International consensus recommendations on the management of people with haemophilia B.

Haemophilia B is a rare X-linked genetic deficiency of coagulation factor IX (FIX) that, if untreated, can cause recurrent and disabling bleeding, potentially leading to severe arthropathy and/or life-threatening haemorrhage. Recent decades have brought significant improvements in haemophilia B management, including the advent of recombinant FIX and extended half-life FIX. This therapeutic landscape continues to evolve with several non-factor replacement therapies and gene therapies under investigation. Given the rarity of haemophilia B, the evidence base and clinical experience on which to establish clinical guidelines are relatively sparse and are further challenged by features that are distinct from haemophilia A, precluding extrapolation of existing haemophilia A guidelines. Due to the paucity of formal haemophilia B-specific clinical guidance, an international Author Group was convened to develop a clinical practice framework. The group comprised 15 haematology specialists from Europe, Australia, Japan, Latin America and North America, covering adult and paediatric haematology, laboratory medicine and biomedical science. A hybrid approach combining a systematic review of haemophilia B literature with discussion of clinical experience utilized a modified Delphi format to develop a comprehensive set of clinical recommendations. This approach resulted in 29 recommendations for the clinical management of haemophilia B across five topics, including product treatment choice, therapeutic agent laboratory monitoring, pharmacokinetics considerations, inhibitor management and preparing for gene therapy. It is anticipated that this clinical practice framework will complement existing guidelines in the management of people with haemophilia B in routine clinical practice and could be adapted and applied across different regions and countries.

Clinical Characteristics and Outcomes of a Cohort of Pediatric Oncohematologic Patients With COVID-19 Infection in the City of Bogotá, Colombia.

BACKGROUND: In children, the complications of severe acute respiratory syndrome coronavirus 2 infection occur less frequently than in adults but the characteristics of this disease in oncology patients are not well characterized. METHODS: This was a retrospective study in patients younger than 18 years of age with coronavirus disease 2019 (COVID-19) and cancer diagnoses between April and September 2020. Demographic variables, laboratory, and radiologic findings and complications of each case were identified. A descriptive analysis was performed. RESULTS: A total of 33 patients were identified; the median age was 10 years. Fifteen patients (42%) were in chemotherapy at the time of the infection diagnosis, in two patients the chemotherapy protocol was permanently suspended. The most common symptom was fever in 20 patients (60%). Seven patients (21.2%) showed mild pneumonia, four patients (12.1%) severe pneumonia, and three cases (9.0%) were classified as critical. In the evaluated cohort, five patients (15.1%) died, and in two of those, death was caused by COVID-19 infection. CONCLUSIONS: Children with an oncologic disease, the search for COVID cases should be oriented to patients with fever, including febrile neutropenia, the presence of respiratory symptoms, and the search for epidemiologic contact. A higher frequency of complications and mortality attributed to COVID-19, two in pediatric oncohematologic patients was found. Institutional strategies to detect the infection early and lower institutional infection are indicated.

Primary prophylaxis was associated with lower arthropathy in Colombian men with haemophilia B: A longitudinal analysis (2015-2019).

INTRODUCTION: The risk of chronic haemophilic arthropathy (CHA) is related to severity. Evidence suggests that primary prophylaxis (PPr) could reduce CHA incidence and its impact on quality of life. AIM: To evaluate the association between PPr and CHA in Colombian males with haemophilia B (HB) during 2015 to 2019. METHODS: A panel-time analysis was performed with data provided by the National Health System to update a nationwide open cohort of people with congenital coagulopathies. The association was evaluated in a logistic random-effect regression model (LRERM), adjusted by age at diagnosis, prophylaxis dose and frequency, severity, haemarthrosis and high-titre inhibitors. RESULTS: During 2015-2019, a total of 362 men with HB and treated with either, primary, secondary or tertiary prophylaxis were identified. At baseline, CHA prevalence in the cohort was 36.84% (n = 133), median age was 19.0 years (IQR: 10.0-27.0), and median age at diagnosis was 1.0 year (IQR: 0.0-4.0). PPr was prescribed in 37.85% (n = 137), and median dose (IU/Kg/dose) was almost the same for primary vs. secondary/tertiary prophylaxis. Patients in PPr had a lower frequency of severe HB, CHA, haemarthrosis, infectious complications and high-titre inhibitors than those in secondary or tertiary prophylaxis (STPr). In the LRERM, PPr was associated with a significant reduction of 89.70% in the odds of CHA (aOR = 0.103, IC 95%: 0.040, 0.270; P < .001), compared with STPr. CONCLUSIONS: PPr decreased the odds of CHA by 89.70% in males with HB in Colombia. Our findings are consistent with previous studies and support the strategy to prescribe PPr to our patients.

National registry of haemophilia and other coagulopathies: A multisector initiative in the Colombian Health System.

