Factors associated with treatment delays in pediatric refractory convulsive status epilepticus.

OBJECTIVE: To identify factors associated with treatment delays in pediatric patients with convulsive refractory status epilepticus (rSE). METHODS: This prospective, observational study was performed from June 2011 to March 2017 on pediatric patients (1 month to 21 years of age) with rSE. We evaluated potential factors associated with increased treatment delays in a Cox proportional hazards model. RESULTS: We studied 219 patients (53% males) with a median (25th-75th percentiles [p25-p75]) age of 3.9 (1.2-9.5) years in whom rSE started out of hospital (141 [64.4%]) or in hospital (78 [35.6%]). The median (p25-p75) time from seizure onset to treatment was 16 (5-45) minutes to first benzodiazepine (BZD), 63 (33-146) minutes to first non-BZD antiepileptic drug (AED), and 170 (107-539) minutes to first continuous infusion. Factors associated with more delays to administration of the first BZD were intermittent rSE (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.14-2.09; p = 0.0467) and out-of-hospital rSE onset (HR 1.5, 95% CI 1.11-2.04; p = 0.0467). Factors associated with more delays to administration of the first non-BZD AED were intermittent rSE (HR 1.78, 95% CI 1.32-2.4; p = 0.001) and out-of-hospital rSE onset (HR 2.25, 95% CI 1.67-3.02; p < 0.0001). None of the studied factors were associated with a delayed administration of continuous infusion. CONCLUSION: Intermittent rSE and out-of-hospital rSE onset are independently associated with longer delays to administration of the first BZD and the first non-BZD AED in pediatric rSE. These factors identify potential targets for intervention to reduce time to treatment.

A clinical rating scale for Batten disease: reliable and relevant for clinical trials.

BACKGROUND: Batten disease (juvenile neuronal ceroid lipofuscinosis [JNCL]) is an autosomal recessive neurodegenerative disorder characterized by blindness, seizures, and relentless decline in cognitive, motor, and behavioral function. Onset is in the early school years, with progression to death typically by late adolescence. Development of a clinical instrument to quantify severity of illness is a prerequisite to eventual assessment of experimental therapeutic interventions. OBJECTIVE: To develop a clinical rating instrument to assess motor, behavioral, and functional capability in JNCL. METHODS: A clinical rating instrument, the Unified Batten Disease Rating Scale (UBDRS), was developed by the authors to assess motor, behavioral, and functional capability in JNCL. Children with verified JNCL were evaluated independently by three neurologists. Intraclass correlation coefficients (ICCs) were used to estimate the interrater reliability for total scores in each domain. Interrater reliability for scale items was assessed with weighted kappa statistics. RESULTS: Thirty-one children with confirmed JNCL (10 boys, 21 girls) were evaluated. The mean age at symptom onset was 6.1 +/- 1.6 years, and the mean duration of illness was 9.0 +/- 4.4 years. The ICCs for the domains were as follows: motor = 0.83, behavioral = 0.68, and functional capability = 0.85. CONCLUSIONS: The Unified Batten Disease Rating Scale (UBDRS) is a reliable instrument that effectively tests for neurologic function in blind and demented patients. In its current form, the UBDRS is useful for monitoring the diverse clinical findings seen in Batten disease.

Inflammation-mediated retinal edema in the rabbit is inhibited by topical nepafenac.

The purpose of this study was to evaluate the ability of the nonsteroidal anti-inflammatory drug nepafenac to prevent development of mitogen-induced pan-retinal edema following topical ocular application in the rabbit. Anesthetized Dutch Belted rabbits were injected intravitreally (30 microg/20 microL) with the mitogen concanavalin A to induce posterior segment inflammation and thickening (edema) of the retina. The Heidelberg Retina Tomograph was used to generate edema maps using custom software. Blood-retinal barrier breakdown was assessed by determining the protein concentration in vitreous humor, whereas analysis of PGE2 in vitreous humor was performed by radioimmunoassay. Inhibition of concanavalin A-induced retinal edema was assessed 72 h after initiation of topical treatment with nepafenac (0.1-1.0%, w/v), dexamethasone (0.1%), VOLTAREN (0.1%), or ACULAR (0.5%). Concanavalin A elicited marked increases in vitreal protein and PGE2 synthesis at 72 h postinjection. Retinal thickness was also increased by 32%, concomitant with the inflammatory response. Topical application of 0.5% nepafenac produced 65% reduction in retinal edema which was correlated with 62% inhibition of blood-retinal barrier breakdown. In a subsequent study, 0.5% nepafenac significantly inhibited (46%) blood-retinal barrier breakdown concomitant with near total suppression of PGE2 synthesis (96%). Neither Voltaren nor Acular inhibited accumulation of these markers of inflammation in the vitreous when tested in parallel. This study demonstrates that nepafenac exhibits superior pharmacodynamic properties in the posterior segment following topical ocular dosing, suggesting a unique therapeutic potential for a variety of conditions associated with retinal edema.

