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This study presents a framework for determining the prioritization of vaccine introduction in the National Immunization Program (NIP) of the Republic of Korea, with a focus on case examples assessed in 2021 and 2023. We describe the predefined criteria for evaluating the prioritization of vaccines in the NIP and the established process in the Republic of Korea. These criteria included disease characteristics, vaccine characteristics, rationality and efficiency of resource allocation, and the acceptance of immunization. The process of prioritizing NIP introduction involved several sequential steps: a demand survey, evidence collection, preliminary evaluation, priority evaluation, and decision making. In 2021 and 2023, 14 and 25 committee members participated in evaluating the prioritization of vaccines in the NIP, respectively. Overall, 13 and 19 NIP vaccine candidates were included in the 2021 and 2023 evaluations, respectively. Through the Delphi survey and consensus processes, the priority order was determined: vaccination against Rotavirus infection was the top priority in 2021, while Influenza 4v (for chronic disease patients) took precedence in 2023. This study demonstrates an evidence-based decision-making process within the healthcare field. The outlined approach may provide valuable guidance for policymakers in other countries seeking to prioritize the inclusion of new vaccines in their NIP.
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The approval of radiation oncology care by insurance companies is burdensome for providers. In this topic discussion, we attempt to provide practical recommendations for how to deal with peer-to-peer phone calls as well as how to improve the timeliness and quality of subsequent letters of appeal.
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Surgery forms the backbone of treatment for most locoregional or advanced oral cavity squamous cell carcinoma. Unfortunately, infectious complications (including orocutaneous fistulas) are common following such extensive surgery and can afflict over half of patients. These complications can lead to delays in adjuvant treatment, prolonged hospitalization, reconstructive failure, and decreased quality of life. The frequency and morbidity associated with infectious complications has led to the search for pre-disposing risk factors; and, several have been identified, including both patient (e.g. diabetes) and surgical (e.g. operative time) factors. However, these findings are inconsistently reproduced, and risk factor modification has had a limited impact on rates of infectious complications. This is striking given that the likely contaminant-the oral microbiome-is a well-studied microbial reservoir. Because many oral cavity cancer surgeries involve violation of oral mucosa and the spillage of the oral microbiome into normally sterile areas (e.g. the neck), variance in oral microbiome composition and function could underly differences in infectious complications. The goal of this perspective is to highlight 1) this knowledge gap and 2) opportunities for studies in this domain. The implication of this line of thought is that the identification of oral microbial dysbiosis in patients undergoing surgery for oral cavity cancer could lead to targeted pre-operative therapeutic interventions, decreased infectious complications, and improved patient outcomes.
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Microbiota , Neoplasias de la Boca , Humanos , Boca/microbiología , Boca/cirugía , Neoplasias de la Boca/cirugía , Neoplasias de la Boca/microbiología , Complicaciones Posoperatorias/microbiología , Factores de Riesgo , Infección de la Herida Quirúrgica/microbiología , Infección de la Herida Quirúrgica/etiologíaRESUMEN
BACKGROUND: There are marked sex differences in the prevalence and severity of asthma, both during childhood and adulthood. There is a relative lack of comprehensive studies exploring sexdifferences in pediatric asthma cohorts. OBJECTIVE: To identify the most relevant sex differences in sociodemographic, clinical, and laboratory variables in a well-characterized large pediatric asthma cohort. METHODS: We performed a cross-sectional analysis of the Mayo Clinic Olmsted County Birth Cohort. In the full birth cohort, we used a natural language-processing algorithm based on the Predetermined Asthma Criteria for asthma ascertainment. In a stratified random sample of 300 children, we obtained additional pulmonary function tests and laboratory data. We identified the significant sex differences among available sociodemographic, clinical, and laboratory variables. RESULTS: Boys were more frequently diagnosed with having asthma than girls and were younger at the time of asthma diagnosis. There were no sex differences in relation to socioeconomic status. We identified a male predominance in the presence of a tympanostomy tube and a female predominance in the history of pneumonia. A higher percentage of boys had a forced expiratory volume in 1 second/forced vital capacity ratio less than 0.85. Blood eosinophilia and atopic sensitization were also more common in boys. Finally, boys had higher levels of serum periostin than girls. CONCLUSION: This study described significant sex differences in a large pediatric asthma cohort. Overall, boys had earlier and more severe asthma than girls. Differences in blood eosinophilia and serum periostin provide insights into possible mechanisms of the sex bias in childhood asthma.
