Lessons from community engagement to improve COVID-19 diagnosis and treatment in Cochabamba, Bolivia.

BACKGROUND: Community engagement is recognized as a vital component of health-related research and programs, particularly during infectious disease outbreaks and epidemics. Despite the importance of engaging communities in the response to COVID-19, relatively little research has examined how this was (or was not) achieved, and even less in low- and middle-income countries. This article describes the community engagement that accompanied efforts to strengthen COVID-19 diagnosis and treatment as part of the ECO Project in Cochabamba, Bolivia and highlights lessons for future pandemic response. METHODS: Community engagement involved formative assessment, co-creation to develop a health information campaign, ongoing community listening and evaluation. Qualitative data were collected during workshops, project meetings and focus groups. Questionnaire-based surveys were conducted to assess COVID-19-related attitudes, knowledge and practices. RESULTS: The collected data highlighted the value of working closely with well-established community health committees and involving community members with social media skills in the design of COVID-19-related messages to address on- and offline misinformation. Co-creation sessions enabled the adjustment of the information campaign in terms of content and approach based on the needs and preferences of community members and health staff. The continuous listening with community and health personnel facilitated the ongoing adaptation of project activities. CONCLUSION: Through a stepped and multi-pronged approach, incorporating co-creation and community listening, the engagement could respond to emerging local challenges during the pandemic. The project created spaces for dialogue and opportunities for collaboration that strengthened links between the community and the health services.

Main findings Key elements of community engagement to improve COVID-19 diagnosis and treatment in Cochabamba, Bolivia, included working closely with well-established community health committees, involving community members with social media skills in the co-design of COVID-19-related messages, and continuous listening with community and health personnel facilitated the ongoing adaptation of project activities.Added knowledge With little research on community engagement for COVID-19 diagnosis and treatment in Latin America, this study reports the results of mixed methods research on the impact of a comprehensive approach to engagement that highlights lessons for future health emergencies.Global health impact for policy and action Lessons for engagement in health emergencies include the need for a multi-pronged approach, incorporating co-creation and community listening, to respond to emerging local challenges.

Antenatal exposure to magnesium sulfate and neonatal outcomes in very low birth weight infants: a multicenter study.

OBJECTIVE: To explore the association between antenatal magnesium sulfate (MgSO4), mortality and incidence of intraventricular hemorrhage (IVH) in very low birth weight (VLBW) infants. STUDY DESIGN: Retrospective, cohort study of infants <32 weeks' GA born at centers of NEOCOSUR Network between January 2015 and December 2020. Subjects were categorized as exposed vs non-exposed to antenatal MgSO4. Primary outcomes were death, incidence of severe IVH (Grade III-IV) and severe IVH/death. Secondary outcomes included relevant morbidities. RESULTS: 7418 VLBW infants were eligible. Antenatal MgSO4 was associated with a significantly decreased death rate after admission (aOR 0.67 [95% CI, 0.49-0.94]) and severe IVH/ death (aOR 0.68 [95% CI, 0.50-0.93]). No significant reduction in severe IVH was observed (aOR 1.11 [95% CI, 0.72-1.71]). No differences between groups were observed in rates of morbidities. CONCLUSION: Antenatal MgSO4 was associated with a decreased death rate after admission and in severe IVH/ death.

[Medullary infarction secondary to endovascular treatment of thoracoabdominal aortic aneurysm] / Infarto medular secundario a tratamiento endovascular de aneurisma de aorta toraco-abdominal.

Medullary infarction is a severe and infrequent pathology, which represents 1% of all ischemic strokes, and is also a rare complication of different surgical procedures. It is caused by the acute interruption of the blood flow of the spinal cord, manifesting itself with clinical neurological deficits related to the affected vascular territory. Methods: We present the case of an 80-year-old patient, with cardiovascular risk factors, who is present on post-surgical day 13, after placement of a vascular endoprosthesis for a thoracoabdominal aneurysm, sudden appearance of paraparesis with progression to paraplegia and hypoesthesia in both lower extremities. CT angiography of the aorta rules out local complications in the endoprosthesis. Medullary MRI showed images compatible with acute dorsal medullary infarction from level D9. Results: On discharge, the patient presented paraplegia and hypoesthesia of both lower extremities with fecal and urinary incontinence. Conclusion: Spinal cord infarction may be limited to a vascular territory or be more extensive according to its pathogenesis. The affectation of the anterior spinal artery is the most common and is characterized by bilateral motor deficits and loss of thermoalgesic sensitivity, which could have a great impact on the quality of life of patients. Its etiology is varied, including aortic surgery within its causes. MRI is very useful for its diagnosis and currently there are no clinical guides for the optimal treatment.

