Incidence of confusional syndrome (delirium) in a Latin American university hospital.

BACKGROUND: Little is known about the incidence of delirium and its subtypes in patients admitted to different departments of university hospitals in Latin America. OBJECTIVE: To determine the incidence of delirium and the frequency of its subtypes, as well as its associated factors, in patients admitted to different departments of a university hospital in Bogotá, Colombia. METHODS: A cohort of patients over 18 years of age admitted to the internal medicine (IM), geriatrics (GU), general surgery (GSU), orthopaedics (OU) and intensive care unit (ICU) services of a university hospital was followed up between January and June 2018. To detect the presence of delirium, we used the CAM (Confusion Assessment Method) and the CAM-ICU if the patient had decreased communication skills. The delirium subtype was characterised using the RASS (Richmond Agitation and Sedation Scale). Patients were assessed on their admission date and then every two days until discharged from the hospital. Those in whom delirium was identified were referred for specialised intra-institutional interdisciplinary management. RESULTS: A total of 531 patients admitted during the period were assessed. The overall incidence of delirium was 12% (95% CI, 0.3-14.8). They represented 31.8% of patients in the GU, 15.6% in the ICU, 8.7% in IM, 5.1% in the OU, and 3.9% in the GSU. The most frequent clinical display was the mixed subtype, at 60.9%, followed by the normoactive subtype (34.4%) and the hypoactive subtype (4.7%). The factors most associated with delirium were age (adjusted RR = 1.07; 95% CI, 1.05-1.09), the presence of four or more comorbidities (adjusted RR = 2.04; 95% CI, 1.31-3.20), and being a patient in the ICU (adjusted RR = 2.02; 95% CI, 1.22-3.35). CONCLUSIONS: The incidence of delirium is heterogeneous in the different departments of the university hospital. The highest incidence occurred in patients that were admitted to the GU. The mixed subtype was the most frequent one, and the main associated factors were age, the presence of four or more comorbidities, and being an ICU patient.

Experience with the use of the DIALOG+ intervention in patients with severe mental illness in outpatient services in Colombia.

INTRODUCTION: Severe mental disorders can cause significant and lasting distress for patients and their families and generate high costs through the need for care and loss of productivity. This study tests DIALOG+, an app-based intervention to make routine patient-clinician meetings therapeutically effective. It combines a structured evaluation of patient satisfaction with a solution-focused approach. METHODS: We conducted a qualitative study, based on a controlled clinical trial, in which 9 psychiatrists and 18 patients used DIALOG+ monthly over a six-month period. Semi-structured interviews were used to explore the experiences of participants and analysed in an inductive thematic analysis focusing on the feasibility and effects of the intervention in the Colombian context. RESULTS: Experiences were grouped into five overall themes: a) impact of the intervention on the consultation and the doctor-patient relationship; b) impact on patients and in promoting change; c) use of the supporting app, and d) adaptability of the intervention to the Colombian healthcare system. CONCLUSIONS: DIALOG+ was positively valued by most of the participants. Participants felt that it was beneficial to the routine consultation, improved communication and empowered patients to take a leading role in their care. More work is required to identify the patient groups that most benefit from DIALOG+, and to adjust it, particularly to fit brief consultation times, so that it can be rolled out successfully in the Colombian healthcare system.

Genetic evaluations of dairy goats with few pedigree data: different approaches to use molecular information.

One of the limitations of implementing animal breeding programs in small-scale or extensive production systems is the lack of production records and genealogical records. In this context, molecular markers could help to gain information for the breeding program. This study addresses the inclusion of molecular data into traditional genetic evaluation models as a random effect by molecular pedigree reconstruction and as a fixed effect by Bayesian clustering. The methods were tested for lactation curve traits in 14 dairy goat herds with incomplete phenotypic data and pedigree information. The results showed an increment of 37.3% of the relationships regarding the originals with MOLCOAN and clustering into five genetic groups. Data leads to estimating additive variance, error variance, and heritability with four different models, including pedigree and molecular information. Deviance Information Criterion (DIC) values demonstrate a greater fitting of the models that include molecular information either as fixed (genetic clusters) or as random (molecular matrix) effects. The molecular information of simple markers can complement genetic improvement strategies in populations with little information.

