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1. Delayed diagnosis of tuberculosis in persons living with HIV in Eastern Europe: associated factors and effect on mortality-a multicentre prospective cohort study

Author

Kraef, Christian, Bentzon, Adrian, Panteleev, Alexander, Skrahina, Alena, Bolokadze, Natalie, Tetradov, Simona, Podlasin, Regina, Karpov, Igor, Borodulina, Elena, Denisova, Elena, Azina, Inga, Lundgren, Jens, Johansen, Isik Somuncu, Mocroft, Amanda, Podlekareva, Daria, Kirk, Ole, Vassilenko, A., Klimuk, D., Kondratenko, O., Zalutskaya, A., Bondarenko, V., Mitsura, V., Kozorez, E., Tumash, O., Suetnov, O., Paduto, D., Iljina, V., Kummik, T., Mshvidobadze, K., Lanchava, N., Goginashvili, L., Mikiashvili, L., Bablishvili, Nino, Rozentale, B., Zeltina, I., Janushkevich, I., Caplinskiene, I., Caplinskas, S., Kancauskiene, Z., Wiercinska-Drapalo, A., Thompson, M., Kozlowska, J., Grezesczuk, A., Bura, M., Knysz, B., Inglot, M., Garlicki, A., Loster, J., uiculescu, D.D., Rakhmanova, A., Panteleev, O., Yakovlev, A., Kozlov, A., Tyukalova, A., Vlasova, Y., rofimov, T.T., Kyselyova, G., Obel, N., Gerstoft, J., Kronborg, G., Payen, M.C., abeya, K.K., Necsoi, C., Dabis, F., Tsaranazy, A., Cazanave, C., Furrer, H., Sagette, M., Rickenbach, M., Sculier, D., Calmy, A., Cavassini, Matthias, Bruno, A., Bernasconi, E., Hoffmann, M., Vernazza, P., Fehr, J., Weber, R., Miller, R., Vora, N., Cooke, G., Mullaney, S., Wilkins, E., George, V., Collini, P., Dockrell, D., Post, F., Campbell, L., Brum, R., Mabonga, E., Saigal, P., Kegg, S., Ainsworth, J., Waters, A., Dhar, J., Ellis, K., Girardi, E., Rianda, A., Galati, V., Pinnetti, C., Tommasi, C., Lapadula, G., Di Biagio, A., Parisini, A., Carbonara, S., Angarano, G., Purgatorio, M., Matteelli, A., Apostoli, A., Miro, J.M., Manzardo, C., Ligero, C., Gonzalez, J., Martinez-Martinez, J.A., Sanchez, F., Knobel Freud, Hernando, Salvadó, M., Lopez-Colomes, J.L., Martínez-Lacasa, X., Cuchí, E., Falcó, Vicenç, Curran, Adrian, Tortola, M.T., Ocaña Rivera, Immaculada, Vidal, R., Sambeat, M.A., Pomar, Virginia, Coll, P., Pozamczer, D., Saumoy, M., Alcaide, Fernando, Caylà, Joan A, Moreno Camacho, Asunción, Millet, Joan-Pau, Orcau, Àngels, Fina, L., Romero, A., Roldan, L.L., Iribarren, J.A., Ibarguren, M., Moreno, S., González, A., Miralles, P., Aldámiz-Echevarría, T., Losso, M., Toibaro, J., Gambardella, L., Moreno Macias, L., Warley, E., Tavella, S., Garcia Messina, O., Gear, O., Laplume, H., Marson, C., Contarelia, J., Michaan, M., Scapellato, P., Bartoletti, B., Palmero, D., Elias, C., Cortes, C., Crabtree, B., Mosqueda Gomez, J.L., Villanueva, J.A., Gonzalez Hernandez, L.A., Badial, F., Kraef, C, Bentzon, A, Panteleev, A, Skrahina, A, Bolokadze, N, Tetradov, S, Podlasin, R, Karpov, I, Borodulina, E, Denisova, E, Azina, I, Lundgren, J, Johansen, I, Mocroft, A, Podlekareva, D, Kirk, O, Vassilenko, A, Klimuk, D, Kondratenko, O, Zalutskaya, A, Bondarenko, V, Mitsura, V, Kozorez, E, Tumash, O, Suetnov, O, Paduto, D, Iljina, V, Kummik, T, Mshvidobadze, K, Lanchava, N, Goginashvili, L, Mikiashvili, L, Bablishvili, N, Rozentale, B, Zeltina, I, Janushkevich, I, Caplinskiene, I, Caplinskas, S, Kancauskiene, Z, Wiercinska-Drapalo, A, Thompson, M, Kozlowska, J, Grezesczuk, A, Bura, M, Knysz, B, Inglot, M, Garlicki, A, Loster, J, Uiculescu, D, Rakhmanova, A, Panteleev, O, Yakovlev, A, Kozlov, A, Tyukalova, A, Vlasova, Y, Rofimov, T, Kyselyova, G, Obel, N, Gerstoft, J, Kronborg, G, Payen, M, Abeya, K, Necsoi, C, Dabis, F, Tsaranazy, A, Cazanave, C, Furrer, H, Sagette, M, Rickenbach, M, Sculier, D, Calmy, A, Cavassini, M, Bruno, A, Bernasconi, E, Hoffmann, M, Vernazza, P, Fehr, J, Weber, R, Miller, R, Vora, N, Cooke, G, Mullaney, S, Wilkins, E, George, V, Collini, P, Dockrell, D, Post, F, Campbell, L, Brum, R, Mabonga, E, Saigal, P, Kegg, S, Ainsworth, J, Waters, A, Dhar, J, Ellis, K, Girardi, E, Rianda, A, Galati, V, Pinnetti, C, Tommasi, C, Lapadula, G, Di Biagio, A, Parisini, A, Carbonara, S, Angarano, G, Purgatorio, M, Matteelli, A, Apostoli, A, Miro, J, Manzardo, C, Ligero, C, Gonzalez, J, Martinez-Martinez, J, Sanchez, F, Knobel, H, Salvado, M, Lopez-Colomes, J, Martinez-Lacasa, X, Cuchi, E, Falco, V, Curran, A, Tortola, M, Ocana, I, Vidal, R, Sambeat, M, Pomar, V, Coll, P, Pozamczer, D, Saumoy, M, Alcaide, F, Cayla, J, Moreno, A, Millet, J, Orcau, A, Fina, L, Romero, A, Roldan, L, Iribarren, J, Ibarguren, M, Moreno, S, Gonzalez, A, Miralles, P, Aldamiz-Echevarria, T, Losso, M, Toibaro, J, Gambardella, L, Moreno Macias, L, Warley, E, Tavella, S, Garcia Messina, O, Gear, O, Laplume, H, Marson, C, Contarelia, J, Michaan, M, Scapellato, P, Bartoletti, B, Palmero, D, Elias, C, Cortes, C, Crabtree, B, Mosqueda Gomez, J, Villanueva, J, Gonzalez Hernandez, L, and Badial, F