Introducción: El infarto medular es una patología severa e infrecuente, que representa el 1% del total de ictus isquémicos, siendo además una complicación rara de distintos procedimientos quirúrgicos. Es causado por la interrupción aguda del flujo sanguíneo de la médula espinal, manifestándose con déficits neurológicos clínicos relacionados con el territorio vascular afectado. Métodos: Presentamos el caso de un paciente de 80 años, con factores de riesgo cardiovascular, quien presenta en día postquirúrgico 13, tras colocación de endoprótesis vascular por aneurisma toraco-abdominal aparición brusca de paraparesia con progresión a paraplejía e hipoestesia en ambas extremidades inferiores.  Angio-TC de aorta descarta complicación local en la endoprótesis. RM medular mostró imágenes compatibles con Infarto agudo de médula dorsal desde el nivel D9. El paciente no fue subsidiario de tratamiento revascularizador. El tratamiento consistió en medidas de soporte. Resultados: Al alta el paciente presentaba paraplejia e hipoestesia de ambas extremidades inferiores con incontinencia fecal y urinaria. Conclusión: El infarto de la médula espinal puede estar limitado a un territorio vascular o estar más extendido según su patogenia. La afectación de la arteria espinal anterior es la más común y se caracteriza por déficits motores bilaterales y pérdida de la sensibilidad termoalgésica, pudiendo llegar a producir un gran impacto en la calidad de vida de los pacientes. Su etiología es variada, incluyéndose la cirugía aórtica dentro de sus causas. La RM es muy útil para su diagnóstico y actualmente no existen guías clínicas para el tratamiento óptimo.

Individualized dose of anti-thymocyte globulin based on weight and pre-transplantation lymphocyte counts in pediatric patients: a single center experience.

Anti-thymocyte globulin (ATG) has become a standard in preventing GVHD in related and unrelated donor transplantation, but there is no consensus on the best administration schedule. The PARACHUTE trial reported excellent CD4 immune reconstitution (CD4 IR) using a dosing schedule based on the patient's weight and pre-conditioning absolute lymphocyte count (ALC). In 2015 we introduced the PARACHUTE dosing schedule for pediatric patients at our center. One hundred one patients were transplanted for malignant and non-malignant diseases. In this non-concurrent cohort CD4 IR+, defined by a single CD4 count >50/µL on day 90, was seen in 81% of patients. The incidence of grade II-IV and III to IV aGvHD was 26.6% and 15.3% and 5% for cGvHD with no severe cases. We found no difference in aGvHD between donor type and stem cell sources. Five-year EFS and OS were 77.5% and 83.5%. Grade III-IV GFRS was 75.2%. CD4 IR+ patients had better EFS (93.1% vs. 77.7%, p = 0.04) and lower non-relapse mortality (2.7% vs. 22.2%, p = 0.002). The PARACHUTE ATG dosing schedule individualized by weight and ALC results in good early immune reconstitution, low incidence of cGvHD, and favorable survival for patients with different disease groups, donor types, and stem cell sources.

Collective and Coordinated Conformational Changes Determine Agonism or Antagonism at the Human Trace Amine-Associated Receptor 1.

The human trace amine-associated receptor (hTAAR1), a G protein-coupled receptor, has been postulated as a new target in the treatment of neuropsychiatric conditions. The mechanism associated with activation or inactivation by agonists or antagonists in hTAAR1 and other GPCRs has not yet been fully elucidated. In this study, we combined computational methods including homology modeling, docking, and molecular dynamic simulations to reveal novel conformational changes associated with agonist and antagonist interactions in hTAAR1. Our findings suggest a differential cascade of coordinated movements based on the presence of either an agonist or antagonist and primarily involving the second extracellular loop, transmembrane domain 5, and the third intracellular domains of hTAAR1. Our study provides an opportunity to predict the effects on new ligands with agonistic or antagonistic activity at hTAAR1 based on the reported conformational changes.

Serotonin secretion by blood platelets: accuracy of high-performance liquid chromatography-electrochemical technique compared with the isotopic test and use in a clinical laboratory.

Background: Mild secretion defects are the most frequent and challenging blood platelet disorders to diagnose. Most δ-granule secretion tests lack validation, are not quantitative, or have unreliable response to weak platelet agonists. Objectives: To compare platelet serotonin secretion by HPLC-electrochemical detection technique (HPLC-ECD) with the reference isotopic test (3H-5-HT), evaluating its performance in clinical laboratories. Methods: The assay validation followed STARD-2015 recommendations. HPLC-ECD measured the nonsecreted serotonin remaining in platelet pellets after aggregation, comparing it with the reference 3H-5-HT assay. We studied subjects with inherited and aspirin-induced blood platelet disorders and assessed the HPLC-ECD operation for routine clinical diagnosis. Results: Calibration curves were linear (R2 = 0.997), with SD for residuals of 3.91% and analytical sensitivity of 5ng/mL. Intra- and interassay imprecision bias ranged between -8.5% and 2.1% and -9% and 3.1%, respectively. Serotonin recovery and stability were >95%, and the variability range of measurements was -5.5% to 4.6%. Statistical differences detected between tests were biologically irrelevant, with bias of 1.48% (SD, 8.43) and CI agreement of -18% to 15%. Both assays distinctly detected platelet secretion induced by 10 µM epinephrine and 4 µmM adenosine diphosphate. However, HPLC-ECD is quantitative and more sensitive to low serotonin content in blood platelets. Reference cutoffs for each agonist were determined in 87 subjects. Initially, the HPLC-ECD requires relatively expensive equipment and trained operators but has remarkably cheap running costs and a turn-around time of 24-36 hours. We have used this diagnostic tool routinely for >8 years. Conclusion: HPLC-ECD assay for platelet serotonin secretion is highly accurate, has advantages over the reference 3H-5-HT test, and is suitable as a clinical laboratory technique.