The value of additional electrodes when stereo-electroencephalography is inconclusive.

OBJECTIVE: Stereo-electroencephalography (SEEG) is the preferred method for intracranial localization of the seizure-onset zone (SOZ) in drug-resistant focal epilepsy. Occasionally SEEG evaluation fails to confirm the pre-implantation hypothesis. This leads to a decision tree regarding whether the addition of SEEG electrodes (two-step SEEG - 2sSEEG) or placement of subdural electrodes (SDEs) after SEEG (SEEG2SDE) would help. There is a dearth of literature encompassing this scenario, and here we aimed to characterize outcomes following unplanned two-step intracranial EEG (iEEG). METHODS: All 225 adult SEEG cases over 8 years at our institution were reviewed to extract patient data and outcomes following a two-step evaluation. Three raters independently quantified benefits of additional intracranial electrodes. The relationship between two-step iEEG benefit and clinical outcome was then analyzed. RESULTS: Fourteen patients underwent 2sSEEG and nine underwent SEEG2SDE. In the former cohort, the second SEEG procedure was performed for these reasons-precise localization of the SOZ (36%); defining margins of eloquent cortex (21%); and broadening coverage in the setting of non-localizable seizure onsets (43% of cases). Sixty-four percent of 2sSEEG cases were consistently deemed beneficial (Light's κ = 0.80). 2sSEEG performed for the first two indications was much more beneficial than when onsets were not localizable (100% vs 17%, p = .02). In the SEEG2SDE cohort, SDEs identified the SOZ and enabled delineation of margins relative to eloquent cortex in all cases. SIGNIFICANCE: The two-step iEEG is useful if the initial evaluation is broadly concordant with the original electroclinical hypothesis, where it can clarify onset zones or delineate safe surgical margins; however, it provides minimal benefit when the implantation hypothesis is erroneous, and we recommend that 2sSEEG not be generally utilized in such cases. SDE implantation after SEEG minimizes the need for SDEs and is helpful in delineating surgical boundaries relative to ictal-onset zones and eloquent cortex.

Feasibility and outcomes of using DIALOG+ in primary care to improve quality of life and mental distress of patients with long-term physical conditions: an exploratory non-controlled study in Bosnia and Herzegovina, Colombia and Uganda.

INTRODUCTION: The management of long-term physical conditions is a challenge worldwide, absorbing a majority resources despite the importance of acute care. The management of these conditions is done largely in primary care and so interventions to improve primary care could have an enormous impact. However, very little data exist on how to do this. Mental distress is frequently comorbid with long term physical conditions, and can impact on health behaviour and adherence, leading to poorer outcomes. DIALOG+ is a low-cost, patient-centred and solution-focused intervention, which is used in routine patient-clinician meetings and has been shown to improve outcomes in mental health care. The question arises as to whether it could also be used in primary care to improve the quality of life and mental health of patients with long-term physical conditions. This is particularly important for low- and middle-income countries with limited health care resources. METHODS: An exploratory non-controlled multi-site trial was conducted in Bosnia and Herzegovina, Colombia, and Uganda. Feasibility was determined by recruitment, retention, and session completion. Patient outcomes (quality of life, anxiety and depression symptoms, objective social situation) were assessed at baseline and after three approximately monthly DIALOG+ sessions. RESULTS: A total of 117 patients were enrolled in the study, 25 in Bosnia and Herzegovina, 32 in Colombia, and 60 in Uganda. In each country, more than 75% of anticipated participants were recruited, with retention rates over 90% and completion of the intervention exceeding 92%. Patients had significantly higher quality of life and fewer anxiety and depression symptoms at post-intervention follow-up, with moderate to large effect sizes. There were no significant improvements in objective social situation. CONCLUSION: The findings from this exploratory trial suggest that DIALOG+ is feasible in primary care settings for patients with long-term physical conditions and may substantially improve patient outcomes. Future research may test implementation and effectiveness of DIALOG+ in randomized controlled trials in wider primary care settings in low- and middle-income countries. TRIAL REGISTRATION: All studies were registered prospectively within the ISRCTN Registry. ISRCTN17003451, 02/12/2020 (Bosnia and Herzegovina), ISRCTN14018729, 01/12/2020 (Colombia) and ISRCTN50335796, 02/12/2020 (Uganda).

