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1.
Blood Adv ; 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38776397

RESUMEN

BCMA-targeting CAR-T cells used in multiple myeloma (MM) are rapidly becoming a mainstay in the treatment of relapsed/refractory (RR) disease, and CAR-T cell expansion post-infusion has been shown to inform depth and duration of response, but measuring this process remains investigational. This multicenter study describes the kinetics and prognostic impact of absolute lymphocyte count (ALC) in the first 15 days after CAR-T infusion in 156 relapsed MM patients treated with the BCMA-targeting agents cilta-cel and ide-cel. Patients with higher maximum ALC (ALCmax) had better depth of response, progression-free survival (PFS), and duration of response (DoR). Patients with ALCmax >1.0 x103/uL had a superior PFS (30.5 versus 6 months, p <0.001) compared to those ≤1.0x103/uL, while patients with ALCmax ≤0.5 x103/uL represent a high-risk group with early disease progression and short PFS (HR 3.4, 95 CI: 2 -5.8, P <0.001). In multivariate analysis, ALCmax >1.0 x103/uL and non-paraskeletal extramedullary disease were the only independent predictors of PFS and DoR after accounting for ISS staging, age, CAR-T product, high-risk cytogenetics and number of previous lines. Moreover, our flow cytometry data suggests that ALC is a surrogate for BCMA CAR-T expansion and can be used as an accessible prognostic marker. We report for the first time the association of ALC after BCMA CAR-T infusion with clinical outcomes and its utility in predicting response in RRMM patients.

2.
PLoS One ; 19(5): e0299980, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38758772

RESUMEN

BACKGROUND: To fulfil the diagnostic criteria of Attention Deficit Hyperactivity Disorder in the Fifth Edition of Diagnostic and Statistical Manual of Mental Disorders (DSM-5), symptoms should be observed in two or more settings. This implies that diagnostic procedures require observations reported from informants in different settings, such as teachers in school and caregivers at home. This study examined parent-teacher agreement in reporting hyperactivity/inattention and its relationship with child's, parent's, and family's characteristics. METHOD: We used data from the 2004 United Kingdom Mental Health of Children and Young People survey, including 7977 children aged 4-17, to investigate cross-informant agreement between parents and teachers on the hyperactivity-inattention subscale of the Strengths and Difficulties Questionnaire. The characteristics of different patterns of informant agreement were assessed using multinomial logistic regression. RESULTS: Cross-informant agreement of parent and teacher was low (weighted kappa = .34, 95% C.I.: .31, .37). Some characteristics, such as male child and parental emotional distress, were associated with higher likelihood of parent-teacher discrepancy. CONCLUSION: We found low informant agreement in the hyperactive/inattention subscale, as hypothesised and consistent with previous studies. The current study has found several factors that predict discrepancy, which were partly consistent with previous research. Possible explanation, implications, and further research on parent-teacher informant discrepancy in reporting hyperactivity/inattention were discussed.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Padres , Maestros , Humanos , Masculino , Femenino , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Niño , Reino Unido/epidemiología , Padres/psicología , Adolescente , Maestros/psicología , Preescolar , Encuestas y Cuestionarios
3.
BMC Oral Health ; 24(1): 264, 2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38388920

RESUMEN

BACKGROUND: This study aims to analyze the longitudinal variation of occlusal force distribution prior to and after fixed restoration for molar full-crowns with T-SCAN III which provide reference for occlusal adjustment and long-term maintenance. METHODS: We enrolled a total of 20 patients who received conventional restorative treatment for molars. The occlusion examination was conducted in 3 stages (before placement, immediately after placement, and 3 months after placement) using T-SCAN III (Tekscan South Boston, MA, USA, 10.0) to examine and measure the occlusal contact areas of the full dentition. RESULTS: The results indicated that the occlusal force distribution in the molar region of the patients changed before and after the fixed restoration, but the percentages of occlusal force in the dental arch of the molar did not differ significantly before and after the restoration (P > 0.05). Three months after the fixed restoration, the percentage of occlusal force in the restored dental arches of lateral teeth increased significantly (P < 0.05). CONCLUSION: The results of this study indicated that the occlusal forces of the patients changed with tooth movement and adaptation, which is mainly reflected in the increasing occlusal force. Quantitative occlusal force analysis using T-SCAN III occlusal analyzer can provide more objective and accurate data to effectively guide clinical occlusion adjustments.


