Reactivation of Trypanosoma cruzi infection in immunosuppressed patients: a systematic review and meta-analysis.

BACKGROUND: The risk of Trypanosoma cruzi reactivation is poorly understood. Previous studies evaluating the risk of reactivation report imprecise findings, and recommendations for monitoring and management from clinical guidelines rely on consensus opinion. OBJECTIVES: We conducted a systematic review and meta-analysis to estimate the cumulative T. cruzi reactivation incidence in immunosuppressed adults, summarize the available evidence on prognostic factors for reactivation, and examine its prognostic effect on mortality. DATA SOURCES: MEDLINE, Embase, LILACS, Clinical Trials, and CENTRAL from inception to 4 July 2022. STUDY ELIGIBILITY CRITERIA: Studies reporting the incidence of T. cruzi reactivation. PARTICIPANTS: Immunosuppressed adults chronically infected by T. cruzi. METHODS: Two authors independently extracted data (including, but not limited to, incidence data, reactivation definition, follow-up, treatment, monitoring schedule, examined prognostic factors) and evaluated the risk of bias. We pooled cumulative incidence using a random-effects model. RESULTS: Twenty-two studies (806 participants) were included. The overall pooled incidence of T. cruzi reactivation was 27% (95% CI, 19-36), with the highest pooled proportion in the sub-group of transplant recipients (36%; 95% CI, 25-48). The highest risk period was in the first 6 months after transplant (32%; 95% CI, 17-58), decreasing drastically the number of new cases later. People living with HIV and patients with autoimmune diseases experienced significantly lower cumulative reactivation incidences (17%; 95% CI, 8-29 and 18%; 95% CI, 9-29, respectively). A single study explored the independent effect of benznidazole and found benefits for preventing reactivations. No studies evaluated the independent association between reactivation and mortality, while sensitivity analysis results using unadjusted estimates were inconclusive. The heterogeneity of diagnostic algorithms was substantial. CONCLUSIONS: Reactivation occurs in three out of ten T. cruzi-seropositive immunosuppressed adults. These findings can assist clinicians and panel guidelines in tailoring monitoring schedules. There is a great need for an accurate definition of reactivation and targeted monitoring.

Corrigendum: CD4/CD8 ratio and CD8+ T-cell count as prognostic markers for non-AIDS mortality in people living with HIV. A systematic review and meta-analysis.

[This corrects the article DOI: 10.3389/fimmu.2024.1343124.].

Specific photoreceptor cell fate pathways are differentially altered in NR2E3-associated diseases.

Mutations in NR2E3, a gene encoding an orphan nuclear transcription factor, cause two retinal dystrophies with a distinct phenotype, but the precise role of NR2E3 in rod and cone transcriptional networks remains unclear. To dissect NR2E3 function, we performed scRNA-seq in the retinas of wildtype and two different Nr2e3 mouse models that show phenotypes similar to patients carrying NR2E3 mutations. Our results reveal that rod and cone populations are not homogeneous and can be separated into different sub-classes. We identify a previously unreported cone pathway that generates hybrid cones co-expressing both cone- and rod-related genes. In mutant retinas, this hybrid cone subpopulation is more abundant and includes a subpopulation of rods transitioning towards a cone cell fate. Hybrid photoreceptors with high misexpression of cone- and rod-related genes are prone to regulated necrosis. Overall, our results shed light on the role of NR2E3 in modulating photoreceptor differentiation towards cone and rod fates and explain how different mutations in NR2E3 lead to distinct visual disorders in humans.

CD4/CD8 ratio and CD8+ T-cell count as prognostic markers for non-AIDS mortality in people living with HIV. A systematic review and meta-analysis.

Background: In people living with HIV (PLHIV), the CD4/CD8 ratio has been proposed as a useful marker for non-AIDS events. However, its predictive ability on mortality over CD4 counts, and the role of CD8+ T-cell counts remain controversial. Methods: We conducted a systematic review and meta-analysis of published studies from 1996 to 2023, including PLHIV on antiretroviral treatment, and reporting CD4/CD8 ratio or CD8+ counts. The primary outcome was non-AIDS mortality or all-cause mortality. We performed a standard random-effects pairwise meta-analysis comparing low versus high CD4/CD8 ratio with a predefined cut-off point of 0.5. (CRD42020170931). Findings: We identified 2,479 studies for screening. 20 studies were included in the systematic review. Seven studies found an association between low CD4/CD8 ratio categories and increased mortality risk, with variable cut-off points between 0.4-1. Four studies were selected for meta-analysis, including 12,893 participants and 618 reported deaths. Patients with values of CD4/CD8 ratio below 0.5 showed a higher mortality risk (OR 3.65; 95% CI 3.04 - 4.35; I2 = 0.00%) compared to those with higher values. While the meta-analysis of CD8+ T-cell counts was not feasible due to methodological differences between studies, the systematic review suggests a negative prognostic impact of higher values (>1,138 to 1,500 cells/uL) in the long term. Conclusions: Our results support the use of the CD4/CD8 ratio as a prognostic marker in clinical practice, especially in patients with values below 0.5, but consensus criteria on ratio timing measurement, cut-off values, and time to event are needed in future studies to get more robust conclusions. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020170931, identifier CRD42020170931.

