Citations

Importance Treatment for cognitive dysfunction due to postacute sequelae of long COVID (ie, symptoms of fatigue, malaise, weakness, confusion that persist beyond 12 weeks after an initial COVID infection) remains a significant unmet need. Objective To test evidence-based rehabilitation strategies for improving cognitive symptoms in persons with long COVID. Design, Setting, and Participants This was a 5-arm, multicenter, randomized clinical trial of 3 remotely delivered interventions conducted between August 17, 2023, and June 10, 2024. The study took place at 22 trial sites and included the screening of individuals with cognitive long COVID. Interventions Participants were randomized to 1 of 5 arms: adaptive computerized cognitive training (BrainHQ [Posit Science]), cognitive-behavioral rehabilitation involving both group and individual counseling sessions (PASC-Cognitive Recovery [PASC-CoRE]) paired with BrainHQ, and transcranial direct current stimulation (tDCS) paired with BrainHQ. Two comparator arms were included as follows: unstructured computer puzzles and games (active comparator) and sham tDCS paired with BrainHQ. The interventions occurred 5 times per week over 10 weeks. Main Outcomes and Measures Cognitive and behavioral in-person assessments were performed at baseline, midintervention, at the end of intervention, and 3 months after the end of the intervention. The primary outcome measure was the modified Everyday Cognition Scale 2 (ECog2) completed at the end of the intervention compared to the baseline visit based on participant self-report looking back over the prior 7 days. Results A total of 378 individuals were screened, from which there were 328 participants (median [IQR] age, 48.0 [37.0-58.0] years; 241 female [73.5%]; race: 15 Asian [4.6%], 47 Black [14.3%], and 235 White [71.6%]; ethnicity: 52 Hispanic [15.9%]). None of the 3 active interventions demonstrated benefits on the modified ECog2 in the intention-to-treat population by the end of the intervention period. The adjusted differences in mean change were 0.0 (95% CI, −0.2 to 0.2) for BrainHQ vs active comparator, 0.1 (95% CI, −0.1 to 0.3) for PASC-CoRE + BrainHQ vs active comparator, 0.0 (95% CI, −0.2 to 0.2) for tDCS-active + BrainHQ vs tDCS-sham + BrainHQ, and 0.1 (95% CI, −0.1 to 0.3) for PASC-CoRE + BrainHQ vs BrainHQ alone. Secondary participant-reported outcomes and neuropsychological tests showed no differential benefits for any treatment arm. All 5 arms demonstrated some improvements over time on the modified ECog2 and on secondary outcomes. There were no serious adverse events attributable to the interventions. Conclusions and Relevance This phase 2 randomized clinical trial failed to demonstrate differential benefits for online cognitive training, a structured cognitive rehabilitation program, and tDCS for cognitive long COVID. Trial Registration ClinicalTrials.gov Identifier: NCT05965739 .

Objective To examine real‐world patterns in pain management among adults with systemic lupus erythematosus (SLE), we focused on the sequencing of pain modalities, polypharmacy, and demographic variation. Methods We conducted a retrospective analysis of electronic health records from adults with SLE treated at a single academic medical center between 2005 and 2024. We included patients who received at least one pain‐related therapy, including glucocorticoids, opioids, nonsteroidal anti‐inflammatory drugs (NSAIDs), antidepressants, anticonvulsants, muscle relaxants, and nonpharmacologic interventions. We used sequence analysis and Sankey diagrams to map treatment trajectories and compared patterns across two periods: 2005 to 2014 and 2015 to 2024. Polypharmacy was defined as receiving five or more pain‐related prescriptions within 12 months. We examined trends by age, sex, and race or ethnicity. Results Among 769 patients, initiation of glucocorticoids and opioids declined over time (58%–51% and 28%–22%, respectively), whereas NSAID use increased (19%–29%). The median number of pain prescriptions decreased, and polypharmacy prevalence dropped from 53% to 45%. In recent years, younger adults and men received more prescriptions, with 69% of men receiving five or more compared with 43% of women. Racial disparities narrowed overall in recent years but persisted in sensitivity analyses excluding glucocorticoids. Conclusion Pain management in SLE is shifting away from high‐risk therapies; however, prescribing intensity remains high and varies by demographic group. Visualizations serve as a complementary lens to traditional prescription counts, allowing representation of polypharmacy not only by volume but also by the diversity and sequencing of therapeutic classes over time.

