 55 pacientes en los que se indicó aislamiento de contacto (tasa de aislamiento 15,2 por 100 pacientes), durante un período de 16 meses. RESULTADOS. Las BPMR motivo de aislamiento han sido: Pseudomonas aeruginosa en 17 casos, Staphylococcus aureus en 17 casos, Stenotrophomonas maltophilia en 15 casos, Acinetobacter baumannii en 4 casos y enterobacterias productoras de betalactamasas de espectro ampliado (BLEAS) en 2 casos. En ninguna ocasión se han identificado Enterococcus spp. resistentes a vancomicina. La duración media de los aislamientos en UCI ha sido de 17,6 5,1 días (límites entre 1 y 75 días).Las BPMR fueron clasificadas como nosocomiales intra-UCI en 39 casos (70,9 por ciento), nosocomiales extra-UCI en 10 casos (18,2 por ciento) y comunitarias en 6 casos (10,9 por ciento). Durante el período de este estudio no se ha detectado ningún brote epidémico por alguna de las BPMR que se han controlado. Las BPMR se han presentado en forma de colonización en 41 casos (74,5 por ciento). El motivo de finalización del aislamiento fue por fallecimiento en 18 casos, por traslado a una unidad de hospitalización (alta de UCI) en 19 casos, y por erradicación de la BPMR en 18 casos. Durante su estancia en el hospital fallecieron 35 (63,6 por ciento) de los 55 pacientes con BPMR, de ellos, 23 (41,8 por ciento) durante su estancia en UCI.CONCLUSIONES. La puesta en funcionamiento de un equipo de trabajo para la detección precoz de BPMR ha supuesto la aplicación de medidas de aislamiento de contacto en el 15,2 por ciento de los pacientes ingresados. La vigilancia del cumplimiento de las medidas de aislamiento en una UCI medicoquirúrgica se ha acompañado de ausencia de brotes epidémicos por BPMR durante el período de estudio (AU)