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1.
PeerJ ; 12: e16714, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38213767

RESUMO

Background: Conflicting messages and misleading information related to the coronavirus (COVID-19) pandemic (SARS-CoV-2) have hindered mitigation efforts. It is important that trust in evidence-based public health information be maintained to effectively continue pandemic mitigation strategies. Officials, researchers, and the public can benefit from exploring how people receive information they believe and trust, and how their beliefs influence their behaviors. Methods: To gain insight and inform effective evidence-based public health messaging, we distributed an anonymous online cross-sectional survey from May to July, 2020 to Virginia residents, 18 years of age or older. Participants were surveyed about their perceptions of COVID-19, risk mitigation behaviors, messages and events they felt influenced their beliefs and behaviors, and where they obtained information that they trust. The survey also collected socio-demographic information, including gender, age, race, ethnicity, level of education, income, employment status, occupation, changes in employment due to the pandemic, political affiliation, sexual orientation, and zip code. Analyses included specific focus on the most effective behavioral measures: wearing a face mask and distancing in public. Results: Among 3,488 respondents, systematic differences were observed in information sources that people trust, events that impacted beliefs and behaviors, and how behaviors changed by socio-demographics, political identity, and geography within Virginia. Characteristics significantly associated (p < 0.025) with not wearing a mask in public included identifying as non-Hispanic white, male, Republican political identity, younger age, lower income, not trusting national science and health organizations, believing one or more non-evidence-based messages, and residing in Southwest Virginia in logistic regression. Similar, lesser in magnitude correlations, were observed for distancing in public. Conclusions: This study describes how information sources considered trustworthy vary across different populations and identities, and how these differentially correspond to beliefs and behaviors. This study can assist decision makers and the public to improve and effectively target public health messaging related to the ongoing COVID-19 pandemic and future public health challenges in Virginia and similar jurisdictions.


Assuntos
COVID-19 , Masculino , Humanos , Feminino , Adolescente , Adulto , COVID-19/epidemiologia , SARS-CoV-2 , Estudos Transversais , Virginia/epidemiologia , Pandemias/prevenção & controle , Fonte de Informação
2.
Artigo em Inglês | MEDLINE | ID: mdl-37620122

RESUMO

OBJECTIVES: (1) To operationalise our previously published definition of neonatal serious illness by applying it to a patient cohort and (2) to evaluate timing of palliative care consultation, goals of care discussions and meeting serious illness criteria. METHODS: This was a retrospective chart review. Inborn neonates delivered between January 2006 and December 2020 who died prior to neonatal intensive care unit discharge were identified through EPIC query. Kruskal-Wallis and Mann-Whitney-U tests were used to compare time intervals relating to transition to serious illness across causes of death and other factors. χ2 tests were used to examine frequency of goals of care conversations by factors. RESULTS: Eighty-eight per cent of patients met criteria for neonatal serious illness within 48 hours of life. There were no significant differences in transition to serious illness between preterm and term infants. Time to identification of serious illness varied significantly by cause of death. Palliative care was consulted for 5.7% of patients. CONCLUSION: All patients met criteria for serious illness early in life based on our definition. This definition may be useful for identifying neonates with serious illness in time to provide support. Additional work is needed to apply this definition prospectively to explore its utility for clinical care and research.

3.
Emerg Infect Dis ; 28(7): 1313-1320, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35731137

RESUMO

In April 2021, a COVID-19 outbreak occurred at a correctional facility in rural Virginia, USA. Eighty-four infections were identified among 854 incarcerated persons by facilitywide testing with reverse transcription quantitative PCR (qRT-PCR). We used whole-genome sequencing to link all infections to 2 employees infected with the B.1.1.7α (UK) variant. The relative risk comparing unvaccinated to fully vaccinated persons (mRNA-1273 [Moderna, https://www.modernatx.com]) was 7.8 (95% CI 4.8-12.7), corresponding to a vaccine effectiveness of 87.1% (95% CI 79.0%-92.1%). Average qRT-PCR cycle threshold values were lower, suggesting higher viral loads, among unvaccinated infected than vaccinated cases for the nucleocapsid, envelope, and spike genes. Vaccination was highly effective at preventing SARS-CoV-2 infection in this high-risk setting. This approach can be applied to similar settings to estimate vaccine effectiveness as variants emerge to guide public health strategies during the ongoing pandemic.


