Teriflunomide: A Once-daily Oral Medication for the Treatment of Relapsing Forms of Multiple Sclerosis

AbstractPurposeThe purpose was to summarize US prescribing information for teriflunomide in the treatment of patients with relapsing forms of multiple sclerosis (RMS), with reference to clinical efficacy and safety outcomes.MethodsIn September 2012, the US Food and Drug Administration granted approval for the use of teriflunomide, 14 mg and 7 mg once daily, to treat RMS on the basis of the results of a Phase II study and the Phase III TEMSO (Teriflunomide Multiple Sclerosis Oral) trial. After recent updates to the prescribing information (October 2014), key findings from these and 2 other Phase III clinical trials, TOWER (Teriflunomide Oral in People With Relapsing Multiple Sclerosis) and TOPIC (Oral Teriflunomide for Patients with a First Clinical Episode Suggestive of Multiple Sclerosis), and practical considerations for physicians are summarized.FindingsTeriflunomide, 14 mg and 7 mg, significantly reduced mean number of unique active lesions on magnetic resonance imaging (MRI; P < 0.05 for both doses) in the Phase II study. In the TEMSO and TOWER studies, the 14-mg dose of teriflunomide significantly reduced annualized relapse rate (31% and 36% relative risk reduction compared with placebo, respectively; both P < 0.001) and risk of disability progression sustained for 12 weeks (hazard ratio vs placebo 0.70 and 0.69, respectively; both P < 0.05). The 7-mg dose significantly (P < 0.02) reduced annualized relapse rate in both studies, although the reduction in risk of disability progression was not statistically significant. Teriflunomide treatment was also associated with significant efficacy on MRI measures of disease activity in TEMSO; both doses significantly reduced total lesion volume and number of gadolinium-enhancing T1 lesions. TOPIC evaluated patients with a first clinical event consistent with acute demyelination and brain MRI lesions characteristic of multiple sclerosis. More patients were free of relapse in the teriflunomide 14-mg and 7-mg groups than in the placebo group (P < 0.05 for both comparisons). In safety data pooled from the 4 studies, adverse events occurring in ≥2% of patients and ≥2% higher than in the placebo group were headache, alanine aminotransferase increase, diarrhea, alopecia (hair thinning), nausea, paresthesia, arthralgia, neutropenia, and hypertension. Routine monitoring procedures before and on treatment are recommended to assess potential safety issues. Women of childbearing potential must use effective contraception and, in the event of pregnancy, undergo an accelerated elimination procedure to reduce plasma concentrations of teriflunomide.ImplicationsClinical evidence suggests that teriflunomide is an effective therapeutic choice for patients with RMS, both as an initial treatment and as an alternative for patients who may have experienced intolerance or inadequate response to a previous or current disease-modifying therapy

Tempering Our Expectations: Drinking, Smoking, and the Economy of a Western Massachusetts Farmstead-Tavern

Between 1800 and 1830, William Sanford and his family operated a tavern in Hawley, a hilltown in western Massachusetts. The establishment was located on the town’s common, adjacent to the community’s Congregational meetinghouse and several other taverns. At the initiative of the local historical preservation group the Sons and Daughters of Hawley, archaeologists, students, teachers, and community members excavated the tavern site between 2011 and 2014. Historical and archaeological research indicates that William Sanford’s homestead functioned not only as a tavern, but also as a farm, store, smithy, and occasionally a court of law. Material evidence of alcohol and tobacco consumption, however, is less pronounced than at heavily-trafficked urban taverns. Research at the Sanford Tavern and other 19th-century public houses indicates that hybrid rural establishments played a variety of social and economic roles within local communities, which is evident in the archaeological record. Our findings show that archaeologists should approach rural farmstead-taverns with a different set of expectations

Calculating and resumming the classical virial expansion using automated algebra

Using schematic model potentials, we calculate exactly the virial coefficients of a classical gas up to sixth order and use them to assess the convergence properties of the virial expansion of basic thermodynamic quantities such as pressure, density, and compressibility. At sufficiently strong couplings, as expected, the virial expansion fails to converge. However, at least for the interactions and parameter ranges we explored, we find that Pad\'e-Borel resummation methods are extremely effective in improving the convergence of the expansion.Comment: 9 pages, 12 figure

