Analytical and Clinical Sample Performance Characteristics of the Onclarity Assay for the Detection of Human Papillomavirus.

The objective of this study was to determine the result reproducibility and performance of the BD Onclarity human papillomavirus (HPV) assay (Onclarity) on the BD Viper LT platform using both contrived and clinical specimens. Reproducibility was assessed in BD SurePath liquid-based cytology (LBC) medium (SurePath) using contrived panels (HPV genotype 16 [HPV16] positive, HPV18 positive, or HPV45 positive) or clinical specimens (HPV16, -18, -31, -33/58, -45, or -52 positive or HPV negative). In addition, specimens from 3,879 individuals from the Onclarity trial were aliquoted prior to or following cytology processing and tested for HPV. Finally, specimens were collected using either the Cervex-Brush or Cytobrush (or Cytobrush/spatula) for comparison of HPV results. Contrived specimens showed >95% concordance with the expected results, and pooled clinical specimens had standard deviations and coefficients of variation ranging from 0.87 to 1.86 and 2.9% to 5.6%, respectively. For precytology and postcytology aliquot analyses, specimens showed >98.0% overall agreement and mean differences in cycle threshold (CT ) scores for HPV ranging from -0.07 to 0.31. Positivity rates were close between the Cervex-Brush and Cytobrush/spatula for all age groups tested. Onclarity results are reproducible and reliable, regardless of sample collection before or after cytology aliquoting. Onclarity performs well regardless of the method of specimen collection (Cervex-Brush or Cytobrush/spatula) for cervical cancer screening.

Clinical Evaluation of BD Veritor SARS-CoV-2 Point-of-Care Test Performance Compared to PCR-Based Testing and versus the Sofia 2 SARS Antigen Point-of-Care Test.

The clinical performance of the BD Veritor System for Rapid Detection of SARS-CoV-2 nucleocapsid antigen (Veritor), a chromatographic immunoassay used for SARS-CoV-2 point-of-care testing, was evaluated using nasal specimens from individuals with COVID-19 symptoms. Two studies were completed to determine clinical performance. In the first study, nasal specimens and either nasopharyngeal or oropharyngeal specimens from 251 participants with COVID-19 symptoms (≤7 days from symptom onset [DSO], ≥18 years of age) were utilized to compare Veritor with the Lyra SARS-CoV-2 PCR assay (Lyra). In the second study, nasal specimens from 361 participants with COVID-19 symptoms (≤5 DSO, ≥18 years of age) were utilized to compare performance of Veritor to that of the Sofia 2 SARS Antigen FIA test (Sofia 2). The positive, negative, and overall percent agreement (PPA, NPA, and OPA, respectively) were the primary outcomes. In study 1, the PPA for Veritor, compared to Lyra, ranged from 81.8 to 87.5% across the 0 to 1 and 0 to 6 DSO ranges. In study 2, Veritor had PPA, NPA, and OPA values of 97.4, 98.1, and 98.1%, respectively, with Sofia 2. Discordant analysis showed one Lyra positive missed by Veritor and five Lyra positives missed by Sofia 2; one Veritor positive result was negative by Lyra. Veritor met FDA emergency use authorization (EUA) acceptance criteria for SARS-CoV-2 antigen testing for the 0 to 5 and 0 to 6 DSO ranges (PPA values of 83.9% and 82.4%, respectively). Veritor and Sofia 2 showed a high degree of agreement for SARS-CoV-2 detection. The Veritor test allows for more rapid COVID-19 testing utilizing easy-to-collect nasal swabs but demonstrated <100% PPA compared to PCR.

HPV infections and cytologic abnormalities in vaccinated women 21-34 years of age: Results from the baseline phase of the Onclarity trial.

OBJECTIVES: Countries with school-based human papillomavirus (HPV) vaccination have seen significant reductions in vaccine-targeted HPV infections, cytologic abnormalities, and high-grade cervical intraepithelial neoplasia (≥CIN2). However, the impact of HPV vaccination in the United States (where vaccination is largely opportunistic) may be less due to lower coverage rates and vaccination in patients at ages beyond the recommended routine vaccination age. METHODS: The Onclarity trial enrolled 33,858 subjects ≥21 years who were screened with cytology and the BD Onclarity HPV Assay. HPV positive women or those with cytologic abnormalities underwent colposcopy and biopsy. The prevalence of HPV, cytologic abnormalities, and ≥CIN2 was compared in a subset of 14,153, vaccinated and unvaccinated women, 21-34 years. Results were compared by vaccination status; Mantel-Haenszel analysis was performed to determine the association between vaccination status and prevalence, adjusting for age. RESULTS: The prevalence of overall HPV, HPV16, 18, 31, and 33/58 were all lower in vaccinated women for each age group; a significant difference (p < 0.001) was observed in vaccinated women for all ages combined. Cytologic low-grade squamous intraepithelial lesion (LSIL) or worse was lower in vaccinated women (p = 0.021), as was ≥CIN2 prevalence associated with HPV 16 or 18 (p = 0.011). CONCLUSIONS: Women with a prior history of HPV vaccination have a lower prevalence of any high-risk HPV, HPV 16, 18, 31, and 33/58; a cytology result of ≥LSIL, and ≥CIN2 associated with HPV 16/18 compared to unvaccinated women. A lower HPV prevalence in older, vaccinated women suggests that "catch-up" vaccination provides benefit.