Impacto del confinamiento durante la pandemia de COVID-19 en la prevalencia de la enfermedad tromboembólica venosa / Impact of strict confinement during the COVID-19 pandemic on the prevalence of venous thromboembolic disease

Objetivo: comparar la frecuencia de eventos tromboembólicos agudos en pacientes atendidos en urgencias de un hospital comarcal durante las primeras semanas de la pandemia de COVID-19 del año 2020 respecto al año anterior.Material y métodos: estudio retrospectivo en pacientes mayores de 40 años atendidos en urgencias del Hospital de Riotinto (Huelva) desde el 15 de marzo al 30 de abril de los años 2019 y 2020. La recogida de información se llevó a cabo a partir de una revisión de historias clínicas y el cuestionario de recogida de datos contenía variables clínicas y sociodemográficas.Resultados: se incluyeron 1.245 pacientes. Edad media: 71,2 años (desviación estándar [DE]: 13,7) y un 51,1% eran mujeres. En 2019 se atendieron a 797 mayores de 40 años y en 2020 fueron 448, suponiendo un descenso del 43,79%. La prevalencia de embolismo pulmonar fue superior en 2020 respecto a 2019 (1,6% frente a 0,4%; p = 0,024). La frecuencia de eventos trombóticos venosos fue superior también en 2020 respecto a 2019 (1,35% frente a 0,4%; p = 0,054). La prevalencia global de la enfermedad tromboembólica venosa con variable compuesta (tromboembolismo pulmonar + trombosis venosa) fue significativamente superior en 2020 frente a 2019 (2,9% frente a 0,8%; p = 0,003). Ningún paciente fue diagnosticado de COVID-19 y tromboembolismo.Conclusiones: en el período de confinamiento durante la pandemia hubo un incremento del número de eventos tromboembólicos agudos en adultos, tanto de tromboembolia pulmonar como de trombosis venosa profunda respecto al año previo. (AU)

Aim: to compare the frequency of acute thromboembolic events in patients visited in the casualty department of a regional hospital during the first few weeks of the COVID-19 pandemic in 2020 with the same period of previous year.Material and methods: retrospective study of patients aged over 40 years of age treated in the casualty department of Hospital de Riotinto (Huelva) from 15 March to 30 April 2019 and same period of 2020. The information was collected from a review of medical records. The data collection questionnaire contained clinical and sociodemographic variables.Results: a total of 1245 patients were included. Mean age was 71.2 (SD:13.7) years old and 51.1% were women. In 2019, 797 patients aged over 40 years of age were treated, while in 2020, the patients seen were 448, which represented a decrease of 43.79%. The prevalence of pulmonary embolism was higher in 2020 compared to 2019 (1.6% vs. 0.4%; P=0.024). The frequency of venous thrombotic events was also higher in 2020 compared to 2019 (1.35% vs. 0.4%; P=0.054). The overall prevalence of venous thromboembolic disease with composite variable (pulmonary thromboembolism + venous thrombosis) was statistically significantly higher in 2020 versus 2019 (2.9% versus 0.8%; P=0.003). None of our patients were diagnosed with COVID-19 and thromboembolism.Conclusions: during the period of confinement during the pandemic there was an increase in the number of acute thromboembolic events in adults, both PE and VTE compared to the previous year.(AU)

Hope, resilience and subjective happiness among general population of Paraguay in the post COVID-19 pandemic.

BACKGROUND: Positive mental health includes not only the absence of mental disorders but also the presence of subjective well-being, good coping strategies for life stress, and strategies for adapting to community life. It is well known that the COVID-19 pandemic has challenged mental health in general population worldwide. However, research has not measured protective factors for mental health in the general population after the declared end of pandemic by the World Health Organization. METHODS: This observational, cross-sectional study surveyed 591 Paraguayan participants aged ⩾18 years, who were recruited through an online survey. Demographic characteristics, socioeconomic status were collected as well as mental health and validated tools for hope, resilience, subjective happiness were administered. RESULTS: Of the participants, 81.6% were women, 54% were married or in a relationship and 90.7% reported an university education. The main source of stress was economic issues (30.3%). A total of 22.7% had been previously diagnosed with a mental disorder, 22.2% had consulted a mental health professional and 10.8% had consumed prescription drugs. 42.6% reported flourishing, 36.2% reported moderate and 21.2% reported languishing mental health. CONCLUSIONS: This large survey has shown that most of participants reported a flourishing mental health with high ratings at hope, resilience, and subjective happiness scales. Also, the main sources of stress were economic issues, not consequently related to the pandemic. This may add evidences to the international debate on the long term effects of the global pandemic and probably suggests that recovery processes have been collectively adopted in Paraguay.

Asociación entre cronotipo y síntomas depresivos: un estudio exploratorio

Introducción: el cronotipo es la predisposición natural de cada individuo a experimentar picos de energía o momentos de descanso en función de su ritmo circadiano. Los individuos pueden tener cronotipos matutinos, vespertinos o intermedios, que pueden tener relación con el desarrollo de depresión. Objetivo: determinar la existencia de asociación entre el cronotipo y la sintomatología depresiva en una muestra de adultos. Metodología: este estudio observacional, descriptivo y exploratorio se realizó en agosto de 2023. Se incluyeron en este estudio adultos de ambos sexos. Se recolectaron datos sociodemográficos, y los participantes respondieron el Morningness-Eveningness Questionnaire de Horne y Östberg para evaluar el cronotipo, y el Patient Health Questionnaire de 2 ítems (PHQ-2) para evaluar los síntomas depresivos. Se utilizaron estadísticas descriptivas para todas las variables. Para la estadística inferencial, se utilizó la prueba de chi-cuadrado con un nivel de confianza del 95 %. Se utilizó odds ratio para cuantificar las relaciones. Resultados: un total de 105 personas participaron en el estudio, de las cuales el 58 % eran mujeres. La edad media de la muestra era de 29,4 ± 11,6 años. El 69 % de la muestra presentaba el cronotipo matutino, mientras que el 31 % presentaba el cronotipo vespertino. Se observó que el 31 % de los participantes puntuaba positivamente para depresión (PHQ-2 ≥ 3). Se encontró una relación entre el cronotipo y los puntos de corte del PHQ-2 (p=0,036). Se halló una OR=2,5 (IC 95%: 1,05-5,95) a favor del cronotipo vespertino para el desarrollo de depresión. Conclusión: casi siete de cada diez participantes tenían un cronotipo matutino, mientras que tres de cada diez dieron positivo en depresión. Los individuos con cronotipos vespertinos son más propensos a desarrollar síntomas depresivos que aquellos con cronotipos matutinos.