Randomized angiographic trial of recombinant tissue-type plasminogen activator (alteplase) in myocardial infarction. RAAMI Study Investigators.

Clot dissolution with restoration of infarct-related artery blood flow is the likely mechanism for the improved prognosis and mortality reduction seen after thrombolytic therapy of acute myocardial infarction. A pilot study has suggested that 100 mg of recombinant tissue-type plasminogen activator (rt-PA) infused over 90 min may lead to higher patency rates than the current standard of 100 mg over 3 h. In this multicenter, randomized, open label trial, 281 patients with acute myocardial infarction receive 100 mg of rt-PA according to either the standard 3-h infusion regimen (an initial 10-mg bolus followed by 50 mg for the 1st h, then 20 mg/h for 2 h) or an accelerated 90-min regimen (15-mg bolus followed by 50 mg over 30 min, then 35 mg over 60 min). All patients also received intravenous heparin and oral aspirin during and after rt-PA infusion. At 60 min after initiation of the rt-PA infusion, the observed angiographic patency rates were 76% (95% confidence intervals 65% to 84%) in the accelerated regimen group and 63% in the control group (52% to 73%, p = 0.03). At 90 min these rates were 81% (73% to 87%) and 77% (68% to 84%), respectively (p = 0.21). Both randomized groups experienced similar rates of recurrent ischemia, reinfarction, angiographic reocclusion, other complications of myocardial infarction (including stroke and death) and bleeding complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Systemic and local saphenous vein graft thrombolysis using a tissue plasminogen activator.

Many studies are currently evaluating the potential role of thrombolytic therapy in patients with ischemic syndromes who have undergone previous coronary artery bypass grafting. Limited experience has been published regarding the use of local urokinase and streptokinase infusions and the use of systemic recombinant tissue-type plasminogen activator as thrombolytic agents in patients with previous coronary artery bypass surgery. To date, however, there has been no published experience regarding the use of recombinant tissue-type plasminogen activator (rt-PA) either systemically or locally in the post-bypass patient where angiographic demonstration of aortocoronary saphenous vein graft obstruction was available pre- and post-therapy. Similarly there has been no previous report of the use of rt-PA infused locally to recanalize an occluded aortocoronary saphenous vein graft. This report describes successful thrombolysis and subsequent balloon angioplasty of saphenous vein grafts with angiographically documented thrombus using systemic and local rt-PA infusion.

Activitrax AAIR pacing for sinus node dysfunction after orthotopic heart transplantation: an initial report.

Donor sinus node dysfunction is an uncommon event after orthotopic heart transplantation. In the past treatment of persistent symptomatic bradycardia in the setting of orthotopic heart transplantation has been accomplished by implantation of a single transvenous lead system with loss of atrioventricular synchrony and rate responsiveness or by implantation of a multiple transvenous lead system in which the multiple leads present a mechanical limitation to endomyocardial biopsy. To preserve atrioventricular synchrony, avoid the mechanical limitations of a ventricular lead at the time of routine biopsies, and maintain some degree of rate responsiveness during exercise, we elected to implant an activity-detecting pacing system with a single bipolar transvenous atrial lead in two of our orthotopic heart transplant recipients with persistent symptomatic donor sinus node dysfunction. This article details the techniques used and the results obtained in what we believe to be the first two implantations of this unique pacing system in orthotopic heart transplant recipients.

Interhospital transport of patients with ongoing intraaortic balloon pumping.