The Onclarity Human Papillomavirus Trial: Design, methods, and baseline results.

OBJECTIVES: The baseline phase of the Onclarity trial was conducted to determine the screening performance of the Onclarity human papillomavirus (HPV) assay for detecting cervical cancer and precancer (≥CIN2) during triage of women ≥21 years with ASC-US cytology, as an adjunct test in women ≥30 years with normal cytology and for primary screening (HPV alone) in women ≥25 years. METHODS: 33,858 women ≥21 years were enrolled during routine clinic visits. All women with abnormal cytology, women ≥25 years that were high-risk HPV positive, and a random subset of women ≥25 years, negative by cytology and for HPV, were referred for colposcopy and cervical biopsy. Verification bias adjustment with 95% confidence intervals was applied. RESULTS: ASC-US prevalence was 5.8%. The overall HPV prevalence was 14.7%; for HPV 16, 18, and the 12 other HPV types it was 2.7%, 0.8%, and 11.2%, respectively. The prevalence of ASC-US and HPV was inversely proportional with age. The verification bias adjusted prevalence of ≥CIN2 and ≥CIN3 was 1.8% and 0.8%, respectively. Overall, five cases of cervical cancer were identified (all were HPV positive). The odds ratios associated with any HPV positive genotype, or with individual genotypes HPV 16, HPV 18, and HPV 31, for ≥CIN3, were statistically significant when compared to negative histology (p < 0.0001 for all). CONCLUSIONS: This report provides demographic information, cytology findings, HPV genotype information, and histopathology for participants in the baseline phase of this trial and offers further evidence to support genotype-specific screening for cervical cancer and precancer. Clinical Trial Registry URL:https://clinicaltrials.gov/ct2/show/NCT01944722.

Nesting ecology of Chelonia mydas (Testudines: Cheloniidae) on the Guanahacabibes Peninsula, Cuba.

The nesting colony of green sea turtles (Chelonia mydas) at Guanahacabibes Peninsula Biosphere Reserve and National Park is one of the largest in the Cuban archipelago; however, little information about its nesting ecology is available. Temporal and spatial variation in nesting and reproductive success as well as morphometric characteristics of gravid females were used to ecologically characterize this colony. Nine beaches of the Southernmost coast of Guanahacabibes Peninsula were monitored for 14 years (1998-2012) to determine green turtle nesting activity, from May to September (peak nesting season in this area). Beach dimensions were measured to determine nest density using the length and the area. Afterward the beaches were divided in two categories, index and secondary. Females were measured and tagged to compare new tagged females (823) with returning tagged females (140). Remigration interval was also determined. Temporal variation was identified as the annual number of nesting emergences and oviposits per female, with apparent peaks in reproductive activity on a biennial cycle in the first six years followed by periods of annual increase in nest number (2003-2008) and periods of decreasing number of nests (2010-2012). We also found intra-seasonal variation with the highest nesting activity in July, particularly in the second half of the month. The peak emergence time was 22:00-02:00 hr. In terms of spatial variation, smaller beaches had the highest nest density and nesting was more frequent 6-9m from the high tide line, where hatchling production was maximized although hatchling success was high on average, above 80%. Morphometric analysis of females was made and newly tagged turtles were smaller on average than remigrants. Our results are only a first attempt at characterizing Guanahacabibes' populations but have great value for establishing conservation priorities within the context of national management plans, and for efficient monitoring and protection of nesting beaches.

Accuracy of an antigen-detecting SARS-CoV-2 assay with self- and provider-collected specimens interpreted visually and with BD Veritor™ Plus analyzer.

