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1.
BMC Public Health ; 24(1): 749, 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38459461

RESUMO

BACKGROUND: Racial/ethnic disparities in the HIV care continuum have been well documented in the US, with especially striking inequalities in viral suppression rates between White and Black persons with HIV (PWH). The South is considered an epicenter of the HIV epidemic in the US, with the largest population of PWH living in Florida. It is unclear whether any disparities in viral suppression or immune reconstitution-a clinical outcome highly correlated with overall prognosis-have changed over time or are homogenous geographically. In this analysis, we 1) investigate longitudinal trends in viral suppression and immune reconstitution among PWH in Florida, 2) examine the impact of socio-ecological factors on the association between race/ethnicity and clinical outcomes, 3) explore spatial and temporal variations in disparities in clinical outcomes. METHODS: Data were obtained from the Florida Department of Health for 42,369 PWH enrolled in the Ryan White program during 2008-2020. We linked the data to county-level socio-ecological variables available from County Health Rankings. GEE models were fit to assess the effect of race/ethnicity on immune reconstitution and viral suppression longitudinally. Poisson Bayesian hierarchical models were fit to analyze geographic variations in racial/ethnic disparities while adjusting for socio-ecological factors. RESULTS: Proportions of PWH who experienced viral suppression and immune reconstitution rose by 60% and 45%, respectively, from 2008-2020. Odds of immune reconstitution and viral suppression were significantly higher among White [odds ratio =2.34, 95% credible interval=2.14-2.56; 1.95 (1.85-2.05)], and Hispanic [1.70 (1.54-1.87); 2.18(2.07-2.31)] PWH, compared with Black PWH. These findings remained unchanged after accounting for socio-ecological factors. Rural and urban counties in north-central Florida saw the largest racial/ethnic disparities. CONCLUSIONS: There is persistent, spatially heterogeneous, racial/ethnic disparity in HIV clinical outcomes in Florida. This disparity could not be explained by socio-ecological factors, suggesting that further research on modifiable factors that can improve HIV outcomes among Black and Hispanic PWH in Florida is needed.


Assuntos
Etnicidade , Infecções por HIV , Humanos , Teorema de Bayes , Florida/epidemiologia , Disparidades em Assistência à Saúde , Hispânico ou Latino , Infecções por HIV/epidemiologia , Brancos , Negro ou Afro-Americano
2.
Cancer Causes Control ; 34(10): 873-881, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37286847

RESUMO

PURPOSE: The gut microbiome is a potentially important contributor to endogenous estrogen levels after menopause. In healthy postmenopausal women, we examined associations of fecal microbiome composition with levels of urinary estrogens, their metabolites, and relevant metabolic pathway ratios implicated in breast cancer risk. METHODS: Eligible postmenopausal women (n = 164) had a body mass index (BMI) ≤ 35 kg/m2 and no history of hormone use (previous 6 months) or cancer/metabolic disorders. Estrogens were quantified in spot urine samples with liquid chromatography-high resolution mass spectrometry (corrected for creatinine). Bacterial DNA was isolated from fecal samples and the V1-V2 hypervariable regions of 16S rRNA were sequenced on the Illumina MiSeq platform. We examined associations of gut microbiome's indices of within-sample (alpha) diversity (i.e., Shannon, Chao1, and Inverse Simpson), phylogenetic diversity, and the ratio of the two main phyla (Firmicutes and Bacteroidetes; F/B ratio) with individual estrogens and metabolic ratios, adjusted for age and BMI. RESULTS: In this sample of 164 healthy postmenopausal women, the mean age was 62.9 years (range 47.0-86.0). We found significant inverse associations of observed species with 4-pathway:total estrogens (p = 0.04) and 4-pathway:2-pathway (p = 0.01). Shannon index was positively associated with 2-catechols: methylated 2-catechols (p = 0.04). Chao1 was inversely associated with E1:total estrogens (p = 0.04), and 4-pathway:2-pathway (p = 0.02) and positively associated with 2-pathway:parent estrogens (p = 0.01). Phylogenetic diversity was inversely associated with 4-pathway:total estrogens (p = 0.02), 4-pathway:parent estrogens (p = 0.03), 4-pathway:2-pathway (p = 0.01), and 4-pathway:16-pathway (p = 0.03) and positively associated with 2-pathway:parent estrogens (p = 0.01). F/B ratio was not associated with any of the estrogen measures. CONCLUSION: Microbial diversity was associated with several estrogen metabolism ratios implicated in breast cancer risk. Further studies are warranted to confirm these findings in a larger and more representative sample of postmenopausal women, particularly with enrichment of minority participants.


