RESUMO
Introduction: Placental examination is valuable for diagnosing congenital syphilis, but the classic histological triad is not always observed. This study aimed to identify additional morphological clues, evaluate the sensitivity of IHC and qPCR, and investigate the impact of HIV co-infection and penicillin treatment on placental morphology. Materials and methods: Two hundred and fifteen placental specimens with treponemal infection were reviewed. Morphological findings, IHC, and qPCR results were analyzed. Results: Chronic villitis (94%), acute chorioamnionitis (91.6%), and villous immaturity (65.6%) were the most common abnormalities. HIV co-infection and penicillin treatment were associated with reduced frequencies of inflammatory lesions. IHC and qPCR exhibited sensitivities of 74.4 and 25.8%, respectively, confirming the diagnosis in 42 cases with negative or unknown serology. Conclusion: Villitis, chorioamnionitis, and villous immaturity were identified as the predominant placental abnormalities. HIV co-infection and penicillin treatment can impact morphology and hamper the diagnosis. IHC and q-PCR are valuable adjuncts when serology is negative.
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Corioamnionite , Coinfecção , Infecções por HIV , Sífilis , Humanos , Feminino , Gravidez , Sífilis/diagnóstico , Sífilis/tratamento farmacológico , Sífilis/complicações , Treponema pallidum/genética , Placenta/patologia , Corioamnionite/diagnóstico , Corioamnionite/tratamento farmacológico , Imuno-Histoquímica , Coinfecção/diagnóstico , Coinfecção/tratamento farmacológico , Coinfecção/complicações , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/patologia , Reação em Cadeia da Polimerase/métodos , Penicilinas/uso terapêuticoRESUMO
Omicron lineages BA.4 and BA.5 drove a fifth wave of COVID-19 cases in South Africa. Here, we use the presence/absence of the S-gene target as a proxy for SARS-CoV-2 variant/lineage for infections diagnosed using the TaqPath PCR assay between 1 October 2021 and 26 April 2022. We link national COVID-19 individual-level data including case, laboratory test and hospitalisation data. We assess severity using multivariable logistic regression comparing the risk of hospitalisation and risk of severe disease, once hospitalised, for Delta, BA.1, BA.2 and BA.4/BA.5 infections. After controlling for factors associated with hospitalisation and severe outcome respectively, BA.4/BA.5-infected individuals had a similar odds of hospitalisation (aOR 1.24, 95% CI 0.98-1.55) and severe outcome (aOR 0.72, 95% CI 0.41-1.26) compared to BA.1-infected individuals. Newly emerged Omicron lineages BA.4/BA.5 showed similar severity to the BA.1 lineage and continued to show reduced clinical severity compared to the Delta variant.
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COVID-19 , SARS-CoV-2 , COVID-19/epidemiologia , Humanos , SARS-CoV-2/genética , África do Sul/epidemiologiaRESUMO
Three lineages (BA.1, BA.2 and BA.3) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern predominantly drove South Africa's fourth Coronavirus Disease 2019 (COVID-19) wave. We have now identified two new lineages, BA.4 and BA.5, responsible for a fifth wave of infections. The spike proteins of BA.4 and BA.5 are identical, and similar to BA.2 except for the addition of 69-70 deletion (present in the Alpha variant and the BA.1 lineage), L452R (present in the Delta variant), F486V and the wild-type amino acid at Q493. The two lineages differ only outside of the spike region. The 69-70 deletion in spike allows these lineages to be identified by the proxy marker of S-gene target failure, on the background of variants not possessing this feature. BA.4 and BA.5 have rapidly replaced BA.2, reaching more than 50% of sequenced cases in South Africa by the first week of April 2022. Using a multinomial logistic regression model, we estimated growth advantages for BA.4 and BA.5 of 0.08 (95% confidence interval (CI): 0.08-0.09) and 0.10 (95% CI: 0.09-0.11) per day, respectively, over BA.2 in South Africa. The continued discovery of genetically diverse Omicron lineages points to the hypothesis that a discrete reservoir, such as human chronic infections and/or animal hosts, is potentially contributing to further evolution and dispersal of the virus.
