Clinical, Radiological and Pathological Features of a Large American Cohort of Spinocerebellar Ataxia (SCA27B).

OBJECTIVES: Spinocerebellar ataxia 27B due to GAA repeat expansions in the fibroblast growth factor 14 (FGF14) gene has recently been recognized as a common cause of late-onset hereditary cerebellar ataxia. Here we present the first report of this disease in the US population, characterizing its clinical manifestations, disease progression, pathological abnormalities, and response to 4-aminopyridine in a cohort of 102 patients bearing GAA repeat expansions. METHODS: We compiled a series of patients with SCA27B, recruited from 5 academic centers across the United States. Clinical manifestations and patient demographics were collected retrospectively from clinical records in an unblinded approach using a standardized form. Post-mortem analysis was done on 4 brains of patients with genetically confirmed SCA27B. RESULTS: In our cohort of 102 patients with SCA27B, we found that SCA27B was a late-onset (57 ± 12.5 years) slowly progressive ataxia with an episodic component in 51% of patients. Balance and gait impairment were almost always present at disease onset. The principal finding on post-mortem examination of 4 brain specimens was loss of Purkinje neurons that was most severe in the vermis most particularly in the anterior vermis. Similar to European populations, a high percent of patients 21/28 (75%) reported a positive treatment response with 4-aminopyridine. INTERPRETATION: Our study further estimates prevalence and further expands the clinical, imaging and pathological features of SCA27B, while looking at treatment response, disease progression, and survival in patients with this disease. Testing for SCA27B should be considered in all undiagnosed ataxia patients, especially those with episodic onset. ANN NEUROL 2024.

The role of mood in shaping reactions to smoking cessation messages among adults who smoke: a multimodal investigation.

INTRODUCTION: Mood-tailored communications may help increase the effectiveness of smoking cessation messaging interventions. We used both self-report and psychophysiological measures to test the impact of mood on responses to cessation messages in adults who smoke. METHODS: In a two-part (crowdsourcing and psychophysiological studies) study, the impact of 30 smoking cessation messages comprised of five themes (i.e., financial, health, quality-of-life, challenges in quitting, motivation to quit) were tested. In a crowdsourcing study, participants (N = 600) were randomly placed into one of three mood induction tasks (i.e., positive, negative, neutral), and then viewed the smoking cessation messages. After each message, they were asked to self-report their motivation to quit, message receptivity, and the perceived relevance of the messages. In an in-lab, psychophysiological study, participants (N = 42) completed the same tasks as the crowdsourcing participants but were monitored for heart rate, skin conductance, and eye-tracking while viewing the cessation messages. Using a multi-attribute decision-making model (MADM) using outcomes from both studies, messages were ranked for each mood state. RESULTS: The top messages for participants in the positive mood condition included the challenges in quitting, financial costs/rewards, and motivations to quit themes. The top messages for participants assigned to the negative mood condition included the challenges in quitting, quality-of-life, and financial costs/rewards themes. For participants in the neutral mood condition, messages in the challenges in quitting and quality of life themes performed best. CONCLUSIONS: Variations in the preferences of messages and themes by mood condition suggest that mood-tailored communication may increase the effectiveness of smoking cessation messages.

The Emerging Threat of (Micro)Thrombosis in COVID-19 and Its Therapeutic Implications.

The recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the ensuing global pandemic has presented a health emergency of unprecedented magnitude. Recent clinical data has highlighted that coronavirus disease 2019 (COVID-19) is associated with a significant risk of thrombotic complications ranging from microvascular thrombosis, venous thromboembolic disease, and stroke. Importantly, thrombotic complications are markers of severe COVID-19 and are associated with multiorgan failure and increased mortality. The evidence to date supports the concept that the thrombotic manifestations of severe COVID-19 are due to the ability of SARS-CoV-2 to invade endothelial cells via ACE-2 (angiotensin-converting enzyme 2), which is expressed on the endothelial cell surface. However, in patients with COVID-19 the subsequent endothelial inflammation, complement activation, thrombin generation, platelet, and leukocyte recruitment, and the initiation of innate and adaptive immune responses culminate in immunothrombosis, ultimately causing (micro)thrombotic complications, such as deep vein thrombosis, pulmonary embolism, and stroke. Accordingly, the activation of coagulation (eg, as measured with plasma D-dimer) and thrombocytopenia have emerged as prognostic markers in COVID-19. Given thrombotic complications are central determinants of the high mortality rate in COVID-19, strategies to prevent thrombosis are of critical importance. Several antithrombotic drugs have been proposed as potential therapies to prevent COVID-19-associated thrombosis, including heparin, FXII inhibitors, fibrinolytic drugs, nafamostat, and dipyridamole, many of which also possess pleiotropic anti-inflammatory or antiviral effects. The growing awareness and mechanistic understanding of the prothrombotic state of COVID-19 patients are driving efforts to more stringent diagnostic screening for thrombotic complications and to the early institution of antithrombotic drugs, for both the prevention and therapy of thrombotic complications. The shifting paradigm of diagnostic and treatment strategies holds significant promise to reduce the burden of thrombotic complications and ultimately improve the prognosis for patients with COVID-19.

COVID-19 Vaccine Fact-Checking Posts on Facebook: Observational Study.

BACKGROUND: Effective interventions aimed at correcting COVID-19 vaccine misinformation, known as fact-checking messages, are needed to combat the mounting antivaccine infodemic and alleviate vaccine hesitancy. OBJECTIVE: This work investigates (1) the changes in the public's attitude toward COVID-19 vaccines over time, (2) the effectiveness of COVID-19 vaccine fact-checking information on social media engagement and attitude change, and (3) the emotional and linguistic features of the COVID-19 vaccine fact-checking information ecosystem. METHODS: We collected a data set of 12,553 COVID-19 vaccine fact-checking Facebook posts and their associated comments (N=122,362) from January 2020 to March 2022 and conducted a series of natural language processing and statistical analyses to investigate trends in public attitude toward the vaccine in COVID-19 vaccine fact-checking posts and comments, and emotional and linguistic features of the COVID-19 fact-checking information ecosystem. RESULTS: The percentage of fact-checking posts relative to all COVID-19 vaccine posts peaked in May 2020 and then steadily decreased as the pandemic progressed (r=-0.92, df=21, t=-10.94, 95% CI -0.97 to -0.82, P<.001). The salience of COVID-19 vaccine entities was significantly lower in comments (mean 0.03, SD 0.03, t=39.28, P<.001) than in posts (mean 0.09, SD 0.11). Third-party fact checkers have been playing a more important role in more fact-checking over time (r=0.63, df=25, t=4.06, 95% CI 0.33-0.82, P<.001). COVID-19 vaccine fact-checking posts continued to be more analytical (r=0.81, df=25, t=6.88, 95% CI 0.62-0.91, P<.001) and more confident (r=0.59, df=25, t=3.68, 95% CI 0.27-0.79, P=.001) over time. Although comments did not exhibit a significant increase in confidence over time, tentativeness in comments significantly decreased (r=-0.62, df=25, t=-3.94, 95% CI -0.81 to -0.31, P=.001). In addition, although hospitals receive less engagement than other information sources, the comments expressed more positive attitudinal valence in comments compared to other information sources (b=0.06, 95% CI 0.00-0.12, t=2.03, P=.04). CONCLUSIONS: The percentage of fact-checking posts relative to all posts about the vaccine steadily decreased after May 2020. As the pandemic progressed, third-party fact checkers played a larger role in posting fact-checking COVID-19 vaccine posts. COVID-19 vaccine fact-checking posts continued to be more analytical and more confident over time, reflecting increased confidence in posts. Similarly, tentativeness in comments decreased; this likewise suggests that public uncertainty diminished over time. COVID-19 fact-checking vaccine posts from hospitals yielded more positive attitudes toward vaccination than other information sources. At the same time, hospitals received less engagement than other information sources. This suggests that hospitals should invest more in generating engaging public health campaigns on social media.

Advances in the Management of Acute Venous Thromboembolism and New Therapeutic Agents.

