Estudio del ruido generado por las actividades académicas y administrativas en UNIMINUTO- Centro Regional Soacha – 2017

Mediante la realización de este estudio, se pretende implementar un programa que logre a nivel pedagógico involucrar a los estudiantes y a los docentes sobre la reducción de ruido en las aulas de clases. Se busca que los alumnos aprendan a reducir o aminorar los ruidos generados en las aulas de clase, involucrar a los alumnos en estos programas y además en temas como capacitaciones de qué es el ruido y los peligros para la salud que este genera

Caracterización de eventos adversos a medicamentos asociados al Whoart alteraciones fetales reportados al programa distrital de farmacovigilancia durante el periodo 2012 a 2017

93 páginas : ilustraciones, gráficasThe use of drugs in the gestational state is of interest in Pharmacovigilance, because of the effects derived from consumption, which are sometimes unknown. In the present study, adverse events to medications related to the WHOART Fetal Alterations, occurred and reported in the city of Bogotá, were analyzed. An analysis was made of the reports between 2012 and 2017 that were notified to the District Pharmacovigilance Program related to the WHOART fetal alterations, classifying them into Adverse Drug Reactions (RAM). The WHO algorithm was used to classify the RAM; The causality of the RAM was evaluated using the WHO algorithm. In summary, 4 abortion notifications, 2 congenital heart diseases, 1 case of polydactyly and 1 of bradycardia were presented. All serious serious reports. According to type of RAM, the majority of reports correspond to type A with 7 cases, type D a case. According to the WHO algorithm, 4 of the cases were classified as Probable, 1 cases as Unclassifiable due to the little information reported by the notifier, 2 possible case, 1 unlikely case. According to the reports analyzed for the WHOART Fetal disorders it was found that, of the 8 cases, 2 were registered by antiepileptics such as Valproic Acid and Levetiracetam. The presence of congenital heart disease in the report of the newborn is probably due to the Levetiracetam to which the mother was exposed, a probable mechanism of the teratogenic action of antiepileptics, is the production of heart rhythm disorders by direct action of drugs on the fetal heart Another case of adverse reaction in newborns occurs in childbirth when peridural anesthesia with bupivacaine is administered in a pregnant mother, developing bradycardia in the newborn. From the report in which abortion was recorded due to the consumption of the antidepressant Bupropion, the literature mentions that the use of this medication during the first trimester has been associated with fetal heart malformations in 1.3% and abortions in 15.4%. medications associated with congenital heart disease presented in the report, are Hydralazine, which has been the most commonly used treatment in severe hypertensive crisis and pre-eclampsia, with no teratogenic effects detected. Information from the present study shows that immunosuppressive therapies are associated with spontaneous abortion, such as fingolimod and natalizumab. According to a case study conducted with Fingolimod in pregnant patients, it is reported that spontaneous abortion occurs in 15% to 20% of known pregnancies, and the main birth defects occur in 4% to 8% of pregnancies. The same happens with natalizumab, which is not recommended for use during breastfeeding or pregnancy. Finally, reported abortion is reported, due to the administration of Tocilizumab in combination with Methotrexate, according to a clinical study it is confirmed that Methotrexate is a known and abortive teratogen.El uso de medicamentos en el estado gestacional es de interés en Farmacovigilancia, en razón los efectos derivados del consumo, que en ocasiones son desconocidos. En el presente estudio se analizaron los eventos adversos a medicamentos relacionados con el WHOART Alteraciones Fetales, ocurridos y reportados en la ciudad de Bogotá. Se realizó un análisis de los reportes entre el 2012 y 2017 que fueron notificados al Programa Distrital de Farmacovigilancia relacionados con el WHOART alteraciones fetales, clasificándolos en Reacciones Adversas a Medicamentos (RAM). Para la clasificación de las RAM se utilizó el algoritmo de la OMS; la causalidad de las RAM se evaluó utilizando el algoritmo de la OMS. En resumen se presentaron 4 notificaciones de aborto, 2 cardiopatías congénitas, 1 caso de polidactilia y 1 de bradicardia. Todos reportes serios graves. Según tipo de RAM la mayoría de reportes corresponden a tipo A con 7 Casos, tipo D un caso. Según algoritmo de la OMS, 4 de los casos fueron clasificados como Probable, 1 casos como Inclasificable debido a la poca información reportada por el notificante, 2 caso posible, 1 caso improbable. De acuerdo a los reportes analizados para el WHOART Alteraciones fetales se encontró que, de los 8 casos, 2 fueron registrados por antiepilépticos como el Ácido Valproico y Levetiracetam. La presencia de cardiopatía congénita en el reporte del recién nacido, probablemente se deba al Levetiracetam al que estuvo expuesta la madre, un mecanismo probable de la acción teratogénica de los antiepilépticos, es la producción de trastornos del ritmo cardiaco por acción directa de los fármacos sobre el corazón fetal. Otro caso de reacción adversa en recién nacido se da en el parto cuando se administra anestesia peridural con bupivacaína en madre gestante, desarrollándose bradicardia en el recién nacido. Del reporte en el que se registró aborto por consumo del antidepresivo Bupropion, la literatura menciona que el uso de este medicamento durante el primer trimestre se ha asociado a malformaciones cardíacas fetales en 1,3% y abortos en un 15,4% Dentro de los medicamentos asociados a cardiopatías congénitas presentados en el reporte, se encuentran la Hidralazina, la cual ha sido el tratamiento más empleado en crisis hipertensivas graves y la pre-eclampsia, sin que se hayan detectado efectos teratogénicos. La información del presente estudio muestra que las terapias con inmunosupresores están asociadas a aborto espontaneo, tales como fingolimod y natalizumab. Según un estudio de caso realizado con Fingolimod en pacientes embarazadas, se presenta que el aborto espontáneo ocurre en el 15% a 20% de los embarazos conocidos, y los principales defectos de nacimiento ocurren en el 4% al 8% de los embarazos. De igual manera ocurre con el natalizumab, el cual no se recomienda su uso ni durante la lactancia ni en embarazo. Finalmente, se reporta aborto retenido, debido a la administración de Tocilizumab en combinación con Metotrexato, de acuerdo a un estudio clínico se confirma que el Metotrexato es un teratógeno conocido y abortivo.Incluye bibliografíaPregradoQuímico(a) Farmacéutic

