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  • 1
    In: International Journal of Epidemiology, Oxford University Press (OUP), Vol. 50, No. Supplement_1 ( 2021-09-01)
    Abstract: Cervical cancer screening can be conducted with cytology and Human Papillomavirus (HPV) testing but few studies have compared the latter directly to concomitant testing (co-testing). We compared these strategies to determine appropriate screening. Methods Within a randomised population-based cohort study conducted around Mainz, Germany, eligible women (≥30 years) were screened via Pap smear, liquid-based cytology (LBC) and HPV testing (HC2) and HPV genotyped post hoc (PCR). These tests formed three strategies: cytology (Pap or LBC) and HPV (HC2 or PCR) stand-alone and co-testing. Screen positives and 5% negative women were invited to colposcopy. Absolute and relative sensitivity, specificity, false positive rates (FPR) and number needed to colposcopy to detect one lesion (NNC) were calculated. Estimates were crude and verification bias-adjusted using stratified sampling with bootstrapped confidence intervals. Results Of 2,627 screened women, cytology stand-alone demonstrated lowest sensitivities (47%) and highest specificities (97%-99%) while HPV stand-alone demonstrated higher sensitivities (79%-95%) but lower specificities (94%-95%). Co-testing increased sensitivity (84%-99%) but not specificity (92%-95%). Relative sensitivities were similar between crude and adjusted estimates, with greater detection via HPV-based strategies. Specificity of co-testing with LBC relative to HPV stand-alone was near unity (0.99, 95% CI 0.99-1.00) but significantly lower than unity with Pap co-testing. FPR and NNC were greatest under co-testing. Conclusions HPV stand-alone screening in women over 30 years appears appropriate over co-testing as a screening strategy. Key messages Co-testing for cervical cancer does not appear to add any benefit in detection and may introduce unnecessary harms compared to HPV stand-alone screening.
    Type of Medium: Online Resource
    ISSN: 0300-5771 , 1464-3685
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1494592-7
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  • 2
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. 9 ( 2022-09), p. 2876-2886
    Abstract: In patients with intracerebral hemorrhage (ICH), the presence of intraventricular hemorrhage constitutes a promising therapeutic target. Intraventricular fibrinolysis (IVF) reduces mortality, yet impact on functional disability remains unclear. Thus, we aimed to determine the influence of IVF on functional outcomes. Methods: This individual participant data meta-analysis pooled 1501 patients from 2 randomized trials and 7 observational studies enrolled during 2004 to 2015. We compared IVF versus standard of care (including placebo) in patients treated with external ventricular drainage due to acute hydrocephalus caused by ICH with intraventricular hemorrhage. The primary outcome was functional disability evaluated by the modified Rankin Scale (mRS; range: 0–6, lower scores indicating less disability) at 6 months, dichotomized into mRS score: 0 to 3 versus mRS: 4 to 6. Secondary outcomes included ordinal-shift analysis, all-cause mortality, and intracranial adverse events. Confounding and bias were adjusted by random effects and doubly robust models to calculate odds ratios and absolute treatment effects (ATE). Results: Comparing treatment of 596 with IVF to 905 with standard of care resulted in an ATE to achieve the primary outcome of 9.3% (95% CI, 4.4–14.1). IVF treatment showed a significant shift towards improved outcome across the entire range of mRS estimates, common odds ratio, 1.75 (95% CI, 1.39–2.17), reduced mortality, odds ratio, 0.47 (95% CI, 0.35–0.64), without increased adverse events, absolute difference, 1.0% (95% CI, −2.7 to 4.8). Exploratory analyses provided that early IVF treatment (≤48 hours) after symptom onset was associated with an ATE, 15.2% (95% CI, 8.6–21.8) to achieve the primary outcome. Conclusions: As compared to standard of care, the administration of IVF in patients with acute hydrocephalus caused by intracerebral and intraventricular hemorrhage was significantly associated with improved functional outcome at 6 months. The treatment effect was linked to an early time window 〈 48 hours, specifying a target population for future trials.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 1467823-8
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  • 3
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 27, No. 8 ( 2021-04-15), p. 2148-2158
    Abstract: Expression-based classifiers to predict pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) are not routinely used in the clinic. We aimed to build and validate a classifier for pCR after NACT. Patients and Methods: We performed a prospective multicenter study (EXPRESSION) including 114 patients treated with anthracycline/taxane-based NACT. Pretreatment core needle biopsies from 91 patients were used for gene expression analysis and classifier construction, followed by validation in five external cohorts (n = 619). Results: A 20-gene classifier established in the EXPRESSION cohort using a Youden index–based cut-off point predicted pCR in the validation cohorts with an accuracy, AUC, negative predictive value (NPV), positive predictive value, sensitivity, and specificity of 0.811, 0.768, 0.829, 0.587, 0.216, and 0.962, respectively. Alternatively, aiming for a high NPV by defining the cut-off point for classification based on the complete responder with the lowest predicted probability of pCR in the EXPRESSION cohort led to an NPV of 0.960 upon external validation. With this extreme-low cut-off point, a recommendation to not treat with anthracycline/taxane-based NACT would be possible for 121 of 619 unselected patients (19.5%) and 112 of 322 patients with luminal breast cancer (34.8%). The analysis of the molecular subtypes showed that the identification of patients who do not achieve a pCR by the 20-gene classifier was particularly relevant in luminal breast cancer. Conclusions: The novel 20-gene classifier reliably identifies patients who do not achieve a pCR in about one third of luminal breast cancers in both the EXPRESSION and combined validation cohorts.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
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  • 4
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 93, No. 12 ( 2019-09-17), p. e1159-e1170
    Abstract: To determine the influence of intracerebral hemorrhage (ICH) location and volume and hematoma surface on perihemorrhagic edema evolution. Methods Patients with ICH of the prospective Universitätsklinikum Erlangen Cohort of Patients With Spontaneous Intracerebral Hemorrhage (UKER-ICH) cohort study ( NCT03183167 ) between 2010 and 2013 were analyzed. Hematoma and edema volume during hospital stay were volumetrically assessed, and time course of edema evolution and peak edema correlated to hematoma volume, location, and surface to verify the strength of the parameters on edema evolution. Results Overall, 300 patients with supratentorial ICH were analyzed. Peak edema showed a high correlation with hematoma surface ( R 2 = 0.864, p 〈 0.001) rather than with hematoma volumes, regardless of hematoma location. Smaller hematomas with a higher ratio of hematoma surface to volume showed exponentially higher relative edema ( R 2 = 0.755, p 〈 0.001). Multivariable logistic regression analysis revealed a cutoff ICH volume of 30 mL, beyond which an increase of total mass lesion volume (combined volume of hematoma and edema) was not associated with worse functional outcome. Specifically, peak edema was associated with worse functional outcome in ICH 〈 30 mL (odds ratio [OR] 2.63, 95% confidence interval [CI] 1.68–4.12, p 〈 0.001), contrary to ICH ≥30 mL (OR 1.20, 95% CI 0.88–1.63, p = 0.247). There were no significant differences between patients with lobar and those with deep ICH after adjustment for hematoma volumes. Conclusions Peak perihemorrhagic edema, although influencing mortality, is not associated with worse functional outcomes in ICH volumes 〉 30 mL. Although hematoma volume correlates with peak edema extent, hematoma surface is the major parameter for edema evolution. The effect of edema on functional outcome is therefore more pronounced in smaller and irregularly shaped hematomas, and these patients may particularly benefit from edema-modifying therapies.
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
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