Assuntos
COVID-19 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Estabelecimentos Correcionais , Surtos de Doenças/prevenção & controle , Humanos , Masculino , SARS-CoV-2/genética , Estados Unidos/epidemiologia , Eficácia de Vacinas
4.
Value Health ; 24(5): 625-631, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33933230

RESUMO

The potential health and economic value of a vaccine for coronavirus disease (COVID-19) is self-evident given nearly 2 million deaths, "collateral" loss of life as other conditions go untreated, and massive economic damage. Results from the first licensed products are very encouraging; however, there are important reasons why we will likely need second and third generation vaccines. Dedicated incentives and funding focused explicitly on nurturing and advancing competing second and third generation vaccines are essential. This article proposes a collaborative, market-based financing mechanism for the world to incentivize and pay for the development of, and provide equitable access to, second and third generation COVID-19 vaccines. Specifically, we propose consideration of a Benefit-Based Advance Market Commitment (BBAMC). The BBAMC uses health technology assessment to determine value-based prices to guarantee overall market revenues, not revenue for any specific product or company. The poorest countries would not pay a value-based price but a discounted "tail-price." Innovators must agree to supply them at this tail price or to facilitate technology transfer to local licensees at low or zero cost to enable them to supply at this price. We expect these purchases to be paid for in full or large part by global donors. The BBAMC therefore sets prices in relation to value, protects intellectual property rights, encourages competition, and ensures all populations get access to vaccines, subject to agreed priority allocation rules.


Assuntos
COVID-19/prevenção & controle , Saúde Global/economia , Programas de Imunização/economia , COVID-19/economia , Vacinas contra COVID-19/economia , Vacinas contra COVID-19/uso terapêutico , Defesa Civil/métodos , Defesa Civil/tendências , Competição Econômica/normas , Competição Econômica/tendências , Saúde Global/tendências , Humanos , Programas de Imunização/métodos , Tratamento Farmacológico da COVID-19
5.
J Clin Oncol ; 39(9): 1020-1028, 2021 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-33529051

RESUMO

PURPOSE: Pembrolizumab, a programmed death 1 inhibitor, demonstrated promising single-agent activity in untreated patients with various cancer types. The phase II KEYNOTE-427 study evaluated efficacy and safety of single-agent pembrolizumab in treatment-naive patients with advanced clear cell renal cell carcinoma (ccRCC; cohort A) and advanced non-ccRCC (cohort B). Results of cohort A are reported. METHODS: In this open-label, single-arm phase II study, patients with advanced ccRCC received pembrolizumab 200 mg every 3 weeks for ≤ 24 months. The primary end point was objective response rate by RECIST, version 1.1. RESULTS: In the total population (N = 110), median time from enrollment to data cutoff was 35.9 (range, 29.5-40.3) months. Objective response rate was 36.4% with four (3.6%) complete responses and 36 (32.7%) partial responses; disease control rate was 58.2% (95% CI, 48.4 to 67.5). Most patients (68.2%) had a decrease in target lesions, including 30.9% with a reduction ≥ 60%. Median duration of response was 18.9 (range, 2.3-37.6+) months; 64.1% of responders had a response ≥ 12 months (Kaplan-Meier). Median progression-free survival was 7.1 months (95% CI, 5.6 to 11.0). Median overall survival was not reached; 12-month and 24-month overall survival rates were 88.2% and 70.8%, respectively. Durable responses were observed across all International Metastatic RCC Database Consortium categories. Grade 3-5 treatment-related adverse events were reported in 30.0% of patients, of which colitis and diarrhea were most frequent. CONCLUSION: Single-agent pembrolizumab showed promising antitumor activity as a first-line treatment in patients with advanced ccRCC, with durable responses across International Metastatic RCC Database Consortium categories. Safety and tolerability profile of pembrolizumab monotherapy was comparable to what has been previously described in other tumor types.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/patologia , Feminino , Seguimentos , Humanos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados não Aleatórios como Assunto , Prognóstico , Taxa de Sobrevida
6.
J Clin Oncol ; 39(9): 1029-1039, 2021 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-33529058