A Systematic Review of Gene Expression Studies in Critically Ill Patients with Sepsis and Community-Acquired Pneumonia.

(1) Background: Sepsis is present in nearly 90% of critically ill patients with community-acquired pneumonia (CAP). This systematic review updates the information on studies that have assessed gene expression profiles in critically ill septic patients with CAP. (2) Methods: We searched for studies that satisfied the following criteria: (a) expression profile in critically ill patients with sepsis due to CAP, (b) presence of a control group, and (c) adult patients. Over-representation analysis was performed with clusterProfiler using the Hallmark and Reactome collections. (3) Results: A total of 4312 differentially expressed genes (DEGs) and sRNAs were included in the enrichment analysis. In the Hallmark collection, genes regulated by nuclear factor kappa B in response to tumor necrosis factor, genes upregulated by signal transducer and activator of transcription 5 in response to interleukin 2 stimulation, genes upregulated in response to interferon-gamma, genes defining the inflammatory response, a subgroup of genes regulated by MYC-version 1 (v1), and genes upregulated during transplant rejection were significantly enriched in critically ill septic patients with CAP. Moreover, 88 pathways were identified in the Reactome database. (4) Conclusions: This study summarizes the reported DEGs in critically ill septic patients with CAP and investigates their functional implications. The results highlight the complexity of immune responses during CAP.

Analysis of perceptions and emotional repercussions in Twitter users in Colombia during the COVID-19 pandemic.

INTRODUCTION: The COVID-19 pandemic has negatively impacted mental health. Up to a quarter of the population has reported mental health disorders. This has been studied mainly from a nosological perspective, according to diagnostic criteria. Nevertheless, we did not find studies that have explored the daily expressions of the population. Our objective was to evaluate the perceptions of the COVID-19 pandemic and its repercussions on the emotional well-being of the Colombian population. METHODS: We performed a Twitter metrics and trend analysis. Initially, in the trend analysis, we calculated the average duration in hours of the 20 most popular trending topics of the day in Colombia and we grouped them into trends related to COVID-19 and unrelated trends. Subsequently, we identified dates of events associated with the pandemic relevant to the country, and they were related to the behaviour of the trends studied. Additionally, we did an exploratory analysis of these, selected the tweets with the greatest reach and categorised them in an inductive way to analyse them qualitatively. RESULTS: Issues not related to COVID-19 were more far-reaching than those related to coronavirus. However, a rise in these issues was seen on some dates consistent with important events in Colombia. We found expressions of approval and disapproval, solidarity and accusation. Inductively, we identified categories of informative tweets, humour, fear, stigma and discrimination, politics and entities, citizen complaints, and self-care and optimism. CONCLUSIONS: The impact of the COVID-19 pandemic generates different reactions in the population, which increasingly have more tools to express themselves and know the opinions of others. Social networks play a fundamental role in the communication of the population, so this content could serve as a public health surveillance tool and a useful and accessible means of communication in the management of health crises.

Development and Implementation of DIALOG+S in the School Setting as a Tool for Promoting Adolescent Mental Well-Being and Resilience in a Post-Armed Conflict Area in Colombia: Exploratory Cluster Randomized Controlled Trial.