Subjects
medicine.medical_specialty, Tuberculosis, Delayed Diagnosis, Aged, Europe, Eastern, Humans, Middle Aged, Prospective Studies, HIV Infections, Tuberculosi, Epidemiology, Tuberculosis/diagnosis, HIV Infections/complications, Infectious and parasitic diseases, RC109-216, Eastern Europe, Eastern, Logistic regression, Europa de l'Est, Medical microbiology, Weight loss, Internal medicine, medicine, VIH (Virus), HIV Infection, Europe, Eastern/epidemiology, Prospective cohort study, Epidemiologia, business.industry, Proportional hazards model, Transmission (medicine), HIV (Viruses), Research, Hazard ratio, Delayed Diagnosi, medicine.disease, Europe, Prospective Studie, Infectious Diseases, medicine.symptom, business, Human
Abstract

Background Early diagnosis of tuberculosis (TB) is important to reduce transmission, morbidity and mortality in people living with HIV (PLWH). Methods PLWH with a diagnosis of TB were enrolled from HIV and TB clinics in Eastern Europe and followed until 24 months. Delayed diagnosis was defined as duration of TB symptoms (cough, weight-loss or fever) for ≥ 1 month before TB diagnosis. Risk factors for delayed TB diagnosis were assessed using multivariable logistic regression. The effect of delayed diagnosis on mortality was assessed using Kaplan–Meier estimates and Cox models. Findings 480/740 patients (64.9%; 95% CI 61.3–68.3%) experienced a delayed diagnosis. Age ≥ 50 years (vs. Conclusion Nearly two thirds of PLWH with TB in Eastern Europe had a delayed TB diagnosis, in particular those of older age, people who inject drugs, ART naïve, with disseminated disease, and presenting with weight loss. Patients with delayed TB diagnosis were subsequently at higher risk of death in unadjusted analysis. There is a need for optimisation of the current TB diagnostic cascade and HIV care in PLWH in Eastern Europe.

Published
2021
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2. Healthcare delivery for HIV-positive people with tuberculosis in Europe

Author

Bentzon, A. K., Panteleev, A., Mitsura, V., Borodulina, E., Skrahina, A., Denisova, E., Tetradov, S., Podlasin, R., Riekstina, V., Kancauskiene, Z., Paduto, D., Mocroft, A., Trofimova, T., Miller, R., Post, F., Grezesczuk, A., Lundgren, J. D., Inglot, M., Podlekareva, D., Bolokadze, N., Kirk, O., Karpov, I., Vassilenko, A., Klimuk, D., Skrahin, A., Kondratenko, O., Zalutskaya, A., Bondarenko, V., Kozorez, E., Tumash, O., Suetnov, O., Iljina, V., Kummik, T., Mshvidobadze, K., Lanchava, N., Goginashvili, L., Mikiashvili, L., Bablishvili, N., Rozentale, B., Zeltina, I., Janushkevich, I., Caplinskiene, I., Caplinskas, S., Wiercinska-Drapalo, A., Thompson, M., Kozlowska, J., Bura, M., Knysz, B., Garlicki, A., Loster, J., Duiculescu, D., Rakhmanova, A., Panteleeva, O., Yakovlev, A., Kozlov, A., Tyukalova, A., Vlasova, Y., Trofimov, T., Kyselyova, G., Obel, N., Gerstoft, J., Kronborg, G., Payen, M. C., Kabeya, K., Necsoi, C., Dabis, F., Tsaranazy, A., Cazanave, C., Furrer, H., Sagette, M., Rickenbach, M., Elzi, L., Battegay, M., Sculier, D., Calmy, A., Cavassini, M., Bruno, A., Bernasconi, E., Hoffmann, M., Vernazza, P., Fehr, J., Weber, R., Vora, N., Cooke, G., Mullaney, S., Wilkins, E., George, V., Collini, P., Dockrell, D., Campbell, L., Brum, R., Mabonga, E., Saigal, P., Kegg, S., Ainsworth, J., Waters, A., Dhar, J., Ellis, K., Spallanzani, O. L., Girardi, E., Rianda, A., Galati, V., Pinnetti, C., Tommasi, C., San Gerardo, A. O., Lapadula, G., Di Biagio, A., Parisini, A., Carbonara, S., Angarano, G., Purgatorio, M., Matteelli, A., Apostoli, A., Miro, J. M., Manzardo, C., Ligero, C., Gonzalez, J., Martinez-Martinez, J. A., Sanchez, F., Knobel, H., Salvado, M., Lopez-Colomes, J. L., Martinez-Lacasa, X., Cuchi, E., Falco, V., Curran, A., Tortola, M. T., Ocana, I., Vidal, R., Sambeat, M. A., Pomar, V., Coll, P., Pozamczer, D., Saumoy, M., Alcaide, F., Cayla, J., Moreno, A., Millet, J. P., Orcau, A., Fina, L., Romero, A., Roldan, L. L., Iribarren, J. A., Ibarguren, M., Moreno, S., Gonzalez, A., Miralles, P., Aldamiz-Echevarria, T., Losso, M., Toibaro, J., Gambardella, L., Ramos Mejia, J. M., Moreno Macias, L., Warley, E., Tavella, S., Garcia Messina, O., Gear, O., Laplume, H., Marson, C., Contarelia, J., Michaan, M., Scapellato, P., Bartoletti, B., Palmero, D., Elias, C., Cortes, C., Crabtree, B., Mosqueda Gomez, J. L., Villanueva, J. A., Gonzalez Hernandez, L. A., and Badial, F.