Introduction: chronotype is the natural predisposition of each individual to experience peaks of energy or moments of rest according to their circadian rhythm. Individuals may have morning, evening, or intermediate chronotypes that may be related to the development of depression. Objective: to determine the existence of an association between chronotype and depressive symptomatology in a sample of adults. Methodology: this observational, descriptive, and exploratory study was conducted in August 2023. Adults of both sexes were included in this study. Sociodemographic data were collected, and participants answered the Morningness-Eveningness Questionnaire by Horne and Östberg to assess chronotype, and the 2-item Patient Health Questionnaire (PHQ-2) to assess depressive symptoms. Descriptive statistics were used for all the variables. For inferential statistics, the chi-squared test was used with a confidence level of 95 %. Odds ratio was used to quantify the relationships. Results: a total of 105 people participated in the study, 58 % of whom were women. The mean age of the sample was 29.4 ± 11.6 years. Sixty-nine percent of the sample presented the morning chronotype, while 31 % presented the evening chronotype. It was found that 31 % of the participants scored positively for depression (PHQ-2 ≥ 3). A relationship was found between chronotype and PHQ-2 cutoff points (p=0.036). An OR=2.5 (95 % CI 1.05-5.95) was found in favor of the evening chronotype for the development of depression. Conclusion: almost seven out of ten participants had a morning chronotype, whereas three out of ten were positive for depression. Individuals with evening chronotypes are more likely to develop depressive symptoms than those with morning chronotypes.

Asociación entre cronotipo y síntomas depresivos: un estudio exploratorio / Association between chronotype and depressive symptoms: an exploratory study

Introducción: el cronotipo es la predisposición natural de cada individuo a experimentar picos de energía o momentos de descanso en función de su ritmo circadiano. Los individuos pueden tener cronotipos matutinos, vespertinos o intermedios, que pueden tener relación con el desarrollo de depresión. Objetivo: determinar la existencia de asociación entre el cronotipo y la sintomatología depresiva en una muestra de adultos. Metodología: este estudio observacional, descriptivo y exploratorio se realizó en agosto de 2023. Se incluyeron en este estudio adultos de ambos sexos. Se recolectaron datos sociodemográficos, y los participantes respondieron el Morningness-Eveningness Questionnaire de Horne y Östberg para evaluar el cronotipo, y el Patient Health Questionnaire de 2 ítems (PHQ-2) para evaluar los síntomas depresivos. Se utilizaron estadísticas descriptivas para todas las variables. Para la estadística inferencial, se utilizó la prueba de chi-cuadrado con un nivel de confianza del 95 %. Se utilizó odds ratio para cuantificar las relaciones. Resultados: un total de 105 personas participaron en el estudio, de las cuales el 58 % eran mujeres. La edad media de la muestra era de 29,4 ± 11,6 años. El 69 % de la muestra presentaba el cronotipo matutino, mientras que el 31 % presentaba el cronotipo vespertino. Se observó que el 31 % de los participantes puntuaba positivamente para depresión (PHQ-2 ≥ 3). Se encontró una relación entre el cronotipo y los puntos de corte del PHQ-2 (p=0,036). Se halló una OR=2,5 (IC 95%: 1,05-5,95) a favor del cronotipo vespertino para el desarrollo de depresión. Conclusión: casi siete de cada diez participantes tenían un cronotipo matutino, mientras que tres de cada diez dieron positivo en depresión. Los individuos con cronotipos vespertinos son más propensos a desarrollar síntomas depresivos que aquellos con cronotipos matutinos.

Introduction: chronotype is the natural predisposition of each individual to experience peaks of energy or moments of rest according to their circadian rhythm. Individuals may have morning, evening, or intermediate chronotypes that may be related to the development of depression. Objective: to determine the existence of an association between chronotype and depressive symptomatology in a sample of adults. Methodology: this observational, descriptive, and exploratory study was conducted in August 2023. Adults of both sexes were included in this study. Sociodemographic data were collected, and participants answered the Morningness-Eveningness Questionnaire by Horne and Östberg to assess chronotype, and the 2-item Patient Health Questionnaire (PHQ-2) to assess depressive symptoms. Descriptive statistics were used for all the variables. For inferential statistics, the chi-squared test was used with a confidence level of 95 %. Odds ratio was used to quantify the relationships. Results: a total of 105 people participated in the study, 58 % of whom were women. The mean age of the sample was 29.4 ± 11.6 years. Sixty-nine percent of the sample presented the morning chronotype, while 31 % presented the evening chronotype. It was found that 31 % of the participants scored positively for depression (PHQ-2 ≥ 3). A relationship was found between chronotype and PHQ-2 cutoff points (p=0.036). An OR=2.5 (95 % CI 1.05-5.95) was found in favor of the evening chronotype for the development of depression. Conclusion: almost seven out of ten participants had a morning chronotype, whereas three out of ten were positive for depression. Individuals with evening chronotypes are more likely to develop depressive symptoms than those with morning chronotypes.

