Advertisement

Health-related quality of life assessment among people living with HIV in Rio de Janeiro, Brazil: a cross-sectional study

  • Rodolfo Castro
  • Raquel B. De Boni
  • Paula M. Luz
  • Luciane Velasque
  • Livia V. Lopes
  • Antonieta Medina-Lara
  • Sandra W. Cardoso
  • Marilia S. De Oliveira
  • Ruth K. Friedman
  • Beatriz Grinsztejn
  • Valdiléa G. Veloso
Article

Abstract

Purpose

To assess health-related quality of life (HRQoL) and its associated factors among people living with HIV/AIDS (PLWHA) in Rio de Janeiro, Brazil.

Methods

A cross-sectional study including PLWHA receiving usual HIV-care at Instituto Nacional de Infectologia Evandro Chagas (INI/Fiocruz) was conducted between 2014 and 2016 in Rio de Janeiro, Brazil. The EQ-5D-3L assessed HRQoL; PHQ-2 and ASSIST were used for screening depression and substance use, respectively. Clinical variables were obtained from the INI/Fiocruz cohort database, and structured questions evaluated intimate partner violence, sexual abstinence and relationship status. Data were analysed using multivariable Tobit regression model.

Results

A total of 1480 PLWHA were included: 64.7% were male at birth (38.4% men who have sex with men [MSM], 24.3% heterosexual men and 2% transgender women [TGW]); median age was 43.1 years, and 95.8% were receiving antiretroviral therapy. The median EQ-5D-3L utility score was 0.801. Results showed that the following factors: MSM and women; older age; lower educational level; no engagement in a relationship; depression screening positive; polysubstance use; and, detectable viral load were independently associated with worse HRQoL.

Conclusions

PLWHA under care at INI/Fiocruz presented good HRQoL. Polysubstance use, depression and lower educational level were among the factors negatively associated with HRQoL. This was the first time that the EQ-5D-3L utility scores were calculated for a considerable number of PLWHA in Brazil, which is a fundamental piece of information for future cost-effectiveness analysis.

Keywords

Quality of life Gender Age factors Educational status Depression Substance abuse Viral load, HIV 

Notes

Acknowledgements

We would like to thank: first the research participants; the nurses Denise Arruda and Giselle Cardoso; all the working team at INI/Fiocruz cohort database, with special mention to Monica Derrico, Mauro Derrico, Flaviana Pavan, Mario Sergio Pereira, Andre Augusto and Ronaldo Moreira. We acknowledge the following funding: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)—Grant Numbers: 476024/2013-7 and 476333/2013-0; Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)—Newton Fund RCUK-CONFAP Research Partnerships call, Grant Number: E-26/170.021/2015; and, Programa Institucional de Bolsas de Iniciação Científica (PIBIC/CNPq).

Author contributions

RC, RBDB, PML, LV, SWC, MSO, RKF, BG and VGV reviewed the study protocol and contributed to its final version. RC did the statistical analysis. All authors contributed to the interpretation the results. RC wrote the first draft of the manuscript, which was revised by RBDB, PML, AML, RKF and BG. All authors contributed to the final version of the manuscript.

Funding

This study was funded by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)—Grant Numbers: 476024/2013-7 and 476333/2013-0; Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Newton Fund RCUK-CONFAP Research Partnerships call, Grant Number: E-26/170.021/2015; and, Programa Institucional de Bolsas de Iniciação Científica (PIBIC/CNPq). These funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

11136_2018_2044_MOESM1_ESM.docx (27 kb)
Supplementary material 1. Online Resource 1. Definition of the independent variables. (DOCX 27 KB)
11136_2018_2044_MOESM2_ESM.docx (20 kb)
Supplementary material 2. Table with disaggregation by Gender Identity of outcomes and independent variables among 1480 PLWHA in Rio de Janeiro, Brazil. (DOCX 20 KB)