Assuntos
Neoplasias da Mama , Microbioma Gastrointestinal , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Pós-Menopausa , RNA Ribossômico 16S/genética , Filogenia , Estrogênios/metabolismo , Neoplasias da Mama/metabolismo , Catecóis
3.
Clin Infect Dis ; 75(9): 1618-1627, 2022 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-35271704

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant has caused a dramatic resurgence in infections in the United Sates, raising questions regarding potential transmissibility among vaccinated individuals. METHODS: Between October 2020 and July 2021, we sequenced 4439 SARS-CoV-2 full genomes, 23% of all known infections in Alachua County, Florida, including 109 vaccine breakthrough cases. Univariate and multivariate regression analyses were conducted to evaluate associations between viral RNA burden and patient characteristics. Contact tracing and phylogenetic analysis were used to investigate direct transmissions involving vaccinated individuals. RESULTS: The majority of breakthrough sequences with lineage assignment were classified as Delta variants (74.6%) and occurred, on average, about 3 months (104 ±â€…57.5 days) after full vaccination, at the same time (June-July 2021) of Delta variant exponential spread within the county. Six Delta variant transmission pairs between fully vaccinated individuals were identified through contact tracing, 3 of which were confirmed by phylogenetic analysis. Delta breakthroughs exhibited broad viral RNA copy number values during acute infection (interquartile range, 1.2-8.64 Log copies/mL), on average 38% lower than matched unvaccinated patients (3.29-10.81 Log copies/mL, P < .00001). Nevertheless, 49% to 50% of all breakthroughs, and 56% to 60% of Delta-infected breakthroughs exhibited viral RNA levels above the transmissibility threshold (4 Log copies/mL) irrespective of time after vaccination. CONCLUSIONS: Delta infection transmissibility and general viral RNA quantification patterns in vaccinated individuals suggest limited levels of sterilizing immunity that need to be considered by public health policies. In particular, ongoing evaluation of vaccine boosters should specifically address whether extra vaccine doses curb breakthrough contribution to epidemic spread.


Assuntos
COVID-19 , Vacinas Virais , Humanos , SARS-CoV-2/genética , RNA Viral/genética , Filogenia , Florida/epidemiologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinação
4.
Cancer Causes Control ; 33(2): 279-291, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34988766

RESUMO

PURPOSE: Circulating estrogens are an established risk factor for postmenopausal breast cancer (BCa). We describe the distribution of urinary estrogens, their metabolites, and relevant metabolic pathway ratios among healthy postmenopausal women and examine associations of several known BCa factors with these estrogen measures. METHODS: Eligible postmenopausal women (n = 167) had no history of hormone use (previous 6 months) and cancer/metabolic disorders and had a body mass index (BMI) ≤ 35 kg/m2. Estrogens were quantified in spot urine samples with liquid chromatography-high-resolution mass spectrometry and corrected for creatinine. We assessed overall distributions of estrogens and associations of age, BMI, race/ethnicity, parity/age at first birth, age at menarche, alcohol, and smoking with log-transformed estrogen measures using multivariate regression. RESULTS: BMI was positively associated with estrone (ß per unit = 0.04, 95% Confidence Interval [CI] 0.00; 0.07), combined parent estrogens (ß = 0.04, 95% CI 0.01; 0.07), and E2:total estrogens (ß = 0.04, 95% CI 0.02; 0.06), and inversely associated with 4-MeOE1 (ß = - 0.17, 95% CI - 0.33; - 0.02), E3:parent estrogens (ß = - 0.04, 95% CI - 0.07; - 0.00), and 16-pathway:parent (ß = - 0.04, 95% CI - 0.07; - 0.01). Being African American vs. white was associated with higher levels of 4-MeOE1 (ß = 3.41, 95% CI 0.74; 6.08), 17-epiE3 (ß = 1.19, 95% CI 0.07; 2.31), 2-pathway:parent (ß = 0.54, 95% CI 0.04; 1.04), and lower levels of E2:total estrogens (ß = - 0.48, 95% CI - 0.83; - 0.13). Having < 7 alcohol drinks/week vs. none was associated with higher levels of 16-ketoE2 (ß = 1.32, 95% CI 0.36; 2.27), 16-epiE3 (ß = 1.02, 95% CI 0.24; 1.79), and 17-epiE3 (ß = 0.55, 95% CI 0.02; 1.08). Smoking was positively associated with E3:parent (ß = 0.29, 95% CI 0.01; 0.57), 16-pathway:parent (ß = 0.25, 95% CI 0.01; 0.49), and inversely associated with estradiol (ß = - 0.52, 95% CI - 0.93; - 0.10). As compared to nulliparous, parous women with age at first birth ≥ 25 years had lower levels of estrone, combined parent estrogens, 2-OHE1, and 2-OHE2. CONCLUSION: Our findings suggest that BMI, race/ethnicity, and some reproductive and lifestyle factors may contribute to postmenopausal BCa through their effects on circulating estrogens.