RESUMO

PURPOSE: Programmed death 1 (PD-1) pathway inhibitors have not been prospectively evaluated in patients with non-clear cell renal cell carcinoma (nccRCC). The phase II KEYNOTE-427 study (cohort B) was conducted to assess the efficacy and safety of single-agent pembrolizumab, a PD-1 inhibitor, in advanced nccRCC. METHODS: Patients with histologically confirmed, measurable (Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1) nccRCC and no prior systemic therapy received pembrolizumab 200 mg intravenously once every 3 weeks for ≤ 24 months. The primary end point was objective response rate (ORR) per RECIST v1.1. RESULTS: Among enrolled patients (N = 165), 71.5% had confirmed papillary, 12.7% had chromophobe, and 15.8% had unclassified RCC histology. Most patients (67.9%) had intermediate or poor International Metastatic RCC Database Consortium risk status and tumors with programmed death ligand 1 (PD-L1) combined positive score (CPS) ≥ 1 (61.8%). The median time from enrollment to database cutoff was 31.5 months (range, 22.7-38.8). In all patients, the ORR was 26.7%. The median duration of response was 29.0 months; 59.7% of responses lasted ≥ 12 months. The ORR by CPS ≥ 1 and CPS < 1 status was 35.3% and 12.1%, respectively. The ORR by histology was 28.8% for papillary, 9.5% for chromophobe, and 30.8% for unclassified. Overall, the median progression-free survival was 4.2 months (95% CI, 2.9 to 5.6); the 24-month rate was 18.6%. The median overall survival was 28.9 months (95% CI, 24.3 months to not reached); the 24-month rate was 58.4%. Overall, 69.7% of patients reported treatment-related adverse events, most commonly pruritus (20.0%) and hypothyroidism (14.5%). Two deaths were treatment related (pneumonitis and cardiac arrest). CONCLUSION: First-line pembrolizumab monotherapy showed promising antitumor activity in nccRCC. The safety profile was similar to that observed in other tumor types.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/patologia , Feminino , Seguimentos , Humanos , Agências Internacionais , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Adulto Jovem
7.
Gates Open Res ; 4: 16, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32185365

RESUMO

The pricing of medicines and health products ranks among the most hotly debated topics in health policy, generating controversy in richer and poorer markets alike. Creating the right pricing structure for pharmaceuticals and other healthcare products is particularly important for low- and middle-income countries, where pharmaceuticals account for a significant portion of total health expenditure; high medicine prices therefore threaten the feasibility and sustainability of nascent schemes for universal health coverage (UHC). We argue that a strategic system of value-based tiered pricing (VBTP), wherein each country would pay a price for each health product commensurate with the local value it provides, could improve access, enhance efficiency, and empower countries to negotiate with product manufacturers. This paper attempts to further understanding on the potential value of tiered pricing, barriers to its implementation, and potential strategies to overcome those.

10.
PLoS One ; 14(10): e0223411, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31584992

RESUMO

INTRODUCTION: Despite increased treatment availability, HIV-infected individuals continue to start antiretroviral therapy (ART) late in disease progression, increasing early mortality risk. MATERIALS AND METHODS: Nested prospective cohort study within a randomized clinical trial of adult patients initiating ART at clinics in urban Nairobi and rural Maseno, Kenya, between 2013-2014. We estimated mortality incidence rates following ART initiation and used Cox proportional hazards regression to identify predictors of mortality within 12 months of ART initiation. Analyses were stratified by clinic site to examine differences in mortality correlates and risk by location. RESULTS: Among 811 participants initiated on ART, the mortality incidence rate within a year of initiating ART was 7.44 per 100 person-years (95% CI 5.71, 9.69). Among 207 Maseno and 612 Nairobi participants initiated on ART, the mortality incidence rates (per 100 person-years) were 12.78 (95% CI 8.49, 19.23) and 5.72 (95% CI 4.05, 8.09). Maseno had a 2.20-fold greater risk of mortality than Nairobi (95% CI 1.29, 3.76; P = 0.004). This association remained [adjusted hazard ratio (HR) = 2.09 (95% CI 1.17, 3.74); P = 0.013] when adjusting for age, gender, education, pre-treatment drug resistance (PDR), and CD4 count, but not when adjusting for BMI. In unadjusted analyses, other predictors (P<0.05) of mortality included male gender (HR = 1.74), age (HR = 1.04 for 1-year increase), fewer years of education (HR = 0.92 for 1-year increase), unemployment (HR = 1.89), low body mass index (BMI<18.5 m/kg2; HR = 4.99), CD4 count <100 (HR = 11.67) and 100-199 (HR = 3.40) vs. 200-350 cells/µL, and pre-treatment drug resistance (PDR; HR = 2.49). The increased mortality risk associated with older age, males, and greater education remained when adjusted for location, age, education and PDR, but not when adjusted for BMI and CD4 count. PDR remained associated with increased mortality risk when adjusted for location, age, gender, education, and BMI, but not when adjusted for CD4 count. CD4 and BMI associations with increased mortality risk persisted in multivariable analyses. Despite similar baseline CD4 counts across locations, mortality risk associated with low CD4 count, low BMI, and PDR was greater in Maseno than Nairobi in stratified analyses. CONCLUSIONS: High short-term post-ART mortality was observed, partially due to low CD4 count and BMI at presentation, especially in the rural setting. Male gender, older age, and markers of lower socioeconomic status were also associated with greater mortality risk. Engaging patients earlier in HIV infection remains critical. PDR may influence short-term mortality and further studies to optimize management will be important in settings with increasing PDR.


