Background Catheter ablation procedures with transseptal punctures (usually for atrial fibrillation) are often associated with migraine-related visual auras, but the mechanism remains unknown. Whether this phenomenon is mediated by the creation of an atrial septal defect from transseptal puncture or by silent acute brain emboli detected on magnetic resonance imaging related to the procedure remains to be investigated. Objective This study aimed to evaluate whether randomization to a transseptal puncture during catheter ablation for ventricular arrhythmias is associated with postprocedural visual auras and assess the relationship between occipital and parietal lobes acute brain emboli and migraine-related visual auras. Methods In the Transseptal Versus Retrograde Aortic Ventricular Entry to Reduce Systemic Emboli trial, patients undergoing catheter ablation for ventricular arrhythmias were randomized to ventricular access via transseptal puncture vs a retrograde aortic approach. All had brain magnetic resonance imaging the day after their procedure and underwent a validated migraine assessment at 1 month. Results No differences in postablation visual auras were observed between transseptal (16% of 63) and retrograde aortic approaches (14% of 57; P = .78). However, more participants with acute brain emboli in the occipital or parietal lobes experienced migraine-related visual auras (38% vs 11%; P < .01). After multivariable adjustment, the presence of acute brain emboli was associated with 12-fold greater odds of visual auras. Conclusion Transseptal puncture was not associated with visual auras; however, acute brain emboli involving the visual cortex were associated with such symptoms. These data suggest that transseptal puncture is not causal in migraine-related visual auras and that postprocedure acute brain emboli are apparently not always clinically silent.

Rationale & Objective: There is known variability in the management of kidney transplant recipients facing graft failure. We hypothesized that variations in the timing of care transitions, immunosuppression weaning, and re-evaluation processes would be associated with differential access to retransplantation and relisting. Study Design: An observational study. Setting & Participants: Survey directed at medical directors of US transplant centers. Exposures: Transplant center-reported practices. Outcomes: Time to retransplantation (and secondarily, relisting) after graft failure. Analytical Approach: Adjusted proportional hazards models with clustering by transplant center. Results: Of the 178 surveyed centers, 77 unique transplant centers (43%) responded. Respondents reported significant variability in the timing of transition of patients back to general nephrologists (ranging from within 1 year of transplantation to never), weaning of immunosuppression with graft failure, and approach to assessments of frailty and adherence during the evaluation for relisting. Transplant centers that transitioned patients back to general nephrologists >3 to <5 years after transplant had lower likelihood of retransplantation (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.73-0.88) and relisting (HR, 0.80; 95% CI, 0.75-0.85) compared with centers that transitioned patients earlier (between 1-3 years of transplantation). Transplant centers that did not oversee weaning of immunosuppression after graft failure had patients with a lower likelihood of retransplantation (HR, 0.89; 95% CI, 0.79-0.99) and relisting (HR, 0.88; 95% CI, 0.82-0.95) compared with centers that oversaw this weaning. Withdrawal of immunosuppression 12-24 months after return to dialysis was associated with a higher likelihood of retransplantation (HR, 1.28; 95% CI, 1.14-1.43) and relisting (HR, 1.15; 95% CI, 1.06-1.26) compared with withdrawal of immunosuppression within 6 months of graft failure. Limitations: Observational nature of data and potential for residual confounding. Conclusions: There is significant variation in the management of patients with graft failure across US transplant centers during the transition of care, and this variation was associated with differential access of patients to retransplantation and relisting. Plain-Language Summary: Transplant centers vary in how they approach the management of transplant recipients with low kidney function facing graft failure. In this study, we surveyed transplant centers about their practices when working with patients with impending graft failure and linked these practices to access of patients to relisting and retransplantation using the national end-stage kidney disease registry. Respondents reported significant variability in the timing of the transition of care for transplant recipients back to general nephrologists, weaning of immunosuppression with graft failure, and approach to assessments of frailty and adherence during the evaluation for relisting and retransplantation. These variations in practice were often associated with differential access of patients to relisting and retransplantation.