Background/Objectives: Erythromelalgia is a rare condition characterized by burning pain, redness, and warmth primarily in the extremities, usually worsened by heat and alleviated by cold. The objective of this study was to identify the top 10 priorities in pediatric erythromelalgia from multiple perspectives, including clinicians, people with lived experience of childhood-onset erythromelalgia, and their family members. Methods: A modified James Lind Alliance Priority-Setting Process was conducted. The top priorities were identified through four phases: (1) an international online survey to gather priorities, (2) data processing, (3) an interim prioritization online survey, and (4) a virtual workshop to set the final priorities. Results: In phase 1, 185 potential priorities were submitted by 74 respondents (53% patients, 24% family members, and 23% clinicians) that were developed into 68 unique research questions (phase 2). In phase 3, of the 68 questions, 50 were rated for importance by 58 participants (38% patients, 36% family members, and 26% clinicians), reducing the list to 25 questions. In phase 4, the top 10 was reached through consensus by 12 participants (33% patients, 25% family members, and 42% clinicians) across Canada, South Africa, the United States of America, and the United Kingdom. Conclusions: The final priorities focused on the treatment of erythromelalgia, understanding underlying mechanisms, the association of erythromelalgia with various body systems, and generating awareness. This list is the first international patient-centered research agenda for childhood-onset erythromelalgia and a call to action from key partners to improve future research and care.

Background: Atrial fibrillation (AF) is the most common sustained arrhythmia with prevalence increasing over the last decade. However, data on recent temporal trends in incidence of AF have been inconsistent, with some reports of increasing trends over time and others indicating no change in incidence over time. Therefore, we aimed to determine how the incidence of AF has changed over the last decade in a community in the Midwest USA. Methods: Between 2013 and 2023, adults (aged 18 and older) with incident AF were identified in a 27-county region in the Midwest. AF was identified using diagnostic codes by employing an electronic algorithm requiring 1 inpatient code or 2 outpatient codes separated by >7 days but within 1 year. For total rates, age - and sex-adjusted incidence rates were standardized to the 2010 US total population. Poisson regression was used to calculate the incidence rate ratio of AF for 2023 vs 2013. Results: We identified 44,930 individuals with incident AF from 2013 to 2023. Of these, 56.4% were male, the mean (SD) age was 72.8 (13.5) years, and 95.8% were non-Hispanic white. The age-and sex-adjusted incidence rates (per 1,000) and 95% confidence intervals standardized to the 2010 US total population were 5.24 (5.07-5.41) in 2013, 5.73 (5.56-5.91) in 2018, and 5.44 (5.28-5.61) in 2023. Although a drop in incidence was observed corresponding to the COVID-19 pandemic, a small increase in the overall incidence of AF was observed over time. The overall incidence rate ratio (95% CI) for 2023 vs 2013 was 1.07 (1.02-1.11), P=0.003. The incidence rates were higher in men compared to women and increased with older age ( Figure 1 ). However, differences in AF incidence by sex were greatest in the youngest age group and attenuated with older age (incidence rate ratio (95% CI): 2.18 (2.10-2.28) for ages 18-64 years, 1.76 (1.70-1.83) for ages 65-74 years, 1.38 (1.33-1.42) for ages 75-84 years, and 1.23 (1.18-1.28) for ages 85 years and older). Conclusion: In this 27-county region in the Midwest, although small in magnitude, a statistically significant increase in AF incidence was observed over time from 2013 to 2023. Furthermore, the incidence of AF was higher in men compared with women, especially in younger age groups.

