The piper at the gates of brain: A systematic review of surface modification strategies on lipid nanoparticles to overcome the Blood-Brain-Barrier.

The Blood-Brain Barrier (BBB) significantly impedes drug delivery to the central nervous system. Nanotechnology, especially surface-functionalized lipid nanoparticles, offers innovative approaches to overcome this barrier. However, choosing an effective functionalization strategy is challenging due to the lack of detailed comparative analysis in current literature. Our systematic review examined various functionalization strategies and their impact on BBB permeability from 2041 identified articles, of which 80 were included for data extraction. Peptides were the most common modification (18) followed by mixed strategies (12) proteins (9), antibodies (7), and other strategies (8). Interestingly, 26 studies showed BBB penetration with unmodified or modified nanoparticles using commonly applied strategies such as PEGylation or surfactant addition. Statistical analysis across 42 studies showed correlation between higher in vivo permeation improvements and nanoparticle type, size, and functionalization category. The highest ratios were found for nanostructured lipid carriers or biomimetic systems, in studies with particle sizes under 150 nm, and in those applying mixed functionalization strategies. The interstudy heterogeneity we observed highlights the importance of adopting standardized evaluation protocols to enhance comparability. Our systematic review aims to provide a comparative insight and identify future research directions in the development of more effective lipid nanoparticle systems for drug delivery to the brain to help improve the treatment of neurological and psychiatric disorders and brain tumours.

Impact of treatment adherence and inhalation technique on asthma outcomes of pediatric patients: a longitudinal study.

Introduction: We aimed to evaluate the longitudinal relationships, both at between- and within-person levels, that adherence to inhaled corticosteroid-based maintenance treatment and inhalation technique present with symptom control, exacerbations, and health-related quality of life (HRQoL) in children and adolescents with asthma. Methods: Participants (6-14 years old) from the ARCA (Asthma Research in Children and Adolescents) cohort-a prospective, multicenter, observational study (NCT04480242)-were followed for a period from 6 months to 5 years via computer-assisted telephone interviews and a smartphone application. The Medication Intake Survey-Asthma (MIS-A) was administered to assess the implementation stage of adherence, and the Inhalation Technique Questionnaire (InTeQ) was used to assess the five key steps when using an inhaler. Symptom control was measured with the Asthma Control Questionnaire (ACQ), and HRQL was measured with the EQ-5D and the Patient-Reported Outcomes Measurement Information System-Pediatric Asthma Impact Scale (PROMIS-PAIS). Multilevel longitudinal mixed models were constructed separately with symptom control, exacerbation occurrence, EQ-5D, and PROMIS-PAIS as the dependent variables. Results: Of the 360 participants enrolled, 303 (1,203 interviews) were included in the symptom control and exacerbation analyses, 265 (732) in the EQ-5D, and 215 (617) in the PROMIS-PAIS. Around 60% of participants were male subjects, and most of them underwent maintenance treatment with inhaled corticosteroids plus long-acting ß-agonists in a fixed dose (73.3%). Within-person variability was 83.6% for asthma control, 98.6% for exacerbations, 36.4% for EQ-5D, and 49.1% for PROMIS-PAIS. At the within-person level, patients with higher adherence had better symptom control (p = 0.002) and HRQoL over time (p = 0.016). Patients with a better inhalation technique reported worse HRQoL simultaneously (p = 0.012), but they showed better HRQoL in future assessments (p = 0.012). The frequency of reliever use was associated with symptom control (p < 0.001), exacerbation occurrence (p < 0.001), and HRQoL (p = 0.042); and boys were more likely to present better symptom control and HRQoL than girls. Conclusion: Our results confirm longitudinal associations at the within-person level of the two indicators of quality use of inhalers: for adherence to maintenance treatment with symptom control and HRQoL, and for the inhalation technique with HRQoL. Although treatment adherence was shown to be excellent, a third of the participants reported a suboptimal inhalation technique, highlighting the need for actions for improving asthma management of the pediatric population.

Montelukast in paediatric asthma and allergic rhinitis: a systematic review and meta-analysis.