Subjects
0301 basic medicine, medicine.medical_specialty, Rifabutin, Tuberculosis, Tuberculosi, Epidemiology, Antitubercular Agents, HIV Infections, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Moxifloxacin, Internal medicine, medicine, clinical management, VIH (Virus), Humans, Pharmacology (medical), 030212 general & internal medicine, Epidemiologia, coinfection, eastern Europe, HIV, tuberculosis, western Europe, Response rate (survey), GeneXpert MTB/RIF, business.industry, HIV (Viruses), Health Policy, medicine.disease, 030112 virology, Europe, Infectious Diseases, HIV-positive people, chemistry, Coinfection, Bedaquiline, business, Europa, Delivery of Health Care, medicine.drug
Abstract

Background: In a 2013 survey, we reported distinct discrepancies in delivery of tuberculosis (TB) and HIV services in eastern Europe (EE) vs. western Europe (WE). Objectives: To verify the differences in TB and HIV services in EE vs. WE. Methods: Twenty-three sites completed a survey in 2018 (EE, 14; WE, nine; 88% response rate). Results were compared across as well as within the two regions. When possible, results were compared with the 2013 survey. Results: Delivery of healthcare was significantly less integrated in EE: provision of TB and HIV services at one site (36% in EE vs. 89% in WE; P = 0.034), and continued TB follow-up in one location (42% vs. 100%; P = 0.007). Although access to TB diagnostics, standard TB and HIV drugs was generally good, fewer sites in EE reported unlimited access to rifabutin/multi-drug-resistant TB (MDR-TB) drugs, HIV integrase inhibitors and opioid substitution therapy (OST). Compared with 2013, routine usage of GeneXpert was more common in EE in 2018 (54% vs. 92%; P = 0.073), as was access to moxifloxacin (46% vs. 91%; P = 0.033), linezolid (31% vs. 64%; P = 0.217), and bedaquiline (0% vs. 25%; P = 0.217). Integration of TB and HIV services (46% vs. 39%; P = 1.000) and provision of OST to patients with opioid dependency (54% vs. 46%; P = 0.695) remained unchanged. Conclusion: Delivery of TB and HIV healthcare, including integration of TB and HIV care and access to MDR-TB drugs, still differs between WE and EE, as well as between individual EE sites.

Published
2020
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3. Tuberculosis-related mortality in people living with HIV in Europe and Latin America: An international cohort study

Author

Podlekareva Daria, N, Efsen Anne Marie, W, Schultze, A, Post Frank, A, Skrahina Alena, M, Panteleev, A, Furrer, H, Miller Robert, F, Losso, M. H, Toibaro, J, Miro Jose, M, Vassilenko, A, Girardi, Enrico, Bruyand, M, Obel, N, Lundgren Jens, D, Mocroft, A, Kirk, O, Karpov, I, Skrahina, A, Klimuk, D, Skrahin, A, Kondratenko, O, Zalutskaya, A, Bondarenko, V, Mitsura, V, Kozorez, E, Tumash, O, Suetnov, O, Paduto, D, Iljina, V, Kummik, T, Bolokadze, N, Mshvidobadze, K, Lanchava, N, Goginashvili, L, Mikiashvili, L, Bablishvili, N, Rozentale, B, Zeltina, I, Janushkevich, I, Caplinskiene, I, Caplinskas, S, Kancauskiene, Z, Podlasin, R, Wiercinska Drapalo, A, Thompson, M, Kozlowska, J, Grezesczuk, A, Bura, M, Knysz, B, Inglot, M, Garlicki, A, Loster, J, Duiculescu, D, Tetradov, S, Rakhmanova, A, Panteleeva, O, Yakovlev, A, Kozlov, A, Tyukalova, A, Vlasova, Y, Trofimov, T, Kyselyova, G, Thorsteinsson, K, Payen, Mc, Kabeya, K, Necsoi, C, Dabis, F, Morlat, P, Dupont, A, Gerard, Y, Bonnal, F, Ceccaldi, J, De Witte, S, Monlun, E, Lataste, P, Chossat, I, Sagette, M, Rickenbach, M, Elzi, L, Battegay, M, Sculier, D, Calmy, A, Cavassini, M, Bruno, A, Bernasconi, E, Hoffmann, M, Vernazza, P, Fehr, J, Weber, R, Aubert, V, Böni, J, Bucher, Hc, Burton Jeangros, C, Dollenmaier, G, Egger, M, Fellay, J, Fux, Ca, Gorgievski, M, Günthard, H, Haerry, D, Hasse, B, Hirsch, Hh, Hösli, I, Kahlert, C, Kaiser, L, Keiser, O, Klimkait, T, Kouyos, R, Kovari, H, Ledergerber, B, Martinetti, G, Martinez de Tejada, B, Metzner, K, Müller, N, Nadal, D, Nicca, D, Pantaleo, G, Rauch, A, Regenass, S, Rudin, C, Schöni Affolter, F, Schmid, P, Schüpbach, J, Speck, R, Tarr, P, Telenti, A, Trkola, A, Yerly, S, Miller, Rf, Vora, N, Cooke, G, Mullaney, S, Wilkins, E, George, V, Collini, P, Dockrell, D, Post, F, Campbell, L, Brum, R, Mabonga, E, Saigal, P, Kegg, S, Ainsworth, J, Waters, A, Dhar, J, Mashonganyika, L, Girardi, E, Rianda, A, Galati, V, Pinnetti, C, Tommasi, C, Lapadula, G, Di Biagio, A, Parisini, A, Carbonara, S, Angarano, G, Purgatorio, M, Matteelli, Alberto, Apostoli, A, Miro, Jm, Manzardo, C, Ligero, C, Gonzalez, J, Martinez Martinez, Ja, Sanchez, F, Knobel, H, Salvadó, M, Lopez Colomes, Jl, Martínez Lacasa, X, Cuchí, E, Falcó, V, Curran, A, Tortola, Mt, Ocaña, I, Vidal, R, Sambeat, Ma, Pomar, V, Coll, P, Pozamczer, D, Saumoy, M, Alcaide, F, Caylà, J, Moreno, A, Millet, Jp, Orcau, A, Fina, L, Romero, A, Roldan, Ll, Iribarren, Ja, Ibarguren, M, Moreno, S, González, A, Miralles, P, Aldámiz Echevarría, T, Losso, M, Gambardella, L, Macias, L, Warley, E, Tavella, S, Messina, O, Gear, O, Laplume, H, Marson, C, Contarelia, J, Michaan, M, Scapellato, P, Alessandro, D, Bartoletti, B, Palmero, D, Elias, C, Cortes, C, Crabtree, B, Gomez, Jl, Hernandez, La, and Badial, F.

