Allergen immunotherapy for atopic dermatitis: Systematic review and meta-analysis of benefits and harms.

BACKGROUND: Atopic dermatitis (AD, eczema) is driven by a combination of skin barrier defects, immune dysregulation, and extrinsic stimuli such as allergens, irritants, and microbes. The role of environmental allergens (aeroallergens) in triggering AD remains unclear. OBJECTIVE: We systematically synthesized evidence regarding the benefits and harms of allergen immunotherapy (AIT) for AD. METHODS: As part of the 2022 American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters AD Guideline update, we searched the MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, Global Resource for Eczema Trials, and Web of Science databases from inception to December 2021 for randomized controlled trials comparing subcutaneous immunotherapy (SCIT), sublingual immunotherapy (SLIT), and/or no AIT (placebo or standard care) for guideline panel-defined patient-important outcomes: AD severity, itch, AD-related quality of life (QoL), flares, and adverse events. Raters independently screened, extracted data, and assessed risk of bias in duplicate. We synthesized intervention effects using frequentist and Bayesian random-effects models. The GRADE approach determined the quality of evidence. RESULTS: Twenty-three randomized controlled trials including 1957 adult and pediatric patients sensitized primarily to house dust mite showed that add-on SCIT and SLIT have similar relative and absolute effects and likely result in important improvements in AD severity, defined as a 50% reduction in SCORing Atopic Dermatitis (risk ratio [95% confidence interval] 1.53 [1.31-1.78]; 26% vs 40%, absolute difference 14%) and QoL, defined as an improvement in Dermatology Life Quality Index by 4 points or more (risk ratio [95% confidence interval] 1.44 [1.03-2.01]; 39% vs 56%, absolute difference 17%; both outcomes moderate certainty). Both routes of AIT increased adverse events (risk ratio [95% confidence interval] 1.61 [1.44-1.79]; 66% with SCIT vs 41% with placebo; 13% with SLIT vs 8% with placebo; high certainty). AIT's effect on sleep disturbance and eczema flares was very uncertain. Subgroup and sensitivity analyses were consistent with the main findings. CONCLUSIONS: SCIT and SLIT to aeroallergens, particularly house dust mite, can similarly and importantly improve AD severity and QoL. SCIT increases adverse effects more than SLIT. These findings support a multidisciplinary and shared decision-making approach to optimally managing AD.

The implementation of multiple interprofessional integrated modules by health sciences faculty in Chile.

Multiple interprofessional integrated modules (MIIM) 1 and 2 are two required, cross-curricular courses developed by a team of health professions faculty, as well as experts in education, within the Faculty of Medicine of the University of Chile. MIIM 1 focused on virtual cases requiring team decision-making in real time. MIIM 2 focused on a team-based community project. The evaluation of MIIM included student, teacher, and coordinator perspectives. To explore the perceptions of this interprofessional experience quantitative data in the form of standardised course evaluations regarding teaching methodology, interpersonal relations and the course organisation and logistics were gathered. In addition, qualitative perceptions were collected from student focus groups and meetings with tutors and coordinators. Between 2010 and 2014, 881 students enrolled in MIIM. Their evaluation scores rated interpersonal relations most highly, followed by organisation and logistics, and then teaching methodology. A key result was the learning related to interprofessional team work by the teaching coordinators, as well as the participating faculty. The strengths of this experience included student integration and construction of new knowledge, skill development in making decisions, and collective self-learning. Challenges included additional time management and tutors' role. This work requires valuation of an alternative way of learning, which is critical for the performance of future health professionals.

S-Adenosyl-l-methionine restores brain mitochondrial membrane fluidity and GSH content improving Niemann-Pick type C disease.

Niemann-Pick type C (NPC) disease is a lysosomal storage disorder characterized by impaired motor coordination due to neurological defects and cerebellar dysfunction caused by the accumulation of cholesterol in endolysosomes. Besides the increase in lysosomal cholesterol, mitochondria are also enriched in cholesterol, which leads to decreased membrane fluidity, impaired mitochondrial function and loss of GSH, and has been shown to contribute to the progression of NPC disease. S-Adenosyl-l-methionine (SAM) regulates membrane physical properties through the generation of phosphatidylcholine (PC) from phosphatidylethanolamine (PE) methylation and functions as a GSH precursor by providing cysteine in the transsulfuration pathway. However, the role of SAM in NPC disease has not been investigated. Here we report that Npc1-/- mice exhibit decreased brain SAM levels but unchanged S-adenosyl-l-homocysteine content and lower expression of Mat2a. Brain mitochondria from Npc1-/- mice display decreased mitochondrial GSH levels and liquid chromatography-high resolution mass spectrometry analysis reveal a lower PC/PE ratio in mitochondria, contributing to increased mitochondrial membrane order. In vivo treatment of Npc1-/- mice with SAM restores SAM levels in mitochondria, resulting in increased PC/PE ratio, mitochondrial membrane fluidity and subsequent replenishment of mitochondrial GSH levels. In vivo SAM treatment improves the decline of locomotor activity, increases Purkinje cell survival in the cerebellum and extends the average and maximal life spam of Npc1-/- mice. These findings identify SAM as a potential therapeutic approach for the treatment of NPC disease.

