Congenital long QT syndrome: considerations for primary care physicians

Congenital long QT syndrome is an inherited disorder of cardiac repolarization that predisposes to syncope and to sudden death from polymorphic ventricular tachycardia. The disorder should be suspected when the electrocardiogram shows characteristic QT abnormalities, or when there is a family history of long QT syndrome or of an event that raises suspicion of long QT syndrome, such as sudden death, syncope, or ill-defined "seizure" disorder. We can now classify some types of congenital long QT syndrome according to their genetic mutations and their triggers, such as exercise, rest, or startle.     

Preparing for the future: nurse education and workforce development

Nurse education needs to be responsive to changes not only within health policy but also those relating to workforce development. Viewed within this context this discussion paper highlights areas of consideration when planning for and responding to such demands.     

Interictal spikes on intracranial recording: behavior, physiology, and implications

Purpose: The physiological, pathological, and clinical meaning of interictal spikes (IISs) remains controversial. We systematically analyzed the frequency, occurrence, and distribution of IISs recorded from multiple intracranial electrodes in 34 refractory epileptic patients with respect to seizures and antiepileptic drug (AED) changes. Methods: Continuous spike counts from all recorded contacts of all implanted electrodes, and also separately for the subset of contacts involved at seizure onset, were tabulated for every hour of every day of recording, and expressed as spikes per hour in six preselected, 24‐h intervals (defined to exclude seizures): (1) on medications; (2) prepreseizure; (3) preseizure; (4) postseizure; (5) off meds; and (6) resumed meds. Mean spike rates were analyzed for differences between designated 24‐h intervals. Results: Spike rate in all recorded contacts consistently and significantly decreased after AED withdrawal, despite variability in initial spike rate, diurnal occurrence, seizure character/number/localization of onset, and type(s) of AED continued or withdrawn (p < 0.0001). A significant increase in spike rate was noted in the 24  h after seizures of medial temporal origin, in the medial temporal lobe contacts; neocortical onset seizures did not show any increase. Conclusions: These observations confirm and extend previous reports, suggesting a general effect of AED withdrawal, and a more specific effect of medial temporal lobe seizures, on IIS rate. AED mechanisms and efficacy might be demonstrated by quantifying IIS with changes in AEDs. Furthermore, variability in IIS rate after seizures distinguishes localization of seizure onset in medial temporal versus neocortical locations.     

A randomized, double-blind comparison of duloxetine and venlafaxine in the treatment of patients with major depressive disorder

BACKGROUND: Clinical trials assessing antidepressant therapies typically include separate assessments of efficacy (benefit) and adverse events (risk). Global benefit-risk (GBR) assessment allows the simultaneous evaluation of both efficacy and adverse events. The objective was to compare the serotonin and norepinephrine reuptake inhibitors (SNRIs) duloxetine and venlafaxine using GBR assessment. METHODS: Data were combined from two similarly designed, multicenter, randomized, double-blind, parallel group studies in which patients with major depressive disorder were randomized to either duloxetine 60 mg/day or venlafaxine extended release (XR) 150 mg/day (75 mg/day for the first 2 weeks) for a 6-week fixed dosing period followed by an additional 6 weeks of treatment in which the dose could be increased up to 120 mg/day for duloxetine and 225 mg/day for venlafaxine. Patients completing the study (or receiving study drug for 2 weeks or more) were eligible to enter a taper period where the dose of study drug was gradually reduced over 1-2 weeks prior to drug discontinuation. The primary outcome measure (defined a priori) was the GBR comparison of duloxetine 60 mg/day and venlafaxine XR 150 mg/day after 6 weeks of treatment. In the GBR analysis, benefit was defined as remission at endpoint [17-item Hamilton Depression Rating Scale (HAMD17) 7]. Risk was defined by four categories: patients having either no adverse events (AEs), AEs with no severity rating greater than moderate, AEs with at least one severity rating of severe, or having discontinued with a reason of self-reported adverse event (regardless of any AE severity). Additional efficacy measures included HAMD17 total score and subscales, HAMA, CGI-S, and PGI-I. Safety and tolerability were assessed via analysis of reasons for discontinuation, treatment-emergent adverse events (TEAEs), discontinuation-emergent adverse events, and changes in vital signs, weight, and laboratory analytes. RESULTS: There were no significant differences between duloxetine 60 mg/day and venlafaxine 150 mg/day as measured by GBR assessment at the end of 6 weeks (-1.418 vs. -1.079, P = 0.217) or 12 weeks (-0.349 vs. -0.121, P = 0.440), nor were there significant differences between treatment groups on the majority of efficacy measures. Significantly more venlafaxine-treated patients (74.5%) completed 12 weeks of treatment compared with duloxetine-treated patients (64.8%, P =.006). Nausea was the most common treatment-emergent adverse event (TEAE) for both drugs, and was significantly higher with duloxetine 60 mg/day compared to venlafaxine 150 mg/day during the first 6 weeks of treatment (43.6% vs. 35.0%, P0.05). During the taper period, significantly more venlafaxine-treated patients reported discontinuation-emergent adverse events (DEAEs) than duloxetine-treated patients. From a safety perspective, significantly more venlafaxine-treated patients (n = 4) than duloxetine-treated patients (n=0, P =.047) experienced sustained elevations of systolic blood pressure during the fixed dosing period. Otherwise, there were few significant differences in safety measures found between treatment groups during 6 and 12 weeks of therapy. CONCLUSIONS: Duloxetine 60 mg/day and venlafaxine XR 150 mg/day have similar benefit-risk profiles on the basis of a comparison utilizing GBR assessment. The implications of the more subtle differences between these drugs, as well as for interpreting the GBR assessment, are discussed.     