Asunto(s)
Fuerza de la Mordida , Oclusión Dental , Humanos , Diente Molar , Coronas , Dentaduras
4.
Prehosp Emerg Care ; 28(3): 515-530, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37477998

RESUMEN

OBJECTIVE: We sought to describe prehospital ultrasound (PHUS) use and trends in PHUS utilization over time using a national database. METHODS: Using the 2018 - 2021 National Emergency Medical Services Information System databases, we identified those EMS activations where PHUS was performed. We evaluated the association between year and number of PHUS exams performed using univariable and multivariable regression analysis. Analysis was performed on the overall group and various subgroups. RESULTS: In total, there were 148,709,000 EMS activations by 13,899 agencies over the 4 years. Of these, 3,291 unique activations (0.002%) involved PHUS, performed by 71 EMS agencies (0.5%). The annual rate of ultrasound evaluations per 1 million EMS activations significantly increased over the study period: 5.2 in 2018, 14.8 in 2019, 18.6 in 2020, and 38.9 in 2021 (p < 0.01). The number of agencies performing PHUS each year increased over the study period from 11 in 2018 to 54 in 2021 (p < 0.05). Each year after 2018 had an increased odds of PHUS use demonstrated with logistic regression (p < 0.01). PHUS was used in each US census region, and paramedics performed most of the PHUS exams (75.5%). We identified 1,060 out-of-hospital cardiac arrest, 820 trauma, and 427 respiratory PHUS cases. These three cohorts accounted for 70.1% of all PHUS cases. CONCLUSION: Prehospital ultrasound use in the United States increased significantly over the study period, but remains exceedingly rare. The performance of PHUS was recorded throughout the United States, with paramedics performing the majority of PHUS studies included in this database.


Asunto(s)
Servicios Médicos de Urgencia , Humanos , Estados Unidos/epidemiología , Incidencia , Ultrasonografía , Bases de Datos Factuales , Modelos Logísticos
5.
Sci Rep ; 13(1): 21861, 2023 12 09.
Artículo en Inglés | MEDLINE | ID: mdl-38071385

RESUMEN

This study evaluates the scale-free network assumption commonly used in COVID-19 epidemiology, using empirical social network data from SARS-CoV-2 Delta variant molecular local clusters in Houston, Texas. We constructed genome-informed social networks from contact and co-residence data, tested them for scale-free power-law distributions that imply highly connected hubs, and compared them to alternative models (exponential, log-normal, power-law with exponential cutoff, and Weibull) that suggest more evenly distributed network connections. Although the power-law model failed the goodness of fit test, after incorporating social network ties, the power-law model was at least as good as, if not better than, the alternatives, implying the presence of both hub and non-hub mechanisms in local SARS-CoV-2 transmission. These findings enhance our understanding of the complex social interactions that drive SARS-CoV-2 transmission, thereby informing more effective public health interventions.


Asunto(s)
COVID-19 , Humanos , COVID-19/epidemiología , SARS-CoV-2/genética , Red Social , Texas/epidemiología
6.
Ophthalmol Ther ; 12(6): 3373-3382, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37851163

RESUMEN

INTRODUCTION: The aim of this work is to determine the interocular differences in peripapillary retinal nerve fiber layer (p-RNFL) thickness and its associations among school children in Hong Kong. METHODS: We conducted a population-based study including 4034 children aged 6-8 years from the Hong Kong Children Eye Study (HKCES). All participants received comprehensive ocular examinations where p-RNFL thickness was measured using spectral-domain optical coherence tomography (SD-OCT). The degree of symmetry between both eyes was analyzed and represented by intraclass correlation coefficient (ICC) values. Multivariable linear regression analysis was used to investigate the associations between ocular and systemic factors with p-RNFL thickness difference. RESULTS: The study included 4034 children with a mean age of 7.61 ± 0.98 years. The mean global p-RNFL thickness was 106.60 ± 9.41 µm in right eyes and 105.99 ± 9.30 µm in left eyes. The ICC for global p-RNFL difference was 0.866 (95% CI 0.858-0.873, p < 0.001). The symmetry displayed the largest values in nasal inferior quadrant with the ICC value of 0.736 (95% CI 0.721-0.749); and the smallest degree of symmetry was found to be in the superior temporal quadrant with the ICC value of 0.567 (95% CI 0.546-0.588). Axial length (AL) difference was found to have more pronounced correlation to interocular symmetry in p-RNFL thickness with the coefficient of 0.514 (p < 0.001). CONCLUSIONS: Normal variation in interocular symmetry exists in children. Our results can contribute to the establishment of a standard reference for interocular differences in OCT parameters in children. The interocular differences in AL should be considered in the interpretation of RNFL symmetry, in terms of identifying children at risk of developing glaucoma or other ocular disorders.