Background South Asian individuals have high risk of atherosclerotic cardiovascular disease (ASCVD). Some investigators suggest smaller coronary artery size may be partially responsible. Methods We compared the left anterior descending (LAD) artery cross-sectional area (CSA) (lumen and arterial wall) among South Asians in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study with White and Black participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study, adjusting for BMI, height, and other ASCVD risk factors. We used thin-slice non-contrast cardiac computed tomography to measure LAD CSA. We used linear regression models to determine whether race/ethnicity was associated with LAD CSA after adjusting for demographic factors, BMI, height, coronary artery calcium (CAC), and traditional cardiovascular risk factors. Results Our sample included 3,353 participants: 513 self-identified as South Asian (44.4% women), 1286 as Black (59.6% women), and 1554 as White (53.5% women). After adjusting for age, BMI, height, there was no difference in LAD CSA between South Asian men and women compared to White men and women, respectively. After full adjustment for CVD risk factors, LAD CSA values were: South Asian women (19.9 mm 2 , 95% CI [18.8 – 20.9]) and men (22.3 mm 2 , 95% CI [21.4 – 23.2]; White women (20.0 mm 2 , 95% CI [19.4—20.5]) and men (23.6 mm 2 , 95% CI [23.0—24.2]); and Black women (21.6 mm 2 , 95% CI [21.0 – 22.2]) and men (26.0 mm 2 , 95% CI [25.3 – 26.7]). Height, BMI, hypertension, CAC, and age were positively associated with LAD CSA; current and former cigarette use were inversely associated. Conclusions South Asian men and women have similar LAD CSA to White men and women, and smaller LAD CSA compared to Black men and women, respectively, after accounting for differences in body size. Future studies should determine whether LAD CSA is associated with future ASCVD events.

Background Oral nirmatrelvir/ritonavir is a treatment for COVID-19, but whether treatment during the acute phase reduces the risk of developing Long COVID is unknown. Methods Using the Covid Citizen Science (CCS) online cohort, we surveyed individuals who reported their first SARS-CoV-2 positive test between March and August 2022 regarding Long COVID symptoms. We excluded those who were pregnant, unvaccinated, hospitalized for COVID-19, or received other antiviral therapy. The primary exposure was oral nirmatrelvir/ritonavir. The primary outcome was the presence of any Long COVID symptoms reported on cross-sectional surveys in November and December 2022. We used propensity-score models and inverse probability of treatment weighting to adjust for differences in treatment propensity. Our secondary question was whether symptom or test positivity rebound were associated with Long COVID. Results 4684 individuals met the eligibility criteria, of whom 988 (21.1%) were treated and 3696 (78.9%) were untreated; 353/988 (35.7%) treated and 1258/3696 (34.0%) untreated responded to the survey. Median age was 55 years and 66% were female. We did not identify an association between nirmatrelvir/ritonavir treatment and Long COVID symptoms (OR 1.15; 95%CI 0.80-1.64). Among n=666 treated with nirmatrelvir/ritonavir who responded who responded to questions about rebound, rebound symptoms or test positivity were not associated with Long COVID symptoms (OR 1.34; 95%CI 0.74-2.41; p=0.33). Conclusions Within this cohort, treatment with nirmatrelvir/ritonavir among vaccinated, non-hospitalized individuals was not associated with lower prevalence of Long COVID symptoms or severity of Long COVID. Experiencing rebound symptoms or test positivity is not strongly associated with developing Long COVID.

