Rho (United States)

Individuals with autoimmune diseases (AD) on immunosuppressants often have suboptimal responses to COVID-19 vaccine. We evaluated the efficacy and safety of additional COVID-19 vaccines in those treated with mycophenolate mofetil/mycophenolic acid (MMF/MPA), methotrexate (MTX), and B cell-depleting therapy (BCDT), including the impact of withholding MMF/MPA and MTX. In this open-label, multicenter, randomized trial, 22 participants taking MMF/MPA, 26 taking MTX, and 93 treated with BCDT who had suboptimal antibody responses to initial COVID-19 vaccines (2 doses of BNT162b2 or mRNA-1273 or 1 dose of AD26.COV2.S) received an additional homologous vaccine. Participants taking MMF/MPA and MTX were randomized (1:1) to continue or withhold treatment around vaccination. The primary outcome was the change in anti-Wuhan-Hu-1 receptor-binding domain (RBD) concentrations at 4 weeks post-additional vaccination. Secondary outcomes included adverse events, COVID-19 , and AD activity through 48 weeks. Additional vaccination increased anti-RBD concentrations in participants taking MMF/MPA and MTX , irrespective of immunosuppressant withholding. BCDT-treated participants also demonstrated increased anti-RBD concentrations, albeit lower than MMF/MPA- and MTX-treated cohorts. COVID-19 occurred in 33% of participants; infections were predominantly mild and included only three non-fatal hospitalizations. Additional vaccination was well-tolerated, with low frequencies of severe disease flares and adverse events. Additional COVID-19 vaccination is effective and safe in individuals with ADs treated with immunosuppressants, regardless of whether MMF/MPA or MTX is withheld. gov (NCT05000216; registered August 6, 2021: https://clinicaltrials.gov/ct2/show/NCT05000216).

Background:It is unknown whether nasal corticosteroid (NCS) or inhaled corticosteroid (ICS) use impacts the susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.Objectives:We sought to examine the associations of NCS and ICS use with the risk of SARS-CoV-2 infection among individuals with allergic rhinitis or asthma.Methods:This is a prospective, multicenter, SARS-CoV-2 surveillance study of households with children. Nasal swabs were obtained from participants every 2 weeks with additional collections based on coronavirus disease 2019–related symptoms. In our primary adjusted models, we examined the association of NCS or ICS use at study entry (in participants with allergic rhinitis or asthma, respectively) with the time to the first SARS-CoV-2–positive quantitative PCR testing using Cox proportional hazard regression.Results:There were 2211 participants in the 1113 households included. The associations of NCS and ICS use with the risk of SARS-CoV-2 infection were modified by age (P for both interactions <.05). NCS and ICS use were individually associated with higher risks of SARS-CoV-2 infection among adults (adjusted hazard ratio [aHR] = 1.88, 95% CI: 1.14-3.12, P = .01, and aHR = 2.15, 95% CI: 1.003-4.63, P = .049, respectively). The association of NCS use with the risk of SARS-CoV-2 infection in adults was consistent in a series of sensitivity analyses. There was no association of NCS or ICS use with the risk of SARS-CoV-2 infection in children.Conclusion:Our findings suggest that the risk of SARS-CoV-2 infection is increased in adults who use NCS but not in children. Similar, albeit less consistent, age-dependent findings were observed for ICS use. While the results of this observational study should be interpreted with caution, they emphasize the need to conduct studies to understand potential mechanisms that could explain these findings.

ObjectiveFibromyalgia is the prototypic nociplastic chronic pain syndrome, characterized by widespread pain, nonrestorative sleep, and fatigue. We evaluated efficacy and safety of bedtime TNX-102 SL (sublingual cyclobenzaprine) 5.6 mg for treatment of fibromyalgia.MethodsThis phase 3, double-blind, multicenter, placebo-controlled trial randomized patients 1:1 to once-nightly TNX-102 SL 2.8 mg for 2 weeks, followed by 5.6 mg for 12 weeks, or to matching placebo (NCT05273749). The primary endpoint was change from baseline at week 14 in weekly average of daily diary pain intensity scores. Secondary endpoints included Patient Global Impression of Change, Fibromyalgia Impact Questionnaire (Revised) Symptoms and Function domains, Patient-Reported Outcomes Measurement Information System instruments for Sleep Disturbance and Fatigue, and daily diary sleep quality scores.ResultsOverall, 81.0% (n = 187/231) and 79.6% (n = 179/225) of patients receiving TNX-102 SL and placebo completed the trial, respectively. Treatment with TNX-102 SL vs placebo was associated with significantly greater reductions in the primary pain endpoint (P < .001; mean [SE], −1.8 [0.12] vs −1.2 [0.12]) and in each of the 6 secondary endpoints (P ≤ .001; all). The most common systemic treatment-emergent adverse events (TEAEs) with TNX-102 SL and placebo were COVID-19 (4.3% vs 3.1%, respectively), headache (3.0% vs 1.8%), and somnolence (3.0% vs 1.3%); the most common TEAEs overall were local administration-site reactions including oral hypoesthesia (23.4% vs 0.4%), product taste abnormal (11.3% vs 0.9%), and oral paresthesia (6.9% vs 0.9%), which were transient and self-limited.ConclusionBedtime TNX-102 SL treatment was associated with significant improvements in fibromyalgia symptoms and function and was well tolerated.Clinical trial registrationClinicalTrials.gov/study/NCT05273749, first patient screened March 21, 2022.