References

  1. 1.
    Serrano-Villar, S., Gutierrez, F., Miralles, C., Berenguer, J., Rivero, A., Martinez, E., & Moreno, S. (2016). Human immunodeficiency virus as a chronic disease: Evaluation and management of nonacquired immune deficiency syndrome-defining conditions. Open Forum Infectious Diseases, 3(2), ofw097.CrossRefGoogle Scholar
  2. 2.
    Bernell, S., & Howard, S. W. (2016). Use Your Words Carefully: What Is a Chronic Disease? Front Public Health, 4, 159.CrossRefGoogle Scholar
  3. 3.
    Wada, N., Jacobson, L. P., Cohen, M., French, A., Phair, J., & Munoz, A. (2014). Cause-specific mortality among HIV-infected individuals, by CD4(+) cell count at HAART initiation, compared with HIV-uninfected individuals. Aids, 28(2), 257–265.CrossRefGoogle Scholar
  4. 4.
    Boussari, O., Subtil, F., Genolini, C., Bastard, M., Iwaz, J., Fonton, N., Etard, J. F., & Ecochard, R. (2015). Impact of variability in adherence to HIV antiretroviral therapy on the immunovirological response and mortality. BMC Medical Research Methodology, 15, 10.CrossRefGoogle Scholar
  5. 5.
    Karimi, M., & Brazier, J. (2016). Health, health-related quality of life, and quality of life: what is the difference? Pharmacoeconomics, 34(7), 645–649.CrossRefGoogle Scholar
  6. 6.
    Mitchell, M. M., Nguyen, T. Q., Isenberg, S. R., Maragh-Bass, A. C., Keruly, J., & Knowlton, A. R. (2016). Psychosocial and service use correlates of health-related quality of life among a vulnerable population living with HIV/AIDS. AIDS Behavior. 21: 1580-1587.Google Scholar
  7. 7.
    Gill, C. J., Griffith, J. L., Jacobson, D., Skinner, S., Gorbach, S. L., & Wilson, I. B. (2002). Relationship of HIV viral loads, CD4 counts, and HAART use to health-related quality of life. Journal of Acquired Immune Deficiency Syndromes, 30(5), 485–492.CrossRefGoogle Scholar
  8. 8.
    Emuren, L., Welles, S., Evans, A. A., Polansky, M., Okulicz, J. F., Macalino, G., & Agan, B. K. (2017). Health-related quality of life among military HIV patients on antiretroviral therapy. PLoS ONE, 12(6), e0178953.CrossRefGoogle Scholar
  9. 9.
    Liu, C., Ostrow, D., Detels, R., Hu, Z., Johnson, L., Kingsley, L., & Jacobson, L. P. (2006). Impacts of HIV infection and HAART use on quality of life. Quality of Life Research, 15(6), 941–949.CrossRefGoogle Scholar
  10. 10.
    Ezeamama, A. E., Woolfork, M. N., Guwatudde, D., Bagenda, D., Manabe, Y. C., Fawzi, W. W., & Smith Fawzi, M. C. (2016). Depressive and anxiety symptoms predict sustained quality of life deficits in HIV-positive Ugandan Adults despite antiretroviral therapy: a prospective cohort study. Medicine (Baltimore), 95(9), e2525.CrossRefGoogle Scholar
  11. 11.
    Venturini, A., Cenderello, G., Di Biagio, A., Giannini, B., Ameri, M., Giacomini, M., Montefiori, M., Setti, M., Mazzarello, G., Merlano, C., Orcamo, P., Viscoli, C., & Cassola, G. (2017). Quality of life in an Italian cohort of people living with HIV in the era of combined antiretroviral therapy (evidence from I.A.N.U.A. study-investigation on antiretroviral therapy). AIDS Care, 29: 1373–1377.CrossRefGoogle Scholar
  12. 12.
    Nobre, N., Pereira, M., Roine, R. P., Sintonen, H., & Sutinen, J. (2017). Factors associated with the quality of life of people living with HIV in Finland. AIDS Care, 29: 1074–1078.CrossRefGoogle Scholar
  13. 13.
    Skevington, S. M., Norweg, S., Standage, M., & Group, W. H. (2010). Predicting quality of life for people living with HIV: international evidence from seven cultures. AIDS Care, 22(5), 614–622.CrossRefGoogle Scholar