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COVID-19 , SARS-CoV-2 , Aminoácidos , Animais , COVID-19/epidemiologia , Humanos , SARS-CoV-2/genética , África do Sul/epidemiologia , Glicoproteína da Espícula de Coronavírus/genéticaRESUMO
BACKGROUND: The SARS-CoV-2 omicron variant of concern was identified in South Africa in November, 2021, and was associated with an increase in COVID-19 cases. We aimed to assess the clinical severity of infections with the omicron variant using S gene target failure (SGTF) on the Thermo Fisher Scientific TaqPath COVID-19 PCR test as a proxy. METHODS: We did data linkages for national, South African COVID-19 case data, SARS-CoV-2 laboratory test data, SARS-CoV-2 genome data, and COVID-19 hospital admissions data. For individuals diagnosed with COVID-19 via TaqPath PCR tests, infections were designated as either SGTF or non-SGTF. The delta variant was identified by genome sequencing. Using multivariable logistic regression models, we assessed disease severity and hospitalisations by comparing individuals with SGTF versus non-SGTF infections diagnosed between Oct 1 and Nov 30, 2021, and we further assessed disease severity by comparing SGTF-infected individuals diagnosed between Oct 1 and Nov 30, 2021, with delta variant-infected individuals diagnosed between April 1 and Nov 9, 2021. FINDINGS: From Oct 1 (week 39), 2021, to Dec 6 (week 49), 2021, 161 328 cases of COVID-19 were reported in South Africa. 38 282 people were diagnosed via TaqPath PCR tests and 29 721 SGTF infections and 1412 non-SGTF infections were identified. The proportion of SGTF infections increased from two (3·2%) of 63 in week 39 to 21 978 (97·9%) of 22 455 in week 48. After controlling for factors associated with hospitalisation, individuals with SGTF infections had significantly lower odds of admission than did those with non-SGTF infections (256 [2·4%] of 10 547 vs 121 [12·8%] of 948; adjusted odds ratio [aOR] 0·2, 95% CI 0·1-0·3). After controlling for factors associated with disease severity, the odds of severe disease were similar between hospitalised individuals with SGTF versus non-SGTF infections (42 [21%] of 204 vs 45 [40%] of 113; aOR 0·7, 95% CI 0·3-1·4). Compared with individuals with earlier delta variant infections, SGTF-infected individuals had a significantly lower odds of severe disease (496 [62·5%] of 793 vs 57 [23·4%] of 244; aOR 0·3, 95% CI 0·2-0·5), after controlling for factors associated with disease severity. INTERPRETATION: Our early analyses suggest a significantly reduced odds of hospitalisation among individuals with SGTF versus non-SGTF infections diagnosed during the same time period. SGTF-infected individuals had a significantly reduced odds of severe disease compared with individuals infected earlier with the delta variant. Some of this reduced severity is probably a result of previous immunity. FUNDING: The South African Medical Research Council, the South African National Department of Health, US Centers for Disease Control and Prevention, the African Society of Laboratory Medicine, Africa Centers for Disease Control and Prevention, the Bill & Melinda Gates Foundation, the Wellcome Trust, and the Fleming Fund.
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COVID-19/fisiopatologia , Hospitalização/estatística & dados numéricos , SARS-CoV-2/genética , Índice de Gravidade de Doença , Adolescente , Adulto , COVID-19/epidemiologia , COVID-19/virologia , Teste de Ácido Nucleico para COVID-19 , Criança , Pré-Escolar , Feminino , Genoma Viral , Humanos , Armazenamento e Recuperação da Informação , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , África do Sul/epidemiologia , Adulto JovemRESUMO
Continued uncontrolled transmission of SARS-CoV-2 in many parts of the world is creating conditions for substantial evolutionary changes to the virus1,2. Here we describe a newly arisen lineage of SARS-CoV-2 (designated 501Y.V2; also known as B.1.351 or 20H) that is defined by eight mutations in the spike protein, including three substitutions (K417N, E484K and N501Y) at residues in its receptor-binding domain that may have functional importance3-5. This lineage was identified in South Africa after the first wave of the epidemic in a severely affected metropolitan area (Nelson Mandela Bay) that is located on the coast of the Eastern Cape province. This lineage spread rapidly, and became dominant in Eastern Cape, Western Cape and KwaZulu-Natal provinces within weeks. Although the full import of the mutations is yet to be determined, the genomic data-which show rapid expansion and displacement of other lineages in several regions-suggest that this lineage is associated with a selection advantage that most plausibly results from increased transmissibility or immune escape6-8.