Assuntos
Neoplasias da Mama , Estrogênios , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Estrona , Feminino , Humanos , Pós-Menopausa , Gravidez , Fatores de Risco
5.
J Med Virol ; 94(7): 3192-3202, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35307848

RESUMO

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) has raised questions regarding vaccine protection against SARS-CoV-2 infection, transmission, and ongoing virus evolution. Twenty-three mildly symptomatic "vaccination breakthrough" infections were identified as early as January 2021 in Alachua County, Florida, among individuals fully vaccinated with either the BNT162b2 (Pfizer) or the Ad26 (Janssen/J&J) vaccines. SARS-CoV-2 genomes were successfully generated for 11 of the vaccine breakthroughs, and 878 individuals in the surrounding area and were included for reference-based phylogenetic investigation. These 11 individuals were characterized by infection with VOCs, but also low-frequency variants present within the surrounding population. Low-frequency mutations were observed, which have been more recently identified as mutations of interest owing to their location within targeted immune epitopes (P812L) and association with increased replicative capacity (L18F). We present these results to posit the nature of the efficacy of vaccines in reducing symptoms as both a blessing and a curse-as vaccination becomes more widespread and self-motivated testing reduced owing to the absence of severe symptoms, we face the challenge of early recognition of novel mutations of potential concern. This case study highlights the critical need for continued testing and monitoring of infection and transmission among individuals regardless of vaccination status.


Assuntos
COVID-19 , SARS-CoV-2 , Vacina BNT162 , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , Filogenia , SARS-CoV-2/genética
6.
AIDS Behav ; 26(10): 3164-3173, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35362911

RESUMO

HIV care engagement is a dynamic process. We employed group-based trajectory modeling to examine longitudinal patterns in care engagement among people who were newly diagnosed with HIV and enrolled in the Ryan White program in Florida (n = 9,755) between 2010 and 2015. Five trajectories were identified (47.9% "in care" with 1-2 care visit(s) per 6 months, 18.0% "frequent care" with 3 or more care visits per 6 months, 11.0% "re-engage", 11.0% "gradual drop out", 12.6% "early dropout") based on the number of care attendances (including outpatient/case management visits, viral load or CD4 test) for each six-month during the first five years since diagnosis. Relative to "in care", people in the "frequent care" trajectory were more likely to be Hispanic/Latino and older at HIV diagnosis, whereas people in the three suboptimal care retention trajectories were more likely to be younger. Area deprivation index, rurality, and county health rankings were also strongly associated with care trajectories. Individual- and community-level factors associated to the three suboptimal care retention trajectories, if confirmed to be causative and actionable, could be prioritized to improve HIV care engagement.


Assuntos
Infecções por HIV , Retenção nos Cuidados , Administração de Caso , Florida/epidemiologia , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Carga Viral
7.
J Infect Dis ; 223(5): 866-875, 2021 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-32644119