Background: SARS-CoV-2 rapid antigen tests (RATs) are in high demand for reducing the spread of SARS-CoV-2. Reduced involvement from health care professionals (HCPs) for collection and interpretation could significantly foster the wide-spread implementation of RATs, but data evaluating RATs, when used by lay people, is limited. Objective: To valuate agreement between BD Veritor test results for self- and HCP-collected specimens, and visually- and analyzer-interpreted results. Methods: Individuals with onset of COVID-19 symptoms within five days of enrollment had three nasal swabs collected; one self-collected and the other two HCP-collected. One HCP-collected swab was stored for future testing while the order of the other two (self and HCP) was randomized before testing. with the BD Veritor System for Rapid Detection of SARS-CoV-2. Results were first assessed visually, followed by interpretation with the analyzer. Results: When self-collection was compared to HCP collection for SARS-CoV-2 detection, interpretation by analyzer resulted in positive percent agreement (PPA) of 94.7% (95% CI 82.7, 98.5) and negative percent agreement (NPA) of 99.0% (95% CI 97.5, 99.6). When visual interpretation was compared to analyzer-read results, collection by HCPs had a PPA of 97.4% (95% CI 86.5, 99.5) and NPA of 99.8% (95% CI 98.6, 100.0) while self-collection resulted in PPA of 94.9% (95% CI 83.1, 98.6) and NPA of 99.8% (95% CI 98.6, 100). Conclusions: Similar PPA and NPA were observed for self- and HCP-collected specimens as well as visually- and analyzer-interpreted tests. The equivalence in performance supports the use of expanded collection and testing methods.

Performance of a Vaginal Panel Assay Compared With the Clinical Diagnosis of Vaginitis.

OBJECTIVE: To compare the performance of vaginitis diagnosis based on clinical assessment to molecular detection of organisms associated with bacterial vaginosis, vulvovaginal candidiasis, and Trichomonas vaginalis using a vaginal panel assay. METHODS: This cross-sectional diagnostic accuracy study included 489 enrolled participants from five collection sites where those with vaginitis symptoms had a vaginal assay swab collected during their visit and a clinical diagnosis made. The swab was later sent to a separate testing site to perform the vaginal panel assay. Outcome measures include positive, negative, and overall percent agreement (and accompanying 95% CIs) of clinical assessment with the vaginal panel assay. P<.05 was used to distinguish significant differences in paired proportions between the vaginal panel assay and clinical diagnosis, using the McNemar test. Inter-rater agreement between the two diagnostic approaches was determined using Cohen's kappa coefficient. RESULTS: Clinical diagnosis had a positive percent agreement with the vaginal panel assay of 57.9% (95% CI 51.5-64.2%), 53.5% (95% CI 44.5-62.4%), and 28.0% (95% CI 12.1-49.4%) for bacterial vaginosis, vulvovaginal candidiasis, and T vaginalis, respectively. Negative percent agreement for clinical diagnosis was 80.2% (95% CI 74.3-85.2%), 77.0% (95% CI 72.1-81.4%), and 99.8% (95% CI 98.7-99.9%), respectively. Sixty-five percent (67/103), 44% (26/59), and 56% (10/18) of patients identified as having bacterial vaginosis, vulvovaginal candidiasis, and T vaginalis by assay, respectively, were not treated for vaginitis based on a negative clinical diagnosis. Compared with the assay, clinical diagnosis had false-positive rates of 19.8%, 23.0%, and 0.2% for bacterial vaginosis, vulvovaginal candidiasis, and T vaginalis, respectively. Significant differences in paired proportions were observed between the vaginal panel assay and clinical diagnosis for detection of bacterial vaginosis and T vaginalis. CONCLUSION: The vaginal panel assay could improve the diagnostic accuracy for vaginitis and facilitate appropriate and timely treatment. FUNDING SOURCE: Becton, Dickinson and Company.

Evaluation of the Onclarity HPV assay on the high-throughput COR system.

Background: Here we compare the performance of the high-throughput BD COR System (COR) to the Viper LT System (Viper) using the BD Onclarity HPV assay.Research Design and Methods: Remnant clinical specimens, contrived specimens in SurePath (BD) and PreservCyt (Hologic) media, and prospective clinical specimens in BD Cervical Brush Diluent (CBD) were tested. Outcomes included intra-laboratory agreement of Onclarity results on COR and inter-system agreement between COR and Viper.Results: Onclarity reproducibility on COR resulted in standard deviation and correlation of variation of Ct values ranging from 0.14 to 1.98 and 0.49% to 2.15%, respectively, for contrived specimens, and 0.9-3.08 and 2.89-9.21%, respectively, for clinical specimens. In the COR and Viper clinical agreement study, OPA for Onclarity ranged from 97.1%-98.9%, depending on the collection media type. PPA values for pooled, HPV(+) specimens at low positive (C95), and moderate positive (3XC95) target concentrations were ≥95.0% and 100%, respectively; PPA values associated with HPV 16, 18, 31, 45, 33/58, 52, 35/39/68, 51, and 56/59/66, individually, ranged from 93.8%-100%.Conclusions: Onclarity performance on COR is equivalent to Viper, and is accurate and reproducible for detection of all high-risk HPV genotypes, with a throughput of 330 results from a single 8-hour shift.