7.
Front Immunol ; 14: 1212203, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37901229

RESUMEN

T cell immunity plays a central role in clinical outcomes of Coronavirus Infectious Disease 2019 (COVID-19) and T cell-focused vaccination or cellular immunotherapy might provide enhanced protection for some immunocompromised patients. Pre-existing T cell memory recognizing SARS-CoV-2 antigens antedating COVID-19 infection or vaccination, may have developed as an imprint of prior infections with endemic non-SARS human coronaviruses (hCoVs) OC43, HKU1, 229E, NL63, pathogens of "common cold". In turn, SARS-CoV-2-primed T cells may recognize emerging variants or other hCoV viruses and modulate the course of subsequent hCoV infections. Cross-immunity between hCoVs and SARS-CoV-2 has not been well characterized. Here, we systematically investigated T cell responses against the immunodominant SARS-CoV-2 spike, nucleocapsid and membrane proteins and corresponding antigens from α- and ß-hCoVs among vaccinated, convalescent, and unexposed subjects. Broad T cell immunity against all tested SARS-CoV-2 antigens emerged in COVID-19 survivors. In convalescent and in vaccinated individuals, SARS-CoV-2 spike-specific T cells reliably recognized most SARS-CoV-2 variants, however cross-reactivity against the omicron variant was reduced by approximately 47%. Responses against spike, nucleocapsid and membrane antigens from endemic hCoVs were significantly more extensive in COVID-19 survivors than in unexposed subjects and displayed cross-reactivity between α- and ß-hCoVs. In some, non-SARS hCoV-specific T cells demonstrated a prominent non-reciprocal cross-reactivity with SARS-CoV-2 antigens, whereas a distinct anti-SARS-CoV-2 immunological repertoire emerged post-COVID-19, with relatively limited cross-recognition of non-SARS hCoVs. Based on this cross-reactivity pattern, we established a strategy for in-vitro expansion of universal anti-hCoV T cells for adoptive immunotherapy. Overall, these results have implications for the future design of universal vaccines and cell-based immune therapies against SARS- and non-SARS-CoVs.


Asunto(s)
COVID-19 , Coronavirus Humano OC43 , Humanos , SARS-CoV-2 , ARN Viral
8.
Commun Med (Lond) ; 3(1): 155, 2023 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-37884789

RESUMEN

BACKGROUND: A recent prospective demonstrated that cardiovascular risk factors in early childhood were associated with later cardiovascular events. However, the impact of secondhand smoke (SHS) on children is unclear. The aims of this study is to determine the effects of SHS exposure on the retinal vasculature of children. METHODS: This is a population-based cross-sectional study of children aged 6 to 8 years. All participants received comprehensive ophthalmic examinations and retinal photography. Data on SHS exposure was derived from a validated questionnaire. A validated deep-learning system was used to automatically estimate retinal arteriolar and venular calibers from retinal photographs. Associations of quantitative retinal vessel caliber values with SHS exposure, number of smokers in the household, and total number of cigarettes smoked were determined by analyses of covariance (ANCOVA) after adjusting for potential confounders. Test of trend was determined by treating categorical risk factors as continuous ordinal variables. RESULTS: Here we show children exposed to SHS have wider retinal arteriolar (CRAE 152.1 µm vs. 151.3 µm, p < 0.001) and venular (CRVE 216.7 µm vs. 215.5 µm, p < 0.001) calibers compared to those in smoke-free homes, after adjustment for different factors. Wider arteriolar and venular calibers are also associated with increasing number of smokers in the family (p trend < 0.001) and more cigarettes smoked among family smokers (p trend<0.001). CONCLUSIONS: Exposure to SHS at home is associated with changes in retinal vasculature among children. This reinforces the adverse effect of secondhand smoking around children though further research incorporating comprehensive assessment of potential confounders is necessary.


