Pharmacokinetics of Vancomycin among Patients with Chemotherapy-Associated Febrile Neutropenia: Which Would Be the Best Dosing to Obtain Appropriate Exposure?

Previous research has determined that the required doses for treating febrile neutropenia with vancomycin are higher than the doses used conventionally. These recommendations have been made considering pharmacotherapeutic goals based on minimum concentration (Cmin) between 15-20 mg/L. This study was developed to evaluate dose recommendations based on the achievement of a target consisting of ratio of area under the curve over minimum inhibitory concentration (AUC24h/MIC) ≥400 in this population of individuals. This study was conducted in a referral hospital for cancer treatment, study participants received vancomycin doses of 1g every 12 h in 2-4-h infusions. Vancomycin was described by a two-compartment pharmacokinetic model with clearance dependent on the estimated glomerular filtration rate. Simulations were performed taking into account a reduced version of the model to establish the influence of controllable and non-controllable variables on the probability of achieving several PK-PD targets. A dose of 2.5g/day in patients with estimated glomerular filtration rate (eGFR) between 80 and 122mL/min/1.73m2 was adequate to achieve the pharmacotherapeutic target. A discrepancy was found between AUC-based and Cmin-based PK/PD indices, the former being affected by the dose and creatinine clearance while the latter highly influenced by the interval between doses.

Effectiveness and safety of the enhanced recovery program in colorectal surgery: overview of systematic reviews / Efectividad y seguridad del programa multimodal perioperatorio en cirugía colorrectal: Revisión sistemática de revisiones

Abstract Introduction Multimodal enhanced recovery programs are a new paradigm in perioperative care. Objective To evaluate the certainty of evidence pertaining to the effectiveness and safety of the multimodal perioperative care program in elective colorectal surgery. Data source: A search was conducted in the Medline, EMBASE, and Cochrane databases, up until February 2020. Eligibility criteria Systematic reviews that take into account the perioperative multimodal program in patients with an indication for colorectal surgery were included. The primary outcomes were morbidity and postoperative deaths. The secondary outcome was hospital length of stay. Study quality and synthesis method The reviews were evaluated with AMSTAR-2 and the certainty of the evidence with the GRADE methodology. The findings are presented with measures of frequency, risk estimators, or differences. Results Six systematic reviews of clinical trials with medium and high quality in AMSTAR-2 were included. Morbidity was reduced between 16 and 48%. Studies are inconclusive regarding postoperative mortality. Hospital length of stay was reduced by an average of 2.5 days (p <0.05). The certainty of the body of evidence is very low. Limitations The effect of the program, depending on the combination of elements, is not clear. Conclusions and implications Despite the proven evidence that the program is effective in reducing global postoperative morbidity and hospital stay, the body of evidence is of very low quality. Consequently, results may change with new evidence and further research is required.

Resumen Introducción Los programas multimodales de cuidado perioperatorio son nuevos paradigmas de atención en salud, particularmente en el paciente quirúrgico. Objetivo Evaluar la certeza en la evidencia de la efectividad y seguridad del programa multimodal perioperatorio en cirugía colorrectal electiva. Fuente de datos Se consultaron las bases de datos Medline, EMBASE y Cochrane hasta febrero de 2020. Criterios de elegibilidad Se incluyeron revisiones sistemáticas que consideraron como intervención el programa multimodal perioperatorio en pacientes con indicación de cirugía colorrectal. Los desenlaces primarios fueron morbilidad y mortalidad postoperatoria. El desenlace secundario fue estancia hospitalaria. Evaluación de los estudios y método de síntesis La calidad de las revisiones fue evaluada con AMSTAR-2 y la certeza de la evidencia con la metodología GRADE. Los hallazgos se presentan con medidas de frecuencia, estimadores de riesgo o diferencias. Resultados Se incluyeron seis revisiones sistemáticas de ensayos clínicos de media y alta calidad en AMSTAR-2. La morbilidad se redujo entre el 16 y el 48 %. Para la mortalidad postoperatoria no se reportan diferencias a favor del programa. La estancia hospitalaria se redujo en promedio 2,5 días (p < 0,05). La certeza del cuerpo de la evidencia es muy baja. Limitaciones El efecto del programa en función de combinación de elementos no es claro. Conclusiones e implicaciones A pesar de que la evidencia sugiere que el programa es efectivo en la reducción de morbilidad postoperatoria global y estancia hospitalaria, el cuerpo de la evidencia es de muy baja calidad, por lo que los resultados podrían cambiar con nueva evidencia. Se requieren nuevas investigaciones.