BACKGROUND: Educational settings are ideal for promoting mental well-being and resilience in children. The challenges of the COVID-19 pandemic made evident the important role that teachers and school counselors play in the mental health of their students. Therefore, it is imperative to develop and implement cost-effective interventions that allow them to identify and address mental health problems early, especially in post-armed conflict areas, to reduce the burden of mental disorders in this population. OBJECTIVE: This study aimed to adapt an existing patient-focused digital intervention called DIALOG+ from an adult clinical setting to an adolescent educational setting and to assess the feasibility, acceptability, and estimated effect of implementing this intervention as a tool for promoting quality of life, mental well-being, and resilience. METHODS: We conducted an exploratory mixed methods study in 2 public schools in postconflict areas in Tolima, Colombia. This study was conducted in 3 phases. In the adaptation phase, focus groups were conducted with students and teachers to identify changes required in DIALOG+ for it to be used in the school setting. The exploration phase consisted of an exploratory cluster randomized controlled trial. A total of 14 clusters, each with 1 teacher and 5 students, were randomly allocated to either the experimental (DIALOG+S) group or to an active control group (counseling as usual). Teachers in both groups delivered the intervention once a month for 6 months. Through screening scales, information was collected on mental health symptoms, quality of life, self-esteem, resilience, and family functionality before and after the intervention. Finally, the consolidation phase explored the experiences of teachers and students with DIALOG+S using focus group discussions. RESULTS: The changes suggested by participants in the adaptation phase highlighted the central importance of the school setting in the mental health of adolescents. In the exploratory phase, 70 participants with a mean age of 14.69 (SD 2.13) years were included. Changes observed in the screening scale scores of the intervention group suggest that the DIALOG+S intervention has the potential to improve aspects of mental health, especially quality of life, resilience, and emotional symptoms. The consolidation phase showed that stakeholders felt that using this intervention in the school setting was feasible, acceptable, and an enriching experience that generated changes in the perceived mental health and behavior of participants. CONCLUSIONS: Our results are encouraging and show that the DIALOG+S intervention is feasible and acceptable as a promising opportunity to promote well-being and prevent and identify mental health problems in the school context in a postconflict area in Colombia. Larger, fully powered studies are warranted to properly assess the efficacy and potential impact of the intervention and to refine implementation plans. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number (ISRCTN) registry ISRCTN14396374; https://www.isrctn.com/ISRCTN14396374. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/40286.

Corrigendum: Cross-reactive humoral and CD4+ T cell responses to Mu and Gamma SARS-CoV-2 variants in a Colombian population.

[This corrects the article DOI: 10.3389/fimmu.2023.1241038.].

Análisis de percepciones y repercusiones emocionales en usuarios de Twitter en Colombia durante la pandemia de COVID-19

Introducción: La pandemia de COVID-19 ha impactado negativamente en la salud mental. Hasta un cuarto de la población ha reportado alteraciones de salud mental. Esto se ha estudiado principalmente desde una perspectiva nosológica según criterios diagnósticos; sin embargo, no encontramos estudios que hayan explorado las expresiones cotidianas de la población. Nuestro objetivo es evaluar las percepciones y repercusiones en el bienestar emocional de la población colombiana por la pandemia de COVID-19. Métodos: Se realizó un análisis de métricas y tendencias en Twitter. Inicialmente, en el análisis de tendencias se calculó el promedio de duración en horas de los 20 temas tendencia del día más populares en Colombia y las agrupamos en relacionadas con la COVID-19 y no relacionadas. Después se identificaron fechas de acontecimientos asociados con la pandemia relevantes para el país, y se relacionaron con el comportamiento de las tendencias estudiadas. Además, se hizo un análisis exploratorio de estas, se seleccionaron los tweets con mayor alcance y se categorizaron de forma inductiva para analizarlos cualitativamente. Resultados: Los temas no relacionados con COVID-19 tuvieron mayor alcance que los relacionados con coronavirus. No obstante, se vio un alza de estos temas en algunas fechas concordantes con hechos importantes en Colombia. Se hallaron manifestaciones de aprobación y desaprobación, de solidaridad y de acusación. De manera inductiva, se identificaron categorías de tweets informativos, humor, miedo, estigma y discriminación, política y entidades, denuncia ciudadana, y autocuidado y optimismo. Conclusiones: El impacto de la pandemia de COVID-19 genera diferentes reacciones en la población, que cada vez tienen más herramientas para expresarse y conocer las opiniones de los demás. Las redes sociales tienen un papel primordial en la comunicación de la población, por lo que este contenido podría servir como herramienta de vigilancia en salud pública y medio de comunicación útil y accesible en el manejo de crisis sanitarias.