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COVID-19/virologia , Mutação , Filogenia , Filogeografia , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/transmissão , Análise Mutacional de DNA , Evolução Molecular , Aptidão Genética , Humanos , Evasão da Resposta Imune , Modelos Moleculares , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade , Seleção Genética , África do Sul/epidemiologia , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Fatores de TempoRESUMO
The first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in South Africa was identified on 5 March 2020, and by 26 March the country was in full lockdown (Oxford stringency index of 90)1. Despite the early response, by November 2020, over 785,000 people in South Africa were infected, which accounted for approximately 50% of all known African infections2. In this study, we analyzed 1,365 near whole genomes and report the identification of 16 new lineages of SARS-CoV-2 isolated between 6 March and 26 August 2020. Most of these lineages have unique mutations that have not been identified elsewhere. We also show that three lineages (B.1.1.54, B.1.1.56 and C.1) spread widely in South Africa during the first wave, comprising ~42% of all infections in the country at the time. The newly identified C lineage of SARS-CoV-2, C.1, which has 16 nucleotide mutations as compared with the original Wuhan sequence, including one amino acid change on the spike protein, D614G (ref. 3), was the most geographically widespread lineage in South Africa by the end of August 2020. An early South African-specific lineage, B.1.106, which was identified in April 2020 (ref. 4), became extinct after nosocomial outbreaks were controlled in KwaZulu-Natal Province. Our findings show that genomic surveillance can be implemented on a large scale in Africa to identify new lineages and inform measures to control the spread of SARS-CoV-2. Such genomic surveillance presented in this study has been shown to be crucial in the identification of the 501Y.V2 variant in South Africa in December 2020 (ref. 5).
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COVID-19/epidemiologia , COVID-19/virologia , SARS-CoV-2/genética , Conjuntos de Dados como Assunto , Genoma Viral , Humanos , Tipagem Molecular , Mutação , Pandemias , Filogenia , Filogeografia , Reação em Cadeia da Polimerase em Tempo Real , SARS-CoV-2/classificação , SARS-CoV-2/isolamento & purificação , Análise de Sequência de RNA , África do Sul/epidemiologia , Sequenciamento Completo do GenomaRESUMO
BACKGROUND: Regular HIV-1 viral load monitoring forms an essential part of any successful HIV-1 treatment programme. Abbott Molecular recently released the Alinity m HIV-1 assay to be run on the Alinity m System, a fully automated, continuous and random access analyser using ReadiFlex™ technology. OBJECTIVES: Our study investigated the performance of the Alinity m HIV-1 assay in comparison to the cobas® HIV-1 test in a high-throughput molecular laboratory. STUDY DESIGN: We compared the performance of the Alinity m HIV-1 assay with the cobas® HIV-1 test, performed on both the cobas® 4800 and cobas® 6800 systems at three clinically relevant thresholds (50, 200 and 1000 cp/mL). RESULTS: Excellent correlation (r = 0.98) and agreement (mean bias -0.004 Log10 cp/mL) was achieved between the cobas® 4800 and Alinity m HIV-1 assay. While there was good correlation between the Alinity m HIV-1 assay and the cobas® 6800 (r = 0.99), Bland-Altman analysis indicated that the cobas® 6800 on average measured 0.22 Log10 cp/mL higher than the Alinity m HIV-1 assay across the dynamic range. Percentage agreement was excellent at the 200 cp/mL and 1000 cp/mL thresholds and was slightly lower at 50 cp/mL in comparison with the cobas® systems. CONCLUSIONS: The Alinity m HIV-1 assay compared well with the cobas® HIV-1 test on both the cobas® 4800 and cobas® 6800 systems in a high-throughput molecular laboratory in South Africa, a low- to middle-income country.