Exposure to secondhand smoke can be harmful, particularly for our heart and lung health as adults. However, the impact of secondhand smoke on children is less clear. Here, we looked at the effects of secondhand smoke exposure on vessels within children's eyes. The health of these vessels is a potential indicator of overall eye health and is also associated with cardiovascular disease. Pictures were taken of children's eyes and analyzed using a computer program. We looked at the association between vessel measurements in the eye and how much secondhand smoke the children are exposed to. We observed differences in the vessels in children exposed to secondhand smoke, compared to those from smoke-free homes. These findings indicate that secondhand smoke may affect the health of children's eyes and highlight the need to promote smoke-free home environments.

9.
Am J Emerg Med ; 72: 183-187, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37544146

RESUMEN

OBJECTIVE: Prior studies identified increased penetrating trauma rates during the earlier phase of the COVID-19 pandemic, but there is limited study of penetrating trauma rates in 2021 or at a national level. We evaluated trends in prehospital encounters for penetrating trauma in 2020 and 2021 using a national database. METHODS: We conducted a retrospective analysis of the National Emergency Medicinal Services (EMS) Information System (NEMSIS) combined 2018-2021 databases of prehospital encounters. We calculated penetrating trauma yearly and monthly rates with 95% confidence; both overall and for each census region. We compared trauma rates in 2020 and 2021 to combined 2018/2019. RESULTS: There were 67,457 (rate of 0.30%) penetrating traumas in 2018, 86,054 (0.30%) in 2019, 95,750 (0.37%) in 2020, and 98,040 (0.34%) in 2021. Nationally, trauma rates were higher from March 2020 to July 2021 than baseline. Penetrating trauma rates from May-December 2021 were lower than May-December of 2020. All census regions similarly had increased trauma rates during from March 2020 to July 2021. CONCLUSION: We identified elevated rates of trauma on 2020 that lasted until July of 2021 that was present in all US census regions.


Asunto(s)
COVID-19 , Servicios Médicos de Urgencia , Heridas Penetrantes , Humanos , Estudios Retrospectivos , Pandemias , COVID-19/epidemiología , COVID-19/terapia , Heridas Penetrantes/epidemiología , Heridas Penetrantes/terapia
11.
Inj Epidemiol ; 10(Suppl 1): 41, 2023 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-37550792

RESUMEN

BACKGROUND: Firearms are a leading cause of death in children. The demand for firearms increased following COVID-19 "stay-at home orders" in March 2020, resulting in record-breaking firearm sales and background checks. We aim to describe the changes in pediatric firearm-related injuries, demographics, and associated risk factors at a Level 1 trauma center in Houston before and during the COVID 19 pandemic. RESULTS: The total number of pediatric firearm-related injury cases increased during March 15th to December 31st, 2020 and 2021 compared to the same time period in 2019 (104 verses 89 verses 78). The demographic group most affected across years were males (87% in 2019 vs 82% in 2020 and 87% in 2021) between 14 and 17 years old (83% in 2019 vs 81% in 2020 and 76% in 2021). There was an increase in firearm injuries among black youth across all years (28% in 2019 vs 41% in 2020 vs 49% in 2021). Injuries in those with mental illness (10% in 2019 vs 24% in 2020 vs 17% in 2021), and injuries where the shooter was a known family member or friend (14% in 2019 vs 18% in 2020 vs. 15% in 2021), increased from 2019 to 2020. CONCLUSION: The total number of pediatric firearm-related injuries increased during the COVID-19 pandemic compared to the previous year despite a decline in overall pediatric emergency department visits. Increases in pediatric firearm-related injuries in already vulnerable populations should prompt further hospital initiatives including counseling on safe firearm storage, implementation of processes to identify children at risk for firearm injuries, and continued research to mitigate the risk of injury and death associated with firearms in our community.

