Use of medicinal cannabis derivatives in a pediatric population in Uruguay during 2019-2021

Florencia Alvarez: Estudiante de Facultad de Medicina, Universidad de la República. Montevideo, Uruguay.-- Antonella Guido: Estudiante de Facultad de Medicina, Universidad de la República. Montevideo, Uruguay.-- Martina Morandi: Estudiante de Facultad de Medicina, Universidad de la República. Montevideo, Uruguay.-- Valeria Oliveira: Estudiante de Facultad de Medicina, Universidad de la República. Montevideo, Uruguay.-- Germán Rivas: Estudiante de Facultad de Medicina, Universidad de la República. Montevideo, Uruguay.-- Luiggi Vega: Estudiante de Facultad de Medicina, Universidad de la República. Montevideo, Uruguay.-- Florencia Galarraga: Docente supervisor. Profesora Adjunta del Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad de la República, Hospital de Clínicas Dr. Manuel Quintela, Montevideo, Uruguay. Correo electrónico: [email protected] Martín Notejane: Docente supervisor. Profesor Adjunto de Clínica Pediátrica “B”, Facultad de Medicina, Universidad de la República, Centro Hospitalario Pereira Rossell, Montevideo, Uruguay. Correo electrónico: [email protected] Irene Wood: Docente supervisor. Asistente del Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad de la República, Hospital de Clínicas Dr. Manuel Quintela, Montevideo, Uruguay. Correo electrónico: [email protected] Noelia Speranza: Docente supervisor. Profesora Agregada del Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad de la República, Hospital de Clínicas Dr. Manuel Quintela, Montevideo, Uruguay. Correo electrónico: [email protected] Uruguay el uso de derivados de cannabis medicinal (DCM) se enmarca en la Ley 19.172, aprobada en 2013. No existen hasta el momento trabajos publicados a nivel nacional que exploren el perfil de uso de DCM en niños, niñas y adolescentes (NNA). El objetivo fue describir los usos de DCM en NNA usuarios del Centro Hospitalario Pereira Rossell (HP-CHPR) y en la Clínica de Endocannabinología del Uruguay (CEDU) entre los años 2019- 2021. Se realizó un estudio descriptivo, transversal; mediante encuesta telefónica y revisión de historias clínicas. Se incluyeron 26 NNA, con una media de edad 7,8 años; 18 varones, procedentes de Uruguay 23 y 3 de Argentina; portadores de enfermedades neurológicas severas con epilepsia refractaria (16/26) y trastorno del espectro autista (TEA) 7, con síntomas múltiples y simultáneos. El DCM más utilizado fue Epifractán® (21/26) por vía oral. De los cuidadores entrevistados 18/26 reportaron que los NNA tuvieron algún tipo de mejoría sintomática global con el DCM; para epilepsia refractaria 13/17 refirieron reducción del número y duración de las crisis. En NNA cuya indicación fueron síntomas vinculados a TEA, reportaron mejoría para insomnio, trastornos del lenguaje, cambios de humor y déficit atencional. Previo al tratamiento, la mayoría de los cuidadores refirieron tener expectativas de mejoría. Se reportaron efectos adversos en 4/26, ninguno requirió hospitalización. Para ambas indicaciones se constataron beneficios y escasos efectos adversos. Será importante continuar analizando los DCM empleados en otras patologías pediátricas y realizar un seguimiento de su efectividad y seguridad.Medical cannabis use in Uruguay is framed in the law number 19.172, approved in 2013. There are no national works published until this point that explore the usage profile of medical cannabis in children and adolescents (C&A). The objective was to describe the uses of medical cannabis in C&A users of Centro Hospitalario Pereira Rossell (HP-CHPR) and Clínica de Endocannabinología del Uruguay (CEDU) between 2019-2021. A descriptive, transversal study was carried out through telephone interviews and medical history revision. 26 children were included, with a mean age of 7.8 years; 18 men, 23 from Uruguay and 3 from Argentina, with severe neurological diseases with refractory epilepsy (16/26) and autism spectrum disorder (ASD) 7, with multiple and simultaneous symptoms. The medical cannabis mostly used was Epifractán® (21/26) orally administered. According to the guardians surveyed, 18/26 C&A have had some global symptomatic improvement with medical cannabis; for refractory epilepsy 13/17 reported a decrease in the number and duration of seizures. On C&A whose indications were ASD symptoms, it was reported there had been improvement in insomnia, language disorders, mood disorders and attention-deficit. Previously to treatment onset, most guardians referred to having expectations of improvements. There were 4/26 adverse effects reported and none required hospitalization. For both indications were corroborated benefits and scarce adverse effects. It’ll be important to continue analyzing the medical cannabis usage on other pathologies and execute a long-term tracking of efficiency and security

Cystatin D locates in the nucleus at sites of active transcription and modulates gene and protein expression

Cystatin D is an inhibitor of lysosomal and secreted cysteine proteases. Strikingly, cystatin D has been found to inhibit proliferation, migration, and invasion of colon carcinoma cells indicating tumor suppressor activity that is unrelated to protease inhibition. Here, we demonstrate that a proportion of cystatin D locates within the cell nucleus at specific transcriptionally active chromatin sites. Consistently, transcriptomic analysis show that cystatin D alters gene expression, including that of genes encoding transcription factors such as RUNX1, RUNX2, and MEF2C in HCT116 cells. In concordance with transcriptomic data, quantitative proteomic analysis identified 292 proteins differentially expressed in cystatin D-expressing cells involved in cell adhesion, cytoskeleton, and RNA synthesis and processing. Furthermore, using cytokine arrays we found that cystatin D reduces the secretion of several protumor cytokines such as fibroblast growth factor-4, CX3CL1/fractalkine, neurotrophin 4 oncostatin-M, pulmonary and activation-regulated chemokine/CCL18, and transforming growth factor B3. These results support an unanticipated role of cystatin D in the cell nucleus, controlling the transcription of specific genes involved in crucial cellular functions, which may mediate its protective action in colon cancer

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Incidence and clinical manifestations of giant cell arteritis in Spain: results of the ARTESER register

Objective This study aimed to estimate the incidence of giant cell arteritis (GCA) in Spain and to analyse its clinical manifestations, and distribution by age group, sex, geographical area and season.Methods We included all patients diagnosed with GCA between 1 June 2013 and 29 March 2019 at 26 hospitals of the National Health System. They had to be aged ≥50 years and have at least one positive results in an objective diagnostic test (biopsy or imaging techniques), meet 3/5 of the 1990 American College of Rheumatology classification criteria or have a clinical diagnosis based on the expert opinion of the physician in charge. We calculated incidence rate using Poisson regression and assessed the influence of age, sex, geographical area and season.Results We identified 1675 cases of GCA with a mean age at diagnosis of 76.9±8.3 years. The annual incidence was estimated at 7.42 (95% CI 6.57 to 8.27) cases of GCA per 100 000 people ≥50 years with a peak for patients aged 80–84 years (23.06 (95% CI 20.89 to 25.4)). The incidence was greater in women (10.06 (95% CI 8.7 to 11.5)) than in men (4.83 (95% CI 3.8 to 5.9)). No significant differences were found between geographical distribution and incidence throughout the year (p=0.125). The phenotypes at diagnosis were cranial in 1091 patients, extracranial in 337 patients and mixed in 170 patients.Conclusions This is the first study to estimate the incidence of GCA in Spain at a national level. We found a predominance among women and during the ninth decade of life with no clear variability according to geographical area or seasons of the year