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The species Rhizobium indigoferae and Sinorhizobium kummerowiae were isolated from legume nodules and the 16S rRNA sequences of their respective type strains, CCBAU 71042T and CCBAU 71714T, were highly divergent from those of the other species of the genera Rhizobium and Sinorhizobium, respectively. However, the 16S rRNA gene sequences obtained for strains CCBAU 71042T and CCBAU 71714T several years after description, were different from the original ones, showing 100â% similarity to the type strains of Rhizobium leguminosarum and Sinorhizobium meliloti, respectively. Phylogenetic analyses of two housekeeping genes, recA and atpD, confirmed the high phylogenetic closeness of strains CCBAU 71042T and CCBAU 71714T to the respective type strains of R. leguminosarum and S. meliloti. In the present work, we compared the genomes of the type strains of R. indigoferae and S. kummerowiae available in several culture collections with those of the respective type strains of R. leguminosarum and S. meliloti, some of them obtained in this study. The calculated average nucleotide identity-blast and digital DNA-DNA hybridization values in both cases were higher than those recommended for species differentiation, supporting the proposal for the reclassification of the type strains of R. indigoferae and S. kummerowiae into the species R. leguminosarum and S. meliloti, respectively.
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Técnicas de Tipificación Bacteriana , ADN Bacteriano , Filogenia , ARN Ribosómico 16S , Rhizobium leguminosarum , Análisis de Secuencia de ADN , Sinorhizobium meliloti , ARN Ribosómico 16S/genética , ADN Bacteriano/genética , Sinorhizobium meliloti/genética , Sinorhizobium meliloti/clasificación , Rhizobium leguminosarum/genética , Rhizobium leguminosarum/clasificación , Genoma Bacteriano , Rhizobium/clasificación , Rhizobium/genética , Rhizobium/aislamiento & purificación , Nódulos de las Raíces de las Plantas/microbiología , Genes Esenciales , Genes Bacterianos , Hibridación de Ácido NucleicoRESUMEN
PD-1 blockade has been approved for head and neck squamous cell carcinoma (HNSCC) patients. However, many HNSCC patients do not respond to this treatment, and other tumor microenvironmental factors may promote resistance to PD-1 blockade. We previously identified increased expression of the inhibitory receptor NKG2A on CD8+ T cells in HNSCC tumors compared with T cells in matching PBMC samples. Mechanisms that promote NKG2A expression and the role of NKG2A on human T cells in the tumor microenvironment, however, are uncertain. In this study, we show that tumor-conditioned media (TCM) of HNSCC cancer cell lines or ascites fluid from colorectal carcinoma patients is sufficient to induce the expression of NKG2A and other inhibitory receptors on activated CD8+ T cells isolated from PBMCs of healthy donors. Boiling or small molecular mass cutoff filtering did not eliminate the effect of TCM, suggesting that a small molecule promotes NKG2A. T cell activation in TCM decreased the basal and maximal mitochondrial respiration to metabolically restrain CD8+ T cells. Functionally, T cell activation in TCM reduced CD8+ T cell cytotoxicity as shown by lower production of cytokines, granzyme B, and perforin. Furthermore, TCM prevented CD8+ T cells from killing cancer cells in response to an anti-CD19/anti-CD3 bispecific T cell engager. Thus, a small secreted molecule from HNSCC cells can induce NKG2A expression and promote T cell dysfunction. Our findings may lead to targets for novel cancer therapies or biomarkers for NKG2A blockade response and provide a model to study T cell dysfunction and impaired metabolism.