INTRODUCTION: Haemophilia is an orphan and high-cost disease worldwide and, especially in middle-income countries as Colombia. Given its burden of disease, in 2014, a national administrative registry was created to centralize demographic, clinical and economic information regarding to haemophilia and other coagulopathies. OBJECTIVE: To describe the building and implementation processes of the Colombian registry of haemophilia and other coagulopathies. METHODS: The 'consensus conference' methodology was used to design the registry. It was a multisector process, which included different actors of the health system (healthcare payers and providers, government institutions, academic and scientific organizations and patients). RESULTS: Colombia's national registry includes 95 variables, grouped in four sections: (1) sociodemographic data, (2) clinical condition, (3) economic costs, and (4) administrative updates. According to a resolution, stated by the Ministry of Health, payers and providers of healthcare must report annually to the registry the information of new and existing patients with coagulopathies. CONCLUSIONS: A national registry serves as an organized and interactive system for monitoring morbidity and mortality, assessing healthcare access and its impact on disease complications, as well as associated costs to medical assistance. Furthermore, registry information can guide a rational making decision process to use economic resources efficiently. On the other hand, data about orphan diseases can encourage health research and evidence-based care to improve quality of life and reduce associated disability.

Molecular characterization of hemophilia B patients in Colombia.

BACKGROUND: Hemophilia B (HB) is a coagulation disorder with an X-linked recessive inheritance pattern, caused by plasma FIX deficiency. In Colombia, HB is considered a rare and high-cost disease, with 362 males reported in 2017. METHODS: Here, we characterized 20 HB apparently unrelated families by PCR amplification and Sanger sequencing. RESULTS: Fourteen unique variants were identified: seven missense, three nonsense, one variant in the 3' UTR region, two large deletions >50 bp, and one intronic substitution that affects splicing c.520+13A>G that was present in 7/20 patients (35%). All these variants have been previously reported in the literature, except for exons 3 and 4, deletions, present in one patient. The genotype-phenotype association correlates with the reported in the literature, with the exception of one patient. CONCLUSION: This molecular analysis allowed us to establish the causal variant of HB in 100% of patients, to provide the appropriate genetic counseling to each of the families, and to propose a more cost-effective carrier analysis. Here, we reported the first variants in Colombian population with Hemophilia B, finding a new variant and one intron recurrent variant present in 35% of patients.

Room for Improvement: Rates of Birth Cohort Hepatitis C Screening in Primary Care Practices-A WWAMI Region Practice and Research Network Study.

Introduction: An estimated 2.4 million people in the United States live with hepatitis C. Though there are effective treatments for chronic hepatitis C, many infected individuals remain untreated because 40% to 50% of individuals with chronic hepatitis C are unaware of their hepatitis C status. In 2013, the United States Preventive Services Task Force (USPSTF) recommended that adults born between 1945 and 1965 should be offered one-time hepatitis C screening. The purpose of this study is to describe rates of birth cohort hepatitis C screening across primary care practices in the WWAMI region Practice and Research Network (WPRN). Methods: Cross-sectional observational study of adult patients born between 1945 and 1965 who also had a primary care visit at 1 of 9 participating health systems (22 primary care clinics) between July 31, 2013 and September 30, 2015. Data extracted from the electronic health record systems at each clinic were used to calculate the proportion of birth cohort eligible patients with evidence of hepatitis C screening as well as proportions of screened patients with positive hepatitis C screening test results. Results: Of the 32 139 eligible patients, only 10.9% had evidence of hepatitis C screening in the electronic health record data (range 1.2%-49.1% across organizations). Among the 4 WPRN sites that were able to report data by race and ethnicity, the rate of hepatitis C screening was higher among African Americans (39.9%) and American Indians/Alaska Natives (23.2%) compared with Caucasians (10.7%; P < .001). Discussion: Rates of birth cohort hepatitis C screening are low in primary care practices. Future research to develop and test interventions to increase rates of birth cohort hepatitis C screening in primary care settings are needed.

Cost of Patients With Hemophilia A and High-Titer Inhibitors in Colombia.

BACKGROUND: In Colombia, hemophilia is considered a high-cost disease, and hemophilia A with high-titer inhibitors may be responsible for a significant economic pressure on the Colombian health system. OBJECTIVES: To estimate the direct cost of care for patients with hemophilia A with high-titer inhibitors in Colombia, from the perspective of the health system. METHODS: A cost-of-illness study was carried out using standard case methodology, which was designed based on literature review and validation by expert consensus. Scenarios were established for adults and children, including cases of prophylaxis, immune tolerance induction, bleeding, and surgery. The frequencies were taken from the official report for Colombia, issued by the High-Cost Account 2017 (reported 2018). The prices were obtained from the list of regulated medicines in the country. The cost estimate is presented with a range of values by weight (between 10 kg and 90 kg). RESULTS: The total estimated cost per year for Colombia was US $44 905 252 (between US $32 260 497 and US $58 202 393). The average cost per year calculated for a patient was US $498 947 (between US $358 450 and US $646 693). A total of 99.8% of the estimated cost was directly related to the cost of the coagulation factors and bypassing agents. CONCLUSIONS: Hemophilia A with high-titer inhibitors is a disease that generates significant pressure on the Colombian health system, mainly linked to the cost of factors and bypassing agents.

Systematic molecular analysis of hemophilia A patients from Colombia.