The 2021 Eurpean Alliance of Associations for Rheumatology/American College of Rheumatology points to consider for diagnosis and management of autoinflammatory type i interferonopathies: CANDLE/PRAAS, SAVI and AGS

Objective: Autoinflammatory type I interferonopathies, chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature/proteasome-associated autoinflammatory syndrome (CANDLE/PRAAS), stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI) and Aicardi-Goutières syndrome (AGS) are rare and clinically complex immunodysregulatory diseases. With emerging knowledge of genetic causes and targeted treatments, a Task Force was charged with the development of \u27points to consider\u27 to improve diagnosis, treatment and long-term monitoring of patients with these rare diseases. Methods: Members of a Task Force consisting of rheumatologists, neurologists, an immunologist, geneticists, patient advocates and an allied healthcare professional formulated research questions for a systematic literature review. Then, based on literature, Delphi questionnaires and consensus methodology, \u27points to consider\u27 to guide patient management were developed. Results: The Task Force devised consensus and evidence-based guidance of 4 overarching principles and 17 points to consider regarding the diagnosis, treatment and long-term monitoring of patients with the autoinflammatory interferonopathies, CANDLE/PRAAS, SAVI and AGS. Conclusion: These points to consider represent state-of-the-art knowledge to guide diagnostic evaluation, treatment and management of patients with CANDLE/PRAAS, SAVI and AGS and aim to standardise and improve care, quality of life and disease outcomes

The 2021 EULAR and ACR points to consider for diagnosis and management of autoinflammatory type I interferonopathies: CANDLE/PRAAS, SAVI and AGS

Objective: Autoinflammatory type I interferonopathies, chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature/proteasome-associated autoinflammatory syndrome (CANDLE/PRAAS), stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI) and Aicardi-Goutières syndrome (AGS) are rare and clinically complex immunodysregulatory diseases. With emerging knowledge of genetic causes and targeted treatments, a Task Force was charged with the development of 'points to consider' to improve diagnosis, treatment and long-term monitoring of patients with these rare diseases. Methods: Members of a Task Force consisting of rheumatologists, neurologists, an immunologist, geneticists, patient advocates and an allied healthcare professional formulated research questions for a systematic literature review. Then, based on literature, Delphi questionnaires and consensus methodology, 'points to consider' to guide patient management were developed. Results: The Task Force devised consensus and evidence-based guidance of 4 overarching principles and 17 points to consider regarding the diagnosis, treatment and long-term monitoring of patients with the autoinflammatory interferonopathies, CANDLE/PRAAS, SAVI and AGS. Conclusion: These points to consider represent state-of-the-art knowledge to guide diagnostic evaluation, treatment and management of patients with CANDLE/PRAAS, SAVI and AGS and aim to standardise and improve care, quality of life and disease outcomes