Comprehensive surgical management of the competitive athlete with effort thrombosis of the subclavian vein (Paget-Schroetter syndrome)

OBJECTIVES: The results of treatment for subclavian vein effort thrombosis were assessed in a series of competitive athletes. METHODS: A retrospective review was conducted of high-performance athletes who underwent multidisciplinary management for venous thoracic outlet syndrome in a specialized referral center. The overall time required to return to athletic activity was assessed with respect to the timing and methods of diagnosis, initial treatment, operative management, and postoperative care. RESULTS: Between January 1997 and January 2007, 32 competitive athletes (29 male and 3 female) were treated for venous thoracic outlet syndrome, of which 31% were in high school, 47% were in college, and 22% were professional. The median age was 20.3 years (range, 16-26 years). Venous duplex ultrasound examination in 21 patients had a diagnostic sensitivity of 71%, and the mean interval between symptoms and definitive venographic diagnosis was 20.2 +/- 5.6 days (range, 1-120 days). Catheter-directed subclavian vein thrombolysis was performed in 26 (81%), with balloon angioplasty in 12 and stent placement in one. Paraclavicular thoracic outlet decompression was performed with circumferential external venolysis alone (56%) or direct axillary-subclavian vein reconstruction (44%), using saphenous vein panel graft bypass (n = 8), reversed saphenous vein graft bypass (n = 3), and saphenous vein patch angioplasty (n = 3). In 19 patients (59%), simultaneous creation of a temporary (12 weeks) adjunctive radiocephalic arteriovenous fistula was done. The mean hospital stay was 5.2 +/- 0.4 days (range, 2-11 days). Seven patients required secondary procedures. Anticoagulation was maintained for 12 weeks. All 32 patients resumed unrestricted use of the upper extremity, with a median interval of 3.5 months between operation and the return to participation in competitive athletics (range, 2-10 months). The overall duration of management from symptoms to full athletic activity was significantly correlated with the time interval from venographic diagnosis to operation (r = 0.820, P < .001) and was longer in patients with persistent symptoms (P < .05) or rethrombosis before referral (P < .01). CONCLUSIONS: Successful outcomes were achieved for the management of effort thrombosis in a series of 32 competitive athletes using a multidisciplinary approach based on (1) early diagnostic venography, thrombolysis, and tertiary referral; (2) paraclavicular thoracic outlet decompression with external venolysis and frequent use of subclavian vein reconstruction; and (3) temporary postoperative anticoagulation, with or without an adjunctive arteriovenous fistula. Optimal outcomes for venous thoracic outlet syndrome depend on early recognition by treating physicians and prompt referral for comprehensive surgical management.     

Effect of cytomegalovirus prophylaxis with acyclovir on renal transplant survival

It is recognized that cytomegalovirus (CMV) infection in transplant recipients may lead to graft loss. Prophylaxis with acyclovir has therefore gained widespread acceptance, but the debate on whether this intervention improves long term graft survival continues. All patients who received renal grafts at the National Renal Transplant Centre, Dublin, between January 1992 and December 1999 were retrospectively analyzed. During this time period, patients who were CMV positive and/or had received grafts from CMV-positive donors were administered prophylactic oral acyclovir 800 mg thrice daily, adjusted for calculated creatinine clearance, from the first day post-transplantation. This treatment was continued for three months unless the graft failed or the patient developed CMV disease or died. Graft and patient outcomes were compared in recipients who received acyclovir with those who did not. Over the study period, 935 patients received renal transplants in our center, of whom 487 were administered acyclovir. The incidence of CMV disease was 3.3 cases per 100 patients per annum in those who required prophylaxis. Despite prophylaxis, graft outcomes were found to be significantly worse (p value < 0.001) in the group that qualified for acyclovir. We conclude that acyclovir provides incomplete protection from the negative impact of CMV on graft survival.