Pharmacotherapeutic profile, polypharmacy and its associated factors in a cohort of people living with HIV in Brazil.

BACKGROUND: The increased survival provided by the access, development, and evolution of antiretroviral drugs (ARV) greatly increased the life expectancy of people living with HIV (PWH). This has also led to an increased occurrence of diseases or morbidities related to aging. In individuals with multiple comorbidities, the simultaneous use of multiple medications, also known as polypharmacy, is common, and rational use of medications is essential. This study aims to describe the pharmacotherapeutic profile, estimate the prevalence of polypharmacy and identify factors associated with polypharmacy in a cohort of adult PWH from a referral unit in Rio de Janeiro, Brazil. METHODS: Cross-sectional study including PWH on ARV who received at least one medical prescription (outpatient/hospitalized) in 2019. We described the proportion of prescribed medications according to ARV and Anatomical Therapeutic Chemical (ATC) classes stratified by age (< 50 vs. ≥50 years). Polypharmacy was defined as ≥ 5 medications prescribed beyond ARV. Logistic regression models assessed demographic and clinical factors associated with polypharmacy. RESULTS: A total of 143,306 prescriptions of 4547 PWH were analyzed. Median age was 44.4 years (IQR:35.4-54.1) and 1615 (35.6%) were ≥ 50 years. A total of 2958 (65.1%) participants self-identified as cisgender man, 1365 (30.0%) as cisgender woman, and 224 (4.9%) as transgender women. Most self-declared Black/Pardo (2582; 65.1%) and 1984 (44.0%) completed elementary education or less. Median time since HIV diagnosis was 10.9 years (IQR:6.2-17.7). Most frequently prescribed concomitant medications were nervous system (64.8%), antiinfectives for systemic use (60.0%), alimentary tract and metabolism (45.9%), cardiovascular system (40.0%) and respiratory system (37.1%). Prevalence of polypharmacy was 50.6% (95%CI: 49.2-52.1). Model results indicated that being older, self-identify as cisgender woman, having less education and longer time since HIV diagnosis increased the odds of polypharmacy. CONCLUSIONS: We found high rates of polypharmacy and concomitant medication use in a cohort of PWH in Brazil. Targeted interventions should be prioritized to prevent interactions and improve treatment, especially among individuals using central nervous system and cardiovascular medications, as well as certain groups such as cisgender women, older individuals and those with lower education. Standardized protocols for continuous review of patients' therapeutic regimens should be implemented.

Clinical effects of durability of immunosuppression in virologically suppressed ART-initiating persons with HIV in Latin America. A retrospective cohort study.

Background: Clinical outcomes are rarely studied in virologically suppressed people living with HIV (PWH) and incomplete CD4 recovery. To explore whether time living with severe immunosuppression predict clinical outcomes better than baseline or time updated CD4, we estimated the association between cumulative percentage of time with CD4 <200 cells/µL during viral suppression (VS) (%tCD4<200), and mortality and comorbidities during 2000-2019. Methods: In a retrospective cohort analysis, we followed PWH initiating ART in Latin America from first VS (HIV-RNA<200 copies/µL) to death, virological failure or loss to follow-up. We fit Cox models to estimate risk of death and/or AIDS-defining and serious non-AIDS-defining events (ADE and SNADE -cancer, cardiovascular, liver, and renal diseases) by %tCD4<200 (continuous variable). We predicted survival probabilities for each event and calculated risks of hypothetical cases of different %tCD4<200. Findings: In 8,369 patients with 34·9 months of follow-up (median, IQR: 16·7, 69·1), 4,274 (51%) started ART with CD4<200 cells/µL. Median %tCD4<200 was 0% (IQR: 0, 15%). We identified 195 (2·3%) deaths and 584 (7·2%) patients with ADE/SNADE. For an increased %tCD4<200 of 15% (e.g., 15% vs. 0%), the adjusted relative hazard (aHR) of death was 1·27 (95% confidence interval [CI]: 1·19 - 1·35), of ADE/SNADE was 1·13 (95%CI: 1·09 - 1·17), of SNADE was 0·96 (95%CI: 0·89 - 1·02) and of death/ADE/SNADE was 1·11 (95%CI: 1·07 - 1·14). Estimates were similar after adjusting for time updated CD4 count. Interpretation: In virologically suppressed PWH, increased time living with severe immunosuppression had an increased risk of death and ADE/SNADE in this Latin American cohort, independently of time updated CD4 count. Funding: This work was supported by the NIH-funded Caribbean, Central and South America network for HIV epidemiology (CCASAnet, U01AI069923), a member cohort of the International Epidemiologic Databases to Evaluate AIDS (leDEA). This award is funded by the following institutes: Eunice Kennedy Shriver National Institute Of Child Health & Human Development (NICHD), National Cancer Institute (NCI), National Institute Of Allergy And Infectious Diseases (NIAID), National Institute Of Mental Health (NIMH), the National Heart, Lung, and Blood Institute (NHLBI), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and the Fogarty International Center (FIC). Specific funding was provided from the Fogarty International Center (FIC) for lead author, Yanink Caro-Vega, for the Fogarty-IeDEA Mentorship Program (FIMP).