  14. 14.
    Millar, B. M., Starks, T. J., Gurung, S., & Parsons, J. T. (2017). The impact of comorbidities, depression, and substance use problems on quality of life among older adults living with HIV. AIDS Behavior, 21(6), 1684–1690.CrossRefGoogle Scholar
  15. 15.
    Bekele, T., Rueda, S., Gardner, S., Raboud, J., Smieja, M., Kennedy, R., Fletcher, D., Burchell, A. N., Bacon, J., & Rourke, S. B. (2017). Trends and correlates of cigarette smoking and its impacts on health-related quality of life among people living with hiv: findings from the ontario hiv treatment network cohort study, 2008–2014. AIDS Patient Care STDS, 31(2), 49–59.CrossRefGoogle Scholar
  16. 16.
    Majeed, Z., van Wijngaarden, E., Dolan, J. G., & Shah, K. N. (2017). Depression partially mediated the relationship between basic psychological needs and quality of life among people living with HIV. AIDS Care, 29: 1399–1403.CrossRefGoogle Scholar
  17. 17.
    Zimpel, R. R., & Fleck, M. P. (2014). Depression as a major impact on the quality of life of HIV-positive Brazilians. Psychology Health Medicine, 19(1), 47–58.CrossRefGoogle Scholar
  18. 18.
    Pokhrel, K. N., Sharma, V. D., Shibanuma, A., Pokhrel, K. G., Mlunde, L. B., & Jimba, M. (2017). Predicting health-related quality of life in people living with HIV in Nepal: mental health disorders and substance use determinants. AIDS Care, 29(9), 1137–1143.CrossRefGoogle Scholar
  19. 19.
    EuroQol. (1990). EuroQol—a new facility for the measurement of health-related quality of life. Health Policy, 16(3), 199–208.CrossRefGoogle Scholar
  20. 20.
    O’Connell, K. A., & Skevington, S. M. (2012). An international quality of life instrument to assess wellbeing in adults who are HIV-positive: a short form of the WHOQOL-HIV (31 items). AIDS Behavior, 16(2), 452–460.CrossRefGoogle Scholar
  21. 21.
    Santos, M., Cintra, M. A., Monteiro, A. L., Santos, B., Gusmao-Filho, F., Andrade, M. V., Noronha, K., Cruz, L. N., Camey, S., Tura, B., & Kind, P. (2016). Brazilian valuation of EQ-5D-3L Health States: Results from a saturation study. Medicine Decision Making, 36(2), 253–263.CrossRefGoogle Scholar
  22. 22.
    Sullivan, K. M., Dean, A., & Soe, M. M. (2009). OpenEpi: A web-based epidemiologic and statistical calculator for public health. Public Health Reports, 124(3), 471–474.CrossRefGoogle Scholar
  23. 23.
    Machado, I. K., Luz, P. M., Lake, J. E., Castro, R., Velasque, L., Clark, J. L., Veloso, V. G., Grinsztejn, B., & De Boni, R. B. (2017). Self-rated health and substance use among individuals in HIV care in Rio de Janeiro, Brazil: a cross-sectional study. International Journal of STD & AIDS, 28: 1175–1783.CrossRefGoogle Scholar
  24. 24.
    Menezes Rde, M., Andrade, M. V., Noronha, K. V., & Kind, P. (2015). EQ-5D-3L as a health measure of Brazilian adult population. Quality of life Research, 24(11), 2761–2776.CrossRefGoogle Scholar
  25. 25.
    Grinsztejn, B., Veloso, V. G., Friedman, R. K., Moreira, R. I., Luz, P. M., Campos, D. P., Pilotto, J. H., Cardoso, S. W., Keruly, J. C., & Moore, R. D. (2009). Early mortality and cause of deaths in patients using HAART in Brazil and the United States. Aids, 23(16), 2107–2114.CrossRefGoogle Scholar
  26. 26.
    Kalichman, S. C., & Rompa, D. (2001). The Sexual Compulsivity Scale: further development and use with HIV-positive persons. Journal of personality assessment, 76(3), 379–395.CrossRefGoogle Scholar
  27. 27.
