The statistical analysis of partially confounded covariates important to neural spiking

A method is presented capable of disambiguating the relative influence of statistical covariates upon neural spiking activity. The method, an extension of the generalized linear model (GLM) methodology introduced in Truccolo et al. (2005) to analyze neural spiking data, exploits projection operations motivated by a geometry present in the Fisher information of the GLM maximum likelihood parameter estimator. By exploiting these projections, neural activity can be divided into three categories. These three categories, neural activity due solely to a set of covariates of interest, neural activity due solely to a set of uninteresting, or nuisance, covariates, and neural activity that cannot be unequivocally assigned to either set of covariates, can be associated with physical variables such as time, position, head-direction and velocity. This association allows the analysis of neural activity that can, for example, be due solely to temporal influence, irrespective of other, identified, influences. The method is applied in simulation to a rat exploring a temporally modulated place field. A portion of the analysis reported in MacDonald et al. (2011), using the methodology described herein, is reproduced. This analysis demonstrates the temporal bridging of a delay period in a sequential memory task by firing activity of cells present in the rodent hippocampus that cannot be explained by rodent position, head direction or velocity.     

Detection of infliximab in breast milk of nursing mothers with inflammatory bowel disease

Introduction

Limited data suggest the absence of infliximab in breast milk, thereby implying the safety of this drug during breast-feeding. We aimed to re-evaluate the presence of infliximab in breast milk of nursing IBD patients.

Methods

Serum and breast milk were obtained post-partum from 3 breast-feeding patients with Crohn's disease before and after re-initiation of infliximab. ELISA assay was employed to measure infliximab level in maternal serum and in breast milk. The level of infliximab was also measured in breast milk of a control group of 8 nursing healthy mothers.

Results

Infliximab was undetectable in breast milk prior to the first infusion and was also not measurable in 8 lactating women not exposed to infliximab. Infliximab levels in breast milk rose up to 101 ng/ml within 2–3 days of the infusion. These levels of infliximab in breast milk were roughly 1/200th of the level in blood.

Conclusions

In contrast with prior reports, infliximab can be detected in the breast milk of nursing mothers. The miniscule amounts of infliximab transferred in breast milk are unlikely to result in systemic immune-suppression of the infant. Nonetheless, local effects of this exposure on the neonates' intestine and potential immune sensitization or tolerization towards the drug can not be excluded and merit further investigations.     

Efficacy and safety of vaccination against pandemic 2009 influenza A (H1N1) virus among patients with rheumatic diseases

Objective

To assess the efficacy and safety of vaccination against pandemic H1N1 virus in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) compared with healthy controls.

Methods

The study population comprised 41 RA patients, 21 SLE patients, 17 PsA patients, 15 AS patients, and 25 healthy controls. All were vaccinated using the Novartis MF59‐adjuvanted H1N1v monovalent influenza vaccine. The immunogenicity of the vaccine was assessed on day 1 and again 4 weeks later by hemagglutination inhibition assay. Geometric mean titers and seroconversion rates were calculated for each group. The safety of the vaccine was evaluated using the 28‐joint Disease Activity Score (DAS28) for RA and PsA, the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI).

Results

The proportion of baseline protective levels of antibodies against H1N1 was similar in all but the AS group, in which it was lower. The geometric mean titers increased significantly in all 5 groups. A substantial proportion of patients and controls responded to the vaccine. The healthy controls demonstrated a better response than each of the other groups: 84% versus 56% for RA, 67% for SLE, 59% for PsA, and 53% for AS. Multivariate logistic regression analysis identified RA and PsA as parameters of significantly lower response. The DAS28, BASDAI, and SLEDAI remained unchanged after vaccination.

Conclusion

Vaccination against pandemic H1N1 using an adjuvanted H1N1v monovalent influenza is safe and induced an appropriate response in patients with RA, SLE, PsA, and AS.     

