Universal screening for Lynch syndrome in uterine cancer patients: A quality improvement initiative.

OBJECTIVE: To determine the feasibility and effectiveness of a quality improvement initiative (QI) to adopt universal screening for Lynch syndrome in uterine cancer patients at an institution that previously employed age-based screening. METHODS: Prior to the initiative, tumors of patients with uterine cancer diagnosed at age ≤ 60 years were screened for mismatch repair deficiency (MMR) and microsatellite instability (MSI). The QI process change model adopted universal testing of all uterine cancer specimens and implemented provider training, standardized documentation, and enhanced use of the electronic medical record (EMR). We compared screening rates, results of screening, follow up of abnormal results, and final diagnoses from the pre- and post-implementation periods. RESULTS: Pre- and post-implementation screening rates for women age ≤ 60 years at the time of diagnosis were 45/78 (57.7%) and 64/68 (94.5%), respectively. The screening rate for all patients with uterine cancer increased from 73/190 (38.4%) to 172/182 (94.5%). The rate of abnormal screening results increased from 15/190 (7.9%) to 44/182 (24.0%) cases. Genetics referral rates among screen positives increased from 3/15 (20.0%) to 16/44 (36.4%). Germline diagnoses increased from 2/190 (1.1%) with two Lynch syndrome diagnoses to 4/182 (2.2%) including three Lynch syndrome diagnoses and one BRCA1 germline diagnosis. The number of patients errantly not screened decreased from at least 32 patients to 3 patients after the intervention. CONCLUSIONS: Adherence to screening guidelines significantly improved after interventions involving provider education, optimal use of the EMR, and simplification of screening indications. These interventions are feasible at other institutions and translatable to other screening indications.

Improving Learners' Comfort With Cesarean Sections Through the Use of High-Fidelity, Low-Cost Simulation.

Introduction: Several studies have demonstrated effective simulation-based training for laparoscopic procedures in OB/GYN, but limited simulation curricula exist for abdominal procedures, particularly cesarean sections (CSs). Methods: We developed a high-fidelity modification of an existing CS model costing about $25 and incorporated it into a 90-minute teaching simulation event for medical students and OB/GYN residents in a single academic program. The simulation included a structured curriculum, pre-/postsimulation surveys, a surgical instrument review, a mannequin with the CS model containing a fetus in breech position, and live video streaming. Our surveys assessed participants' comfort with the procedure and its related components on a 5-point scale, and we used a paired t test to analyze our data. Results: Twenty-two learners (eight third-year medical students, one fourth-year medical student, three first-year residents, four second-year residents, one third-year resident, four fourth-year residents, and one unknown level) participated in this simulation. We found a statistically significant improvement in perceived CS instrument knowledge, suturing skills, and satisfaction with the model among all participants. Only third-year medical students had a statistically significant increase in comfort level in performing a CS after the simulation. Video streaming engaged a wider audience, but poor lighting and audio limited its efficacy. Discussion: Using this simulation model at the end of medical school or early in residency may have the greatest positive effect on resident comfort with CSs. This low-cost and versatile model can be used across educational settings, including OB/GYN interest group activities, intern boot camp, and interprofessional emergency drills.

Gs-coupled adenosine receptors differentially limit antigen-induced mast cell activation.

Mast cell activation results in the immediate release of proinflammatory mediators prestored in cytoplasmic granules, as well as initiation of lipid mediator production and cytokine synthesis by these resident tissue leukocytes. Allergen-induced mast cell activation is central to the pathogenesis of asthma and other allergic diseases. Presently, most pharmacological agents for the treatment of allergic disease target receptors for inflammatory mediators. Many of these mediators, such as histamine, are released by mast cells. Targeting pathways that limit antigen-induced mast cell activation may have greater therapeutic efficacy by inhibiting the synthesis and release of many proinflammatory mediators produced in the mast cell. In vitro studies using cultured human and mouse mast cells, and studies of mice lacking A(2B) receptors, suggest that adenosine receptors, specifically the G(s)-coupled A(2A) and A(2B) receptors, might provide such a target. Here, using a panel of mice lacking various combinations of adenosine receptors, and mast cells derived from these animals, we show that adenosine receptor agonists provide an effective means of inhibition of mast cell degranulation and induction of cytokine production both in vitro and in vivo. We identify A(2B) as the primary receptor limiting mast cell degranulation, whereas the combined activity of A(2A) and A(2B) is required for the inhibition of cytokine synthesis.