12.
J Mater Chem B ; 11(22): 4865-4873, 2023 06 07.
Artículo en Inglés | MEDLINE | ID: mdl-37161476

RESUMEN

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder characterized by the synaptic and neuronal loss, which results in cognitive impairment in particular learning and memory. Currently, AD is incurable and no single confirmative test can clinically be used to diagnose AD. In light of the complex and multifactorial nature of AD etiology, the development of multifunctional/multi-target drugs that act on multiple pathological pathways and mechanisms shows great therapeutic potential for intervention of this devastating disease. We report herein a multifunctional theranostic cyanine, SLCOOH, which serves not only as a highly sensitive fluorescent probe for real-time imaging of amyloid-ß (Aß) contents in different age groups of transgenic (Tg) AD mice but also as an effective therapeutic agent for early AD intervention via multiple pathological targets in the AD mouse model. Remarkably, treatment with SLCOOH gives rise to multiple therapeutic benefits, including the amelioration of cognitive decline, a reduction in Aß levels, a decrease in hyperphosphorylated tau proteins and tau depositions, and the alleviation of synaptic loss and dysfunctions in young triple Tg AD mice. Our results have demonstrated that in addition to superior Aß imaging capability, SLCOOH exhibits versatile and effective multiple modes of drug action, signifying outstanding therapeutic potential to treat early onset AD. Our work also paves the way for the development of effective Aß-targeted theranostic agents for AD.


Asunto(s)
Enfermedad de Alzheimer , Ratones , Animales , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Medicina de Precisión , Péptidos beta-Amiloides/metabolismo , Proteínas tau , Ratones Transgénicos , Carbazoles/uso terapéutico
13.
Invest Ophthalmol Vis Sci ; 64(4): 4, 2023 04 03.
Artículo en Inglés | MEDLINE | ID: mdl-37022704

RESUMEN

Purpose: This study aimed to assess the prevalence and characteristics of the peripapillary gamma zone in myopic, emmetropic, and hyperopic eyes of Chinese children. Methods: Overall, 1274 children aged 6 to 8 years from the Hong Kong Children Eye Study underwent ocular examinations, including measurements of cycloplegic auto-refraction and axial length (AL). The optic disc was imaged using a Spectralis optical coherence tomography (OCT) unit and a protocol involving 24 equally spaced radial B-scans. The Bruch's membrane opening (BMO) was identified in over 48 meridians in each eye. The peripapillary gamma zone was defined as the region between the BMO and the border of the optic disc, identified by the OCT. Results: The prevalence of the peripapillary gamma zone was higher in myopic eyes (36.3%) than in emmetropic (16.1%) and hyperopic eyes (11.5%, P < 0.001). AL (per 1 mm; odds ratio [OR]) = 1.861, P < 0.001) and a more oval disc shape (OR = 3.144, P < 0.001) were associated with the presence of a peripapillary gamma zone after adjusting for demographic, systemic, and ocular variables. In the subgroup analysis, a longer AL was associated with the presence of a peripapillary gamma zone in myopic eyes (OR = 1.874, P < 0.001), but not in emmetropic (OR = 1.033, P = 0.913) or hyperopic eyes (OR = 1.044, P = 0.883). A peripapillary zone was not observed in the region nasal to the optic nerve in myopic eyes, in contrast to its presence in the same region in 1.9% of emmetropic eyes and 9.3% of hyperopic eyes; these intergroup differences were statistically significant (P < 0.001). Conclusions: Although peripapillary gamma zones were observed in the eyes of both myopic and non-myopic children, their characteristics and distribution patterns were substantially different.


Asunto(s)
Hiperopía , Miopía , Disco Óptico , Humanos , Niño , Hong Kong/epidemiología , Prevalencia , Miopía/epidemiología , Refracción Ocular , Hiperopía/epidemiología , Tomografía de Coherencia Óptica/métodos
14.
Stat Med ; 42(12): 1965-1980, 2023 05 30.
Artículo en Inglés | MEDLINE | ID: mdl-36896833

RESUMEN

Hypertension significantly increases the risk for many health conditions including heart disease and stroke. Hypertensive patients often have continuous measurements of their blood pressure to better understand how it fluctuates over the day. The continuous-time Markov chain (CTMC) is commonly used to study repeated measurements with categorical outcomes. However, the standard CTMC may be restrictive, because the rates of transitions between states are assumed to be constant through time, while the transition rates for describing the dynamics of hypertension are likely to be changing over time. In addition, the applications of CTMC rarely account for the effects of other covariates on state transitions. In this article, we considered a non-homogeneous continuous-time Markov chain with two states to analyze changes in hypertension while accounting for multiple covariates. The explicit formulas for the transition probability matrix as well as the corresponding likelihood function were derived. In addition, we proposed a maximum likelihood estimation algorithm for estimating the parameters in the time-dependent rate function. Lastly, the model performance was demonstrated through both a simulation study and application to ambulatory blood pressure data.


