RESUMEN
OBJECTIVE: Models of psychometric screening to identify individuals with neurodevelopmental disabilities (NDDs) have had limited success. In Aotearoa/New Zealand, routine developmental surveillance of preschool children is undertaken using the Before School Check (B4SC), which includes psychometric and physical health screening instruments. This study aimed to determine whether combining multiple screening measures could improve the prediction of NDDs. METHODS: Linked administrative health data were used to identify NDDs, including attention deficit hyperactivity disorder, autism spectrum disorder and intellectual disability, within a multi-year national cohort of children who undertook the B4SC. Cox proportional hazards models, with different combinations of potential predictors, were used to predict onset of a NDD. Harrell's c-statistic for composite models were compared with a model representing recommended cutoff psychometric scores for referral in New Zealand. RESULTS: Data were examined for 287,754 children, and NDDs were identified in 10,953 (3.8%). The best-performing composite model combining the Strengths and Difficulties Questionnaire, the Parental Evaluation of Developmental Status, vision screening and biological sex had 'excellent' predictive power (C-statistic: 0.83) compared with existing referral pathways which had 'poor' predictive power (C-statistic: 0.68). In addition, the composite model was able to improve the sensitivity of NDD diagnosis detection by 13% without any reduction in specificity. CONCLUSIONS: Combination of B4SC screening measures using composite modelling could lead to significantly improved identification of preschool children with NDDs when compared with surveillance that rely on individual psychometric test results alone. This may optimise access to academic, personal and family support for children with NDDs.
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Trastorno por Déficit de Atención con Hiperactividad , Trastorno del Espectro Autista , Humanos , Preescolar , Trastorno del Espectro Autista/diagnóstico , Trastorno del Espectro Autista/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Instituciones Académicas , Escolaridad , Nueva Zelanda/epidemiologíaRESUMEN
Importance: Autistic students often experience poor educational outcomes that have implications for later life, including unemployment, interactions with the criminal justice system, increased risk for substance abuse, and low socioeconomic status. Improving educational outcomes is critical for ensuring that autistic young people can reach their potential. Objective: To quantify differences in suspension rates between autistic and nonautistic students and to assess whether high-need education-based funding for autistic students is associated with reduced rates of school suspension. Design, Setting, and Participants: This national cohort study used linked health and education data from New Zealand's Integrated Data Infrastructure. Data were obtained for students aged 5 to 16 years from January 1 to December 31, 2018, and analyzed July 7, 2021, to January 1, 2022. A novel case identification method was used to identify autistic students. Exposures: High-need education-based funding (Ongoing Resourcing Scheme [ORS]) obtained before 2019. Main Outcomes and Measures: Rates of suspension from school. Crude and adjusted analyses of the association between suspension rates and autism among the full population with adjustment made for sociodemographic characteristics (sex, age, ethnicity, deprivation, and urban or rural profile of residence) were conducted using complete-case, 2-level random intercept logistic multivariable regressions. To assess the association between ORS funding and suspension, analysis was restricted to autistic students. Results: Of the 736â¯911 students in the study population, 9741 (1.3%) were identified as autistic (median [SD] age, 10 [3.2] years; 7710 [79.1%] boys), and 727â¯170 (98.7%) as nonautistic (median [SD] age, 10 [3.4] years; 369â¯777 [50.9%] boys). School suspension was experienced by 504 autistic students (5.2%) and 13â¯845 nonautistic students (1.9%). After adjustment for demographic characteristics, autistic students had significantly higher odds of suspension than their nonautistic peers (adjusted odds ratio, 2.81; 95% CI, 2.55-3.11). Of the 9741 autistic students, 2895 (29.7%) received high-need education-based (ORS) funding. Suspensions were experienced by 57 autistic students (2.0%) with high-need funding and 447 autistic students (6.5%) without high-need funding. After adjustment for demographic characteristics, co-occurring conditions, and level of disability support need, autistic students with high-need funding had significantly lower odds of suspension than autistic students without high-need funding (adjusted odds ratio, 0.29; 95% CI, 0.21-0.40). Conclusions and Relevance: In this cohort study, the findings of disparities in suspension rates between autistic and nonautistic students underscore the challenges faced in providing inclusive education for all young people, regardless of disability status. This study found that high-need funding was associated with reduced suspension rates among autistic students, suggesting that if appropriate supports are afforded to autistic students, a more inclusive education can be provided.
