Interstitial macrophage phenotypes in Schistosoma-induced pulmonary hypertension.

Background: Schistosomiasis is a common cause of pulmonary hypertension (PH) worldwide. Type 2 inflammation contributes to the development of Schistosoma-induced PH. Specifically, interstitial macrophages (IMs) derived from monocytes play a pivotal role by producing thrombospondin-1 (TSP-1), which in turn activates TGF-ß, thereby driving the pathology of PH. Resident and recruited IM subpopulations have recently been identified. We hypothesized that in Schistosoma-PH, one IM subpopulation expresses monocyte recruitment factors, whereas recruited monocytes become a separate IM subpopulation that expresses TSP-1. Methods: Mice were intraperitoneally sensitized and then intravenously challenged with S. mansoni eggs. Flow cytometry on lungs and blood was performed on wildtype and reporter mice to identify IM subpopulations and protein expression. Single-cell RNA sequencing (scRNAseq) was performed on flow-sorted IMs from unexposed and at day 1, 3 and 7 following Schistosoma exposure to complement flow cytometry based IM characterization and identify gene expression. Results: Flow cytometry and scRNAseq both identified 3 IM subpopulations, characterized by CCR2, MHCII, and FOLR2 expression. Following Schistosoma exposure, the CCR2+ IM subpopulation expanded, suggestive of circulating monocyte recruitment. Schistosoma exposure caused increased monocyte-recruitment ligand CCL2 expression in the resident FOLR2+ IM subpopulation. In contrast, the vascular pathology-driving protein TSP-1 was greatest in the CCR2+ IM subpopulation. Conclusion: Schistosoma-induced PH involves crosstalk between IM subpopulations, with increased expression of monocyte recruitment ligands by resident FOLR2+ IMs, and the recruitment of CCR2+ IMs which express TSP-1 that activates TGF-ß and causes PH.

User Information Sharing and Hospital Website Privacy Policies.

Importance: Hospital websites frequently use tracking technologies that transfer user information to third parties. It is not known whether hospital websites include privacy policies that disclose relevant details regarding tracking. Objective: To determine whether hospital websites have accessible privacy policies and whether those policies contain key information related to third-party tracking. Design, Setting, and Participants: In this cross-sectional content analysis of website privacy policies of a nationally representative sample of nonfederal acute care hospitals, hospital websites were first measured to determine whether they included tracking technologies that transferred user information to third parties. Hospital website privacy policies were then identified using standardized searches. Policies were assessed for length and readability. Policy content was analyzed using a data abstraction form. Tracking measurement and privacy policy retrieval and analysis took place from November 2023 to January 2024. The prevalence of privacy policy characteristics was analyzed using standard descriptive statistics. Main Outcomes and Measures: The primary study outcome was the availability of a website privacy policy. Secondary outcomes were the length and readability of privacy policies and the inclusion of privacy policy content addressing user information collected by the website, potential uses of user information, third-party recipients of user information, and user rights regarding tracking and information collection. Results: Of 100 hospital websites, 96 (96.0%; 95% CI, 90.1%-98.9%) transferred user information to third parties. Privacy policies were found on 71 websites (71.0%; 95% CI, 61.6%-79.4%). Policies were a mean length of 2527 words (95% CI, 2058-2997 words) and were written at a mean grade level of 13.7 (95% CI, 13.4-14.1). Among 71 privacy policies, 69 (97.2%; 95% CI, 91.4%-99.5%) addressed types of user information automatically collected by the website, 70 (98.6%; 95% CI, 93.8%-99.9%) addressed how collected information would be used, 66 (93.0%; 95% CI, 85.3%-97.5%) addressed categories of third-party recipients of user information, and 40 (56.3%; 95% CI, 44.5%-67.7%) named specific third-party companies or services receiving user information. Conclusions and Relevance: In this cross-sectional study of hospital website privacy policies, a substantial number of hospital websites did not present users with adequate information about the privacy implications of website use, either because they lacked a privacy policy or had a privacy policy that contained limited content about third-party recipients of user information.

Type-I-interferon-responsive microglia shape cortical development and behavior.

Microglia are brain-resident macrophages that shape neural circuit development and are implicated in neurodevelopmental diseases. Multiple microglial transcriptional states have been defined, but their functional significance is unclear. Here, we identify a type I interferon (IFN-I)-responsive microglial state in the developing somatosensory cortex (postnatal day 5) that is actively engulfing whole neurons. This population expands during cortical remodeling induced by partial whisker deprivation. Global or microglial-specific loss of the IFN-I receptor resulted in microglia with phagolysosomal dysfunction and an accumulation of neurons with nuclear DNA damage. IFN-I gain of function increased neuronal engulfment by microglia in both mouse and zebrafish and restricted the accumulation of DNA-damaged neurons. Finally, IFN-I deficiency resulted in excess cortical excitatory neurons and tactile hypersensitivity. These data define a role for neuron-engulfing microglia during a critical window of brain development and reveal homeostatic functions of a canonical antiviral signaling pathway in the brain.