RESUMO

BACKGROUND: Persons living with human immunodeficiency virus (HIV) with resistance to antiretroviral therapy are vulnerable to adverse HIV-related health outcomes and can contribute to transmission of HIV drug resistance (HIVDR) when nonvirally suppressed. The degree to which HIVDR contributes to disease burden in Florida-the US state with the highest HIV incidence- is unknown. METHODS: We explored sociodemographic, ecological, and spatiotemporal associations of HIVDR. HIV-1 sequences (n = 34 447) collected during 2012-2017 were obtained from the Florida Department of Health. HIVDR was categorized by resistance class, including resistance to nucleoside reverse-transcriptase , nonnucleoside reverse-transcriptase , protease , and integrase inhibitors. Multidrug resistance and transmitted drug resistance were also evaluated. Multivariable fixed-effects logistic regression models were fitted to associate individual- and county-level sociodemographic and ecological health indicators with HIVDR. RESULTS: The HIVDR prevalence was 19.2% (nucleoside reverse-transcriptase inhibitor resistance), 29.7% (nonnucleoside reverse-transcriptase inhibitor resistance), 6.6% (protease inhibitor resistance), 23.5% (transmitted drug resistance), 13.2% (multidrug resistance), and 8.2% (integrase strand transfer inhibitor resistance), with significant variation by Florida county. Individuals who were older, black, or acquired HIV through mother-to-child transmission had significantly higher odds of HIVDR. HIVDR was linked to counties with lower socioeconomic status, higher rates of unemployment, and poor mental health. CONCLUSIONS: Our findings indicate that HIVDR prevalence is higher in Florida than aggregate North American estimates with significant geographic and socioecological heterogeneity.


Assuntos
Fármacos Anti-HIV , Farmacorresistência Viral , Infecções por HIV , HIV-1 , Fármacos Anti-HIV/uso terapêutico , RNA Polimerases Dirigidas por DNA , Florida/epidemiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , HIV-1/efeitos dos fármacos , HIV-1/genética , Humanos , Transmissão Vertical de Doenças Infecciosas , Mutação , Nucleosídeos/uso terapêutico , Estudos Retrospectivos , Inibidores da Transcriptase Reversa/uso terapêutico , Fatores Sociodemográficos , Análise Espaço-Temporal
8.
Cancer Causes Control ; 32(7): 681-692, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33772705

RESUMO

PURPOSE: We examined gut microbiome (GM) profiles in relation to mammographic breast density (BD) and body mass index (BMI) in healthy postmenopausal women. METHODS: Eligible women were postmenopausal, had a BMI ≤ 35 kg/m2, and had not recently taken oral/IV antibiotics. All women provided a fecal sample and information on breast cancer risk factors. Mammographic BD was classified with the American College of Radiology's BI-RADS BD classification system. Bacterial DNA was isolated from fecal samples and the V1-V2 hypervariable regions of 16S rRNA were sequenced on the Illumina MiSeq platform. We examined associations of GM with indices of within-sample (alpha) diversity and the ratio of the two main phyla (Firmicutes and Bacteroidetes; F/B ratio) with BD and BMI. RESULTS: Among 69 women with BD data, 39 had low BD (BI-RADS I/II) and 30 had high BD (BI-RADS III/IV). BMI was inversely associated with BD (mean BMI = 23.8 and 28.0 in women with high and low BD, respectively, p = 1.07 × 10-5). Similar levels of GM diversity were found across weight groups according to Shannon (p = 0.83); Inverse Simpson (p = 0.97); and Chao1 (p = 0.31) indices. F/B ratio and microbiota diversity were suggestively greater in women with high vs. low BD (p = 0.35, 0.14, 0.15, and 0.17 for F/B ratio, Shannon, Inverse Simpson and Chao1, respectively). CONCLUSION: Suggestive differences observed in women with high and low BD with respect to GM alpha diversity and prevalence of specific GM taxa need to be confirmed in larger studies.


Assuntos
Peso Corporal , Microbioma Gastrointestinal/genética , Microbiota , Idoso , Índice de Massa Corporal , Densidade da Mama , Fezes/microbiologia , Feminino , Humanos , Pessoa de Meia-Idade , Pós-Menopausa , RNA Ribossômico 16S/genética
9.
J Neurovirol ; 27(1): 101-115, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33405206

RESUMO

Despite improvements in antiretroviral therapy, human immunodeficiency virus type 1 (HIV-1)-associated neurocognitive disorders (HAND) remain prevalent in subjects undergoing therapy. HAND significantly affects individuals' quality of life, as well as adherence to therapy, and, despite the increasing understanding of neuropathogenesis, no definitive diagnostic or prognostic marker has been identified. We investigated transcriptomic profiles in frontal cortex tissues of Simian immunodeficiency virus (SIV)-infected Rhesus macaques sacrificed at different stages of infection. Gene expression was compared among SIV-infected animals (n = 11), with or without CD8+ lymphocyte depletion, based on detectable (n = 6) or non-detectable (n = 5) presence of the virus in frontal cortex tissues. Significant enrichment in activation of monocyte and macrophage cellular pathways was found in animals with detectable brain infection, independently from CD8+ lymphocyte depletion. In addition, transcripts of four poly (ADP-ribose) polymerases (PARPs) were up-regulated in the frontal cortex, which was confirmed by real-time polymerase chain reaction. Our results shed light on involvement of PARPs in SIV infection of the brain and their role in SIV-associated neurodegenerative processes. Inhibition of PARPs may provide an effective novel therapeutic target for HIV-related neuropathology.