ABSTRACTImportanceProlonged symptoms following SARS-CoV-2 infection, or Long COVID, is common, but few prospective studies of Long COVID risk factors have been conducted.ObjectiveTo determine whether sociodemographic factors, lifestyle, or medical history preceding COVID-19 or characteristics of acute SARS-CoV-2 infection are associated with Long COVID.DesignCohort study with longitudinal assessment of symptoms before, during, and after SARS-CoV-2 infection, and cross-sectional assessment of Long COVID symptoms using data from the COVID-19 Citizen Science (CCS) study.SettingCCS is an online cohort study that began enrolling March 26, 2020. We included data collected between March 26, 2020, and May 18, 2022.ParticipantsAdult CCS participants who reported a positive SARS-CoV-2 test result (PCR, Antigen, or Antibody) more than 30 days prior to May 4, 2022, were surveyed.ExposuresAge, sex, race/ethnicity, education, employment, socioeconomic status/financial insecurity, self-reported medical history, vaccination status, time of infection (variant wave), number of acute symptoms, pre-COVID depression, anxiety, alcohol and drug use, sleep, exercise.Main OutcomePresence of at least 1 Long COVID symptom greater than 1 month after acute infection. Sensitivity analyses were performed considering only symptoms beyond 3 months and only severe symptoms.Results13,305 participants reported a SARS-CoV-2 positive test more than 30 days prior, 1480 (11.1% of eligible) responded to a survey about Long COVID symptoms, and 476 (32.2% of respondents) reported Long COVID symptoms (median 360 days after infection).Respondents’ mean age was 53 and 1017 (69%) were female. Common Long COVID symptoms included fatigue, reported by 230/476 (48.3%), shortness of breath (109, 22.9%), confusion/brain fog (108, 22.7%), headache (103, 21.6%), and altered taste or smell (98, 20.6%). In multivariable models, number of acute COVID-19 symptoms (OR 1.30 per symptom, 95%CI 1.20-1.40), lower socioeconomic status/financial insecurity (OR 1.62, 95%CI 1.02-2.63), pre-infection depression (OR 1.08, 95%CI 1.01-1.16), and earlier variants (OR 0.37 for Omicron compared to ancestral strain, 95%CI 0.15-0.90) were associated with Long COVID symptoms.Conclusions and RelevanceVariant wave, severity of acute infection, lower socioeconomic status and pre-existing depression are associated with Long COVID symptoms.Key PointsQuestionWhat are the patterns of symptoms and risk factors for Long COVID among SARS-CoV-2 infected individuals?FindingsPersistent symptoms were highly prevalent, especially fatigue, shortness of breath, headache, brain fog/confusion, and altered taste/smell, which persisted beyond 1 year among 56% of participants with symptoms; a minority of participants reported severe Long COVID symptoms. Number of acute symptoms during acute SARS-CoV-2 infection, financial insecurity, pre-existing depression, and infection with earlier variants are associated with prevalent Long COVID symptoms independent of vaccination, medical history, and other factors.MeaningSeverity of acute infection, SARS-CoV-2 variant, and financial insecurity and depression are associated with Long COVID symptoms.

Importance Self-measured blood pressure (SMBP) with commercially available connected smartphone applications may help patients effectively use SMBP measurements. Objective To determine if enhanced SMBP paired with a connected smartphone application was superior to standard SMBP for blood pressure (BP) reduction or patient satisfaction. Design, Setting, and Participants This randomized clinical trial was conducted among 23 health systems participating in PCORnet, the National Patient-Centered Clinical Research Network, and included patients who reported having uncontrolled BP at their last clinic visit, a desire to lower their BP, and a smartphone. Enrollment and randomization occurred from August 3, 2019, to December 31, 2020, which was followed by 6 months of follow-up for each patient. Analysis commenced shortly thereafter. Interventions Eligible participants were randomly assigned to enhanced SMBP using a device that paired with a connected smartphone application (enhanced) or a standard device (standard). Participants received their device in the mail, along with web-based educational materials and phone-based support as needed. No clinician engagement was undertaken, and the study provided no special mechanisms for delivering measurements to clinicians for use in BP management. Main Outcomes and Measures Reduction in systolic BP, defined as the difference between clinic BP at baseline and the most recent clinic BP extracted from electronic health records at 6 months. Results Enrolled participants (1051 enhanced [50.0%] vs 1050 standard [50.0%]; 1191 women [56.7%]) were mostly middle-aged or older (mean [SD] age, 58 [13] years), nearly a third were Black or Hispanic (645 [31%]), and most were relatively comfortable using technology (mean [SD], 4.1 [1.1] of 5). The mean (SD) change in systolic BP from baseline to 6 months was -10.8 (18) mm Hg vs -10.6 (18) mm Hg (enhanced vs standard: adjusted difference, -0.19 mm Hg; 95% CI, -1.83 to 1.44; P = .81). Secondary outcomes were mostly null, except for documented attainment of BP control to lower than 140/<90 mm Hg, which occurred in 32% enhanced vs 29% standard groups (odds ratio, 1.15; 95% CI, 1.01-1.34). Most participants were very likely to recommend their SMBP device to a friend (70% vs 69%). Conclusions and Relevance This randomized clinical trial found that enhanced SMBP paired with a smartphone application is not superior to standard SMBP for BP reduction or patient satisfaction. Trial Registration ClinicalTrials.gov Identifier: NCT03796689.