Medical Students Training and Mental Health: An Exploratory Study

Introduction: Medical students are vulnerable to psychological distress and face a number of stressors such as academic pressures, economic concerns, and difficulties in interpersonal relationships. The quality of their educational training may also impact their mental health and subjective well-being. Objective: to describe their perception of subjective well-being and the impact of medical training on their own mental health. Methods: We surveyed 119 medical students and administered the "Perception survey on vocation, living and recreational habits, training and professional attitudes," the CAGE questionnaire, the Generalized Anxiety Disorder-7 (GAD-7) and the Patient Health Questionnaire-2 (PHQ-2). Results: Students' mean age was 22.5±2.28 years old and 59.7 % of participants were women, their lifestyle habits were scored as acceptable, and the employment of cell-phones and social networks ranged 76-99%; 24.1 % recognized a problematic alcohol, 67.2 % reported anxiety according to the GAD-7, and 49.6 % depression according to PHQ-2. Symptoms of anxiety were frequent among females and were higher when the perceived quality of training and student/teacher ratio were lower. Discussion: Students' perceptions of lower quality of training and resources seemed to be associated with higher levels of anxiety, which may suggest that educational policies and resources should be carefully revised and implemented to improve students' health and well-being.

Introducción: los estudiantes de medicina son vulnerables al malestar psicológico y se enfrentan a una serie de factores estresantes como las presiones académicas, las preocupaciones económicas y las dificultades en las relaciones interpersonales. La calidad de su formación educativa también puede influir en su salud mental y bienestar subjetivo. Objetivo: describir su percepción de bienestar subjetivo y el impacto de la formación médica en su propia salud mental. Metodología: se encuestó a 119 estudiantes de medicina y se les administró la "Encuesta de percepción sobre vocación, hábitos de vida y recreación, formación y actitudes profesionales", el cuestionario CAGE, el Trastorno de Ansiedad Generalizada-7 (TAG-7) y el Cuestionario de Salud del Paciente-2 (PHQ-2). Resultados: la edad media de los estudiantes fue de 22,5±2,28 años y el 59,7 % de los participantes eran mujeres; sus hábitos de vida se calificaron como aceptables, y el empleo de teléfonos móviles y redes sociales osciló entre el 76 y el 99 %; el 24,1 % reconoció un consumo problemático de alcohol, el 67,2 % manifestó ansiedad según el TAG-7, y el 49,6 % depresión según el PHQ-2. Los síntomas de ansiedad eran frecuentes entre las mujeres y eran mayores cuando la calidad percibida de la formación y la proporción alumnos/profesor eran menores. Discusión: la percepción por parte de los estudiantes de una menor calidad de la formación y de los recursos parecía estar asociada a mayores niveles de ansiedad, lo que puede sugerir que las políticas y los recursos educativos deberían revisarse y aplicarse cuidadosamente para mejorar la salud y el bienestar de los estudiantes.

Longitudinal characterization of TK6 cells sequentially adapted to animal product-free, chemically defined culture medium: considerations for genotoxicity studies.

Introduction: In vitro approaches are an essential tool in screening for toxicity of new chemicals, products and therapeutics. To increase the reproducibility and human relevance of these in vitro assessments, it is advocated to remove animal-derived products such as foetal bovine serum (FBS) from the cell culture system. Currently, FBS is routinely used as a supplement in cell culture medium, but batch-to-batch variability may introduce inconsistency in inter- and intra-lab assessments. Several chemically defined serum replacements (CDSR) have been developed to provide an alternative to FBS, but not every cell line adapts easily and successfully to CDSR-supplemented medium, and the long-term effect on cell characteristics remains uncertain. Aim: The aim of this study was to adapt the TK6 cell line to animal-product free CDSR-supplemented medium and evaluate the long-term effects on cell health, growth, morphology, phenotype, and function. This included a provisional assessment to determine the suitability of the transitioned cell line for standardised genotoxicity testing using the "in vitro mammalian cell micronucleus test" (OECD TG 487). Materials and methods: Gradual adaptation and direct adaptation methodologies were compared by assessing the cell proliferation, size and viability every passage until the cells were fully adapted to animal-free CDSR. The metabolic activity and membrane integrity was assessed every 4-8 passages by PrestoBlue and CytoTox-ONE™ Homogeneous Membrane Integrity Assay respectively. A detailed morphology study by high content imaging was performed and the expression of cell surface markers (CD19 and CD20) was conducted via flow cytometry to assess the potential for phenotypic drift during longer term culture of TK6 in animal-free conditions. Finally, functionality of cells in the OECD TG 487 assay was evaluated. Results: The baseline characteristics of TK6 cells cultured in FBS-supplemented medium were established and variability among passages was used to set up acceptance criteria for CDSR adapted cells. TK6 were adapted to CDSR supplemented medium either via direct or gradual transition reducing from 10% v/v FBS to 0% v/v FBS. The cell growth rate was compromised in the direct adaptation and therefore the gradual adaptation was preferred to investigate the long-term effects of animal-free CDSR on TK6 cells. The new animal cells showed comparable (p > 0.05) viability and cell size as the parent FBS-supplemented cells, with the exception of growth rate. The new animal free cells showed a lag phase double the length of the original cells. Cell morphology (cellular and nuclear area, sphericity) and phenotype (CD19 and CD20 surface markers) were in line (p > 0.05) with the original cells. The new cells cultured in CDSR-supplemented medium performed satisfactory in a pilot OECD TG 487 assay with compounds not requiring metabolic activation. Conclusion: TK6 cells were successfully transitioned to FBS- and animal product-free medium. The new cell cultures were viable and mimicked the characteristics of FBS-cultured cells. The gradual transition methodology utilised in this study can also be applied to other cell lines of interest. Maintaining cells in CDSR-supplemented medium eliminates variability from FBS, which in turn is likely to increase the reproducibility of in vitro experiments. Furthermore, removal of animal derived products from cell culture techniques is likely to increase the human relevance of in vitro methodologies.

