Examination of the performance of different pointwise linear regression progression criteria to detect glaucomatous visual field change

Background: We aimed to investigate the performance of five different trend analysis criteria for the detection of glaucomatous progression and to determine the most frequently and rapidly progressing locations of the visual field. Design: Retrospective cohort. Participants or Samples: Treated glaucoma patients with =8 Swedish Interactive Thresholding Algorithm (SITA)-standard 24-2 visual field tests. Methods: Progression was determined using trend analysis. Five different criteria were used: (A) =1 significantly progressing point; (B) =2 significantly progressing points; (C) =2 progressing points located in the same hemifield; (D) at least two adjacent progressing points located in the same hemifield; (E) =2 progressing points in the same Garway-Heath map sector. Main Outcome Measures: Number of progressing eyes and false-positive results. Results: We included 587 patients. The number of eyes reaching a progression endpoint using each criterion was: A = 300 (51%); B = 212 (36%); C = 194 (33%); D = 170 (29%); and E = 186 (31%) (P = 0.03). The numbers of eyes with positive slopes were: A = 13 (4.3%); B = 3 (1.4%); C = 3 (1.5%); D = 2 (1.1%); and E = 3 (1.6%) (P = 0.06). The global slopes for progressing eyes were more negative in Groups B, C and D than in Group A (P = 0.004). The visual field locations that progressed more often were those in the nasal field adjacent to the horizontal midline. Conclusions: Pointwise linear regression criteria that take into account the retinal nerve fibre layer anatomy enhances the specificity of trend analysis for the detection glaucomatous visual field progression.

Covariates of high-risk human papillomavirus (HPV) infections are distinct for incident CIN1, CIN2 and CIN3 as disclosed by competing-risks regression models

Background: In addition to the oncogenic human papillomavirus (HPV), several cofactors are needed in cervical carcinogenesis, but whether the HPV covariates associated with incident i) CIN1 are different from those of incident ii) CIN2 and iii) CIN3 needs further assessment. Objectives: To gain further insights into the true biological differences between CIN1, CIN2 and CIN3, we assessed HPV covariates associated with incident CIN1, CIN2, and CIN3. Study Design and Methods: HPV covariates associated with progression to CIN1, CIN2 and CIN3 were analysed in the combined cohort of the NIS (n = 3,187) and LAMS study (n = 12,114), using competing-risks regression models (in panel data) for baseline HR-HPV-positive women (n = 1,105), who represent a sub-cohort of all 1,865 women prospectively followed-up in these two studies. Results: Altogether, 90 (4.8%), 39 (2.1%) and 14 (1.4%) cases progressed to CIN1, CIN2, and CIN3, respectively. Among these baseline HR-HPV-positive women, the risk profiles of incident GIN I, CIN2 and CIN3 were unique in that completely different HPV covariates were associated with progression to CIN1, CIN2 and CIN3, irrespective which categories (non-progression, CIN1, CIN2, CIN3 or all) were used as competing-risks events in univariate and multivariate models. Conclusions: These data confirm our previous analysis based on multinomial regression models implicating that distinct covariates of HR-HPV are associated with progression to CIN1, CIN2 and CIN3. This emphasises true biological differences between the three grades of GIN, which revisits the concept of combining CIN2 with CIN3 or with CIN1 in histological classification or used as a common end-point, e.g., in HPV vaccine trials.