Assuntos
Transtornos Cognitivos/virologia , Lobo Frontal/metabolismo , Lobo Frontal/virologia , Poli(ADP-Ribose) Polimerases/metabolismo , Síndrome de Imunodeficiência Adquirida dos Símios/metabolismo , Animais , Transtornos Cognitivos/metabolismo , Macaca mulatta , Masculino , Síndrome de Imunodeficiência Adquirida dos Símios/virologia
10.
Eur J Nutr ; 59(4): 1633-1639, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31152213

RESUMO

PURPOSE: Previous studies suggest that coffee and caffeine intake may be associated with reduced breast cancer risk. To date, there is limited and inconsistent epidemiologic evidence for associations of adolescent diet with mammographic breast density, a strong and consistent predictor of breast cancer. We investigated the association of adolescent caffeine intake with mammographic density in premenopausal women. METHODS: This study included 751 cancer-free women within the Nurses' Health Study II cohort. Percent breast density (PD), absolute dense (DA) and non-dense areas (NDA) were measured from digitized film mammograms using a computer-assisted thresholding technique; all measures were square root-transformed. Energy-adjusted adolescent caffeine intake was estimated using the data from a food frequency questionnaire. Information regarding breast cancer risk factors was obtained from questionnaires closest to the mammogram date. We used generalized linear regression to quantify associations of caffeine intake with breast density measures. RESULTS: In multivariable analyses, adolescent caffeine intake was not associated with any of the density phenotypes (caffeine 4th vs. 1st quartile: ß = - 1.27, 95% CI - 4.62; 2.09, p-trend = 0.55 for percent density; ß = - 0.21, 95% CI - 0.76, 0.34, p-trend = 0.65 for absolute dense area, and ß = 0.23, 95% CI - 0.28, 0.74, p-trend = 0.50 for non-dense area). Additional adjustment of the models for body mass index at age 18 resulted in attenuation of the risk estimates. CONCLUSIONS: Our findings do not support the hypothesis that adolescent caffeine intake is associated with premenopausal mammographic breast density.


Assuntos
Densidade da Mama/fisiologia , Cafeína/administração & dosagem , Dieta/métodos , Pré-Menopausa , Adolescente , Adulto , Estudos de Coortes , Feminino , Humanos , Mamografia , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e Questionários
11.
Cancer Causes Control ; 29(6): 519-525, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29651651

RESUMO

PURPOSE: We investigated the association of coffee consumption with postmenopausal breast cancer risk, overall and by the status of postmenopausal hormone therapy (PMH). METHODS: This study included 126,182 postmenopausal women (2,636 with breast cancer and 123,546 without) from UK Biobank. Cancer diagnoses were ascertained through the linkage to the UK National Health Service Central Registers. Information on breast cancer risk factors and coffee consumption was collected at baseline and updated during follow-up. We used Cox proportional hazards regression to evaluate associations between coffee consumption and breast cancer, overall and in stratified analyses by woman's PMH status (none, past, current). RESULTS: In the overall analysis, coffee consumption was not associated with breast cancer risk (Hazard Ratio [HR] 1.00, 95% CI 0.91-1.11 for 2-3 cups/day, and HR 0.98, 95% CI 0.87-1.10 for ≥ 4 cups/day, p-trend = 0.69). Women with no PMH history who consumed ≥ 4 cups/day had a 16% reduced risk of breast cancer as compared to women who consumed < 7 cups/week (HR 0.84, 95% CI 0.71-1.00). Among women with past PMH, those consuming ≥ 4 cups/day had a 22% greater risk of breast cancer than women consuming < 7 cups/week (HR 1.22, 95% CI 1.01-1.47). No association was found among current PMH users. We found no significant interaction between PMH and coffee consumption (p = 0.24). CONCLUSIONS: Coffee consumption might be associated with increased breast cancer risk in women who used hormones in the past. Further studies are warranted to confirm these findings and elucidate potential biological mechanisms underlying the observed associations.