The 2021 EULAR and ACR points to consider for diagnosis and management of autoinflammatory type I interferonopathies: CANDLE/PRAAS, SAVI and AGS

Objective: Autoinflammatory type I interferonopathies, chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature/proteasome-associated autoinflammatory syndrome (CANDLE/PRAAS), stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI) and Aicardi-Goutières syndrome (AGS) are rare and clinically complex immunodysregulatory diseases. With emerging knowledge of genetic causes and targeted treatments, a Task Force was charged with the development of 'points to consider' to improve diagnosis, treatment and long-term monitoring of patients with these rare diseases. Methods: Members of a Task Force consisting of rheumatologists, neurologists, an immunologist, geneticists, patient advocates and an allied healthcare professional formulated research questions for a systematic literature review. Then, based on literature, Delphi questionnaires and consensus methodology, 'points to consider' to guide patient management were developed. Results: The Task Force devised consensus and evidence-based guidance of 4 overarching principles and 17 points to consider regarding the diagnosis, treatment and long-term monitoring of patients with the autoinflammatory interferonopathies, CANDLE/PRAAS, SAVI and AGS. Conclusion: These points to consider represent state-of-the-art knowledge to guide diagnostic evaluation, treatment and management of patients with CANDLE/PRAAS, SAVI and AGS and aim to standardise and improve care, quality of life and disease outcomes

Autoantibodies Against Proteins Previously Associated With Autoimmunity in Adult and Pediatric Patients With COVID-19 and Children With MIS-C

The antibody profile against autoantigens previously associated with autoimmune diseases and other human proteins in patients with COVID-19 or multisystem inflammatory syndrome in children (MIS-C) remains poorly defined. Here we show that 30% of adults with COVID-19 had autoantibodies against the lung antigen KCNRG, and 34% had antibodies to the SLE-associated Smith-D3 protein. Children with COVID-19 rarely had autoantibodies; one of 59 children had GAD65 autoantibodies associated with acute onset of insulin-dependent diabetes. While autoantibodies associated with SLE/Sjögren’s syndrome (Ro52, Ro60, and La) and/or autoimmune gastritis (gastric ATPase) were detected in 74% (40/54) of MIS-C patients, further analysis of these patients and of children with Kawasaki disease (KD), showed that the administration of intravenous immunoglobulin (IVIG) was largely responsible for detection of these autoantibodies in both groups of patients. Monitoring in vivo decay of the autoantibodies in MIS-C children showed that the IVIG-derived Ro52, Ro60, and La autoantibodies declined to undetectable levels by 45-60 days, but gastric ATPase autoantibodies declined more slowly requiring >100 days until undetectable. Further testing of IgG and/or IgA antibodies against a subset of potential targets identified by published autoantigen array studies of MIS-C failed to detect autoantibodies against most (16/18) of these proteins in patients with MIS-C who had not received IVIG. However, Troponin C2 and KLHL12 autoantibodies were detected in 2 of 20 and 1 of 20 patients with MIS-C, respectively. Overall, these results suggest that IVIG therapy may be a confounding factor in autoantibody measurements in MIS-C and that antibodies against antigens associated with autoimmune diseases or other human proteins are uncommon in MIS-C

JAK1/2 inhibition with baricitinib in the treatment of autoinflammatory interferonopathies

