Cost-effectiveness analysis of the human recombinant epidermal growth factor in the management of patients with diabetic foot ulcers.

Introduction: Diabetic foot ulcers are one of the most frequent complications of diabetes; such ulcers cause an increase in the costs of the health care of the diabetic patient and can even cause disability due to amputation in the patient. Although a proportion of patients achieve a spontaneous closure of ulcers, others require medical or surgical treatment. Objective: To determine the cost-effectiveness of the intra- and perilesional application of recombinant human epidermal growth factor (rhEGF), as opposed to conventional therapy for the management of patients diagnosed with Wagner's 3 or 4 diabetic foot ulcer in Colombia. Methodology: Using a Markov model, the process of care of a diabetic patient with diagnosis of Wagner's 3 or 4 ulcer receiving conventional treatment, or intra- and perilesional rhEGF, is configured. The evaluation cycles of the treatments are weekly over a 5-year horizon and the outcomes evaluated are quality-adjusted life years (QALYs) and the number of amputations avoided by each treatment scheme, in addition to the total costs for treatments. Results: For the analysed base case, in the outcome of amputations, it was found that the factor presents 39 fewer amputations, in a cohort of 100 patients, compared with conventional treatment. Likewise, QALYs are 0.65 more with the use of rhEGF in an average patient. The estimated cost-utility ratio for the base case would be below the threshold established for Colombia. Conclusions: The intra- and perilesional application of rhEGF is a more effective therapeutic option than conventional therapy in the treatment of patients with Wagner's 3 or 4 diabetic foot ulcers and is cost-effective, taking as an outcome the QALYs for Colombia from the perspective of the health system.

Combined use of Quantiferon and HBHA-based IGRA supports tuberculosis diagnosis and therapy management in children.

OBJECTIVES: Interferon-γ release assays (IGRA) are designed for diagnosis of tuberculosis (TB) infection, and do not discriminate latent TB infection (LTBI) from active TB. Heparin-binding hemagglutinin antigen (HBHA) emerged as a promising antigen for TB diagnosis when used in IGRA format. Aim of this study was to prospectively evaluate the performance of an HBHA-based IGRA to support TB diagnosis and TB therapy monitoring in children with TB infection or active TB disease. METHODS: Following clinical, microbiological and radiological assessment, children (0-14 years old) were tested by the QuantiFERON TB-Gold In tube (QFT) assay and an aliquot of whole-blood was stimulated with HBHA and IFNγ evaluated only in QFT-positive subjects. RESULTS: Among the 550 children tested, 486 (88.4%) scored negative and 64 (11.6%) positive. None of the QFT-negative had active TB. Among the QFT-positive, 45 were with LTBI and 19 active TB. HBHA-IGRA scored positive in 41/45 children (91.1%) with LTBI and in 6/19 active TB children (31.6%) at diagnosis (p = 0.001); remarkably, 5 of these 6 children with active TB scoring HBHA-positive were asymptomatic. Moreover, following TB-specific therapy, most of the non-HBHA-responding children, gained an HBHA-positive response. CONCLUSIONS: HBHA-based IGRA is a useful support in TB diagnosis and TB-therapy monitoring in children.

Public health impact and economic benefits of quadrivalent influenza vaccine in Latin America.

Annual trivalent influenza vaccines (TIV) containing 2 A strains and one B lineage have been recommended for the prevention of influenza in most of Latin American countries. However, the circulation of 2 B lineages (Victoria and Yamagata) and difficulties in predicting the predominating lineage have led to the development of quadrivalent influenza vaccines (QIV), including both B lineages. Thus, the objective was to estimate the public health impact and influenza-related costs if QIV would have been used instead of TIV in 3 Latin American countries. We used a static model over the seasons 2010-2014 in Brazil, 2007-2014 in Colombia and 2006-2014 in Panama, focusing on population groups targeted by local vaccination recommendations: young children, adults with risk factors and the elderly. In Brazil, between 2010 and 2014, using QIV instead of TIV would have avoided US$ 6,200 per 100,000 person-years in societal costs, based on 168 influenza cases, 89 consultations, 3.2 hospitalizations and 0.38 deaths per 100,000 person-years. In Colombia and Panama, these would have ranged from US$ 1,000 to 12,700 (based on 34 cases, 13-25 consultations, 0.6-8.9 hospitalizations and 0.04-1.74 deaths) and from US$ 3,000 to 33,700 (based on 113 cases, 55-82 consultations, 0.5-27.8 hospitalizations and 0.08-6.87 deaths) per 100,000 person-years, respectively. Overall, the broader protection offered by QIV would have reduced the influenza humanistic and economic burden in the 3 countries. Despite the lack of local data leading to several extrapolations, this study is the first to give quantitative estimates of the potential benefits of QIV in Latin America.

Carga económica de la fibrilación auricular en Colombia / Financial burden of atrial defibrillation in Colombia

Resumen Objetivo: Determinar la carga económica de la fibrilación auricular en Colombia. Materiales y métodos: Se realizó un estudio retrospectivo sobre bases de datos de atención de pacientes con diagnóstico de fibrilación auricular. Los pacientes fueron identificados a partir de los diagnósticos registrados en las atenciones ambulatorias y hospitalarias, utilizando como referencia el código diagnóstico CIE-10 de fibrilación auricular (I48x). Luego de la identificación de los pacientes se construyó un algoritmo que simulaba la historia natural y de atención de la enfermedad, el cual fue elaborado a partir de guías de manejo de la enfermedad. Se utilizó una técnica de microcosteo en función de una base de datos oficial de una aseguradora colombiana, teniendo en cuenta la historia natural de la enfermedad construida. Resultados: El costo anual de un paciente con fibrilación auricular diagnosticada correctamente es de $6.218.179, el de un paciente con evento tromboembólico agudo o signos inespecíficos como primera manifestación de la enfermedad es de $23.665.300, y el de un paciente con un infarto previo al diagnóstico de fibrilación auricular es de $37.493.968. Conclusiones: En términos de costos, el paciente que se mantiene controlado pese a que se incurra en costos de tecnologías para su control, es menos costoso que aquel que genera episodios agudos.