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Linfocitos T CD8-positivos , Subfamília C de Receptores Similares a Lectina de Células NK , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Subfamília C de Receptores Similares a Lectina de Células NK/metabolismo , Subfamília C de Receptores Similares a Lectina de Células NK/inmunología , Línea Celular Tumoral , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Medios de Cultivo Condicionados/farmacología , Microambiente Tumoral/inmunología , Activación de Linfocitos/inmunología , Neoplasias de Cabeza y Cuello/inmunología , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/patología , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patologíaRESUMEN
OBJECTIVE: To set up and evaluate a new surveillance system for severe acute respiratory infection (SARI) in Scotland. STUDY DESIGN: Cross-sectional study and evaluation of surveillance system. METHODS: The SARI case definition comprised patients aged 16 years or over with an acute respiratory illness presentation requiring testing for influenza and SARS-CoV-2 and hospital admission. Data were collected from SARI cases by research nurses in one tertiary teaching hospital using a bespoke data collection tool from November 2021 to May 2022. Descriptive analyses of SARI cases were carried out. The following attributes of the surveillance system were evaluated according to Centers for Disease Control and Prevention (CDC) guidelines: stability, data quality, timeliness, positive predictive value, representativeness, simplicity, acceptability and flexibility. RESULTS: The final surveillance dataset comprised 1163 records, with cases peaking in ISO week 50 (week ending 19/12/2021). The system produced a stable stream of surveillance data, with the proportion of SARI records with sufficient information for effective surveillance increasing from 65.4% during the first month to 87.0% over time. Similarly, the proportion where data collection was completed promptly was low initially, but increased to 50%-65% during later periods. CONCLUSION: SARI surveillance was successfully established in one hospital, but for a national system, additional sentinel hospital sites across Scotland, with flexibility to ensure consistently high data completeness and timeliness are needed. Data collection should be automated where possible, and demands on clinicians minimised. SARI surveillance should be embedded and resourced as part of a national respiratory surveillance strategy.
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COVID-19 , Centros de Atención Terciaria , Humanos , Escocia/epidemiología , Estudios Transversales , Femenino , COVID-19/epidemiología , Masculino , Adulto , Persona de Mediana Edad , Anciano , Adolescente , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/diagnóstico , SARS-CoV-2 , Adulto Joven , Gripe Humana/epidemiología , Gripe Humana/diagnóstico , Vigilancia de la Población/métodosRESUMEN
This study investigates the structure of factors that influence consumer intentions to both try and to consume cultured proteins, and their intentions to substitute vegan, vegetarian and omnivore diets with these alternative protein sources. Comprehensive survey data (N = 3862) was collected from three Nordic countries (Denmark, Finland, and Norway) and analysed using confirmatory factor analysis and structural equation modelling. Theoretically, this article draws from behavioural models of environmental psychology, identity theory, and attitude theory. Results indicate that beliefs about the necessity of an industry producing cultured proteins and impacts of cultured proteins on the global economy are significant predictors of consumer intentions. Moreover, participants who exhibited high levels of general and food innovativeness were more likely to express positive intentions to consume cultured proteins. Social norms influenced consumer intentions: Individuals surrounded by positive attitudes and intentions toward cultured proteins within their social networks were more inclined to want to consume these products. The predictor variables in the final model accounted for between 39% and 66% of the variance in the different cultured proteins related intentions. Understanding consumer intentions better can inform targeted communication strategies aimed at promoting the advantages of cultured proteins and facilitating its adoption.
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Comportamiento del Consumidor , Intención , Carne , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Adulto Joven , Preferencias Alimentarias/psicología , Productos Lácteos , Animales , Encuestas y Cuestionarios , Finlandia , Adolescente , Dieta Vegetariana/psicología , Peces , Anciano , Normas Sociales , Proteínas en la Dieta , Alimentos Marinos , Noruega , Conocimientos, Actitudes y Práctica en Salud , Dieta/psicología , Carne in VitroRESUMEN
PURPOSE: This study aimed to propose a revision of the evaluation objectives of the Korean Dentist Clinical Skill Test by analyzing the opinions of those involved in the examination after a review of those objectives. METHODS: The clinical skill test objectives were reviewed based on the national-level dental practitioner competencies, dental school educational competencies, and the third dental practitioner job analysis. Current and former examinees were surveyed about their perceptions of the evaluation objectives. The validity of 22 evaluation objectives and overlapping perceptions based on area of specialty were surveyed on a 5-point Likert scale by professors who participated in the clinical skill test and dental school faculty members. Additionally, focus group interviews were conducted with experts on the examination. RESULTS: It was necessary to consider including competency assessments for "emergency rescue skills" and "planning and performing prosthetic treatment." There were no significant differences between current and former examinees in their perceptions of the clinical skill test's objectives. The professors who participated in the examination and dental school faculty members recognized that most of the objectives were valid. However, some responses stated that "oromaxillofacial cranial nerve examination," "temporomandibular disorder palpation test," and "space management for primary and mixed dentition" were unfeasible evaluation objectives and overlapped with dental specialty areas. CONCLUSION: When revising the Korean Dentist Clinical Skill Test's objectives, it is advisable to consider incorporating competency assessments related to "emergency rescue skills" and "planning and performing prosthetic treatment."