X-band electron spin resonance spectroscopy was used to study the binding of vanadium (IV), or vanadyl, to the brain serine/threonine phosphatase-2B, calcineurin, Spectra were determined on frozen solutions of vanadyl and calcineurin at pH 7.4 in the presence of 20% (v/v) glycerol, The binding of vanadyl to the enzyme was established, and the data suggested the presence of two classes of sites, the higher affinity class of which contained two binding sites for vanadyl, The calcium-binding B subunit of the heterodimeric protein was also shown to bind vanadyl, The holoprotein appeared to be stabilized by vanadyl, and vanadyl enhanced enzymatic activity when assayed with or without calmodulin in the absence of calcium.

IMPORTANCE Active SARS-CoV-2 (coronavirus) transmission continues in the US. It is unclear whether better access to coronavirus testing and more consistent use of testing could substantially reduce transmission. OBJECTIVE To describe coronavirus testing in persons with new onset of febrile illness and analyze whether there are changes over time and differences by race and ethnicity. DESIGN, SETTING, AND PARTICIPANTS This cohort study used data from the COVID-19 Citizen Science Study, launched in March 2020, which recruited participants via press release, word-of-mouth, and partner organizations. Participants completed daily surveys about COVID-19 symptoms and weekly surveys about coronavirus testing. All adults (aged at least 18 years) with a smartphone were eligible to join. For this analysis, US participants with new onset of febrile illness from April 2020 to October 2020 were included. Data analysis was performed from November 2020 to March 2021. MAIN OUTCOMES AND MEASURES Receipt of a coronavirus test result within 7 days of febrile illness onset. RESULTS Of the 2679 participants included in this analysis, the mean (SD) age was 46.3 (13.4) years, 1983 were female (74%), 2017 were college educated (75%), and a total of 3865 distinct new febrile illness episodes were reported (300 episodes [7.8%] from Hispanic participants, 71 episodes [1.8%] from Black participants, and 3494 episodes [90.4%] from not Black, not Hispanic participants) between April 2 and October 23, 2020. In weekly surveys delivered during the 14 days after fever onset, 12% overall (753 participants) indicated receipt of a test result. Using serial survey responses and parametric time-to-event modeling, it was estimated that by 7 days after onset of febrile illness, a total of 20.5% (95% CI, 19.1%-22.0%) had received a test result. This proportion increased from 9.8% (95% CI, 7.5%-12.0%) early in the epidemic to 24.1% (95% CI, 21.5%-26.7%) at the end of July, but testing rates did not substantially improve since then, increasing to 25.9% (95% CI; 21.6%-30.3%) in late October at the start of the winter surge. Black participants reported receiving a test result about half as often as others (7% [7 of 103] of survey responses vs 12% [53 of 461] for Hispanic vs 13% [693 of 5516] for not Black, not Hispanic; P = .03). This association was not statistically significant in adjusted time-to-event models (hazard ratio = 0.59 vs not Black, not Hispanic participants; 95% CI, 0.26-1.34). CONCLUSIONS AND RELEVANCE Systematic underuse of coronavirus testing was observed in this cohort study through late October 2020, at the beginning of the winter COVID-19 surge, which may have contributed to preventable coronavirus transmission.