Assuntos
Infecções por HIV/mortalidade , Saúde da População Rural , Saúde da População Urbana , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Acessibilidade aos Serviços de Saúde , Humanos , Incidência , Estimativa de Kaplan-Meier , Quênia/epidemiologia , Mortalidade , Modelos de Riscos Proporcionais , Fatores Socioeconômicos , Tempo para o Tratamento
11.
J Biopharm Stat ; 29(4): 696-713, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31304861

RESUMO

The sequential parallel comparison design (SPCD), with sequence groups P:P, P:T, and T:T, together with the exclusion of the second-period information from placebo responders in the first period, can serve usefully for studies with highly favorable placebo response, for example, psychiatric clinical trials. This paper presents a methodology for the first-period treatment difference in the overall population and the second-period treatment difference in the placebo nonresponders for the first period, as well as other available sources of information that could be of potential interest. Without any assumptions, a hypothesis testing method is proposed based on the randomization distribution of comparisons using the covariance structure for the randomized population under the null hypothesis to control type I error. Randomization-based analysis of covariance (ANCOVA) is introduced to adjust for baseline and for the observations that serve as baselines for the second period. Related methods are proposed for the study population as a simple random sample of an almost infinite population. The statistical properties of the proposed methods are described with simulation studies; and the use of the methods is illustrated for an example based on the data from the ADAPT-A clinical trial.


Assuntos
Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Simulação por Computador , Humanos , Distribuição Aleatória
12.
Sex Transm Dis ; 46(8): 493-501, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31295215

RESUMO

BACKGROUND: Sexually transmitted disease (STD) partner services (PS) are a core component of STD programs. Data on costs are needed to support PS programming. METHODS: In Washington State STD PS programs, disease intervention specialists (DIS) conduct telephone-based interviews and occasional field visits, offer expedited partner therapy to heterosexuals with gonorrhea or chlamydia, and promote human immunodeficiency virus (HIV) testing, preexposure prophylaxis, and HIV care. We conducted activity-based microcosting of PS, including: observational and self-reported time studies and interviews. We analyzed cost, surveillance, and service delivery data to determine costs per program outcomes. RESULTS: In King, Pierce, and Spokane counties, respectively, DIS allocated 6.5, 6.4, and 28.8 hours per syphilis case and 1.5, 1.6, and 2.9 hours per gonorrhea/chlamydia case, on average. In 2016, each full-time DIS investigated 270, 268, and 61 syphilis and 1177, 1105, and 769 gonorrhea/chlamydia cases. Greater than 80% of syphilis cases in King and Pierce were among men who have sex with men versus 38% in Spokane. Disease intervention specialists spent 12% to 39% of their time actively interviewing cases and notifying partners (clients), and the remaining time locating clients, coordinating and verifying care, and managing case reports. Time spent on expedited partner therapy, HIV testing, and referrals to HIV treatment or preexposure prophylaxis, was minimal (<5 minutes per interview) at locations with resources outside PS staff. Program cost-per-interview ranged from US $527 to US $2210 for syphilis, US $219 to US $484 for gonorrhea, and US $164 to US $547 for chlamydia. DISCUSSION: The STD PS resource needs depended on epidemic characteristics and program models. Integrating HIV prevention objectives minimally impacted PS-specific program costs. Results can inform program planning, future budget impact, and cost-effectiveness analyses.


