Increasing interstitial fibrosis (IF) in native and kidney transplant biopsies is associated with functional decline and serves as a clinical trial end point. A Banff 2009 Conference survey revealed a range in IF assessment practices. Observers from multiple centers were asked to assess 30 renal biopsies with a range of IF and quantitate IF using two approaches on trichrome, Periodic acid-Schiff (PAS) and computer-assisted quantification of collagen III immunohistochemistry (C-IHC) slides, as well as assessing percent of cortical tubular atrophy% (TA%) and Banff total cortical inflammation score (ti-score). C-IHC using whole slide scans was performed. C-IHC assessment showed a higher correlation with organ function (r ¼ À0.48) than did visual assessments (r ¼ À0.32-À0.42); computerized and visual C-IHC assessment also correlated (r ¼ 0.64-0.66). Visual assessment of trichrome and C-IHC showed better correlations with organ function and C-IHC, than PAS, TA% and ti-score. However, visual assessment of IF, independent of approach, was variable among observers, and differences in correlations with organ function were not statistically significant among C-IHC image analysis and visual assessment methods. C-IHC image analysis correlated among three centers (r > 0.90, p < 0.0001, between all centers). Given the difficulty of visual IF assessment standardization, C-IHC image could potentially accomplish standardized IF assessment in multicenter settings.

Immunohistochemistry is the gold standard for diagnosing (positive versus negative) polyomavirus BK (BKV) nephropathy and has the potential for disease staging based on staining intensity and quantification of infected cells. This multicenter trial evaluated the reproducibility of BKV immunohistochemistry among 81 pathologists at 60 institutions. Participants stained tissue microarray slides and scored them for staining intensity and percentage of positive nuclei. Staining protocol details and evaluation scores were collected online. Slides were returned for centralized panel re-evaluation and kappa statistics were calculated. Individual assessment of staining intensity and percentage was more reproducible than combined scoring. Inter-institutional reproducibility was moderate for staining intensity (κ=0.49) and percentage (κ=0.42), fair for combined (κ=0.25), and best for simple positive/negative scoring (κ=0.63). Inter-observer reproducibility was substantial for intensity (κ=0.74), percentage (κ=0.66), and positive/negative (κ=0.67), and moderate for combined scoring (κ=0.43). Inter-laboratory reproducibility was fair for intensity (κ=0.37), percentage (κ=0.40), and combined (κ=0.24), but substantial for positive/negative scoring (κ=0.78). BKV RNA copies/cell correlated with staining intensity (r=0.56) and percentage (r=0.62). These results indicate that BKV immunohistochemistry is reproducible between observers but scoring should be simplified to a single-feature schema. Standardization of tissue processing and staining protocols would further improve inter-laboratory reproducibility.

Detection of C4d is crucial for diagnosing antibodymediated-rejection. We conducted a multicenter trial to assess the reproducibility for C4d immunohistochemistry on paraffin tissue. Unstained slides from a tissue microarray (TMA) comprising 44 kidney allograft specimens representing a full analytical spectrum for C4d were distributed to 73 institutions. Participants stained TMA slides using local protocols and evaluated their slides following the Banff C4d schema. Local staining details and evaluation scores were collected online. Stained slides were returned for centralized panel re-evaluation. Kappa statistics were used to determine reproducibility. Poor interinstitutional reproducibility was observed (kappa 0.17), which was equally due to limitations in interobserver (kappa 0.44) and interlaboratory reproducibility (kappa 0.46). Depending on the cut-off, reproducibility could be improved by omitting C4d grading and only considering ± calls. Heat-induced epitope recovery (pH 6-7, 20-30 min, citrate buffer) with polyclonal antibody incubation (<1:80, >40 min) appeared as best practice. The BIFQUIT trial results indicated that C4d staining on paraffin sections varies considerably between laboratories. Refinement of the current Banff C4d scoring schema and harmonization of tissue processing and staining protocols is necessary to achieve acceptable reproducibility.

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Background: Caregivers experience significant strains as a result of navigating the complex mental health and/or addiction (MHA) system for their youth with MHA issues. We examined the characteristics of Ontario families with youth with MHA issues and their service needs. Methods: A cross-sectional survey study investigated the characteristics and service needs of families with youth with MHA issues across the province of Ontario, Canada. A total of 840 caregivers were recruited. Results: 259 participants (Mage = 45.94, SD = 7.11) identified as caregiving for at least one youth with MHA issues. The majority of the participants were female (70.7%), married (73.4%), and completed at least some college/ Bachelor degree (59.1%). The mean age of youth was 16.72 years (SD = 5.33) and the most frequently reported diagnoses were Depression (30.1%), ADHD (27.8%) and Generalized Anxiety Disorder (21.2%). Regression results demonstrated that presently accessing services, presently seeking services, and higher levels of barriers MHA services were significantly predictive of identifying navigation as helpful for finding appropriate MHA services (χ 2 (7) = 28.69, p < .001, Nagelkerke R 2 = .16). Furthermore, presently accessing services was significantly predictive of identifying case management as helpful (χ 2 (7) = 29.59, p < .001, Nagelkerke R 2 = .156), and of identifying a primary healthcare provider as helpful (χ 2 (7) = 38.75, p < .001, Nagelkerke R 2 = .197) for finding appropriate MHA services. Conclusion: Identifying the nature and extent of youth MHA issues, service needs, and family preferences can inform the development of services that address families' needs and lend vital support for accessing services within a complex system.

Background Family navigation in mental health and addictions is a mode of support aimed at helping families through the complex mental health and addictions system, making well-informed service matches, and engaging with families throughout their care journeys. As family navigation services emerge and grow, understanding their unique features and impacts is essential to defining evaluation measures and driving good outcomes for families. Methods This Delphi study investigated the defining features of family mental health and addictions navigation, factors involved in a successful service match, and important outcomes of the process through perspectives of clients and team members of a family navigation program, as well as those of local mental health and/or addictions service providers. In the first phase, participants ( n = 41), were asked to respond to a series of prompts pertaining to 1) the key features of a successful family navigation process, 2) the features of good matches between youth or families and the services to which they are navigated, and 3) the outcomes of importance in family navigation. In Phase 2, findings from Phase 1 were presented to participants ( n = 32) to select and rank their top ten responses to each prompt. Responses which passed a cut-point were carried into Phase 3, in which participants ( n = 20), rated the importance of the remaining items. Items rated as “very” or “extremely” important by 80% or more of participants in Phase 3 had achieved consensus. Intra-class correlation coefficients were calculated to confirm participant agreement on all items having achieved consensus. Results Sample items with 100% consensus were as follows: navigator determines the best fit by understanding and considering the youth and families’ needs, by collaborating with team members and service providers, and by providing individualized suggestions; navigation involves knowledge and understanding of mental health and addictions system and existing services; referred service providers are knowledgeable and up-to-date on evidence-based practice and have multidisciplinary perspectives in service. Overall ICC across all finalized statements following Phase 3 was .84. Conclusions Exploring the key features of successful navigation, outcomes of importance to stakeholders, and elements of successful matches can inform the development of navigation services that address families’ needs, can support service providers in ensuring well-matched services, and lend vital support to families seeking services within a complex system. Electronic supplementary material The online version of this article (10.1186/s12913-019-3968-6) contains supplementary material, which is available to authorized users.

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