Hemophilia A (HA) is an X-linked recessive disorder and the second most common coagulation disorder with an incidence of 1 in 5,000 live born males. Worldwide, there are 178,500 affected individuals, 60% with the severe form of the disease. Intron 22 and 1 inversions (Inv22 and Inv1) are the most frequent molecular alterations found in severe HA patients with a frequency of 45-50% and 0.5-5%, respectively. We have implemented a systematic cost-effective strategy for the identification of the molecular alteration in HA patients using Inverse shifting-PCR for Inv22 and Inv1, followed by the analysis of the F8 gene coding region by means of high resolution melting (HRM) PCR and Sanger sequencing in Inv22 and Inv1 negative patients. A total of 33 male HA patients and 6 women were analyzed. Inversion 22 was detected in 14/33 male patients (42.4%), 3/33 (9.1%) had Inv1, 3/33 (9.1%) had large structural variants, and 11/33 (33.3%) single nucleotide/ small frameshift variants. No genetic variant was found in 2/33 patients (6%). With this systematic approach we detected pathogenic variants in 31 out of 33 male affected individuals (94%) tested for the first time.in a cohort of patients from Colombia.

Haemophilia care in Latin America: Assessment and perspectives.

INTRODUCTION: The study is the first application of the Principles of Haemophilia Care for Europe (PHCE) in other regions of the world, specifically in Latin America. OBJECTIVE: To identify strengths in the care of haemophilia, and the aspects that should be improved. METHODS: The information was obtained through a questionnaire designed according to the PHCE and answered by specialists in mid-2016. The countries included were as follows: Argentina, Brazil, Chile, Colombia, Costa Rica, El Salvador, Mexico, Panama, Dominican Republic and Venezuela. RESULTS: In most countries, there is a central organization for haemophilia care supported by local groups. The existence of a national registry of people with haemophilia (PWH) was verified in eight countries. Centres of integrated care are located in large cities. In the majority of countries, there was no evidence of the participation of multiple actors in the decision-making. The supply of factor concentrates presents constraints, although it is reported as adequate in half of the countries. In most countries, home treatment is available under special conditions. In most countries, there are restrictions on the use of prophylaxis. The coordination of specialized and emergency services depends on each centre. Unrestricted treatment of inhibitors is performed in most countries. In all countries, there are human resources training programmes; however, clinical and health services researches are not widely developed. CONCLUSION: The study identifies the initial situation of principles of care, as well as the alternatives that must be implemented to achieve improvements in the quality of life of PWH in the region.

Terapia secuencial: una opción en el paciente hemofílico que no responde al manejo con monoterapia con agentes puente, estudio observacional del GrHeCol (Grupo Hemofilia Colombia) / Sequential therapy: an option for hemophiliac patients not responding to monotherapy with bypassing agents. Observational study of the GrHeCol (Grupo Hemofilia Colombia)

RESUMEN Introducción: la hemofilia A y B severa son condiciones que predisponen al sangrado espontáneo. Una de las complicaciones de la terapia con concentrados de factores de coagulación es el desarrollo de anticuerpos o inhibidores contra los factores VIII o IX. El tratamiento en casos de inhibidores de título alto, para el control de la hemorragia, es la administración de agentes puente como el complejo protrombínico activado y Factor VII recombinante activado. La respuesta a cada uno de ellos no es predecible, en algunos casos puede ser necesario el uso de la terapia secuencial cuando esta estrategia falla. Objetivo: reportar cinco casos de hemofilia A severa e inhibidores de título alto con sangrado severo, sin respuesta clínica con monoterapia y que recibieron terapia secuencial. Métodos: estudio multicéntrico, descriptivo, observacional. Las variables cualitativas se presentan con frecuencias absolutas y relativas, y las cuantitativas se resumen con medidas de tendencia central. Resultados: cuatro pacientes evaluados que aportaron cinco eventos, la mediana de edad 20 años; mediana de días de monoterapia 10; 8,6 días de terapia secuencial, tiempo a resolver el sangrado cuatro días. Ausencia de complicaciones trombóticas. Conclusiones: la terapia secuencial es una opción para aquellos pacientes que no responden a la monoterapia y requieren control hemostático. En los cinco casos reportados, la terapia secuencial logró controlar el sangrado sin complicaciones.

SUMMARY Introduction and objectives: Patients diagnosed with severe hemophilia are at risk of developing inhibitors of low or high title, being the treatment of choice for this latter group of patients the immune tolerance therapy (ITI). In cases where the immune tolerance fails or presents bleeding events, we can use activated prothrombin complex (APCC) or Recombinant activated factor VII (rFVIIa); however, patients may fail to these agents as monotherapy. The aim of this paper is to report five cases of severe hemophilia and high titer inhibitors with mayor bleeding, which fail to respond to monotherapy and required sequential therapy. Methods: Case report study, qualitative variables are presented as absolute and relative frequencies and quantitative are summarized with measures of central tendency. Results: Five patients with median age 20 years; monotherapy treatment with median 10 days; 8.6 days of sequential therapy, time to control the bleeding: 4 days. There were no thrombotic complications. Conclusions: Sequential therapy is an option for patients who do not respond to monotherapy and requires hemostatic control. In all the cases of this report, the patients were responsive with bleeding control.