Assuntos
Recursos em Saúde/economia , Serviços Preventivos de Saúde/economia , Parceiros Sexuais , Infecções Sexualmente Transmissíveis/economia , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções por Chlamydia/economia , Busca de Comunicante/economia , Efeitos Psicossociais da Doença , Feminino , Gonorreia/economia , Homossexualidade Masculina/estatística & dados numéricos , Humanos , Incidência , Masculino , Estudos Observacionais como Assunto , Desenvolvimento de Programas/economia , Infecções Sexualmente Transmissíveis/prevenção & controle , Sífilis/economia , Washington/epidemiologia
13.
AIDS ; 33(6): 941-951, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30946148

RESUMO

OBJECTIVES: Among women initiating first-line nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based-ART with and without a history of single-dose nevirapine (sdNVP) with or without zidovudine with or without lamivudine (ZDV with and without 3TC) for prevention of mother-to-child HIV transmission (PMTCT), we hypothesized that pre-ART HIV-drug resistance would be associated with virologic failure DESIGN/METHODS:: In a prospectively enrolled study, three genotypic drug-resistance assays [oligonucleotide-ligation-assay (OLA), consensus sequencing, and next-generation sequencing by Illumina] were retrospectively performed to detect pre-ART drug resistance. Minority or majority drug-resistant variants identified in pre-ART RNA and/or DNA, a history of antiretrovirals for PMTCT, and other risk factors were assessed for association with virologic failure. RESULTS: Failure occurred in 38/169 (22.5%) women, and was associated with pre-ART drug resistance detected by any assay (OLA of plasma or PBMC, consensus sequencing of PBMC and/or plasma, and next-generation sequencing of PBMC at frequencies of at least 10% and as minority variants; all P < 0.0001). Failure was also associated with PMTCT using sdNVP and ZDV with or without 3TC, but not sdNVP only; however, the longer time-interval between PMTCT and ART initiation observed for sdNVP-only women showed no interaction with failure. Viral loads and OLA of PBMC in longitudinal specimens demonstrated rapid failure and emergence of drug resistance, particularly among sdNVP and ZDV with or without 3TC-experienced women with pre-ART drug-resistant minority variants by next-generation sequencing but without drug resistance by OLA or consensus sequencing. CONCLUSION: Pre-ART drug resistance was detected similarly by OLA of PBMC or plasma and by consensus sequencing, and was associated with virologic failure soon after initiation of first-line NVP-based ART. A history of sdNVP and ZDV with or without 3TC for PMTCT or minority variants detected by next-generation sequencing identified additional women with failure. These findings emphasize the value of assessing individual antiretroviral history, particularly nonsuppressive antiretrovirals with at least two drug classes, and testing for pre-ART drug resistance, including minority variants.


Assuntos
Antirretrovirais/farmacologia , Farmacorresistência Viral , Genótipo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/genética , Adolescente , Adulto , Feminino , Técnicas de Genotipagem , HIV-1/isolamento & purificação , Humanos , Quênia , Mutação , Estudos Retrospectivos , Adulto Jovem
15.
Stat Med ; 37(9): 1454-1466, 2018 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-29462838

RESUMO

Sequential parallel comparison design (SPCD) has been proposed to increase the likelihood of success of clinical trials especially trials with possibly high placebo effect. Sequential parallel comparison design is conducted with 2 stages. Participants are randomized between active therapy and placebo in stage 1. Then, stage 1 placebo nonresponders are rerandomized between active therapy and placebo. Data from the 2 stages are pooled to yield a single P value. We consider SPCD with binary and with time-to-event outcomes. For time-to-event outcomes, response is defined as a favorable event prior to the end of follow-up for a given stage of SPCD. We show that for these cases, the usual test statistics from stages 1 and 2 are asymptotically normal and uncorrelated under the null hypothesis, leading to a straightforward combined testing procedure. In addition, we show that the estimators of the treatment effects from the 2 stages are asymptotically normal and uncorrelated under the null and alternative hypothesis, yielding confidence interval procedures with correct coverage. Simulations and real data analysis demonstrate the utility of the binary and time-to-event SPCD.


