Sceloporus slevini

Number of Pages: 6Integrative BiologyGeological Science

Measuring Fatigue in Multiple Sclerosis: There may be Trouble Ahead

Introduction Poorly developed patient-reported outcome measures (PROs) risk type-II errors (i.e. false negatives) in clinical trials, resulting in erroneous failure to achieve trial endpoints. Validity is a fundamental requirement of fit-for-purpose PROs, with the main determinant of validity being the PROs items, i.e. content validity. Here, we sought to identify fatigue PRO instruments used in multiple sclerosis (MS) studies and to assess the extent to which their development satisfied current content validity standards. Methods We searched Embase® and Medline® for MS studies using fatigue-based PROs. Abstracts were screened, PROs identified, and their relevant development papers assessed against seven Consensus Standards for Measurement Instruments (COSMIN) criteria for content development. Results From 3814 abstracts, 18 fatigue PROs met our inclusion criteria. Most PROs did not satisfy at least one COSMIN content validity standard. Frequent omissions during PRO development include: clearly defined constructs; conceptual frameworks; qualitative research in representative samples; and literature reviews. PRO development quality has improved significantly since FDA guidance was published (U = 10.0, p = 0.02). However, scatterplots and correlations between PRO COSMIN scores and citation frequency (rho = − 0.62) and clinical trials usage (rho = + 0.18) implied that PRO quality is unrelated to choice. COSMIN scores implied that the Fatigue Symptoms and Impact Questionnaire—Relapsing Multiple Sclerosis (FSIQ-RMS) and Neurological Fatigue Index—Multiple Sclerosis (NFI-MS) had the strongest evidence for adequate content validity. Conclusion Most existing fatigue PROs do not meet COSMIN content validity requirements. Although two PROs scored well on aggregate (NFI-MS and FSIQ-RMS), our subsequent evaluation of the item sets that generated their scores implied that both PROs have weaker content validity than COSMIN suggests. This indicates that COSMIN criteria require further development, and raises significant concerns about how we have measured one of the most common and burdensome MS symptoms. A detailed head-to-head psychometric evaluation is needed to determine the impact of different PRO development qualities and the implications of the problems implied by our analyses, on measurement performance

The Ontology of Intentional Agency in Light of Neurobiological Determinism: Philosophy Meets Folk Psychology

The moot point of the Western philosophical rhetoric about free will consists in examining whether the claim of authorship to intentional, deliberative actions fits into or is undermined by a one-way causal framework of determinism. Philosophers who think that reconciliation between the two is possible are known as metaphysical compatibilists. However, there are philosophers populating the other end of the spectrum, known as the metaphysical libertarians, who maintain that claim to intentional agency cannot be sustained unless it is assumed that indeterministic causal processes pervade the action-implementation apparatus employed by the agent. The metaphysical libertarians differ among themselves on the question of whether the indeterministic causal relation exists between the series of intentional states and processes, both conscious and unconscious, and the action, making claim for what has come to be known as the event-causal view, or between the agent and the action, arguing that a sort of agent causation is at work. In this paper, I have tried to propose that certain features of both event-causal and agent-causal libertarian views need to be combined in order to provide a more defendable compatibilist account accommodating deliberative actions with deterministic causation. The ‘‘agent-executed-eventcausal libertarianism’’, the account of agency I have tried to develop here, integrates certain plausible features of the two competing accounts of libertarianism turning them into a consistent whole. I hope to show in the process that the integration of these two variants of libertarianism does not challenge what some accounts of metaphysical compatibilism propose—that there exists a broader deterministic relation between the web of mental and extra-mental components constituting the agent’s dispositional system—the agent’s beliefs, desires, short-term and long-term goals based on them, the acquired social, cultural and religious beliefs, the general and immediate and situational environment in which the agent is placed, etc. on the one hand and the decisions she makes over her lifetime on the basis of these factors. While in the ‘‘Introduction’’ the philosophically assumed anomaly between deterministic causation and the intentional act of deciding has been briefly surveyed, the second section is devoted to the task of bridging the gap between compatibilism and libertarianism. The next section of the paper turns to an analysis of folk-psychological concepts and intuitions about the effects of neurochemical processes and prior mental events on the freedom of making choices. How philosophical insights can be beneficially informed by taking into consideration folk-psychological intuitions has also been discussed, thus setting up the background for such analysis. It has been suggested in the end that support for the proposed theory of intentional agency can be found in the folk-psychological intuitions, when they are taken in the right perspective

The Cannabinoid Use in Progressive Inflammatory brain Disease (CUPID) trial: a randomised double-blind placebo-controlled parallel-group multicentre trial and economic evaluation of cannabinoids to slow progression in multiple sclerosis.

