Human papillomavirus testing in primary cervical screening and the cut-off level for hybrid capture 2 tests: systematic review

Objective To determine the trade-off between the sensitivity and the specificity for high grade cervical intraepithelial neoplasia at hybrid capture 2 cut-off values above the standard ≥1 relative light units/cut-off level (rlu/co)

Rumlig organisering for læring: Arkitektstuderendes oplevelser af en tegnesal til 180 personer

Denne undersøgelse handler om arkitektstuderendes oplevelse af at studere i en tegnesal på 750 m2 med 180 studerende. Casen er et obligatorisk kursus for førsteårsstuderende og det empiriske afsæt er studerendes ugentlige logbøger, interviews og egne noter fra forfatterne, der er ansvarlige undervisere. Der anlægges det perspektiv, at læring konstitueres i dynamiske fællesskaber af aktør-netværk af bl.a. mennesker, traditioner, rum og materialitet (Latour, 2005; Akrich 1992, Lave & Wenger 2003; Keiding, 2012; Tanggaard & Szulevicsz 2013). Undersøgelsen udfolder oplevede fordele og ulemper ved at studere i tegnesalen, ligesom den peger på præsentationer i plenum, antallet af personer og kurset 1:1 dimension, som centrale opmærksomhedspunkter

Accuracy of genotyping for HPV16 and 18 to triage women with low-grade squamous intraepithelial lesions: a pooled analysis of VALGENT studies

Background: Genotyping for the most carcinogenic human papillomavirus (HPV) types (HPV16/HPV18) can identify high risk of underlying cervical precancer and guide further management.Research design and methods: A pooled analysis was performed of the clinical accuracy of high-risk HPV (hrHPV) testing and HPV16/18 genotyping in triage of women with low-grade squamous intraepithelial lesions (LSIL). Data regarding 24 assays evaluated in four VALGENT validation panels were used.Results: In women with LSIL, hrHPV had a pooled sensitivity for CIN2+ of 95.5% (95% CI: 91.0-97.8%) and a specificity of 25.3% (95% CI: 22.2-28.6%). HPV16/18 genotyping had a sensitivity and specificity for CIN2+ of 52.9% (95% CI: 48.4-57.4%) and 83.5% (95% CI: 79.9-86.5%), respectively. The average risk of CIN2+ was 46.1% when HPV16/18-positive, 15.5% in women who were HPV16/18-negative but positive for other hrHPV types and 4.3% for hrHPV-negative women.Conclusions: Triage of women with LSIL with HPV16/18 genotyping increases the positive predictive value compared to hrHPV testing but at the expense of lower sensitivity. Arguably, women testing positive for HPV16/18 need further clinical work-up. Whether colposcopy referral or further surveillance is recommended for women with other hrHPV types may depend on the post-test risk of precancer and the local risk-based decision thresholds

Different Professional Ideal Types in the Inter-sectoral Management of Psychiatric Healthcare Trajectories

Aim: To investigate how differences in types of professions and rationalities affect the management of inter-sectoral trajectories in psychiatric health care in the Capital Region of Denmark. Background: Some psychiatry users experience a lack of coherence between the mental health care treatment provided at hospitals and run by the regions, and that provided at residential psychiatric units run by municipalities. The literature points to various challenges in this field of research, related to transitions that need rethinking and further examination. Method: The approach is an eclectic use of theory and methods in a theory-governed analysis of empirical data built up from focus group interviews with professionals in mental health care centres and social psychiatric residencies. We classify the positions from the data using a theoretical framework based on Max Weber's theory of ideal types and from Pierre Bourdieu's concept of habitus. Our analysis outlines a theory about the practice of transitions in inter-sectoral trajectories in psychiatric health care.  Results: From the empirical material, we were able to construct different professional ideal types related to mental health care psychiatry and social psychiatry. The construction points to differences in the habitual basis of action that maintains institutional distinctions. Discussion: Differences in ideal types are connected to the prevailing positions of the two sectors, in which management in health care centres follows a dominant medical rationality, and management in residencies draws on a social and social educational legitimacy. Conclusion: We find differences between the rationalities and habitus of staff at regional hospitals and municipal residencies that enable us to explain how management contributes to trajectories in psychiatric health care. Choices concerning trajectory transitions relate to a combination of habitual professional inclinations and the management of trajectories streamlined through illness classification based on a neoliberal governance model. Future management must be aware of the different rationalities linked to professional and institutional logics when planning; and this requires reflexivity and awareness of the management of intersectoral collaboration

