The Effect of Antiepileptic Drugs on Cognition: Patient Perceived Cognitive Problems of Topiramate versus Levetiracetam in Clinical Practice

Summary:  Introduction: Neurocognitive complaints may interfere with long-term antiepileptic drug (AED) treatment and are an important issue in clinical practice. Most data about drug-induced cognitive problems are derived from highly controlled short-term clinical trials. We analyzed such cognitive complaints for the two most commonly used AEDs in a clinical setting using patient perceived problems as primary outcome measure.
Method: All patients of the epilepsy center Kempenhaeghe that received topiramate (TPM) or levetiracetam (LEV) from the introduction to mid 2004 were analyzed using a medical information system, an automated medical file. Patients were analyzed after 6, 12, and 18 months of treatment.
Results: Four hundred and two patients used either TPM (n = 260) or LEV (n = 142); 18 months retention showed a statistically significant difference, revealing 15% more patients that continued LEV compared to TPM: 18 months retention 46% for TPM and 61% for LEV [F (1.400) = 3.313, p = 0.043]. Neurocognitive complaints accounted for a significant number of drug discontinuations and especially the high frequency of neurocognitive complaints in the first period of TPM treatment appeared to be significant different from LEV [F(2,547) = 3.192, p = 0.042]. In the remaining patients, the difference in neurocognitive complaints was not statistically significant.
Conclusion: cognitive complaints are common in TPM treatment and frequently lead to drug withdrawal. The impact of LEV on cognitive function is only mild. This leads to a much higher (15%) drug discontinuation rate for TPM compared to LEV.     

Benefit of combined resynchronization and defibrillator therapy in heart failure patients with and without ventricular arrhythmias.

OBJECTIVES: We attempted to assess the efficacy of combined cardiac resynchronization therapy-implantable cardioverter-defibrillator (CRT-ICD) in heart failure patients with and without ventricular arrhythmias. BACKGROUND: Because CRT and ICDs both lower all-cause mortality in patients with advanced heart failure, combination of both therapies in a single device is challenging. METHODS: A total of 191 consecutive patients with advanced heart failure, left ventricular ejection fraction <35%, and a QRS duration >120 ms received CRT-ICD. Seventy-one patients had a history of ventricular arrhythmias (secondary prevention); 120 patients did not have prior ventricular arrhythmias (primary prevention). During follow-up, ICD therapy rate, clinical improvement after 6 months, and mortality rate were evaluated. RESULTS: During follow-up (18 +/- 4 months), primary prevention patients experienced less appropriate ICD therapies than secondary prevention patients (21% vs. 35%, p < 0.05). Multivariate analysis revealed, however, no predictors of ICD therapy. Furthermore, a similar, significant, improvement in clinical parameters was observed at 6 months in both groups. Also, the mortality rate in the primary prevention group was lower than in the secondary prevention group (3% vs. 18%, p < 0.05). CONCLUSIONS: As 21% of the primary prevention patients and 35% of the secondary prevention patients experienced appropriate ICD therapy within 2 years after implant, and no predictors of ICD therapy could be identified, implantation of a CRT-ICD device should be considered in all patients eligible for CRT.     

Identification of successful catheter ablation sites in patients with ventricular tachycardia based on electrogram characteristics during sinus rhythm

BACKGROUND: Zones of slow conduction facilitate reentry, the major mechanism of ventricular tachycardia (VT) after myocardial infarction (MI). Identification of these zones during sinus rhythm (SR) is desirable for radiofrequency (RF) catheter ablation of VT. Local conduction velocity may correlate with electrogram duration. OBJECTIVES: The purpose of this study was to revise the definition of normal electrogram characteristics and to reevaluate the significance of low-amplitude, long-duration electrograms recorded during SR to select RF catheter ablation sites in patients with VT. METHODS: Electroanatomic mapping was performed during SR in 10 control patients with normal left ventricles (LVs) and in 10 patients with stable VT after MI. From the controls, reference values for electrogram amplitude, duration (first peak to last peak distance), and fragmentation (positive deflection) were derived. In patients after MI, areas with signals exceeding these values were annotated and related to successful ablation sites. RESULTS: Ninety-five percent of normal LV electrograms were > or =1.0 mV and < or =28 ms (range 5-39 ms) and all had < or =4 deflections. Based on these results, cutoff values were set at 1 mV, four deflections, and 40 ms. In infarcted hearts, 653 electrograms (44%) were <1.0 mV and of these, 303 were > or =40 ms with >4 deflections and restricted to circumscribed areas. Twenty-seven of 28 targeted VTs remained noninducible after RF catheter ablation within these areas, resulting in 86% sensitivity and 94% specificity for low-amplitude, long-duration electrograms predicting successful ablation sites. CONCLUSION: Identification of successful RF target areas during SR in patients with VT is feasible with high sensitivity and specificity using a mapping strategy based on voltage and duration criteria.     

