Teriflunomide reduces relapse-related neurological sequelae, hospitalizations and steroid use

Multiple sclerosis (MS) relapses impose a substantial clinical and economic burden. Teriflunomide is a new oral disease-modifying therapy approved for the treatment of relapsing MS. We evaluated the effects of teriflunomide treatment on relapse-related neurological sequelae and healthcare resource use in a post hoc analysis of the Phase III TEMSO study. Confirmed relapses associated with neurological sequelae [defined by an increase in Expanded Disability Status Scale/Functional System (sequelae-EDSS/FS) ≥30 days post relapse or by the investigator (sequelae-investigator)] were analyzed in the modified intention-to-treat population (n = 1086). Relapses requiring hospitalization or intravenous (IV) corticosteroids, all hospitalizations, emergency medical facility visits (EMFV), and hospitalized nights for relapse were also assessed. Annualized rates were derived using a Poisson model with treatment, baseline EDSS strata, and region as covariates. Risks of sequelae and hospitalization per relapse were calculated as percentages and groups were compared with a χ² test. Compared with placebo, teriflunomide reduced annualized rates of relapses with sequelae-EDSS/FS [7 mg by 32 % (p = 0.0019); 14 mg by 36 % (p = 0.0011)] and sequelae-investigator [25 % (p = 0.071); 53 % (p < 0.0001)], relapses leading to hospitalization [36 % (p = 0.015); 59 % (p < 0.0001)], and relapses requiring IV corticosteroids [29 % (p = 0.001); 34 % (p = 0.0003)]. Teriflunomide-treated patients spent fewer nights in hospital for relapse (p < 0.01). Teriflunomide 14 mg also decreased annualized rates of all hospitalizations (p = 0.01) and EMFV (p = 0.004). The impact of teriflunomide on relapse-related neurological sequelae and relapses requiring healthcare resources may translate into reduced healthcare costs.     

Comparison of warfarin with direct oral anticoagulants for thromboembolic prophylaxis after catheter ablation of ventricular tachycardia

Introduction

Thromboembolic events after catheter ablation of ventricular tachycardia (VT) can result in significant morbidity. Thromboembolic prophylaxis after catheter ablation can be achieved by the use of antiplatelet agents, vitamin K antagonists, or direct oral anticoagulants (DOACs). The relative safety and efficacy of these modes of prophylaxis are uncertain. We sought to compare the outcomes of patients who received warfarin or DOACs for thromboembolic prophylaxis after catheter ablation of VT.

Methods and Results

Anticoagulation with DOACS was started after left ventricular VT ablation in a series of 42 consecutive patients with structural heart disease (67 ± 11 years, 3 women, ejection fraction 32 ± 14%). Duration of hospital stay, bleeding episodes, and thromboembolic events were compared to a historic consecutive group of patients (n = 38, 65 ± 13 years, 14 women, ejection fraction 36 ± 13%) in whom anticoagulation with a formerly described protocol of heparin and vitamin K antagonist was used after VT ablation procedures. Hospital stay was significantly shorter in the group where DOACs were used as compared to vitamin K antagonists (3.3 ± 1.8 vs. 5.0 ± 2.5 days postablation; p = 0.001) without an increase of bleeding or thromboembolic events.

Conclusion

Anticoagulation with DOACs is safe and shortens hospital stay in patients with structural heart disease undergoing left ventricular VT ablation procedures.     

Peripapillary hyperreflective ovoid mass-like structures: Multimodal imaging—A review

Peripapillary hyperreflective ovoid mass-like structures (PHOMS) are a laterally bulging herniation of distended axons into the peripapillary region above the level of Bruch's membrane opening. Increased use of enhanced depth imaging-optical coherence tomography (EDI-OCT) in our evaluation of the optic nerve head (ONH) and greater recognition of the vast range of optic nerve pathologies with which PHOMS is associated provides convincing evidence that PHOMS is not just buried optic disc drusen (ODD) as previously described. The frequent coexistence of PHOMS with ODD, papilloedema, anterior ischaemic optic neuropathy, tilted optic disc syndrome, inflammatory demyelinating disorders and other diseases associated with axoplasmic stasis provides insight into its underlying pathophysiology. The present review will discuss the role of key imaging modalities in the differential diagnosis of PHOMS, explore the current literature on the relationship between PHOMS and common neuro-ophthalmic conditions, and highlight the gaps in our knowledge, with respect to disease classification and prognosis, to pave the way for future directions of research.     