BACKGROUND: We aim to assess the impact of montelukast on paediatric patients with asthma/allergic rhinitis, measured using patient-reported outcome measures, compared with other treatments or placebo. METHODS: Protocol registration CRD42020216098 (www.crd.york.ac.uk/PROSPERO). MEDLINE and Embase databases were used to conduct the search. Two authors independently selected studies and extracted data, and a third reviewer resolved discrepancies. Meta-analyses were constructed to estimate the standardised mean difference (SMD) using a random-effects model. RESULTS: Out of 3937 articles identified, 49 studies met the inclusion criteria, mostly randomised clinical trials (sample sizes: 21-689 patients). The SMD of change pooled estimators for the global, mental and physical domains of health-related quality of life were not statistically significant. For daytime and night-time symptoms scores, the SMD (95% CI) was in favour of inhaled corticosteroids (-0.12, -0.20- -0.05 and -0.23, -0.41- -0.06, respectively). The pooled estimator for global asthma symptoms was better for montelukast when compared with placebo (0.90, 0.44-1.36). CONCLUSIONS: The synthesis of the available evidence suggests that, in children and adolescents, montelukast was effective in controlling asthma symptoms when compared with placebo, but inhaled corticosteroids were superior in controlling symptoms, especially at night-time. These findings of our systematic review concur with current guidelines for asthma treatment.

Measurement properties of the EQ-5D-Y administered through a smartphone app in children with asthma: a longitudinal questionnaire study.

BACKGROUND: Asthma impacts children's physical, emotional, and psychosocial Health-Related Quality of Life (HRQL). The EQ-5D-Y is a generic econometric instrument developed to measure HRQL in children. OBJECTIVE: Evaluation of feasibility, validity, reliability, and responsiveness of EQ-5D-Y descriptive system and utility index to allow the assessment of HRQL in children with asthma, aged 8-11 years (self-response version) or under 8 years old (proxy-response version). METHODS: We used data from baseline to 10 months of follow-up of an observational, prospective study of children with persistent asthma recruited by pediatricians in Spain (2018-2020). HRQL instruments were administered through a smartphone application: ARCA app. The EQ-5D-Y is composed of a 5-dimension descriptive system, a utility index ranging from 1 to - 0.5392, and a general health visual analogue scale (EQ-VAS). The Pediatric Asthma Impact Scale (PROMIS-PAIS) includes 8 items, providing a raw score. Construct validity hypotheses were stated a priori, and evaluated following two approaches, multitrait-multimethod matrix and known groups' comparisons. Reliability and responsiveness subsamples were defined by stability or change in EQ-VAS and the Asthma Control Questionnaire (ACQ), to estimate the intraclass correlation coefficient (ICC) and the magnitude of change over time. RESULTS: The EQ-5D-Y was completed at baseline for 119 children (81 self-responded and 38 through proxy response), with a mean age of 9.1 (1.7) years. Mean (SD) of the EQ-5D-Y utility index was 0.93 (0.11), with ceiling and floor effects of 60.3% and 0%, respectively. Multitrait-multimethod matrix confirmed the associations previously hypothesized for the EQ-5D-Y utility index [moderate with PROMIS-PAIS (0.38) and weak with ACQ (0.28)], and for the EQ-5D-Y dimension "problems doing usual activities" [moderate with the ACQ item (0.35) and weak with the PROMIS-PAIS item (0.17)]. Statistically significant differences were found in the EQ-5D-Y between groups defined by asthma control, reliever inhalers use, and second-hand smoke exposure, with mostly moderate effect sizes (0.45-0.75). The ICC of the EQ-5D-Y utility index in the stable subsamples was high (0.81 and 0.79); and responsiveness subsamples presented a moderate to large magnitude of change (0.68 and 0.78), though without statistical significance. CONCLUSIONS: These results support the use of the EQ-5D-Y as a feasible, valid, and reliable instrument for evaluating HRQL in children with persistent asthma. Further studies are needed on the responsiveness of the EQ-5D-Y in this population.

The Inhaler Technique Questionnaire (InTeQ): Development and Validation of a Brief Patient-Reported Measure.