Sudden cardiac death is common in the early post-myocardial infarction (MI) period. It is not known if ventricular tachyarrhythmias (VT/VF) are more common in certain parts of the day. To analyze the time of day of VT/VF events leading to appropriate shocks among participants in the VEST Trial. In the VEST trial, patients with MI and an ejection fraction of ≤35% were randomized to a wearable cardioverter-defibrillator (WCD) plus guideline-directed medical therapy (GDMT), or GDMT alone. Among those with VT/VF leading to appropriate shocks, their demographics, comorbidities, and timing of shocks were summarized. Among 2302 participants in the VEST trial, 21 participants had an appropriate shock. The median age was 55.3 years (interquartile range [IQR] 50.5-64.4), with 86% male. The median body-mass index was 28.1 kg/m2 (IQR 26.0-33.3). Comorbidities included diabetes (52%), hypertension (38%), and prior MI (33%). Participants had a post-MI ejection fraction of <25% (43% of participants) or 25-35% (57%). There were 44 appropriate shocks for VT/VF, with a median of 1 (IQR 1-3) shock(s) per participant. Shocks were most common in the morning (6am-12pm, 59%, Fisher's exact p<0.001; Figure), compared to other time periods: afternoon (12pm-6pm, 9%), evening (6pm-12am, 14%), and overnight (12am-6am, 18%). The first shock by WCD was successful in all VT/VF episodes; however, 6/21 (29%) participants died during the 3-month follow-up. In patients with recent MI, VT/VF occurred more frequently during the morning hours, possibly related to sympathetic surges. Therapies aimed at decreasing morning sympathetic surges may be beneficial.

Objective Older adult falls are a national issue comprising 3 million emergency department (ED) visits and significant mortality. We sought to understand whether ED revisits and hospitalisations for fallers differed from non-fall patients through a secondary analysis of a longitudinal, statewide cohort of patients.Design We performed a secondary analysis using the non-public Patient Discharge Database and the ED data from the California Office of Statewide Health Planning and Development. This is a 5-year, longitudinal observational dataset, which was used to assess outcomes for fallers and non-fall patients, defined as anyone who did not carry a fall diagnosis during this time period.Setting 2005–2010 non-public Patient Discharge Database and the ED Data from the state of California.Participants Older adults 65 years and olderMain outcome measure ED revisits and hospitalisations for fallers and non-fall patients.Results Patients who came to the ED with an index visit of a fall were more likely to be discharged home after their fall (61.1% vs 45.0%, p<0.001). Fallers who were discharged or hospitalised after their index visit were more likely to come back to the ED for a fall related complaint compared with non-fallers (median time: 151 days vs 352 days, p<0.001 and hospitalised: 45 days vs 119 days, p<0.01) and fallers who were initially discharged also returned to the ED sooner for a non-fall related complaint (median time: 325 days vs 352 days, p<0.001).Conclusion Fall patients tend to be discharged home more often after their index visit, but returned to the ED sooner compared with their non-fall counterparts. Given a faller’s rates of ED revisits and hospitalisations, EDs should consider a fall as a poor prognostic indicator for future healthcare utilisation.

Long-term outcomes related to emergency department revisit, hospital readmission, and all-cause mortality, have not been well characterized across the spectrum of pediatric traumatic brain injury (TBI). We evaluated emergency department visit outcomes up to 1 year after pediatric TBI, in comparison to a referent group of trauma patients without TBI. We performed a longitudinal, retrospective study of all pediatric trauma patients who presented to emergency departments and hospitals in California from 2005 to 2014. We compared emergency department visits, dispositions, revisits, readmissions, and mortality in pediatric trauma patients with a TBI diagnosis to those without TBI (Other Trauma patients). We identified 208,222 pediatric patients with an index diagnosis of TBI and 1,314,064 patients with an index diagnosis of Other Trauma. Population growth adjusted TBI visits increased by 5.6% while those for Other Trauma decreased by 40.7%. The majority of patients were discharged from the emergency department on their first visit (93.2% for traumatic brain injury vs. 96.5% for Other Trauma). A greater proportion of TBI patients revisited the emergency department (33.4% vs. 3.0%) or were readmitted to the hospital (0.9% vs. 0.04%) at least once within a year of discharge. The health burden within a year after a pediatric TBI visit is considerable and is greater than that of non-TBI trauma. These data suggest that outpatient strategies to monitor for short-term and longer-term sequelae after pediatric TBI are needed to improve patient outcomes, lessen the burden on families, and more appropriately allocate resources in the healthcare system.