Factors influencing the implementation of shared decision-making in breast cancer care: protocol for a mixed-methods study.

INTRODUCTION: Chile is committed to actively involving patients in their healthcare. However, little is known about how this is translated into clinical encounters. Breast cancer (BC) is the first cause of cancer-related death in Chilean women. National policy guarantees standard care, and treatment decisions should be made along this process that can have long-term consequences for women. So, BC is a particularly well-suited case study to understand the complexity of patient participation in decision-making. OBJECTIVE: To identify the factors that affect the active involvement of patients in the BC treatment decision-making process, considering the perspectives and practices of health professionals and women facing the disease. METHOD AND ANALYSIS: We will conduct a mixed-method study through a convergent parallel design in three stages: (1) A qualitative study: non-participant observation of the tumour board (TB) meetings; semi-structured interviews with key informants from TBs; documentary analyses; semi-structured interviews with women facing BC; and non-participant observations of clinical encounters; (2) a cross-sectional study with 445 women facing BC stages I-III from three hospitals in Santiago, Chile. We will measure the level of expected participation, experienced participation, decisional conflict, quality of life (QoL) and satisfaction with healthcare. Descriptive analysis will be performed, and multivariable binary logistic regression models will be adjusted to identify factors associated with high levels of QoL or satisfaction; (3) an integration study will bring together the data through a joint display technique. ETHICS AND DISSEMINATION: The study has been conceived and will be conducted according to international and local agreements for ethical research. Ethical approval has been granted by two Ethics Committees in Chile.The results will be disseminated to scientific and lay audiences (publications in scientific journals and conferences, seminars and a website for plain language dissemination).

Real-World Safety and Efficacy Clinical Data of an Improved Allergen-Specific Immunotherapy Product for the Treatment of Bee Venom Allergy.

The aim of this study is to explore the safety and efficacy of bee venom immunotherapy without HSA, in real-life patients. Methods: This is an observational retrospective study developed in seven hospitals in Spain, where patients treated with this immunotherapy were included. They gathered the protocol used to initiate the immunotherapy, adverse reactions, field re-stings, and the patient clinical data (clinical history, biomarkers, and skin prick test). Results: A total of 108 patients were included. In total, 4 protocols were used (5 weeks reaching 200 µg, and 4, 3, and 2 weeks reaching 100 µg). An incidence of systemic adverse reactions for each 100 injections of 1.5, 1.7, 0, and 0.58, respectively, was found. The demographic data showed not to directly affect the appearance of adverse reactions, except for those having a grade 2 systemic reaction with immunotherapy previously had a grade 4 systemic reaction; the IgE to Apis mellifera was 3 times higher in patients with systemic reactions of grade 1 than in the general group, and other specific IgEs were lower in those with systemic reactions. Most of the patients recognized Api m 1 followed by Api m 10. In the sample, 32% experienced spontaneous re-stings, without presenting systemic reactions, after a year of treatment.

Childhood Obesity and Plasma Micronutrient Deficit of Chilean Children between 4 and 14 Years Old.

OBJECTIVE: To analyze the nutritional status and plasma levels of vitamins and minerals in a cohort of Chilean children between 4 and 14 years old from three cities in Chile (Santiago, Antofagasta, and Concepcion). DESIGN: This is a descriptive analysis of micronutrient levels in Chilean children as it relates to obesity and food consumption. SETTING: This study included 1235 children from schools in Santiago (central area), Antofagasta (northern area), and Concepcion (southern area) in Chile. RESULTS: Plasma levels of micronutrients revealed deficiencies in children from all these cities. Copper (26.4%) and calcium (33.0%) deficiencies were found in the children from Antofagasta, whereas iron (26.7%) and zinc (20.8%) deficiencies were found in the children from Concepcion and Santiago, respectively. The percentage of children with vitamin D deficiencies was exceptionally high in all cities (over 78%). The analysis of micronutrients and nutritional status revealed that vitamin D deficiencies were significantly higher (p = 0.02) in overweight children, particularly in Antofagasta. In the analysis of the nutritional status of children and their food consumption habits, the proportion of overweight and obesity was significantly higher (p = 0.001) in children that skipped breakfast compared to children that did not. Finally, children from low socioeconomic levels were significantly more overweight and obese compared to children from high socioeconomic levels (p < 0.05). CONCLUSIONS: this is the first study to describe plasma levels of micronutrients in Chilean children and adolescents. High percentages of obesity, overweight, and vitamin D deficiency were detected in children. These results are of significant relevance to future public health policies in Chile.