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Infecções por HIV , HIV-1 , Infecções por HIV/diagnóstico , HIV-1/genética , Humanos , Laboratórios , RNA , RNA Viral , Kit de Reagentes para Diagnóstico , Sensibilidade e Especificidade , África do Sul , Carga ViralRESUMO
BACKGROUND: Accurate molecular methods to detect and quantify hepatitis B virus (HBV) DNA are essential to diagnose chronic infections, guide treatment decisions, assess response to treatment, and determine risk of HBV-related complications. New generations of real-time HBV DNA assay platforms provide results in less than 2-3 h, with continuous loading of specimens and true random-access capability. OBJECTIVES: We examined the clinical performance of the new Alinity m HBV assay, run on the fully automated, continuous, random-access Alinity m platform, to accurately detect and quantify HBV DNA in a large series of patient samples infected with different HBV genotypes frequently encountered in clinical practice. STUDY DESIGN: This international, multisite study assessed the precision and reproducibility of the Alinity m HBV assay and compared its performance to four HBV assays currently in clinical use. RESULTS: The Alinity m HBV assay demonstrated linear quantitation of HBV DNA in plasma samples, with high precision (coefficient of variation 4.1 %-8.8 %) and reproducibility. The Alinity m HBV assay showed excellent correlation (correlation coefficients ≥0.947) with comparator HBV assays, with an overall observed bias ranging from -0.07 to 0.17 Log10 IU/mL. 97 % of quantifiable patient results were <1 Log10 IU/mL different than the respective comparator assays, with comparable results across HBV genotypes. CONCLUSIONS: The newly developed real-time PCR-based Alinity m HBV assay is sensitive, reproducible, and accurately quantifies HBV DNA levels from HBsAg-positive patients across the full dynamic range of quantification.
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Vírus da Hepatite B , Hepatite B , DNA Viral , Vírus da Hepatite B/genética , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Carga ViralRESUMO
BACKGROUND: Nucleic acid testing is essential for the detection and quantification of HCV RNA in the diagnosis of HCV infection and treatment monitoring. The Alinity m HCV assay was recently developed by Abbott Molecular for rapid detection and quantification of HCV RNA on the fully automated, continuous, random-access Alinity m analyzer. OBJECTIVES: Our study assessed the performance of the new Alinity m HCV assay for detection and quantification of HCV RNA in a large series of patient samples of various genotypes. This international, multicentric study evaluated the linearity, precision, and reproducibility of the Alinity m HCV assay and its performance in comparison to three other HCV assays currently used in clinical practice. RESULTS: The Alinity m HCV assay demonstrated high linearity (correlation coefficient râ¯=â¯1.00), precision (coefficients of variation [CV] 6.6-13.5 %) and reproducibility (CV 1.7-4.3 % across three control lots). At a concentration near the lower limit of detection, the Alinity m HCV assay exhibited >98 % detectability. The Alinity m HCV assay showed excellent correlation with comparator HCV assays in serum (nâ¯=â¯406) and plasma (nâ¯=â¯1401) samples (correlation coefficients ≥0.96, bias 0.01 to 0.14 Log10 IU/mL). More than 95 % of the quantified results with the Alinity m HCV assay were less than mean bias ± 1.96 SD different from those of the comparator assays. CONCLUSIONS: The newly developed Alinity m HCV assay is sensitive, reproducible, and accurately quantifies HCV RNA levels in serum and plasma samples from patients with chronic HCV infection, with no impact of HCV genotype on assay performance.