Important advances in the understanding and management of venous thromboembolism (VTE) have enhanced our ability to diagnose, prevent, and treat VTE. In this narrative review, we discuss how recent advances in the understanding and management of VTE are changing practice, highlight ongoing unmet needs in VTE management, and outline how novel therapeutic targets with little or no influence on hemostasis may help address these unmet needs.

Platelets as Central Actors in Thrombosis-Reprising an Old Role and Defining a New Character.

Platelets have long been considered simple anucleate cells that rapidly adhere and aggregate at sites of vascular injury. However, recent in vivo experimental data have shed new light on the platelet response to vascular injury. These data have unexpectedly revealed that platelet thrombus formation is a highly dynamic process and yields a platelet thrombus with a distinct hierarchical structure composed of a "core" of highly activated platelets and a "shell" of platelets in a low activation state. This has given rise to the concept that therapeutic targeting of the propagating thrombus shell may hold promise as a means to target thrombosis while sparing hemostasis. While platelets have been historically considered central to arterial thrombosis, they have been traditionally viewed as minor contributors to the formation of venous thrombosis. However, this concept has recently been challenged with the emergence of a large body of evidence highlighting the important proinflammatory function of platelets. The proinflammatory function of platelets is afforded by their ability to induce neutrophil extracellular trap formation, enhance leucocyte recruitment, and secrete granular contents such as high mobility group protein B1 and polyphosphate. These proinflammatory processes trigger coagulation, via the intrinsic pathway, and are central to the formation of venous thrombosis, a condition now appreciated to be a form of sterile inflammation. These data now place platelets at the center stage in orchestrating the thromboinflammatory response underpinning venous thrombosis and have provided new hope that novel platelet-targeted therapeutics may represent a safe and effective approach to prevent venous thrombosis.

Weight-Based Enoxaparin for Venous Thromboembolism in Obesity Gives Similar Anti-Xa Levels to Patients <100 kg, with No Increase in Major Bleeding.

In trials assessing venous thromboembolism (VTE) treatment, obese patients are under-represented or excluded. The main objective of this article is to examine the safety of weight-based enoxaparin dosing in obesity, as assessed by anti-factor Xa (anti-Xa) activity, bleeding, and recurrence. A 5-year retrospective audit of patients with acute VTE, weighing > 100 kg, prescribed enoxaparin 1 mg/kg twice daily, with an anti-Xa level 2 to 6 hours post-dose. The primary outcome was anti-Xa levels, and the secondary outcomes were bleeding and recurrence. Results were compared with patients weighing < 100 kg (n = 64), and obese patients prescribed doses < 1 mg/kg (n = 28). One-hundred sixty-six patients weighing > 100 kg with VTE were identified, with 64 excluded for not fulfilling criteria. The remaining 102 patients had a median weight of 130 kg (range: 105-222 kg). The median peak anti-Xa level was 0.93 U/mL, with 56% of levels being in the proposed therapeutic range (0.5-1.0 U/mL), 40% > 1.0 U/mL, and 4% < 0.5 U/mL. The median anti-Xa levels and distribution were not significantly different between patients > 100 kg and patients < 100 kg, while obese patients prescribed < 1 mg/kg were more frequently subtherapeutic (21%). Regardless of weight, the majority of patients with moderate renal impairment (eGFR 30-59 mL/min) had an anti-Xa level > 1.0 U/mL (61%). In the obese patients, there was no major bleeding or recurrence within 30 days. In comparison, patients weighing < 100 kg, despite similar peak anti-Xa levels, had higher rates of bleeding and recurrence. This was likely due to their older age and comorbidities, particularly renal impairment and cancer. These data support weight-based dosing of enoxaparin in obesity with no maximum dose, ensuring therapeutic drug levels, with anti-Xa levels suggested in obese patients with clinical risk factors for bleeding.

Update on diagnosis and anticoagulant therapy for venous thromboembolism.