Costo efectividad de las pruebas para estratificar riesgo en el tratamiento de la leucemia mieloide aguda (LMA) en población pediátrica / Cost-effectiveness of risk stratification tests for the treatment of acute myeloid leukemia in pediatric patients

RESUMEN Objetivo Estimar la razón de costo-efectividad de las pruebas para estratificación del riesgo en pacientes pediátricos con Leucemia Mieloide Aguda (LMA). Métodos Se construyó un árbol de decisión con años de vida ganados como medida de efectividad. Los costos fueron estimados desde la perspectiva del sistema de salud colombiano. En los costos de la estratificación se incluyeron los costos del tratamiento consecuente con ella. Los precios de medicamentos fueron tomados del SISMED 2008 y el valor monetario de los procedimientos se extrajo del manual tarifario del ISS 2001 adicionando el 30 %. Todos los costos se expresaron en pesos colombianos del 2010 y el producto interno per-cápita de ese año fue empleado como umbral de costo efectividad. Se condujeron análisis de sensibilidad univariados y probabilísticos. Resultados La razón de costo-efectividad incremental de las pruebas de estratificación a todos los pacientes, fue de $8 559 944. Los resultados son sensibles a las probabilidades de recaída, supervivencia al trasplante y efectos secundarios. Conclusión Las pruebas para estratificación del riesgo en LMA son costo-efectivas dentro del sistema de salud colombiano.(AU)

ABSTRACT Objective To estimate the cost-effectiveness of risk-stratification tests for the treatment of acute myeloid leukemia (AML) in pediatric patients. Methods A decision-tree model was built using Life Years Gained as a measure of effectiveness. Costs were estimated considering the perspective of the Colombian health system. Stratification costs included treatment costs based on said stratification. Drug prices were taken from SISMED (Drug Price Information System) 2008 and the monetary value of the procedures was extracted from the ISS 2001 rate manual, plus 30%. All costs were expressed in Colombian pesos for 2010 and the gross domestic product per capita of the same year was used as a cost-effective threshold. Univariate and probabilistic sensitivity analyzes were performed. Results Risk stratification tests have an incremental cost-effectiveness ratio of COP 8,559,944. These results are sensitive to changes in probabilities of relapse, transplant survival and side effects. Conclusion Risk stratification tests for AML treatment in pediatric patients are cost-effective in the context of the Colombian health care system.(AU)

Estudio molecular de la inversión de los intrones 1 y 22 del factor VIII de la coagulación en niños con hemofilia A severa utilizando técnica de PCR de larga distancia / Molecular study in children with hemophilia A in Colombia: analysis of Intron 1 and 22 inversion using long-distance PCR technique

Resumen Introducción. La hemofilia A es una enfermedad recesiva ligada al cromosoma X, con una incidencia de 1 en 5 000 a 10 000 varones y es el trastorno hemostático congénito más frecuente en varones. En pacientes con fenotipo severo, las inversiones de los intrones 22 y 1 son las mutaciones más comunes con una prevalencia del 45% a 50% y del 1% al 5% de los pacientes, respectivamente. Objetivo. Determinar la frecuencia de la inversión de los intrones 1 y 22 del gen del factor VIII de la coagulación en menores de 18 años con hemofilia A severa en Bogotá D.C. Materiales y métodos. Estudio descriptivo y transversal. La identificación de la inversión de los intrones 1 y 22 del gen del factor VIII se realizó mediante técnicas de reacción en cadena de polimerasa de larga distancia. Resultados. Se estudiaron 30 pacientes y se encontró inversión del intrón 22 en 12 pacientes (40%) e inversión 1 en 3 pacientes, cifras similares a las observadas en otros estudios. Conclusiones. Se encontraron las inversiones de los intrones 1 y 22 en la mitad de los pacientes evaluados. Los resultados son reproducibles, por lo que constituyen una herramienta útil para la identificación de las dos mutaciones más frecuentes en hemofilia A severa.

Abstract Introduction: Hemophilia A is an X-linked recessive disease with an incidence of 1 in 5 000 to 10 000 males. It is the most common congenital hemostatic disorder in men. The inversion of introns 1 and 22 in patients with a severe phenotype is considered the most frequent abnormality, with a prevalence of 1 to 5% and 45 to 50%, respectively. Objective: To determine the frequency of introns 1 and 22 inversions in factor VIII gene in children under 18 years with severe hemophilia A in Bogotá. Materials and methods: This is a non-experimental, descriptive, transverse study. The inversions of introns 1 and 22 for factor VIII gene were identified using long-distance polymerase chain reaction techniques in pediatric patients with severe Hemophilia A treated in different centers of Bogotá, Colombia. Results: Thirty patients were analyzed. Inversion of intron 22 was found in 12 patients (40%), while inversion of intron 1 was observed in 3 patients. These findings are similar to other studies. Conclusions: Inversions of intron 22 and 1 were found in half of this group of patients. These results are reproducible and useful to identify the two most frequent mutations in severe hemophilia A patients.