Introduction: The COVID-19 pandemic has negatively impacted mental health. Up to a quarter of the population has reported mental health disorders. This has been studied mainly from a nosological perspective, according to diagnostic criteria. Nevertheless, we did not find studies that have explored the daily expressions of the population. Our objective was to evaluate the perceptions of the COVID-19 pandemic and its repercussions on the emotional well-being of the Colombian population. Methods: We performed a Twitter metrics and trend analysis. Initially, in the trend analysis, we calculated the average duration in hours of the 20 most popular trending topics of the day in Colombia and we grouped them into trends related to COVID-19 and unrelated trends. Subsequently, we identified dates of events associated with the pandemic relevant to the country, and they were related to the behaviour of the trends studied. Additionally, we did an exploratory analysis of these, selected the tweets with the greatest reach and categorized them in an inductive way to analyse them qualitatively. Results: Issues not related to COVID-19 were more far-reaching than those related to coronavirus. However, a rise in these issues was seen on some dates consistent with important events in Colombia. We found expressions of approval and disapproval, solidarity and accusation. Inductively, we identified categories of informative tweets, humour, fear, stigma and discrimination, politics and entities, citizen complaints, and self-care and optimism. Conclusions: The impact of the COVID-19 pandemic generates different reactions in the population, which increasingly have more tools to express themselves and know the opinions of others. Social networks play a fundamental role in the communication of the population, so this content could serve as a public health surveillance tool and a useful and accessible means of communication in the management of health crises.

Cross-reactive humoral and CD4+ T cell responses to Mu and Gamma SARS-CoV-2 variants in a Colombian population.

The SARS CoV-2 antibody and CD4+ T cell responses induced by natural infection and/or vaccination decline over time and cross-recognize other viral variants at different levels. However, there are few studies evaluating the levels and durability of the SARS CoV-2-specific antibody and CD4+ T cell response against the Mu, Gamma, and Delta variants. Here, we examined, in two ambispective cohorts of naturally-infected and/or vaccinated individuals, the titers of anti-RBD antibodies and the frequency of SARS-CoV-2-specific CD4+ T cells up to 6 months after the last antigen exposure. In naturally-infected individuals, the SARS-CoV-2 antibody response declined 6 months post-symptoms onset. However, the kinetic observed depended on the severity of the disease, since individuals who developed severe COVID-19 maintained the binding antibody titers. Also, there was detectable binding antibody cross-recognition for the Gamma, Mu, and Delta variants, but antibodies poorly neutralized Mu. COVID-19 vaccines induced an increase in antibody titers 15-30 days after receiving the second dose, but these levels decreased at 6 months. However, as expected, a third dose of the vaccine caused a rise in antibody titers. The dynamics of the antibody response upon vaccination depended on the previous SARS-CoV-2 exposure. Lower levels of vaccine-induced antibodies were associated with the development of breakthrough infections. Vaccination resulted in central memory spike-specific CD4+ T cell responses that cross-recognized peptides from the Gamma and Mu variants, and their duration also depended on previous SARS-CoV-2 exposure. In addition, we found cross-reactive CD4+ T cell responses in unexposed and unvaccinated individuals. These results have important implications for vaccine design for new SARS-CoV-2 variants of interest and concern.

Comparison of Cost and Potency of Human Mesenchymal Stromal Cell Conditioned Medium Derived from 2- and 3-Dimensional Cultures.

Mesenchymal stromal cell (MSC)-derived products, such as trophic factors (MTFs), have anti-inflammatory properties that make them attractive for cell-free treatment. Three-dimensional (3D) culture can enhance these properties, and large-scale expansion using a bioreactor can reduce manufacturing costs. Three lots of MTFs were obtained from umbilical cord MSCs produced by either monolayer culture (Monol MTF) or using a 3D microcarrier in a spinner flask dynamic system (Bioreactor MTF). The resulting MTFs were tested and compared using anti-inflammatory potency assays in two different systems: (1) a phytohemagglutinin-activated peripheral blood mononuclear cell (PBMNC) system and (2) a lipopolysaccharide (LPS)-activated macrophage system. Cytokine expression by macrophages was measured via RT-PCR. The production costs of hypothetical units of anti-inflammatory effects were calculated using the percentage of TNF-α inhibition by MTF exposure. Bioreactor MTFs had a higher inhibitory effect on TNF (p < 0.01) than monolayer MTFs (p < 0.05). The anti-inflammatory effect of Bioreactor MTFs on IL-1ß, TNF-α, IL-8, IL-6, and MIP-1 was significantly higher than that of monolayer MTFs. The production cost of 1% inhibition of TNF-α was 11-40% higher using monolayer culture compared to bioreactor-derived MTFs. A 3D dynamic culture was, therefore, able to produce high-quality MTFs, with robust anti-inflammatory properties, more efficiently than monolayer static systems.