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Hepacivirus , Hepatite C , Genótipo , Hepacivirus/genética , Humanos , RNA Viral , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Carga ViralRESUMO
BACKGROUND: Accurate, rapid detection of HIV-1 RNA is critical for early diagnosis, treatment decision making, and long-term management of HIV-1 infection. OBJECTIVE: We evaluated the diagnostic performance of the Alinity m HIV-1 assay, which uses a dual target/dual probe design against highly conserved target regions of the HIV-1 genome and is run on the fully automated Alinity m platform. STUDY DESIGN: This was an international, multisite study that compared the diagnostic performance of the Alinity m HIV-1 assay to four commercially available HIV-1 assays routinely used in nine independent clinical laboratories. Alinity m HIV-1 assay precision, detectability, and reproducibility was compared across four study sites. RESULTS: The Alinity m HIV-1 assay produced comparable results to currently available HIV-1 assays (correlation coefficient >0.995), with an overall bias of -0.1 to 0.10 Log10 copies/mL. The Alinity m HIV-1 assay and its predecessor m2000 HIV-1 assay demonstrated comparable detection of 16 different HIV-1 subtypes (R2â¯=â¯0.956). A high level of agreement (>88 %) between all HIV-1 assays was seen near clinical decision points of 1.7 Log10 copies/mL (50 copies/mL) and 2.0 Log10 copies/mL (200 copies/mL). Alinity m HIV-1 assay precision was 0.08 and 0.21 Log10 copies/mL at VLs of 1000 and 50 copies/mL, respectively, with a high level of detectability (≥97 % hit rate) and reproducibility across sites. CONCLUSIONS: The Alinity m HIV-1 assay provides comparable diagnostic accuracy to current HIV-1 assays, and when run on the Alinity m system, has the capacity to shorten the time between diagnosis and treatment.
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Infecções por HIV , HIV-1 , HIV-1/genética , Humanos , RNA Viral , Kit de Reagentes para Diagnóstico , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Carga ViralRESUMO
OBJECTIVE: There are limited long-term data that has examined postoperative quality-of-life measures following placement of midurethral sling (MUS) for stress urinary incontinence (SUI). The SEAPI incontinence questionnaire includes 5 data points that rate severity of specific urinary symptoms. Our aim was to describe changes in SEAPI questionnaire outcomes 1 year following sling placement. METHODS: We retrospectively reviewed women who underwent MUS for SUI from 2005 to 2012. We included those women who had completed preoperative and postoperative (>12 months) SEAPI scores. Individual S, E, A, P, I score cure was defined as postoperative score of 0 (>0 preoperative). Logistic regression analysis was used to model the effects of patient characteristics on incontinence cure and S, E, A, P, I scores. RESULTS: A total of 584 women were included. Median follow-up was 25.4 months (12-126.8 months). Follow-up duration and baseline S, P, and I scores were associated with significantly lower odds of overall incontinence cure, whereas rectocele grade has positive association (odds ratio, 1.31; P = 0.040). Type of sling did not impact overall incontinence cure or cure of individual SEAPI scores. CONCLUSIONS: Preoperative S, P, and I scores had negative association with stress incontinence cure. Cure of individual S, E, A, P, I scores was impacted differently by various patient factors. The SEAPI questionnaire provides a unique profile of patient-reported and functional measures in women with SUI and may be helpful in those who undergo MUS.
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Qualidade de Vida , Incontinência Urinária por Estresse/cirurgia , Humanos , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Retrospectivos , Slings Suburetrais/classificação , Inquéritos e Questionários , Incontinência Urinária por Estresse/psicologiaRESUMO
OBJECTIVES: To review the role of multiparametric magnetic resonance imaging (mpMRI) for active surveillance (AS) of prostate cancer. MATERIALS AND METHODS: We performed a comprehensive search of Medline and Embase databases for relevant articles in the English language. Search terms included 'prostate cancer', 'active surveillance' or 'monitoring', 'expectant management', and 'MRI'. We also reviewed practice guidelines from recognized international associations or societies involved in prostate cancer care. Articles were selected by both authors for relevance to the subject matter. RESULTS: The ability of mpMRI to visualize primarily high-grade tumours within the prostate may improve risk stratification for men considering AS for prostate cancer. Multiple mostly single-institution studies have found that the addition of mpMRI and a targeted biopsy strategy can improve AS patient selection over standard TRUS biopsy alone. The high negative predictive value of mpMRI may allow men to avoid early repeat biopsy and may offer the possibility to tailor biopsy strategies. The presence of a radiographically positive lesion on mpMRI at baseline is predictive of higher likelihood of radiographic progression over time while on AS. CONCLUSIONS: MRI has shown promise in both patient selection and monitoring for men who undergo AS for prostate cancer. There are multiple barriers to the widespread use of mpMRI for AS including quality, cost and access to care.