Mortality in very low birth weight (VLBW) infants in South American NEOCOSUR Neonatal Network: timing and causes / Mortalidad en recién nacidos de muy bajo peso al nacer en la Red Neonatal NEOCOSUR: causalidad y temporalidad.

INTRODUCTION: Mortality in very low birth weight infants (VLBWIs) has remained at ~26% in the past 16 years in the NEOCOSUR Neonatal Network. OBJECTIVE: Mortality in very low birth weight infants (VLBWIs) has remained at ~26% in the past 16 years in the NEOCOSUR Neonatal Network. POPULATION AND METHODS: Observational, multicenter cohort study; retrospective analysis of data collected prospectively. Newborn infants born between 24 and 31+6 weeks of gestation age with a birth weight between 500 and 1500 g in the 26 sites of the NEOCOSUR Neonatal Network were included. The causes of death were analyzed depending on whether they occurred in the delivery room (DR) or in the neonatal intensive care unit (NICU). The postnatal age at time of death was determined using the KaplanMeier test. RESULTS: Observational, multicenter cohort study; retrospective analysis of data collected prospectively. Newborn infants born between 24 and 31+6 weeks of gestation age with a birth weight between 500 and 1500 g in the 26 sites of the NEOCOSUR Neonatal Network were included. The causes of death were analyzed depending on whether they occurred in the delivery room (DR) or in the neonatal intensive care unit (NICU). The postnatal age at time of death was determined using the KaplanMeier test. CONCLUSIONS: Important differences were observed in the causes of death of VLBWIs depending on their occurrence in the DR or the NICU. Infectious and respiratory conditions were the most relevant factors following admission to the NICU.

Introducción. La mortalidad de los recién nacidos de muy bajo peso de nacimiento (RNMBPN) se ha mantenido en ~26 % en los últimos 16 años en la Red Neonatal NEOCOSUR. Objetivo. Determinar la causa de muerte de los RNMBPN y su temporalidad en el período 20072016 en la Red Neonatal NEOCOSUR. Población y métodos. Estudio observacional de cohorte multicéntrica; análisis retrospectivo de datos obtenidos prospectivamente. Se incluyeron recién nacidos entre 24 y 31+6 semanas de edad gestacional y peso de nacimiento de 500-1500 g, en 26 centros de la Red Neonatal NEOCOSUR. Las causas de muerte se analizaron según ocurriera en sala de partos (SP) o durante la estadía en la unidad de cuidados intensivos neonatales (UCIN). La edad posnatal de muerte se determinó a través de análisis de Kaplan-Meier. Resultados. Se incluyeron un total de 11753 RNMBPN con una mortalidad global del 25,6 %. Las causas de muerte predominantes en SP fueron malformaciones congénitas (43,3 %), enfermedades respiratorias (14,3 %) y prematuridad (11,4 %). Las causas de muerte predominantes en UCIN fueron las respiratorias (24,2 %) e infecciosas (24,1 %). La edad promedio de muerte fue de 10,2 días y mediana de 4 días. El 10,2 % de las muertes ocurrieron en SP; el 21,5 %, durante el primer día; el 52 % ocurrió en los primeros 4 días y el 63,8 %, durante la primera semana de vida. , A través de los años, la mortalidad de los recién nacidos de muy bajo peso de nacimiento (RNMBPN) se ha mantenido estable, en torno al 26 % en la Red Neonatal NEOCOSUR.1 Esta mortalidad es mayor que la reportada por otras redes neonatales de países desarrollados. Así, los datos de la Red Suiza dan cuenta de una mortalidad de solo un 11 % entre los años 2012 a 2014 para el mismo grupo de recién nacidos.2 La red internacional iNEO, que agrupa 10 redes a lo largo del mundo, describe una mortalidad global del 9,1 % en RNMBPN de entre 24 a 32 semanas de edad gestacional entre los años 2007 y 2015.3 Por otra parte, la Red Neonatal Brasilera informa una mortalidad de 30 % en RNMBPN.4 f. Red Neonatal del Cono Sur (www. neocosur.org). Correspondencia: Alberto Toso: aatoso@ uc.cl Financiamiento: Ninguno. Conflicto de intereses: Ninguno que declarar. Recibido: 12-8-2021 Aceptado: 12-1-2022 Conclusiones. Se encuentran importantes diferencias en las causas de muerte de RNMBPN según ocurra en SP o en UCIN. Las infecciosas y respiratorias son las más relevantes luego del ingreso a la unidad de cuidados intensivos.