Health Care Cost for Multiple Sclerosis: The Case of a Health Insurer in Colombia.

BACKGROUND: There have been many studies on the cost of multiple sclerosis in countries with high prevalence, whereas in Latin America such analyses are few. Taking into consideration the burden of this disease and the high financial impact of treatment on the health care system, it is necessary to know the behavior of cost of illness. OBJECTIVES: To describe the direct costs associated with health care in patients with multiple sclerosis affiliated with a health insurer in Colombia. METHODS: An analysis of direct costs of disease was performed from the perspective of the third-party payer. A direct measurement from the technical costing "top-down" approach was used. Data were adjusted for inflation and expressed in 2014 US dollars. RESULTS: The average annual cost per patient for the country was $29,339 (2010), $20,956 (2011), $23,892 (2012), $24,148 (2013), and $22,688 (2014). Drug therapy represented 86.1% of the total cost. Between 2010 and 2013, interferons accounted for the largest proportion of the costs of drug treatment (98.5% to 53%), whereas fingolimod showed an increase and accounted for 47% in 2014. CONCLUSIONS: Medications account for the largest proportion of disease costs, with few variations in the last 5 years; nevertheless, the increase in the use of new pharmaceuticals poses a challenge to maintain the financial balance of health insurance.

Costo- Efectividad Del Uso Profiláctico Del Factor Estimulante De Colonias De Granulocitos En Adultos Con Leucemia Linfoblástica Aguda en Colombia.

OBJECTIVE: To assess the cost-effectiveness of prophylactic administration of Granulocyte Colony-Stimulating Factor (G-CSF) compared with no use of it, during the induction phase of chemotherapy in Adults with Acute Lymphoblastic Leukemia (ALL) in Colombia. METHODS: A decision tree with a time horizon of 30 days was built under colombian health system perspective including only direct costs. The costs of procedures and medications were taken from official sources and an institution of national reference of oncology services. The safety and effectiveness data were taken from the literature and two Colombian cohorts with patients older than 15 years. The unit of outcome was the proportion of deaths avoided. RESULTS: Base-case results on a clinical trial indicate that using factor is a dominant strategy. The variable that most impacted the outcome was the incidence of febrile neutropenia. Considering a threshold of $22.228 USD in 80% of cases using factor was cost effective. However, the use of factor is not cost-effective for the country for incidences of febrile neutropenia > 48%. It was not possible to establish cost-effectiveness of pegfilgrastim because no information was found. CONCLUSION: As per Colombian data, the use of prophylactic factor under chemotherapeutic induction in adults with ALL, turns out to be not cost effective. The difference in the results suggests the need of a careful extrapolation of information from clinical trials (ideal world) for developing economic evaluations in Colombia.

Revisión sistemática de estudios de costo-efectividad del test de portadores para fibrosis quística / Systematic review of studies on cost-effectiveness of cystic fibrosis carrier testing