    Kroenke, K., Spitzer, R. L., & Williams, J. B. (2003). The Patient Health Questionnaire-2: Validity of a two-item depression screener. Medicine Care, 41(11), 1284–1292.CrossRefGoogle Scholar
  28. 28.
    ASSIST. (2002). The alcohol, smoking and substance involvement screening test (ASSIST): Development, reliability and feasibility. Addiction, 97(9), 1183–1194.CrossRefGoogle Scholar
  29. 29.
    de Lima Osorio, F., Vilela Mendes, A., Crippa, J. A., & Loureiro, S. R. (2009). Study of the discriminative validity of the PHQ-9 and PHQ-2 in a sample of Brazilian women in the context of primary health care. Perspectives in Psychiatric Care, 45(3), 216–227.CrossRefGoogle Scholar
  30. 30.
    Henrique, I. F., De Micheli, D., Lacerda, R. B., Lacerda, L. A., & Formigoni, M. L. (2004). Validation of the Brazilian version of alcohol, smoking and substance involvement screening test (ASSIST). Revista da Associação Médica Brasileira, 50(2), 199–206.CrossRefGoogle Scholar
  31. 31.
    Scanavino Mde, T., Ventuneac, A., Rendina, H. J., Abdo, C. H., Tavares, H., Amaral, M. L., Messina, B., Reis, S. C., Martins, J. P., Gordon, M. C., Vieira, J. C., & Parsons, J. T. (2016). Sexual compulsivity scale, compulsive sexual behavior inventory, and hypersexual disorder screening inventory: Translation, adaptation, and validation for use in Brazil. Archives of Sexual Behavior, 45(1), 207–217.CrossRefGoogle Scholar
  32. 32.
    Ramos-Goñi, J. M., & Rivero-Arias, O. (2011). Eq. 5d: A command to calculate index values for the EQ-5D quality-of-life instrument. Stata Journal, 11(1), 120–125.Google Scholar
  33. 33.
    StataCorp. (2017). Stata Statistical Software: Release 15. College Station. TX: StataCorp LLC.Google Scholar
  34. 34.
    Silva, M. T., Roa, C., M., & Galvao, T. F. (2017). Health-related quality of life in the Brazilian Amazon: A population-based cross-sectional study. Health and Quality of Life Outcomes, 15(1), 159.CrossRefGoogle Scholar
  35. 35.
    Miners, A., Phillips, A., Kreif, N., Rodger, A., Speakman, A., Fisher, M., Anderson, J., Collins, S., Hart, G., Sherr, L., & Lampe, F. C. (2014). Health-related quality-of-life of people with HIV in the era of combination antiretroviral treatment: a cross-sectional comparison with the general population. The Lancet HIV, 1(1), e32–e40.CrossRefGoogle Scholar
  36. 36.
    Zimpel, R. R., & Fleck, M. P. (2007). Quality of life in HIV-positive Brazilians: Application and validation of the WHOQOL-HIV, Brazilian version. AIDS Care, 19(7), 923–930.CrossRefGoogle Scholar
  37. 37.
    Rzeszutek, M., Gruszczynska, E., & Firlag-Burkacka, E. (2017). Coping profiles and subjective well-being among people living with HIV: less intensive coping corresponds with better well-being. Quality of Life Research. 26: 2805–2814CrossRefGoogle Scholar
  38. 38.
    Medeiros, R., Medeiros, J. A., Silva, T., Andrade, R. D., Medeiros, D. C., Araujo, J. S., Oliveira, A. M. G., Costa, M. A. A., & Dantas, P. M. S. (2017). Quality of life, socioeconomic and clinical factors, and physical exercise in persons living with HIV/AIDS. Revista de saude publica, 51, 66.CrossRefGoogle Scholar
  39. 39.
    Fleming, C. A., Christiansen, D., Nunes, D., Heeren, T., Thornton, D., Horsburgh, C. R. Jr., Koziel, M. J., Graham, C., & Craven, D. E. (2004). Health-related quality of life of patients with HIV disease: Impact of hepatitis C coinfection. Clinical Infectious Disease, 38(4), 572–578.CrossRefGoogle Scholar
  40. 40.