Assuntos
Neoplasias da Mama/epidemiologia , Café/efeitos adversos , Pós-Menopausa , Idoso , Bancos de Espécimes Biológicos , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Reino Unido
14.
Artigo em Inglês | MEDLINE | ID: mdl-38514461

RESUMO

BACKGROUND AND AIMS: Louse-borne Bartonella quintana infection and flea-borne murine typhus are two potentially serious vector-borne diseases that have led to periodic outbreaks among people experiencing homelessness in the United States. Little is known about louse- and flea-borne disease awareness and prevention among staff who provide services to the population. We surveyed staff in seven US states to identify gaps in knowledge and prevention practices for these diseases. METHODS AND RESULTS: Surveys were administered to 333 staff at 89 homeless shelters and outreach teams in California, Colorado, Georgia, Maryland, Minnesota, New York and Washington from August 2022 to April 2023. Most participants (>68%) agreed that body lice and fleas are a problem for people experiencing homelessness. About half were aware that diseases could be transmitted by these vectors; however, most could not accurately identify which diseases. Less than a quarter of staff could describe an appropriate protocol for managing body lice or fleas. Misconceptions included that clients must isolate or be denied services until they are medically cleared. CONCLUSIONS: Our findings reveal significant knowledge gaps among staff who provide services to people experiencing homelessness in the prevention and control of louse- and flea-borne diseases. This demonstrates an urgent need for staff training to both reduce disease and prevent unnecessary restrictions on services and housing.

15.
Eur J Med Res ; 28(1): 292, 2023 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-37596688

RESUMO

BACKGROUND: Integrase strand transferase inhibitors (INSTI), including raltegravir (RAL), elvitegravir (ELV), and dolutegravir (DTG), have demonstrated better efficacy and tolerability than other combination antiretroviral therapy (cART) classes in clinical trials; however, studies of sustainability of INSTI-containing therapy in the long-term are sparse. The purpose of this study was to provide an epidemiological overview comparing the outcome performance of different INSTI-based regimens longitudinally, including the metrics of efficacy, safety, convenience, and durability among a large, nationally representative cohort of persons living with HIV in Italy. METHODS: We selected subjects in the MaSTER cohort (an Italian multicenter, hospital-based cohort established in the mid-1990s that currently has enrolled over 24,000 PLWH) who initiated an INSTI-based regimen either when naïve or following a regimen switch. Cox proportional hazards regression models were fitted to evaluate associations between therapy interruptions and age, sex, nationality, transmission risk group, viral suppression status, CD4 + T-cell count, diagnosis year, cART status (naïve or experienced), and hepatitis coinfection. Results were stratified by cART INSTI type. RESULTS: There were 8173 participants who initiated an INSTI-based cART regimen in the MaSTER cohort between 2009 and 2017. The population was majority male (72.6%), of Italian nationality (88.6%), and cART-experienced (83.0%). Mean age was 49.7 (standard deviation: 13.9) years. In total, interruptions of the 1st INSTI-based treatment were recorded in 34% of cases. The most frequently cited reason for interruption among all three drug types was safety problems. In the survival analysis, past history of cART use was associated with higher hazards of interruption due to poor efficacy for all three drug types when compared to persons who were cART naïve. Non-viral suppression and CD4 + T-cell count < 200/mm3 at baseline were associated with higher hazards of interruption due to efficacy, safety, and durability reasons. Non-Italian nationality was linked to higher hazards of efficacy interruption for RAL and EVG. Age was negatively associated with interruption due to convenience and positively associated with interruption due to safety reasons. People who injects drugs (PWID) were associated with higher hazards of interruption due to convenience problems. Hepatitis coinfection was linked to higher hazards of interruption due to safety concerns for people receiving RAL. CONCLUSION: One-third of the population experienced an interruption of any drugs included in INSTI therapy in this study. The most frequent reason for interruption was safety concerns which accounted for one-fifth of interruptions among the full study population, mainly switched to DTG. The hazard for interruption was higher for low baseline CD4 + T-cell counts, higher baseline HIV-RNA, non-Italian nationality, older age, PWID and possible co-infections with hepatitis viruses. The risk ratio was higher for past history of cART use compared to persons who were cART naive, use of regimens containing 3 drugs compared to regimens containing 2 drugs. Durability worked in favor of DTG which appeared to perform better in this cohort compared to RAL and EVG, though length of follow-up was significantly shorter for DTG. These observational results need to be confirmed in further perspective studies with longer follow-up.


