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BACKGROUND: Persons experiencing homelessness (PEH) are vulnerable emergency department (ED) patients due to high rates of multi-comorbidity and mortality, as well as a lack of follow up care. Communication of test results pending at discharge (TPAD) is an important area of post-ED follow up care. We examined phone access, successful contact, and change in treatment among PEH and non-PEH with TPAD from the ED. METHODS: We performed a retrospective cohort study and included all abnormal TPAD and patient telephone notes regarding TPAD over 7 months extracted from the electronic health record of a single, high-volume, urban, safety-net hospital in Denver, Colorado. Two investigators reviewed all data to determine phone access, successful contact, and recommended treatment change. Descriptive statistics were calculated for all variables and compared between PEH and non-PEH. We assessed associations between homelessness and successful contact and phone access while adjusting for age and sex using multivariable logistic regression. RESULTS: A total of 940 patient encounters with TPAD were included. 142 telephone notes regarding abnormal TPAD were included, of which 33 (23 %) were to PEH. Compared to PEH, housed patients were significantly more likely to have access to a phone (+31 %, 95 % CI: 14-48 %), have an active phone (+46 %, 95 % CI: 29-64 %), and be successfully contacted (+42 %, 95 % CI: 24-60 %), but were less likely to have a recommended change in treatment (-14 %, 95 % CI: -24 to -5 %). Homelessness was significantly associated with decreased successful contact (odds ratio [OR] 0.16, 95 % CI: 0.07-0.38) and decreased phone access (OR 0.11, 95 % CI: 0.04-0.33) after adjusting for age and sex. In the subgroup of patients with phone access (n = 124), homelessness was significantly associated with decreased successful contact (OR 0.26, 95 % CI: 0.10-0.70) after adjusting for age and sex. CONCLUSION: PEH are less likely to have phone access and be successfully contacted regarding TPAD, resulting in untreated or improperly treated infectious disease. Thus, EDs and hospital systems should explore innovative communication solutions, such as shared responsibility models and partnerships with shelters and healthcare for the homeless clinics to improve successful contact with PEH regarding TPAD.

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BACKGROUND: Emergency departments (EDs) are often patients' first point of contact with the health care system. Race, ethnicity, and language all influence factors leading up to ED visits and patient experiences within the ED. There is limited evidence showing how race, ethnicity, and language interact to shape ED experiences, particularly during the COVID-19 pandemic when EDs were extremely strained. OBJECTIVES: Using a retrospective review, we evaluated the association of race, ethnicity and preferred language on hospital admissions from the ED for patients with COVID-19 in an urban, safety-net hospital during the first year of the COVID-19 pandemic before vaccines were widely available. METHODS: We performed a nested regression analysis using generalized estimating equation (GEE) logit models to estimate the impact of language, race, and ethnicity on hospital admissions while controlling for other health conditions and healthcare utilization. RESULTS: Patients who spoke Spanish and were Latino had 72% higher odds [95% confidence interval (CI):1.34-2.2] of hospital admission compared to patients who were White and spoke English. Patients who were Asian, the majority of whom also spoke languages other than English, had 130% higher odds (95% CI: 1.39-3.92) of hospital admission compared to patients who were White and English Speaking. CONCLUSIONS: Findings suggest multiple mechanisms influence hospital admissions for patients who are racially and ethnically minoritized and speak Spanish. Providers may have admitted patients as a precaution rather than because of more advanced illness. Evaluating race, ethnicity, and language concurrently can reveal how intersectional factors shape patient experiences in the ED.