Patient perceptions of behavioral flags in the emergency department: A qualitative analysis.

BACKGROUND: To combat increasing levels of violence in the emergency department (ED), hospitals have implemented several safety measures, including behavioral flags. These electronic health record (EHR)-based notifications alert future clinicians of past incidents of potentially threatening patient behavior, but observed racial disparities in their placement may unintentionally introduce bias in patient care. Little is known about how patients perceive these flags and the disparities that have been found in their placement. OBJECTIVE: This study aims to investigate patient perceptions and perceived benefits and harms associated with the use of behavioral flags. METHODS: Twenty-five semistructured qualitative interviews were conducted with a convenience sample of patients in the ED of a large, urban, academic medical center who did not have a behavioral flag in their EHR. Interviews lasted 10-20 min and were recorded then transcribed. Thematic analysis of deidentified transcripts took place in NVivo 20 software (QSR International) using a general inductive approach. RESULTS: Participant perceptions of behavioral flags varied, with both positive and negative opinions being shared. Five key themes, each with subthemes, were identified: (1) benefits of behavioral flags, (2) concerns and potential harms of flags, (3) transparency with patients, (4) equity, and (5) ideas for improvement. CONCLUSIONS: Patient perspectives on the use of behavioral flags in the ED vary. While many saw flags as a helpful tool to mitigate violence, concerns around negative impacts on care, transparency, and equity were also shared. Insights from this stakeholder perspective may allow for health systems to make flags more effective without compromising equity or patient ideals.

Identifying low acuity Emergency Department visits with a machine learning approach: The low acuity visit algorithms (LAVA).

OBJECTIVE: To improve the performance of International Classification of Disease (ICD) code rule-based algorithms for identifying low acuity Emergency Department (ED) visits by using machine learning methods and additional covariates. DATA SOURCES: We used secondary data on ED visits from the National Hospital Ambulatory Medical Survey (NHAMCS), from 2016 to 2020. STUDY DESIGN: We established baseline performance metrics with seven published algorithms consisting of International Classification of Disease, Tenth Revision codes used to identify low acuity ED visits. We then trained logistic regression, random forest, and gradient boosting (XGBoost) models to predict low acuity ED visits. Each model was trained on five different covariate sets of demographic and clinical data. Model performance was compared using a separate validation dataset. The primary performance metric was the probability that a visit identified by an algorithm as low acuity did not experience significant testing, treatment, or disposition (positive predictive value, PPV). Subgroup analyses assessed model performance across age, sex, and race/ethnicity. DATA COLLECTION: We used 2016-2019 NHAMCS data as the training set and 2020 NHAMCS data for validation. PRINCIPAL FINDINGS: The training and validation data consisted of 53,074 and 9542 observations, respectively. Among seven rule-based algorithms, the highest-performing had a PPV of 0.35 (95% CI [0.33, 0.36]). All model-based algorithms outperformed existing algorithms, with the least effective-random forest using only age and sex-improving PPV by 26% (up to 0.44; 95% CI [0.40, 0.48]). Logistic regression and XGBoost trained on all variables improved PPV by 83% (to 0.64; 95% CI [0.62, 0.66]). Multivariable models also demonstrated higher PPV across all three demographic subgroups. CONCLUSIONS: Machine learning models substantially outperform existing algorithms based on ICD codes in predicting low acuity ED visits. Variations in model performance across demographic groups highlight the need for further research to ensure their applicability and fairness across diverse populations.

Initiation of Extended-release Depot Buprenorphine in a Patient Subject to a Community Treatment Order for Both Antipsychotic and Opioid Agonist Treatments.

ABSTRACT: Opioid use disorder (OUD) and schizophrenia are commonly comorbid, and patient outcomes are improved when these conditions are managed concurrently. Medication for OUD such as methadone and buprenorphine are treatments for OUD, yet psychosis introduces additional challenges in retaining patients in care. Extended-release depot buprenorphine is an emerging option for the treatment of moderate-to-severe OUD, and it may provide certain benefits in patients with concurrent OUD and psychosis. We present the case of a 32-year-old man with schizophrenia, traumatic brain injury, and OUD with a history of multiple opioid-related overdoses, followed by an assertive community treatment team, and subject to a community treatment order for both his primary psychotic disorder and OUD treatments. We discuss the role of extended-release depot buprenorphine in this unique patient population and the ethical considerations of involuntary treatment of OUD in patients lacking capacity to consent to treatment.