There is a need for instruments designed for patients with asthma to self-report their performance of inhaling steps. We aimed to develop an accessible and easy-to-use patient-reported tool for inhaler technique assessment, which could also serve as a training and monitoring resource for any type of inhaler device, and to evaluate its feasibility, validity, and reliability in adults with asthma. The development was based on literature review and pilot testing with clinicians and patients. The Inhaler Technique Questionnaire (InTeQ) asks about the frequency of performing five steps when using inhalers (on a five-point Likert scale). We analyzed data from adults with persistent asthma (n = 361). We examined the measurement model using Mokken scaling analysis, construct validity by assessing hypotheses on expected discrimination among known groups, and reliability based on internal consistency and reproducibility. Means of the InTeQ items were in the range of 0.23-1.61, and coefficients of homogeneity were above the cutoff point, demonstrating the unidimensionality of the scale. Known groups' global score differences were statistically significant between patients reporting having "Discussed in detail" or having "Not discussed/Only in general" the inhaler technique with their healthcare providers (p = 0.023). The Cronbach's alpha coefficient was 0.716, and the intraclass correlation coefficient was 0.775. The InTeQ is a feasible, valid, and reliable instrument for self-reporting inhaler technique on any type of device.

Alfabetización en salud y necesidades para el etiquetado de medicamentos identificadas en población indígena de Alto Telire del Área de Salud Talamanca, Costa Rica / Health literacy and drug labeling needs identified in indigenous population of Alto Telire, Talamanca Health Area, Costa Rica

Resumen Introducción: Conocer los aspectos sociodemográficos de la alfabetización en salud y las necesidades relacionadas con el etiquetado de medicamentos permite crear las bases para canalizar las acciones de los profesionales para la mejora de la atención sanitaria que se brinda a poblaciones vulnerables. Metodología: A partir de ello, se realizó una investigación de tipo cuantitativa, observacional, con un alcance exploratorio que abordó la población indígena residente en el sector de Alto Telire, localizado en la provincia de Limón, Costa Rica. Esta se caracteriza por su aislamiento y baja escolaridad. En este artículo se presenta la caracterización de aspectos sociodemográficos y de alfabetización en salud, así como la identificación de necesidades relacionadas con el etiquetado de medicamentos para un grupo de pacientes de la etnia cabécar, atendidos en el mes de mayo del 2018 por personeros de la Caja Costarricense del Seguro Social (CCSS). Los resultados se obtuvieron mediante la realización de entrevistas directas a pacientes. Resultados: Los resultados obtenidos del estudio destacan que el 57 % de la población participante es del sexo femenino, con edades entre los 18 y 45 años. Además, el nulo acceso a la educación que tuvo la población hasta el año 2009 explica por qué el 70,42 % de las personas participantes no cuentan con ningún tipo de escolaridad, lo cual está relacionado con que el 100 % presentaran un bajo nivel de alfabetización en salud. Por otro lado, las principales formas de las personas participantes de reconocer sus medicamentos es por el nombre, uso y características físicas, siendo el uso que se le da al medicamento la principal manera de reconocerle. Conclusiones: La población incluida en este estudio cuenta con baja escolaridad y un nivel inadecuado de alfabetización para la salud. Las necesidades con respecto al etiquetado de medicamentos están relacionadas principalmente con el motivo de uso y la persona que lo debe utilizar. Adicionalmente, el etiquetado de los medicamentos es la única fuente de información que tiene esta población al alcance para utilizar racionalmente los medicamentos.

Abstract Introduction: The understanding of sociodemographic characteristics, health literacy, and drug labeling needs allows to create the bases for professionals to target actions for the improvement of healthcare among vulnerable populations. Methodology: From this, a quantitative, observational research was carried out, with an exploratory scope; that addressed the indigenous population residing in the Alto Telire sector, located in the province of Limón, Costa Rica, which is characterized by its isolation and low schooling. This article presents the characterization of sociodemographic aspects, health literacy, as well as the identification of needs related to the labeling of medicines for a group of patients of the Cabécar ethnic group, attended in May 2018 by representatives of the Costa Rican Social Security Fund (CCSS). The results were obtained through direct interviews with patients. Results: The results obtained from the study highlight that 57% of the participating population is female, with ages between 18 and 45 years. Furthermore, the lack of access to education that the population had until 2009 explains why 70 42% of the participants do not have any type of education, which is related to the fact that a 100% have low health literacy level. On the other hand, participants recognize their medications principally by the name, use and physical characteristics, being the use given to the medication the main way to recognize it. Conclusions:The population included in this study has low education and an inadequate level of health literacy. Drug labeling needs are primarily related to indications and the person intended to use it. Furthermore, drug labels are the only source of information available to this population in order to rationally use their treatments.