Online interprofessional education materials through a community learning program during the COVID 19 pandemic in Chile.

This article aims to share the online collaborative experience of interprofessional teamwork among healthcare undergraduate students based on community learning during the coronavirus disease 2019 (COVID-19) pandemic in Chile. This experience took place in 48 different communities in Chile from November 10, 2020 to January 12, 2021. It was a way of responding to the health education needs of the community when the entire Chilean population was in confinement. Students managed to adapt to the COVID-19 pandemic despite the challenges, including internet connectivity problems and the limited time available to do the work. The educational programs and videos shared in this article will be helpful for other interprofessional health educators to implement the same kind of program.

Implementation challenges to patient safety in Guatemala: a mixed methods evaluation.

BACKGROUND: Little is known about factors affecting implementation of patient safety programmes in low and middle-income countries. The goal of our study was to evaluate the implementation of a patient safety programme for paediatric care in Guatemala. METHODS: We used a mixed methods design to examine the implementation of a patient safety programme across 11 paediatric units at the Roosevelt Hospital in Guatemala. The safety programme included: (1) tools to measure and foster safety culture, (2) education of patient safety, (3) local leadership engagement, (4) safety event reporting systems, and (5) quality improvement interventions. Key informant staff (n=82) participated in qualitative interviews and quantitative surveys to identify implementation challenges early during programme deployment from May to July 2018, with follow-up focus group discussions in two units 1 year later to identify opportunities for programme modification. Data were analysed using thematic analysis, and integrated using triangulation, complementarity and expansion to identify emerging themes using the Consolidated Framework for Implementation Research. Salience levels were reported according to coding frequency, with valence levels measured to characterise the degree to which each construct impacted implementation. RESULTS: We found several facilitators to safety programme implementation, including high staff receptivity, orientation towards patient-centredness and a desire for protocols. Key barriers included competing clinical demands, lack of knowledge about patient safety, limited governance, human factors and poor organisational incentives. Modifications included use of tools for staff recognition, integration of education into error reporting mechanisms and designation of trained champions to lead unit-based safety interventions. CONCLUSION: Implementation of safety programmes in low-resource settings requires recognition of facilitators such as staff receptivity and patient-centredness as well as barriers such as lack of training in patient safety and poor organisational incentives. Embedding an implementation analysis during programme deployment allows for programme modification to enhance successful implementation.

Interprofessional health education teacher training at the University of Chile.

The first interprofessional course that included students in the 8 undergraduate health programs at the Faculty of Medicine of the University of Chile was implemented in 2015. For the 700 students, 35 teachers were trained as facilitators. The use of several strategies to train facilitators in interprofessional health education, such as working in small groups, role-playing, case analysis, personal development workshops with experts' participation, teamwork skills, feedback, videos, and reading articles, proved to be helpful. Facilitators highlighted the use of syllabi as a fundamental tool for teaching and coordination. This guide describes the experience of interprofessional health education teacher training from 2015 to 2019, highlighting the following lessons learned: the importance of support from university authorities, raising faculty awareness about interprofessional health education and collaborative practice, creating a teachers' coordination team including representatives from all health programs, and ongoing monitoring and feedback from participants.

Macrophages From Subjects With Isolated GH/IGF-I Deficiency Due to a GHRH Receptor Gene Mutation Are Less Prone to Infection by Leishmania amazonensis.

Isolated growth hormone (GH) deficiency (IGHD) affects approximately 1 in 4,000 to 1 in 10,000 individuals worldwide. We have previously described a large cohort of subjects with IGHD due to a homozygous mutation in the GH releasing hormone (GHRH) receptor gene. These subjects exhibit throughout the life very low levels of GH and its principal mediator, the Insulin Growth Factor-I (IGF-I). The facilitating role of IGF-I in the infection of mouse macrophages by different Leishmania strains is well-known. Nevertheless, the role of IGF-I in Leishmania infection of human macrophages has not been studied. This study aimed to evaluate the behavior of Leishmania infection in vitro in macrophages from untreated IGHD subjects. To this end, blood samples were collected from 14 IGHD individuals and 14 age and sex-matched healthy controls. Monocytes were isolated and derived into macrophages and infected with a strain of Leishmania amazonensis. In addition, IGF-I was added to culture medium to evaluate its effect on the infection. Cytokines were measured in the culture supernatants. We found that macrophages from IGHD subjects were less prone to Leishmania infection compared to GH sufficient controls. Both inflammatory and anti-inflammatory cytokines increase only in the supernatants of the control macrophages. Addition of IGF-I to the culture medium increased infection rates. In conclusion, we demonstrated that IGF-I is crucial for Leishmania infection of human macrophages.