During a 5-year period (1979 to 1983), 50 consecutive patients undergoing continuous intraaortic balloon (IAB) pumping were transferred from Evanston Hospital to Northwestern Memorial Hospital (16 miles), where they underwent cardiac operation. All patients had cardiac catheterization before transfer. Indications for IAB were cardiogenic shock (9 patients), postinfarction angina (18 patients), unstable angina (9 patients), evolving myocardial infarction (3 patients), accelerating angina or hemodynamic instability during cardiac catheterization (9 patients) and prophylactic insertion for high-grade left main stenosis (2 patients). Transportation after stabilization was uneventful in all patients. All patients underwent operative coronary revascularization. There was concomitant mitral valve replacement in 3 patients, acute ventricular septal defect repair in 1 patient, aortic valve replacement in 1, and ventricular aneurysmectomy in 1. Three patients (5%) died postoperatively. Nine patients (20%) had complications directly related to IAB insertion. One patient required femoral-femoral arterial bypass preoperatively, 4 patients had postoperative lower limb ischemia treated by IAB removal or thrombectomy and 1 patient had thrombocytopenia (less than 60,000/mm3), 1 false aneurysm, 1 anterior compartment syndrome and 1 prolonged bleeding at the insertion site. Interhospital transfer with IAB pumping in progress should not be restricted to patients with cardiogenic shock, but can be effectively used for all patients who require preoperative IAB insertion.(ABSTRACT TRUNCATED AT 250 WORDS)

Sinus node function and dysfunction.

The wide range of normal sinus node function makes identification of dysfunction difficult. Emphasis is placed upon real time correlation of ECG bradyarrhythmia with typical symptoms. A spectrum of atrial electrical dysfunction is described which includes abnormalities of the sinus and AV nodes as well as failure of escape pacemakers and atrial tachyarrhythmias.

Atrial fibrillation and flutter. Immediate control and conversion with intravenously administered verapamil.

The safety and efficacy of the intravenous (IV) calcium channel blocker, verapamil, in controlling the ventricular response or converting to sinus rhythm patients with atrial flutter or atrial fibrillation were assessed. Seventeen patients (nine with atrial flutter and eight with atrial fibrillation) with these arrhythmias that were difficult to control pharmacologically were chosen for the study. All patients at the time of study were receiving digoxin. Either verapamil or placebo was chosen randomly and a bolus of 0.075 mg/kg (up to 5 mg) was administered. Twelve patients had a marked reduction in their ventricular response after IV administration of verapamil (seven with atrial flutter and five with atrial fibrillation). None of these 12 patients converted (nonconverters). The average reduction in heart rate was from 120 +/- 6 beats per minute to a minimum of 83 +/- 13 beats per minute within 20 minutes after drug administration. Verapamil was found to convert five patients with atrial arrhythmias to sinus rhythm (two with atrial flutter and three with atrial fibrillation) (converters). In addition, three patients with atrial arrhythmias of less than one month who did not convert with parenteral drug therapy converted within 24 hours while receiving the oral drug. Converters had their supraventricular arrhythmias of significantly shorter duration (median, three hours v 30 days) and tended to have smaller left atrial size (3.8 +/- 0.7 cm v 4.3 +/- 1.3 cm) compared with the nonconverters. We conclude that verapamil is safe and effective when administered IV to patients with atrial flutter and fibrillation for control of ventricular response. In short duration atrial arrhythmias, conversion to sinus rhythm is likely once the ventricular response is controlled.

Vertical structure of the ionosphere and upper neutral atmosphere of saturn from the pioneer radio occultation.

Radio occultation measurements at S band (2.293 gigahertz) of the ionosphere and upper neutral atmosphere of Saturn were obtained during the flyby of the Pioneer 11 Saturn spacecraft on 5 September 1979. Preliminary analysis of the occultation exit data taken at a latitude of 9.5 degrees S and a solar zenith angle of 90.6 degrees revealed the presence of a rather thin ionosphere, having a main peak electron density of about 9.4 x 10/(3) per cubic centimeter at an altitude of about 2800 above the level of a neutral number density of 10(19) per cubic centimeter and a lower peak of about 7 x 10(3) per cubic centimeter at 2200 kilometers. Data in the neutral atmosphere were obtained to a pressure level of about 120 millibars. The temperature structure derived from these data is consistent with the results of the Pioneer 11 Saturn infrared radiometer experiment (for a helium fraction of 15 percent) and with models derived from Earth-based observations for a helium fraction by number of about 4 to 10 percent. The helium fraction will be further defined by mutual iteration with the infrared radiometer team.