BACKGROUND. Monogenic IFN-mediated autoinflammatory diseases present in infancy with systemic inflammation, an IFN response gene signature, inflammatory organ damage, and high mortality. We used the JAK inhibitor baricitinib, with IFN-blocking activity in vitro, to ameliorate disease. METHODS. Between October 2011 and February 2017, 10 patients with CANDLE (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures), 4 patients with SAVI (stimulator of IFN genes-associated [STING-associated] vasculopathy with onset in infancy), and 4 patients with other interferonopathies were enrolled in an expanded access program. The patients underwent dose escalation, and the benefit was assessed by reductions in daily disease symptoms and corticosteroid requirement. Quality of life, organ inflammation, changes in IFN-induced biomarkers, and safety were longitudinally assessed. RESULTS. Eighteen patients were treated for a mean duration of 3.0 years (1.5-4.9 years). The median daily symptom score decreased from 1.3 (interquartile range [IQR], 0.93-1.78) to 0.25 (IQR, 0.1-0.63) (P < 0.0001). In 14 patients receiving corticosteroids at baseline, daily prednisone doses decreased from 0.44 mg/kg/day (IQR, 0.31-1.09) to 0.11 mg/kg/day (IQR, 0.02-0.24) (P < 0.01), and 5 of 10 patients with CANDLE achieved lasting clinical remission. The patients' quality of life and height and bone mineral density Z-scores significantly improved, and their IFN biomarkers decreased. Three patients, two of whom had genetically undefined conditions, discontinued treatment because of lack of efficacy, and one CANDLE patient discontinued treatment because of BK viremia and azotemia. The most common adverse events were upper respiratory infections, gastroenteritis, and BK viruria and viremia. CONCLUSION. Upon baricitinib treatment, clinical manifestations and inflammatory and IFN biomarkers improved in patients with the monogenic interferonopathies CANDLE, SAVI, and other interferonopathies. Monitoring safety and efficacy is important in benefit-risk assessment

An activating NLRC4 inflammasome mutation causes autoinflammation with recurrent macrophage activation syndrome

Inflammasomes are innate immune sensors that respond to pathogen and damage-associated signals with caspase-1 activation, IL-1β and IL-18 secretion, and macrophage pyroptosis. The discovery that dominant gain-of-function mutations in NLRP3 cause the Cryopyrin Associated Periodic Syndromes (CAPS) and trigger spontaneous inflammasome activation and IL-1β oversecretion, led to successful treatment with IL-1 blocking agents1. Herein, we report a de novo missense mutation, c.1009A>T, p.Thr337Ser, in the nucleotide-binding domain of inflammasome component NLRC4 (IPAF/CARD12) that causes early-onset recurrent fever flares and Macrophage Activation Syndrome (MAS). Functional analyses demonstrated spontaneous inflammasome formation and production of the inflammasome-dependent cytokines IL-1β and IL-18, the latter exceeding levels in CAPS. The NLRC4 mutation caused constitutive caspase-1 cleavage in transduced cells and increased production of IL-18 by both patient and NLRC4 mutant macrophages. Thus, we describe a novel monoallelic inflammasome defect that expands the monogenic autoinflammatory disease spectrum to include MAS and suggests novel targets for therapy

Immunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19

: Pediatric Coronavirus Disease 2019 (pCOVID-19) is rarely severe; however, a minority of children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might develop multisystem inflammatory syndrome in children (MIS-C), with substantial morbidity. In this longitudinal multi-institutional study, we applied multi-omics (analysis of soluble biomarkers, proteomics, single-cell gene expression and immune repertoire analysis) to profile children with COVID-19 (n = 110) and MIS-C (n = 76), along with pediatric healthy controls (pHCs; n = 76). pCOVID-19 was characterized by robust type I interferon (IFN) responses, whereas prominent type II IFN-dependent and NF-κB-dependent signatures, matrisome activation and increased levels of circulating spike protein were detected in MIS-C, with no correlation with SARS-CoV-2 PCR status around the time of admission. Transient expansion of TRBV11-2 T cell clonotypes in MIS-C was associated with signatures of inflammation and T cell activation. The association of MIS-C with the combination of HLA A*02, B*35 and C*04 alleles suggests genetic susceptibility. MIS-C B cells showed higher mutation load than pCOVID-19 and pHC. These results identify distinct immunopathological signatures in pCOVID-19 and MIS-C that might help better define the pathophysiology of these disorders and guide therapy

Reversal of Alopecia Areata Following Treatment With the JAK1/2 Inhibitor Baricitinib

Background: Alopecia areata (AA) is an autoimmune disease resulting in hair loss with devastating psychosocial consequences. Despite its high prevalence, there are no FDA-approved treatments for AA. Prior studies have identified a prominent interferon signature in AA, which signals through JAK molecules. Methods: A patient with AA was enrolled in a clinical trial to examine the efficacy of baricitinib, a JAK1/2 inhibitor, to treat concomitant CANDLE syndrome. In vivo, preclinical studies were conducted using the C3H/HeJ AA mouse model to assess the mechanism of clinical improvement by baricitinib. Findings: The patient exhibited a striking improvement of his AA on baricitinib over several months. In vivo studies using the C3H/HeJ mouse model demonstrated a strong correlation between resolution of the interferon signature and clinical improvement during baricitinib treatment. Interpretation: Baricitinib may be an effective treatment for AA and warrants further investigation in clinical trials