Venous thromboembolism (VTE) continues to be a common medical problem requiring the need for rapid treatment with anticoagulant therapy. Until the recent availability of the direct oral anticoagulants for treatment of VTE, the option for oral anticoagulation was limited to warfarin therapy. The addition of these new medications has been welcomed, but has led to added complexities in deciding the most appropriate agent for each patient based on individual risk factors. Furthermore, there are several circumstances where optimal duration of therapy is not well established. This article will focus on the diagnosis of VTE, the choice of anticoagulant and treatment duration.

MicroRNA-143 Activation Regulates Smooth Muscle and Endothelial Cell Crosstalk in Pulmonary Arterial Hypertension.

RATIONALE: The pathogenesis of pulmonary arterial hypertension (PAH) remains unclear. The 4 microRNAs representing the miR-143 and miR-145 stem loops are genomically clustered. OBJECTIVE: To elucidate the transcriptional regulation of the miR-143/145 cluster and the role of miR-143 in PAH. METHODS AND RESULTS: We identified the promoter region that regulates miR-143/145 microRNA expression in pulmonary artery smooth muscle cells (PASMCs). We mapped PAH-related signaling pathways, including estrogen receptor, liver X factor/retinoic X receptor, transforming growth factor-ß (Smads), and hypoxia (hypoxia response element), that regulated levels of all pri-miR stem loop transcription and resulting microRNA expression. We observed that miR-143-3p is selectively upregulated compared with miR-143-5p during PASMC migration. Modulation of miR-143 in PASMCs significantly altered cell migration and apoptosis. In addition, we found high abundance of miR-143-3p in PASMC-derived exosomes. Using assays with pulmonary arterial endothelial cells, we demonstrated a paracrine promigratory and proangiogenic effect of miR-143-3p-enriched exosomes from PASMC. Quantitative polymerase chain reaction and in situ hybridization showed elevated expression of miR-143 in calf models of PAH and in samples from PAH patients. Moreover, in contrast to our previous findings that had not supported a therapeutic role in vivo, we now demonstrate a protective role of miR-143 in experimental pulmonary hypertension in vivo in miR-143-/- and anti-miR-143-3p-treated mice exposed to chronic hypoxia in both preventative and reversal settings. CONCLUSIONS: MiR-143-3p modulated both cellular and exosome-mediated responses in pulmonary vascular cells, whereas inhibition of miR-143-3p blocked experimental pulmonary hypertension. Taken together, these findings confirm an important role for the miR-143/145 cluster in PAH pathobiology.

A Sex-Specific MicroRNA-96/5-Hydroxytryptamine 1B Axis Influences Development of Pulmonary Hypertension.

RATIONALE: Females are predisposed to pulmonary arterial hypertension (PAH); evidence suggests that serotonin, mutations in the bone morphogenetic protein receptor (BMPR) II gene, and estrogens influence development of PAH. The 5-hydroxytryptamine 1B receptor (5-HT1BR) mediates human pulmonary artery smooth muscle cell (hPASMC) proliferation. OBJECTIVES: We aimed to determine whether selected microRNAs (miRNAs) expressed in PASMCs are influenced by sex, BMPR-II mutations, and estrogens, and contribute to PASMC proliferation in PAH. METHODS: Expression levels of miRNAs targeting genes related to PAH, estrogen, and serotonin were determined by quantitative RT-PCR in hPASMCs and mouse PASMCs harboring a heterozygous mutation in BMPR-II (BMPR-II(R899X+/-) PASMCs). miRNA-96 targets 5-HT1BR and was selected for further investigation. miRNA target validation was confirmed by luciferase reporter assay. Precursor miRNA-96 was transfected into hPASMCs to examine effects on proliferation and 5-HT1BR expression. The effect of a miRNA-96 mimic on the development of hypoxic pulmonary hypertension in mice was also assessed. MEASUREMENTS AND MAIN RESULTS: miRNA-96 expression was reduced in BMPR-II(R899X+/-) PASMCs from female mice and hPASMCs from female patients with PAH; this was associated with increased 5-HT1BR expression and serotonin-mediated proliferation. 5-HT1BR was validated as a target for miRNA-96. Transfection of precursor miRNA-96 into hPASMCs reduced 5-HT1BR expression and inhibited serotonin-induced proliferation. Restoration of miRNA-96 expression in pulmonary arteries in vivo via administration of an miRNA-96 mimic reduced the development of hypoxia-induced pulmonary hypertension in the mouse. CONCLUSIONS: Increased 5-HT1BR expression may be a consequence of decreased miRNA-96 expression in female patient PASMCs, and this may contribute to the development of PAH.

