High Levels of Circulating Type II Collagen Degradation Marker (CTx-II) Are Associated with Specific VDR Polymorphisms in Patients with Adult Vertebral Osteochondrosis

Both vitamin D and collagen have roles in osteocartilaginous homeostasis. We evaluated the association between the circulating 25-hydroxyvitamin D (25(OH)D) type I and II collagen degradation products (CTx-I, and CTx-II), and four vitamin D receptor gene (VDR) polymorphisms, in Italian males affected by low back pain (LBP) due to herniation/discopathy and/or vertebral osteochondrosis. FokI, BsmI, ApaI, and TaqI VDR-polymorphisms were detected through PCR-restriction fragment length polymorphism (RFLP), and circulating 25(OH)D, CTx-I and CTx-II were measured by immunoassays in 79 patients (of which 26 had osteochondrosis) and 79 age-, sex- and body mass index (BMI)-matched healthy controls. Among all 158 subjects, carriers of FF and Ff genotypes showed lower 25(OH)D than ff, which suggested a higher depletion of vitamin D in F allele carriers. Higher CTx-I concentrations were observed in TT versus Tt among controls, and Tt versus tt among LBP cases, which suggested a higher bone-cartilaginous catabolism in subjects bearing the T allele. Higher CTx-II concentrations were observed in patients with osteochondrosis bearing FF, bb, TT, or Aa genotypes in comparison with hernia/discopathy patients and healthy controls. Vertebral osteochondrosis shows peculiar genotypic and biochemical features related to vitamin D and the osteocartilaginous metabolism. Vitamin D has roles in the pathophysiology of osteochondrosis

Do neurologists agree in diagnosing drug resistance in adults with focal epilepsy?

OBJECTIVE: To evaluate interrater agreement in categorizing treatment outcomes and drug responsiveness status according to the International League Against Epilepsy (ILAE) definition of drug-resistant epilepsy. METHODS: A total of 1053 adults with focal epilepsy considered by the investigators to meet ILAE criteria for drug resistance were enrolled consecutively at 43 centers and followed up prospectively for 18-34 months. Treatment outcomes for all antiepileptic drugs (AEDs) used up to enrollment (retrospective assessment), and on an AED newly introduced at enrollment, were categorized by individual investigators and by 2 rotating members of a 16-member expert panel (EP) that reviewed the patient records independently. Interrater agreement was tested by Cohen's kappa (k) statistics and rated according to Landis and Koch's criteria. RESULTS: Agreement between EP members in categorizing outcomes on the newly introduced AED was almost perfect (90.1%, k = 0.84, 95% confidence interval [CI] 0.80-0.87), whereas agreement between the EP and individual investigators was moderate (70.4%, k = 0.57, 95% CI 0.53-0.61). Similarly, categorization of outcomes on previously used AEDs was almost perfect between EP members (91.7%, k = 0.83, 95% CI 0.81-0.84) and moderate between the EP and investigators (68.2%, k = 0.50, 95% CI 0.48-0.52). Disagreement was related predominantly to outcomes considered to be treatment failures by the investigators but categorized as undetermined by the EP. Overall, 19% of patients classified as having drug-resistant epilepsy by the investigators were considered by the EP to have "undefined responsiveness." SIGNIFICANCE: Interrater agreement in categorizing treatment outcomes according to ILAE criteria ranges from moderate to almost perfect. Nearly 1 in 5 patients considered by enrolling neurologists to be "drug-resistant" were classified by the EP as having "undefined responsiveness.

Cities, Inequalities and the Geography of Societal Discontent in European Regions

The "urban wellbeing paradox" is a recurring theme in research examining the differences in life satisfaction across settlements of varying sizes, suggesting that large cities are consistently associated with higher levels of dissatisfaction due to disproportionately high interpersonal income inequalities. This paper re-evaluates that conclusion by analysing the relationship between individual dissatisfaction, conditions of personal disadvantage, and income inequality in large cities. Our extensive study, based on self-reported dissatisfaction from over 760,000 citizens living in EU and UK NUTS2 regions between 2013 and 2018, reveals that individuals facing occupational and economic disadvantages are the most negatively affected by living in urban areas. However, urbanization economies partially offset these negative effects, particularly for those individuals in disadvantaged conditions

Validated outcome of treatment changes according to International League Against Epilepsy criteria in adults with drug-resistant focal epilepsy.