Mortalidad en recién nacidos de muy bajo peso al nacer en la Red Neonatal NEOCOSUR: causalidad y temporalidad / Mortality in very low birth weight (VLBW) infants in South American NEOCOSUR Neonatal Network: timing and causes

Introducción. La mortalidad de los recién nacidos de muy bajo peso de nacimiento (RNMBPN) se ha mantenido en ~26 % en los últimos 16 años en la Red Neonatal NEOCOSUR. Objetivo. Determinar la causa de muerte de los RNMBPN y su temporalidad en el período 20072016 en la Red Neonatal NEOCOSUR. Población y métodos. Estudio observacional de cohorte multicéntrica; análisis retrospectivo de datos obtenidos prospectivamente. Se incluyeron recién nacidos entre 24 y 31+6 semanas de edad gestacional y peso de nacimiento de 500-1500 g, en 26 centros de la Red Neonatal NEOCOSUR. Las causas de muerte se analizaron según ocurriera en sala de partos (SP) o durante la estadía en la unidad de cuidados intensivos neonatales (UCIN). La edad posnatal de muerte se determinó a través de análisis de Kaplan-Meier. Resultados. Se incluyeron un total de 11.753 RNMBPN con una mortalidad global del 25,6 %. Las causas de muerte predominantes en SP fueron malformaciones congénitas (43,3 %), enfermedades respiratorias (14,3 %) y prematuridad (11,4 %). Las causas de muerte predominantes en UCIN fueron las respiratorias (24,2 %) e infecciosas (24,1 %). La edad promedio de muerte fue de 10,2 días y mediana de 4 días. El 10,2 % de las muertes ocurrieron en SP; el 21,5 %, durante el primer día; el 52 % ocurrió en los primeros 4 días y el 63,8 %, durante la primera semana de vida. Conclusiones. Se encuentran importantes diferencias en las causas de muerte de RNMBPN según ocurra en SP o en UCIN. Las infecciosas y respiratorias son las más relevantes luego del ingreso a la unidad de cuidados intensivos.

Introduction. Mortality in very low birth weight infants (VLBWIs) has remained at ~26% in the past 16 years in the NEOCOSUR Neonatal Network. Objective. To determine the cause of death of VLBWIs and its temporality in the 2007-2016 period in the NEOCOSUR Neonatal Network. Population and methods. Observational, multicenter cohort study; retrospective analysis of data collected prospectively. Newborn infants born between 24 and 31+6 weeks of gestation age with a birth weight between 500 and 1500 g in the 26 sites of the NEOCOSUR Neonatal Network were included. The causes of death were analyzed depending on whether they occurred in the delivery room (DR) or in the neonatal intensive care unit (NICU). The postnatal age at time of death was determined using the KaplanMeier test. Results. A total of 11 753 VLBWIs were included; overall mortality was 25.6%. The prevailing causes of death in the DR were congenital malformations (43.3%), respiratory diseases (14.3%), and prematurity (11.4%). The prevailing causes of death in the NICU were respiratory diseases (24.2%) and infections (24.1%). The average and median age at death were 10.2 and 4 days, respectively. Also, 10.2% of deaths occurred in the DR; 21.5% on day 1, 52% in the first 4 days, and 63.8% in the first week of life. Conclusions. Important differences were observed in the causes of death of VLBWIs depending on their occurrence in the DR or the NICU. Infectious and respiratory conditions were the most relevant factors following admission to the NICU.

Neural tube defects prevalence does not increase after modification of the folic acid fortification program in Chile.

BACKGROUND: In 2000, Chile's Ministry of Health mandated fortification of wheat flour with folic acid at a concentration of 2.2 mg/kg to prevent neural tube defects (NTDs), resulting in a 50% reduction in NTD prevalence. Concerns about possible collateral effects of high folic acid intake led, in 2009, to decrease the folic acid fortification to 1.8 mg/kg of flour. Our study evaluated the impact of this modification on the prevalence of NTDs in Santiago. METHODS: This study measured the prevalence of NTDs in live births and stillbirths born in Santiago. We calculated prevalence ratios (PR) and 95% confidence intervals (CI) between pre-folic acid fortification (1999-2000), post-folic acid fortification (2001-2009), and post-modified folic acid fortification (2010-2015) periods for all NTDs and their specific types. We used chi-square tests to analyze proportions, and a Joinpoint regression to visualize prevalence time trends. RESULTS: The NTD prevalence for the period 2001-2015 was 8.9 per 10,000 births, which represents a 48% reduction (PR = 0.52; 95% CI = 0.45-0.61; p < .001) from the pre-folic acid fortification period. During 2010-2015, the NTD prevalence was 9.5/10,000 births, which was higher, but not statistically significantly different from 2001 to 2009 prevalence of 8.6/10,000 (PR = 1.11; 95% CI = 0.96-1.30, p = .17). CONCLUSIONS: Decreasing the concentration of folic acid fortification was not associated with a statistically significant change in the prevalence of NTDs. Mandatory folic acid fortification continues to be a safe and highly effective policy to prevent NTDs. Future studies should evaluate the prevalence of NTDs across Chile and adherence to folic acid fortification mandates.

Reducing stigma toward mental illness and substance use issues in primary health care in Chile: Protocol of a cluster controlled trial study.