[Cost-effectiveness of risk stratification tests for the treatment of acute myeloid leukemia in pediatric patients]. / Costo efectividad de las pruebas para estratificar riesgo en el tratamiento de la leucemia mieloide aguda (LMA) en población pediátrica.

OBJECTIVE: To estimate the cost-effectiveness of risk-stratification tests for the treatment of acute myeloid leukemia (AML) in pediatric patients. METHODS: A decision-tree model was built using Life Years Gained as a measure of effectiveness. Costs were estimated considering the perspective of the Colombian health system. Stratification costs included treatment costs based on said stratification. Drug prices were taken from SISMED (Drug Price Information System) 2008 and the monetary value of the procedures was extracted from the ISS 2001 rate manual, plus 30%. All costs were expressed in Colombian pesos for 2010 and the gross domestic product per capita of the same year was used as a cost-effective threshold. Univariate and probabilistic sensitivity analyzes were performed. RESULTS: Risk stratification tests have an incremental cost-effectiveness ratio of COP 8,559,944. These results are sensitive to changes in probabilities of relapse, transplant survival and side effects. CONCLUSION: Risk stratification tests for AML treatment in pediatric patients are cost-effective in the context of the Colombian health care system.

OBJETIVO: Estimar la razón de costo-efectividad de las pruebas para estratificación del riesgo en pacientes pediátricos con Leucemia Mieloide Aguda (LMA). MÉTODOS: Se construyó un árbol de decisión con años de vida ganados como medida de efectividad. Los costos fueron estimados desde la perspectiva del sistema de salud colombiano. En los costos de la estratificación se incluyeron los costos del tratamiento consecuente con ella. Los precios de medicamentos fueron tomados del SISMED 2008 y el valor monetario de los procedimientos se extrajo del manual tarifario del ISS 2001 adicionando el 30 %. Todos los costos se expresaron en pesos colombianos del 2010 y el producto interno per-cápita de ese año fue empleado como umbral de costo efectividad. Se condujeron análisis de sensibilidad univariados y probabilísticos. RESULTADOS: La razón de costo-efectividad incremental de las pruebas de estratificación a todos los pacientes, fue de $8 559 944. Los resultados son sensibles a las probabilidades de recaída, supervivencia al trasplante y efectos secundarios. CONCLUSIÓN: Las pruebas para estratificación del riesgo en LMA son costo-efectivas dentro del sistema de salud colombiano.

Exploring the barriers and facilitators to use of point of care tests in family medicine clinics in the United States.

BACKGROUND: Point-of-care tests (POCTs) are increasingly used in family medicine clinics in the United States. While the diagnostics industry predicts significant growth in the number and scope of POCTs deployed, little is known about clinic-level attitudes towards implementation of these tests. We aimed to explore attitudes of primary care providers, laboratory and clinic administrative/support staff to identify barriers and facilitators to use of POCTs in family medicine. METHODS: Seven focus groups and four semi-structured interviews were conducted with a total of 52 clinic staff from three family medicine clinics in two US states. Qualitative data from this exploratory study was analyzed using the constant comparison method. RESULTS: Five themes were identified which included the impact of POCTs on clinical decision-making; perceived inaccuracy of POCTs; impact of POCTs on staff and workflow; perceived patient experience and patient-provider relationship, and issues related to cost, regulation and quality control. Overall, there were mixed attitudes towards use of POCTs. Participants believed the added data provided by POCT may facilitate prompt clinical management, diagnostic certainty and patient-provider communication. Perceived barriers included inaccuracy of POCT, shortage of clinic staff to support more testing, and uncertainty about their cost-effectiveness. CONCLUSIONS: The potential benefits of using POCTs in family medicine clinics are countered by several barriers. Clinical utility of many POCTs will depend on the extent to which these barriers are addressed. Engagement between clinical researchers, industry, health insurers and the primary care community is important to ensure that POCTs align with clinic and patient needs.

Intensive chemotherapy in children with acute lymphoblastic leukemia. Interim analysis in a referral center in Colombia / Quimioterapia intensiva en niños con leucemia linfoblástica aguda. Análisis ínterin en un centro de referencia en Colombia

Abstract Background: Acute lymphoblastic leukemia is the most common cancer in children. In developed countries, overall survival rates are around 80%, while in developing countries, survival rate is much lower due to high rates of relapse, and abandonment and complications arising from the disease treatment. Objectives: To assess induction mortality, relapse and treatment abandonment. To describe the most frequent side effects of chemotherapy. To evaluate survival rates of patients and compare the findings found in this study with the existing literature. Material and methods: A retrospective cohort study was conducted on patients aged 1 to 18 with acute lymphoblastic leukemia, who received treatment under the BFM ALL IC 2009 protocol at Fundación Hospital La Misericordia (HOMI), from November 2012 to December 2014. Results: 119 patients were included. Death occurred in two cases during induction (1.67%) and in nine (7.7%) due to treatment, all of them caused by infection/sepsis and in complete remission. Six patients abandoned treatment (5%), while seven relapses occurred (5.9%). All patients experienced some type of side effect related to chemotherapy, the most frequent being febrile neutropenia (41.2%) and grade 3-4 infections (15.8%). Overall survival and event-free survival rates were 79.9% and 73.3%, respectively. Conclusions: Evaluating complications of treatment and death allows adopting measures and strategies to reduce such complications.