Abstract Objective: To determine the financial cost of atrial defibrillation in Colombia. Materials and methods: A retrospective study was carried out using health care data bases on patients with a diagnosis of atrial fibrillation. The patients were identified from the diagnoses recorded in ambulatory and hospital care registers, using the atrial fibrillation ICD-10 diagnostic (I48x). After the patients were identified, an algorithm was constructed by using the management guidelines for the disease and that simulated the natural history and care of the disease. A micro-costing technique was used in accordance with an official data base of a Colombian insurance Company, taking into account the natural history of the disease constructed. Results: The mean annual cost of a patient correctly diagnosed with atrial fibrillation is $6,218.179, that of the patient with an acute thrombo-embolic event or non-specific signs as a first manifestation of the disease is $23,665.300, and that of the patient with an infarction prior to the diagnosis of atrial fibrillation is $37,493.968. Conclusions: In terms of costs, the patient that is maintained under control, despite the technological costs of their control, is less costly than one that has acute episodes.

Accuracy of QuantiFERON-TB Gold Test for Tuberculosis Diagnosis in Children.

OBJECTIVES: To evaluate the accuracy of the QuantiFERON-TB Gold assay (QFT-IT) in children with suspected active or latent TB infection (LTBI). METHODS: A retrospective study was conducted on 621 children (0-14 years old) evaluated for TB infection or disease. Following clinical assessment, children were tested with the QFT-IT assay. RESULTS: Among the 140 active TB suspects, we identified 19 cases of active disease. The overall sensitivity for active TB was 87.5%, ranging from 62.5% in children 25-36 months old to 100% in children older than 49 months. The overall specificity for active TB was 93.6%. Among the 481 children tested for LTBI screening, 38 scored positive and all but 2 had at least one risk factor for TB infection. Among the 26 children with indeterminate results, bacterial, viral or fungal pneumonia were later diagnosed in 11 (42.3%) cases and non-TB related extra-pulmonary infections in 12 (46.1%). CONCLUSIONS: Our results indicate that the children's response to QFT-IT associates to active TB and risk factors for LTBI. Moreover, we show that mitogen response is also found in children of 1 year of age, providing support for QFT-IT use also in young children.

Functional dissection of protein domains involved in the immunomodulatory properties of PE_PGRS33 of Mycobacterium tuberculosis.

PE_PGRSs are a large family of proteins identified in Mycobacterium tuberculosis complex and in few other pathogenic mycobacteria. The PE domain of PE_PGRS33 mediates localization of the protein on the mycobacterial cell surface, where the PGRS domain is available to interact with host components. In this study, PE_PGRS33 and its functional deletion mutants were expressed in M. smegmatis, and in vitro and in vivo assays were used to dissect the protein domains involved in the immunomodulatory properties of the protein. We demonstrate that PE_PGRS33-mediated secretion of TNF-α by macrophages occurs by extracellular interaction with TLR2. Our results also show that while the PGRS domain of the protein is required for triggering TNF-α secretion, mutation in the PE domain affects the pro-inflammatory properties of the protein. These results indicate that PE_PGRS33 is a protein with immunomodulatory activity and that protein stability and localization on the mycobacterial surface can affect these properties.

A twenty-year retrospective study of pediatric tuberculosis in two tertiary hospitals in Rome.

BACKGROUND: Tuberculosis (TB) is among the top 10 causes of child death worldwide. Nevertheless, childhood disease has been neglected by tuberculosis control programs. METHODS: This was a retrospective study of patients < 16 years of age diagnosed with active TB in 2 tertiary hospitals in Rome (Italy), between 1990 and 2009. RESULTS: Two hundred fourteen cases of active tuberculosis were identified (132 definite, 82 probable). Pulmonary involvement was the most common form (75.5%), followed by lymphadenopathy (15.4%) and central nervous system TB (11%). Fever (51.86%) and cough (40%) were the most common presenting symptoms. A total of 23.4% of children were asymptomatic on admission. Sensitivities of the tuberculin skin test and the quantiferon test were 93.4% and 97%, respectively. Both tests performed in 52 children agreed in 49 cases (94%). Sensitivities for culture, Ziehl-Neelsen staining and polymerase chain reaction were 58%, 25% and 66.3%, respectively. The adult source case was identified in 28% of cases. History of contact with a patient with active TB was associated with pulmonary TB (P = 0.0014), whereas negative history of contact was associated with lymph node (P = 0.0064) and central nervous system TB (P = 0.05). CONCLUSIONS: Our study emphasizes the difficulty in managing children with suspected TB, because the absence of constitutional symptoms cannot exclude TB, and bacteriologic confirmation is the exception. Immunologic diagnosis can be a valuable tool to identify TB-infected children because the quantiferon test showed high sensitivity in all age groups. This is of primary importance because early identification of children with latent tuberculous infection and appropriate chemoprophylaxis represent, to date, the most important tool to reduce the burden of TB.