Objective Patients with chronic illness share their experiences in online communities and generate rich data on pain management. This study applied natural language processing methods, including large language models (LLMs), to Reddit discussions from lupus communities to characterize multidimensional pain experiences framed in the biopsychosocial model. Methods We extracted Reddit posts from the r/Lupus and r/LupusSupport subreddits posted from June 9, 2010, through December 31, 2023. Pain‐related posts were identified using a clinically informed pain lexicon. Topic modeling was used to identify thematic patterns, which were then compared with structured summaries generated by LLM instructions that were fine‐tuned using the biopsychosocial model of pain. Two reviewers conducted content analysis of the LLM‐generated summaries, evaluating thematic accuracy and coverage. Results Data from Reddit included 31,785 posts from 10,857 authors. We identified common pain complaints, management strategies, and sociocultural, affective, and nociplastic dimensions of pain. Instruction fine‐tuned LLMs produced structured summaries with an average thematic accuracy score of 3.1 of 4 (kappa = .09) and content coverage score of 2.9 of 4 (kappa = .38). Sociocultural features presented in 123 posts (33.8%), including peer support and validation (n = 106) and provider interactions or access issues (n = 35). Nociplastic pain presented in 205 posts (56.3%). Conclusion Natural language processing methods can be used to extract rich, multidimensional insights into pain experiences from online communities focused on lupus. These approaches highlight the psychological, social, and cultural facets of pain that may be underrepresented in clinical settings, supporting more patient‐centered approaches to care in rheumatology.

BACKGROUND: Acute mesenteric ischemia (AMI) is a vascular emergency where delays in diagnosis or treatment can lead to irreversible bowel injury and death. Many patients initially present to hospitals without surgical or vascular capabilities and require interhospital transfer. The clinical impact of such transfers on treatment and outcomes in AMI remains poorly defined. STUDY DESIGN: We performed a retrospective cohort study using the National Inpatient Sample (2019 to 2021) to evaluate the association between interhospital transfer and outcomes in patients with AMI. Adult patients with a primary diagnosis of AMI were identified using ICD-10 codes. Patients were categorized by transfer status. Multivariable logistic regression was used to evaluate associations with in-hospital mortality and procedural interventions, adjusting for age and comorbidity burden. RESULTS: Of 39,690 hospitalizations for AMI, 14.6% involved interhospital transfer. Transferred patients had a higher comorbidity burden and were more often treated at rural or micropolitan hospitals. They were significantly more likely to undergo major surgical and vascular procedures, including bowel resection (odds ratio [OR] 3.48), mesenteric bypass (OR 3.32), and angioplasty (OR 2.66; all p < 0.0001). Markers of critical illness, such as intubation (OR 2.15) and dialysis (OR 1.30), were also more frequent in this group. In-hospital mortality was significantly higher among transferred patients (OR 2.05), and transfer remained independently associated with increased mortality after adjusting for age and comorbidity burden (adjusted OR 1.67, 95% CI 1.32 to 2.10). CONCLUSIONS: Interhospital transfer in AMI is strongly associated with increased clinical severity and in-hospital mortality. These findings emphasize the urgency of early diagnosis, rapid triage, and timely access to definitive care, supporting the need for structured regional systems and transfer protocols for AMI.

A 59-year-old woman presented with a persistent, nonpruritic erythematous rash on both lower extremities. Dermoscopy showed petechiae and hemosiderin deposition, and biopsy revealed perivascular lymphocytic infiltration with red blood cell extravasation, confirming Schamberg disease. Laboratory studies were unremarkable. Minimal improvement with topical corticosteroids prompted addition of oral rutoside, ascorbic acid, and pentoxifylline, resulting in gradual fading of lesions. Schamberg disease is a benign, chronic pigmented purpuric dermatosis that can mimic vasculitis. Diagnosis requires clinical and histologic correlation, and management focuses on cosmetic improvement and patient reassurance regarding its nonprogressive nature.

