Neurostimulators in epilepsy

A review of electrical stimulation in patients with refractory epilepsy, including animal and human data, shows that there is anatomic and physiologic evidence supporting the role of the thalamus in epilepsy. The most recent reports in patients with refractory epilepsy suggest that deep brain stimulation and cortical electrical stimulation of the anterior thalamic nucleus and hippocampus may reduce seizure frequency in patients with refractory partial and secondarily generalized seizures. This has led to a multicenter, prospective randomized trial called the Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy (SANTE trial) that is currently being conducted at several centers in the United States. There is also a multicenter clinical trial for patients with refractory partial epilepsy treated with a cranially implanted responsive neurostimulator (RNS) system. Preliminary reports from the RNS system feasibility trial (the NeuroPace trial) suggest that electrographic seizures can be detected before they evolve into clinical seizures, and that electrical stimulation of the epileptogenic zone can then terminate the electrographic seizures. The preliminary data in patients using deep brain stimulation of the anterior thalamic nucleus and hippocampus, and cortical stimulation studies of the epileptogenic zone are promising and suggest a reduction in seizure frequency in some patients with refractory partial and secondarily generalized seizures. The exact mechanism of action and the best parameters used during electrical stimulation remain unknown and are the subject of ongoing research.     

An examination of the association between seeing smoking in films and tobacco use in young adults in the west of Scotland: cross-sectional study

The objective is to examine the association between the amount of smoking seen in films and current smoking in young adults living in the west of Scotland in the UK. Cross-sectional analyses (using multivariable logistic regression) of data collected at age 19 (2002-04) from a longitudinal cohort originally surveyed at age 11 (1994-95) were conducted. The main outcome measure is smoking at age 19. No association was found between the number of occurrences of smoking estimated to have been seen in films (film smoking exposure) and current (or ever) smoking in young adults. This lack of association was unaffected by adjustment for predictors of smoking, including education, risk-taking orientation and smoking among peers. There was no association between film smoking exposure and smoking behaviour for any covariate-defined subgroup. Associations have been found between film smoking exposure and smoking initiation in younger adolescents in the United States. In this study, conducted in Scotland, no similar association was seen, suggesting that there may be age or cultural limitations on the effects of film smoking exposure on smoking. The lack of association could be due to methodological issues or greater sophistication of older adolescents and young adults in interpreting media images or the greater ubiquity of real-life smoking instances in Scotland. If the latter, film smoking exposure could become a more important risk factor for smoking uptake and maintenants in older adolescents following the recent ban on smoking in public places in Scotland.     

Venetoclax ramp-up strategies for chronic lymphocytic leukaemia in the United Kingdom: a real world multicentre retrospective study

This retrospective, observational study evaluated patterns of inpatient versus outpatient tumour lysis syndrome (TLS) monitoring during venetoclax ramp-up in 170 patients with chronic lymphocytic leukaemia. The primary outcome was clinical/biochemical TLS. Two clinical and four biochemical TLS occurred (4.1%). Five of the six events occurred in high-risk patients, four occurred at 20 mg dose and three at the 6-h time-point. Inpatient versus outpatient TLS rates within the high-risk subgroup were 15% and 8%. Risk category was the only predictor of TLS events in multivariate analysis. Outpatient escalation did not associate with clinically meaningful TLS events, suggesting outpatient escalation has manageable associated TLS risks, including in high-risk cohorts. These observations require confirmation in larger studies.     

Mutual Enhancements of CFD Modeling and Experimental Data: A Case Study of 1-μm Particle Deposition in a Branching Airway Model

In order to better understand aerosol dynamics and deposition in the complex flow field of the respiratory tract, both in vitro experiments and numerical modeling techniques have widely been employed. Computational fluid dynamics (CFD) modeling offers the flexibility of easily modifying system parameters such as flow rates, particle sizes, system geometry, and heterogeneous outlet conditions. However, a number of numerical errors and artifacts can lead to nonphysical CFD results. Experimental methods offer the advantage of physical realism; however, parameter variation is often difficult. The objective of this study is to illustrate the use of CFD to enhance the understanding of experimental results. In parallel, the selected experimental results have been used to partially validate the CFD predictions. A specific case study has been considered focusing on 1-μm particle depositions in a physiologically realistic bifurcation (PRB) model of respiratory generations 3–5. Previous experiments in this system report a deposition rate of approximately 0.01%. An in-depth CFD analysis has been employed to evaluate two cases of the empirical model. The first case consists of only the PRB double bifurcation geometry. The second case includes a portion of the experimental particle delivery system, which may influence the entering velocity and particle profiles. To assess the influence of upstream transition and turbulence, each of the two cases considered has been evaluated using laminar and low Reynolds number k–ω approximations. Results indicate that both upstream flow effects and turbulent or transitional flow play a significant role in determining the deposition of 1-μm particles in the model considered. Simulating upstream flow effects and laminar flow was required to match the empirically reported deposition fraction and provided a two orders of magnitude improvement over initial CFD estimates. This study highlights the need to consider the effects of experimental particle generation systems on velocity and particle profiles entering respiratory models. Future work is necessary to investigate the mechanisms responsible for the experimentally observed local deposition patterns.     

