Best Practices for the Electronic Implementation and Migration of Patient-Reported Outcome Measures.

While the use of electronic methods to collect patient-reported outcome data in clinical trials continues to increase, it remains the case that many patient-reported outcome measures (PROMs) have originally been developed and validated on paper. Careful consideration during the move from paper PROMs to electronic format is required to preserve the integrity of the measure and ensure a "faithful migration." Relevant literature has long called out the importance of following migration best practices during this process; nevertheless, such best practices are distributed across multiple documents. This article consolidates and builds upon existing electronic PROM implementation best practice recommendations to provide a comprehensive, up-to-date, single point of reference. It reflects the current consensus based on the significant advances in technology capabilities and knowledge gleaned from the growing evidence base on electronic migration and implementation, to balance the need for maintaining the integrity of the measure while optimizing respondent usability. It also specifies whether the practice is rooted in evidence or expert consensus, to enable those using these best practices to make informed and considered decisions when conducting migration.

Crowding changes appearance systematically in peripheral, amblyopic, and developing vision.

Visual crowding is the disruptive effect of clutter on object recognition. Although most prominent in adult peripheral vision, crowding also disrupts foveal vision in typically developing children and those with strabismic amblyopia. Do these crowding effects share the same mechanism? Here we exploit observations that crowded errors in peripheral vision are not random: Target objects appear either averaged with the flankers (assimilation) or replaced by them (substitution). If amblyopic and developmental crowding share the same mechanism, then their errors should be similarly systematic. We tested foveal vision in children aged 3 to 8 years with typical vision or strabismic amblyopia and peripheral vision in typical adults. The perceptual effects of crowding were measured by requiring observers to adjust a reference stimulus to match the perceived orientation of a target "Vac-Man" element. When the target was surrounded by flankers that differed by ± 30°, all three groups (adults and children with typical or amblyopic vision) reported orientations between the target and flankers (assimilation). Errors were reduced with ± 90° differences but primarily matched the flanker orientation (substitution) when they did occur. A population pooling model of crowding successfully simulated this pattern of errors in all three groups. We conclude that the perceptual effects of amblyopic and developing crowding are systematic and resemble the near periphery in adults, suggesting a common underlying mechanism.

Vincristine-induced peripheral neuropathy is driven by canonical NLRP3 activation and IL-1ß release.

Vincristine is an important component of many regimens used for pediatric and adult malignancies, but it causes a dose-limiting sensorimotor neuropathy for which there is no effective treatment. This study aimed to delineate the neuro-inflammatory mechanisms contributing to the development of mechanical allodynia and gait disturbances in a murine model of vincristine-induced neuropathy, as well as to identify novel treatment approaches. Here, we show that vincristine-induced peripheral neuropathy is driven by activation of the NLRP3 inflammasome and subsequent release of interleukin-1ß from macrophages, with mechanical allodynia and gait disturbances significantly reduced in knockout mice lacking NLRP3 signaling pathway components, or after treatment with the NLRP3 inhibitor MCC950. Moreover, treatment with the IL-1 receptor antagonist anakinra prevented the development of vincristine-induced neuropathy without adversely affecting chemotherapy efficacy or tumor progression in patient-derived medulloblastoma xenograph models. These results detail the neuro-inflammatory mechanisms leading to vincristine-induced peripheral neuropathy and suggest that repurposing anakinra may be an effective co-treatment strategy to prevent vincristine-induced peripheral neuropathy.

Crowding for faces is determined by visual (not holistic) similarity: Evidence from judgements of eye position.

Crowding (the disruption of object recognition in clutter) presents the fundamental limitation on peripheral vision. For simple objects, crowding is strong when target/flanker elements are similar and weak when they differ - a selectivity for target-flanker similarity. In contrast, the identification of upright holistically-processed face stimuli is more strongly impaired by upright than inverted flankers, whereas inverted face-targets are impaired by both - a pattern attributed to an additional stage of crowding selective for "holistic similarity" between faces. We propose instead that crowding is selective for target-flanker similarity in all stimuli, but that this selectivity is obscured by task difficulty with inverted face-targets. Using judgements of horizontal eye-position that are minimally affected by inversion, we find that crowding is strong when target-flanker orientations match and weak when they differ for both upright and inverted face-targets. By increasing task difficulty, we show that this selectivity for target-flanker similarity is obscured even for upright face-targets. We further demonstrate that this selectivity follows differences in the spatial order of facial features, rather than "holistic similarity" per se. There is consequently no need to invoke a distinct stage of holistic crowding for faces - crowding is selective for target-flanker similarity, even with complex stimuli such as faces.