Abstract Oxygen deprivation within large or poorly vascularized bone defects remains a key barrier to successful regeneration, especially during the early postimplantation period before vascular ingrowth. Here, the development of COSnPPOD (CaO 2 –Silica NP Platform for Osteogenic Development) is reported, a visible light digital light processing‐printed hydrogel scaffold that integrates oxygen‐releasing nanoparticles (NPs) within a Primitive‐type triply periodic minimal surface architecture. The scaffold combines a gelatin methacrylate‐poly(ethylene glycol) diacrylate matrix with calcium peroxide (CaO 2 )‐loaded hollow silica NPs, enabling localized, short‐term oxygen release while preserving structural fidelity. COSnPPOD scaffolds demonstrate favorable degradation kinetics, tunable stiffness, and increased protein adsorption in vitro. In a preosteoblast model, COSnPPOD maintains cell viability and supports osteogenic gene expression without cytotoxic effects. While overall gene expression is comparable to controls, a 16‐fold increased expression of phosphoprotein 1 (Spp1) suggests scaffold‐driven activation of matrix remodeling pathways. In vivo, COSnPPOD scaffolds enhance bone regeneration in a murine calvarial defect model, with significantly greater bone formation and collagen deposition than untreated defects and hydrogel controls. Additionally, vascular endothelial growth factor immunostaining is increased within the defect, consistent with a proangiogenic response, and no systemic toxicity is observed. These findings establish COSnPPOD as a promising scaffold system that combines sustained oxygenation with biomimetic geometry to support localized bone regeneration.

Bone health is a key determinant of success in spine surgery, making preoperative assessment of bone quality essential to optimal surgical risk stratification. Magnetic resonance imaging (MRI)-based vertebral bone quality (VBQ) score offers a novel approach to assess bone health in spine surgery candidates. The ability of MRI to assess bone quality without exposure to ionizing radiation makes it a potentially advantageous alternative to other traditional measures of bone density. VBQ has additionally shown potential to predict adverse outcomes, such as fragility fractures, instrumentation failure, subsidence and proximal junctional kyphosis. Variations of VBQ, such as endplate bone quality, S1 VBQ, and cervical VBQ, provide targeted insights at specific anatomical regions and potentially enhance the predictive accuracy of VBQ. However, clinical application of VBQ is limited by variability in MRI systems, patient-specific factors, and lack of standardized threshold values. This review aims to critically evaluate VBQ scores as an opportunistic, MRI-based assessment of bone health and its potential role in predicting surgical outcomes. While VBQ may provide some valuable insights into bone health, its role in preoperative risk assessment likely remains supplementary and requires further research to establish clinical validity and optimal cutoffs.

Background Catatonia in medically ill patients is rare but often unrecognized. This monograph summarizes current knowledge on the diagnosis, epidemiology, etiology, and management of catatonia occurring in the medical setting. Methods PubMed searches were used to identify relevant articles from 1962 to present. Results More than 3,000 articles were obtained and reviewed for relevance, including references of articles identified by the initial search. Several areas were identified as important, including: (1) catatonia and delirium; (2) malignant catatonia; (3) pediatric catatonia; (4) catatonia associated with another medical condition (CAMC); (5) drug exposure and withdrawal syndromes associated with catatonia; and (6) treatment of catatonia in the medical setting. Conclusions Catatonia in the medically ill appears to have numerous etiologies, although etiology does not seem to modify the general treatment approach of prompt administration of lorazepam. Delirium and catatonia are commonly comorbid in the medical setting and should not be viewed as mutually exclusive. Electroconvulsive therapy should be offered to patients who do not respond to benzodiazepines or have malignant features. Removing offending agents and treating the underlying medical condition is paramount when treating CAMC. Memantine or amantadine may be helpful adjunctive agents. There is not enough evidence to support the use of antipsychotics or stimulants in treating CAMC.