BestFLR Trial: Liver Regeneration at CT before Major Hepatectomies for Liver Cancer-A Randomized Controlled Trial Comparing Portal Vein Embolization with N-Butyl-Cyanoacrylate Plus Iodized Oil versus Polyvinyl Alcohol Particles Plus Coils.

Background In patients with liver cancer, portal vein embolization (PVE) is recommended to promote liver growth before major hepatectomies. However, the optimal embolization strategy has not been established. Purpose To compare liver regeneration as seen at CT in participants with liver cancer, before major hepatectomies, with N-butyl-cyanoacrylate (NBCA) plus iodized oil versus standard polyvinyl alcohol (PVA) particles plus coils, for PVE. Materials and Methods In this single-center, prospective, randomized controlled trial (Best Future Liver Remnant, or BestFLR, trial; International Standard Randomized Controlled Trial Number 16062796), PVE with NBCA plus iodized oil was compared with standard PVE with PVA particles plus coils in participants with liver cancer. Participant recruitment started in November 2017 and ended in March 2020. Participants were randomly assigned to undergo PVE with PVA particles plus coils or PVE with NBCA plus iodized oil. The primary end point was liver growth assessed with CT 14 days and 28 days after PVE. Secondary outcomes included posthepatectomy liver failure, surgical complications, and length of intensive care treatment and hospital stay. The Mann-Whitney U test was used to compare continuous outcomes according to PVE material, whereas the Χ2 test or Fisher exact test was used for categoric variables. Results Sixty participants (mean age, 61 years ± 11 [standard deviation]; 32 men) were assigned to the PVA particles plus coils group (n = 30) or to the NBCA plus iodized oil group (n = 30). Interim analysis revealed faster and superior liver hypertrophy for the NBCA plus iodized oil group versus the PVA particles plus coils group 14 days and 28 days after PVE (absolute hypertrophy of 46% vs 30% [P < .001] and 57% vs 37% [P < .001], respectively). Liver growth for the proposed hepatectomy was achieved in 87% of participants (26 of 30) in the NBCA plus iodized oil group versus 53% of participants (16 of 30) in the PVA particles plus coils group (P = .008) 14 days after PVE. Liver failure occurred in 13% of participants (three of 24) in the NBCA plus iodized oil group and in 27% of participants (six of 22) in the PVA particles plus coils group (P = .27). Conclusion Portal vein embolization with N-butyl-cyanoacrylate plus iodized oil produced greater and faster liver growth as seen at CT in participants with liver cancer, compared with portal vein embolization with polyvinyl alcohol particles plus coils, allowing for earlier surgical intervention. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Arellano in this issue.

Cobertura da vacina papilomavírus humano (HPV) no Brasil: heterogeneidade espacial e entre coortes etárias / Human papillomavirus (HPV) vaccination coverage in Brazil: spatial and age cohort heterogeneity

RESUMO: Objetivo: Estimar a cobertura da primeira e da segunda dose da vacina papilomavírus humano (HPV) no Brasil, conforme a microrregião, comparando-se as coortes de meninas com 14, 15 e 16 anos em 2017, e investigar a associação da heterogeneidade espacial na cobertura vacinal com variáveis sociodemográficas. Métodos: A informação sobre doses aplicadas nos anos de 2013 a 2017 por idade foi obtida do Programa Nacional de Imunizações. O número de meninas residentes com sete, oito e nove anos em 2010, em cada microrregião, é oriundo do censo brasileiro de 2010. Para a análise, a cobertura vacinal acumulada por microrregião (n = 558) foi categorizada em baixa (< 80%) e adequada (≥ 80%), e um modelo logístico com intercepto aleatório foi ajustado, tendo cobertura vacinal adequada como desfecho. O efeito aleatório (unidade da federação) foi incluído para captar a correlação entre microrregiões que pertencem ao mesmo estado. Resultados: O percentual de microrregiões que alcançou a cobertura vacinal adequada foi significativamente maior para a primeira dose (entre 91,8 e 159,2%), independentemente da coorte. Observou-se menor cobertura da segunda dose (entre 7 e 79,9%), com heterogeneidade associada ao grau de urbanização e à presença de domicílios com banheiro de uso próprio no município. O efeito aleatório mostrou forte poder explicativo, sugerindo importantes diferenças entre os estados brasileiros no alcance da cobertura vacinal. Conclusão: Apesar de a vacina HPV estar disponível no Programa de Imunização, os achados do presente estudo apontam para uma dificuldade do alcance da cobertura vacinal adequada.

ABSTRACT: Objective: To estimate the coverage of the first and second dose of the human papillomavirus (HPV) vaccine in Brazil according to microregion, comparing cohorts of girls aged 14, 15, and 16 years in 2017, and investigate the association between spatial heterogeneity in vaccination coverage and sociodemographic variables. Methods: Information about the doses administered from 2013 to 2017 by age was gathered from the National Immunization Program. The number of girls aged seven, eight, and nine years living in each microregion in 2010 was obtained from the 2010 Brazilian Census. For the analysis, the cumulated vaccination coverage per microregion (n = 558) was categorized as low (< 80%) and adequate (≥ 80%), and a random intercept logistic model was adjusted, with adequate vaccination coverage as the outcome. The random effect (federative unit) was included to identify the correlation between microregions that belong to the same state. Results: The percentage of microregions with adequate vaccination coverage was significantly higher in the first dose (between 91.8 and 159.2%), regardless of the cohort. The coverage of the second dose was lower (between 7 and 79.9%), with heterogeneity associated with the degree of urbanization and households with private bathrooms in the municipality. The random effect showed a strong explanatory power, suggesting important differences among Brazilian states as to the outreach of vaccination coverage. Conclusion: Although the HPV vaccine is available through the Immunization Program, the findings of the present study point to a difficulty in achieving adequate vaccination coverage.