Assuntos
Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Estatística como Assunto , Interpretação Estatística de Dados , Humanos , Modelos Estatísticos , Fatores de Tempo , Resultado do Tratamento
16.
J Lesbian Stud ; 22(1): 85-93, 2018 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-28318432

RESUMO

This autoethnographic study of femme friendship explores the connection and relationship between two femme lesbians-my femme friend Amber and myself. The shared experience of invisibility and the related perils and privileges that come with passing as straight enact a bond unlike any either of us have previously experienced. Meeting within the context of a polyamorous relationship adds a layer of complexity to our friendship that deepens the relationship. The story of our friendship showcases a specific sort of friendship, one grounded in theories of gender performance, sexuality, invisibility, and language.


Assuntos
Amigos , Homossexualidade Feminina/psicologia , Adulto , Feminino , Humanos
17.
Abdom Radiol (NY) ; 43(3): 702-712, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28721479

RESUMO

PURPOSE: Our objective is to determine the accuracy of multiparametric MRI (mpMRI) in predicting pathologic grade of prostate cancer (PCa) after radical prostatectomy (RP) using simple apparent diffusion coefficient metrics and, specifically, whether mpMRI can accurately separate disease into one of two risk categories (low vs. higher grade) or one of three risk categories (low, intermediate, or high grade) corresponding to the new prognostic grade group (PGG) criteria. METHODS: This retrospective, HIPAA-compliant, IRB-approved study included 140 patients with PCa who underwent 3 T mpMRI with endorectal coil and transrectal ultrasound-guided (TRUS-G) biopsy before RP. MpMRI was used to classify lesions using a two-tier (low-grade/PGG 1 vs. high-grade/PGG 2-5) or a three-tier system (low-grade/PGG 1 vs. intermediate-grade/PGG 2 vs. high-grade/PGG 3-5). Accuracy of mpMRI was compared against RP for each system. RESULTS: The predictive accuracy of mpMRI using the two-tier system is higher than when using three-tier system (0.77 and 0.45, respectively). There were similar rates of undergrading between mpMRI and TRUS-G biopsy compared to RP (16% & 21%; respectively); rate of overgrading was higher for mpMRI vs. TRUS-G biopsy compared to RP (42% & 17%, respectively). When mpMRI and TRUS-G biopsy are combined, rate of undergrading is 1.4% and overgrading is 11%. CONCLUSIONS: MpMRI predictive accuracy is higher when using a two-tier vs. a three-tier system, suggesting that advanced metrics may be necessary to delineate intermediate- from high-grade disease. Rates of under- and overgrading decreased when mpMRI and TRUS-G biopsy are combined, suggesting that these techniques may be complementary in predicting tumor grade.


Assuntos
Imageamento por Ressonância Magnética/métodos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Idoso , Meios de Contraste , Gadolínio DTPA , Humanos , Biópsia Guiada por Imagem , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Valor Preditivo dos Testes , Prognóstico , Prostatectomia , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos , Ultrassonografia de Intervenção
18.
J Infect Dis ; 216(12): 1569-1578, 2017 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-29040633

RESUMO

Background: Pre-antiretroviral-treatment drug resistance (PDR) is a predictor of human immunodeficiency virus (HIV) treatment failure. We determined PDR prevalence and correlates in a Kenyan cohort. Methods: We conducted a cross-sectional analysis of antiretroviral (ARV) treatment-eligible HIV-infected participants. PDR was defined as ≥2% mutant frequency in a participant's HIV quasispecies at pol codons K103N, Y181C, G190A, M184 V, or K65R by oligonucleotide ligation assay and Illumina sequencing. PDR prevalence was calculated by demographics and codon, stratifying by prior ARV experience. Poisson regression was used to estimate prevalence ratios. Results: PDR prevalences (95% confidence interval [CI]) in 815 ARV-naive adults, 136 ARV-experienced adults, and 36 predominantly ARV-naive children were 9.4% (7.5%-11.7%), 12.5% (7.5%-19.3%), and 2.8% (0.1%-14.5%), respectively. Median mutant frequency within an individual's HIV quasispecies was 67%. PDR prevalence in ARV-naive women 18-24 years old was 21.9% (9.3%-40.0%). Only age in females associated with PDR: A 5-year age decrease was associated with adjusted PDR prevalence ratio 1.20 (95% CI, 1.06-1.36; P = .004). Conclusions: The high PDR prevalence may warrant resistance testing and/or alternative ARVs in high HIV prevalence settings, with attention to young women, likely to have recent infection and higher rates of resistance. Clinical Trials Registration: NCT01898754.