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Competencia Clínica , Evaluación Educacional , Grupos Focales , Humanos , Competencia Clínica/normas , República de Corea , Evaluación Educacional/métodos , Encuestas y Cuestionarios , Odontólogos , Educación en Odontología/métodos , MasculinoRESUMEN
IMPORTANCE: Adaptive surgical trials are scarce, but adopting these methods may help elevate the quality of surgical research when large-scale RCTs are impractical. OBJECTIVE: Randomized-controlled trials (RCTs) are the gold standard for evidence-based healthcare. Despite an increase in the number of RCTs, the number of surgical trials remains unchanged. Adaptive clinical trials can streamline trial design and time to trial reporting. The advantages identified for ACTs may help to improve the quality of future surgical trials. We present a scoping review of the methodological and reporting quality of adaptive surgical trials. EVIDENCE REVIEW: We performed a search of Ovid, Web of Science, and Cochrane Collaboration for all adaptive surgical RCTs performed from database inception to October 12, 2023. We included any published trials that had at least one surgical arm. All review and abstraction were performed in duplicate. Risk of bias (RoB) was assessed using the RoB 2.0 instrument and reporting quality was evaluated using CONSORT ACE 2020. All results were analyzed using descriptive methods. FINDINGS: Of the 1338 studies identified, six trials met inclusion criteria. Trials were performed in cardiothoracic, oral, orthopedic, and urological surgery. The most common type of adaptive trial was group sequential design with pre-specified interim analyses planned for efficacy, futility, and/or sample size re-estimation. Two trials did use statistical simulations. Our risk of bias evaluation identified a high risk of bias in 50% of included trials. Reporting quality was heterogeneous regarding trial design and outcome assessment and details in relation to randomization and blinding concealment. CONCLUSION AND RELEVANCE: Surgical trialists should consider implementing adaptive components to help improve patient recruitment and reduce trial duration. Reporting of future adaptive trials must adhere to existing CONSORT ACE 2020 guidelines. Future research is needed to optimize standardization of adaptive methods across medicine and surgery.
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Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto/normas , Proyectos de Investigación/normas , Ensayos Clínicos Adaptativos como Asunto/métodos , Procedimientos Quirúrgicos Operativos/normasRESUMEN
Background: Whereas clinical experience in dementia indicates high risk for financial mismanagement, there has been little formal study of real world financial errors in dementia. Objective: We aimed to compare caregiver-reported financial mistakes among people with Alzheimer's disease, behavioral variant frontotemporal dementia (bvFTD), and primary progressive aphasia (PPA). Methods: Caregivers reported whether participants with dementia had made financial mistakes within the last year; and if so, categorized these as resulting from: (a) being too trusting or gullible, (b) being wasteful or careless with money, or (c) trouble with memory. In a pre-registered analysis https://archive.org/details/osf-registrations-vupj7-v1), we examined the hypotheses that (1) financial mistakes due to impaired socioemotional function and diminished sensitivity to negative outcomes are more prevalent in bvFTD than in Alzheimer's disease, and (2) financial mistakes due to memory are more prevalent in Alzheimer's disease than in bvFTD. Exploratory analyses addressed vulnerability in PPA and brain-behavior relationships using voxel-based morphometry. Results: Concordant with our first hypothesis, bvFTD was more strongly associated than Alzheimer's disease with mistakes due to being too trusting/gullible or wasteful/careless; contrary to our second hypothesis, both groups were similarly likely to make mistakes due to memory. No differences were found between Alzheimer's disease and PPA. Exploratory analyses indicated associations between financial errors and atrophy in right prefrontal and insular cortex. Conclusions: Our findings cohere with documented socioemotional and valuation impairments in bvFTD, and with research indicating comparable memory impairment between bvFTD and Alzheimer's disease.