Human papillomavirus (HPV) vaccination coverage in Brazil: spatial and age cohort heterogeneity. / Cobertura da vacina papilomavírus humano (HPV) no Brasil: heterogeneidade espacial e entre coortes etárias.

OBJECTIVE: To estimate the coverage of the first and second dose of the human papillomavirus (HPV) vaccine in Brazil according to microregion, comparing cohorts of girls aged 14, 15, and 16 years in 2017, and investigate the association between spatial heterogeneity in vaccination coverage and sociodemographic variables. METHODS: Information about the doses administered from 2013 to 2017 by age was gathered from the National Immunization Program. The number of girls aged seven, eight, and nine years living in each microregion in 2010 was obtained from the 2010 Brazilian Census. For the analysis, the cumulated vaccination coverage per microregion (n = 558) was categorized as low (< 80%) and adequate (≥ 80%), and a random intercept logistic model was adjusted, with adequate vaccination coverage as the outcome. The random effect (federative unit) was included to identify the correlation between microregions that belong to the same state. RESULTS: The percentage of microregions with adequate vaccination coverage was significantly higher in the first dose (between 91.8 and 159.2%), regardless of the cohort. The coverage of the second dose was lower (between 7 and 79.9%), with heterogeneity associated with the degree of urbanization and households with private bathrooms in the municipality. The random effect showed a strong explanatory power, suggesting important differences among Brazilian states as to the outreach of vaccination coverage. CONCLUSION: Although the HPV vaccine is available through the Immunization Program, the findings of the present study point to a difficulty in achieving adequate vaccination coverage.

OBJETIVO: Estimar a cobertura da primeira e da segunda dose da vacina papilomavírus humano (HPV) no Brasil, conforme a microrregião, comparando-se as coortes de meninas com 14, 15 e 16 anos em 2017, e investigar a associação da heterogeneidade espacial na cobertura vacinal com variáveis sociodemográficas. MÉTODOS: A informação sobre doses aplicadas nos anos de 2013 a 2017 por idade foi obtida do Programa Nacional de Imunizações. O número de meninas residentes com sete, oito e nove anos em 2010, em cada microrregião, é oriundo do censo brasileiro de 2010. Para a análise, a cobertura vacinal acumulada por microrregião (n = 558) foi categorizada em baixa (< 80%) e adequada (≥ 80%), e um modelo logístico com intercepto aleatório foi ajustado, tendo cobertura vacinal adequada como desfecho. O efeito aleatório (unidade da federação) foi incluído para captar a correlação entre microrregiões que pertencem ao mesmo estado. RESULTADOS: O percentual de microrregiões que alcançou a cobertura vacinal adequada foi significativamente maior para a primeira dose (entre 91,8 e 159,2%), independentemente da coorte. Observou-se menor cobertura da segunda dose (entre 7 e 79,9%), com heterogeneidade associada ao grau de urbanização e à presença de domicílios com banheiro de uso próprio no município. O efeito aleatório mostrou forte poder explicativo, sugerindo importantes diferenças entre os estados brasileiros no alcance da cobertura vacinal. CONCLUSÃO: Apesar de a vacina HPV estar disponível no Programa de Imunização, os achados do presente estudo apontam para uma dificuldade do alcance da cobertura vacinal adequada.

How heuristics and cognitive biases affect vaccination decisions / Cómo los sesgos heurísticos y cognitivos afectan a las decisiones de vacunación / Como as heurísticas e os vieses cognitivos afetam as decisões sobre vacinação

Abstract: Immunization, the most successful public health intervention to date, can only be effective if eligible individuals or their legal representatives have access to vaccines and subsequently comply with their use. Under-vaccination stems from multiple causes: access, affordability, awareness, acceptance and activation. In this paper, we focus on acceptance and, specifically, on factors pertaining to individual or parental compliance, specifically the psychology of judgment and decision making. We describe how heuristics and cognitive biases - a facet of thoughts and feelings - affect vaccination decision making. Additionally, we address when and how social processes play a role and how attitudes towards vaccines might reflect a more general underlying attitude or ideology. The understanding of how decision making, with regards to vaccines occurs, and the role played by heuristics and cognitive biases can help inform more appropriate public health interventions.

