BACKGROUND Adverse event reports from North America have raised concerns that medications for attention deficit-hyperactivity disorder (ADHD) increase risk of serious cardiovascular events. METHODS We conducted a retrospective cohort study with automated data from four health plans (Tennessee Medicaid, Kaiser Permanente California, OptumInsight Epidemiology, Washington State Medicaid), with 1,200,438 children and youth aged 2–24 years and 2,579,104 person-years of follow-up, including 373,667 person-years of current ADHD medication use. We identified serious cardiovascular events (sudden cardiac death, acute myocardial infarction, and stroke) from health plan data and vital records, with endpoints validated by medical record review. We estimated the relative risk for endpoints in current users compared to nonusers with hazard ratios from Cox regression models. RESULTS Cohort members had 81 serious cardiovascular events (3.1/100,000 person-years). Current ADHD medication users had no increased risk for serious cardiovascular events (adjusted hazard ratio 0.75; 95% confidence interval [CI] 0.31 to 1.85). Risk was not increased for any of the individual endpoints, or for current users compared to former users (adjusted hazard ratio 0.70; 95% CI 0.29 to 1.72). Alternative analyses addressing several study assumptions also found no significant association between ADHD medication use and the risk of study endpoints. CONCLUSIONS Although there was no evidence of increased risk of serious cardiovascular events for current users of ADHD medications, the upper bound of the 95% confidence interval indicates that up to a two-fold increased risk cannot be ruled out. However, the absolute magnitude of such an increased risk would be low.

We reviewed the records of all children (younger than 16 years of age) who presented with a diagnosis of optic neuritis (ON) identified through the comprehensive records-linkage system at the Mayo Clinic and identified 94 cases between 1950 and 1988 with a documented history of idiopathic ON. Detailed follow-up information was available on 79 patients, with a median length of follow-up of 19.4 years. Life-table analysis showed that 13% of the 79 patients with isolated ON had progressed to clinically or laboratory-supported definite multiple sclerosis (MS) by 10 years of follow-up, 19% by 20 years, 22% by 30 years, and 26% by 40 years. Gender, age, funduscopic findings, visual acuity, or family history of either ON or MS did not predict the development of MS. The presence of bilateral sequential or recurrent ON increased the risk of developing MS (p = 0.002; hazard ratio = 5.09), whereas the presence of infection within 2 weeks before the onset of ON decreased the risk of developing MS (p = 0.060; hazard ratio = 0.24). This study of childhood ON supports the lower risk of recurrence and progression to MS compared with adults.

Background and Purpose A promising method for identifying hemodynamic impairment that may serve as a biomarker for stroke risk in patients with intracranial (IC) stenosis is cerebrovascular reactivity (CVR) mapping using non-invasive MRI. Here, abilities to measure CVR safely in the clinic using hypercarbic hyperoxic (carbogen) gas challenges, which increase oxygen delivery to tissue, are investigated. Methods In sequence with structural and angiographic imaging, blood-oxygenation-level-dependent (BOLD) carbogen-induced CVR scans were performed in patients with symptomatic IC stenosis (n=92) and control (n=10) volunteers, with a subgroup of patients (n=57) undergoing cerebral blood flow-weighted (CBFw) pseudo-continuous arterial spin labeling (pCASL) CVR. Subjects were stratified for four sub-studies: to evaluate relationships between (i) carbogen and hyercarbic normoxic (HN) CVR in healthy tissue (n=10), (ii) carbogen CBF CVR and BOLD CVR in IC stenosis patients (n=57), (iii) carbogen CVR and clinical measures of disease in patients with asymmetric IC atherosclerotic (n=31) and moyamoya (n=29) disease, and (iv) the CVR scan and immediate and longer-term complications (n=92). Results Non-invasive BOLD carbogen-induced CVR values correlate with (i) lobar HN gas stimuli in healthy tissue (R=0.92; P<0.001), (ii) carbogen-induced CBF CVR in IC stenosis patients (R=0.30–0.33; P<0.012), and (iii) angiographic measures of disease severity both in atherosclerotic and moyamoya patients after appropriate processing. No immediate stroke-related complications were reported in response to carbogen administration; longer-term neurological events fell within the range for expected events in this patient population. Conclusions Carbogen-induced CVR elicited no added adverse events and provided a surrogate marker of cerebrovascular reserve consistent with IC vasculopathy.

ImportanceIn patients with severe aortic valve stenosis at intermediate surgical risk, transcatheter aortic valve replacement (TAVR) with a self-expanding supra-annular valve was noninferior to surgery for all-cause mortality or disabling stroke at 2 years. Comparisons of longer-term clinical and hemodynamic outcomes in these patients are limited.ObjectiveTo report prespecified secondary 5-year outcomes from the Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement (SURTAVI) randomized clinical trial.Design, Setting, and ParticipantsSURTAVI is a prospective randomized, unblinded clinical trial. Randomization was stratified by investigational site and need for revascularization determined by the local heart teams. Patients with severe aortic valve stenosis deemed to be at intermediate risk of 30-day surgical mortality were enrolled at 87 centers from June 19, 2012, to June 30, 2016, in Europe and North America. Analysis took place between August and October 2021.InterventionPatients were randomized to TAVR with a self-expanding, supra-annular transcatheter or a surgical bioprosthesis.Main Outcomes and MeasuresThe prespecified secondary end points of death or disabling stroke and other adverse events and hemodynamic findings at 5 years. An independent clinical event committee adjudicated all serious adverse events and an independent echocardiographic core laboratory evaluated all echocardiograms at 5 years.ResultsA total of 1660 individuals underwent an attempted TAVR (n = 864) or surgical (n = 796) procedure. The mean (SD) age was 79.8 (6.2) years, 724 (43.6%) were female, and the mean (SD) Society of Thoracic Surgery Predicted Risk of Mortality score was 4.5% (1.6%). At 5 years, the rates of death or disabling stroke were similar (TAVR, 31.3% vs surgery, 30.8%; hazard ratio, 1.02 [95% CI, 0.85-1.22]; P = .85). Transprosthetic gradients remained lower (mean [SD], 8.6 [5.5] mm Hg vs 11.2 [6.0] mm Hg; P &amp;lt; .001) and aortic valve areas were higher (mean [SD], 2.2 [0.7] cm2 vs 1.8 [0.6] cm2; P &amp;lt; .001) with TAVR vs surgery. More patients had moderate/severe paravalvular leak with TAVR than surgery (11 [3.0%] vs 2 [0.7%]; risk difference, 2.37% [95% CI, 0.17%- 4.85%]; P = .05). New pacemaker implantation rates were higher for TAVR than surgery at 5 years (289 [39.1%] vs 94 [15.1%]; hazard ratio, 3.30 [95% CI, 2.61-4.17]; log-rank P &amp;lt; .001), as were valve reintervention rates (27 [3.5%] vs 11 [1.9%]; hazard ratio, 2.21 [95% CI, 1.10-4.45]; log-rank P = .02), although between 2 and 5 years only 6 patients who underwent TAVR and 7 who underwent surgery required a reintervention.Conclusions and RelevanceAmong intermediate-risk patients with symptomatic severe aortic stenosis, major clinical outcomes at 5 years were similar for TAVR and surgery. TAVR was associated with superior hemodynamic valve performance but also with more paravalvular leak and valve reinterventions.