Assuntos
Coinfecção , Infecções por HIV , Abuso de Substâncias por Via Intravenosa , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por HIV/tratamento farmacológico , Itália/epidemiologia
16.
AIDS ; 37(11): 1739-1746, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37289578

RESUMO

OBJECTIVE: HIV molecular transmission network typologies have previously demonstrated associations to transmission risk; however, few studies have evaluated their predictive potential in anticipating future transmission events. To assess this, we tested multiple models on statewide surveillance data from the Florida Department of Health. DESIGN: This was a retrospective, observational cohort study examining the incidence of new HIV molecular linkages within the existing molecular network of persons with HIV (PWH) in Florida. METHODS: HIV-1 molecular transmission clusters were reconstructed for PWH diagnosed in Florida from 2006 to 2017 using the HIV-TRAnsmission Cluster Engine (HIV-TRACE). A suite of machine-learning models designed to predict linkage to a new diagnosis were internally and temporally externally validated using a variety of demographic, clinical, and network-derived parameters. RESULTS: Of the 9897 individuals who received a genotype within 12 months of diagnosis during 2012-2017, 2611 (26.4%) were molecularly linked to another case within 1 year at 1.5% genetic distance. The best performing model, trained on two years of data, was high performing (area under the receiving operating curve = 0.96, sensitivity = 0.91, and specificity = 0.90) and included the following variables: age group, exposure group, node degree, betweenness, transitivity, and neighborhood. CONCLUSIONS: In the molecular network of HIV transmission in Florida, individuals' network position and connectivity predicted future molecular linkages. Machine-learned models using network typologies performed superior to models using individual data alone. These models can be used to more precisely identify subpopulations for intervention.


Assuntos
Infecções por HIV , HIV-1 , Humanos , Infecções por HIV/epidemiologia , Estudos de Coortes , Epidemiologia Molecular , Análise por Conglomerados , HIV-1/genética
17.
JMIR Form Res ; 7: e39409, 2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-36848460

RESUMO

BACKGROUND: In the wake of the SARS-CoV-2 pandemic, scientists have scrambled to collect and analyze SARS-CoV-2 genomic data to inform public health responses to COVID-19 in real time. Open source phylogenetic and data visualization platforms for monitoring SARS-CoV-2 genomic epidemiology have rapidly gained popularity for their ability to illuminate spatial-temporal transmission patterns worldwide. However, the utility of such tools to inform public health decision-making for COVID-19 in real time remains to be explored. OBJECTIVE: The aim of this study is to convene experts in public health, infectious diseases, virology, and bioinformatics-many of whom were actively engaged in the COVID-19 response-to discuss and report on the application of phylodynamic tools to inform pandemic responses. METHODS: In total, 4 focus groups (FGs) occurred between June 2020 and June 2021, covering both the pre- and postvariant strain emergence and vaccination eras of the ongoing COVID-19 crisis. Participants included national and international academic and government researchers, clinicians, public health practitioners, and other stakeholders recruited through purposive and convenience sampling by the study team. Open-ended questions were developed to prompt discussion. FGs I and II concentrated on phylodynamics for the public health practitioner, while FGs III and IV discussed the methodological nuances of phylodynamic inference. Two FGs per topic area to increase data saturation. An iterative, thematic qualitative framework was used for data analysis. RESULTS: We invited 41 experts to the FGs, and 23 (56%) agreed to participate. Across all the FG sessions, 15 (65%) of the participants were female, 17 (74%) were White, and 5 (22%) were Black. Participants were described as molecular epidemiologists (MEs; n=9, 39%), clinician-researchers (n=3, 13%), infectious disease experts (IDs; n=4, 17%), and public health professionals at the local (PHs; n=4, 17%), state (n=2, 9%), and federal (n=1, 4%) levels. They represented multiple countries in Europe, the United States, and the Caribbean. Nine major themes arose from the discussions: (1) translational/implementation science, (2) precision public health, (3) fundamental unknowns, (4) proper scientific communication, (5) methods of epidemiological investigation, (6) sampling bias, (7) interoperability standards, (8) academic/public health partnerships, and (9) resources. Collectively, participants felt that successful uptake of phylodynamic tools to inform the public health response relies on the strength of academic and public health partnerships. They called for interoperability standards in sequence data sharing, urged careful reporting to prevent misinterpretations, imagined that public health responses could be tailored to specific variants, and cited resource issues that would need to be addressed by policy makers in future outbreaks. CONCLUSIONS: This study is the first to detail the viewpoints of public health practitioners and molecular epidemiology experts on the use of viral genomic data to inform the response to the COVID-19 pandemic. The data gathered during this study provide important information from experts to help streamline the functionality and use of phylodynamic tools for pandemic responses.