Resumen: La inmunización es la intervención en salud pública más exitosa hasta la fecha. No obstante, sólo puede ser efectiva si las personas elegibles, o sus representantes legales, tienen acceso a las vacunas y, consecuentemente, cumplen con su uso. Existen múltiples causas de infravacunación: acceso, asequibilidad, concienciación, aceptación y activación. En este trabajo, nos enfocamos en la aceptación y esceficamente, centrándonos en factores respecto a la conformidad individual o parental, específicamente en cuanto a la psicología de juicio y toma de decisiones. Describimos como sesgos heurísticos y cognitivos -una faceta de pensamientos y sentimientos- que afectan a la toma de decisiones sobre la vacunación. Asimismo, nos centramos en cuándo y cómo los procesos sociales desempeñan un papel y cómo las actitudes hacia las vacunas quizás reflejen una actitud subyacente más general o ideológica. La compresión sobre cómo se toman las decisiones, en relación a cuándo se tienen que tomar las vacunas y el papel desempeñado por sesgos heurísticos y cognitivos puede informarnos más apropiadamente sobre las intervenciones en salud pública.

Resumo: A imunização, a intervenção da saúde pública mais bem sucedida até hoje, só pode ser eficaz se as pessoas elegíveis ou seus representantes legais tiverem acesso às vacinas e aderirem ao seu uso. A subvacinação pode resultar de várias causas: acesso, viabilidade, conscientização, aceitação e ativação. Neste trabalho, focamos na aceitação e, especificamente, nos concentramos nos fatores relativos à cooperação do indivíduo ou de seus pais, especificamente a psicologia do julgamento e da tomada de decisões. Descrevemos como as heurísticas e os vieses cognitivos - um aspecto dos pensamentos e sentimentos - afetam a tomada de decisão quanto à vacinação. Além disso, abordamos quando e como os processos sociais desempenham um papel e como as atitudes em relação às vacinas podem refletir uma atitude ou ideologia subjacente mais geral. A compreensão de como a tomada de decisões em relação às vacinas ocorre e o papel desempenhado pelas heurísticas e pelos vieses cognitivos pode ajudar a informar as intervenções de saúde pública de forma mais adequada.

Preditores de aceitação da vacina contra influenza: tradução para o português e validação de um questionário / Predictores de la aceptación de la vacuna contra la gripe: traducción para el portugués y validación de un cuestionario / Predictors of influenza vaccine uptake: translation into Portuguese and validation of a questionnaire

Resumo: A dificuldade de alcançar coberturas ideais para a vacina contra influenza no Brasil e a crescente onda do movimento antivacina no mundo apontam a necessidade de aprofundar a compreensão dos determinantes individuais de adesão a essa vacina. O Modelo de Crenças em Saúde, um modelo teórico que objetiva explicar e predizer o comportamento em relação à saúde, sugere que crenças individuais influenciam a adoção de comportamentos relacionados a essa área. Este trabalho teve como objetivo a adaptação transcultural de um instrumento para avaliar os preditores de aceitação da vacina da influenza em adultos no Brasil. Realizaram-se a tradução, a retrotradução, a validade de face e um inquérito para validade de construto. Também foram analisados os fatores associados à adesão à vacina da influenza em 2017. Um instrumento, originalmente com sete domínios, foi identificado e selecionado. Na análise fatorial, quatro dos sete construtos do modelo teórico foram validados: Suscetibilidade, Barreiras, Estímulos para a ação e Motivação para a saúde. No inquérito das 396 pessoas, 59,3% relataram vacinação contra influenza na última campanha de 2017. Sexo feminino, idade > 50 anos, gestante, vacina na rede privada, vacinação contra a hepatite B e influenza antes de 2017 mostraram-se como fatores associados à vacinação em 2017. No modelo logístico final, a percepção de Barreiras apresentou-se como um forte Estímulo para não vacinação, ao passo que Estímulos para a ação atuou aumentando a chance de vacinação.

Resumen: La dificultad de alcanzar coberturas ideales para la vacuna contra la gripe en Brasil y la creciente ola del movimiento antivacunas en el mundo apunta la necesidad de profundizar la comprensión de los determinantes individuales de adhesión a esa vacuna. El Modelo de Creencias en Salud, un modelo teórico que tiene como objetivo explicar y predecir el comportamiento en relación con la salud, sugiere que las creencias individuales influencian la adopción de comportamientos relacionados con esa área. El objetivo de este trabajo es la adaptación transcultural de un instrumento para evaluar los predictores de aceptación de la vacuna de la gripe en adultos en Brasil. Se realizó la traducción, retrotraducción, validez de la presentación, así como una encuesta para la validez del constructo. También se analizaron los factores asociados con la adhesión a la vacuna de la gripe en 2017. Un instrumento, originalmente con siete dominios, fue identificado y seleccionado. En el análisis factorial, cuatro de los siete constructos del modelo teórico fueron evaluados: Susceptibilidad, Barreras, Estímulos para la acción y Motivación para la salud. En el cuestionario a las 396 personas, 59,3% informaron haber sido vacunadas contra la gripe en la última campaña de 2017. Sexo femenino, edad > 50 años, embarazada, vacunada en la red privada, vacunación contra la hepatitis B y gripe antes de 2017 se mostraron como factores asociados a la vacunación en 2017. En el modelo logístico final, la percepción de Barreras se presentó como un fuerte Estímulo para la no vacunación, al paso que Estímulos para la acción actuó aumentando la oportunidad de vacunación.