This is a freely-available open access publication. Please cite the published version which is available via the DOI link in this record.The Cannabinoid Use in Progressive Inflammatory brain Disease (CUPID) trial aimed to determine whether or not oral Δ(9)-tetrahydrocannabinol (Δ(9)-THC) slowed the course of progressive multiple sclerosis (MS); evaluate safety of cannabinoid administration; and, improve methods for testing treatments in progressive MS.The National Institute for Health Research Health Technology Assessment programmeMedical Research Council Efficacy and Mechanism Evaluation programmeMultiple Sclerosis SocietyMultiple Sclerosis Trus

The size of the treatment effect: do patients and proxies agree?

Background: This study examined whether MS patients and proxy respondents agreed on change in disease impact, which was induced by treatment. This may be of interest in situations when patients suffer from limitations that interfere with reliable self-assessment, such as cognitive impairment.Methods: MS patients and proxies completed the Multiple Sclerosis Impact Scale (MSIS-29) before and after intravenous steroid treatment. Analyses focused on patient-proxy agreement between MSIS-29 change scores. Transition ratings were used to measure the patient's judgement of change and whether this change was reflected in the MSIS-29 change of patients and proxies. Receiver operating characteristic (ROC) analyses were also performed to examine the diagnostic properties of the MSIS-29 when completed by patients and proxies.Results: 42 patients and proxy respondents completed the MSIS-29 at baseline and follow-up. Patient-proxy differences between change scores on the physical and psychological MSIS-29 subscale were quite small, although large variability was found. The direction of mean change was in concordance with the transition ratings of the patients. Results of the ROC analyses of the MSIS-29 were similar when completed by patients (physical scale: AUC = 0.79, 95% CI: 0.65 - 0.93 and 0.66, 95% CI: 0.48 - 0.84 for the psychological scale) and proxies (physical scale: 0.80, 95% CI: 0.72 - 0.96 and 0.71, 95% CI: 0.56 - 0.87 for the psychological scale)Conclusion: Although the results need to be further explored in larger samples, these results do point towards possible use of proxy respondents to assess patient perceived treatment change at the group level

Nonlinear stability of oscillatory wave fronts in chains of coupled oscillators

We present a stability theory for kink propagation in chains of coupled oscillators and a new algorithm for the numerical study of kink dynamics. The numerical solutions are computed using an equivalent integral equation instead of a system of differential equations. This avoids uncertainty about the impact of artificial boundary conditions and discretization in time. Stability results also follow from the integral version. Stable kinks have a monotone leading edge and move with a velocity larger than a critical value which depends on the damping strength.Comment: 11 figure

Static solitons with non-zero Hopf number

We investigate a generalized non-linear O(3) $\sigma$-model in three space dimensions where the fields are maps $S^3 \mapsto S^2$. Such maps are classified by a homotopy invariant called the Hopf number which takes integer values. The model exhibits soliton solutions of closed vortex type which have a lower topological bound on their energies. We explicitly compute the fields for topological charge 1 and 2 and discuss their shapes and binding energies. The effect of an additional potential term is considered and an approximation is given for the spectrum of slowly rotating solitons.Comment: 13 pages, RevTeX, 7 Postscript figures, minor changes have been made, a reference has been corrected and a figure replace

What Does Weight Have to Do with It? Parent Perceptions of Weight and Pain in a Pediatric Chronic Pain Population

Tailored pain management strategies are urgently needed for youth with co-occurring chronic pain and obesity; however, prior to developing such strategies, we need to understand parent perspectives on weight in the context of pediatric chronic pain. Participants in this study included 233 parents of patients presenting to a multidisciplinary pediatric chronic pain clinic. Parents completed a brief survey prior to their child\u27s initial appointment; questions addressed parents\u27 perceptions of their child\u27s weight, and their perceptions of multiple aspects of the relationship between their child\u27s weight and chronic pain. The majority (64%) of parents of youth with obesity accurately rated their child\u27s weight; this group of parents was also more concerned (p \u3c 0.05) about their child\u27s weight than parents of youth with a healthy weight. However, the majority of parents of youth with obesity did not think their child\u27s weight contributed to his/her pain, or that weight was relevant to their child\u27s pain or pain treatment. Overall, only half of all parents saw discussions of weight, nutrition, and physical activity as important to treating their child\u27s pain. Results support the need for addressing parents\u27 perceptions of their child\u27s weight status, and educating parents about the relationship between excessive weight and chronic pain