Granulocyte-colony stimulating factor in acute-on-chronic liver failure: Systematic review and meta-analysis of randomized controlled trials / Factor estimulante de colonias de granulocitos en el fallo hepático agudo sobre crónico: revisión sistemática y metaanálisis de estudios aleatorizados controlados

Background and aims: A dysfunctional immune response is key to the pathogenesis of acute-on-chronic liver failure (ACLF). It has been suggested that treatment with granulocyte colony-stimulating factor (G-CSF) increases survival in patients with ACLF by improving immune cell dysfunction and promoting liver regeneration. The aim of the study is to evaluate the survival benefit associated with G-CSF administration compared with standard medical therapy (SMT) in ACLF. Methods: Systematic review and meta-analysis of randomized controlled trials. The primary outcome was survival at 60–90 days. We searched Ovid Medline, EMBASE, and Cochrane Central Register of Controlled Trials from inception to August 2021. Manual searches of reference lists in relevant articles and conference proceedings were also included. The revised Cochrane risk-of-bias tool was used for quality and risk of bias assessment. Two independent investigators extracted the data, and disagreements were solved by a third collaborator. Results: The initial search identified 142 studies. Four randomized controlled trials were selected for quantitative analysis including 310 patients (154 G-CSF and 156 SMT). Significant heterogeneity was observed (I2=74%, Chi2=11.57, p=0.009). G-CSF administration did not improve survival in patients with ACLF (random-effects model, risk ratio=0.64 [95% CI 0.39, 1.07]). However, when considering only the results from the studies performed in Asia, a significant decrease on mortality was observed (risk ratio=0.53 [95% CI 0.35, 0.81]). Severity scores (MELD and Child) and CD34+ peripheral cells mobilization did not significantly improve with G-CSF. Conclusion. In a systematic review and meta-analysis, G-CSF administration did not significantly improve overall survival compared to SMT in patients with ACLF...(AU)

Antecedentes y objetivos: La respuesta inmune disfuncional es clave en la patogénesis del fallo hepático agudo sobre crónico (ACLF). Se ha sugerido que la utilización de factor estimulante de colonias de granulocitos (G-CSF) aumenta la supervivencia de los pacientes con ACLF al mejorar la disfunción inmune y promover la regeneración hepática. El objetivo del estudio es evaluar el beneficio en supervivencia que proporciona la administración de G-CSF en comparación con el tratamiento médico estándar (SMT) en pacientes con ACLF. Métodos: Se llevó a cabo una revisión sistemática y meta-análisis de estudios aleatorizados y controlados. El objetivo principal fue analizar la supervivencia a los 60-90 días. Se realizó una búsqueda en Ovid Medline, EMBASE, y el registro central de estudios controlados de Cochrane desde su inicio hasta agosto 2021. También se realizaron búsquedas manuales en la bibliografía de artículos relevantes y presentaciones a congresos. Se utilizó la herramienta revisada de Cochrane para analizar la calidad y el riesgo de sesgos. Los datos fueron extraídos por dos investigadores independientes y las discrepancias fueron resueltas por un tercer investigador. Resultados: La búsqueda inicial identificó 142 estudios. De estos, 4 aleatorizados y controlados fueron elegidos para el análisis cuantitativo, incluyendo un total de 310 pacientes (154 G-CSF y 156 SMT). Se objetivó un alto grado de heterogeneidad entre los estudios (I2 = 74%, Chi 2 = 11.57, p = 0.009). La administración de G-CSF no aumentó la supervivencia en el grupo de pacientes con ACLF (modelo de efectos aleatorios, risk ratio = 0.64 [95% CI 0.39, 1.07]). Sin embargo, cuando se analizó el subgrupo de estudios realizados en Asia, sí se objetivó una disminución significativa de la mortalidad (risk ratio = 0.53 [95% CI 0.35, 0.81]). Las escalas de gravedad (MELD y Child) y la movilización de células CD34+ periféricas no mejoró significativamente tras la administración de G-CSF....(AU)

Suicides among adults in Paraguay: An 18-year national exploratory study (2004-2022).

BACKGROUND: The number of suicides has been increasing worldwide, year after year, becoming the fourth leading cause of death among young people between 15 and 29 years of age. AIM: In this study, we explored the frequency and characteristics of suicides among the adult general population in Paraguay between 2004 and 2022, considering that suicide attempts and suicidal risk/ideation are frequent and relevant issues in the consultation activity, even if epidemiological evidence on the national rates of suicide is scarce. METHODS: In this observational, descriptive, and exploratory study, official records of all deaths by suicide were reviewed and information analyzed. In addition, an attempt was made to predict the number of suicides in the next 5 years according to a mathematical modeling. RESULTS: In the 18-year period, 5,527 suicides of adults were recorded. Patients' mean age was 36.8 ± 17 years old. A 76.77% of them were males, 77.44% were from an urban area and 25.98% from the Greater Asunción and Central Department of Paraguay. The most frequently used method of suicide was intentional self-inflicted injury by hanging, strangulation, or suffocation (all 67.6%). The expected number of national suicides in the following years from 2023 to 2027 will range between 462 and 530. Limitations include the lack of information regarding diagnoses and personal history in the suicide reports as well as the possibility of underreporting of national suicide cases. CONCLUSION: Our results represent the first large national epidemiological report of suicides in Paraguay and may be of interest for mental health professionals and health authorities in order to reduce the suicide mortality rate within the country.