Abstract: The difficulty in achieving ideal coverage rates with the influenza vaccine in Brazil and the growing wave of antivaccine movements in the world point to the need for a more in-depth understanding of the individual determinants of to this vaccine uptake. The Health Belief Model, a theoretical model that aims to explain and predict health-related behaviors, suggests that individual beliefs influence the adoption of health-related behaviors. The objective of this study was a cross-cultural adaptation of an instrument to assess predictors of influenza vaccine uptake in Brazilian adults. The authors conducted translation, back-translation, face validity, and a survey for construct validity. They also analyzed the factors associated with influenza vaccine uptake in 2017. An instrument originally with seven domains was identified and selected. In the factor analysis, four of the model's seven constructs were validated: Susceptibility, Barriers, Cues to action, and Self-efficacy. In the survey with 396 persons, 59.3% reported having received the influenza vaccine in the last campaign in 2017. Female sex, age > 50 years, pregnancy, vaccination in private healthcare services, hepatitis B vaccination, and influenza vaccination prior to 2017 were associated with vaccination in 2017. In the final logistic regression model, perceived Barriers appeared as a strong factor for non-vaccination, while Cues to action increased the odds of vaccination.

Transcendendo: A Cohort Study of HIV-Infected and Uninfected Transgender Women in Rio de Janeiro, Brazil.

Purpose: Worldwide, the burden of adverse health conditions is substantial among travestis and transgender women (trans women). Transcendendo, the first trans-specific cohort in a low- or middle-income country, is an open cohort established in August 2015 to longitudinally evaluate the health aspects of trans women aged ≥18 years in Rio de Janeiro, Brazil. Methods: Study visits occur on an annual basis. Data on sociodemographics, behavioral, gender transition, affirmation procedures, hormone use, discrimination, violence, clinical and mental health, HIV prevention, and care (for those HIV-infected) are collected. Physical examination, anthropometric measurements, and laboratory tests are performed. Results: As of July 2017, 322 trans women were enrolled in the cohort with a median age of 31.5 years (interquartile range 25.7-39.5), of whom 174 (54%) were HIV-infected. The Transcendendo baseline information reinforces the scenario of marginalization and deprivation surrounding trans women. Most participants had low income (62.0% were living with below US$ 10.00/day), showed a very high engagement in sex work (78.6%), and reported increased occurrence of sexual (46.3%) and physical (54.0%) violence. Pre-exposure peophylaxis (PReP) was used by 18.8% of the HIV-uninfected trans women, only through research participation. Positive screening for depression (57.8%) and problematic use of tobacco (56.6%), cannabis (28.9%), cocaine (23.8%), and alcohol (21.5%) were high. Almost all participants (94.8%) reported hormone use at some point, mostly without medical supervision (78.7%). Conclusion: Our results describe a context of exclusion experienced by trans women, exposing vulnerabilities of this population in a middle-income country, with poor access to trans-specific care, HIV prevention and care, and mental health care. Addressing transgender experiences and needs can help the development of strategies to diminish stigma, improve health care environment, guide future research on trans morbidities, substance use, and trans-specific interventions to support health-related recommendations. Ultimately, it contributes to close the gaps concerning transgender health and reinforces that trans care cannot be disentangled from the social environment that surrounds trans women.

Portal vein embolization with n-butyl-cyanoacrylate through an ipsilateral approach before major hepatectomy: single center analysis of 50 consecutive patients.

PURPOSE: To evaluate the efficacy of portal vein embolization (PVE) with n-Butyl-cyanoacrylate (NBCA) through an ipsilateral approach before major hepatectomy. Secondary end-points were PVE safety, liver resection and patient outcome. METHODS: Over a 5-year period 50 non-cirrhotic consecutive patients were included with primary or secondary liver cancer treatable by hepatectomy with a liver remnant (FLR) volume less than 25% or less than 40% in diseased livers. RESULTS: There were 37 men and 13 women with a mean age of 57 years. Colorectal liver metastases were the most frequent tumor and patients were previously exposed to chemotherapy. FLR increased from 422 ml to 629 ml (P < 0.001) after PVE, corresponding to anincrease of 52%. The FLR ratio increased from 29.6% to 42.3% (P < 0.001). Kinetic growth rate was 2.98%/week. A negative association was observed between increase in the FLR and FLR ratio and FLR volume before PVE (P = 0.002). In 31 patients hepatectomy was accomplished and only one patient presented with liver insufficiency within 30 days after surgery. CONCLUSIONS: PVE with NBCA through an ipsilateral puncture is effective before major hepatectomy. Meticulous attention is needed especially near the end of the embolization procedure to avoid complications. TRIAL REGISTRATION: Clinical Study ISRCTN registration number: ISRCTN39855523 . Registered March 13th 2017.

Screening for decreased glomerular filtration rate and associated risk factors in a cohort of HIV-infected patients in a middle-income country.