Comparing Offline Decoding Performance in Physiologically Defined Neuronal Classes

Objective: Recently, several studies have documented the presence of a bimodal distribution of spike waveform widths in primary motor cortex. Although narrow and wide spiking neurons, corresponding to the two modes of the distribution, exhibit different response properties, it remains unknown if these differences give rise to differential decoding performance between these two classes of cells. Approach: We used a Gaussian mixture model to classify neurons into narrow and wide physiological classes. Using similar-size, random samples of neurons from these two physiological classes, we trained offline decoding models to predict a variety of movement features. We compared offline decoding performance between these two physiologically defined populations of cells. Main results: We found that narrow spiking neural ensembles decode motor parameters better than wide spiking neural ensembles including kinematics, kinetics, and muscle activity. Significance: These findings suggest that the utility of neural ensembles in brain machine interfaces may be predicted from their spike waveform widths

Thermodynamic Studies of [H_(2)Rh(diphosphine)_2]^+ and [HRh(diphosphine)_(2)(CH_(3)CN)]^(2+) Complexes in Acetonitrile

Thermodynamic studies of a series of [H_(2)Rh(PP)_2]^+ and [HRh(PP)_(2)(CH_(3)CN)]^(2+) complexes have been carried out in acetonitrile. Seven different diphosphine (PP) ligands were selected to allow variation of the electronic properties of the ligand substituents, the cone angles, and the natural bite angles (NBAs). Oxidative addition of H_2 to [Rh(PP)_2]^+ complexes is favored by diphosphine ligands with large NBAs, small cone angles, and electron donating substituents, with the NBA being the dominant factor. Large pK_a values for [HRh(PP)_(2)(CH_(3)CN)]^(2+) complexes are favored by small ligand cone angles, small NBAs, and electron donating substituents with the cone angles playing a major role. The hydride donor abilities of [H_(2)Rh(PP)_2]^+ complexes increase as the NBAs decrease, the cone angles decrease, and the electron donor abilities of the substituents increase. These results indicate that if solvent coordination is involved in hydride transfer or proton transfer reactions, the observed trends can be understood in terms of a combination of two different steric effects, NBAs and cone angles, and electron-donor effects of the ligand substituents

Local to Continental-Scale Variation in the Richness and Composition of an Aquatic Food Web

Organismic and Evolutionary Biolog

Access to Emergency Contraception After Removal of Age Restrictions

BACKGROUND: Levonorgestrel emergency contraception (EC) is safe and effective for postcoital pregnancy prevention. Starting in 2013, the US Food and Drug Administration removed age restrictions, enabling EC to be sold over the counter to all consumers. We sought to compare the availability and access for female adolescents with the 2012 study, using the same study design. METHODS: Female mystery callers posing as 17-year-old adolescents in need of EC used standardized scripts to telephone 979 pharmacies in 5 US cities. Using 2015 estimated census data and the federal poverty level, we characterized income levels of pharmacy neighborhoods. RESULTS: Of 979 pharmacies, 827 (83%) indicated that EC was available. This proportion did not vary by pharmacy neighborhood income level, nor was significantly different from the 2012 study (P = .78). When examining access, 8.3% of the pharmacies reported it was impossible to obtain EC under any circumstances, which occurred more often in low-income neighborhoods (10.3% vs 6.3%, adjusted odds ratio 1.5; 95% confidence interval 1.20-1.94). This was not significantly different from 2012 (P = .66). Correct information regarding over-the-counter access was conveyed only 51.6% of the time; accuracy did not differ by pharmacy's neighborhood income (47.9% vs 55.3%, adjusted odds ratio 0.89; 95% confidence interval 0.71-1.11) and was not significantly different from 2012 (P = .37). CONCLUSIONS: A majority of pharmacies have EC available; however, barriers to and disparities in access for adolescents persist and have not changed since the previous study despite regulatory changes that were designed to improve access to EC