HPV Testing With 16, 18, and 45 Genotyping Stratifies Cancer Risk for Women With Normal Cytology.

OBJECTIVES: To determine the BD Onclarity human papillomavirus (HPV) assay performance and risk values for cervical intraepithelial neoplasia grade 2 (CIN2) or higher and cervical intraepithelial neoplasia grade 3 (CIN3) or higher during Papanicolaou/HPV cotesting in a negative for intraepithelial lesions or malignancies (NILM) population. METHODS: In total, 22,383 of the 33,858 enrolled women were 30 years or older with NILM cytology. HPV+ and a subset of HPV- patients (3,219/33,858 combined; 9.5%) were referred to colposcopy/biopsy. RESULTS: Overall, 7.9% of women were Onclarity positive; HPV 16 had the highest prevalence (1.5%). Verification bias-adjusted (VBA) CIN2 or higher and CIN3 or higher prevalences were 0.9% and 0.3%, respectively. Onclarity had VBA CIN2 or higher (44.1%) and CIN3 or higher (69.5%) sensitivities, as well as CIN2 or higher (92.4%) and CIN3 or higher (92.3%) specificities-all similar to Hybrid Capture 2. HPV 16, 18, 45, and the other 11 genotypes had CIN3 or higher risks of 6.9%, 2.6%, 1.1%, and 2.2%, respectively. CONCLUSIONS: Onclarity is clinically validated for cotesting in NILM women. Genotyping actionably stratifies women at greater CIN3 or higher risk.

Detection of Cervical Neoplasia by Human Papillomavirus Testing in an Atypical Squamous Cells-Undetermined Significance Population: Results of the Becton Dickinson Onclarity Trial.

Objectives: To determine clinical utility of Onclarity human papillomavirus (HPV) assay for atypical squamous cells-undetermined significance (ASC-US) triage, and the value of HPV genotyping within ASC-US. Methods: Women (n = 33,858; 21 years or older) had HPV testing using Onclarity and Hybrid Capture 2 (HC2). ASC-US individuals (n = 1,960, 5.8%) were referred to colposcopy. Results: Of ASC-US, 39.1% were HPV positive by Onclarity; HPV 16 was the most prevalent genotype (7.4%). Cervical intraepithelial neoplasia grade 2 (CIN 2) and CIN 3+ prevalences were 4.4% and 2.2%, respectively. Onclarity had sensitivity for CIN 2+ (85.7%) and CIN 3+ (91.4%), and specificities for CIN 2+ (64.1%) and CIN 3+ (62.0%), similar to HC2. Risks for CIN 3+ were 16.1%, 2.8%, 2.5%, and 2.7% with HPV 16, 18, 45, and 11 other genotypes, respectively. Conclusions: Onclarity is clinically validated for ASC-US triage. Through risk stratification, genotyping could help identify women at highest risk for CIN 3+.

Modeling loggerhead turtle movement in the Mediterranean: importance of body size and oceanography.

Adapting state-space models (SSMs) to telemetry data has been helpful for dealing with location error and for modeling animal movements. We used a combination of two hierarchical Bayesian SSMs to estimate movement pathways from Argos satellite-tag data for 15 juvenile loggerhead turtles (Caretta caretta) in the western Mediterranean Sea, and to probabilistically assign locations to one of two behavioral movement types and relate those behaviors to environmental features. A Monte Carlo procedure helped propagate location uncertainty from the first SSM into the estimation of behavioral states and environment--behavior relationships in the second SSM. Turtles using oceanic habitats of the Balearic Sea (n = 9 turtles) within the western Mediterranean were more likely to exhibit "intensive search" behavior as might occur during foraging, but only larger turtles responded to variations in sea-surface height. This suggests that they were better able than smaller turtles to cue on environmental features that concentrate prey resources or were more dependent on high-quality feeding areas. These findings stress the importance of individual heterogeneity in the analysis of movement behavior and, taken in concert with descriptive studies of Pacific loggerheads, suggest that directed movements toward patchy ephemeral resources may be a general property of larger juvenile loggerheads in different populations. We discovered size-based variation in loggerhead distribution and documented use of the western Mediterranean Sea by turtles larger than previously thought to occur there. With one exception, only individuals > 57 cm curved carapace length used the most westerly basin in the Mediterranean (western Alborán Sea). These observations shed new light on loggerhead migration phenology.