Cross-reactivity profiles of hybrid capture II, cobas, and APTIMA human papillomavirus assays:split-sample study

BACKGROUND: High-risk Human Papillomavirus (HPV) testing is replacing cytology in cervical cancer screening as it is more sensitive for preinvasive cervical lesions. However, the bottleneck of HPV testing is the many false positive test results (positive tests without cervical lesions). Here, we evaluated to what extent these can be explained by cross-reactivity, i.e. positive test results without evidence of high-risk HPV genotypes. The patterns of cross-reactivity have been thoroughly studied for hybrid capture II (HC2) but not yet for newer HPV assays although the manufacturers claimed no or limited frequency of cross-reactivity. In this independent study we evaluated the frequency of cross-reactivity for HC2, cobas, and APTIMA assays. METHODS: Consecutive routine cervical screening samples from 5022 Danish women, including 2859 from women attending primary screening, were tested with the three evaluated DNA and mRNA HPV assays. Genotyping was undertaken using CLART HPV2 assay, individually detecting 35 genotypes. The presence or absence of cervical lesions was determined with histological examinations; women with abnormal cytology were managed as per routine recommendations; those with normal cytology and positive high-risk HPV test results were invited for repeated testing in 18 months. RESULTS: Cross-reactivity to low-risk genotypes was detected in 109 (2.2 %) out of 5022 samples on HC2, 62 (1.2 %) on cobas, and 35 (0.7 %) on APTIMA with only 10 of the samples cross-reacting on all 3 assays. None of the 35 genotypes was detected in 49 (1.0 %), 162 (3.2 %), and 56 (1.1 %) samples, respectively. In primary screening at age 30 to 65 years (n = 2859), samples of 72 (25 %) out of 289 with high-risk infections on HC2 and < CIN2 histology were due to cross-reactivity. On cobas, this was 106 (26 %) out of 415, and on APTIMA 48 (21 %) out of 224. CONCLUSIONS: Despite manufacturer claims, all three assays showed cross-reactivity. In primary cervical screening at age ≥30 years, cross-reactivity accounted for about one quarter of false positive test results regardless of the assay. Cross-reactivity should be addressed in EU tenders, as this primarily technical shortcoming imposes additional costs on the screening programmes

Multi-center real-world comparison of the fully automated Idylla™ microsatellite instability assay with routine molecular methods and immunohistochemistry on formalin-fixed paraffin-embedded tissue of colorectal cancer

Colorectal cancer; FFPE clinical tissue samples; Microsatellite instabilityCancer colorrectal; Muestras de tejido clínico FFPE; Inestabilidad de microsatélitesCàncer colorectal; Mostres de teixit clínic FFPE; Inestabilitat del microsatèl·litsMicrosatellite instability (MSI) is present in 15–20% of primary colorectal cancers. MSI status is assessed to detect Lynch syndrome, guide adjuvant chemotherapy, determine prognosis, and use as a companion test for checkpoint blockade inhibitors. Traditionally, MSI status is determined by immunohistochemistry or molecular methods. The Idylla™ MSI Assay is a fully automated molecular method (including automated result interpretation), using seven novel MSI biomarkers (ACVR2A, BTBD7, DIDO1, MRE11, RYR3, SEC31A, SULF2) and not requiring matched normal tissue. In this real-world global study, 44 clinical centers performed Idylla™ testing on a total of 1301 archived colorectal cancer formalin-fixed, paraffin-embedded (FFPE) tissue sections and compared Idylla™ results against available results from routine diagnostic testing in those sites. MSI mutations detected with the Idylla™ MSI Assay were equally distributed over the seven biomarkers, and 84.48% of the MSI-high samples had ≥ 5 mutated biomarkers, while 98.25% of the microsatellite-stable samples had zero mutated biomarkers. The concordance level between the Idylla™ MSI Assay and immunohistochemistry was 96.39% (988/1025); 17/37 discordant samples were found to be concordant when a third method was used. Compared with routine molecular methods, the concordance level was 98.01% (789/805); third-method analysis found concordance for 8/16 discordant samples. The failure rate of the Idylla™ MSI Assay (0.23%; 3/1301) was lower than that of referenced immunohistochemistry (4.37%; 47/1075) or molecular assays (0.86%; 7/812). In conclusion, lower failure rates and high concordance levels were found between the Idylla™ MSI Assay and routine tests