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Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias da Próstata/diagnóstico por imagem , Progressão da Doença , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Próstata/diagnóstico por imagem , Próstata/patologia , Neoplasias da Próstata/patologiaRESUMO
BACKGROUND: Data on the susceptibility of influenza viruses from South Africa to neuraminidase inhibitors (NAIs) are scarce, and no extensive analysis was done. OBJECTIVES: We aimed to determine oseltamivir and zanamivir susceptibility of influenza A and B virus neuraminidases (NAs), 2007-2013, South Africa. PATIENTS/METHODS: We enrolled participants through national influenza-like illness surveillance, 2007-2013. Influenza diagnosis was by virus isolation and quantitative polymerase chain reaction (qPCR). Drug susceptibility was determined by chemiluminescence-based NA-STAR/NA-XTD assay. Sanger sequencing was used to determine molecular markers of NAI resistance. RESULTS: Forty percent (6341/15 985) of participants were positive for influenza viruses using virus isolation (2007-2009) and qPCR (2009-2013) methods. A total of 1236/6341 (19.5%) virus isolates were generated of which 307/1236 (25%) were tested for drug susceptibility. During 2007-2008, the median 50% inhibitory concentration (IC50 ) of oseltamivir for seasonal influenza A(H1N1) increased from of 0.08 nmol/L (range 0.01-3.60) in 2007 to 73 nmol/L (range 1.56-305 nmol/L) in 2008. Influenza A isolates from 2009 to 2013 were susceptible to oseltamivir [A(H3N2) median IC50 = 0.05 nmol/L (range 0.01-0.08); A(H1N1)pdm09 = 0.11 nmol/L (range 0.01-0.78)] and zanamivir [A(H3N2) median IC50 = 0.56 nmol/L (range 0.47-0.66); A(H1N1)pdm09 = 0.35 nmol/L (range 0.27-0.533)]. Influenza B viruses were susceptible to both NAIs. NAI resistance-associated substitutions H275Y, E119V, and R150K (N1 numbering) were not detected in influenza A viruses that circulated in 2009-2013. CONCLUSIONS: We confirm replacement of NAI susceptible by resistant phenotype influenza A(H1N1) in 2008. Influenza A and B viruses (2009-2013) remained susceptible to NAIs; therefore, these drugs are useful for treating influenza-infected patients.
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Farmacorresistência Viral/genética , Inibidores Enzimáticos/farmacologia , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A/efeitos dos fármacos , Vírus da Influenza B/efeitos dos fármacos , Substituição de Aminoácidos , Humanos , Vírus da Influenza A Subtipo H1N1/enzimologia , Vírus da Influenza A Subtipo H1N1/genética , Influenza Humana/virologia , Concentração Inibidora 50 , Neuraminidase/antagonistas & inibidores , Oseltamivir/uso terapêutico , Fenótipo , Estações do Ano , Vigilância de Evento Sentinela , África do Sul , Proteínas Virais/antagonistas & inibidores , Zanamivir/uso terapêuticoRESUMO
For men with lower risk prostate cancer, there is ever-growing literature that demonstrates the oncologic safety of deferring radical treatment and opting for regular monitoring for disease progression. This strategy's success is largely owed to appropriate, systematic monitoring protocols that typically employ various prostate specific antigen (PSA) metrics or digital rectal exam (DRE) findings. Novel biologic markers and advanced imaging techniques have shown promise in active surveillance (AS) populations such as for use of patient candidacy as well as detection of disease progression. This review summarizes contemporary surveillance protocols as well as the emerging technologies which demonstrate significant potential to improve such protocols.