    Preau, M., Marcellin, F., Carrieri, M. P., Lert, F., Obadia, Y., & Spire, B. (2007). Health-related quality of life in French people living with HIV in 2003: Results from the national ANRS-EN12-VESPA Study. Aids, 21(Suppl 1), S19–S27.CrossRefGoogle Scholar
  41. 41.
    Catalan, J., Tuffrey, V., Ridge, D., & Rosenfeld, D. (2017). What influences quality of life in older people living with HIV? AIDS Research and Therapy, 14, 22.CrossRefGoogle Scholar
  42. 42.
    Yeoh, H. L., Cheng, A., Palmer, C., Crowe, S. M., & Hoy, J. F. (2017). Frailty in men living with HIV: a cross-sectional comparison of three frailty instruments. Antiviral Therapy. 23:117–127CrossRefGoogle Scholar
  43. 43.
    Tran, B. X., Ohinmaa, A., & Nguyen, L. T. (2012). Quality of life profile and psychometric properties of the EQ-5D-5L in HIV/AIDS patients. Health and Quality of Life Outcomes, 10, 132.CrossRefGoogle Scholar
  44. 44.
    Mafirakureva, N., Dzingirai, B., Postma, M. J., van Hulst, M., & Khoza, S. (2016). Health-related quality of life in HIV/AIDS patients on antiretroviral therapy at a tertiary care facility in Zimbabwe. AIDS Care, 28(7), 904–912.CrossRefGoogle Scholar
  45. 45.
    Delany-Moretlwe, S., Cowan, F. M., Busza, J., Bolton-Moore, C., Kelley, K., & Fairlie, L. (2015). Providing comprehensive health services for young key populations: needs, barriers and gaps. Journal of the International AIDS Society, 18(2 Suppl 1), 19833.PubMedPubMedCentralGoogle Scholar
  46. 46.
    Risher, K., Adams, D., Sithole, B., Ketende, S., Kennedy, C., Mnisi, Z., Mabusa, X., & Baral, S. D. (2013). Sexual stigma and discrimination as barriers to seeking appropriate healthcare among men who have sex with men in Swaziland. Journal of the International AIDS Society, 16(3 Suppl 2), 18715.CrossRefGoogle Scholar
  47. 47.
    De Boni, R. B., Machado, I. K., De Vasconcellos, M. T. L., Hoagland, B., Kallas, E. G., Madruga, J. V., Fernandes, N. M., Cerqueira, N. B., Moreira, R. I., Goulart, S. P., Veloso, V. G., Grinsztejn, B., & Luz, P. M. (2018). Syndemics among individuals enrolled in the PrEP Brasil Study. Drug and Alcohol Dependence, 185, 168–172.CrossRefGoogle Scholar
  48. 48.
    Siemieniuk, R. A., Krentz, H. B., Miller, P., Woodman, K., Ko, K., & Gill, M. J. (2013). The clinical implications of high rates of intimate partner violence against HIV-positive women. JAIDS Journal of Acquired Immune Deficiency Syndromes, 64(1), 32–38.CrossRefGoogle Scholar
  49. 49.
    Miller, P., Siemieniuk, R. A. C., Woodman, K., Krentz, H. B., & Gill, M. J. (2015). Interpersonal violence and its impact on persons living with HIV: A social work response. Journal of HIV/AIDS & Social Services, 14(3), 308–318.CrossRefGoogle Scholar
  50. 50.
    Bernier, A., Lefevre, M., Henry, E., Verdes, L., Acosta, M. E., Benmoussa, A., Mukumbi, H., Cisse, M., Otis, J., & Preau, M. (2016). HIV seropositivity and sexuality: cessation of sexual relations among men and women living with HIV in five countries. AIDS Care, 28(Suppl 1), 26–31.CrossRefGoogle Scholar
  51. 51.
    Wagner, G. J., Ghosh-Dastidar, B., Holloway, I. W., Kityo, C., & Mugyenyi, P. (2012). Depression in the pathway of HIV antiretroviral effects on sexual risk behavior among patients in Uganda. AIDS Behavior, 16(7), 1862–1869.CrossRefGoogle Scholar
  52. 52.
    Xiao, Z., Li, X., Qiao, S., Zhou, Y., & Shen, Z. (2017). Social support, depression, and quality of life among people living with HIV in Guangxi, China. AIDS Care, 29(3), 319–325.CrossRefGoogle Scholar
  53. 53.
