UCSF

OBJECTIVE: Health literacy is a critical health determinant, for which few computerized, self-administered assessments exist. This study adapted and tested the reliability of the Newest Vital Sign© (NVS) as a computerized, self-administered health literacy screener. METHODS: Phase one involved 33 participants to create response options for a computerized, self-administered NVS (C-NVS). Phase two was a randomized crossover trial to test the consistency of C-NVS and original, interviewer-administered NVS (I-NVS) scores in 89 participants. RESULTS: Linear mixed-effects regression model results showed a significant carryover effect (p < .001). Crossover trial data from time 1 showed that participants who initially received the C-NVS had significantly higher average scores (M = 5.7, SD = 0.6) than participants who received the I-NVS (M = 4.5, SD = 1.5; t(87) = 5.25, p < .001). Exploratory analysis results showed that when the washout period was longer than 33 days (75th percentile) the carryover effect was not statistically significant (p = .077). CONCLUSION AND INNOVATION: Findings suggest learning can occur when health literacy screeners are administered more than once in less than a months time and computerized, self-administered health literacy screeners may produce ceiling effects. A universal precautions approach to health literacy therefore remains germane.

OBJECTIVE: To pilot test and assess the feasibility and acceptability of chaplain-led decision coaching alongside the GOALS (Getting Optimal Alignment around Life Support) decision support tool to enhance decision-making in threatened periviable delivery. METHODS: Pregnant people admitted for threatened periviable delivery and their important other (IO) were enrolled. Decisional conflict, acceptability, and knowledge were measured before and after the intervention. Chaplains journaled their impressions of training and coaching encounters. Descriptive analysis and conventional content analysis were completed. RESULTS: Eight pregnant people and two IOs participated. Decisional conflict decreased by a mean of 6.7 (SD = 9.4) and knowledge increased by a mean of 1.4 (SD = 1.8). All rated their experience as good or excellent, and the amount of information was just right. Participants found it helpful to have someone to talk to and noted chaplains helped them reach a decision. Chaplains found the intervention a valuable use of their time and skillset. CONCLUSION: This is the first small-scale pilot study to utilize chaplains as decision coaches. Our results suggest that chaplain coaching with a decision support tool is feasible and well-accepted by parents and chaplains. INNOVATIONS: Our findings recognize chaplains as an underutilized, yet practical resource in value-laden clinical decision-making.

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We previously reported two siblings with inherited PD-1 deficiency who died from autoimmune pneumonitis at 3 and 11 years of age after developing other autoimmune manifestations, including type 1 diabetes (T1D). We report here two siblings, aged 10 and 11 years, with neonatal-onset T1D (diagnosed at the ages of 1 day and 7 wk), who are homozygous for a splice-site variant of CD274 (encoding PD-L1). This variant results in the exclusive expression of an alternative, loss-of-function PD-L1 protein isoform in overexpression experiments and in the patients primary leukocytes. Surprisingly, cytometric immunophenotyping and single-cell RNA sequencing analysis on blood leukocytes showed largely normal development and transcriptional profiles across lymphoid and myeloid subsets in the PD-L1-deficient siblings, contrasting with the extensive dysregulation of both lymphoid and myeloid leukocyte compartments in PD-1 deficiency. Our findings suggest that PD-1 and PD-L1 are essential for preventing early-onset T1D but that, unlike PD-1 deficiency, PD-L1 deficiency does not lead to fatal autoimmunity with extensive leukocytic dysregulation.

Early stages of deadly respiratory diseases including COVID-19 are challenging to elucidate in humans. Here, we define cellular tropism and transcriptomic effects of SARS-CoV-2 virus by productively infecting healthy human lung tissue and using scRNA-seq to reconstruct the transcriptional program in "infection pseudotime" for individual lung cell types. SARS-CoV-2 predominantly infected activated interstitial macrophages (IMs), which can accumulate thousands of viral RNA molecules, taking over 60% of the cell transcriptome and forming dense viral RNA bodies while inducing host profibrotic (TGFB1, SPP1) and inflammatory (early interferon response, CCL2/7/8/13, CXCL10, and IL6/10) programs and destroying host cell architecture. Infected alveolar macrophages (AMs) showed none of these extreme responses. Spike-dependent viral entry into AMs used ACE2 and Sialoadhesin/CD169, whereas IM entry used DC-SIGN/CD209. These results identify activated IMs as a prominent site of viral takeover, the focus of inflammation and fibrosis, and suggest targeting CD209 to prevent early pathology in COVID-19 pneumonia. This approach can be generalized to any human lung infection and to evaluate therapeutics.