Mental health problems and resilience in adolescents during the COVID-19 pandemic in a post-armed conflict area in Colombia.

The impact of COVID-19 pandemic on mental health of adolescents are emerging and require particular attention in settings where challenges like armed conflict, poverty and internal displacement have previously affected their mental wellbeing. This study aimed to determine the prevalence of anxiety symptoms, depressive symptomatology, probable post-traumatic stress disorder and resilience in school-attending adolescents in a post-conflict area of Tolima, Colombia during the COVID-19. A cross-sectional study was carried out with 657 adolescents from 12 to 18 years old, recruited by convenience sampling in 8 public schools in the south of Tolima, Colombia, who completed a self-administered questionnaire. Mental health information was obtained through screening scales for anxiety symptoms (GAD-7), depressive symptomatology (PHQ-8), probable post-traumatic stress disorder (PCL-5) and resilience (CD-RISC-25). The prevalence observed for moderate to severe anxiety symptoms was 18.9% (95% CI 16.0-22.1) and for moderate to severe depressive symptomatology was 30.0% (95% CI 26.5-33.7). A prevalence of probable post-traumatic stress disorder (PTSD) of 22.3% (95% CI 18.1-27.2) was found. The CD-RISC-25 results for resilience had a median score of 54 [IQR 30]. These results suggest that approximately two-thirds of school-attending adolescents in this post-conflict area experienced at least one mental health problem such as anxiety symptoms, depressive symptomatology or probable PTSD during the COVID-19 pandemic. Future studies are of interest to establish the causal relationship between these findings and the impact of the pandemic. These findings highlight the challenge that schools have after pandemic to address the mental health of their students in order to promoting adequate coping strategies and implement prompt multidisciplinary interventions to reduce the burden of mental health problems in adolescents.

Development of Leishmania Species Strains with Constitutive Expression of eGFP.

Protozoan parasites of the genus Leishmania cause leishmaniasis, a disease with variable clinical manifestations that affects millions of people worldwide. Infection with L. donovani can result in fatal visceral disease. In Panama, Colombia, and Costa Rica, L. panamensis is responsible for most of the reported cases of cutaneous and mucocutaneous leishmaniasis. Studying a large number of drug candidates with the methodologies available to date is quite difficult, given that they are very laborious for evaluating the activity of compounds against intracellular forms of the parasite or for performing in vivo assays. In this work, we describe the generation of L. panamensis and L. donovani strains with constitutive expression of the gene that encodes for an enhanced green fluorescent protein (eGFP) integrated into the locus that encodes for 18S rRNA (ssu). The gene encoding eGFP was obtained from a commercial vector and amplified by polymerase chain reaction (PCR) to enrich it and add restriction sites for the BglII and KpnI enzymes. The eGFP amplicon was isolated by agarose gel purification, digested with the enzymes BglII and KpnI, and ligated into the Leishmania expression vector pLEXSY-sat2.1 previously digested with the same set of enzymes. The expression vector with the cloned gene was propagated in E. coli, purified, and the presence of the insert was verified by colony PCR. The purified plasmid was linearized and used to transfect L. donovani and L. panamensis parasites. The integration of the gene was verified by PCR. The expression of the eGFP gene was evaluated by flow cytometry. Fluorescent parasites were cloned by limiting dilution, and clones with the highest fluorescence intensity were selected using flow cytometry.

Pharmacogenomic profile of actionable molecular variants related to drugs commonly used in anesthesia: WES analysis reveals new mutations.