Asunto(s)
Monitoreo Ambulatorio de la Presión Arterial , Hipertensión , Humanos , Cadenas de Markov , Funciones de Verosimilitud , Simulación por Computador
15.
Clin Nutr ESPEN ; 54: 382-397, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36963884

RESUMEN

BACKGROUND & AIMS: Malnutrition, sarcopenia, and frailty are three prevalent wasting conditions among older rehabilitation patients that lead to multiple health-related negative outcomes. This systematic review and meta-analysis aimed to determine the post-discharge consequences of malnutrition, sarcopenia, and frailty in older adults admitted to inpatient rehabilitation. METHODS: MEDLINE, Embase, Web of Science, and CINAHL databases were searched on 20 April, 2021 for longitudinal studies in older adults (≥65 years) admitted for inpatient rehabilitation. This systematic review included and synthesised studies that 1) measured malnutrition, sarcopenia, and/or frailty using a validated assessment tool or guideline; and 2) reported the association with post-discharge mortality, physical function, quality of life, or discharge location. The Academy of Nutrition & Dietetics Quality Criteria Checklist and GRADE criteria were used to assess risk of bias and evidence certainty. Where possible, data were pooled using Revman. RESULTS: Twenty-six observational studies (n = 9709 participants in total) with similarly aged populations were included. Eight, seven, and eleven studies assessed malnutrition, sarcopenia, and frailty, respectively. Follow-up periods ranged from immediate to 7 years post-rehabilitation. Malnutrition was associated with discharge to a higher level of care (GRADE: very low), and worse quality of life (GRADE: very low) and physical function (GRADE: very low). Sarcopenia was associated with worse physical function (GRADE: very low) and lower rate of home discharge (OR: 0.14; 95%CI: 0.09-0.20; I2:30%; GRADE: low). Frailty was associated with increased mortality (GRADE: very low), hospital readmission (GRADE: very low), and decreased home discharge (GRADE: very low). CONCLUSION: Wasting conditions in older adults during rehabilitation admission may be associated with poorer quality of life, lower rates of home discharge, and higher rates of health service use, physical dysfunction, and mortality following discharge. Further research is needed to investigate the comparative and combined impacts, as well as the overlap of malnutrition, sarcopenia, and frailty during and after rehabilitation to guide priority screening and intervention.


Asunto(s)
Fragilidad , Desnutrición , Desnutrición Proteico-Calórica , Sarcopenia , Humanos , Anciano , Alta del Paciente , Sarcopenia/epidemiología , Sarcopenia/complicaciones , Fragilidad/epidemiología , Fragilidad/complicaciones , Desnutrición Proteico-Calórica/epidemiología , Desnutrición Proteico-Calórica/complicaciones , Calidad de Vida , Cuidados Posteriores , Desnutrición/epidemiología , Desnutrición/complicaciones
16.
bioRxiv ; 2023 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-36711835

RESUMEN

T cell immunity plays a central role in clinical outcomes of Coronavirus Infectious Disease 2019 (COVID-19). Therefore, T cell-focused vaccination or cellular immunotherapy might provide enhanced protection for immunocompromised patients. Pre-existing T cell memory recognizing SARS-CoV2 antigens antedating COVID-19 infection or vaccination, may have developed as an imprint of prior infections with endemic non-SARS human coronaviruses (hCoVs) OC43, HKU1, 229E, NL63, pathogens of "common cold". In turn, SARS-CoV2-primed T cells may recognize emerging variants or other hCoV viruses and modulate the course of subsequent hCoV infections. Cross-immunity between hCoVs and SARS-CoV2 has not been well characterized. Here, we systematically investigated T cell responses against the immunodominant SARS-CoV2 spike, nucleocapsid and membrane proteins and corresponding antigens from α- and ß-hCoVs among vaccinated, convalescent, and unexposed subjects. Broad T cell immunity against all tested SARS-CoV2 antigens emerged in COVID-19 survivors. In convalescent and in vaccinated individuals, SARS-CoV2 spike-specific T cells reliably recognized most SARS-CoV2 variants, however cross-reactivity against the omicron variant was reduced by approximately 50%. Responses against spike, nucleocapsid and membrane antigens from endemic hCoVs were more extensive in COVID-19 survivors than in unexposed subjects and displayed cross-reactivity between α- and ß-hCoVs. In some, non-SARS hCoVspecific T cells demonstrated a prominent non-reciprocal cross-reactivity with SARS-CoV2 antigens, whereas a distinct anti-SARS-CoV2 immunological repertoire emerged post-COVID-19, with relatively limited cross-recognition of non-SARS hCoVs. Based on this cross-reactivity pattern, we established a strategy for in-vitro expansion of universal anti-hCoV T cells for adoptive immunotherapy. Overall, these results have implications for the future design of universal vaccines and cell-based immune therapies against SARS- and non-SARS-CoVs.