Ansiedad, depresión y vulnerabilidad al estrés en personas con diagnóstico de artritis reumatoidea: un estudio exploratorio del Hospital de Clínicas de la Universidad Nacional de Asunción / Anxiety, depression, and vulnerability to stress in people diagnosed with rheumatoid arthritis: An exploratory study at the Hospital de Clínicas of the Universidad Nacional de Asunción

Antecedentes: Estudios observacionales han descrito una alta prevalencia de depresión y ansiedad en la artritis reumatoidea: los trastornos depresivos mayores se detectan en el 17 % de los pacientes con la patología, y la inflamación local y sistémica desempeña un papel importante en la ansiedad y la depresión. Objetivos: El objetivo general de esta investigación fue determinar la frecuencia de ansiedad, depresión y vulnerabilidad al estrés en pacientes con diagnóstico de artritis reumatoidea. Materiales y métodos: Este fue un estudio observacional, descriptivo de asociación cruzada y temporalmente prospectivo. El muestreo fue no probabilístico de casos consecutivos. Se incluyó a personas adultas con diagnóstico de artritis reumatoide que consultaron en el Departamento de Reumatología del Hospital de Clínicas, entre agosto y octubre del 2022. Para el diagnóstico psiquiátrico se utilizaron los siguientes instrumentos: Escala de Ansiedad Generalizada (GAD-7), Patient Health Questionnaire (PHQ-2) y Escala de Vulnerabilidad al Estrés de Smith y Miller. Resultados: Se incluyó a 36 pacientes, todas mujeres, con edades comprendidas entre los 20 y 77 años. El 27,8 % tenía depresión, según los puntos de corte del PHQ-2. El 22,2 % presentaba ansiedad, según los puntos de corte de GAD-7. En cuanto al estrés, el 22,2 % tenía vulnerabilidad a este y el 5,6 % era seriamente vulnerable. Conclusión: Depresión, ansiedad y vulnerabilidad al estrés son comorbilidades frecuentemente observadas en pacientes con artritis reumatoidea. Se requieren de intervenciones específicas de salud mental para abordar estas cuestiones y mejorar la calidad de vida de los pacientes afectados.

Background: Observational studies have described a high prevalence of depression and anxiety in rheumatoid arthritis: major depressive disorders are detected in 17 % of patients with the pathology, and local and systemic inflammation play an important role in anxiety and depression. Objectives: The overall objective of this research was to determine the frequency of anxiety, depression, and vulnerability to stress in patients diagnosed with rheumatoid arthritis. Materials and methods: This was an observational, descriptive, temporally prospective, cross-association study. Sampling was non-probabilistic of consecutive cases. We included adults with a diagnosis of rheumatoid arthritis who consulted at the Rheumatology Department of the Hospital de Clínicas between August and October 2022. The following instruments were used for psychiatric diagnosis: Generalized Anxiety Scale (GAD-7), Patient Health Questionnaire (PHQ-2) and Smith and Miller's Stress Vulnerability Scale. Results: Thirty-six patients, all women, aged between 20 and 77 years, were included in the study. The 27.8 % had depression, according to the cut-off points of the PHQ-2. Anxiety was present in 22.2 %, according to the GAD-7 cut-off points. Regarding stress, 22.2 % were vulnerable to stress and 5.6 % were seriously vulnerable. Conclusion: Depression, anxiety and vulnerability to stress are frequently observed comorbidities in patients with rheumatoid arthritis. Specific mental health interventions are required to address these issues and improve the quality of life of affected patients.

Contribution of Low CD4 Cell Counts and High Human Immunodeficiency Virus (HIV) Viral Load to the Efficacy of Preferred First-Line Antiretroviral Regimens for Treating HIV Infection: A Systematic Review and Meta-Analysis.

We assessed whether low CD4 count and high viral load (VL) affect the response to currently preferred ART. We performed a systematic review of randomized, controlled clinical trials that analyzed preferred first-line ART and a subgroup analysis by CD4 count (≤ or >200 CD4/µL) or VL (≤ or >100 000 copies/mL). We computed the odds ratio (OR) of treatment failure (TF) for each subgroup and individual treatment arm. Patients with ≤200 CD4 cells or VL ≥100 000 copies/mL showed an increased likelihood of TF at 48 weeks: OR, 1.94; 95% confidence interval (CI): 1.45-2.61 and OR, 1.75; 95% CI: 1.30-2.35, respectively. A similar increase in the risk of TF was observed at 96 weeks. There was no significant heterogeneity regarding integrase strand transfer inhibitor or nucleoside reverse transcriptase inhibitor backbone. Our results show that CD4 <200 cells/µL and VL ≥100,000 copies/mL impair ART efficacy in all preferred regimens.

Satisfaction with Telepsychiatry during the COVID-19 pandemic: Patients' and psychiatrists' report from a University Hospital.

BACKGROUND: The COVID-19 pandemic has led to important changes in the approach to patients worldwide. Different agencies have proposed and implemented telemedicine-based care services in order to ensure access to health care for all people. AIM: The aim of this study was to determine the satisfaction of patients using the Telepsychiatry service offered by the Department of Psychiatry of the Hospital de Clínicas (National University of Asunción, Paraguay). METHODS: A cross sectional and descriptive study has been conducted. Participants were recruited through a phone-based survey. Satisfaction with Telepsychiatry has been measured with an adapted version of a satisfaction survey in Teleneurology. As a complement, psychiatrists from the Hospital de Clínicas were also interviewed about their rate of satisfaction with Telepsychiatry. RESULTS: A total of 530 patients were included, 51.3% of whom were women. The consultation satisfaction scale ranged between 2.15 and 4.30 with a mean score of 3.02 ± 0.32. Cronbach's alpha for the scale was .897, indicating a good internal consistency. Patients' satisfaction was higher for the perception of Telepsychiatry and lower for the doctor-patient relationship. Of the physicians, 87.5% were satisfied with the Telepsychiatry service. CONCLUSION: The satisfaction overall score indicates patients' general satisfaction with the quality of care in Telepsychiatry, mainly regarding the perception of health care. and lower satisfaction with the doctor-patient relationship. Nine out of 10 psychiatrists felt satisfied with the Telepsychiatry service and considered that the degree of patient's satisfaction was acceptable during the Telepsychiatry consultation.