Vest Prevention of Early Sudden Death Trial did not demonstrate a significant reduction in arrhythmic death with the wearable cardioverter‐defibrillator (WCD), but compliance with the device may have substantially affected the results. ThePletcher influence of WCD compliance on outcomes has not yet been fully evaluated.

Background: There is scant research on the effect of wearable cardioverter-defibrillators (WCDs) on quality of life (QOL). One retrospective observational study concluded that WCDs have a negative impact. The VEST Trial was a randomized controlled trial of the WCD allowing a more definitive and complete analysis of QOL among WCD users. Hypothesis: We sought to determine if the WCD impacts patient-reported QOL, including depression, anxiety, and physical activity levels. Methods: In the VEST trial, participants with severe left ventricular dysfunction (EF≤35%) after MI were randomized in a 2:1 ratio to receive a WCD plus guideline directed therapy (GDMT) versus GDMT alone. During the 3-month follow-up period, participants were asked to complete QOL assessments and health questionnaires. Results: 1524 participants were randomized to WCD plus GDMT versus 778 participants to GDMT alone. The mean age was 60.9±12.6 years and 61.4±12.3 years in the two groups, respectively. Participants were 73.5% male, had an average body-mass index of 28.4±5.5 kg/m2, and a mean EF of 28%. During a mean follow-up of 84.3±15.6 days, health questionnaires and QOL assessments were completed by 1340 participants, including 898 receiving WCD plus GDMT, and 442 receiving GDMT alone. See Table 1 for the results of QOL assessments and health questionnaires. There were no differences in QOL according to the SF-36 physical and mental component scores, and EQ-5D scores between WCD plus GDMT versus GDMT alone. There were also no differences in depression (CES-D 10), anxiety (State-Trait Anxiety Inventory), physical activity (International Physical Activity Questionnaire), or self-reported health scale between groups (all p>0.05). Conclusions: In post-MI patients with low EF, the WCD does not affect QOL, depression, anxiety, physical activity, or self-reported health. Prescribers can be reassured that the WCD has no detrimental impact on patient-reported health measures.

ObjectiveTo describe visits and visit rates of adults presenting to emergency departments (EDs) with a diagnosis of traumatic brain injury (TBI). TBI is a major cause of death and disability in the USA; yet, current literature is limited because few studies examine longer-term ED revisits and hospital readmission patterns of TBI patients across a broad spectrum of injury severity, which can help inform potential unmet healthcare needs.DesignWe performed a retrospective cohort study.SettingWe analysed non-public patient-level data from California’s Office of Statewide Health Planning and Development for years 2005 to 2014.ParticipantsWe identified 1.2 million adult patients aged ≥18 years presenting to California EDs and hospitals with an index diagnosis of TBI.Primary and secondary outcome measuresOur main outcomes included revisits, readmissions and mortality over time. We also examined demographics, mechanism and severity of injury and disposition at discharge.ResultsWe found a 57.7% increase in the number of TBI ED visits, representing a 40.5% increase in TBI visit rates over the 10-year period (346–487 per 100 000 residents). During this time, there was also a 33.8% decrease in the proportion of patients admitted to the hospital. Older, publicly insured and black populations had the highest visit rates, and falls were the most common mechanism of injury (45.5% of visits). Of all patients with an index TBI visit, 40.5% of them had a revisit during the first year, with 46.7% of them seeking care at a different hospital from their initial hospital or ED visit. Additionally, of revisits within the first year, 13.4% of them resulted in hospital readmission.ConclusionsThe large proportion of patients with TBI who are discharged directly from the ED, along with the high rates of revisits and readmissions, suggest a role for an established system for follow-up, treatment and care of TBI.