17.
Ophthalmol Ther ; 12(2): 925-938, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36574139

RESUMEN

INTRODUCTION: This study aimed to evaluate the habitual reading distance among non-myopic children and also myopic children with undercorrection and with full correction. METHODS: This was a population-based cross-sectional study with a total of 2363 children aged 6-8 years who were recruited from the Hong Kong Children Eye Study. Cycloplegic autorefraction, subjective refraction, habitual visual acuity, and best corrected visual acuity were measured. The entire reading process (9 min) was recorded using a hidden video camera placed 5 m away from the reading desk. Reading distances were taken at 6, 7, 8, and 9 min after the child began reading and were measured using a customized computer program developed in MATLAB. The main outcome was the association of habitual reading distances with refraction status. Habitual reading distances of children were documented via video camera footage. RESULTS: The habitual reading distances of undercorrected myopic children (23.37 ± 4.31 cm) were the shortest when compared to non-myopic children (24.20 ± 4.73 cm, P = 0.002) and fully corrected myopic children (24.81 ± 5.21 cm, P < 0.001), while there was no significant difference between the last two children groups (P = 0.17). A shorter reading distance was associated with myopia (OR 1.67; 95% CI 1.11-2.51; P = 0.013) after adjusting for age, sex, height, near work time, outdoor time, and parental myopia. The association of reading distance with myopia did not hold after undercorrected myopic children were excluded (OR 0.97, 95% CI 0.55-1.73; P = 0.92). A shorter reading distance correlated with poorer vision under habitual correction (ß = - 0.003, P < 0.001). CONCLUSION: A shorter reading distance was present among undercorrected myopic children. Myopia undercorrection is not recommended as a strategy for slowing myopic progression.

18.
Prehosp Emerg Care ; 27(2): 177-183, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35254200

RESUMEN

INTRODUCTION: Recent clinical trials have failed to identify a benefit of antiarrhythmic administration during cardiac arrest. However, little is known regarding the time to administration of antiarrhythmic drugs in clinical practice or its impact on return of spontaneous circulation (ROSC). We utilized a national EMS registry to evaluate the time of drug administration and association with ROSC. METHODS: We utilized the 2018 and 2019 NEMSIS datasets, including all non-traumatic, adult 9-1-1 EMS activations for cardiac arrests with initial shockable rhythm and that received an antiarrhythmic. We calculated the time from 9-1-1 call to administration of antiarrhythmic. We excluded cases with erroneous time stamps. Stratified by initial antiarrhythmic (amiodarone and lidocaine), we created a mixed-effect logistic regression model evaluating the association between every 5-minute increase in time to antiarrhythmic and ROSC. We modeled EMS agency as a random intercept and adjusted for confounders. RESULTS: There were 449,630 adults, non-traumatic cardiac arrests identified with 11,939 meeting inclusion criteria. 9,236 received amiodarone and 1,327 received lidocaine initially. The median time in minutes to initial dose for amiodarone was 19.9 minutes (IQR 15.8-25.6) and for lidocaine was 19.5 minutes (IQR 15.2-25.4). Increasing time to initial antiarrhythmic was associated with decreased odds of ROSC for both amiodarone (aOR 0.9; 95% CI 0.9-0.94) and lidocaine (aOR 0.9; 95% CI 0.8-0.97). CONCLUSION: Time to administration of anti-arrhythmic medication varied, but most patients received the first dose of anti-arrhythmic drug more than 19 minutes after the initial 9-1-1 call. Longer time to administration of an antiarrhythmic in patients with an initial shockable rhythm was associated with decreased ROSC rates.