Resumen Introducción. La fibrosis quística es considerada la enfermedad autosómica con afecciones multisistémicas más común en población blanca no hispánica. Objetivo. Revisar la evidencia disponible sobre costo-efectividad del test de portador para fibrosis quística en comparación con la no intervención. Materiales y métodos. Se realizó una revisión sistemática de evaluación de costo-efectividad del test genético para portadores de fibrosis quística a través de las base de datos MEDLINE, Embase, NHS, EBM Reviews - Cochrane Database of Systematic Reviews, LILACS, Health Technology Assessment, Genetests.org, Genetsickkids.org y Web of Science. Fueron incluidos estudios de costo-efectividad sin restricción de lenguaje ni fecha de publicación. Resultados. Solo 13 estudios fueron relevantes para su revisión completa. Se encontraron estrategias de tamizaje prenatal, preconcepcional y mixto. La perspectiva en salud fue la más usada; la tasa de descuento aplicada fue heterogénea entre 3.5% y 5%; la unidad de análisis principal fue el costo por pareja portadora detectada seguida de costo por nacimiento evitado con fibrosis quística. Se evidenció que la estrategia más costo-efectiva fue la del tamizaje preconcepcional asociada al test prenatal. Conclusiones. Se encontró marcada heterogeneidad en la metodología aplicada, lo que llevo a que los resultados no fueran comparables y se concluyera que existen diferentes enfoques de este test genético.

Abstract Introduction: Cystic fibrosis is considered the most common autosomal disease with multisystem complications in non-Hispanic white population. Objective: To review the available evidence on cost-effectiveness of the cystic fibrosis carrier testing compared to no intervention. Materials and methods: The databases of MEDLINE, Embase, NHS, EBM Reviews - Cochrane Database of Systematic Reviews, LILACS, Health Technology Assessment, Genetests.org, Genetsickkids.org and Web of Science were used to conduct a systematic review of the cost-effectiveness of performing the genetic test in cystic fibrosis patients. Cost-effectiveness studies were included without language or date of publication restrictions. Results: Only 13 studies were relevant for full review. Prenatal, preconception and mixed screening strategies were found. Health perspective was the most used; the discount rate applied was heterogeneous between 3.5% and 5%; the main analysis unit was the cost per detected carrier couple, followed by cost per averted birth with cystic fibrosis. It was evident that the most cost- effective strategy was preconception screening associated with prenatal test. Conclusions: A marked heterogeneity in the methodology was found, which led to incomparable results and to conclude that there are different approaches to this genetic test.

Prevalencia de artritis reumatoide en Colombia: una aproximación basada en la carga de laenfermedad durante el ano˜ 2005 / Rheumatoid arthritis prevalence in Colombia: An approach based on burden of disease study during 2005

(AU) IntroducciónEn Colombia, a la fecha, se desconoce la prevalencia de artritis reumatoide (AR). El propósito de este estudio fue hacer una aproximación a la prevalencia de la AR en Colombia con respecto a bases documentales.Materiales y métodosMediante una revisión de bases administrativas, se identificaron los casos prevalentes de AR, notificados por el estudio Carga de Enfermedad Colombia 2005, de los Registros Individuales de Prestación de Servicios de Salud, correspondientes a la clasificación internacional de enfermedades, décima revisión, M05 y M06; dividiendo los casos prevalentes por las bases de población reportadas por el Departamento Nacional de Estadística en Colombia para el mismo año, se estimaron las prevalencias específicas por edad y sexo.ResultadosSe encontraron 267.628 casos prevalentes en el año 2005 en Colombia, la prevalencia global de AR correspondió a 0,9/100 habitantes, la razón mujer/hombre de AR fue 4:1, se apreció un incremento progresivo con la edad (pico en el grupo de mayores de 80 años).ConclusiónEste es el primer estudio de prevalencia de AR en Colombia con base en registros administrativos, la prevalencia por esta metodología fue similar a la encontrada por otros estudios en poblaciones de Europa y Sudamérica

Costo-efectividad del diagnóstico etiológico de la cervicitis por c. trachomatis basado en pruebas rápidas comparado con el abordaje sindrómico, en mujeres no gestantes con síntomas de infección del tracto genital inferior / Cost-effectiveness of etiologic diagnosis for C. trachomatis infection based on rapid tests versus syndromic approach in non-pregnant women with symptoms of lower genital tract infection