Nurse Practitioners' Knowledge,Attitudes, and Clinical Practices Regarding Treatment of Tobacco Use and Dependence

This article describes knowledge, attitudes, and clinical practices regarding treatment of tobacco use and dependence reported by nurse practitioners (NPs) interested in learning about evidence-based practices. Researchers analyzed baseline data from 193 licensed NPs prior to participating in Providers Practice Prevention: Treating Tobacco Use and Dependence. Results revealed domains where participants practiced in accordance with clinical practice guidelines and some areas where additional education and support may be necessary. NPs have a tremendous opportunity to reduce tobacco-related morbidity and mortality by addressing tobacco use, making it vitally important to support their implementation of evidence-based strategies.     

Budesonide/formoterol maintenance and reliever therapy versus conventional best practice

Budesonide/formoterol maintenance and reliever therapy (Symbicort SMART^®) reduces asthma exacerbations and symptoms versus fixed-dose regimens plus short-acting β₂-agonists (SABA) in double-blind trials. Information is lacking regarding its effectiveness versus conventional best practice (CBP).This pooled analysis of six 6-month, randomized, open-label studies examined asthma control and exacerbation risk in asthmatics (aged≥12 years). Patients (N = 7855) symptomatic on inhaled corticosteroids (ICS) or stable/symptomatic on ICS/long-acting β₂-agonists (LABA) received budesonide/formoterol maintenance and reliever therapy (160/4.5 μg bid and as needed) or CBP (ICS or ICS/LABA ± other agents at an approved dose plus as-needed SABA). Overall asthma control was assessed comparing the incidence of exacerbations and levels of asthma control using the asthma control questionnaire (ACQ).Budesonide/formoterol maintenance and reliever therapy did not significantly reduce time to first severe exacerbation (primary variable) versus CBP (P = 0.062). However, patients in this group experienced 15% fewer exacerbations (0.20 versus 0.24/patient/year; P = 0.021) and used 27% less ICS (P < 0.0001). Odds of remaining well controlled (ACQ ≤0.75) over 6 months were higher with budesonide/formoterol maintenance and reliever therapy versus CBP (45% versus 41%, odds ratio [OR] 1.29; P < 0.01) while risk of remaining uncontrolled decreased (25% versus 29%, OR 0.81; P < 0.01).Budesonide/formoterol maintenance and reliever therapy improves key aspects of asthma control versus physicians' choice of CBP.     

Comparison of low-dose intramuscular and intravenous salcatonin in the treatment of primary hyperparathyroidism.

The treatment of hypercalcaemia with low-dose salcatonin (100 U/d), administered either as a single intramuscular bolus or as a continuous intravenous infusion for five days, was examined in two groups of 10 patients with primary hyperparathyroidism, in a randomized open parallel study. Both the peak (0.31 +/- 0.035 mmol/L v 0.13 +/- 0.034 mmol/L) and overall (0.073 +/- 0.016 mmol/L v 0.018 +/- 0.016 mmol/L) hypocalcaemic responses were greater in the infusion group. The peak reduction in serum calcium occurred on day 2 of treatment after which there was a progressive attenuation of response. All the differences between the two methods of administration wer due to renal rather than bony effects of salcatonin. Possible causes of progressive resistance to treatment included reductions in sodium excretion and serum phosphate. It is concluded that low-dose salcatonin administered as a continuous infusion was more effective than the same dose given as a bolus. The kidney played a pivotal role both in the cause of the hypercalcaemia and in the response to treatment, including the rapid development of resistance which limits the use of salmon calcitonin in primary hyperparathyroidism to short-term reduction of serum calcium.