Successful Veterans Affairs initiative to prevent methicillin-resistant Staphylococcus aureus infections revisited

In 2011 Jain et al reported a 62% reduction of healthcare-associated methicillin-resistant Staphylococcus aureus infections that resulted from an intervention bundle. Here we present a mathematical model and prove, using parameters from the study by Jain et al, that the universal screen and isolate strategy can have contributed only marginally to the reduction in infections.     

Systematic Review of Adrenalectomy and Lymph Node Dissection in Locally Advanced Renal Cell Carcinoma

Context

Controversy remains over whether adrenalectomy and lymph node dissection (LND) should be performed concomitantly with radical nephrectomy (RN) for locally advanced renal cell carcinoma (RCC) cT3–T4N0M0.

Objective

To systematically review all relevant literature comparing oncologic, perioperative, and quality-of-life (QoL) outcomes for locally advanced RCC managed with RN with or without concomitant adrenalectomy or LND.

Evidence acquisition

Relevant databases were searched up to August 2012. Randomised controlled trials (RCTs) and comparative studies were included. Outcome measures were overall survival, QoL, and perioperative adverse effects. Risks of bias (RoB) were assessed using Cochrane RoB tools. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach.

Evidence synthesis

A total of 3658 abstracts and 252 full-text articles were screened. Eight studies met the inclusion criteria: six LNDs (one RCT and five nonrandomised studies [NRSs]) and two adrenalectomies (two NRSs). RoB was high across the evidence base, and the quality of evidence from outcomes ranged from moderate to very low. Meta-analyses were not undertaken because of diverse study designs and data heterogeneity. There was no significant difference in survival between the groups, even though 5-yr overall survival appears better for the RN plus LND group compared with the no-LND group in one randomised study. There was no evidence of a difference in adverse events between the RN plus LND and no-LND groups. No studies reported QoL outcomes. There was no evidence of an oncologic difference between the RN with adrenalectomy and RN without adrenalectomy groups. No studies reported adverse events or QoL outcomes.

Conclusions

There is insufficient evidence to draw any conclusions on oncologic outcomes for patients having concomitant LND or ipsilateral adrenalectomy compared with patients having RN alone for cT3–T4N0M0 RCC. The quality of evidence is generally low and the results potentially biased. Further research in adequately powered trials is needed to answer these questions.     

Identifying viable theoretical frameworks with essential parameters for real-time and real world alcohol craving research: a systematic review of craving models

Background: Substance use is known to be episodic, dynamic, complex, and highly influenced by the environment, therefore a situational and momentary focus to alcohol craving research is appropriate. Current advances in mobile and wearable technology provide novel opportunities for craving research. However, the lack of consensus within craving theory impedes the identification and prioritization of parameters to be monitored. The aim of this study is to critically review current craving models in order to determine viable theoretical frameworks of alcohol craving and its essential parameters.

Methods: Eighteen models of craving were reviewed by applying a literature search with a five-step strategy that accounted for the momentary nature of craving and included a snowballing search and a key term extraction algorithm. Based on this review, multiple decision criteria were defined upon which to evaluate the models.

Results: Six models for alcohol craving were supported by sufficient empirical research to be eligible. The inferences drawn on these six models resulted in three decision criteria: the model should (1) incorporate negative affect as a predictor of relapse; (2) explain that dependent drinkers have a higher attentional bias towards alcohol cues than nondependent drinkers; (3) incorporate increased risk of relapse with heightened stress levels.

Conclusions: The affective processing model of negative reinforcement, the cognitive processing model, the incentive sensitization theory of addiction and the theory of neural opponent motivation are classified as viable theoretical frameworks, resulting in negative affect and stress as relevant parameters to include in real-time craving monitoring research.