Subjects
Adult, Male, 0301 basic medicine, Pediatrics, medicine.medical_specialty, Latin Americans, Tuberculosis, Anti-HIV Agents, Epidemiology, 030106 microbiology, Population, Infectious Diseases, Immunology, Virology, Antitubercular Agents, HIV Infections, Cohort Studies, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Tuberculosis, Multidrug-Resistant, medicine, Humans, Prospective Studies, 030212 general & internal medicine, Young adult, Epidemics, education, Prospective cohort study, education.field_of_study, AIDS-Related Opportunistic Infections, business.industry, Mortality rate, Middle Aged, medicine.disease, Europe, Latin America, Female, business, Developed country, Demography, Cohort study
Abstract

Management of tuberculosis in patients with HIV in eastern Europe is complicated by the high prevalence of multidrug-resistant tuberculosis, low rates of drug susceptibility testing, and poor access to antiretroviral therapy (ART). We report 1 year mortality estimates from a multiregional (eastern Europe, western Europe, and Latin America) prospective cohort study: the TB:HIV study.Consecutive HIV-positive patients aged 16 years or older with a diagnosis of tuberculosis between Jan 1, 2011, and Dec 31, 2013, were enrolled from 62 HIV and tuberculosis clinics in 19 countries in eastern Europe, western Europe, and Latin America. The primary endpoint was death within 12 months after starting tuberculosis treatment; all deaths were classified according to whether or not they were tuberculosis related. Follow-up was either until death, the final visit, or 12 months after baseline, whichever occurred first. Risk factors for all-cause and tuberculosis-related deaths were assessed using Kaplan-Meier estimates and Cox models.Of 1406 patients (834 in eastern Europe, 317 in western Europe, and 255 in Latin America), 264 (19%) died within 12 months. 188 (71%) of these deaths were tuberculosis related. The probability of all-cause death was 29% (95% CI 26-32) in eastern Europe, 4% (3-7) in western Europe, and 11% (8-16) in Latin America (p0·0001) and the corresponding probabilities of tuberculosis-related death were 23% (20-26), 1% (0-3), and 4% (2-8), respectively (p0·0001). Patients receiving care outside eastern Europe had a 77% decreased risk of death: adjusted hazard ratio (aHR) 0·23 (95% CI 0·16-0·31). In eastern Europe, compared with patients who started a regimen with at least three active antituberculosis drugs, those who started fewer than three active antituberculosis drugs were at a higher risk of tuberculosis-related death (aHR 3·17; 95% CI 1·83-5·49) as were those who did not have baseline drug-susceptibility tests (2·24; 1·31-3·83). Other prognostic factors for increased tuberculosis-related mortality were disseminated tuberculosis and a low CD4 cell count. 18% of patients were receiving ART at tuberculosis diagnosis in eastern Europe compared with 44% in western Europe and 39% in Latin America (p0·0001); 12 months later the proportions were 67% in eastern Europe, 92% in western Europe, and 85% in Latin America (p0·0001).Patients with HIV and tuberculosis in eastern Europe have a risk of death nearly four-times higher than that in patients from western Europe and Latin America. This increased mortality rate is associated with modifiable risk factors such as lack of drug susceptibility testing and suboptimal initial antituberculosis treatment in settings with a high prevalence of drug resistance. Urgent action is needed to improve tuberculosis care for patients living with HIV in eastern Europe.EU Seventh Framework Programme.

Published
2016

4. Short- and long-term mortality and causes of death in HIV/tuberculosis patients in Europe

Author

Podlekareva, D. N., Panteleev, A. M., Grint, D., Post, F. A., Miro, J. M., Bruyand, M., Furrer, H., Obel, N., Girardi, E., Vasilenko, A., Losso, M. H., Arenas-Pinto, A., Cayla, J., Rakhmanova, A., Zeltina, I., Werlinrud, A. M., Lundgren, J. D., Mocroft, A., Kirk, O., Toibaro, J. J., Warley, E., Tamayo, N., Cristina Ortiz, M., Scapelatto, P., Bottaro, E., Murano, F., Miachans, M., Contarelli, J., Massera, L., Corral, J., Hualde, M., Miglioranza, C., Corti, M., Metta, H., Casiro, A., Cuini, R., Laplume, H., David, D., Marson, C., Lupo, S., Trape, L., Garcia Messina, O., Gear, O., Bruguera, J. M., Karpov, I., Skrahina, E., Skrahin, A., Mitsura, V., Kozorez, E., Ruzanov, D., Bondarenko, V., Suetnov, O., Paduto, D., Dabis, F., Matteelli, A., Carvalho, A. C., Basche, R., Hamad, I. E., Ricci, B. A., Maggiolo, F., Ravasio, V., Mussini, C., Prati, F., Castelletti, S., Spallanzani, L., Antinori, A., Antonucci, G., Bibbolino, C., Bove, G., Busi Rizzi, E., Cicalini, S., Conte, A., Cuzzi, G., De Mori, P., Festa, A., Goletti, D., Grisetti, S., Gualano, G., Lauria, F. N., Maddaluno, R., Migliorisi Ramazzini, P., Narciso, P., Parracino, L., Palmieri, F., Petrosillo, N., Pucillo, L., Puro, V., Vanacore, P., Urso, R., d'Arminio Monforte, A., Riekstina, V., Aldins, P., Duiculescu, D., Malashenkov, E., Kozlov, A., Buzunova, S., Manzardo, C., Garcia-Goez, J. F., Moreno-Camacho, A., Martinez, J. A., Gonzalez, J., Garcia-Alcaide, F., Perez, I., Gatell, J. M., Sanchez, P., Lopez-Colomes, J. L., Martinez-Lacasa, X., Falco, V., Imaz, A., Ocana, I., Vidal, R., Sambeat, M. A., Moreno-Martinez, A., Millet, J. P., Fina, L., del Bano, L., Orcau, A., Barth, J., Battegay, M., Bernasconi, E., Boni, J., Bucher, H. C., Burton-Jeangros, C., Calmy, A., Cavassini, M., Cellerai, C., Egger, M., Elzi, L., Fehr, J., Fellay, J., Flepp, M., Fux, C. A., Gorgievski, M., Gunthard, H., Haerry, D., Hasse, B., Hirsch, H. H., Hirschel, B., Hosli, I., Kahlert, C., Kaiser, L., Keiser, O., Kind, C., Klimkait, T., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Muller, N., Nadal, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schoni-Affolter, F., Schupbach, J., Speck, R., Taffe, P., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., Yerly, S., Campbell, L., Miller, R., Chentsova, N., Podlekareva, D., Kjaer, J., and Duiculesku, D.