Background: Chile is implementing a Community Mental Health Model with a strong role of primary health care (PHC). PHC has great potential to early detection and provision of accessible and coordinated services to people who present mental illness and/or substance use issues (MISUI). However, stigma toward people with MISUI among PHC professionals is a significant barrier to accessing good quality of care. A wealth of literature supports the importance of reducing stigma for this population. The main goal of this research project is to determine the effectiveness of a comprehensive anti-stigma intervention in reducing stigmatizing attitudes and behaviors among PHC providers toward individuals with MISUI in the Chilean context, using Centros de Salud Familiar (CESFAMs) as the point of intervention. Methods: The intervention is based on an initiative that was previously developed in Canada and then also pilot-tested in Lima, Peru, with the Center for Addiction and Mental Health (Ontario, Canada). The model will be culturally adapted with CESFAM PHC provider and user inputs to be relevant and valid to Chile. The 18-month intervention includes five (5) components that are simultaneously implemented in CESFAMs: (1) Develop a Team of Local Champions in each intervention CESFAM, comprising PHC providers and users; (2) Analysis of Internal CESFAM Policies, Procedures, and Protocols to determine areas of improvement in service delivery for individuals with MISUI; (3) Raising Awareness of stigma toward MISUI using various forms of media within the CESFAM; (4) Innovative Contact-Based Education workshops on anti-stigma and recovery principles, co-lead by academic/clinical trainers and a person with lived experience of MISUI; and (5) Recovery-Based Arts, a multi-week arts workshop for PHC providers and users to produce artwork related to MISUI and recovery, culminating in an exhibition to showcase artwork for the CESFAM providers, users, and community. The expected intervention outcomes are the following: Participation in the experimental group will result in a significant decrease in stigmatizing attitudes among PHC providers toward individuals with MISUI compared with the control group as measured by the Chilean version of the Opening Minds Scale for Health Care Providers Scale (OMS-HC); Participation in the experimental group will result in a significant decrease of PHC users experiences of stigma conveyed by PHC providers compared with the control group as measured by the Internalized Stigma of Mental Illness (ISMI) scale, validated for the Chilean population. The changes in attitudes and behaviors within the experimental group will be sustained over time as measured at 6 months-follow-up. To evaluate the effectiveness of this 18-month intervention, a 4-year, two-arm, cluster-randomized controlled trial is proposed, with CESFAMs being the unit of randomization (or "cluster"). Implementation Science approach will be taken to measure relevant implementation outcomes for each component of the intervention, and through qualitative data collection with CESFAM providers and authorities. Data analysis will be carried out using SAS 9.4 (specifically, using POC MIXED and PROC GENMOD) and R 3.5. Mixed-effect modeling will used for both PHC provider and user data, which will include individuals and CESFAMs as random effects and group (intervention/control) as fixed effects. Discussion: This study represents a new stage of relevant and innovative research in mental health and stigma in Chile that will contribute to improving access and quality of care for people with MISUI. Evaluating the impact of the intervention model and its implementation will provide the necessary tools to scale the intervention up to other CESFAMs across Chile. Clinical trial registration: [www.ClinicalTrials.gov], identifier [NCT05578066].

Effect of music on pediatric endoscopic examinations: a randomized controlled trial.

Background and study aims The primary objective was to measure the effect of music as an adjunct to sedation in patient anxiety levels during pediatric endoscopic examinations. Patients and methods We performed a single-blind randomized controlled trial comparing music with no music in children aged 2 to 18 years. Anxiety was measured using the Modified Yale Preoperative Anxiety Scale (m-YPAS) and the Visual Analog Anxiety Scale (VAS-anxiety). Patient perception of pain was evaluated with the Wong-Baker Faces Pain Rating Scale (WBFPRS). Patient experience, family satisfaction, and endoscopist perception of difficulty were evaluated. Sedative doses were recorded. Results A total of 51 children were randomized to the experimental group and 49 children to the control group. The mean ages were 10.5 years and 12.3 years, respectively. There were 63 % female subjects with no differences between groups. Overall, there were 85 upper endoscopies and 15 colonoscopies. In the recovery unit, the experimental group had lower average m-YPAS scores (mean score 27.7 vs 34.7; P  < 0.001), a higher proportion of them had low m-YPAS scores (80 % vs 49 % P  < 0.001), had lower VAS-anxiety scores [mean score 0.55 vs 1.57 ( P  = 0.003)], and had lower WBFPRS scores [mean score 2.7 vs 1.3 ( P  = 0.001)]. There were no statistically significant differences found in the amount of standard sedation given to the groups, nor in additional sedation administered. In the experimental group, the patient-reported experience was significantly better. Conclusions The study results show that music reduces anxiety and pain associated with endoscopic procedures in children. It also facilitates these procedures and improves patient satisfaction.

[Adaptation and validation in Chile of the patient identification instrument needing palliative care: NECPAL-CCOMS-ICO 3.1©]. / Adaptación y validación en Chile del instrumento de identificación de pacientes con necesidad de atención paliativa: NECPAL-CCOMS-ICO 3.1©.