A role for miR-145 in pulmonary arterial hypertension: evidence from mouse models and patient samples.

RATIONALE: Despite improved understanding of the underlying genetics, pulmonary arterial hypertension (PAH) remains a severe disease. Extensive remodeling of small pulmonary arteries, including proliferation of pulmonary artery smooth muscle cells (PASMCs), characterizes PAH. MicroRNAs (miRNAs) are noncoding RNAs that have been shown to play a role in vascular remodeling. OBJECTIVE: We assessed the role of miR-145 in PAH. METHODS AND RESULTS: We localized miR-145 in mouse lung to smooth muscle. Using quantitative PCR, we demonstrated increased expression of miR-145 in wild-type mice exposed to hypoxia. PAH was evaluated in miR-145 knockout and mice treated with anti-miRs via measurement of systolic right ventricular pressure, right ventricular hypertrophy, and percentage of remodeled pulmonary arteries. miR-145 deficiency and anti-miR-mediated reduction resulted in significant protection from the development of PAH. In contrast, miR-143 anti-miR had no effect. Furthermore, we observed upregulation of miR-145 in lung tissue of patients with idiopathic and heritable PAH compared with unaffected control subjects and demonstrated expression of miR-145 in SMC of remodeled vessels from such patients. Finally, we show elevated levels of miR-145 expression in primary PASMCs cultured from patients with BMPR2 mutations and also in the lungs of BMPR2-deficient mice. CONCLUSIONS: miR-145 is dysregulated in mouse models of PAH. Downregulation of miR-145 protects against the development of PAH. In patient samples of heritable PAH and idiopathic PAH, miR-145 is expressed in remodeled vessels and mutations in BMPR2 lead to upregulation of miR-145 in mice and PAH patients. Manipulation of miR-145 may represent a novel strategy in PAH treatment.

Does source matter? Examining the effects of health experts, friends, and social media influencers on young adult perceptions of Instagram e-cigarette education messages.

PURPOSE: Young adults' e-cigarette use is a leading public health concern. Using messages from credible sources can help improve message acceptance, yet little research has examined the role of source credibility on young adults' responses to e-cigarette education messages. METHODS: We examined the impact of source on young adults' perceptions of e-cigarette education messages and e-cigarettes. In July 2022, we conducted an experimental study using an online sample of young adults (N=459, Mage=24.6) who were randomized to one of three source conditions: expert, friend, or influencer, and viewed e-cigarette education messages. We used one-way ANOVA to estimate the association between the conditions and outcomes (perceived source credibility, message trust, curiosity, use interests, perceived message effectiveness, beliefs, harm perceptions, and intentions to refrain). RESULTS: The expert condition was associated with significantly higher perceived source credibility (vs. friend, influencer; p<0.001), message trust (vs. friend, influencer; p<0.001), and curiosity (vs. influencer; p's<0.05). CONCLUSIONS: Public health campaigns may leverage health experts to deliver e-cigarette education messages targeting young adults to improve effectiveness of the messages.

Plasma from patients with vaccine-induced immune thrombotic thrombocytopenia displays increased fibrinolytic potential and enhances tissue-type plasminogen activator but not urokinase-mediated plasminogen activation.