    Alsayed, N. S., Sereika, S. M., Albrecht, S. A., Terry, M. A., & Erlen, J. A. (2017). Testing a model of health-related quality of life in women living with HIV infection. Quality of Life Research, 26(3), 655–663.CrossRefGoogle Scholar
  54. 54.
    Prasithsirikul, W., Chongthawonsatid, S., Ohata, P. J., Keadpudsa, S., Klinbuayaem, V., Rerksirikul, P., Kerr, S. J., Ruxrungtham, K., Ananworanich, J., & Avihingsanon, A. (2017). Depression and anxiety were low amongst virally suppressed, long-term treated HIV-infected individuals enrolled in a public sector antiretroviral program in Thailand. AIDS Care, 29(3), 299–305.CrossRefGoogle Scholar
  55. 55.
    WHO. (2008). mhGAP: Mental Health Gap Action Programme: scaling up care for mental, neurological and substance use disorders. Geneva: WHO.Google Scholar
  56. 56.
    Quatremere, G., Guiguet, M., Girardi, P., Liaud, M. N., Mey, C., Benkhoucha, C., Barbier, F., Cattaneo, G., Simon, A., & Castro, R., D. (2017). How are women living with HIV in France coping with their perceived side effects of antiretroviral therapy? Results from the EVE study. PLoS ONE, 12(3), e0173338.CrossRefGoogle Scholar
  57. 57.
    Degroote, S., Vogelaers, D., & Vandijck, D. M. (2014). What determines health-related quality of life among people living with HIV: An updated review of the literature. Archives of Public Health, 72(1), 40.CrossRefGoogle Scholar
  58. 58.
    Bhatta, D. N., & Liabsuetrakul, T. (2017). Efficacy of a social self-value empowerment intervention to improve quality of life of HIV infected people receiving antiretroviral treatment in Nepal: A randomized controlled trial. AIDS Behavior, 21(6), 1620–1631.CrossRefGoogle Scholar
  59. 59.
    Dickerson, J. F., Feeny, D. H., Clarke, G. N., MacMillan, A. L., & Lynch, F. L. (2017). Evidence on the longitudinal construct validity of major generic and utility measures of health-related quality of life in teens with depression. Quality of Life Research. 27:447–454CrossRefGoogle Scholar
  60. 60.
    Jia, Y. X., Cui, F. Q., Li, L., Zhang, D. L., Zhang, G. M., Wang, F. Z., Gong, X. H., Zheng, H., Wu, Z. H., Miao, N., Sun, X. J., Zhang, L., Lv, J. J., & Yang, F. (2014). Comparison between the EQ-5D-5L and the EQ-5D-3L in patients with hepatitis B. Quality of Life Research, 23(8), 2355–2363.CrossRefGoogle Scholar
  61. 61.
    Rodger, A. J., Cambiano, V., Bruun, T., et al. (2016). Sexual activity without condoms and risk of HIV transmission in serodifferent couples when the HIV-positive partner is using suppressive antiretroviral therapy. JAMA, 316(2), 171–181.CrossRefGoogle Scholar
  62. 62.
    The Lancet, H. I. V. (2017). U = U taking off in 2017. The Lancet HIV, 4(11), e475.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Rodolfo Castro
    • 1
    • 2
  • Raquel B. De Boni
    • 1
  • Paula M. Luz
    • 1
  • Luciane Velasque
    • 3
  • Livia V. Lopes
    • 1
  • Antonieta Medina-Lara
    • 4
  • Sandra W. Cardoso
    • 1
  • Marilia S. De Oliveira
    • 1
  • Ruth K. Friedman
    • 1
  • Beatriz Grinsztejn
    • 1
  • Valdiléa G. Veloso
    • 1
  1. 1.Instituto Nacional de Infectologia Evandro ChagasFundação Oswaldo CruzRio de JaneiroBrazil
  2. 2.Instituto de Saúde ColetivaUniversidade Federal do Estado do Rio de JaneiroRio de JaneiroBrazil
  3. 3.Universidade Federal do Estado do Rio de Janeiro, Departamento de Matemática e EstatísticaRio de JaneiroBrazil
  4. 4.University of Exeter, Health Economics Group, South CloistersExeterUK

Personalised recommendations