Background: Genetic interindividual variability is associated with adverse drug reactions (ADRs) and affects the response to common drugs used in anesthesia. Despite their importance, these variants remain largely underexplored in Latin-American countries. This study describes rare and common variants found in genes related to metabolism of analgesic and anaesthetic drug in the Colombian population. Methods: We conducted a study that included 625 Colombian healthy individuals. We generated a subset of 14 genes implicated in metabolic pathways of common medications used in anesthesia and assessed them by whole-exome sequencing (WES). Variants were filtered using two pipelines: A) novel or rare (minor allele frequency-MAF <1%) variants including missense, loss-of-function (LoF, e.g., frameshift, nonsense), and splice site variants with potential deleterious effect and B) clinically validated variants described in the PharmGKB (categories 1, 2 and 3) and/or ClinVar databases. For rare and novel missense variants, we applied an optimized prediction framework (OPF) to assess the functional impact of pharmacogenetic variants. Allelic, genotypic frequencies and Hardy-Weinberg equilibrium were calculated. We compare our allelic frequencies with these from populations described in the gnomAD database. Results: Our study identified 148 molecular variants potentially related to variability in the therapeutic response to 14 drugs commonly used in anesthesiology. 83.1% of them correspond to rare and novel missense variants classified as pathogenic according to the pharmacogenetic optimized prediction framework, 5.4% were loss-of-function (LoF), 2.7% led to potential splicing alterations and 8.8% were assigned as actionable or informative pharmacogenetic variants. Novel variants were confirmed by Sanger sequencing. Allelic frequency comparison showed that the Colombian population has a unique pharmacogenomic profile for anesthesia drugs with some allele frequencies different from other populations. Conclusion: Our results demonstrated high allelic heterogeneity among the analyzed sampled, enriched by rare (91.2%) variants in pharmacogenes related to common drugs used in anesthesia. The clinical implications of these results highlight the importance of implementation of next-generation sequencing data into pharmacogenomic approaches and personalized medicine.

Evolución clínica en neuromielitis óptica comparando el manejo con azatioprina o rituximab / Clinical evolution in neuromyelitis optica when comparing management with azathioprine and rituximab

RESUMEN INTRODUCCIÓN: El espectro de trastornos de neuromielitis óptica (NMOSD) es un grupo de enfermedades desmielinizantes, inflamatorias y autoinmunes, caracterizadas por episodios recurrentes de neuritis óptica y mielitis transversa longitudinal extensa, entre otras manifestaciones clínicas. Su tratamiento crónico se basa en el uso de terapias inmunosupresoras como azatioprina (AZA), micofenolato mofetilo (MFM) o rituximab (RTX). El objetivo del presente estudio es realizar un análisis comparativo de la respuesta al tratamiento con AZA o RTX. MATERIALES Y MÉTODOS: Se realizó un estudio observacional, analítico, retrospectivo, en el cual se incluyeron inicialmente 69 pacientes con diagnóstico confirmado de NMOSD. Tras aplicar los criterios de inclusión y exclusión 59 pacientes fueron incluidos en el análisis final. RESULTADOS: En el grupo de RTX se evidenció una mejoría importante en el estado funcional en comparación con el grupo de AZA, en el que se vio un empeoramiento de este al año de seguimiento. El perfil de seguridad fue similar entre ambos grupos, con una adherencia significativamente superior en el grupo de RTX. DISCUSIÓN: Los hallazgos del presente estudio respecto a las ventajas del uso de RTX sobre AZA se encuentran en concordancia con resultados de estudios previos reportados en la literatura. CONCLUSIONES: Los resultados respaldan el uso de RTX sobre AZA como terapia de mantenimiento para pacientes con NMOSD, al estar asociado principalmente con una mejoría notable en la funcionalidad de los pacientes, al igual que una mayor adherencia al tratamiento.

ABSTRACT INTRODUCTION: Neuromyelitis Optica Spectrum Disorders (NMOSD) is a group of inflammatory, autoimmune, and demyelinating disorders. Its hallmark behavior is characterized by recurrent episodes of optic neuritis and longitudinally extensive transverse myelitis, among other clinical manifestations. Chronic therapy is based primarily in immunosuppressive therapies such as azathioprine (AZA), mycophenolate mofetil (MMF), or rituximab (RTX). The goal of this study is to perform a comparative analysis of response rates to chronic treatment with either AZA or RTX. MATERIALS AND METHODS: A retrospective observational analytic study was designed with an initial cohort of 69 patients with a diagnosis of NMOSD. After application of the inclusion and exclusion criteria a total of 59 patients were finally included in the analysis. RESULTS: The RTX group had an improved functional status when compared to the AZA group; in the latter this feature worsened after a one-year follow-up. There was also a comparable safety profile between the two groups with a significantly greater adherence to RTX regimes. DISCUSSION: The findings of the current study as to the benefits of RTX in comparison to AZA are similar to the results of previous studies. CONCLUSION: These results favor the use of RTX as maintenance treatment of NMOSD, because of its greater benefit mainly in the improvement in functional status of patients, as well as a greater adherence to treatment.