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BACKGROUND: CFAP410 (Cilia and Flagella Associated Protein 410) encodes a protein that has an important role in the development and function of cilia. In ophthalmology, pathogenic variants in CFAP410 have been described in association with cone rod dystrophy, retinitis pigmentosa, with or without macular staphyloma, or with systemic abnormalities such as skeletal dysplasia and amyotrophic lateral sclerosis. Herein, we report a consanguineous family with a novel homozygous CFAP410 c.335_346del variant with cone only degeneration and no systemic features. METHODS: A retrospective analysis of ophthalmic history, examination, retinal imaging, electrophysiology and microperimetry was performed as well as genetic testing with in silico pathogenicity predictions and a literature review. RESULTS: A systemically well 28-year-old female of Pakistani ethnicity with parental consanguinity and no relevant family history, presented with childhood-onset poor central vision and photophobia. Best-corrected visual acuity and colour vision were reduced (0.5 LogMAR, 6/17 Ishihara plates (right) and 0.6 LogMAR, 3/17 Ishihara plates (left). Fundus examination showed no pigmentary retinopathy, no macular staphyloma and autofluorescence was unremarkable. Optical coherence tomography showed subtle signs of intermittent disruption of the ellipsoid zone. Microperimetry demonstrated a reduction in central retinal sensitivity. Electrodiagnostic testing confirmed a reduction in cone-driven responses. Whole-genome sequencing identified an in-frame homozygous deletion of 12 base pairs at c.335_346del in CFAP410. CONCLUSIONS: The non-syndromic cone dystrophy phenotype reported herein expands the genotypic and phenotypic spectra of CFAP410-associated ciliopathies and highlights the need for light of potential future genetic therapies.

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INTRODUCTION: Molecular confirmation of pathogenic sequence variants in the CHM gene is required prior to enrolment in retinal gene therapy clinical trials for choroideremia. Individuals with mild choroideremia have been reported. The molecular basis of genotype-phenotype associations is of clinical relevance since it may impact on selection for retinal gene therapy. METHODS AND MATERIALS: Genetic testing and RNA analysis were undertaken in a patient with mild choroideremia to confirm the pathogenicity of a novel intronic variant in CHM and to explore the mechanism underlying the mild clinical phenotype. RESULTS: A 42-year-old male presented with visual field loss. Fundoscopy and autofluorescence imaging demonstrated mild choroideremia for his age. Genetic analysis revealed a variant at a splice acceptor site in the CHM gene (c.1350-3C > G). RNA analysis demonstrated two out-of-frame transcripts, suggesting pathogenicity, without any detectable wildtype transcripts. One of the two out-of-frame transcripts is present in very low levels in healthy controls. DISCUSSION: Mild choroideremia may result from +3 or -3 splice site variants in CHM. It is presumed that the resulting mRNA transcripts may be partly functional, thereby preventing the development of the null phenotype. Choroideremia patients with such variants may present challenges for gene therapy since there may be residual transcript activity which could result in long-lasting visual function which is atypical for this disease.

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BACKGROUND: MERTK (MER proto-oncogene, tyrosine kinase) is a transmembrane protein essential in regulating photoreceptor outer segment phagocytosis. Biallelic mutations in MERTK cause retinal degeneration. Here we present the retinal phenotype of three patients with missense variants in MERTK. MATERIALS AND METHODS: All patients underwent a full clinical examination, fundus photography, short-wavelength fundus autofluorescence and optical coherence tomography imaging. Two patients also underwent Goldmann visual field testing and electroretinography was undertaken for the third patient. Molecular genetic testing was undertaken using next generation or whole-exome sequencing with all variants confirmed by Sanger sequencing. RESULTS: The first patient was a 29-year-old female heterozygous for a missense variant (c.1133C>T, p.Thr378 Met) and a nonsense variant (c.1744_1751delinsT, p.Ile582Ter) in MERTK. The second patient was a 26-year-old male homozygous for a c.2163T>A, p.His721Gln variant in MERTK. The third patient was an 11-year-old female heterozygous for a deletion of exons 5-19 and a missense variant (c.1866 G>C, p.Lys622Asn) in MERTK. Reduced night vision was the initial symptom in all patients. Fundoscopy revealed typical signs of retinitis pigmentosa (RP) with early-onset macular atrophy. All three MERTK missense variants affect highly conserved residues within functional domains, have low population frequencies and are predicted to be pathogenic in silico. CONCLUSIONS: We report three missense variants in MERTK and present the associated phenotypic data, which are supportive of non-syndromic RP. MERTK is a promising candidate for viral-mediated gene replacement therapy. Moreover, one variant represents a single nucleotide transition, which is theoretically targetable with CRISPR-Cas9 base-editing.