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OBJECTIVE: Recently approved direct acting antivirals provide transformative therapies for chronic hepatitis C virus (HCV) infection. The major clinical challenge remains to identify the undiagnosed patients worldwide, many of whom live in low-income and middle-income countries, where access to nucleic acid testing remains limited. The aim of this study was to develop and validate a point-of-care (PoC) assay for the qualitative detection of HCV RNA. DESIGN: We developed a PoC assay for the qualitative detection of HCV RNA on the PCR Genedrive instrument. We validated the Genedrive HCV assay through a case-control study comparing results with those obtained with the Abbott RealTime HCV test. RESULTS: The PoC assay identified all major HCV genotypes, with a limit of detection of 2362 IU/mL (95% CI 1966 to 2788). Using 422 patients chronically infected with HCV and 503 controls negative for anti-HCV and HCV RNA, the Genedrive HCV assay showed 98.6% sensitivity (95% CI 96.9% to 99.5%) and 100% specificity (95% CI 99.3% to 100%) to detect HCV. In addition, melting peak ratiometric analysis demonstrated proof-of-principle for semiquantification of HCV. The test was further validated in a real clinical setting in a resource-limited country. CONCLUSION: We report a rapid, simple, portable and accurate PoC molecular test for HCV, with sensitivity and specificity that fulfils the recent FIND/WHO Target Product Profile for HCV decentralised testing in low-income and middle-income countries. This Genedrive HCV assay may positively impact the continuum of HCV care from screening to cure by supporting real-time treatment decisions. TRIAL REGISTRATION NUMBER: NCT02992184 .
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Hepacivirus/genética , Hepatite C Crônica/virologia , RNA Viral/genética , Carga Viral/métodos , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Sistemas Automatizados de Assistência Junto ao Leito , Reação em Cadeia da Polimerase/métodos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Anterior zone (AZ) disease is present in one-fifth of men with newly diagnosed prostate cancer and has been associated with poor pathologic features. However, anterior targeted biopsies are not a routine part of active surveillance (AS) protocols. Our purpose is to assess the utility of AZ sampling for prostate biopsy in patients undergoing surveillance for low-risk prostate cancer. METHODS: A prospective data collection of men enrolled in AS between 2006 and 2014 was performed. Patient and disease characteristics were collected, including number of positive cores and Gleason score on all diagnostic and surveillance biopsies. Progression was defined as incident Gleason > 6 in any core and/or receipt of definitive therapy including radical prostatectomy or radiotherapy. Rate of anterior disease and relationship to subsequent disease progression was assessed. RESULTS: A total of 85 men were included, of which 45% demonstrated progression. Median follow-up was 40 months. Among those undergoing AZ sampling at initial diagnosis, 37% presented with AZ disease. A total of 47% of men with AZ-only disease progressed, whereas 78% of men with AZ and peripheral zone disease progressed. This compares with a 39% rate of progression among men with only peripheral zone disease. Multivariable logistic regression identified increasing body mass index as a significant predictor of disease progression (odds ratio, 5.18; 95% confidence interval, 1.06-25.31; P = .04). CONCLUSIONS: Over one-third of men enrolled in AS for low-risk prostate cancer had AZ disease on diagnostic biopsy. Progression occurred in the majority of these men. AZ sampling should be considered in biopsy surveillance strategies.
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PURPOSE: A variety of clinical and imaging findings are used by clinicians to determine utility of renal angioembolization (AE) in managing renal trauma. Our purpose was to investigate specific criteria that clinicians who manage high-grade renal trauma (HGRT) utilize in decision-making for primary or delayed AE. METHODS: A total of 413 urologists and interventional radiologists (IRs) who practice at level 1 or 2 trauma centers within the United States were provided an original survey via email on experience and opinions regarding the utility of AE for HGRT. We described overall practice patterns and assessed differences by clinician type, using the Fisher's exact test. RESULTS: A total of 79 (20 %) clinicians completed the survey. All clinicians had AE capability for HGRT management. A higher proportion of IRs reported using AE for grade I-II (33 vs. 3 %, p = 0.002), grade III (65 vs. 26 %, p = 0.001), and penetrating injuries (83 vs. 58 %, p = 0.02). A greater proportion of urologists reported using AE for grade V injuries (81 vs. 56 %, p = 0.03). Clinicians most commonly cited computed tomography evidence of active arterial bleeding (97 %), or arteriovenous fistula/pseudoaneurysm (94 %) as indications for primary AE, and 62 % identified concurrent visceral injury as factor that would necessitate surgical intervention. CONCLUSION: In a survey of clinicians, we report that IRs and urologists utilize AE differently when managing HGRT, as a higher proportion of IRs use AE to manage lower grade as well as penetrating injuries. Validation studies are needed to establish algorithms to identify patients with HGRT who would benefit from selective renal AE.