Subjects
Pulmonary and Respiratory Medicine, Adult, Male, medicine.medical_specialty, Multivariate analysis, Tuberculosis, Anti-HIV Agents, Antitubercular Agents, Argentina, HIV Infections, Rate ratio, Cohort Studies, symbols.namesake, Cause of Death, Coinfection, Europe, Female, Humans, Multivariate Analysis, Internal medicine, medicine, Poisson regression, Cause of death, business.industry, Mortality rate, medicine.disease, 3. Good health, Surgery, Cohort, symbols, business, Cohort study
Abstract

Mortality of HIV/tuberculosis (TB) patients in Eastern Europe is high. Little is known about their causes of death. This study aimed to assess and compare mortality rates and cause of death in HIV/TB patients across Eastern Europe and Western Europe and Argentina (WEA) in an international cohort study. Mortality rates and causes of death were analysed by time from TB diagnosis (3 months, 3-12 months or12 months) in 1078 consecutive HIV/TB patients. Factors associated with TB-related death were examined in multivariate Poisson regression analysis. 347 patients died during 2625 person-years of follow-up. Mortality in Eastern Europe was three- to ninefold higher than in WEA. TB was the main cause of death in Eastern Europe in 80%, 66% and 61% of patients who died3 months, 3-12 months or12 months after TB diagnosis, compared to 50%, 0% and 15% in the same time periods in WEA (p0.0001). In multivariate analysis, follow-up in WEA (incidence rate ratio (IRR) 0.12, 95% CI 0.04-0.35), standard TB-treatment (IRR 0.45, 95% CI 0.20-0.99) and antiretroviral therapy (IRR 0.32, 95% CI 0.14-0.77) were associated with reduced risk of TB-related death. Persistently higher mortality rates were observed in HIV/TB patients in Eastern Europe, and TB was the dominant cause of death at any time during follow-up. This has important implications for HIV/TB programmes aiming to optimise the management of HIV/TB patients and limit TB-associated mortality in this region.

Published
2014

5. TB Meningitis in HIV-Positive Patients in Europe and Argentina: Clinical Outcome and Factors Associated with Mortality