Resumen Introducción. La leucemia linfoblástica aguda es el cáncer más frecuente en los niños. La sobrevida en países desarrollados está alrededor de 80%, mientras que en países de bajos ingresos la tasa de supervivencia es menor debido a altas cifras de recaída, abandono de tratamiento y complicaciones relacionadas con el tratamiento. Objetivos. Hacer una evaluación de muerte en inducción relacionada con el tratamiento, las recaídas y los abandonos de tratamiento; describir las reacciones adversas más observadas relacionadas con medicamentos de quimioterapia; evaluar la sobrevida, y comparar los hallazgos con publicaciones previas. Materiales y métodos. Estudio de cohorte retrospectivo. Se incluyeron pacientes con edades entre 1 y 18 años, con diagnóstico de leucemia linfoblástica aguda tratada entre noviembre de 2012 y diciembre de 2014 en la Fundación Hospital La Misericordia de Bogotá (HOMI) y a quienes se les había aplicado tratamiento con el protocolo BFM ALL IC 2009. Resultados. Se incluyeron 119 pacientes. Se presentaron dos (1.67%) muertes en inducción y nueve (7.7%) relacionadas con tratamiento -todas por infección/sepsis y en remisión completa-, seis abandonos (5%) y siete recaídas (5.9%). Todos los pacientes presentaron algún tipo de reacción adversa relacionada con medicamentos de quimioterapia, las más frecuentes fueron neutropenia febril (41.2%) e infecciones grado 3-4 (15.8%). Las sobrevidas global y libre de evento fueron de 79.9% y 73.3%, respectivamente. Conclusiones. La evaluación de los efectos deletéreos del tratamiento y muerte durante tratamiento permiten tomar medidas para disminuir estas complicaciones.

Recomendaciones basadas en la evidencia de terapia transfusional en el paciente oncológico en pediatría / Transfusion therapy evidence-based recommendations for the pediatric cancer patient

Introduction: Transfusion therapy is probably one of the most widely used therapies with poor supporting evidence, despite the long years of practical clinical use. Objective: To adapt the evidence-based recommendations on the use of blood products to the Colombian setting: red blood cells, platelets, cryoprecipitates and irradiated blood products in cancer patients under 18 years of age. Methods: Standard methodologies were followed in the development of recommendations. First, the clinical questions were addressed, and the evidence-based clinical practice guidelines were identified, graded and selected to answer the clinical questions. A systematic methodology was used to qualify, obtain and describe the relevant information to generate recommendations based on the SIGN system. The results were then presented and discussed in a group of experts to establish the practical value of the evidence and to adapt the recommendations to the Colombian environment. Results: Out of 107,441 preliminary titles, 56 studies were analyzed, and from them 3 clinical practice guidelines and 4 Cochrane systematic reviews were selected. This evidence was evaluated using AGREE II and AMSTAR. Red blood cells transfusion support is recommended using the restrictive strategy. Prophylactic platelet transfusion is the recommended indication. Cryoprecipitate is recommended when fibrinogen levels fall below 100mg/dL, and indications on irradiated blood products were established. Conclusion: This paper is an evidence-base approach on the recommendations for transfusion therapy in children with cancer.

Introducción: La terapia transfusional es quizá una de los tratamientos de mayor uso sin buen respaldo de evidencia, a pesar de muchos años de uso en la práctica clínica. Objetiuo:Adaptar recomendaciones basadas en evidencia al contexto colombiano sobre el uso de hemocomponentes: glóbulos rojos, plaquetas, crioprecipitados y hemocomponentes irradiados en el paciente oncológico menor de 18 años. Métodos: Se utilizaron metodologías estándares para el desarrollo de las recomendaciones. Primero se formularon las preguntas clínicas, se identificaron, calificaron y seleccionaron las guías de práctica clínica basadas en la evidencia que respondían las preguntas clínicas, utilizando una metodología sistemática se realizó la calificación, extracción y descripción de los aspectos relevantes para generar recomendaciones usando el sistema SIGN, luego se realizaron exposición y discusión de los resultados obtenidos con un grupo de expertos para seleccionar la utilidad de la evidencia y adaptar las recomendaciones al contexto colombiano. Resultados: De 107.441 títulos preliminares, se analizaron 56 estudios, y de estos se escogieron 3 guías de práctica clínica y 4 revisiones sistemáticas Cochrane. Se evaluó esta evidencia con AGREE II y AMSTAR. Se recomienda soporte transfusional de glóbulos rojos usando la estrategia restrictiva, la estrategia transfusional profiláctica de plaquetas es la indicación recomendada. El valor de fibrinógeno menor de 100mg/dl es el recomendado para utilizar crioprecipitados y se determinaron las indicaciones sobre hemocomponentes irradiados. Conclusiones Este trabajo representa un enfoque basado en la evidencia sobre las recomendaciones de terapia transfusional para niños con cáncer.