OBJECTIVE: Adapt and validate the NECPAL instrument in Chile. DESIGN: Prospective, longitudinal, analytical study for validation of the instrument in 5 stages: cultural adaptation, content validation, pilot test, application, and statistical analysis. PLACE: Four primary care centers of the South East Metropolitan Health Service, in Santiago, Chile. PARTICIPANTS: Primary health care physicians and nurses for cultural adaptation and application, and palliative care experts for content validation. MAIN MEASUREMENTS: Cultural adaptation was carried out through cognitive interviews. Content validity was measured using Delphi method and the Lawshe content validity ratio (CVR) was obtained. In the pilot test, we measured stability (test-retest), inter judge harmony and application time in 14 chronic advanced patients (CAP). The test was applied to this same group, calculating the sample according to Nunally's recommendation. RESULTS: A sample of 118 CAP was obtained. The CVR was 0.75 and the average testing time was 6.7 min (SD = 4.01). The test-retest obtained a Kappa test concordance index between 0.632 and 1.0; and the interjudge harmony agreement between 0.192 and 0.692. The surprise question (PS) was positive in 20.3% of the sample. The main conditions associated with the disease-specific severity item, were fragility (23.7%), chronic heart disease (21.2%) and chronic lung disease (12.7%). The demand group and specific severity indicators obtained a greater predictive capacity of PS+, with an area under the curve of 0.808 (95% CI: 0.697-0.918). CONCLUSIONS: NECPAL is feasible to be used in Chile, has adequate psychometric properties and will allow early detection of patients in need of palliative care.

Early versus deferred anti-SARS-CoV-2 convalescent plasma in patients admitted for COVID-19: A randomized phase II clinical trial.

BACKGROUND: Convalescent plasma (CP), despite limited evidence on its efficacy, is being widely used as a compassionate therapy for hospitalized patients with COVID-19. We aimed to evaluate the efficacy and safety of early CP therapy in COVID-19 progression. METHODS AND FINDINGS: The study was an open-label, single-center randomized clinical trial performed in an academic medical center in Santiago, Chile, from May 10, 2020, to July 18, 2020, with final follow-up until August 17, 2020. The trial included patients hospitalized within the first 7 days of COVID-19 symptom onset, presenting risk factors for illness progression and not on mechanical ventilation. The intervention consisted of immediate CP (early plasma group) versus no CP unless developing prespecified criteria of deterioration (deferred plasma group). Additional standard treatment was allowed in both arms. The primary outcome was a composite of mechanical ventilation, hospitalization for >14 days, or death. The key secondary outcomes included time to respiratory failure, days of mechanical ventilation, hospital length of stay, mortality at 30 days, and SARS-CoV-2 real-time PCR clearance rate. Of 58 randomized patients (mean age, 65.8 years; 50% male), 57 (98.3%) completed the trial. A total of 13 (43.3%) participants from the deferred group received plasma based on clinical aggravation. We failed to find benefit in the primary outcome (32.1% versus 33.3%, odds ratio [OR] 0.95, 95% CI 0.32-2.84, p > 0.999) in the early versus deferred CP group. The in-hospital mortality rate was 17.9% versus 6.7% (OR 3.04, 95% CI 0.54-17.17 p = 0.246), mechanical ventilation 17.9% versus 6.7% (OR 3.04, 95% CI 0.54-17.17, p = 0.246), and prolonged hospitalization 21.4% versus 30.0% (OR 0.64, 95% CI, 0.19-2.10, p = 0.554) in the early versus deferred CP group, respectively. The viral clearance rate on day 3 (26% versus 8%, p = 0.204) and day 7 (38% versus 19%, p = 0.374) did not differ between groups. Two patients experienced serious adverse events within 6 hours after plasma transfusion. The main limitation of this study is the lack of statistical power to detect a smaller but clinically relevant therapeutic effect of CP, as well as not having confirmed neutralizing antibodies in donor before plasma infusion. CONCLUSIONS: In the present study, we failed to find evidence of benefit in mortality, length of hospitalization, or mechanical ventilation requirement by immediate addition of CP therapy in the early stages of COVID-19 compared to its use only in case of patient deterioration. TRIAL REGISTRATION: NCT04375098.

Validación del instrumento Informed Choice para medir la decisión informada de mamografía en mujeres chilenas usuarias de atención primaria / Validation of the Informed Choice instrument for Chilean women facing a mammography decision in primary care