Author

Efsen, A. M. W., Panteleev, A. M., Grint, D., Podlekareva, D. N., Vassilenko, A., Rakhmanova, A., Zeltina, I., Losso, M. H., Miller, R. F., Girardi, E., Cayla, J., Post, F. A., Miro, J. M., Bruyand, M., Furrer, H., Obel, N., Lundgren, J. D., Mocroft, A., Kirk, O., Toibaro, J. J., Warley, E., Tamayo, N., Cristina Ortiz, M., Scapelatto, P., Bottaro, E., Murano, F., Miachans, M., Contarelli, J., Massera, L., Corral, J., Hualde, M., Miglioranza, C., Corti, M., Metta, H., Casiro, A., Cuini, R., Laplume, H., David, D., Marson, C., Lupo, S., Trape, L., Garcia Messina, O., Gear, O., Bruguera, J. M., Karpov, I., Skrahina, E., Skrahin, A., Zhavoronok, S., Mitsura, V., Ruzanov, D., Bondarenko, V., Suetnov, O., Paduto, D., Gerstoft, J., Kronborg, G., Pedersen, C., Larsen, C. S., Pedersen, G., Laursen, A. L., Nielsen, L., Jensen, J., Dabis, F., Chene, G., Lawson-Ayayi, S., Thiebaut, R., Wittkop, L., Morlat, P., Bonnet, F., Bernard, N., Hessamfar, M., Lacoste, D., Vandenhende, M. A., Dupon, M., Dauchy, F. A., Dutronc, H., Longy-Boursier, M., Mercie, P., Duffau, P., Roger Schmeltz, J., Malvy, D., Pistone, T., Receveur, M. C., Neau, D., Cazanave, C., Ochoa, A., Vareil, M. O., Pellegrin, J. L., Viallard, J. F., Greib, C., Lazaro, E., Fleury, H., Lafon, M. E., Reigadas, S., Trimoulet, P., Breilh, D., Molimard, M., Bouchet, S., Titier, K., Moreau, J. F., Pellegrin, I., Haramburu, F., Arcachon, G., Dupont, A., Gerard, Y., Caunegre, L., Andre, K., Bonnal, F., Farbos, S., Gemain, M. C., Ceccaldi, J., Tchamgoue, S., De Witte, S., Courtault, K., Monlun, E., Gaborieau, V., Lataste, P., Meraud, J. P., Chossat, I., Carvalho, A. C., Basche, R., Hamad, I. E., Ricci, B. A., Maggiolo, F., Ravasio, V., Mussini, C., Prati, F., Castelletti, S., Ammassari, A., Antinori, A., Bellagamba, R., Busi Rizzi, E., Cicalini, S., Corpolongo, A., Capaldo, A., Di Caro, A., Goletti, D., Grisetti, S., Gualano, G., Lauria, F. N., Parracino, L., Palmieri, F., Petrosillo, N., Pinetti, C., Sampaolesi, A., Moroni, M., Angarano, G., Armignacco, O., d'Arminio Monforte, A., Castelli, F., Cauda, R., Di Perri, G., Galli, M., Iardino, R., Guzzinati, Ippolito, Lazzarin, A., Perno, C. F., von Schloesser, F., Viale, P., Castagna, A., Ceccherini-Silberstein, F., Cozzi-Lepri, A., Lo Caputo, S., Puoti, M., Andreoni, M., Balotta, C., Bonfanti, P., Bonora, S., Borderi, M., Capobianchi, M. R., Cingolani, A., Cinque, P., De Luca, A., Di Biagio, A., Gianotti, N., Gori, A., Guaraldi, G., Lapadula, G., Lichtner, M., Madeddu, G., Marchetti, G., Marcotullio, S., Monno, L., Quiros Roldan, E., Rusconi, S., Cicconi, P., Fanti, I., Formenti, T., Galli, L., Lorenzini, P., Giacometti, A., Costantini, A., Carrisa, C., Suardi, C., Vanino, E., Verucchi, G., Minardi, C., Quirino, T., Abeli, C., Manconi, P. E., Piano, P., Vecchiet, J., Falasca, K., Sighinolfi, L., Segala, D., Mazzotta, F., Cassola, G., Viscoli, G., Alessandrini, A., Piscopo, R., Mazzarello, G., Mastroianni, C., Belvisi, V., Caramma, I., Castelli, A. P., Rizzardini, G., Ridolfo, A. L., Piolini, R., Salpietro, S., Carenzi, L., Moioli, M. C., Puzzolante, C., Abrescia, N., Chirianni, A., Guida, M. G., Gargiulo, M., Baldelli, F., Francisci, D., Parruti, G., Ursini, T., Magnani, G., Ursitti, M. A., Vullo, V., D'Avino, A., Gallo, L., Nicastri, E., Acinapura, R., Capozzi, M., Libertone, R., Tebano, G., Cattelan, A., Mura, M. S., Caramello, P., Orofino, G. C., Sciandra, M., Pellizzer, G., Manfrin, V., Riekstina, V., Aldins, P., Duiculescu, D., Malashenkov, E., Kozlov, A., Buzunova, S., Garcia-Goez, J. F., Moreno Camacho, A., Martinez, J. A., Gonzalez, J., Garcia-Alcaide, F., de Lazzari, E., Gatell, J. M., Sanchez, P., Lopezcolomes, J. L., Martinez-Lacasa, X., Falco, V., Imaz, A., Ocana, I., Vidal, R., Sambeat, M. A., Moreno-Martinez, A., Orcau, A., Weber, R., Battegay, M., Hirschel, B., Cavassini, M., Bernasconi, E., Schmid, P., Rickenbach, M., Campbell, L., Arenas-Pinto, A., Chentsova, N., Kjaer, J., Efsen, Anne Marie W., Panteleev, Alexander M., Grint, Daniel, Podlekareva, Daria N., Vassilenko, Anna, Rakhmanova, Aza, Zeltina, Indra, Losso, Marcelo H., Miller, Robert F., Girardi, Enrico, Caylã¡, Joan, Post, Frank A., Miro, Jose M., Bruyand, Mathia, Furrer, Hansjakob, Obel, Niel, Lundgren, Jens D., Mocroft, Amanda, Kirk, Ole, Hiv/tb Study, Group, Castagna, Antonella, Efsen, A, Panteleev, A, Grint, D, Podlekareva, D, Vassilenko, A, Rakhmanova, A, Zeltina, I, Losso, M, Miller, R, Girardi, E, Caylá, J, Post, F, Miro, J, Bruyand, M, Furrer, H, Obel, N, Lundgren, J, Mocroft, A, Kirk, O, and Gori, A

Subjects
Genetics and Molecular Biology (all), Male, Pediatrics, Meningeal, Immunology and Microbiology (all), lcsh:Medicine, HIV Infections, Kaplan-Meier Estimate, Rate ratio, Biochemistry, Risk Factors, Adult, Argentina, CD4 Lymphocyte Count, Europe, Female, HIV, Humans, Treatment Outcome, Tuberculosis, Meningeal, Biochemistry, Genetics and Molecular Biology (all), HIV Infection, Mortality rate, General Medicine, symbols, Meningitis, Human, Research Article, medicine.medical_specialty, Tuberculosis, Settore MED/17 - Malattie Infettive, Article Subject, General Biochemistry, Genetics and Molecular Biology, Tuberculous meningitis, NO, symbols.namesake, Pharmacotherapy, medicine, Poisson regression, General Immunology and Microbiology, business.industry, Public health, Risk Factor, lcsh:R, medicine.disease, Immunology, business
Abstract

Objectives.The study aimed at describing characteristics and outcome of tuberculous meningitis (TBM) in HIV-positive patients and comparing these parameters with those of extrapulmonary TB (TBEP) and pulmonary TB (TBP).Methods.Kaplan-Meier estimation and Poisson regression models were used to assess the mortality following TB diagnosis and to evaluate potential prognostic factors for the 3 groups of TB patients separately.Results.A total of 100 patients with TBM, 601 with TBEP, and 371 TBP were included. Patients with TBM had lower CD4 cell counts and only 17.0% received antiretroviral therapy (ART) at TB diagnosis. The cumulative probability of death at 12 months following TB was 51.2% for TBM (95% CI 41.4–61.6%), 12.3% for TBP (8.9–15.7%), and 19.4% for TBEP (16.1–22.6) (P<0.0001; log-rank test). For TBM, factors associated with a poorer prognosis were not being on ART (adjusted incidence rate ratio (aIRR) 4.00 (1.72–9.09), a prior AIDS diagnosis (aIRR=4.82(2.61–8.92)), and receiving care in Eastern Europe (aIRR=5.41(2.58–11.34))).Conclusions.TBM among HIV-positive patients was associated with a high mortality rate, especially for patients from Eastern Europe and patients with advanced HIV-infection, which urgently calls for public health interventions to improve both TB and HIV aspects of patient management.