Análisis de impacto presupuestal de la introducción de fingolimod en el tratamiento de esclerosis múltiple en Colombia: a budget impact analysis / Introduction of fingolimod for the treatment of multiple sclerosis in Colombia

La esclerosis múltiple está asociada con discapacidad a largo plazo y un significativo impacto social. La introducción de fingolimod, un medicamento eficaz en la reducción de recaídas, en comparación con interferon beta 1a, justifica un análisis de impacto presupuestal desde la perspectiva del sistema de salud colombiano. OBJETIVO: desarrollar un análisis de impacto presupuestal, para los años 2012 a 2016 de la introducción de fingolimod en el sistema de salud de Colombia. MATERIALES Y MÉTODOS: usando la perspectiva del sistema de salud, se diseñó un modelo de impacto presupuestal para determinar el efecto que la introducción del fingolimod para el tratamiento de pacientes con esclerosis múltiple remitente recurrente tendría sobre los recursos del sistema de salud. La información clínica y de prevalencia fue obtenidas de la literatura, los costos fueron tomados de registros hospitalarios. Se realizó una simulación de Monte Carlo como parte del análisis de sensibilidad. RESULTADOS: el costo neto anual (2012-2016) para el escenario sin fingolimod fue, en miles de millones de pesos, $20,96, $22,29, $23,37, $24,68, y $25,98. En el escenario con fingolimod el costo neto fue: $21,01, $22,42, $23,50, $24,91 y $26,39. Por otro lado, fingolimod se asoció con 91 recaídas evitadas en este periodo de cinco años. La simulación de Monte Carlo no mostró diferencias significativas de los costos entre los dos escenarios. CONCLUSIÓN: considerando estos supuestos, la introducción de fingolimod en el sistema de salud colombiano no implica un impacto presupuestal significativo, y representa una importante reducción en el número de recaídas prevenidas.

INTRODUCTION: multiple sclerosis (MS) is associated with long-term disability and significant social impact. First-line disease modifying treatments for MS (interferons and glatiramer acetate) have moderate efficacy and must be administered in daily or weekly injections. The introduction of fingolimod, a molecule with superior efficacy in reducing MS relapses compared to interferon-beta 1a justifies a budget impact analysis from a Colombian health system perspective. OBJETIVES: to develop a budget impact analysis, for years 2012 to 2016, of the introduction of fingolimod in the Colombian health system. MATERIALS AND METHODS: using the perspective of the Colombian health system, we designed a budget impact model to determine the effect that the introduction of fingolimod for patients with relapsing-remitting MS would have on the resources of the health system. Clinical data and prevalence were obtained from published literature, costs were collected from local sources. A Monte Carlo simulation was done as part of the sensitivity analysis. Exchange rate used was 2,565 pesos per euro (July 2011). RESULTS: total annual net costs (2012-2016) for the scenario without fingolimod were, in million euros, €8.17, €€8.69, €9.11, €9.62, and €10.13. In the fingolimod scenario net costs were: €8.19, €8.74, €9.16, €9.71 and €10.29. On the other hand, fingolimod was associated with 91 relapses averted in this five-year period. Monte Carlo simulation does not show relevant differences in costs between both scenarios. CONCLUSION: under these assumptions, the introduction of fingolimod in Colombian health care system does not imply a significant budget impact but represents an important reduction in the number MS relapses.

Efecto hemolítico de la cloroquina en estudiantes deficientes de glucosa-6-fosfato deshidrogenasa / Hemolytic effect of chloroquine in students with glucose-6-phosphate dehydrogenase deficiency

Se estudió la presencia de estudiantes portadores de la deficiencia en la enzima glucosa-6-fosfato deshidrogenasa eritrocitaria en el Instituto de Ciencias Básicas y Preclínicas "Victoria de Girón" mediante el método del azul de metileno, la actividad enzimática y la electroforesis en geles de almidón. Luego se estudió el efecto hemolítico de la administración profiláctica de fosfato de cloroquina en estos sujetos, estudiando las variaciones con significación clínica en la concentración de hemoglobina y el hematócrito, antes y después del tratamiento con este fármaco. Se descartó la presencia de enfermedades asociadas a cuadros hemolíticos en sujetos portadores de esta deficiencia. De los 994 estudiantes latinoamericanos que arribaron al instituto en el año 2001, 8 fueron confirmados como deficientes de G6PD y el tratamiento de cloroquina suministrado no provocó hemólisis

Efecto hemolítico de la cloroquina en estudiantes deficientes de glucosa-6-fosfato deshidrogenasa / Hemolytic effect of chloroquine in students with glucose-6-phosphate dehydrogenase deficiency

Se estudió la presencia de estudiantes portadores de la deficiencia en la enzima glucosa-6-fosfato deshidrogenasa eritrocitaria en el Instituto de Ciencias Básicas y Preclínicas "Victoria de Girón" mediante el método del azul de metileno, la actividad enzimática y la electroforesis en geles de almidón. Luego se estudió el efecto hemolítico de la administración profiláctica de fosfato de cloroquina en estos sujetos, estudiando las variaciones con significación clínica en la concentración de hemoglobina y el hematócrito, antes y después del tratamiento con este fármaco. Se descartó la presencia de enfermedades asociadas a cuadros hemolíticos en sujetos portadores de esta deficiencia. De los 994 estudiantes latinoamericanos que arribaron al instituto en el año 2001, 8 fueron confirmados como deficientes de G6PD y el tratamiento de cloroquina suministrado no provocó hemólisis(AU)