Assuntos
Traumatismos Abdominais/cirurgia , Embolização Terapêutica/métodos , Hemorragia/terapia , Rim/lesões , Artéria Renal/lesões , Traumatismos Abdominais/complicações , Traumatismos Abdominais/diagnóstico , Adulto , Idoso , Angiografia/métodos , Feminino , Hemorragia/diagnóstico por imagem , Hemorragia/etiologia , Humanos , Rim/irrigação sanguínea , Rim/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Artéria Renal/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
OBJECTIVE: To characterize complications of prostate cancer therapy and operative management in patients referred to our institution for surgical intervention. MATERIALS AND METHODS: Data was abstracted from a retrospectively collected single surgeon database at a large tertiary care referral-based medical center. Variables included age, prostate cancer therapy, complication(s) and their management, and number of operations. Descriptive statistics were used. RESULTS: From 2006-2010, 890 patients underwent genitourinary surgery, of which 139 were to treat complications arising from prostate cancer therapy. Complications stemmed from radical prostatectomy (RP) monotherapy, RP and external beam radiation therapy (EBRT) or brachytherapy (BT), EBRT only, BT only, and combination EBRT and BT. Complications included urinary incontinence (UI), urethral strictures, bladder neck contractures, and fistulas. UI and bladder neck contractures were more common in patients treated with RP or RP with EBRT or BT. Strictures and fistulas were common in patients treated with EBRT or BT. Interventions included direct vision internal urethrotomy, artificial urinary sphincter, urethral reconstruction, UroLume urethral stent, urethral sling, repair of fistulas, and balloon dilation. Forty eight percent of patients required multiple operations. The median number of interventions was two. CONCLUSIONS: We operatively managed patients treated with non-surgical and surgical modalities for prostate cancer. Complications included UI, fistulas, strictures, and bladder neck contractures. These were managed with a variety of operative interventions. As more men undergo treatment for localized disease, more will inevitably have complications stemming from interventions.
RESUMO
OBJECTIVE: To describe the effect of serial prostate biopsy on lower urinary tract symptoms (LUTS) in men who undergo active surveillance (AS) at a large academic institution. MATERIALS AND METHODS: This is a retrospective study of men enrolled in AS for ≥6 months who underwent ≥1 biopsy and completed ≥1 International Prostate Symptom Score (IPSS) questionnaire. In additional to total IPSS, we report the mean difference between the first and last questionnaires for patients who completed ≥2 questionnaires. Multivariate models, adjusting for disease features, age, race, prostate volume and baseline, or incident benign prostatic hypertrophy (BPH), were used to assess relationships between IPSS and total biopsy exposure. RESULTS: Four hundred eighty-two men were eligible, and 291 completed ≥2 IPSS questionnaires. Overall, mean (standard deviation) age was 61.7 (7.8) years, and median prostate volume (interquartile range) was 42 (34-61) mL. At baseline, 11% provided history of BPH. Among men who completed multiple questionnaires, 25% experienced clinically significant worsening (IPSS increase ≥4 points). In regression model, total IPSS was not significantly associated with greater biopsy exposure (P = .25). IPSS change from initial and the latest questionnaire was not significantly associated with initial or interval biopsy exposure in an adjusted longitudinal model (P = .64 and .50, respectively), but a trend was observed with greater age decade (+4.07 points, 95% CI -0.30 to 8.4; P = .07). CONCLUSION: Repeated prostate biopsy does not appear to independently pose additional risk of LUTS in an AS population. In unadjusted analyses, greater biopsy exposure is a surrogate for increasing follow-up time, age, and BPH risk, and thus, risk of LUTS onset and progression.