With the introduction of combined active antiretroviral therapy and the improved survival of HIV-infected patients, degenerative diseases and drug toxicity have emerged as long-term concerns. We studied the prevalence of decreased glomerular filtration rate (GFR) and associated risk factors in a cohort of HIV-infected patients from a middle-income country. Our cross-sectional study included all adult patients who attended an urban outpatient clinic in 2008. GFR was estimated using the CKD-EPI equation. The prevalence ratio (PR) of decreased GFR (defined as <60 mL/min/1.73 m(2)) was estimated using generalizing linear models assuming a Poisson distribution. We analyzed data from 1,970 patients, of which 82.9% had been exposed to ART. A total of 249 patients (12.6%) had a GFR between 60 and 89 mL/min/1.73 m(2), 3.1% had a GFR between 30 and 59, 0.3% had a GFR between 15 and 29, and 0.4% had a GFR <15. Decreased GFR was found in only 74 patients (3.8%). In the multivariate regression model, the factors that were independently associated with a GFR below 60 mL/min/1.73 m(2) were as follows: age ≥ 50 years (PR = 3.4; 95% CI: 1.7-6.8), diabetes (PR = 2.0; 95% CI: 1.2-3.4), hypertension (PR = 2.0; 95% CI: 1.3-3.2), current CD4+ cell count <350 cells/mm3 (PR = 2.1; 95% CI: 1.3-3.3), past exposure to tenofovir (PR = 4.7; 95% CI: 2.3-9.4) and past exposure to indinavir (PR =1.7; 95% CI: 1.0-2.8). As in high-income countries, CKD was the predominant form of kidney involvement among HIV-infected individuals in our setting. The risk factors associated with decreased glomerular filtration were broad and included virus-related factors as well as degenerative and nephrotoxic factors. Despite the potential for nephrotoxicity associated with some antiretroviral drugs, in the short-term, advanced chronic renal disease remains very rare.

Trends in overall opportunistic illnesses, Pneumocystis carinii pneumonia, cerebral toxoplasmosis andMycobacterium avium complex incidence rates over the 30 years of the HIV epidemic: a systematic review

BACKGROUND: The natural history of HIV infection has changed dramatically after the introduction of highly active antiretroviral therapy. Currently, opportunistic illnesses still represent a major cause of death and hospitalization in this population. In this study, we review the trends in opportunistic illnesses incidence rates and compare the results observed in high-income settings with that for low/middle-income settings, with special attention given to studies from Brazil. METHODS: We systematically searched Pubmed, Web of Science, Lilacs and Google scholar for publications on HIV associated opportunistic illness. Studies reporting rates based on person-time for all opportunistic illnesses and/or the three opportunistic infections of interest, namely,Pneumocystis carinii pneumonia, cerebral toxoplasmosis, and Mycobacterium avium complex were included. RESULTS: Significant reductions in the incidence rates were demonstrated for opportunistic illnesses overall and also for the specific opportunistic infections included in the present study, both in high and low/middle-income settings. Out of the 37 studies included in the present review, almost 70% were from high-income settings. All the studies conducted in low/middle-income settings were single center studies and four were from Brazil. We found no study from Brazil reporting annual incidence rates of opportunistic illnesses. CONCLUSIONS: Opportunistic illnesses remain an important public health problem. To better guide health policies in low/middle-income settings, multicenter cohort studies should be encouraged. Studies from Brazil are urgently needed to assess the current burden of opportunistic illnesses in our population and to support the planning of HIV/AIDS health care services organization. .

The epidemic wave of influenza A (H1N1) in Brazil, 2009 / A onda epidêmica de Influenza A (H1N1) no Brasil, 2009

This study describes the main features of pandemic influenza A (H1N1) in Brazil during 2009. Brazil is a large country that extends roughly from latitudes 5ºN to 34ºS. Brazil has tropical and sub-tropical climates, a heterogeneous population distribution, and intense urbanization in the southern portions of the country and along its Atlantic coast. Our analysis points to a wide variation in infection rates throughout the country, and includes both latitudinal effects and strong variations in detection rates. Two states (out of a total of 23) were responsible for 73% of all cases reported. Real time reproduction numbers demonstrate that influenza transmission was sustained in the country, beginning inMay of 2009. Finally, this study discusses the challenges in understanding the infection dynamics of influenza and the adequacy of Brazil's influenza monitoring system.

Este estudo descreve a primeira onda de influenza A (H1N1) no Brasil, um país que se estende entre as latitudes 5ºN e 34ºS, caracterizado por climas tropicais e subtropicais, com distribuição populacional heterogênea e intensa urbanização ao longo da costa e na região sul-sudeste. Nossa análise indica grande variação geográfica nas taxas de ataque no país, com efeitos longitudinais e variação na taxa de detecção. Dois estados foram responsáveis por 73% de todos os casos registrados: São Paulo e Paraná. O número reprodutivo em tempo real demonstra que a transmissibilidade se sustentou no país desde maio de 2009 até pelo menos agosto de 2009. Este trabalho por fim discute os desafios de estudar e monitorar doenças emergentes de sintomatologia inespecífica, como a influenza, e a adequação do sistema de vigilância.

Economic modelling assessment of the HPV quadrivalent vaccine in Brazil: a dynamic individual-based approach.