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Trastorno Autístico , Adolescente , Trastorno Autístico/epidemiología , Niño , Estudios de Cohortes , Femenino , Humanos , Masculino , Nueva Zelanda/epidemiología , Instituciones Académicas , EstudiantesRESUMEN
The availability of a real-time assay to experimentally investigate the release of encapsulated proteins would be beneficial given the interest in the use of liposomes as a drug delivery vehicle. Although simple assays for small molecular weight substances exist, assays to evaluate macromolecules do not. Here we describe a method that detects the release of model macromolecules from liposomes in real time. The assay employs the intermolecular distance-dependent phenomenon of fluorescence resonance energy transfer (FRET) between the fluorophore donor, fluorescein (FITC), and fluorescent quencher, QSY® 9. The macromolecular species were conjugated to the markers fluorescein (44kDa dextran) and QSY® 9 (67 kDa bovine serum albumin, BSA). Following confirmation of quenching between FITC-Dex and QSY® 9-BSA, liposomes were loaded with the macromolecular markers and subjected to various treatments (high-pressure extrusion and Triton X solubilisation) to cause release from liposomes. An increase in FITC fluorescence was observed when liposomes were subjected to extrusion cycles. Surprisingly, the addition of Triton X did not cause an increase in fluorescence probably because the FRET pair became associated with mixed micelles. This assay method should be useful in studies to investigate the mechanisms by which macromolecules are released from liposomes, particularly when liposomes are exposed to release-triggers (eg, temperature change, pH change, ultrasound). Such understanding will underpin the formulation of triggered liposomal delivery systems for macromolecules.
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Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Liposomas/química , Sustancias Macromoleculares/análisis , Animales , Dextranos/química , Dextranos/metabolismo , Fluoresceína/química , Fluoresceína/metabolismo , Transferencia Resonante de Energía de Fluorescencia , Técnicas In Vitro , Piperidinas/química , Piperidinas/metabolismo , Pirrolidinas/química , Pirrolidinas/metabolismo , Albúmina Sérica Bovina/química , Albúmina Sérica Bovina/metabolismo , Xantenos/química , Xantenos/metabolismoRESUMEN
CONTEXT: Triggering drug release from delivery vehicles with ultrasound has potential applications in targeted drug delivery. It was hypothesized that the addition of bile salts would increase the sensitivity of liposomes to ultrasound through creation of defects. OBJECTIVE: The aim of this study was to investigate whether incorporating bile salts into liposomes would lead to differential effects on their response to low and high frequency ultrasound. MATERIALS AND METHODS: Cholate, chenodeoxycholate, ursodeoxycholate, glycocholate and taurocholate were the selected bile salts. Response to ultrasound was characterized by measuring the release of carboxyfluorescein (CF). RESULTS: At 30 kHz ultrasound, taurocholate containing liposomes were most responsive and released 70% (± 2) CF after 30 seconds of sonication. Compared to this, liposomes that did not contain bile salts released just 7% (± 2). At 1.1 MHz ultrasound, all liposome formulations were unresponsive. To increase the response of liposomes at 1.1 MHz ultrasound, a combination of membrane destabilizers were added to DSPC liposomes. DOPE, a hexagonal phase lipid was used in combination with taurocholate. Surprisingly, liposomes containing DOPE and taurocholate were more resistant to 1.1 MHz ultrasound than ones containing only DOPE. DISCUSSION: This suggests that the sensitivity of liposomes towards ultrasound may not simply be defined by a single membrane component but instead depends on the interaction between constituting lipid components. Furthermore, strategies other than membrane destabilization may be required to sensitize liposomes towards high frequency ultrasound. CONCLUSION: Bile salts may be used to increase or decrease the sensitivity of liposomes to low frequency ultrasound.
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Ácidos y Sales Biliares/química , Liposomas/química , Ondas Ultrasónicas , Fluoresceínas/análisisRESUMEN
Delivering drugs to the brain is challenging given the selective permeability of the blood brain barrier (BBB). Targeted colloidal carriers containing drug payloads offer some promise for enhanced and perhaps selective delivery to brain. This review examines the recent literature and identifies issues to be addressed if these systems are to be rationally designed. These include opsonization of nanoparticles and off-target clearance; the cerebral microvasculature, flow of nanoparticles in capillaries and binding to the capillary wall; and transcytosis. Capillary architecture, blood flow and BBB permeability are affected by disease and age and there are species differences. These complexities caution against making extravagant claims for a particular nanosystem but they also highlight the rich opportunities and need for critical research in this field.