Objetivo: estimar la razón costo-efectividad del diagnóstico etiológico con pruebas rápidas para la cervicitis por C. trachomatis frente al diagnóstico sindrómico, en mujeres no gestantes con síntomas de infección del tracto genital inferior en Colombia. Materiales y métodos: se construyó un árbol de decisión para determinar la razón de costo-efectividad de la aproximación etiológica con las pruebas rápidas Acon®Plate, Acon®Duo y QuickVue® para la detección de C. trachomatis comparada con el diagnóstico sindrómico. La perspectiva fue la del sistema de salud colombiano incluyendo todos los costos médicos directos. El horizonte de tiempo fue de 15 días, ya que la unidad de resultado fue el número de casos correctamente identificados (número de verdaderos positivos y verdaderos negativos). Las características operativas de las pruebas se obtuvieron en un estudio de corte transversal diseñado y conducido para este propósito. Resultados: la alternativa más costosa y más efectiva fue QuickVue® seguida de Acon®Plate y del abordaje sindrómico. Acon®Duo fue una estrategia dominada. La razón de costo-efectividad incremental de QuickVue®, comparada con Acon®Plate, fue de $ 430.671; la de Acon®Plate, comparada con el abordaje sindrómico, fue de $ 79.747. Conclusión: si la disponibilidad a pagar (DAP) por un caso correctamente identificado adicional es mayor que $ 430.671, QuickVue® sería la mejor alternativa en términos de costo-efectividad; de otro lado, si la DAP está entre $ 79.747 y $ 430.671, Acon®Plate sería la alternativa costo-efectiva. Finalmente, si la DAP es menor que $ 79.747, el abordaje sindrómico sería la mejor alternativa en términos de costo-efectividad.

Objective: To estimate the cost-effectiveness of etiological approach with rapid tests for C. trachomatis cervicitis versus syndromic diagnosis, in non-pregnant women with symptoms of lower genital tract infection in Colombia. Materials and methods: A decision tree was developed for determining the cost-effectiveness ratio of the aetiological approach using the Acon®Plate, Acon®Duo and QuickVue® quick tests for the detection of C. trachomatis, compared with the syndromic diagnosis. The perspective was that of the Colombian healthcare system, including medical direct costs. The time period was 15 days, considering that the outcome unit was the number of cases identified correctly (number of true positives and true negatives). The operational characteristics of the tests were derived from a cross-sectional study designed and conducted for that specific purpose. Results: The more costly and effective option was QuickVue®, followed by Acon®Plate and the syndromic approach. Acon®Duo was a dominated strategy. The incremental cost-effectiveness ratio for QuickVue® compared with Acon®Plate was $430.671, and that of Acon®Plate compared with the syndromic approach was $79.747. Conclusion: If the willingness to pay (WTP) for an additional case that is correctly identified is greater than $430.671, QuickVue® would be the best option in cost-effectiveness terms. On the other hand, if the WTP is between $79.747 and $430.671, Acon®Plate would be the cost-effective strategy. Finally, if the WTP is less than $79.747, the syndromic approach would be the best option in cost-effectiveness terms.

Impact of group purchasing in cooperative of hospital in Colombia, using a price index from 1999 to 2012 / Impacto del grupo de compra en la cooperativa de hospital en Colombia, con un índice de precios de 1999 a 2012

The application of price indices is useful to analyze the behavior of prices as an important component in patients´ access to essential medications over a period of time. The present work analyzed the variation in the prices of 303 medications sold by a cooperative of hospitals in central Colombia between 1999 and 2010 by applying inflation-adjusted price indices and Laspeyres-Paasche quantities by ABC groups and principal therapeuticals in the first and second ATC (anatomic, therapeutical, chemical) level, taking 1999 as the starting year. The medications of type A and B, as well as those belonging to the first four therapeutical groups in the first ATC level in cost and for seven groups in the second ATC level, registered a drop between 40 and 53% (P < 0.05) in the applied price indices. In addition, all the ABC and ATC groups showed increases between 9 and 12 times (P < 0.01) when applying the indices on units sold. The estimated net saving in 2010 at prices of 1999, went above $ 16.9 billion COP. This impact on prices has helped to expand the coverage in essential medications supplied to the public hospitals which are afterwards administered to the patients of this region of Colombia.