Granulocyte-colony stimulating factor in acute-on-chronic liver failure: Systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: A dysfunctional immune response is key to the pathogenesis of acute-on-chronic liver failure (ACLF). It has been suggested that treatment with granulocyte colony-stimulating factor (G-CSF) increases survival in patients with ACLF by improving immune cell dysfunction and promoting liver regeneration. The aim of the study is to evaluate the survival benefit associated with G-CSF administration compared with standard medical therapy (SMT) in ACLF. METHODS: Systematic review and meta-analysis of randomized controlled trials. The primary outcome was survival at 60-90 days. We searched Ovid Medline, EMBASE, and Cochrane Central Register of Controlled Trials from inception to August 2021. Manual searches of reference lists in relevant articles and conference proceedings were also included. The revised Cochrane risk-of-bias tool was used for quality and risk of bias assessment. Two independent investigators extracted the data, and disagreements were solved by a third collaborator. RESULTS: The initial search identified 142 studies. Four randomized controlled trials were selected for quantitative analysis including 310 patients (154 G-CSF and 156 SMT). Significant heterogeneity was observed (I2=74%, Chi2=11.57, p=0.009). G-CSF administration did not improve survival in patients with ACLF (random-effects model, risk ratio=0.64 [95% CI 0.39, 1.07]). However, when considering only the results from the studies performed in Asia, a significant decrease on mortality was observed (risk ratio=0.53 [95% CI 0.35, 0.81]). Severity scores (MELD and Child) and CD34+ peripheral cells mobilization did not significantly improve with G-CSF. CONCLUSION: In a systematic review and meta-analysis, G-CSF administration did not significantly improve overall survival compared to SMT in patients with ACLF. The beneficial effects observed in Asian studies, as opposed to the European region, suggest that specific populations may benefit from further research aiming to identify certain subgroups with favourable outcomes when using G-CSF.

Factores asociados y propiedades psicométricas de la versión en español del Test Breve de Irritabilidad (BITe) en población paraguaya / Associated factors and psychometric properties of the Spanish version of the Brief Irritability Test (BITe) in Paraguayan population

Antecedentes: La irritabilidad, como síntoma transdimensional, está presente en varios trastornos mentales. Este estudio investigó las propiedades psicométricas de la versión española del Test Breve de Irritabilidad (BITe). Sujetos y métodos: el reclutamiento se realizó a través de una encuesta en línea lanzada a través de las redes sociales comunes (Facebook, Twitter) y aplicaciones de mensajería (WhatsApp, Telegram) del 1 al 31 de mayo de 2022. Los sujetos incluidos fueron personas ≥ 18 años de edad de ambos sexos 1920 individuos fueron calificados para el analisis de validacion. El BITe ha sido traducido al español y validado mediante análisis factorial confirmatorio. Los participantes también han sido puntuados con el Cuestionario de Agresión (AQ). Resultados: la prueba de Kaiser-Meyer-Olkin (KMO) fue adecuada (KMO=0,880) y la esfericidad se probó significativamente (p<0,001). El análisis confirmatorio que garantiza que la escala es unidimensional. El ajuste del modelo fue bueno, según todos los índices de ajuste. El alfa de Cronbach también garantiza una excelente consistencia interna (α=0,91). Las calculadoras entre las dos escalas (BITe y AQ) han mostrado una buena convergencia (r=0,512; p<0,001). Conclusiones: La versión en español del BITe es una escala unidimensional de cinco elementos tipo Likert que muestra buena validez interna y alta confiabilidad, lo que implica que esta versión tiene excelentes propiedades psicométricas tanto para hombres como para mujeres hispanohablantes.

Background: Irritability, as a trans dimensional symptom, is present in several mental disorders.This study investigated the psychometric properties of the Spanish version of the Brief Irritability Test (BITe). Subjects and Methods: The recruitment has been performed through an online survey launched through common social media (Facebook, Twitter) and messaging apps (WhatsApp, Telegram) from 1st to 31st May 2022. Subjects included were individuals ≥18 years old of age of both sexes. 1920 individuals were rated for the validation analysis. The BITe has been translated into Spanish and validated through confirmatory factor analysis. Participants have been also scored with the Aggression Questionnaire (AQ). Results: Kaiser-Meyer-Olkin (KMO) test was adequate (KMO=0.880) and sphericity tested significantly (p<0.001). The confirmatory analysis confirmed that the scale is one- imensional. The model adjustment was good, according to all fit indices. Cronbach's alpha also confirmed an excellent internal consistency (α=0.91). Scores between the two scales (the BITe and the AQ) have shown a good convergence (r=0.512; p<0.001). Conclusions: The Spanish version of the BITe is a unidimensional scale of five Likerttype items that shows good internal validity and high reliability, which implies that this version has excellent psychometric properties for both male and female Spanish-speakers

Smartphone-RCCT: an online repository of randomized controlled clinical trials of smartphone applications for chronic conditions.