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Enfermedad de Alzheimer , Afasia Progresiva Primaria , Demencia Frontotemporal , Humanos , Enfermedad de Alzheimer/economía , Enfermedad de Alzheimer/psicología , Afasia Progresiva Primaria/economía , Afasia Progresiva Primaria/psicología , Demencia Frontotemporal/economía , Demencia Frontotemporal/psicología , Femenino , Masculino , Anciano , Cuidadores/psicología , Cuidadores/economía , Persona de Mediana Edad , Pruebas Neuropsicológicas , Imagen por Resonancia MagnéticaRESUMEN
The alphaproteobacterial order Hyphomicrobiales consists of 38 families comprising at least 152 validly published genera as of January 2024. The order Hyphomicrobiales was first described in 1957 and underwent important revisions in 2020. However, we show that several inconsistencies in the taxonomy of this order remain and we argue that there is a need for a consistent framework for defining families within the order. We propose a common genome-based framework for defining families within the order Hyphomicrobiales, suggesting that families represent monophyletic groups in core-genome phylogenies that share pairwise average amino acid identity values above ~75â% when calculated from a core set of 59 proteins. Applying this framework, we propose the formation of four new families and to reassign the genera Salaquimonas, Rhodoblastus, and Rhodoligotrophos into Salaquimonadaceae fam. nov., Rhodoblastaceae fam. nov., and Rhodoligotrophaceae fam. nov., respectively, and the genera Albibacter, Chenggangzhangella, Hansschlegelia, and Methylopila into Methylopilaceae fam. nov. We further propose to unify the families Bartonellaceae, Brucellaceae, Phyllobacteriaceae, and Notoacmeibacteraceae as Bartonellaceae; the families Segnochrobactraceae and Pseudoxanthobacteraceae as Segnochrobactraceae; the families Lichenihabitantaceae and Lichenibacteriaceae as Lichenihabitantaceae; and the families Breoghaniaceae and Stappiaceae as Stappiaceae. Lastly, we propose to reassign several genera to existing families. Specifically, we propose to reassign the genus Pseudohoeflea to the family Rhizobiaceae; the genera Oricola, Roseitalea, and Oceaniradius to the family Ahrensiaceae; the genus Limoniibacter to the emended family Bartonellaceae; the genus Faunimonas to the family Afifellaceae; and the genus Pseudochelatococcus to the family Chelatococcaceae. Our data also support the recent proposal to reassign the genus Prosthecomicrobium to the family Kaistiaceae.
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Alphaproteobacteria , Beijerinckiaceae , Humanos , Filogenia , Análisis de Secuencia de ADN , Ácidos Grasos/química , ARN Ribosómico 16S/genética , ADN Bacteriano/genética , Composición de Base , Técnicas de Tipificación Bacteriana , Beijerinckiaceae/genéticaRESUMEN
BACKGROUD: The genus Mesorhizobium is shown by phylogenomics to be paraphyletic and forms part of a complex that includes the genera Aminobacter, Aquamicrobium, Pseudaminobacter and Tianweitania. The relationships for type strains belong to these genera need to be carefully re-evaluated. RESULTS: The relationships of Mesorhizobium complex are evaluated based on phylogenomic analyses and overall genome relatedness indices (OGRIs) of 61 type strains. According to the maximum likelihood phylogenetic tree based on concatenated sequences of 539 core proteins and the tree constructed using the bac120 bacterial marker set from Genome Taxonomy Database, 65 type strains were grouped into 9 clusters. Moreover, 10 subclusters were identified based on the OGRIs including average nucleotide identity (ANI), average amino acid identity (AAI) and core-proteome average amino acid identity (cAAI), with AAI and cAAI showing a clear intra- and inter-(sub)cluster gaps of 77.40-80.91% and 83.98-86.16%, respectively. Combined with the phylogenetic trees and OGRIs, the type strains were reclassified into 15 genera. This list includes five defined genera Mesorhizobium, Aquamicrobium, Pseudaminobacter, Aminobacterand Tianweitania, among which 40/41 Mesorhizobium species and one Aminobacter species are canonical legume microsymbionts. The other nine (sub)clusters are classified as novel genera. Cluster III, comprising symbiotic M. alhagi and M. camelthorni, is classified as Allomesorhizobium gen. nov. Cluster VI harbored a single symbiotic species M. albiziae and is classified as Neomesorhizobium gen. nov. The remaining seven non-symbiotic members were proposed as: Neoaquamicrobium gen. nov., Manganibacter gen. nov., Ollibium gen. nov., Terribium gen. nov., Kumtagia gen. nov., Borborobacter gen. nov., Aerobium gen. nov.. Furthermore, the genus Corticibacterium is restored and two species in Subcluster IX-1 are reclassified as the member of this genus. CONCLUSION: The Mesorhizobium complex are classified into 15 genera based on phylogenomic analyses and OGRIs of 65 type strains. This study resolved previously non-monophyletic genera in the Mesorhizobium complex.