We examined the cost-effectiveness of the quadrivalent HPV vaccine for the pre-adolescent female population of Brazil. Using demographic, epidemiological and cancer data, we developed a dynamic individual-based model representing the natural history of HPV/cervical cancer as well as the impact of screening and vaccination programmes. Assuming the current screening strategies, we calculated the incremental cost-effectiveness ratio (ICER) for cohorts with and without vaccination taking into account different combinations of vaccination coverage (50%, 70%, 90%) and cost per vaccinated woman (US$25, US$55, US$125, US$556). The results varied from cost-saving (coverage 50% or 70% and cost per vaccinated woman US$25) to 5950 US$/QALY (coverage 90% and cost per vaccinated 556 US$). In a scenario in which a booster shot was needed after 10 years in order to secure lifelong protection, the ICER resulted in 13,576 US$/QALY. Considering the very cost-effective and cost-effective thresholds based on Brazil's GDP per capita, apart from the booster scenario which would be deemed cost-effective, all the other scenarios would be deemed very cost-effective. Both the cost per dose of vaccine and discount rate (5%) had an important impact on the results. Vaccination in addition to the current screening programme is likely to save years of life and, depending on the cost of vaccination, may even save resources. Price negotiations between governments and manufacturers will be paramount in determining that the vaccine not only represents good value for money, but is also affordable in middle-income countries like Brazil.

Análise da tendência da mortalidade por acidente vascular cerebral no Brasil no século XXI / Analysis of the mortality trend due to cerebrovascular accident in Brazil in the XXI century

FUNDAMENTO: Embora seja mundialmente a segunda principal causa de óbitos, o Acidente Vascular Cerebral (AVC) vem apresentando uma importante redução das taxas de mortalidade nas últimas décadas. OBJETIVO: Avaliar a tendência da taxa de mortalidade por acidente vascular cerebral no Brasil, em ambos os sexos, a partir dos 30 anos de idade, entre 2000 e 2009. MÉTODOS: Os dados populacionais foram obtidos no banco de dados do Instituto Brasileiro de Geografia e Estatística e os óbitos, por meio do Sistema de Informações sobre Mortalidade da Secretaria de Vigilância em Saúde do Ministério da Saúde, sendo incluídos os códigos I60 a I69 de acordo com a 10ª Classificação Internacional de Doenças. Foi calculada a incidência de óbitos/1.000 habitantes, as taxas de mortalidade bruta e padronizada/100.000 habitantes. A modelagem da tendência das taxas foi feita com modelos de regressão. RESULTADOS: Observou-se um aumento na incidência de óbitos até 2006, seguindo-se um declínio até 2009, quando ocorreu a incidência mínima. Comparando os anos 2000 e 2009, nota-se uma tendência de queda da taxa de mortalidade padronizada em ambos os sexos (masculino = -14,69%; feminino = -17%) e no total (-14,99%), com oscilações no período. Entre 30 e 49 anos em ambos os sexos, houve uma tendência de redução contínua e linear da taxa de mortalidade, enquanto os demais grupos etários apresentaram uma função curvilínea, culminando com uma efetiva diminuição dos valores. CONCLUSÃO: Houve uma tendência de queda na taxa de mortalidade em todas as faixas etárias e em ambos os sexos. A redução da taxa de mortalidade bruta foi mais acentuada no sexo masculino, enquanto a taxa de mortalidade padronizada mostrou uma maior redução no sexo feminino.

BACKGROUND: Although it is the second leading cause of deaths worldwide, the cerebrovascular accident (CVA) has shown a significant reduction in mortality rates in recent decades. OBJECTIVE: To evaluate the trend of CVA mortality rate in Brazil, in both sexes, older than 30 years old, between 2000 and 2009. METHODS: Population data were obtained from the database of the Brazilian Institute of Geography and Statistics (IBGE) and deaths through the Mortality Information System of the Health Surveillance Secretariat of the Ministry of Health, and included codes I60 to I69 according to 10th International Classification of Diseases. We calculated the incidence of deaths/1,000 inhabitants, gross and standardized mortality rates /100,000 inhabitants. The modeling of the trend of rates was performed using regression models. RESULTS: There was an increase in mortality until 2006, followed by a decline until 2009, when the incidence was the lowest. Comparing the years 2000 and 2009, there is a downward trend in standardized mortality rate in both sexes (male = -14.69% and female = -17%) and total (-14.99%), with fluctuations during the period. Between 30 and 49 years in both sexes, there was a trend of continuous and linear decrease in mortality rate, while the other age groups showed a curvilinear function, leading to an effective decrease in values. CONCLUSION: There was a downward trend in mortality in all age groups and both sexes. The reduction in gross mortality rate was more pronounced in males, while the standardized mortality rate showed a greater reduction in females.

Cervical cancer screening among HIV-infected women: an economic evaluation in a middle-income country.

Due to the recent widespread availability of highly active antiretroviral therapy (HAART) in middle-income countries, there has been an increase in life expectancy for women on HAART, but no corresponding decrease in cervical cancer incidence. This study evaluates the optimal cervical cancer screening strategy for HIV-infected women in a middle-income country. We developed a mathematical model, which simulates the natural history of the HPV infection, as well as the HIV-mediated immunosupression among women in Brazil. Our model was calibrated using data from the IPEC/FIOCRUZ Women's HIV-infected cohort. The model compares the lifetime effects, costs and cost-effectiveness of strategies combining cytology, HPV DNA test and colposcopy at different screening intervals for different CD4 count strata (27 strategies in total). We found that the strategy with the best cost-effectiveness profile (cost-effectiveness ratio-U$4,911/year of life saved [YLS] and probability of being cost-effective-86%) was HPV testing followed by cytology triage every year for all HIV infected women, considering a very cost-effective threshold given by Brazil's GDP per capita (US$8,625/YLS). The results were robust to changes in the input parameters as demonstrated in one-way, scenario, threshold and probabilistic sensitivity analysis. Our study indicates that annual HPV testing followed by cytology triage for all HIV-infected women is likely to be very cost-effective in a middle-income country like Brazil. The results reflect the synergic effect of using a highly sensitive screening test (HPV DNA test) in sequence with a highly specific test (cytology).