BACKGROUND: Chronic health conditions have a big impact on disability, morbidity, and mortality worldwide. Smartphone health applications (apps) can improve the health of patients with chronic conditions and enhance the quality and efficiency of healthcare. The number of randomized controlled trials (RCTs) of smartphone health apps is increasing, but a collection of the available evidence into a single database is still missing. The purpose of this study is to describe Smartphone-RCCT, which is an in-progress database of RCTs of smartphone apps for chronic conditions. METHODS: For a study to be included in the database, the following criteria had to be met: (a) RCT published in a peer-reviewed journal; (b) population: adult study participants with one or several chronic conditions that represent the main health problem addressed by the study intervention; (c) intervention: smartphone health app used by the patient; (d) comparator: any control condition; (e) outcomes: any patient-reported health outcome (studies exclusively measuring the patients' knowledge about the chronic conditions or their satisfaction with the smartphone app were excluded); (f) sample size: at least 15 participants per study arm. We searched in electronic databases and other resources to identify relevant studies. Two reviewers selected the studies and extracted data independently. Annual updates are planned. RESULTS: The proposed database is called Smartphone-RCCT, an open-access repository collecting bibliographic references and important characteristics of RCTs of smartphone apps for chronic conditions. The database is available for free in Open Science Framework (OSF): https://osf.io/nxerf/ . To date, it includes 70 trials. Their references can be exported to standard reference management software and the extracted data is available in a Microsoft Excel file. CONCLUSIONS: Smartphone-RCCT is the first systematic open-access database collecting peer-reviewed publications of RCTs of smartphone apps for patients with chronic conditions. The database accelerates the delivery of evidence-based information in a dynamic research field. It represents an essential resource for different stakeholders, such as professionals working in evidence synthesis, meta-epidemiological studies, or planning an RCT.

Cannabis use and the development of psychosis or schizophrenia, analysis of current legislation and regional mapping: A systematic review

Objective: This systematic review aims to summarize the findings of studies that investigated the risk, precocity and intensity of psychosis in cannabis users, taking into account the status of legalization and/or decriminalization of cannabis use in different countries. Methodology: Articles published up to May 2018 were included, in English, Portuguese and Spanish, all extracted from the PubMed and SciELO databases, respecting the inclusion and exclusion criteria. Results: 19 studies from 18 countries were included. The relationship of cannabis use and the onset of psychotic symptoms was sufficiently substantiated. However, there was no data that supported an increase in the risk, precocity or intensity of psychosis in cannabis users from countries with higher levels of legalization/decriminalization of cannabis use to the date of the present study. Conclusion: The use of cannabis is associated with the development of psychosis. So far, there is no data pointing to an increase in the precocity, risk or intensity of psychosis in cannabis users, due to the legalization or decriminalization of the use of cannabis. However, the absence of data to date does not exclude these possibilities, since none of the studies analyzed in this review specifically assessed the effects of legalization/decriminalization policies on those outcomes. Therefore, prospective studies focused on the effects of legalization or decriminalization policies should be conducted in countries such as Canada, Spain, the United States of America (some states), the Netherlands, and Uruguay.

Objetivo: esta revisión sistemática pretende resumir los hallazgos de los estudios que investigaron el riesgo, la precocidad y la intensidad de la psicosis en los consumidores de cannabis, teniendo en cuenta el estado de legalización y/o despenalización del consumo de cannabis en diferentes países. Metodología: fueron incluidos artículos publicados hasta mayo de 2018, en lengua inglesa, portuguesa y española, todos extraídos de las bases de datos PubMed y SciELO, respetando los criterios de inclusión y exclusión. Resultados: se incluyeron 19 estudios de 18 países. La relación entre el consumo de cannabis y el inicio de síntomas psicóticos estuvo suficientemente fundamentada. Sin embargo, no hubo datos que respaldaran un aumento en el riesgo, la precocidad o la intensidad de la psicosis en los consumidores de cannabis de países con niveles más altos de legalización/despenalización del uso de cannabis hasta la fecha del presente estudio. Conclusión: el consumo de cannabis está asociado con el desarrollo de psicosis. Hasta el momento, no hay datos que indiquen un aumento en la precocidad, el riesgo o la intensidad de la psicosis en usuarios de cannabis, debido a la legalización o despenalización del uso de cannabis. Sin embargo, la ausencia de datos hasta la fecha no excluye estas posibilidades, ya que ninguno de los estudios analizados en esta revisión evaluó específicamente los efectos de las políticas de legalización/despenalización en esos resultados. Por ello, los estudios prospectivos centrados en los efectos de las políticas de legalización o despenalización deben llevarse a cabo en países como Canadá, España, los Estados Unidos de América (algunos estados), los Países Bajos y Uruguay.

Anxiety, Addiction to Social Networks, Internet and Smartphones in Paraguayan Adolescents: A Brief Report.

Background: Several authors have pointed out that the use of smartphones might have an impact on mental health in general. Most of the evidences are focused on the incorrect or overblown use of smartphones, videogame or Internet, particularly focusing on related addiction problems among adolescents. Objective: The present study, although preliminary, aims to report the first evidence in Paraguay regarding the association between anxiety and addiction to social networks/internet as well as the use of smartphones among adolescents. Method: Participants (100 adolescents, aged 12- 17 years old) were assessed in a school setting with the Beck Anxiety Inventory (BAI) and the Scale of risk of Addiction to Social Networks and Internet for adolescents (ERA-RSI). Categorical variables and associations were statistically assessed. Results: The average smartphone use in boys rated 8.06 ±3.81 hours and in girls 9.46 ±4.4 hours. The BAI mean score was 20.71 ± 13.2. Of the participants, 27% reported moderate anxiety, and 36% severe anxiety and scores on this scale were not associated with hours of smartphone use. The ERA-RSI mean score was 1.94 ± 0.46 and anxiety was related to the symptoms-addiction, social-use, and nomophobia dimensions of the scale. Conclusion: The misuse of smartphones in the Paraguayan pediatric population has been reported to be closely related to anxious symptoms. Our results suggest further research with an impact on possible public health policies aimed at preserving the mental health of children and adolescents exposed to internet and electronic devices.