Glioblastoma is a clinically and molecularly heterogeneous disease, and new predictive biomarkers are needed to identify those patients most likely to respond to specific treatments. Through prospective genomic profiling of 459 consecutive primary treatment-naïve IDH-wildtype glioblastomas in adults, we identified a unique subgroup (2%, 9/459) defined by somatic hypermutation and DNA replication repair deficiency due to biallelic inactivation of a canonical mismatch repair gene. The deleterious mutations in mismatch repair genes were often present in the germline in the heterozygous state with somatic inactivation of the remaining allele, consistent with glioblastomas arising due to underlying Lynch syndrome. A subset of tumors had accompanying proofreading domain mutations in the DNA polymerase POLE and resultant "ultrahypermutation". The median age at diagnosis was 50 years (range 27-78), compared with 63 years for the other 450 patients with conventional glioblastoma (p < 0.01). All tumors had histologic features of the giant cell variant of glioblastoma. They lacked EGFR amplification, lacked combined trisomy of chromosome 7 plus monosomy of chromosome 10, and only rarely had TERT promoter mutation or CDKN2A homozygous deletion, which are hallmarks of conventional IDH-wildtype glioblastoma. Instead, they harbored frequent inactivating mutations in TP53, NF1, PTEN, ATRX, and SETD2 and recurrent activating mutations in PDGFRA. DNA methylation profiling revealed they did not align with known reference adult glioblastoma methylation classes, but instead had unique globally hypomethylated epigenomes and mostly classified as "Diffuse pediatric-type high grade glioma, RTK1 subtype, subclass A". Five patients were treated with immune checkpoint blockade, four of whom survived greater than 3 years. The median overall survival was 36.8 months, compared to 15.5 months for the other 450 patients (p < 0.001). We conclude that "De novo replication repair deficient glioblastoma, IDH-wildtype" represents a biologically distinct subtype in the adult population that may benefit from prospective identification and treatment with immune checkpoint blockade.

In the pursuit of ending the HIV epidemic, U.S. emergency departments (EDs) have emerged as a valuable setting to increase HIV testing and linkage to care. There is limited data available, however, describing the incorporation of HIV prevention initiatives in U.S. EDs. Over the last decade, HIV pre-exposure prophylaxis (PrEP) has significantly changed the HIV prevention landscape globally and very little is known about the provision of PrEP in U.S. EDs. To address this gap in the literature, we conducted a systematic review of peer-reviewed quantitative studies and conference abstracts spanning July 2012 - October 2022. Of 433 citations, 11 articles and 13 abstracts meet our inclusion criteria, representing 18 unique studies addressing PrEP screening, prescribing, and/or linkage to PrEP care.Most studies describe screening processes to identify PrEP-eligible patients (n = 17); most studies leveraged a patients STI history as initial PrEP eligibility screening criteria. Fewer studies describe PrEP prescribing (n = 2) and/or linkage to PrEP care (n = 8).Findings from this systematic review highlight the potential for U.S. EDs to increase PrEP uptake among individuals at risk for HIV infection. Despite a growing number of studies exploring processes for incorporating PrEP into the ED setting, such studies are small-scale and time limited. Models providing prescribing PrEP in the ED show higher initiation rates than post-discharge engagement models. Electronic health record (EHR)-based HIV screening is valuable, but post-ED linkage rates are low. Our findings emphasize the need to establish best practices for initiating and supporting prevention effective PrEP use in the ED setting.

This article describes the methods used to build a large-scale database of more than 250,000 electronic fetal monitoring (EFM) records linked to a comprehensive set of clinical information about the infant, the mother, the pregnancy, labor, and outcome. The database can be used to investigate how birth outcome is related to clinical and EFM features. The main steps involved in building the database were: (1) Acquiring the raw EFM recording and clinical records for each birth. (2) Assigning each birth to an objectively defined outcome class that included normal, acidosis, and hypoxic-ischemic encephalopathy. (3) Removing all personal health information from the EFM recordings and clinical records. (4) Preprocessing the deidentified EFM records to eliminate duplicates, reformat the signals, combine signals from different sensors, and bridge gaps to generate signals in a format that can be readily analyzed. (5) Post-processing the repaired EFM recordings to extract key features of the fetal heart rate, uterine activity, and their relations. (6) Populating a database that links the clinical information, EFM records, and EFM features to support easy querying and retrieval. •A multi-step process is required to build a comprehensive database linking electronic temporal fetal monitoring signals to a comprehensive set of clinical information about the infant, the mother, the pregnancy, labor, and outcome.•The current database documents more than 250,000 births including almost 4,000 acidosis and 400 HIE cases. This represents more than 80% of the births that occurred in 15 Northern California Kaiser Permanente Hospitals between 2011-2019. This is a valuable resource for studying the factors predictive of outcome.•The signal processing code and schemas for the database are freely available. The database will not be permitted to leave Kaiser firewalls, but a process is in place to allow interested investigators to access it.

A teenage girl presented with fever and altered mental status. MRI showed diffuse leptomeningeal enhancement of the brain and spine. She was diagnosed by a positive cerebrospinal fluid (CSF) culture with tuberculous (TB) meningitis and was started on anti-TB medications and corticosteroids. Her mental status improved, but she was noted to have proximal weakness of the lower extremities. In the course of tapering corticosteroids at week 11 of anti-TB therapy, she became acutely confused and febrile. MRI demonstrated interval development of tuberculomas in the brain and a mass lesion in the thoracic spine causing cord compression. Given the clinical picture was suggestive of a paradoxical reaction, the dose of corticosteroids was increased. Infliximab was added when repeat MRI revealed enlargement of the mass lesion in the spine with worsening cord compression. She was successfully tapered off of corticosteroids. Over several months, the patient's motor function recovered fully, and she returned to ambulating without assistance.