Published
2013
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6. Health care index score and risk of death following tuberculosis diagnosis in HIV-positive patients

Author

Podlekareva, D. N., Grint, D., Post, F. A., Mocroft, A., Panteleev, A. M., Miller, R. F., Miro, J. M., Bruyand, M., Furrer, H., Riekstina, V., Girardi, E., Losso, M. H., Cayla, J. A., Malashenkov, E. A., Obel, N., Skrahina, A. M., Lundgren, J. D., Kirk, O., Chentsova, N., Duiculesku, D., Toibaro, J. J., Warley, E., Tamayo, N., Ortiz, M. C., Scapelatto, P., Bottaro, E., Murano, F., Miachans, M., Contarelli, J., Massera, L., Corral, J., Hualde, M., Miglioranza, C., Corti, M., Metta, H., Casiro, A., Cuini, R., Laplume, H., David, D., Marson, C., Lupo, S., Trape, L., Garcia Messina, O., Gear, O., Bruguera, J. M., Karpov, I., Vasilenko, A., Skrahina, E., Mitsura, V., Kozorez, E., Ruzanov, D., Bondarenko, V., Suetnov, O., Paduto, D., Dabis, F., Matteelli, A., Carvalho, A. C., Basche, R., Hamad, I. E., Ricci, B. A., Maggiolo, F., Ravasio, V., Mussini, C., Prati, F., Castelletti, S., Spallanzani, L., Antinori, A., Antonucci, G., Bibbolino, C., Bove, G., Busi Rizzi, E., Cicalini, S., Conte, A., Cuzzi, G., De Mori, P., Festa, A., Goletti, D., Grisetti, S., Gualano, G., Lauria, F. N., Maddaluno, R., Migliorisi Ramazzini, P., Narciso, P., Parracino, L., Palmieri, F., Petrosillo, N., Pucillo, L., Puro, V., Vanacore, P., Urso, R., Aldins, P., Zeltina, I., Duiculescu, D., Rakhmanova, A., Kozlov, A., Buzunova, S., Manzardo, C., Garcia-Goez, J. F., Moreno-Camacho, A., Martinez, J. A., Gonzalez, J., Garcia-Alcaide, F., Perez, I., Gatell, J. M., Sanchez, P., Lopez-Colomes Mutua de Terrassa, J. L., Martinez-Lacasa, X., Imaz, V. F., Ocana, I., Vidal, R., Sambeat, M. A., Moreno-Martinez, A., Millet, J. P., Fina, L., del Bano, L., Orcau, A., Barth, J., Battegay, M., Bernasconi, E., Boni, J., Bucher, H. C., Burton-Jeangros, C., Calmy, A., Cavassini, M., Cellerai, C., Egger, M., Elzi, L., Fehr, J., Fellay, J., Flepp, M., Fux, C. A., Gorgievski, M., Gunthard, H., Haerry, D., Hasse, B., Hirsch, H. H., Hirschel, B., Hosli, I., Kahlert, C., Kaiser, L., Keiser, O., Kind, C., Klimkait, T., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Muller, N., Nadal, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schoni-Affolter, F., Schupbach, J., Speck, R., Taffe, P., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., Yerly, S., Campbell, L., Arenas-Pinto, A., Kjaer, J., and Ellefson, M.

Subjects
Pulmonary and Respiratory Medicine, Adult, Male, medicine.medical_specialty, Tuberculosis, TB-HIV co-infection, Health care index score, Outcome of TB-HIV patients, TB-HIV health care utilisation, AIDS-Related Opportunistic Infections, Cause of Death, Coinfection, Delivery of Health Care, Female, Follow-Up Studies, Global Health, HIV Seropositivity, Humans, Proportional Hazards Models, Retrospective Studies, Risk Assessment, Risk Factors, Severity of Illness Index, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Severity of illness, Health care, medicine, 030212 general & internal medicine, Cause of death, business.industry, Proportional hazards model, Retrospective cohort study, medicine.disease, 3. Good health, Surgery, Regimen, Infectious Diseases, Risk assessment, business
Abstract

OBJECTIVES: To assess health care utilisation for patients co-infected with TB and HIV (TB-HIV), and to develop a weighted health care index (HCI) score based on commonly used interventions and compare it with patient outcome. METHODS: A total of 1061 HIV patients diagnosed with TB in four regions, Central/Northern, Southern and Eastern Europe and Argentina, between January 2004 and December 2006 were enrolled in the TB-HIV study. A weighted HCI score (range 0–5), based on independent prognostic factors identified in multivariable Cox models and the final score, included performance of TB drug susceptibility testing (DST), an initial TB regimen containing a rifamycin, isoniazid and pyrazinamide, and start of combination antiretroviral treatment (cART). RESULTS: The mean HCI score was highest in Central/Northern Europe (3.2, 95%CI 3.1–3.3) and lowest in Eastern Europe (1.6, 95%CI 1.5–1.7). The cumulative probability of death 1 year after TB diagnosis decreased from 39% (95%CI 31–48) among patients with an HCI score of 0, to 9% (95%CI 6–13) among those with a score of ≥4. In an adjusted Cox model, a 1-unit increase in the HCI score was associated with 27% reduced mortality (relative hazard 0.73, 95%CI 0.64–0.84). CONCLUSIONS: Our results suggest that DST, standard anti-tuberculosis treatment and early cART may improve outcome for TB-HIV patients. The proposed HCI score provides a tool for future research and monitoring of the management of TB-HIV patients. The highest HCI score may serve as a benchmark to assess TB-HIV management, encouraging continuous health care improvement.

