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Importance: Existing therapies to slow geographic atrophy (GA) enlargement in age-related macular degeneration (AMD) have relatively modest anatomic efficacy, require intravitreal administration, and increase the risk of neovascular AMD. Additional therapeutic approaches are desirable., Objective: To evaluate the safety and possible anatomic efficacy of oral minocycline, a microglial inhibitor, for the treatment of GA in AMD., Design, Setting, and Participants: This was a phase 2, prospective, single-arm, 45-month, nonrandomized controlled trial conducted from December 2016 to April 2023. Patients with GA from AMD in 1 or both eyes were recruited from the National Institutes of Health (Bethesda, Maryland) and Bristol Eye Hospital (Bristol, UK). Study data were analyzed from September 2022 to May 2023., Intervention: After a 9-month run-in phase, participants began oral minocycline, 100 mg, twice daily for 3 years., Main Outcomes and Measures: The primary outcome measure was the difference in rate of change of square root GA area on fundus autofluorescence between the 24-month treatment phase and 9-month run-in phase., Results: Of the 37 participants enrolled (mean [SD] age, 74.3 [7.6] years; 21 female [57%]), 36 initiated the treatment phase. Of these participants, 21 (58%) completed at least 33 months, whereas 15 discontinued treatment (8 by request, 6 for adverse events/illness, and 1 death). Mean (SE) square root GA enlargement rate in study eyes was 0.31 (0.03) mm per year during the run-in phase and 0.28 (0.02) mm per year during the treatment phase. The primary outcome measure of mean (SE) difference in enlargement rates between the 2 phases was -0.03 (0.03) mm per year (P = .39). Similarly, secondary outcome measures of GA enlargement rate showed no differences between the 2 phases. The secondary outcome measures of mean difference in rate of change between 2 phases were 0.2 letter score per month (95% CI, -0.4 to 0.9; P = .44) for visual acuity and 0.7 μm per month (-0.4 to 1.8; P = .20) for subfoveal retinal thickness. Of the 129 treatment-emergent adverse events among 32 participants, 49 (38%) were related to minocycline (with no severe or ocular events), including elevated thyrotropin level (15 participants) and skin hyperpigmentation/discoloration (8 participants)., Conclusions and Relevance: In this phase 2 nonrandomized controlled trial, oral minocycline was not associated with a decrease in GA enlargement over 24 months, compared with the run-in phase. This observation was consistent across primary and secondary outcome measures. Oral minocycline at this dose is likely not associated with slower rate of enlargement of GA in AMD.

Introduction: We describe the California Healthy Places Index (HPI) and its performance relative to other indexes for measuring community well-being at the census-tract level. The HPI arose from a need identified by health departments and community organizations for an index rooted in the social determinants of health for place-based policy making and program targeting. The index was geographically granular, validated against life expectancy at birth, and linked to policy actions., Materials and Methods: Guided by literature, public health experts, and a positive asset frame, we developed a composite index of community well-being for California from publicly available census-tract data on place-based factors linked to health. The 25 HPI indicators spanned 8 domains; weights were derived from their empirical association with tract-level life expectancy using weighted quantile sums methods., Results: The HPI's domains were aligned with the social determinants of health and policy action areas of economic resources, education, housing, transportation, clean environment, neighborhood conditions, social resources, and health care access. The overall HPI score was the sum of weighted domain scores, of which economy and education were highly influential (50% of total weights). The HPI was strongly associated with life expectancy at birth ( r = 0.58). Compared with the HPI, a pollution-oriented index did not capture one-third of the most disadvantaged quartile of census tracts (representing 3 million Californians). Overlap of the HPI's most disadvantaged quartile of census tracts was greater for indexes of economic deprivation. We visualized the HPI percentile ranking as a web-based mapping tool that presented the HPI at multiple geographies and that linked indicators to an action-oriented policy guide., Practice Implications: The framing of indexes and specifications such as domain weighting have substantial consequences for prioritizing disadvantaged populations. The HPI provides a model for tools and new methods that help prioritize investments and identify multisectoral opportunities for policy action.

Astrocytoma grade IV (glioblastoma multiforme) is the most common and most malignant tumor of the central nervous system and is currently noncurable. Here, we have examined a population-based cohort of 47 patients with grade IV astrocytoma, who underwent tumor surgery at Sahlgrenska University Hospital in Sweden and who survived after surgery for less than 200 days (short survivors, 28 patients) and more than 500 days (long survivors, 19 patients). For each tumor, we ascertained information on patient age, sex, tumor location, oncological treatment, and survival after surgery. The analysis of the tumor volume and the extent of tumor resection (incomplete versus complete resection of the macroscopic tumor) was made retrospectively from the preoperative radiological investigations and, when available, also from postoperative radiology. We performed semiquantitative immunohistochemical evaluation of the presence of intermediate filament (nanofilament) proteins glial fibrillary acidic protein, vimentin, nestin, and synemin in tumor cells. The intermediate filament system helps cells and tissues to cope with various types of stress, and thus, it might affect the malignant potential of grade IV astrocytoma. We propose a subclassification of astrocytomas grade IV with respect to the expression of the intermediate filament proteins glial fibrillary acidic protein, vimentin, nestin, and synemin, namely, type A, B, and C. Our results suggest that the expression of the intermediate filament proteins glial fibrillary acidic protein, vimentin, nestin, and synemin is coregulated in grade IV astrocytomas. The expression patterns of the intermediate filament proteins in astrocytoma type A, B, and C might have biological and clinical significance., (Copyright © 2013 Elsevier Inc. All rights reserved.)