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INTRODUCTION: Traumatic brain injury is a leading cause of death and disability globally with an estimated African incidence of approximately 8 million cases annually. A person suffering from a TBI is often aged 20-30, contributing to sustained disability and large negative economic impacts of TBI. Effective emergency care has the potential to decrease morbidity from this multisystem trauma. OBJECTIVES: Identify and summarize key recommendations for emergency care of patients with traumatic brain injuries using a resource tiered framework. METHODS: A literature review was conducted on clinical care of brain-injured patients in resource-limited settings, with a focus on the first 48 h of injury. Using the AfJEM resource tiered review and PRISMA guidelines, articles were identified and used to describe best practice care and management of the brain-injured patient in resource-limited settings. KEY RECOMMENDATIONS: Optimal management of the brain-injured patient begins with early and appropriate triage. A complete history and physical can identify high-risk patients who present with mild or moderate TBI. Clinical decision rules can aid in the identification of low-risk patients who require no neuroimaging or only a brief period of observation. The management of the severely brain-injured patient requires a systematic approach focused on the avoidance of secondary injury, including hypotension, hypoxia, and hypoglycaemia. Most interventions to prevent secondary injury can be implemented at all facility levels. Urgent neuroimaging is recommended for patients with severe TBI followed by consultation with a neurosurgeon and transfer to an intensive care unit. The high incidence and poor outcomes of traumatic brain injury in Africa make this subject an important focus for future research and intervention to further guide optimal clinical care.

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Importance: Pathogenic variants in retinitis pigmentosa GTPase regulator (RPGR) gene typically lead to a severe form of X-linked retinitis pigmentosa, which is associated with early severe vision loss. Objective: To investigate an X-linked retinal degeneration family with atypical preservation of visual acuity in the presence of a novel deep intronic splice site RPGR c.779-5T>G variant. Design, Setting, and Participants: In this case series, 3 members of an X-linked retinal degeneration family were studied by in-depth phenotyping and genetic screening at a single center. Data were collected and analyzed from November 2018 to March 2020. Main Outcomes and Measures: Data were collected on full ophthalmic history, examination, and retinal imaging. A full retinitis pigmentosa gene panel was analyzed by next-generation sequencing. The pathogenicity of the RPGR c.779-5T>G variant was assessed by in silico splice prediction tools and by purpose-designed in vitro splicing assay. Results: An 84-year-old man was referred with clinical diagnosis of choroideremia and possible inclusion into a gene therapy trial. He presented with late-stage retinal degeneration and unusually preserved visual acuity (78 and 68 ETRDS letters) that clinically resembled choroideremia. His 23-year-old grandson was still in early stages of degeneration but showed a very different clinical picture, typical of retinitis pigmentosa. Next-generation sequencing identified a sole RPGR c.779-5T>G variant of undetermined pathogenicity in both cases. The daughter of the proband showed an RPGR carrier phenotype and was confirmed to carry the same variant. The molecular analysis confirmed that the RPGR c.779-5T>G variation reduced the efficiency of intron splicing compared with wild type, leading to a population of mutant and normal transcripts. The predicted consequences of the pathogenic variant are potential use of an alternative splice acceptor site or complete skipping of exon 8, resulting in truncated forms of the RPGR protein with different levels of glutamylation. Conclusions and Relevance: These results support the importance of careful interpretation of inconsistent clinical phenotypes between family members. Using a molecular splicing assay, a new pathogenic variant in a noncoding region of RPGR was associated with a proportion of normal and hypomorphic RPGR, where cones are likely to survive longer than expected, potentially accounting for the preserved visual acuity observed in this family.

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Because of the magnitude of women's health issues within the larger context of public health and healthcare systems, this paper was written to help define the current status of women's health in Wisconsin. Utilizing critical women's health areas identified by the Wisconsin Women's Health Foundation and the Wisconsin Division of Public Health, 16 specific measures of women's health were chosen for this analysis. The most recent data available for each measure were collected with Wisconsin data being compared to national averages as well as to Healthy People 2010: Objectives for Improving Health targets. Wisconsin women fare better than national averages in nine of the selected health measures; however, there are still many improvements to be made in order to meet Healthy People 2010 targets. The areas where the most improvements are needed include binge drinking, tobacco use, diabetes, and stroke mortality. Other significant findings include the lack of uniformly collected data in the areas of domestic violence, osteoporosis, and mental illness.

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