BACKGROUND: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare complication of adenovirus vector-based COVID-19 vaccines. VITT is associated with markedly raised levels of D-dimer; yet, how VITT modulates the fibrinolytic system is unknown. OBJECTIVES: We aimed to compare changes in fibrinolytic activity in plasma from patients with VITT, patients diagnosed with venous thromboembolism (VTE) after vaccination but without VITT (VTE-no VITT), and healthy vaccinated controls. METHODS: Plasma levels of plasmin-antiplasmin (PAP) complexes, plasminogen, and alpha-2-antiplasmin (α2AP) from 10 patients with VITT, 10 patients with VTE-no VITT, and 14 healthy vaccinated controls were evaluated by enzyme-linked immunosorbent assay and/or Western blotting. Fibrinolytic capacity was evaluated by quantitating PAP levels at baseline and after ex vivo plasma stimulation with 50-nM tissue-type plasminogen activator (tPA) or urokinase for 5 minutes. RESULTS: Baseline PAP complex levels in control and VTE-no VITT individuals were similar but were ∼7-fold higher in plasma from patients with VITT (P < .0001). VITT samples also revealed consumption of α2AP and fibrinogenolysis consistent with a hyperfibrinolytic state. Of interest, VITT plasma produced significantly higher PAP levels after ex vivo treatment with tPA, but not urokinase, compared to the other groups, indicative of increased fibrinolytic potential. This was not due to D-dimer as addition of D-dimer to VTE-no VITT plasma failed to potentiate tPA-induced PAP levels. CONCLUSION: A marked hyperfibrinolytic state occurs in patients with VITT, evidenced by marked elevations in PAP, α2AP consumption, and fibrinogenolysis. An unidentified plasma cofactor that selectively potentiates tPA-mediated plasminogen activation also appears to exist in the plasma of patients with VITT.

Cross-Sectional Analysis of Exome Sequencing Diagnosis in Patients With Neurologic Phenotypes Facing Barriers to Clinical Testing.

Background and Objectives: Exome sequencing (ES) demonstrates a 20-50 percent diagnostic yield for patients with a suspected monogenic neurologic disease. Despite the proven efficacy in achieving a diagnosis for such patients, multiple barriers for obtaining exome sequencing remain. This study set out to assess the efficacy of ES in patients with primary neurologic phenotypes who were appropriate candidates for testing but had been unable to pursue clinical testing. Methods: A total of 297 patients were identified from the UCLA Clinical Neurogenomics Research Center Biobank, and ES was performed, including bioinformatic assessment of copy number variation and repeat expansions. Information regarding demographics, clinical indication for ES, and reason for not pursuing ES clinically were recorded. To assess diagnostic efficacy, variants were interpreted by a multidisciplinary team of clinicians, bioinformaticians, and genetic counselors in accordance with the American College of Medical Genetics and Genomics variant classification guidelines. We next examined the specific barriers to testing for these patients, including how frequently insurance-related barriers such as coverage denials and inadequate coverage of cost were obstacles to pursuing exome sequencing. Results: The cohort primarily consisted of patients with sporadic conditions (n = 126, 42.4%) of adult-onset (n = 239, 80.5%). Cerebellar ataxia (n = 225, 75.8%) was the most common presenting neurologic phenotype. Our study found that in this population of mostly adult patients with primary neurologic phenotypes that were unable to pursue exome sequencing clinically, 47 (15.8%) had diagnostic results while an additional 24 patients (8.1%) had uncertain results. Of the 297 patients, 206 were initially recommended for clinical exome but 88 (42.7%) could not pursue ES because of insurance barriers, of whom 14 (15.9%) had diagnostic findings, representing 29.8% of all patients with diagnostic findings. In addition, the incorporation of bioinformatic repeat expansion testing was valuable, identifying a total of 8 pathogenic repeat expansions (17.0% of all diagnostic findings) including 3 of the common spinocerebellar ataxias and 2 patients with Huntington disease. Discussion: These findings underscore the importance and value of clinical ES as a diagnostic tool for neurogenetic disease and highlight key barriers that prevent patients from receiving important clinical information with potential treatment and psychosocial implications for patients and family members.

Incivility in COVID-19 Vaccine Mandate Discourse and Moral Foundations: Natural Language Processing Approach.