La aplicación de los índices de precios es útil para analizar el comportamiento de los precios como un componente importante en el acceso de los pacientes a los medicamentos esenciales en un determinado período de tiempo. El presente trabajo analiza la variación de los precios de 303 medicamentos comercializados por una cooperativa de hospitales en el centro de Colombia entre 1999 y 2010 mediante la aplicación de los índices de precios ajustados a la inflación, según las expresiones de Laspeyres y Paasche por grupos ABC y de principales agentes terapéuticos en el primer y segundo nivel ATC (anatómico, terapéutico, químico), tomando 1999 como año de partida. Los medicamentos de tipo A y B, así como los que pertenecen a los cuatro primeros grupos terapéuticos en el primer nivel de ATC en el costo, y considerando siete grupos en el segundo nivel de ATC, registraron una caída entre 40% y 53% (P < 0,05) en los índices de precios aplicados. Además, todos los grupos ABC y ATC mostraron aumentos entre 9 y 12 veces (P < 0,01) al aplicar los índices en las unidades vendidas. El ahorro neto estimado en 2010 a precios de 1999, pasó por encima de 16,9 mil millones de pesos colombianos. Este impacto en los precios ha contribuido a ampliar la cobertura en los medicamentos esenciales suministrados a los hospitales públicos, y que luego son administrados a los pacientes de esta región de Colombia.

Comportamiento de la intoxicación por sustancias químicas, medicamentos y sustancias psicoactivas en Colombia, 2010, reportados en Sivigila / Behavior of poisoning due to chemical compounds, drugs and psychoactive substances in Colombia during 2010 according to Sivigila

Las intoxicaciones por sustancias químicas representan un problema de salud pública. En Colombia hay poca información al respecto. Se llevó a cabo un estudio descriptivo-retrospectivo longitudinal del comportamiento de la intoxicación originada por exposición a sustancias químicas y notificadas a través del Sistema de Vigilancia en Salud Pública (Sivigila) en Colombia durante el 2010. Los principales casos que presentan la mayor incidencia de intoxicación por sustancias químicas en Colombia son, en orden descendente, los plaguicidas, los medicamentos y otras sustancias químicas con el 89,65% del total de la notificación. El principal tipo de exposición fue la intencional suicida con el 44,04% de la notificación; la principal vía de exposición, la oral con el 72,14% de los casos notificados. El grupo de edad con el mayor número de casos notificados se concentró entre los 15 y 19 años, con el 22,17% del total de la notificación. El grado de escolaridad con el mayor número de casos de intoxicación correspondió a la educación secundaria, que representó el 47,47% de la notificación. El método de confirmación para la intoxicación fue la clínica con el 92,87% de la notificación.

The chemical poisoning is a public health problem. In Colombia there is little information. They conducted a retrospective longitudinal study of the behavior of the poisoning that was caused by chemical exposure and reported through the surveillance system in public health (Sivigila) in Colombia during 2010. The main events that have the highest incidence of chemical poisoning in Colombia are in descending order pesticides, drugs and other chemicals with 89.65% of the notification. The main type of exposure was intentional suicide with 44.04% of the notification, the main route of oral exposure to 72.14% of the reported cases. The age group with the highest number of reported cases was between 15 and 19 years with 22.17% of the notification. The level of education with the largest number of cases of poisoning was secondary education accounted for 47.47% of the notification. The method of confirming the poisoning was the clinic with 92.87% of the notification.

Status Update of the Reimbursement Review Environment in the Public Sector across Four Latin American Countries.