Reactive high-spin iron(IV)-oxo sites through dioxygen activation in a metal-organic framework.

In nature, nonheme iron enzymes use dioxygen to generate high-spin iron(IV)=O species for a variety of oxygenation reactions. Although synthetic chemists have long sought to mimic this reactivity, the enzyme-like activation of O2 to form high-spin iron(IV) = O species remains an unrealized goal. Here, we report a metal-organic framework featuring iron(II) sites with a local structure similar to that in α-ketoglutarate-dependent dioxygenases. The framework reacts with O2 at low temperatures to form high-spin iron(IV) = O species that are characterized using in situ diffuse reflectance infrared Fourier transform, in situ and variable-field Mössbauer, Fe Kß x-ray emission, and nuclear resonance vibrational spectroscopies. In the presence of O2, the framework is competent for catalytic oxygenation of cyclohexane and the stoichiometric conversion of ethane to ethanol.

Accuracy of a Glycerol Dehydrogenase Assay for Ethylene Glycol Detection.

INTRODUCTION: Ethylene glycol (EG) is a frequently considered toxicant in poisoned patients. Definitive diagnosis relies on gas chromatography (GC), but this is unavailable at most hospitals. A glycerol dehydrogenase (GDH)-based assay rapidly detects EG. A rapid turnaround time and wide availability of necessary instrumentation suggest this method could facilitate the rapid detection of EG. METHODS: This is a prospective, observational analysis of banked, remnant serum samples submitted to the laboratory of a large, multi-hospital healthcare system. Samples were submitted over a 12-month period for the explicit purpose of testing for suspected EG ingestion. All samples underwent GC and the GDH-based assay. RESULTS: Of the 118 analyzed samples, 88 had no EG detected by GC, and 30 were "positive." At the manufacturer's threshold of 6 mg/dL EG, there was 100% (95%CI; 88.7-100) positive percent agreement (PPA) and 98% (92.1-99.6) negative percent agreement (NPA). Adjusted to a threshold of 9 mg/dL, both the PPA and NPA were 100%. Deming regression of the observed concentrations revealed a slope of 1.16 (1.01 to 1.32) and intercept of -5.3 (-8.9 to -1.7). CONCLUSIONS: The GDH assay provides a sensitive and specific method for the detection and quantification of EG that is comparable to a GC-based method. More widespread use of this rapid, inexpensive assay could improve the care of patients with suspected toxic alcohol exposure. Further study is needed to evaluate the test performance in real-time patient treatment decisions.

Medical journals and advertiser tracking-Consequences for patients, clinicians, and editors.

Medical journal websites frequently contain tracking code that transfers data about journal readers to third parties. These data give drug, device, and other medical product companies a potentially powerful resource for targeting advertisements and other marketing materials to journal readers based on unique attributes and medical interests that can be inferred from the articles they read. Thus, while editors may strictly regulate the content of advertisements that such companies place in their journals' pages, they simultaneously provide those companies with the means to target readers in other forums, possibly in ways that subvert editorial guidelines. We examine the implications of third-party tracking on medical journal webpages, and recommend actions that publishers, editors, and academic societies can take to curb it.

The Scope and Legal Implications of Tracking Technologies on Hospital Websites.

This Viewpoint analyzes the scope and legal implications of tracking on hospital websites, including potential HIPAA and state privacy law violations, and suggests that hospitals limit such tracking.

Patient and clinician perspectives of a remote monitoring program for COVID-19 and lessons for future programs.

COVID Watch is a remote patient monitoring program implemented during the pandemic to support home dwelling patients with COVID-19. The program conferred a large survival advantage. We conducted semi-structured interviews of 85 patients and clinicians using COVID Watch to understand how to design such programs even better. Patients and clinicians found COVID Watch to be comforting and beneficial, but both groups desired more clarity about the purpose and timing of enrollment and alternatives to text-messages to adapt to patients' preferences as these may have limited engagement and enrollment among marginalized patient populations. Because inclusiveness and equity are important elements of programmatic success, future programs will need flexible and multi-channel human-to-human communication pathways for complex clinical interactions or for patients who do not desire tech-first approaches.

Hypertensive emergencies: guidelines and best-practice recommendations.

Due to a variety of demographic and public health factors, the number of emergency department visits related to hypertensive emergencies has increased dramatically in recent decades, making it imperative that clinicians clearly understand the current treatment guidelines and definitions for the spectrum of hypertensive disease. This issue reviews current evidence on identifying and managing hypertensive emergencies and the differences between expert opinions on diagnosing and managing these emergencies. Clear protocols differentiating patients with hypertension from patients with hypertensive emergencies are needed to appropriately manage this patient population.