Asunto(s)
Amiodarona , Reanimación Cardiopulmonar , Servicios Médicos de Urgencia , Paro Cardíaco Extrahospitalario , Adulto , Humanos , Estados Unidos , Antiarrítmicos/uso terapéutico , Retorno de la Circulación Espontánea , Paro Cardíaco Extrahospitalario/tratamiento farmacológico , Amiodarona/uso terapéutico , Lidocaína/uso terapéutico
19.
Br J Ophthalmol ; 107(9): 1344-1349, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-35649695

RESUMEN

BACKGROUND/AIMS: To identify normative values and determinants for Bruch's membrane opening (BMO) and the minimum rim width of BMO (BMO-MRW) among healthy children. METHODS: A population-based cross-sectional study from the Hong Kong Children Eye Study, recruiting 1, 226 children aged 6-8 years. Spherical refractive error, axial length (AL), body mass index and intraocular pressure (IOP) were measured. The optic nerve head and the peripapillary retinal nerve fibre layer (p-RNFL) were imaged through spectral domain-optical coherence tomography, using 24 equally spaced radial B-scans. Global and sectoral BMO-MRW values, BMO area and fovea-to-BMO (FoBMO) angle were calculated. Multiple regression analysis was performed to define the determinants of BMO area and BMO-MRW in relation to demographic and ocular parameters. RESULTS: The mean values for global BMO-MRW, BMO area and FoBMO angle among children were 345.76±54.08 µm, 2.34±0.49 mm2 and -5.45±4.36°, respectively. Global and sectoral values for BMO-MRW correlated with p-RNFL thickness (r=0.11-0.35, p<0.001). After adjusting for demographic and ocular parameters, global BMO-MRW increased with age (ß=6.4, p<0.001) and greater global p-RNFL thickness (ß=1.41, p<0.001), but decreased with larger BMO area (ß=-47.46, p<0.001) and higher IOP (ß=-1.73, p<0.001). Global BMO-MRW did not associate with AL, whereas both BMO area and FoBMO angle associated with AL (ß=0.04, p=0.02 and ß=0.31, p=0.03, respectively), but not with age. CONCLUSION: We observed that BMO-MRW increases with age among children. Our results provide normative values and the determinants of BMO parameters among Chinese children.


Asunto(s)
Lámina Basal de la Coroides , Células Ganglionares de la Retina , Humanos , Niño , Hong Kong/epidemiología , Estudios Transversales , Fibras Nerviosas , Presión Intraocular , Tomografía de Coherencia Óptica/métodos
20.
J Am Coll Emerg Physicians Open ; 3(6): e12849, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36425644

RESUMEN

Objective: To determine whether emergency physician productivity is associated with the risk of medical errors. Methods: We retrospectively analyzed quality assurance (QA) and billing data over 3 years at 2 urban emergency departments. Faculty physicians working 400 hours or more at either site were included. We measured physician years of experience, age, gender, patients seen per hour (PPH), and relative value units billed per hour (RVU/h). From an established QA process, we obtained adjudicated medical errors to calculate rates of medical errors per 1000 patients seen as the outcome. We discretized numeric variables and used Kruskal-Wallis testing to examine relationships between independent variables and rates of medical errors. Results: We included data for 39 physicians at site A and 42 at site B. The median rate of errors per 1000 patients was 1.6 (interquartile range [IQR], 1.1-1.9) at site A and 3.3 (IQR, 2.4-3.9) at site B. At site A, RVU/h was associated with error rates (P = 0.03), with medians of 2.0, 1.2, 1.7, and 1.3 errors per 1000 patients, from slowest to fastest quartiles. At site B, PPH was associated with error rates (P < 0.01), with medians of 3.9, 3.7, 2.4, and 2.7 errors per 1000 patients, from slowest to fastest quartiles. There was no significant relationship between error rates and PPH at site A or RVU/h at site B. Conclusions: Rates of medical errors were associated with 1 metric of physician productivity at each site, with higher error rates seen among physicians with slower productivity.

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