Published
2013

7. Management of MDR-TB in HIV co-infected patients in Eastern Europe: Results from the TB:HIV study

Author

A.M.W. Efsen, A. Schultze, R.F. Miller, A. Panteleev, A. Skrahin, D.N. Podlekareva, J.M. Miro, E. Girardi, H. Furrer, M.H. Losso, J. Toibaro, J.A. Caylà, A. Mocroft, J.D. Lundgren, F.A. Post, O. Kirk, I. Karpov, A. Vassilenko, A. Skrahina, D. Klimuk, O. Kondratenko, A. Zalutskaya, V. Bondarenko, V. Mitsura, E. Kozorez, O. Tumash, O. Suetnov, D. Paduto, V. Iljina, T. Kummik, N. Bolokadze, K. Mshvidobadze, N. Lanchava, L. Goginashvili, L. Mikiashvili, N. Bablishvili, B. Rozentale, I. Zeltina, I. Janushkevich, I. Caplinskiene, S. Caplinskas, Z. Kancauskiene, R. Podlasin, A. Wiercinska-Drapalo, M. Thompson, J. Kozlowska, A. Grezesczuk, M. Bura, B. Knysz, M. Inglot, A. Garlicki, J. Loster, S. Tetradov, D. Duiculescu, A. Rakhmanova, O. Panteleeva, A. Yakovlev, A. Kozlov, A. Tyukalova, Y. Vlasova, T. Trofimov, G. Kyselyova, A.B. Andersen, K. Thorsteinsson, M.C. Payen, K. Kabeya, C. Necsoi, F. Dabis, M. Bruyand, P. Morlat, A. Dupont, Y. Gerard, F. Bonnal, J. Ceccaldi, S. De Witte, E. Monlun, P. Lataste, I. Chossat, R. Miller, N. Vora, G. Cooke, S. Mullaney, E. Wilkins, V. George, P. Collini, D. Dockrell, F. Post, L. Campbell, R. Brum, E. Mabonga, P. Saigal, S. Kegg, J. Ainsworth, A. Waters, J. Dhar, L. Mashonganyika, A. Rianda, V. Galati, C. Pinnetti, C. Tommasi, G. Lapadula, A. Di Biagio, A. Parisini, S. Carbonara, G. Angarano, M. Purgatorio, A. Matteelli, A. Apostoli, L. Moreno Macias, E. Warley, S. Tavella, O. Garcia Messina, O. Gear, H. Laplume, C. Marson, J. Contarelia, M. Michaan, P. Scapellato, D.D. Alessandro, B. Bartoletti, D. Palmero, C. Elias, C. Cortes, B. Crabtree, J.L. Mosqueda Gomez, A. Villanueva, L.A. Gonzalez Hernandez, Universitat de Barcelona, Efsen, A, Schultze, A, Miller, R, Panteleev, A, Skrahin, A, Podlekareva, D, Miro, J, Girardi, E, Furrer, H, Losso, M, Toibaro, J, Cayla, J, Mocroft, A, Lundgren, J, Post, F, Kirk, O, Karpov, I, Vassilenko, A, Skrahina, A, Klimuk, D, Kondratenko, O, Zalutskaya, A, Bondarenko, V, Mitsura, V, Kozorez, E, Tumash, O, Suetnov, O, Paduto, D, Iljina, V, Kummik, T, Bolokadze, N, Mshvidobadze, K, Lanchava, N, Goginashvili, L, Mikiashvili, L, Bablishvili, N, Rozentale, B, Zeltina, I, Janushkevich, I, Caplinskiene, I, Caplinskas, S, Kancauskiene, Z, Podlasin, R, Wiercinska-Drapalo, A, Thompson, M, Kozlowska, J, Grezesczuk, A, Bura, M, Knysz, B, Inglot, M, Garlicki, A, Loster, J, Tetradov, S, Duiculescu, D, Rakhmanova, A, Panteleeva, O, Yakovlev, A, Kozlov, A, Tyukalova, A, Vlasova, Y, Trofimov, T, Kyselyova, G, Andersen, A, Thorsteinsson, K, Payen, M, Kabeya, K, Necsoi, C, Dabis, F, Bruyand, M, Morlat, P, Dupont, A, Gerard, Y, Bonnal, F, Ceccaldi, J, De Witte, S, Monlun, E, Lataste, P, Chossat, I, Vora, N, Cooke, G, Mullaney, S, Wilkins, E, George, V, Collini, P, Dockrell, D, Campbell, L, Brum, R, Mabonga, E, Saigal, P, Kegg, S, Ainsworth, J, Waters, A, Dhar, J, Mashonganyika, L, Rianda, A, Galati, V, Pinnetti, C, Tommasi, C, Lapadula, G, Di Biagio, A, Parisini, A, Carbonara, S, Angarano, G, Purgatorio, M, Matteelli, A, Apostoli, A, Macias, L, Warley, E, Tavella, S, Garcia Messina, O, Gear, O, Laplume, H, Marson, C, Contarelia, J, Michaan, M, Scapellato, P, Alessandro, D, Bartoletti, B, Palmero, D, Elias, C, Cortes, C, Crabtree, B, Mosqueda Gomez, J, Villanueva, A, and Gonzalez Hernandez, L

Subjects
Male, Pediatrics, Art initiation, Antitubercular Agents, Human immunodeficiency virus (HIV), HIV Infections, Hiv management, Eastern, medicine.disease_cause, Cohort Studies, 0302 clinical medicine, Antiretroviral Therapy, Highly Active, Tuberculosis, Multidrug-Resistant, Health care, Medicine, Europe, Eastern, Prospective Studies, 030212 general & internal medicine, Viral suppression, Prospective cohort study, Coinfection, Disease Management, Multidrug-Resistant, 3. Good health, Europe, Infectious Diseases, Female, Eastern Europe, HIV, MDR-TB, Tuberculosis, Microbiology (medical), Viral load, HIV infections, Adult, medicine.medical_specialty, Anti-HIV Agents, Tuberculosi, Antiretroviral Therapy, Article, 03 medical and health sciences, Humans, Highly Active, business.industry, medicine.disease, 030228 respiratory system, Infeccions per VIH, business
Abstract

Summary Objectives Mortality among HIV patients with tuberculosis (TB) remains high in Eastern Europe (EE), but details of TB and HIV management remain scarce. Methods In this prospective study, we describe the TB treatment regimens of patients with multi-drug resistant (MDR) TB and use of antiretroviral therapy (ART). Results A total of 105 HIV-positive patients had MDR-TB (including 33 with extensive drug resistance) and 130 pan-susceptible TB. Adequate initial TB treatment was provided for 8% of patients with MDR-TB compared with 80% of those with pan-susceptible TB. By twelve months, an estimated 57.3% (95%CI 41.5–74.1) of MDR-TB patients had started adequate treatment. While 67% received ART, HIV-RNA suppression was demonstrated in only 23%. Conclusions Our results show that internationally recommended MDR-TB treatment regimens were infrequently used and that ART use and viral suppression was well below the target of 90%, reflecting the challenging patient population and the environment in which health care is provided. Urgent improvement of management of patients with TB/HIV in EE, in particular for those with MDR-TB, is needed and includes widespread access to rapid TB diagnostics, better access to and use of second-line TB drugs, timely ART initiation with viral load monitoring, and integration of TB/HIV care.

Published
2017
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