Objetivo: Adaptar y validar el instrumento Informed Choice (IC) para la decisión de mamografía al contexto chileno. Diseño: Estudio transversal, analítico, de adaptación y validación psicométrica. Emplazamiento: Centro de atención primaria del sector sur oriente de Santiago de Chile. Métodos: 1) traducir y contra-traducir IC; 2) realizar un grupo focal para la relevancia cultural/lingüística; 3) examinar la validez del contenido; 4) pilotar el instrumento; 5) aplicar para validación. Para la consistencia interna se usó el alfa de Cronbach, prueba de esfericidad de Bartlett y la medida de Kaiser-Meyer-Olkin para determinar correlaciones entre las variables y análisis factorial. Resultados: Se construyeron 3 versiones del IC, modificándose según la opinión de usuarios y expertos. La validación se llevó a cabo en una muestra de 70 mujeres. La edad media fue de 54,4 años, el 47,1% de educación secundaria completa y el 92,9% al menos se había realizado alguna vez una mamografía. Se realizó análisis factorial del IC y se eliminó uno de sus ítems. El alfa de Cronbach final fue 0,79. Conclusión: El uso de instrumentos de medición requiere de su validación previa ya que la versión original puede variar de acuerdo al contexto cultural donde será aplicado y las necesidades locales particulares. El proceso de validación del IC permite contar con un instrumento confiable para medir la decisión de las mujeres que deben realizarse la mamografía en la dimensión conocimiento, actitud e intención hacia el examen.(AU)

Objective: To adapt and validate for the Chilean context the instrument Informed Choice (IC) to measure informed decision for mammography. Location: Primary Health Care Center in southeast Santiago, Chile. Design: Individual, transversal, analytical and psychometric adaptation and validation study. Methods: We 1) translated and back-translated IC; 2) conducted a focus group for cultural/linguistic relevance; 3) reviewed content validity; 4) piloted the instrument; 5) applied IC for validation. Analysis was performed by using Cronbach alpha, correlation, Bartlett's test of sphericity, Kaiser-Meyer-Olkin measure and factor analysis. Results: Three versions of the IC were developed, which included changes according to the views of users and experts. Validation was conducted in a sample of 70 women. Mean age was 54,4 years, 47,1% had completed secondary school and 92,9% have had at least one mammography. After factor analysis item 1 was removed and the final Cronbach Alpha was 0,79. Conclusions: The Chilean IC is reliable to measure decision women for mammography, this evaluate knowledge, attitude and intention towards the screening. The validation of an instrument to the cultural context is necessary and may have any variations to the original version according to local needs.(AU)

[Validation of the Informed Choice instrument for Chilean women facing a mammography decision in primary care]. / Validación del instrumento Informed Choice para medir la decisión informada de mamografía en mujeres chilenas usuarias de atención primaria.

OBJECTIVE: To adapt and validate for the Chilean context the instrument Informed Choice (IC) to measure informed decision for mammography. LOCATION: Primary Health Care Center in southeast Santiago, Chile. DESIGN: Individual, transversal, analytical and psychometric adaptation and validation study. METHODS: We 1) translated and back-translated IC; 2) conducted a focus group for cultural/linguistic relevance; 3) reviewed content validity; 4) piloted the instrument; 5) applied IC for validation. Analysis was performed by using Cronbach alpha, correlation, Bartlett's test of sphericity, Kaiser-Meyer-Olkin measure and factor analysis. RESULTS: Three versions of the IC were developed, which included changes according to the views of users and experts. Validation was conducted in a sample of 70 women. Mean age was 54,4 years, 47,1% had completed secondary school and 92,9% have had at least one mammography. After factor analysis item 1 was removed and the final Cronbach Alpha was 0,79. CONCLUSIONS: The Chilean IC is reliable to measure decision women for mammography, this evaluate knowledge, attitude and intention towards the screening. The validation of an instrument to the cultural context is necessary and may have any variations to the original version according to local needs.

Safety and immunogenicity evaluation of recombinant BCG vaccine against respiratory syncytial virus in a randomized, double-blind, placebo-controlled phase I clinical trial.

BACKGROUND: Respiratory syncytial virus (RSV) is responsible for most respiratory tract infections and hospitalizations in infants and represents a significant economic burden for public health. The development of a safe, effective, and affordable vaccine is a priority for the WHO. METHODS: We conducted a double-blinded, escalating-dose phase 1 clinical trial in healthy males aged 18-50 years to evaluate safety, tolerability, and immunogenicity of a recombinant Mycobacterium bovis BCG vaccine expressing the nucleoprotein of RSV (rBCG-N-hRSV). Once inclusion criteria were met, volunteers were enrolled in three cohorts in an open and successive design. Each cohort included six volunteers vaccinated with 5 × 103, 5 × 104, or 1 × 105 CFU, as well as two volunteers vaccinated with the full dose of the standard BCG vaccine. This clinical trial (clinicaltrials.gov NCT03213405) was conducted in Santiago, Chile. FINDINGS: The rBCG-N-RSV vaccine was safe, well-tolerated, and no serious adverse events related to the vaccine were recorded. Serum IgG-antibodies directed against Mycobacterium and the N-protein of RSV increased after vaccination, which were capable of neutralizing RSV in vitro. Additionally, all volunteers displayed increased cellular response consisting of IFN-γ and IL-2 production against PPD and the N-protein, starting at day 14 and 30 post-vaccination respectively. INTERPRETATION: The rBCG-N-hRSV vaccine had a good safety profile and induced specific cellular and humoral responses. FUNDING: This work was supported by Millennium Institute on Immunology and Immunotherapy from Chile (P09/016), FONDECYT 1190830, and FONDEF D11E1098.