18.
AMIA Jt Summits Transl Sci Proc ; 2022: 274-283, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35854723

RESUMO

Drug-resistant bacterial infections are a global health concern with high mortality and limited treatment options. Several clinical risk-severity scores are available, e.g. qPitt, but their predictive performance is moderate. Here, we leveraged machine learning and electronic health records (EHRs) to improve prediction of mortality due to bloodstream infection with Klebsiella pneumoniae. We tested the qPitt score and new EHR variables (either expert-chosen or the full set of diagnostic codes), fitting LASSO, boosted logistic regression (BLR), support vector machines, decision trees, and random forests. The qPitt score showed moderate discriminative ability (AUROC=0.63), whilst machine learning models significantly improved its performance (best AUROC by BLR 0.80 for expert-chosen and 0.88 for full code set). Similar results were obtained in critically ill patients, and when excluding potential non-causal variables to evaluate an actionable model. In conclusion, current risk scores for bacteremia mortality can be improved and, with opportune causal modelling, considered for deployment in clinical decision-making.

19.
Infect Dis Ther ; 11(5): 1869-1882, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35908268

RESUMO

INTRODUCTION: Urinary tract infections (UTIs) are common infections for which initial antibiotic treatment decisions are empirically based, often without antibiotic susceptibility testing to evaluate resistance, increasing the risk of inappropriate therapy. We hypothesized that models based on electronic health records (EHR) could assist in the identification of patients at higher risk for antibiotic-resistant UTIs and help guide the selection of antimicrobials in hospital and clinic settings. METHODS: EHR from multiple centers in North-Central Florida, including patient demographics, previous diagnoses, prescriptions, and antibiotic susceptibility tests, were obtained for 9990 patients diagnosed with a UTI during 2011-2019. Decision trees, boosted logistic regression (BLR), and random forest models were developed to predict resistance to common antibiotics used for UTI management [sulfamethoxazole-trimethoprim (SXT), nitrofurantoin (NIT), ciprofloxacin (CIP)] and multidrug resistance (MDR). RESULTS: There were 6307 (63.1%) individuals with a UTI caused by a resistant microorganism. Overall, the population was majority female, white, non-Hispanic, and older aged (mean = 60.7 years). The BLR models yielded the highest discriminative ability, as measured by the out-of-bag area under the receiver-operating curve (AUROC), for the resistance outcomes [AUROC = 0.58 (SXT), 0.62 (NIT), 0.64 (CIP), and 0.66 (MDR)]. Variables in the best performing model were sex, history of UTIs, catheterization, renal disease, dementia, hemiplegia/paraplegia, and hypertension. CONCLUSIONS: The discriminative ability of the prediction models was moderate. Nonetheless, these models based solely on EHR demonstrate utility for the identification of patients at higher risk for resistant infections. These models, in turn, may help guide clinical decision-making on the ordering of urine cultures and decisions regarding empiric therapy for these patients.

20.
Disaster Med Public Health Prep ; 17: e176, 2022 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-35492011

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic continues to present unique public health challenges both within the United States and across the globe. Institutions of higher learning are tasked with preventing and responding to COVID-19 on campus while also considering implications for the surrounding communities. The process of re-opening campus, whether at full or partial capacity, has tasked these institutions with overcoming complex challenges associated with balancing the resumption of campus operations while simultaneously protecting university affiliates and surrounding community members from COVID-19 through robust surveillance, contact tracing, and testing efforts. Here, we provide a concise outline related to the development and implementation of the comprehensive and sustainable COVID-19 surveillance program at the University of Florida. We also critically discuss the successes and pitfalls of this program while also providing recommendations for the development of similar programs in the future.


Assuntos
COVID-19 , Estados Unidos/epidemiologia , Humanos , COVID-19/epidemiologia , Universidades , Sudeste dos Estados Unidos/epidemiologia , Saúde Pública , Busca de Comunicante
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