Guía de atención integral para la detección oportuna, diagnóstico, tratamiento y seguimiento de leucemia linfoide aguda en niños, niñas y adolescentes / Comprehensive guide for early detection, diagnosis, treatment and monitoring of acute leukemia lymphocytic leukaemiaid children and teens

La leucemia linfoide aguda (LLA) es el cáncer más frecuente en niños. A nivel mundial se estima que cerca del 30% corresponde a la totalidad de las neoplasias malignas que se presentan en niños y, de estas, más del 75% son LLA. En Colombia no existe aún un registro nacional de cáncer que nos permita evaluar exactamente la carga de la enfermedad por esta patología; sin embargo, se estima que se presentan aproximadamente 2.080 casos nuevos por año de cáncer en pacientes pediátricos y de estos 500 corresponden a LLA. Con el objetivo de disminuir la mortalidad y mejorar la oportunidad en el diagnóstico y en el tratamiento de los niños afectados por esta patología, se desarrolló esta Guía de práctica clínica (GPC) como producto del trabajo durante meses de un grupo organizado y motivado de médicos especialistas en el área (epidemiólogos, economistas, entre otros), quienes elaboraron recomendaciones para las diferentes etapas tanto para la prevención, sospecha, diagnóstico, tratamiento, seguimiento de los niños y adolescentes con diagnóstico de LLA.

Acute lymphocytic leukaemia (ALL) is the most common cancer in children. Globally, it is estimated that nearly 30% correspond to the total of malignant tumours in children, and 75% of them are ALL. There is no national cancer registry in Colombia that would allow us to precisely assess the burden of the disease for this condition; however, calculations have shown that there are 2,080 new paediatric cancer cases every year, and of those 500 correspond to ALL. With the goal of reducing mortality and improving the chances for a diagnosis and treatment of children affected by this condition, the present clinical practice guide (CPG) was developed after a work of months carried out by an organised and motivated group of physicians specialised in the field (epidemiologists and economists, among others), who formulated recommendations for the different stages: prevention, suspicion, diagnosis, treatment and follow-up of children and teens diagnosed with ALL.

Costo-efectividad de los tratamientos de consolidación para la leucemia mieloide aguda en niños en riesgo alto en el sistema de salud colombiano / Cost-effectiveness of consolidation treatments for acute myeloid leukemia in high-risk pediatric patients within the Colombian healthcare system

Introducción. La leucemia mieloide aguda representa alrededor del 20 % de las leucemias en menores de 18 años. Actualmente, solo existen dos alternativas de tratamiento de consolidación: la quimioterapia y el trasplante con progenitores hematopoyéticos. Objeti vo. Evaluar el costo-efectividad del trasplante alogénico con progenitores hematopoyéticos de donantes emparentados o no emparentados, en comparación con la quimioterapia de consolidación en niños de alto riesgo con leucemia mieloide aguda. Materiales y métodos. Se construyó un árbol de decisiones utilizando los años de vida ganados como resultado. Los costos y probabilidades se extrajeron de estudios y reportes que se encuentran en la literatura científica. El umbral de costo-efectividad fue tres veces el producto interno bruto per cápita de 2010. Se hicieron análisis de sensibilidad univariados y probabilísticos, así como una curva de aceptabilidad. Resultados. Al comparar el trasplante de donante emparentado o no emparentado con los ciclos de quimioterapia, se obtuvieron tasas de costo-efectividad incremental de COP$ 9´226.421 (USD$ 4.820) y COP$ 6´544.116 (USD$ 3.419), respectivamente, cifras estas inferiores al producto interno bruto per cápita: COP$ 12´047.418 (USD$ 6.294). El trasplante resultó ser costo-efectivo en 70 % de las simulaciones y con mayor probabilidad de serlo cuando había disposición a pagar cantidades superiores a COP$ 7´200.000 (USD$ 3.762). Conclusión. El trasplante alogénico (emparentado o no) en Colombia resultó ser costo-efectivo frente al tratamiento de consolidación en niños de alto riesgo con leucemia mieloide aguda.

Introduction: Acute myeloid leukemia represents about 20% of leukemias in minors under 18 years old. At present, there are only two consolidation treatment alternatives: Chemotherapy and stem-cell transplantation. Objective: To evaluate the cost-effectiveness of unrelated and related hematopoietic stem cell transplantations, versus chemotherapy consolidation in pediatric patients with high-risk acute myeloid leukemia. Materials and methods: A decision tree was constructed with life-years gained as the outcome. Costs and probabilities were extracted from the literature. Probabilistic sensitivity analyses and acceptability curves were computed. The cost-effectiveness threshold was three times the 2010 per capita gross domestic product. Results: When compared to consolidation chemotherapy cycles, related and unrelated hematopoietic stem-cell transplantation had incremental cost-effectiveness ratios of COP$ 9,226,421 (USD$ 4,820) and COP$ 6,544,116 (USD$ 3,419) respectively, which are lower than the per capita gross domestic product (COP$ 12,047,418, USD$ 6,294). Transplant proved to be cost-effective in 70% of the simulations and had a higher probability of the willingness to pay being over than COP$ 7,200,000 (USD$ 3,762). Conclusion: In Colombia, related and unrelated hematopoietic stem-cell transplants are cost-effective alternatives to consolidation treatment for high-risk acute myeloid leukemia in pediatric patients.