Expression and regulation of small proline-rich protein 2 in allergic inflammation

Asthma is a complex inflammatory pulmonary disorder that is on the rise despite intense ongoing research. We aimed to elucidate novel pathways involved in the pathogenesis of asthma. Employing asthma models induced by different allergens (ovalbumin and Aspergillus fumigatus), we uncovered the involvement of two members of the small proline-rich protein (SPRR) family, SPRR2a and SPRR2b, known to be involved in epithelial differentiation but not allergic disease. In situ hybridization revealed induction of SPRR2 signal in a subset of bronchial epithelial cells and mononuclear cells associated with inflammation after allergen challenge. Allergen-induced SPRR2 mRNA accumulation in the lung occurred in a time-dependent manner, with peak expression 10-96 h after a second ovalbumin challenge. Transgenic overexpression of interleukin (IL)-13 in the lungs resulted in a marked increase of SPRR2 expression, and allergen-induced SPRR2 expression was significantly decreased in IL-13-deficient mice. Studies in gene-targeted mice revealed that allergen-induced SPRR2 was dependent upon STAT6. Finally, we aimed to determine if the induction of SPRR2 by allergen was tissue specific. Notably, SPRR2 was markedly increased in the small intestine after induction of allergic gastrointestinal inflammation. Thus, SPRR2 is an allergen- and IL-13-induced gene in experimental allergic responses that may be involved in disease pathophysiology.     

Molecular characterization of human parainfluenza virus type 1 in infants attending Mbagathi District Hospital, Nairobi, Kenya: a retrospective study

Human parainfluenza virus type 1 (HPIV-1), a paramyxovirus, is a leading cause of pediatric respiratory hospitalizations globally. Currently, there is no clinically successful vaccine against HPIV-1. Hence, there is a need to characterize circulating strains of this virus to establish the feasibility of developing a vaccine against the virus. The variable HPIV-1 hemagglutin–neuraminidase (HN) protein is found in the envelope of HPIV-1, where it initiates the infection process by binding to cellular receptors. HN is also the major antigen against which the human immune response is directed against. The present study focused on identifying mutations in the HN gene that would be useful in understanding the evolution of HPIV-1. 21 HPIV-1 isolates were obtained after screening nasopharyngeal samples from patients with influenza-like illness. The samples were collected from Mbagathi District Hospital Nairobi from the period July 2007 to December 2010. RT-PCR was carried out on the isolates using HN-specific primers to amplify a 360 nt in the most polymorphic region and the amplicons sequenced. Genomic data were analysed using a suite of bioinformatic software. Forty eight polymorphic sites with a total of 55 mutations were identified at the nucleotide level and 47 mutations at 23 positions at the amino acid level. There was more radical nonsynonymous amino acid changes (seven positions) observed than conservative nonsynonymous changes (one position) on the HN gene fragment. No positively selected sites were found in the HN protein. The result from the analysis of 21 HPIV-1 Mbagathi isolates demonstrated that the HN gene which is the major antigenic target was under purifying (negative) selection displaying evolutionary stasis.     

Nintendo® Wii Fit based sleepiness tester detects impairment of postural steadiness due to 24 h of wakefulness

A field-usable sleepiness tester could reduce sleepiness related accidents. 15 subjects’ postural steadiness was measured with a Nintendo^® Wii Fit balance board every hour for 24 h. Body sway was quantified with complexity index, C_I, and the correlation between C_I and alertness predicted by a three-process model of sleepiness was calculated. The C_I group average was 8.9 ± 1.3 for alert and 7.9 ± 1.4 for sleep deprived subjects (p < 0.001, ρ = 0.94). The Wii Fit board detects the impairment of postural steadiness. This may allow large scale sleepiness testing outside the laboratory setting.