Mycobacterium leprae Recombinant Antigen Induces High Expression of Multifunction T Lymphocytes and Is Promising as a Specific Vaccine for Leprosy.

Leprosy is a chronic disease caused by M. leprae infection that can cause severe neurological complications and physical disabilities. A leprosy-specific vaccine would be an important component within control programs but is still lacking. Given that multifunctional CD4 T cells [i.e., those capable of simultaneously secreting combinations of interferon (IFN)-γ, interleukin (IL)-2, and tumor necrosis factor (TNF)] have now been implicated in the protective response to several infections, we tested the hypothesis if a recombinant M. leprae antigen-specific multifunctional T cells differed between leprosy patients and their healthy contacts. We used whole blood assays and peripheral blood mononuclear cells to characterize the antigen-specific T cell responses of 39 paucibacillary (PB) and 17 multibacillary (MB) leprosy patients and 31 healthy household contacts (HHC). Cells were incubated with either crude mycobacterial extracts (M. leprae cell sonicate-MLCS) and purified protein derivative (PPD) or recombinant ML2028 protein, the homolog of M. tuberculosis Ag85B. Multiplex assay revealed antigen-specific production of IFN-γ and IL-2 from cells of HHC and PB, confirming a Th1 bias within these individuals. Multiparameter flow cytometry then revealed that the population of multifunctional ML2028-specific T cells observed in HHC was larger than that observed in PB patients. Taken together, our data suggest that these multifunctional antigen-specific T cells provide a more effective response against M. leprae infection that prevents the development of leprosy. These data further our understanding of M. leprae infection/leprosy and are instructive for vaccine development.

Infectious diseases and immunological responses in adult subjects with lifetime untreated, congenital GH deficiency.

Growth hormone is important for the development and function of the immune system, but there is controversy on whether growth hormone deficiency is associated to immune disorders. A model of isolated growth hormone deficiency may clarify if the lack of growth hormone is associated with increased susceptibility to infections, or with an altered responsiveness of the immune system. We have studied the frequency of infectious diseases and the immune function in adults with congenital, untreated isolated growth hormone deficiency. In a cross-sectional study, 35 adults with isolated growth hormone deficiency due to a homozygous mutation in the growth hormone releasing hormone receptor gene and 31 controls were submitted to a clinical questionnaire, physical examination serology for tripanosomiasis, leishmaniasis, HIV, tetanus, hepatitis B and C, and serum total immunoglobulin G, M, E and A measurement. The immune response was evaluated in a subset of these subjects by skin tests and response to vaccination for hepatitis B, tetanus, and bacillus Calmette-Guérin. There was no difference between the groups in history of infectious diseases and baseline serology. Isolated growth hormone deficiency subjects had lower total IgG, but within normal range. There was no difference in the response to any of the vaccinations or in the positivity to protein Purified Derived, streptokinase or candidin. Adult untreated isolated growth hormone deficiency does not cause an increased frequency of infectious diseases, and does not alter serologic tests, but is associated with lower total IgG levels, without detectable clinical impact.

Propuesta para el uso de métodos problemicos aplicados a la materia de Neuropsicología en el Instituto Normal Superior Simón Bolívar / Proposal for the use of problemicos to the matter of neuropsicology in the Normal Superior

La inquietud por el presente trabajo ha surgido de la experiencia como docente del Instituto Normal Superior Simón Bolivar. Se ha observado falencias en cuanto a la forma de organizar el proceso cognoscitivo de los estudiantes que deben ser corregidas. Por lo tanto se ha visto por conveniente buscar un método de enseñanza que permita alcanzar un cambio significativo y se ha considerado la aplicación del método problémico. Los resultados de la categorización mostraron que los profesores aún se encuentran utilizando un enfoque teórico y aqunque la metodología no es del todo tradicional aún no se maneja lo problemico ni se ayuda a los alumnos en su asimilación a través de diversos recursos de enseñanza o con la organización de actividades quepermitan la relaciñon de conocimientos nuevos con los adquiridos. Una vez puestos en marcha los métodos problémicos, los alumnos del semestre pasado obtuvieron procentajes más elevados demostrando que han adquirido una serie de habilidades que ayudan a una mejor asimilación de los contenidos. Los alumnos del primer semestre auqnue en su mayoría se encuentran utilizando las habilidades que recien adquieren, lo demás de su completa utilidad. Los exámenes muestran un nivel de desarrollo en crecimient. En General se ha podido notar una mejor asimilación del contenido de la materia y el logro de un nivel de idependencia cognoscitiva. Las conclusiones a las que se llegó son las siguientes. Es necesario capacitar a los profesores de la materia para que empleen de forma correcta los métodos problémicos. La experiencia con los semestres con los cuales se trabajó permite concluir que estos metodos permiten una mejor asimilación de contendos por parte de los alumnos así como la motivación para la búsqueda independiente y el desarrollo de capacidades creadoras.