Assuntos
Farmacorresistência Viral , Infecções por HIV/virologia , HIV/efeitos dos fármacos , Adolescente , Adulto , Fatores Etários , Idoso , Estudos Transversais , Feminino , Genótipo , Técnicas de Genotipagem , HIV/genética , Infecções por HIV/epidemiologia , Humanos , Quênia/epidemiologia , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Hibridização de Ácido Nucleico , Prevalência , Análise de Sequência de DNA , Fatores Sexuais , Adulto Jovem , Produtos do Gene pol do Vírus da Imunodeficiência Humana/genética
19.
AIDS ; 31(8): 1143-1148, 2017 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-28301421

RESUMO

OBJECTIVES: We set out to examine the prevalence and persistence of mutations conferring high-level nonnucleoside reverse transcriptase (NNRTI)-resistance in a cohort of HIV-infected children who had failed prophylaxis to prevent mother-to-child-transmission (PMTCT). DESIGN: A prospective observational cohort study at the Pediatric HIV Clinic at Kalafong Provincial Tertiary Hospital in Pretoria, South Africa. METHODS: Children referred for initiation of antiretroviral therapy (ART) were enrolled from July 2010 through February 2013. HIV drug resistance testing was performed using the oligonucleotide ligation assay (OLA) on dried blood spots (DBS) collected at enrolment and monthly follow-up visits for 2 years. RESULTS: South African children who failed HIV-prophylaxis had a high prevalence of NNRTI-resistant HIV (46/88; 52%). Among children with NNRTI-resistance, the frequency of the predominant resistant variant in each child's HIV-quasispecies was high (median 96%) at study entry (median age 7.5 months), and in 26 out of 27 followed a median of 13 months persisted at a high frequency (median 89%). CONCLUSION: Our finding that infants who fail HIV-prophylaxis frequently have long-lived NNRTI-resistant HIV suggests that resistance will likely persist through 36 months of age, when children qualify for NNRTI-based ART. These children may benefit from HIV drug resistance testing to guide selection of their treatment.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Farmacorresistência Viral , Infecções por HIV/prevenção & controle , Infecções por HIV/virologia , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Nevirapina/administração & dosagem , Fármacos Anti-HIV/farmacologia , Pré-Escolar , Feminino , Técnicas de Genotipagem , Infecções por HIV/epidemiologia , Humanos , Lactente , Recém-Nascido , Masculino , Testes de Sensibilidade Microbiana , Nevirapina/farmacologia , Prevalência , Estudos Prospectivos , África do Sul/epidemiologia
20.
Transl Vis Sci Technol ; 6(1): 9, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28180033

RESUMO

PURPOSE: We determine whether the automated segmentation software, Duke Optical Coherence Tomography Retinal Analysis Program (DOCTRAP), can measure, in a platform-independent manner, retinal thickness on Cirrus and Spectralis spectral domain optical coherence tomography (SD-OCT) images in eyes with diabetic macular edema (DME) under treatment in a clinical trial. METHODS: Automatic segmentation software was used to segment the internal limiting membrane (ILM), inner retinal pigment epithelium (RPE), and Bruch's membrane (BM) in SD-OCT images acquired by Cirrus and Spectralis commercial systems, from the same eye, on the same day during a clinical interventional DME trial. Mean retinal thickness differences were compared across commercial and DOCTRAP platforms using intraclass correlation (ICC) and Bland-Altman plots. RESULTS: The mean 1 mm central subfield thickness difference (standard error [SE]) comparing segmentation of Spectralis images with DOCTRAP versus HEYEX was 0.7 (0.3) µm (0.2 pixels). The corresponding values comparing segmentation of Cirrus images with DOCTRAP versus Cirrus software was 2.2 (0.7) µm. The mean 1 mm central subfield thickness difference (SE) comparing segmentation of Cirrus and Spectralis scan pairs with DOCTRAP using BM as the outer retinal boundary was -2.3 (0.9) µm compared to 2.8 (0.9) µm with inner RPE as the outer boundary. CONCLUSIONS: DOCTRAP segmentation of Cirrus and Spectralis images produces validated thickness measurements that are very similar to each other, and very similar to the values generated by the corresponding commercial software in eyes with treated DME. TRANSLATIONAL RELEVANCE: This software enables automatic total retinal thickness measurements across two OCT platforms, a process that is impractical to perform manually.

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