In Latin America, social security and public sectors represent the largest financiers and providers of health care. Many countries in the region have compulsory packages of basic health care benefits. As part of an effort to improve quality of care and access, several health technology assessment agencies, both governmental and academia, among a number of Latin American countries have been formally established in the past few years. Several Latin American countries have recently developed and published methodological guidelines in economic evaluation, indicating that there is a growing interest in evaluating health-related products, drugs, and technologies used by the population. Presentations on the health care system and the role of health technology assessment, pharmacoeconomics, and risk sharing policies, from the public sector perspective, in the Latin American countries Argentina, Brazil, Colombia, and Mexico were made at the 3rd Latin American ISPOR Conference held in Mexico City in 2011 and are discussed in this article. In conclusion, there is a clear need for Latin American countries to evaluate the value of new technologies that are being incorporated into their health care system. In addition, health technology assessment guidelines are important for their local needs in terms of regulation along with common country unions. In the future, the Latin American region needs to increase drug access along with implementing cost-containment measures to improve quality and health outcomes.

Cáncer de colon: análisis del costo de enfermedad para los estadios III y IV en Cansercoop ips / Colon cancer: analysis of disease cost to iii and iv stages in Cansercoop ips

El cáncer de colon presenta una incidencia creciente en la sociedad colombiana y es una de las principales causas de morbi-mortalidad en este grupo de enfermedades, con una gran carga emocional y económica. Desde el punto de vista del efecto económico no hay mucha información en el contexto colombiano. Por tal razón, este trabajo hace un análisis de caso en una institución prestadora de servicios (ips), aplicando la metodología de “costo enfermedad” basada en la prevalencia de la enfermedad. Objetivo: estimar costos totales, directos e indirectos, para cáncer de colon, establecer una distribución de recursos para estadios iii y iv. Método: se empleó el modelo de análisis de costo de enfermedad por prevalencia, en pacientes diagnosticados en estadios iii y iv con cáncer de colon, entre enero de 2005 y octubre de 2007, y se revisó una base de datos en cansercoop ips. Resultados: se identificaron 79 individuos, 44 en estadio iii de la enfermedad y 35 en estadio iv; el 59,5 son mujeres. De acuerdo con la edad, el 45,6 son mayores de 60 años, y el 58,2 están afiliados a Salud Total como empresa promotora de salud (eps). El costo total fue $ 348.254.762; 98,41 costos directos y 1,59 costos indirectos; el costo promedio por paciente fue $ 1.700.816 (49.288-11.529.013), estadio iii y $ 7.653.742 (13.523-70.354.423), estadio iv. El 65,66 de los costos totales corresponde a medicamentos. Conclusiones: los costos totales, de acuerdo con los estadios iii y iv de cáncer de colon, son de $ 77.143.347 y $ 271.111.415, respectivamente, en los que los medicamentos representan $ 42.444.492 para el estadio iii y $ 182.570.717 para el iv. Este análisis puede considerarse un estudio preliminar; sin embargo, representa un paso para posteriores evaluaciones económicas en salud.

The cancer colon has an increased incidence in Colombia and is a leading causes of mortality and morbidity in this group of diseases with a high economic and emotional burden, from the standpoint of economic impact there is little information in the Colombian context, for this reason, this work makes a case study in a health institution providing services, applying the methodology of “Cost of Illness” based on the prevalence of disease. Aim: To estimate the whole costs, both direct and indirect to cancer colon; establishing a distribution resources to iii and iv stages. Method: analysis cost of Illness was used in patients were diagnosed as having both iii and iv stages with cancer colon, from January 2005 to October 2007; checking a base data in cansercoop ips. Results: 79 people were identified, 44 (iii stage) and 35 (iv stage), 59.9 of all of them are women up to 60 years old and 58.2 belong to Salud Total. The total cost was $ 348.254.762, 98.4 were direct costs and 1.59 were indirect costs. Average cost for each patient was $ 1.700.816 (49.288-11.529.013), iii stage and $ 7.653.742 (13.523-70.354.423), iv stage. 65.66 are medicines. Conclusions: the total costs, both iii and iv stages were $ 77.143.347 and $ 271.111.415 in iii stage and $182.570.717 in iv stage. This analysis can be considered as a preliminary study; however it means a step to subsequent economic health assessments.