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Genoma Bacteriano , Mesorhizobium , Filogenia , Mesorhizobium/genética , Mesorhizobium/clasificación , Genómica/métodosRESUMEN
RATIONALE: Intensive care units (ICUs) admit the most severely ill patients. Once these patients are discharged from the ICU to a step-down ward, they continue to have their vital signs monitored by nursing staff, with Early Warning Score (EWS) systems being used to identify those at risk of deterioration. OBJECTIVES: We report the development and validation of an enhanced continuous scoring system for predicting adverse events, which combines vital signs measured routinely on acute care wards (as used by most EWS systems) with a risk score of a future adverse event calculated on discharge from the ICU. DESIGN: A modified Delphi process identified candidate variables commonly available in electronic records as the basis for a 'static' score of the patient's condition immediately after discharge from the ICU. L1-regularised logistic regression was used to estimate the in-hospital risk of future adverse event. We then constructed a model of physiological normality using vital sign data from the day of hospital discharge. This is combined with the static score and used continuously to quantify and update the patient's risk of deterioration throughout their hospital stay. SETTING: Data from two National Health Service Foundation Trusts (UK) were used to develop and (externally) validate the model. PARTICIPANTS: A total of 12 394 vital sign measurements were acquired from 273 patients after ICU discharge for the development set, and 4831 from 136 patients in the validation cohort. RESULTS: Outcome validation of our model yielded an area under the receiver operating characteristic curve of 0.724 for predicting ICU readmission or in-hospital death within 24 hours. It showed an improved performance with respect to other competitive risk scoring systems, including the National EWS (0.653). CONCLUSIONS: We showed that a scoring system incorporating data from a patient's stay in the ICU has better performance than commonly used EWS systems based on vital signs alone. TRIAL REGISTRATION NUMBER: ISRCTN32008295.
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Readmisión del Paciente , Medicina Estatal , Humanos , Mortalidad Hospitalaria , Unidades de Cuidados Intensivos , Cuidados CríticosRESUMEN
The liquid structure of three common ionic liquids (ILs) was investigated by neutron scattering for the first time. The ILs were based on the bis(trifluoromethanesulfonyl)imide anion, abbreviated in the literature as [NTf2]- or [TFSI]-, and on the following cations: 1-ethyl-3-methylimidazolium, [C2mim]+; 1-decyl-3-methylimidazolium, [C10mim]+; and trihexyl(tetradecyl)phosphonium, [P666,14]+. Comparative analysis of the three ILs confirmed increased size of nonpolar nanodomains with increasing bulk of alkyl chains. It also sheds light on the cation-anion interactions, providing experimental insight into strength, directionality, and angle of hydrogen bonds between protons on the imidazolium ring, as well as H-C-P protons in [P666,14]+, to oxygen and nitrogen atoms in the [NTf2]-. The new Dissolve data analysis package enabled, for the first time, the analysis of neutron scattering data of ILs with long alkyl chains, in particular, of [P666,14][NTf2]. Results generated with Dissolve were validated by comparing outputs from three different models, starting from three different sets of cation charges, for each of the three ILs, which gave convergent outcomes. Finally, a modified method for the synthesis of perdeuterated [P666,14][NTf2] has been reported, with the aim of reporting a complete set of synthetic and data processing approaches, laying robust foundations that enable the study of the phosphonium ILs family by neutron scattering.
