ABSTRACT
OBJECTIVE: To compare the costs and clinical consequences of treating mild-to-moderate joint bleeds with recombinant activated factor VII (rFVIIa) versus plasma-derived activated prothrombin complex concentrate (pd-aPCC) in pediatric patients with hemophilia A with inhibitors in Mexico. METHODS: A cost-effectiveness model was developed using TreeAge Pro v14.2.2 software (licensed in the USA) and adapted from a previously published model, with adjustments to reflect local clinical practice. Expert opinion was sought regarding patients' clinical management and resource utilization in Mexico to ensure that the current model was appropriate and relevant. The model compared rFVIIa and pd-aPCC for the treatment of mild-to-moderate joint bleeds in children <14 years old (assumed average weight: 30 kg). The analysis outcome was incremental cost per resolved mild-to-moderate joint bleed. One-way sensitivity analysis and probabilistic sensitivity analysis were used to assess specific assumptions and to address any uncertainty in the model. RESULTS: The cost of treating mild-to-moderate joint bleeds was lower for rFVIIa versus pd-aPCC after 7 days (MX$105,581 vs. MX$132,024), assuming complete bleed resolution. After 48 hours, rFVIIa was associated with an 8% improvement in bleed resolution versus pd-aPCC, resulting in cost savings of MX$16,754. Probabilistic sensitivity analysis indicated that rFVIIa treatment was more cost-effective than pd-aPCC in 67% (at 7 days) and 72% (at 48 hours) of Monte Carlo simulations. CONCLUSION: Accounting for model uncertainty, rFVIIa provided cost savings over pd-aPCC for the Mexican public health care payer in the management of mild-to-moderate joint bleeds in pediatric hemophilia A with inhibitors.
Subject(s)
Blood Coagulation Factor Inhibitors/blood , Blood Coagulation Factors/economics , Cost-Benefit Analysis , Factor VIIa/economics , Hemophilia A/drug therapy , Adolescent , Blood Coagulation Factors/therapeutic use , Child , Child, Preschool , Factor VIIa/therapeutic use , Hemophilia A/complications , Humans , Infant , Infant, Newborn , Mexico , Recombinant Proteins/economicsABSTRACT
BACKGROUND: Controlled exposures of animals and humans to particulate matter (PM) or ozone air pollution cause an increase in plasma levels of endothelin-1, a potent vasoconstrictor that regulates pulmonary arterial pressure. OBJECTIVES: The primary objective of this field study was to determine whether Mexico City children, who are chronically exposed to levels of PM and O(3) that exceed the United States air quality standards, have elevated plasma endothelin-1 levels and pulmonary arterial pressures. METHODS: We conducted a study of 81 children, 7.9 +/- 1.3 years of age, lifelong residents of either northeast (n = 19) or southwest (n = 40) Mexico City or Polotitlán (n = 22), a control city with PM and O(3) levels below the U.S. air quality standards. Clinical histories, physical examinations, and complete blood counts were done. Plasma endothelin-1 concentrations were determined by immunoassay, and pulmonary arterial pressures were measured by Doppler echocardiography. RESULTS: Mexico City children had higher plasma endothelin-1 concentrations compared with controls (p < 0.001). Mean pulmonary arterial pressure was elevated in children from both northeast (p < 0.001) and southwest (p < 0.05) Mexico City compared with controls. Endothelin-1 levels in Mexico City children were positively correlated with daily outdoor hours (p = 0.012), and 7-day cumulative levels of PM air pollution < 2.5 mum in aerodynamic diameter (PM(2.5)) before endothelin-1 measurement (p = 0.03). CONCLUSIONS: Chronic exposure of children to PM(2.5) is associated with increased levels of circulating endothelin-1 and elevated mean pulmonary arterial pressure.
Subject(s)
Air Pollutants/toxicity , Air Pollution/adverse effects , Endothelin-1/blood , Pulmonary Artery/drug effects , Adolescent , Air Pollutants/analysis , Air Pollution/analysis , Blood Pressure/drug effects , Child , Cities , Echocardiography, Doppler , Female , Humans , Leukocyte Count , Male , Mexico , Neutrophils/drug effects , Ozone/analysis , Ozone/toxicity , Particulate Matter/analysis , Particulate Matter/toxicity , Pulmonary Artery/physiopathologyABSTRACT
Southwest Metropolitan Mexico City (SWMMC) children are chronically exposed to complex mixtures of air pollutants. In a cross-sectional arm of our study, we investigated the association between exposure to SWMMC atmosphere and nasal abnormalities, hyperinflation, and interstitial markings assessed by chest X-rays, lung function changes, several serum cytokines, and endothelin-1 in 174 children aged 5-17 years vs. 27 control children residents in low-polluted areas. Control children had no nasal lesions, and only one child showed an abnormal chest X-ray. SWMMC children exhibited nasal abnormalities (22%), hyperinflation (67%), interstitial markings (49%), and a mild restrictive pattern by spirometry (10%). Interstitial markings were associated with a decrease in predicted values of FEF(25-75), FEF(75), and the FEV(1)/FVC ratio. Boys had a higher probability of developing interstitial markings with age (P = 0.004). Blood smear findings included toxic granulations in neutrophils and schistocytes. SWMMC children had more serum IL10 and IL6 and less IL8 than controls. In a longitudinal arm of our study, we found a significant seasonal drop in FVC and FEV(1) associated with a 6-month period of high ozone and PM(10) levels. Our data strongly suggest that a lifelong exposure to urban air pollution causes respiratory damage in children. Moreover, a cytokine network becomes imbalanced, with a shift towards upregulation of anti-inflammatory cytokines. Consequently, these children are potentially at risk for developing chronic lung disease and other systemic effects later in life.
Subject(s)
Air Pollutants/toxicity , Inhalation Exposure/adverse effects , Urban Population , Adolescent , Age Factors , Air Pollutants/analysis , Case-Control Studies , Child , Child, Preschool , Cross-Sectional Studies , Cytoplasmic Granules/pathology , Endothelin-1/blood , Erythrocytes, Abnormal/pathology , Female , Humans , Hyperemia/diagnosis , Interleukins/blood , Longitudinal Studies , Lung/diagnostic imaging , Lung/physiopathology , Male , Mexico/epidemiology , Nasal Cavity/abnormalities , Neutrophils/pathology , Ozone/analysis , Radiography , Seasons , Sex FactorsABSTRACT
El estudio citogenético en la médula ósea de 61 pacientes pediátricos con hemopatías malignas mostró que 36 (59 por ciento) tenían un cariotopo anormal al momento del diagnóstico. De éstos, 15 tenían anormalidades estructurales y en ocho el cromosoma 1 estaba involucrado en alguno de los rearreglos. El objetivo del presente etudio fue analizar las alteraciones del cromosoma 1 y el estado clínico de los pacientes porque otros autores han observado la aparición de estos rearreglos en enfermos con recaída o en estado terminal. En tres casos la alteración en la que participaba el cromosoma 1 fueron primarias; y en los restantes fueron cambios clonales secundarios que aparecen durante la evolución de la enfermedad. Al momento del diagnóstico, cinco de estos pacientes tenían cuentas elevadas de leucocitos o enfermedad extramedular y la respuesta al tratamiento en general fue mala. Se asume que la alta frecuencia de alteraciones del cromosoma 1 en la población estudiada se debe a que los pacientes llegan al Instituto para su diagnóstico y tratamiento cuando su padecimiento está avanzado, existe evolución clonal de las células leucémicas y el pronóstico es malo.