Localization of active, dually phosphorylated extracellular signal-regulated kinase 1 and 2 in colorectal cancer with or without activating BRAF and KRAS mutations

SummaryColorectal cancers (CRC) often show activating mutations of the KRAS or BRAF genes, which stimulate the extracellular signal-regulated kinase (ERK) pathway, thus increasing cell proliferation and inhibiting apoptosis. However, immunohistochemical results on ERK activation in such tumors differ greatly. Recently, using a highly optimized immunohistochemical method, we obtained evidence that high levels of ERK activation in rectal adenocarcinomas were associated with resistance to radiochemotherapy. In order to determine whether KRAS and/or BRAF mutations correlate to immunohistochemically detectable increases in phosphorylation of ERK (pERK), we stained biopsies from 36 CRC patients with activating mutations in the BRAF gene (BRAFV600E: BRAFm), the KRAS gene (KRASm) or in neither (BRAF/KRASn) with this optimized method. Staining was scored in blind-coded specimens by two observers. Staining of stromal cells was used as a positive control. BRAFm or KRASm tumors did not show higher staining scores than BRAF/KRASn tumors. Although BRAFV600E staining occurred in over 90% of cancer cells in all 9 BRAFm tumors, 3 only showed staining for pERK in less than 10% of cancer cell nuclei. The same applied to 4 of the 14 KRASm tumors. A phophorylation-insensitive antibody demonstrated that lack of pERK staining did not reflect defect expression of ERK1/2 protein. Thus, increased staining for pERK does not correlate to BRAF or KRAS mutations even with a highly optimized procedure. Further studies are required to determine whether this reflects differences in expression of counterregulatory molecules, including ERK phosphatases

Noise-Induced Hearing Loss - A Preventable Disease?:Results of a 10-Year Longitudinal Study of Workers Exposed to Occupational Noise

Aims: To survey current, Danish industrial noise levels and the use of hearing protection devices (HPD) over a 10-year period and to characterise the association between occupational noise and hearing threshold shift in the same period. Furthermore, the risk of hearing loss among the baseline and the follow-up populations according to first year of occupational noise exposure is evaluated. Materials and Methods: In 2001–2003, we conducted a baseline survey of noise- and hearing-related disorders in 11 industries with suspected high noise levels. In 2009–2010, we were able to follow up on 271 out of the 554 baseline workers (49%). Mean noise levels per industry and self-reported HPD use are described at baseline and follow-up. The association between cumulative occupational noise exposure and hearing threshold shift over the 10-year period was assessed using linear regression, and the risk of hearing loss according to year of first occupational noise exposure was evaluated with logistic regression. Results: Over the 10-year period, mean noise levels declined from 83.9 dB(A) to 82.8 dB(A), and for workers exposed >85 dB(A), the use of HPD increased from 70.1 to 76.1%. We found a weak, statistically insignificant, inverse association between higher ambient cumulative noise exposure and poorer hearing (−0.10 dB hearing threshold shift per dB-year (95% confidence interval (CI): −0.36; 0.16)). The risk of hearing loss seemed to increase with earlier first year of noise exposure, but odds ratios were only statistically significant among baseline participants with first exposure before the 1980s (odds ratio: 1.90, 95% CI: 1.11; 3.22). Conclusions: We observed declining industrial noise levels, increased use of HPD and no significant impact on hearing thresholds from current ambient industrial noise levels, which indicated a successful implementation of Danish hearing conservation programs