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BACKGROUND: Sweat chloride (SC) concentrations in people with cystic fibrosis (PwCF) reflect relative CF transmembrane conductance regulator (CFTR) protein function, the primary CF defect. Populations with greater SC concentrations tend to have lesser CFTR function and more severe disease courses. CFTR modulator treatment can improve CFTR function within specific CF genotypes and is commonly associated with reduced SC concentration. However, SC concentrations do not necessarily fall to concentrations seen in the unaffected population, suggesting potential for better CFTR treatment outcomes. We characterized post-modulator SC concentration variability among CHEC-SC study participants by genotype and modulator. METHODS: PwCF receiving commercially approved modulators for ≥90 days were enrolled for a single SC measurement. Clinical data were obtained from chart review and the CF Foundation Patient Registry (CFFPR). Variability of post-modulator SC concentrations was assessed by cumulative SC concentration frequencies. RESULTS: Post-modulator SC concentrations (n = 3787) were collected from 3131 PwCF; most (n = 1769, 47 %) were collected after elexacaftor/tezacaftor/ivacaftor (ETI) treatment. Modulator use was associated with lower SC distributions, with post-ETI concentrations the lowest on average. Most post-ETI SC concentrations were <60 mmol/L (79 %); 26 % were <30 mmol/L. Post-ETI distributions varied by genotype. All genotypes containing at least one F508del allele had individuals with post-ETI SC ≥60 mmol/L, with the largest proportion being F508del/minimal function (31 %). CONCLUSIONS: Post-modulator SC concentration heterogeneity was observed among all genotypes and modulators, including ETI. The presence of PwCF with post-modulator SC concentrations within the CF diagnostic range suggests room for additional treatment-associated CFTR restoration in this population.
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Aminofenoles , Benzodioxoles , Cloruros , Regulador de Conductancia de Transmembrana de Fibrosis Quística , Fibrosis Quística , Combinación de Medicamentos , Indoles , Quinolonas , Sudor , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/genética , Fibrosis Quística/metabolismo , Humanos , Sudor/química , Sudor/metabolismo , Cloruros/análisis , Cloruros/metabolismo , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Masculino , Femenino , Benzodioxoles/uso terapéutico , Aminofenoles/uso terapéutico , Quinolonas/uso terapéutico , Indoles/uso terapéutico , Agonistas de los Canales de Cloruro/uso terapéutico , Adulto , Genotipo , Adolescente , Niño , Quinolinas , Pirazoles/uso terapéutico , PiridinasRESUMEN
BACKGROUND: Despite effective vaccines against influenza, pneumococcus, and COVID-19, uptake has been suboptimal. RESEARCH QUESTION: Although disparities in vaccination by race and ethnicity have been observed, what is the role of other sociodemographic factors in US vaccine uptake? STUDY DESIGN AND METHODS: We conducted a population-based study using the Rochester Epidemiology Project (REP), a comprehensive medical records linkage system, to assess effects of sociodemographic factors including race, ethnicity, individual-level socioeconomic status (SES) via the housing-based socioeconomic status index, education, population density (urban or nonurban), and marital status with uptake of influenza, pneumococcal, and COVID-19 vaccination in high-risk adults. Adults at high risk of invasive pneumococcal disease residing in four counties in southeastern Minnesota who were aged 19 to 64 years were identified. Vaccination data were obtained from the Minnesota Immunization Information Connection and REP from January 1, 2010, through December 31, 2021. RESULTS: We identified 45,755 residents. Most were White (82%), non-Hispanic (94%), married (56%), and living in an urban setting (81%), with three-quarters obtaining at least some college education (74%). Although 45.1% were up to date on pneumococcal vaccines, 60.1% had completed the primary COVID-19 series. For influenza and COVID-19, higher SES, living in an urban setting, older age, and higher education positively correlated with vaccination. Magnitude of differences in race, education, and SES widened with booster vaccines. INTERPRETATION: This high-risk population is undervaccinated against preventable respiratory diseases, especially influenza and pneumococcus. Although national data reported improvement of disparities in COVID-19 vaccination uptake observed early in the pandemic, our data demonstrated gaps related to race, education level, SES, and age that widened with booster vaccines. Communities with high social vulnerabilities often show increased risk of severe disease outcomes, yet demonstrate lower uptake of preventive services. This highlights the need to understand better vaccine compliance and access in rural, lower SES, less-educated, Black, Hispanic, and younger populations, each of which were associated independently with decreased vaccination.