Evolution from active surveillance to focal therapy in the management of prostate cancer

Organ-preserving therapies are widely accepted in many facets of medicine and, more recently, in oncology. For example, partial nephrectomy is now accepted as a preferred alternative over radical nephrectomy for small (up to 4 cm or T1) tumors. Focal therapy (FT) is another organ-preserving strategy applying energy (cryotherapy, laser ablation and/or high-intensity focused ultrasound) to destroy tumors while leaving the majority of the organ, surrounding tissue and structures unscathed and functional. Owing to the perceived multifocality of prostate cancer (PCa) technology limitations, in the past PCa was not considered suitable for FT. However, with the rise of active surveillance for the management of low-risk PCa in carefully selected patients, FT is emerging as an alternative. This is owing to technology improvements in imaging and energy-delivery systems to ablate tissue, as well as the realization that many men and clinicians still desire tumor control. With the postulated ability to ablate tumors with minimal morbidity, FT may have found a role in the management of PCa; the aim of FT a being long-term cancer control without the morbidity associated with radical therapies. Data for FT in PCa have been derived from case series and small Phase I trials, with larger cohort studies with longer follow-up having only just commenced. More data from large trials on the safety and efficacy of FT are required before this approach can be recommended in men with PCa. Importantly, studies must confirm that no viable cancer cells remain in the region of ablation. FT might eventually prove to be a 'middle ground' between active surveillance and radical treatment, combining minimal morbidity with cancer control and the potential for retreatment.     

Lidocaine gel as an anesthetic protocol for nasogastric tube insertion in the ED

Objective

The aim of the study was to evaluate the efficacy of topical 2% lidocaine gel in reducing pain and discomfort associated with nasogastric tube insertion (NGTI) and compare lidocaine to ordinary lubricant gel in the ease in carrying out the procedure.

Methods

This prospective, randomized, double-blind, placebo-controlled, convenience sample trial was conducted in the emergency department of our tertiary care university-affiliated hospital. Five milliliters of 2% lidocaine gel or placebo lubricant gel were administered nasally to alert hemodynamically stable adult patients 5 minutes before undergoing a required NGTI. The main outcome measures were overall pain, nasal pain, discomfort (eg, choking, gagging, nausea, vomiting), and difficulty in performing the procedure. Standard comparative statistical analyses were used.

Results

The study cohort included 62 patients (65% males). Thirty-one patients were randomized to either lidocaine or placebo groups. Patients who received lidocaine reported significantly less intense overall pain associated with NGTI compared to those who received placebo (37 ± 28 mm vs 51 ± 26 mm on 100-mm visual analog scale; P < .05). The patients receiving lidocaine also had significantly reduced nasal pain (33 ± 29 mm vs 48 ± 27 mm; P < .05) and significantly reduced sensation of gagging (25 ± 30 mm vs 39 ± 24 mm; P < .05). However, conducting the procedure was significantly more difficult in the lidocaine group (2.1 ± 0.9 vs 1.4 ± 0.7 on 5-point Likert scale; P < .05).

Conclusion

Lidocaine gel administered nasally 5 minutes before NGTI significantly reduces pain and gagging sensations associated with the procedure but is associated with more difficult tube insertion compared to the use of lubricant gel.     

Modulating oscillatory brain activity correlates of behavioral inhibition using transcranial direct current stimulation

ObjectiveStudies have mainly documented behavioral changes induced by transcranial direct current stimulation (tDCS), but recently cortical modulations of tDCS have also been investigated. Our previous work revealed behavioral inhibition modulation by anodal tDCS over the right inferior frontal gyrus (rIFG); however, the electrophysiological correlates underlying this stimulation montage have yet to be established. The current work aimed to evaluate the distribution of neuronal oscillations changes following anodal tDCS over rIFG coupled with cathodal tDCS over left orbitofrontal cortex (lOFC) using spectral power analysis.MethodsHealthy subjects underwent sham and real tDCS (15 min, 1.5 mA, anodal rIFG; cathodal lOFC) stimulation conditions in a single-blind, placebo-controlled cross-over trial. Following tDCS session, resting EEG recordings were collected during 15 min.ResultsAnalysis showed a significant and selective diminution of the power of theta band. The theta diminution was observed in the rIFG area (represented the anode electrode), and was not found in the lOFC area (represented the cathode electrode). A significant effect was observed only in the theta but not in other bands.ConclusionsThese results are the first demonstration of modulating oscillatory activity as measured by EEG with tDCS over rIFG in general, and documenting theta band reduction with this montage in particular.SignificanceOur results may explain the improvement in behavioral inhibition reported in our previous work, and although this study was conducted with healthy subjects, the findings suggest that tDCS may also modulate electrophysiological changes among ADHD patients, where decreasing theta activity is the target of neuro-feedback methods aimed to improve cognitive control.