Effectiveness of a Patient-Centered Assessment With a Solution-Focused Approach (DIALOG-A) in the Routine Care of Colombian Adolescents With Depression and Anxiety: Protocol for a Multicenter Cluster Randomized Controlled Trial.

BACKGROUND: Colombia is a middle-income country in South America, which has historically had high rates of mental health problems, coupled with a scarcity of mental health care. There is growing concern for the mental health of the adolescent population within this region. There is a significant treatment gap for young people, especially those living in the most vulnerable areas. DIALOG+ is a low-cost patient-centered intervention that can potentially improve the delivery of care and quality of life for adolescents with mental health problems. OBJECTIVE: This exploratory randomized controlled trial aims to evaluate the effectiveness, acceptability, and feasibility of an adapted version of the DIALOG+ intervention (DIALOG-A) in the community treatment of Colombian adolescents with depression and anxiety. METHODS: In total, 18 clinicians and 108 adolescents will be recruited from primary health care services in Bogota and Duitama, Colombia. Clinicians will be randomized 2:1 to either the intervention (12 clinicians:72 adolescents) or control group (6 clinicians:36 adolescents). In the intervention arm, clinicians will use DIALOG-A with adolescents once per month over 6 months. The control arm will continue to receive routine care. Outcomes will be measured at baseline, 6 months, and 9 months following randomization. Semistructured interviews with all clinicians and a subset of adolescents in the intervention arm will be conducted at the end of the intervention period. Quantitative and qualitative analysis of the data will be conducted. RESULTS: Trial recruitment was completed toward the end of October 2022, and follow-up is anticipated to last through to October 2023. CONCLUSIONS: This is the first study to test an adapted resource-orientated intervention (DIALOG-A) in the treatment of adolescents with depression and anxiety attending primary care services. If the results are positive, DIALOG-A can be implemented in the routine care of adolescents with these mental health problems and provide valuable insight to other middle-income countries. TRIAL REGISTRATION: ISRCTN Registry ISRCTN13980767; https://www.isrctn.com/ISRCTN13980767?q=ISRCTN13980767. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/43401.

Integrating Depression and Alcohol Use Care Into Primary Care in Low- and Middle-Income Countries: A Meta-Analysis.

OBJECTIVE: Evaluation of the effectiveness of integration of depression and alcohol use disorder care into primary health care in low- and middle-income countries (LMICs) is limited. The authors aimed to quantify the effectiveness of integrating mental health care into primary care by examining depression and alcohol use disorder outcomes. The study updates a previous systematic review summarizing research on care integration in LMICs. METHODS: Following PRISMA guidelines, the authors included studies from the previous review and studies published from 2017 to 2020 that included adults with alcohol use disorder or depression. Studies were evaluated for type of integration model with the typology developed previously. A meta-analysis using a random-effects model to assess effectiveness of integrated interventions was conducted. Meta-regression analyses to examine the impact of study characteristics on depression and alcohol use disorder outcomes were conducted. RESULTS: In total, 49 new articles were identified, and 74 articles from the previous and current studies met inclusion criteria for the meta-analysis. Overall random effect sizes were 0.28 (95% CI=0.22-0.35) and 0.17 (95% CI=0.11-0.24) for studies targeting care integration for depression or for alcohol use disorder, respectively, into primary care in LMICs. High heterogeneity within and among studies was observed. No significant association was found between country income level and depression and alcohol use outcomes. However, differences in effect sizes between types of integration model were statistically significant (p<0.001). CONCLUSIONS: Integration of mental health care into primary health care in LMICs was found to improve depression and alcohol use disorder outcomes. This evidence should be considered when designing interventions to improve mental health screening and treatment in LMICs.