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Vacunas contra la COVID-19 , COVID-19 , Vacunas contra la Influenza , Gripe Humana , Infecciones Neumocócicas , Vacunas Neumococicas , Cobertura de Vacunación , Humanos , Adulto , Persona de Mediana Edad , Minnesota/epidemiología , Masculino , Femenino , COVID-19/prevención & control , COVID-19/epidemiología , Vacunas Neumococicas/administración & dosificación , Cobertura de Vacunación/estadística & datos numéricos , Adulto Joven , Gripe Humana/prevención & control , Gripe Humana/epidemiología , Infecciones Neumocócicas/prevención & control , Infecciones Neumocócicas/epidemiología , SARS-CoV-2 , Disparidades en Atención de Salud/estadística & datos numéricos , Disparidades en Atención de Salud/etnologíaRESUMEN
BACKGROUND: Personalized asthma management depends on a clinician's ability to efficiently review patient's data and make timely clinical decisions. Unfortunately, efficient and effective review of these data is impeded by the varied format, location, and workflow of data acquisition, storage, and processing in the electronic health record. While machine learning (ML) and clinical decision support tools are well-positioned as potential solutions, the translation of such frameworks requires that barriers to implementation be addressed in the formative research stages. OBJECTIVE: We aimed to use a structured user-centered design approach (double-diamond design framework) to (1) qualitatively explore clinicians' experience with the current asthma management system, (2) identify user requirements to improve algorithm explainability and Asthma Guidance and Prediction System prototype, and (3) identify potential barriers to ML-based clinical decision support system use. METHODS: At the "discovery" phase, we first shadowed to understand the practice context. Then, semistructured interviews were conducted digitally with 14 clinicians who encountered pediatric asthma patients at 2 outpatient facilities. Participants were asked about their current difficulties in gathering information for patients with pediatric asthma, their expectations of ideal workflows and tools, and suggestions on user-centered interfaces and features. At the "define" phase, a synthesis analysis was conducted to converge key results from interviewees' insights into themes, eventually forming critical "how might we" research questions to guide model development and implementation. RESULTS: We identified user requirements and potential barriers associated with three overarching themes: (1) usability and workflow aspects of the ML system, (2) user expectations and algorithm explainability, and (3) barriers to implementation in context. Even though the responsibilities and workflows vary among different roles, the core asthma-related information and functions they requested were highly cohesive, which allows for a shared information view of the tool. Clinicians hope to perceive the usability of the model with the ability to note patients' high risks and take proactive actions to manage asthma efficiently and effectively. For optimal ML algorithm explainability, requirements included documentation to support the validity of algorithm development and output logic, and a request for increased transparency to build trust and validate how the algorithm arrived at the decision. Acceptability, adoption, and sustainability of the asthma management tool are implementation outcomes that are reliant on the proper design and training as suggested by participants. CONCLUSIONS: As part of our comprehensive informatics-based process centered on clinical usability, we approach the problem using a theoretical framework grounded in user experience research leveraging semistructured interviews. Our focus on meeting the needs of the practice with ML technology is emphasized by a user-centered approach to clinician engagement through upstream technology design.
RESUMEN
Autophagy is a degradative pathway that plays an important role in maintaining cellular homeostasis. Dysfunction of autophagy is associated with the progression of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Although one of the typical features of brain aging is an accumulation of redox-active metals that eventually lead to neurodegeneration, a plausible link between trace metal-induced neurodegeneration and dysregulated autophagy has not been clearly determined. Here, we used a cupric chloride-induced neurodegeneration model in MN9D dopaminergic neuronal cells along with ultrastructural and biochemical analyses to demonstrate impaired autophagic flux with accompanying lysosomal dysfunction. We found that a surge of cytosolic calcium was involved in cupric chloride-induced dysregulated autophagy. Consequently, buffering of cytosolic calcium by calbindin-D28K overexpression or co-treatment with the calcium chelator BAPTA attenuated the cupric chloride-induced impairment in autophagic flux by ameliorating dysregulation of lysosomal function. Thus, these events allowed the rescue of cells from cupric chloride-induced neuronal death. These phenomena were largely confirmed in cupric chloride-treated primary cultures of cortical neurons. Taken together, these results suggest that abnormal accumulation of trace metal elements and a resultant surge of cytosolic calcium leads to neuronal death by impairing autophagic flux at the lysosomal level.