Potential impact of a presumed increase in the biting activity of dengue-virus-infected Aedes aegypti (Diptera: Culicidae) females on virus transmission dynamics

Recently, we showed that infection with dengue virus increases the locomotor activity of Aedes aegypti females. We speculate that the observed increased locomotor activity could potentially increase the chances of finding a suitable host and, as a consequence, the relative biting rate of infected mosquitoes. We used a mathematical model to investigate the impact of the increased locomotor activity by assuming that this activity translated into an increased biting rate for infected mosquitoes. The results show that the increased biting rate resulted in dengue outbreaks with greater numbers of primary and secondary infections and with more severe biennial epidemics.

[Performance by cytology and hybrid capture II in screening for high-grade squamous intraepithelial lesions in women with HIV]. / Desempenho do exame citológico e da captura híbrida II no rastreamento de lesões intraepiteliais escamosas de alto grau em mulheres HIV+

HIV-infected women are at increased risk of developing high-grade squamous intraepithelial lesions (HSIL), the precursor lesions for cervical cancer. This study estimated and compared the performance of cytology and hybrid capture II in screening for precursor lesions of cervical cancer among HIV-infected women. The study population consisted of women from the open prospective cohort at the Evandro Chagas Clinical Research Institute, Oswaldo Cruz Foundation (IPEC/Fiocruz). Colposcopy and histology were considered jointly in defining the gold standard. Cytology showed 31.8% sensitivity and 95.5% specificity, while hybrid capture II showed higher sensitivity (100%) and lower specificity (52%). The positive likelihood ratio was 7.1 for cytology and 2.1 for hybrid capture II, while the negative likelihood ratio was 0.7 for cytology and 0.0 for hybrid capture II.

Breast cancer in a cohort of human immunodeficiency virus (HIV)-infected women from Rio de Janeiro, Brazil: a cases series report and an incidence rate estimate.

Highly active antiretroviral therapy (HAART) has changed the morbidity pattern affecting HIV-infected individuals to include non-AIDS-defining cancers. We describe the breast cancer cases occurring in a cohort of 860 HIV-infected women followed in Rio de Janeiro, Brazil, and estimate the incidence rate of breast cancer for this population. Nine cases were identified; median age at diagnosis was 46 years. Median survival after breast cancer diagnosis was 12 months. Breast cancer diagnosis was made within 2 to 15 years of HIV-infection diagnosis. At breast cancer diagnosis, CD4 counts ranged from 135 to 782 cells/mm3; six women were receiving HAART. Histological analysis indicated infiltrating ductal carcinoma in all cases. The incidence rate of breast cancer was 133 cases per 100,000 persons-year. Patients from our case series were late diagnosed with breast cancer and thus suffered from worse prognosis. Strategies targeting earlier diagnosis and prompt initiation of treatment are needed.

Desempenho do exame citológico e da captura híbrida II no rastreamento de lesões intraepiteliais escamosas de alto grau em mulheres HIV+ / Performance by cytology and hybrid capture II in screening for high-grade squamous intraepithelial lesions in women with HIV

As lesões intraepiteliais escamosas de alto grau (HSIL) são precursoras do câncer do colo do útero, com maior risco de ocorrência e desenvolvimento em mulheres HIV+. Neste trabalho, estimamos e comparamos o desempenho do exame citológico e da captura híbrida II no rastreamento das lesões precursoras em mulheres HIV+. A população de estudo compreendeu mulheres acompanhadas na coorte prospectiva aberta do Instituto de Pesquisa Clínica Evandro Chagas da Fundação Oswaldo Cruz (IPEC/Fiocruz). A colposcopia e histologia foram consideradas conjuntamente na definição do teste de referência. O exame citológico apresentou sensibilidade de 31,8 por cento e especificidade de 95,5 por cento, enquanto a captura híbrida II apresentou maior sensibilidade (100 por cento) e menor especificidade (52 por cento). As razões de verossimilhança para o teste positivo e negativo foram estimadas em 7,1 e 0,7 para o exame citológico e em 2,1 e 0,0 para a captura híbrida II, respectivamente.

HIV-infected women are at increased risk of developing high-grade squamous intraepithelial lesions (HSIL), the precursor lesions for cervical cancer. This study estimated and compared the performance of cytology and hybrid capture II in screening for precursor lesions of cervical cancer among HIV-infected women. The study population consisted of women from the open prospective cohort at the Evandro Chagas Clinical Research Institute, Oswaldo Cruz Foundation (IPEC/Fiocruz). Colposcopy and histology were considered jointly in defining the gold standard. Cytology showed 31.8 percent sensitivity and 95.5 percent specificity, while hybrid capture II showed higher sensitivity (100 percent) and lower specificity (52 percent). The positive likelihood ratio was 7.1 for cytology and 2.1 for hybrid capture II, while the negative likelihood ratio was 0.7 for cytology and 0.0 for hybrid capture II.