Rationale: Chronic lung allograft dysfunction (CLAD) hinders lung transplant success. A 2019 consensus refined CLAD diagnosis, introducing probable or definite CLAD based on persistence of lung function decline. Outcomes and risks for probable CLAD remain uncertain. Objectives: We sought to determine the prognosis and clinical risks for probable CLAD in a prospective multicenter cohort. Methods: Clinical Trials in Organ Transplantation-20 included 745 CLAD-eligible adult lung recipients at five centers and applied rigorous methods to prospectively adjudicate probable CLAD. The impact of probable CLAD on graft loss was determined using a Cox model that considered CLAD as a time-dependent covariate. Regularized Cox modeling with least absolute shrinkage and selection operator (LASSO) penalty was used to evaluate donor or recipient characteristics and the occurrence and timing of posttransplant events as probable CLAD risks. Similar analyses were performed for definite CLAD. Measurements and Main Results: Probable CLAD occurred in 29.7% of patients at 3 years posttransplant and conferred a marked increase in risk for graft loss (unadjusted hazard ratio = 4.38, P < 0.001). Most patients (80%) with probable CLAD progressed to definite CLAD. Cytomegalovirus infection and, specifically, late presence (>90 d posttransplant) of donor-specific alloantibodies, acute rejection, acute lung injury, or organizing pneumonia contributed the greatest independent information about probable CLAD risk. Definite CLAD risks were similar. Conclusions: Probable CLAD identifies patients at high risk for graft loss, supporting prospective identification of this condition for early initiation of CLAD-directed interventions. More effective strategies to prevent posttransplant cytomegalovirus, inhibit allospecific immunity, and reduce tissue injury are needed to reduce probable CLAD and improve lung recipient survival. Clinical trial registered with www.clinicaltrials.gov (NCT02631720).

Today's digital phased array architectures face the challenges of exponential growth in processing and digital data flow as arrays increase in size, element count, instantaneous bandwidth, and other factors. Traditional methods of beamforming, adaptive beamforming, and heretofore unexplored array functions cannot be sustained due to processing and data flow bottlenecks common to current digital architectures, which remain linked to inherently analog methods of beam-oriented array processing. DARPA's Scalable On-Array Processing (SOAP) [1] aims to look at new architectures that support new forms of on-array distributed processing architectures and data flow management to enable digital arrays to realize their full potential.

Tunable optical materials can enable more functionality while maintaining flexibility in a single aperture, which is relevant to making visible and infrared image sensing more context aware. DARPA’s Accelerating discovery of Tunable Optical Materials (ATOM) program is exploring fundamental insights into the physics of tunable optical materials with the goal of developing new materials for optic and photonic applications. The specific characteristics of interest are a large change in refractive index (Δn) to delay light, low loss for high transmissivity (k), and fast switching speeds. Rare earth nickelates and phase change materials, integrated with machine learning to accelerate insights into new materials, show initial promise toward the ATOM program goals.

This study aimed to evaluate misinformation surrounding infertility and the COVID-19 vaccine on X (formerly known as Twitter) by analyzing the prevalence and content of this misinformation across a sample of posts on X. This study is a retrospective review of posts on X (formerly known as tweets) from the COVID-19-TweetIDs dataset from July 2021 and November 2021. Included posts were from crucial time points in the COVID-19 vaccine discourse and contained at least one word related to COVID-19 vaccination and fertility. Posts were analyzed and categorized based on factuality, common words, and hashtags. Descriptive statistics on total followers, account verification status, and engagement were obtained. Differences between posts on X classified as factual and misinformation were examined using analysis of variance or χ2 tests. Sentiment analysis determined if post content was generally positive, neutral, or negative. A total of 17,418 relevant posts on X were reviewed: 11,436 from timeframe 1 (July 2021) and 5982 from timeframe 2 (December 2021). Misinformation posts rose from 29.9% in July 2021 to 45.1% in November 2021. In both timeframes, accounts sharing factual information had more followers (p < 0.001), and verified users were more likely to share accurate posts (p ≤ 0.001). Factual and misinformation posts had similar engagement. Sentiment analysis identified that real posts were more positive and misinformation posts were more negative (p < 0.001). Misinformation about the COVID-19 vaccine and fertility is highly prevalent on X and threatens vaccine uptake in patients desiring future fertility. Accounts sharing factual information were likely to have more followers and be verified; therefore, verifying more physicians sharing accurate information is critical.