Profilaxis con CCPa en pacientes con hemofilia A con inhibidores de alta respuesta Una estrategia alternativa al estándar de tratamiento / Prophylaxis with activated prothrombin complex concentrate in patients with hemophilia A with high response inhibitors An alternative approach to standard treatment

Introducción: la complicación más grave de los pacientes con hemofilia es el desarrollo de anticuerpos inhibidores; hasta un 30% de los pacientes con hemofilia A severa los desarrollan. Para erradicarlos, la inducción de tolerancia inmune es el tratamiento de elección; cuando persisten, los tratamientos profilácticos con agentes de puente como el concentrado de complejo de protrombina activado CCPa (FEIBA®) o rFVIIa (Novoseven®) ofrecen una alternativa terapéutica para reducir lossangrados y la artropatía hemofílica. Para evaluar la eficacia de profilaxis con CCPa se compararon los sangrados antes y después de recibir profilaxis (11-12 meses) en ocho pacientes hemofílicos con inhibidores de alta respuesta. Material y métodos: se realizó un estudio multicéntrico, se incluyeron niños y adultos con diagnóstico de hemofilia A, con título de inhibidores altos, de cuatro centros de atención en dos ciudades. Se excluyeron pacientes con hemofilia adquirida. Resultados: seis pacientes tenían hemofilia A severa y dos moderada; 7/8 pacientes tenían artropatía hemofílica. La media de edad fue 19 años (rango 7-38) y la del título de inhibidor 80 UB (rango 15-1178). La dosis de CCPa fluctuó entre 40 y 75 U/kg, dos a tres veces por semana. Las tasas anuales de sangrado global y de hemartrosis previas a profilaxis fueron (8/año y 3.1/año)y después de profilaxis durante un periodo de 11-12 meses fueron (1.08/año y 1/año); se encontró una reducción de 86 y 68% respectivamente. No hubo eventos de trombosis. El cumplimiento del esquema de tratamiento con CCPa fue mayor a 80%. Conclusiones: este es el primer reporte de casos en Colombia sobre el uso de CCPa en pacientes hemofílicos con inhibidores del factor VIII de alta respuesta. Persisten interrogantes sobre la duración o ajustes al esquema de tratamiento. (Acta Med Colomb 2015; 40:288-293).

The most serious complication of hemophilia patients is the development of inhibitory antibodies; up to 30% of patients with severe hemophilia A develop them. To eradicate these antibodies, induction of immune tolerance is the treatment of choice; when they persist, prophylactic treatment with bridge agents as activated prothrombin complex concentrate aPCC (FEIBA®) or rFVIIa (Novoseven®) offer a therapeutic alternative for reducing bleeding and hemophilic arthropathy. To evaluate the efficacy of prophylaxis with aPCC, bleeds were compared before and after receiving prophylaxis (11-12 months) in 8 hemophilia patients with high response inhibitors. Material and methods: a multicenter study was conducted in children and adults with a diagnosis of hemophilia A with high titer inhibitors in 4 attention centers in two cities. Patients with acquired haemophilia were excluded. Results: six patients had severe hemophilia A and 2 moderate; 7/8 patients had hemophilic arthropathy. The mean age was 19 years (range 7-38) and mean inhibitor titer was 80 UB (range 151178). aPCC dose ranged from 40-75 U / kg, 2-3 times a week. The overall annual rates of bleeding and hemarthrosis pre-prophylaxis were (8 / year and 3.1 / yr) and after prophylaxis during a period of 11- 12 months were (1.08 / year and 1 / year); a reduction of 86% and 68% respectively was found. There were no thrombotic events. Compliance scheme of aPCC treatment was higher than 80%. Conclusions: this is the first case report in Colombia on the use of aPCC in haemophilia patients with high responding inhibitors to factor VIII. Questions remain about the length or adjustments to the treatment schedule. (Acta Med Colomb 2015; 40:88-293).

Evaluating the Development, Implementation and Dissemination of a Multisite Card Study in the WWAMI Region Practice and Research Network.

BACKGROUND: Practice-based research networks (PBRNs) promote the conduct of research in real-world settings by engaging primary care clinicians as champion research collaborators. Card studies are brief surveys administered to patients or clinicians at the point of care. The objective of this paper is to describe the design and evaluation of a card study methodology that the WWAMI Region Practice and Research Network (WPRN) used to develop research partnerships across multiple member sites. METHODS: We used a collaborative model to develop, implement and disseminate the results of a network-wide card study to assess patient preferences for weight loss in primary care. After the card study data collection was completed, we conducted individual and focus group interviews and a brief survey of participating practice champions. RESULTS: Increased research engagement and personal and professional developments were the primary motivators for participating in the development of the card study. Increasing research activity at practices and learning information about patients were motivators for implementing the study. Their participation resulted in champions reporting increased confidence in collaborating on research projects as well as the development of new clinical services for patients. DISCUSSION: This collaborative model positively influenced research capacity in the WPRN and may be a useful strategy for helping PBRNs conducted translational research.