Hospital Mexico's preoperative antibiotic prophylaxis protocol for orthopedic patients: a compliance analysis.

OBJECTIVE: To analyze compliance with a prescribed pre-surgical antibiotic prophylaxis protocol established by the Antimicrobial Stewardship Program team and the Orthopedics Department of Hospital Mexico, a public hospital located in Costa Rica, from February to March 2019. No assessments of compliance with the protocol had been conducted since its introduction in 2018, nor had variations in surgical site infection rates been determined. METHOD: This is a retrospective observational study that extended from February 1st to March 31st, 2019. We identified patients hospitalized during the study period in the hospital's Orthopedics Department. We reviewed each patient's medical record to record their prescribed antibiotic prophylaxis. Following an analysis of the overall compliance with the protocol, we made an estimation of the surgical site infection rate as well as a descriptive analysis of the studied population. RESULTS: The study included 110 clinical records. The most frequently prescribed antibiotics were clindamycin and gentamicin. Compliance with the protocol ranged between 89.1% and 100% across the different criteria, except for dosing appropriateness and prescription of antibiotics at discharge (14.3% and 65.8%, respectively). The most  common non compliance factor was gentamicin´s dosing. The surgical site infection rate was 5%. CONCLUSIONS: The preoperative antibiotic prophylaxis protocol established between the Antimicrobial Stewardship Program team and the Orthopedic Department reduced the length of exposure to postoperative antibiotics to only 24 hours and enjoyed widespread acceptance and a high compliance rate. However, compliance with some criteria must be improved, such as dosing appropriateness and prescription of antibiotics at discharge. Involvement of the pharmacist is vital for the compliance with and auditing of these types of protocols as pharmacists are uniquely positioned to ensure that high-quality antibiotic prophylaxis is provided in all surgical procedures that require it.

Objetivo: Analizar el cumplimiento en la prescripción de la profilaxis antibiótica prequirúrgica, según el protocolo establecido por el Programa de Optimización de Antibióticos y el Servicio de Ortopedia del Hospital México, Caja Costarricense del Seguro Social, ubicado en San José, Costa Rica, de febrero a marzo de 2019. Desde la instauración del protocolo en 2018 no se ha realizado una evaluación de su cumplimiento ni se ha determinado la tasa de infección del sitio quirúrgico.Método: Estudio observacional retrospectivo; se identificaron los pacientes hospitalizados en el Servicio de Ortopedia desde el 1 de febrero al 31 de marzo de 2019. Se accedió al expediente digital de cada paciente, se caracterizó la profilaxis antibiótica prescrita y se analizó el cumplimiento según el protocolo vigente. Se estimó la tasa de infección de sitio quirúrgico. Se realizó un análisis descriptivo de la población.Resultados: El estudio incluyó 110 expedientes clínicos. Los antibióticos más prescritos fueron clindamicina y gentamicina de manera  concomitante. El cumplimiento de la prescripción de profilaxis antibiótica osciló entre 89,1% y 100% para los criterios considerados en el protocolo, exceptuando dosis y antibiótico al alta (14,3 y 65,8%, respectivamente).  El criterio de incumplimiento más frecuente fue la dosis de gentamicina. La tasa de infección de sitio quirúrgico fue del 5%.Conclusiones: El protocolo de profilaxis antibiótica prequirúrgica establecido entre el equipo Programa de Optimización de Antibióticos y el Servicio de Ortopedia disminuyó el tiempo de exposición a antibióticos postoperatorios a únicamente 24 horas, y tiene una aceptación y cumplimiento positivo. Sin embargo, deben mejorarse puntos como la prescripción adecuada de la dosis y la no prescripción de antibiótico al egreso. La participación del farmacéutico es vital para el cumplimiento y auditoría de este tipo de protocolos, de modo que la calidad de la profilaxis antibiótica sea garantizada en todos los procedimientos quirúrgicos que así lo requieran.