Multi-National, Multi-Institutional Analysis of Clinical Decision Support Data Needs to Inform Development of the HL7 Virtual Medical Record Standard.

An important barrier to the widespread dissemination of clinical decision support (CDS) is the heterogeneity of information models and terminologies used across healthcare institutions, health information systems, and CDS resources such as knowledge bases. To address this problem, the Health Level 7 (HL7) Virtual Medical Record project (an open, international standards development effort) is developing community consensus on the clinical information exchanged between CDS engines and clinical information systems. As a part of this effort, the HL7 CDS Work Group embarked on a multinational, collaborative effort to identify a representative set of clinical data elements required for CDS. Based on an analysis of CDS systems from 20 institutions representing 4 nations, 131 data elements were identified as being currently utilized for CDS. These findings will inform the development of the emerging HL7 Virtual Medical Record standard and will facilitate the achievement of scalable, standards-based CDS.

Nesting ecology of Chelonia mydas Testudines: Cheloniidae on the Guanahacabibes Peninsula, Cuba

The nesting colony of green sea turtles Chelonia mydas at Guanahacabibes Peninsula Biosphere Reserve and National Park is one of the largest in the Cuban archipelago; however, little information about its nesting ecology is available. Temporal and spatial variation in nesting and reproductive success as well as morphometric characteristics of gravid females were used to ecologically characterize this colony. Nine beaches of the Southernmost coast of Guanahacabibes Peninsula were monitored for 14 years 1998-2012 to determine green turtle nesting activity, from May to September peak nesting season in this area. Beach dimensions were measured to determine nest density using the length and the area. Afterward the beaches were divided in two categories, index and secondary. Females were measured and tagged to compare new tagged females 823 with returning tagged females 140. Remigration interval was also determined. Temporal variation was identified as the annual number of nesting emergences and oviposits per female, with apparent peaks in reproductive activity on a biennial cycle in the first six years followed by periods of annual increase in nest number 2003-2008 and periods of decreasing number of nests 2010-2012. We also found intra-seasonal variation with the highest nesting activity in July, particularly in the second half of the month. The peak emergence time was 22:00-02:00hr. In terms of spatial variation, smaller beaches had the highest nest density and nesting was more frequent 6-9m from the high tide line, where hatchling production was maximized although hatchling success was high on average, above 80. Morphometric analysis of females was made and newly tagged turtles were smaller on average than remigrants. Our results are only a first attempt at characterizing Guanahacabibes populations but have great value for establishing conservation priorities within the context of national management plans, and for efficient monitoring and protection of nesting beaches.

La colonia de Tortuga verde Chelonia mydas que anida en la Península de Guanahacabibeses es una de las más grandes del archipiélago cubano pero existe poca información disponible sobre la misma. Por ello utilizamos la variación espacial y temporal de la anidación así como el éxito reproductivo y las características morfométricas de las hembras grávidas para realizar la primera caracterización ecológica de esta colonia. Se estudiaron nueve playas durante 14 años 1998-2012 desde mayo hasta septiembre pico de anidación. Estas se dividieron en dos categorías: índices y secundarias. Las hembras fueron medidas y marcadas para comparar las nuevas hembras marcadas 823 con las remigrantes 140. Se detectó una variación temporal en la anidación a tres niveles: interanual, dentro de la temporada y durante la noche. Se observa un ciclo bienal en los primeros seis años, luego un incremento anual 2003-2008 seguido por un período de decrecimiento en las anidaciones 2010-2012. Dentro de la temporada se encontró un pico en el mes de julio aunque cambia de la primera quincena a la segunda en años diferentes y la hora de emergencia preferentemente de 22:00-02:00hr. En la variación espacial, las playas pequeñas tuvieron mayor densidad de anidación, especialmente entre los 6-9m hasta la línea media de marea alta, donde se maximiza la producción de neonatos, aunque el éxito de emergencia de los neonatos se mantuvo como promedio por encima del 80 en toda la playa. Morfométricamente las hembras remigrantes resultaron mayores como promedio que las marcadas por primera vez. Estos resultados son una primera aproximación para la caracterización de la colonia de Guanahacabibes pero tienen gran valor para establecer prioridades de conservación dentro del contexto de los planes de manejo nacionales así como para garantizar un monitoreo eficiente y la protección de las playas de anidación.