BACKGROUND: Vaccine hesitancy poses a substantial threat to efforts to mitigate the harmful effects of the COVID-19 pandemic. To combat vaccine hesitancy, officials in the United States issued vaccine mandates, which were met with strong antivaccine discourse on social media platforms such as Reddit. The politicized and polarized nature of COVID-19 on social media has fueled uncivil discourse related to vaccine mandates, which is known to decrease confidence in COVID-19 vaccines. OBJECTIVE: This study examines the moral foundations underlying uncivil COVID-19 vaccine discourse. Moral foundations theory poses that individuals make decisions to express approval or disapproval (ie, uncivil discourse) based on innate moral values. We examine whether moral foundations are associated with dimensions of incivility. Further, we explore whether there are any differences in the presence of incivility between the r/coronaviruscirclejerk and r/lockdownskepticism subreddits. METHODS: Natural language processing methodologies were leveraged to analyze the moral foundations underlying uncivil discourse in 2 prominent antivaccine subreddits, r/coronaviruscirclejerk and r/lockdownskepticism. All posts and comments from both of the subreddits were collected since their inception in March 2022. This was followed by filtering the data set for key terms associated with the COVID-19 vaccine (eg, "vaccinate" and "Pfizer") and mandates (eg, "forced" and "mandating"). These key terms were selected based on a review of existing literature and because of their salience in both of the subreddits. A 10% sample of the filtered key terms was used for the final analysis. RESULTS: Findings suggested that moral foundations play a role in the psychological processes underlying uncivil vaccine mandate discourse. Specifically, we found substantial associations between all moral foundations (ie, care and harm, fairness and cheating, loyalty and betrayal, authority and subversion, and sanctity and degradation) and dimensions of incivility (ie, toxicity, insults, profanity, threat, and identity attack) except for the authority foundation. We also found statistically significant differences between r/coronaviruscirclejerk and r/lockdownskepticism for the presence of the dimensions of incivility. Specifically, the mean of identity attack, insult, toxicity, profanity, and threat in the r/lockdownskepticism subreddit was significantly lower than that in the r/coronaviruscirclejerk subreddit (P<.001). CONCLUSIONS: This study shows that moral foundations may play a substantial role in the presence of incivility in vaccine discourse. On the basis of the findings of the study, public health practitioners should tailor messaging by addressing the moral values underlying the concerns people may have about vaccines, which could manifest as uncivil discourse. Another way to tailor public health messaging could be to direct it to parts of social media platforms with increased uncivil discourse. By integrating moral foundations, public health messaging may increase compliance and promote civil discourse surrounding COVID-19.

Extubation to High-Flow Nasal Cannula in Infants Following Cardiac Surgery: A Retrospective Cohort Study.

High-flow nasal cannula (HFNC) therapy is commonly used in the pediatric intensive care unit (PICU) for postextubation respiratory support. This hypothesis-generating retrospective cohort study aimed to compare postextubation PICU length of stay in infants extubated to HFNC and low flow oxygen (LF) in PICU following cardiac surgery. Of 136 infants (newborn to 1 year) who were intubated and mechanically ventilated in PICU following cardiac surgery, 72 (53%) were extubated to HFNC and 64 (47%) to LF. Compared with patients extubated to LF, those extubated to HFNC had significantly longer durations of cardiopulmonary bypass (152 vs. 109 minutes; p = 0.002), aortic cross-clamp (90 vs. 63 minutes; p = 0.003), and invasive mechanical ventilation (3.2 vs. 1.6 days; p < 0.001), although demographic and preoperative clinical variables were similar. No significant difference was observed in postextubation PICU length of stay between HFNC and LF groups in unadjusted analysis (3.3 vs. 2.6 days, respectively; p = 0.19) and after controlling for potential confounding variables (F [1,125] = 0.17, p = 0.68, R 2 = 0.16). Escalation of therapy was similar between HFNC and LF groups (8.3 vs. 14.1%; p = 0.41). HFNC was effective as rescue therapy for six patients in the LF group requiring escalation of therapy. Need for reintubation was similar between HFNC and LF groups (8.3 vs. 4.7%; p = 0.5). Although extubation to HFNC was associated with a trend toward longer postextubation PICU length of stay and was successfully used as rescue therapy for several infants extubated to LF, our results must be interpreted with caution given the limitations of our study.