Primary prevention implantable cardioverter defibrillator recipients: the need for defibrillator back-up after an event-free first battery service-life

ICD Replacement After a Therapy‐Free First Service‐Life . Introduction: In primary prevention implantable cardioverter defibrillator (ICD) patients, the relatively low incidence of ventricular arrhythmias (VA) combined with the limited battery service‐life potentially results in a large group of patients who have had no benefit of the ICD during first service‐life. Data on the occurrence of VA after device replacement remain scarce. The purpose of this study was to give clinicians better insight in the dilemma whether or not to replace an ICD after an event‐free first battery service‐life. Methods and Results: All patients treated with an ICD for primary prevention who had a replacement because of battery depletion and who did not receive appropriate therapy before device replacement were included in this analysis. Of 154 primary prevention ICD patients needing replacement because of battery depletion, 114 (74%) patients (mean age 61 ± 11 years, 80% male) had not received appropriate ICD therapy for VA. Follow‐up was 71 ± 24 months after the initial implantation and 25 ± 21 months after device replacement. Following replacement, 3‐year cumulative incidence of appropriate therapy in response to ventricular tachycardia or ventricular fibrillation was 14% (95% CI 5–22%). Conclusion: The majority of primary prevention ICD patients do not experience VA during first battery service‐life. However, a substantial part of these patients does experience appropriate ICD therapy after replacement. (J Cardiovasc Electrophysiol, Vol. 22, pp. 1346‐1350, December 2011)     

Evaluation of saliva as an alternative matrix for monitoring plasma Zidovudine, Lamivudine and nevirapine concentrations in Rwanda

Saliva may provide interesting advantages as matrix for compliance measurements, pharmacokinetic studies and therapeutic drug monitoring in resource limited countries. We investigated the feasibility of using saliva for compliance monitoring of zidovudine (ZDV), lamivudine (3TC) and nevirapine (NVP) in 29 HIV-1 infected patients from Rwanda. ZDV, 3TC and NVP drug levels were quantified by an LC/MS-MS method in plasma and stimulated saliva samples and compared using Bland-Altman analysis. Seven patients demonstrated undetectable saliva ZDV levels while five out of these seven also showed no 3TC salivary concentrations. For the other samples, we observed a good agreement between salivary and plasma concentrations of each antiretroviral drug. A significant relation between the difference in saliva and plasma ZDV concentrations and the average ZDV concentration in the two matrices was deduced as follow: y = -380.15 + 1.79 x. The log saliva and plasma concentration difference of both 3TC and NVP was consistent across the range of average log concentration. Overall, we showed large agreement limits suggesting a wide inter patient variability that may result to non-reliable plasma level predictions from saliva drug measurements. Therefore, our results indicate that saliva may serve as a valuable tool only for NVP compliance testing because of its high salivary concentration.     

Sensorimotor and cognitive functions in a SOD1(G37R) transgenic mouse model of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurological disorder involving degeneration of motor neurons in brain and spinal cord, leading to progressive atrophy of skeletal muscles and, ultimately, paralysis and death. Copper-mediated oxidative damage is proposed to play a critical role in the pathogenesis of Cu/Zn superoxide dismutase (SOD1) - linked hereditary amyotrophic lateral sclerosis. To understand more clearly the pathogenesis of sensorimotor dysfunction and to find the most appropriate methods for early detection of symptoms and for monitoring them across time, a murine model was assessed at three time points (5, 8, and 11 months). Transgenic mice with the G37R mutation of human SOD1 exhibited earliest signs of dysfunction at 8 months in terms of a pathological hindpaw clasping reflex, as well as slowed movement time on a suspended bar, anomalies in footprint patterns, weaker grip strength, raised somatosensory thresholds, and deficits in passive avoidance learning, yielding a margin of 3-4 months before death to test experimental therapies.