OBJECTIVE: Although many studies have attempted to describe treatment outcomes in patients with drug-resistant epilepsy, results are often limited by the adoption of nonhomogeneous criteria and different definitions of seizure freedom. We sought to evaluate treatment outcomes with a newly administered antiepileptic drug (AED) in a large population of adults with drug-resistant focal epilepsy according to the International League Against Epilepsy (ILAE) outcome criteria. METHODS: This is a multicenter, observational, prospective study of 1053 patients with focal epilepsy diagnosed as drug-resistant by the investigators. Patients were assessed at baseline and 6, 12, and 18 months, for up to a maximum of 34 months after introducing another AED into their treatment regimen. Drug resistance status and treatment outcomes were rated according to ILAE criteria by the investigators and by at least two independent members of an external expert panel (EP). RESULTS: A seizure-free outcome after a newly administered AED according to ILAE criteria ranged from 11.8% after two failed drugs to 2.6% for more than six failures. Significantly fewer patients were rated by the EP as having a "treatment failure" as compared to the judgment of the investigator (46.7% vs 62.9%, P < 0.001), because many more patients were rated as "undetermined outcome" (45.6% vs 27.7%, P < 0.001); 19.3% of the recruited patients were not considered drug-resistant by the EP. SIGNIFICANCE: This study validates the use of ILAE treatment outcome criteria in a real-life setting, providing validated estimates of seizure freedom in patients with drug-resistant focal epilepsy in relation to the number of previously failed AEDs. Fewer than one in 10 patients achieved seizure freedom on a newly introduced AED over the study period. Pseudo drug resistance could be identified in one of five cases

RELIABILITY OF STATED PREFERENCE METHODS

Many times governments and policy makers have to choose among different projects or policies to implement. In principle, the best choice is the one which maximizes the social welfare that, in turn, depends on individual preferences. But very often preferences are unknown and even not observable. In practice, a common procedure is to directly ask a sample of individuals about their preferences, which are therefore stated by agents rather than revealed by their behaviour. Methods for preference revelation can be classified into two broad families. The first one involves the case in which respondents are asked to simulate their market behaviour in a fictitious context designed by the researcher. The final goal of these studies is the estimation of willingness to pay (WTP), or willingness to accept (WTA), for changes in provision of non-market goods. A large literature investigates both theoretical issues connected with these procedures (Bates, 1988) and empirical results from country experiences (Mackie at al., 2003). The second family of surveys are commonly employed in public opinion analysis. In this case respondents are asked to reveal their current attitudes, whilst in some circumstances they are required to state their satisfaction with a certain policy or service. In the last decades the interest towards such analysis largely increased and a broad amount of surveys have been systematically collected (Rabin, 2002). Whatever the kind of analysis, when individuals correctly report the behaviour they would keep in a real context, or honestly admit their attitudes and perceptions, the target of the policy maker is reached. Hence, the issue of reliability of stated preferences becomes crucial in order to understand what we can learn from surveys and how SP analysis can be exploited by policy makers. Our research question is simply the following one: can we trust in SP methods? In order to answer this question the work is organised in three sections. The first one is devoted to the definition of the concept of \u201creliability\u201d. In the first place, the latter depends on the family of SP methods we are dealing with. When individuals are required to replicate their market behaviour in a fictitious scenario, two perspectives can be applied: the first one based on mainstream economic theory (Hicks and Allen, 1934) and the other one in accordance to the so called behavioural programme (Sunstein and Thaler, 2008). Both approaches are discussed, pointing out the problematic issues which characterise each methodology and trying to propose a definition for the concept of reliability. The second family of surveys can be classified into two sub-groups, based on the object of the analysis. The first group includes all situations where agents are required to reveal their actual behaviour (Bertrand and Mullainathan, 2001) while the second one is composed by those studies in which agents are asked to express their feelings or perceptions about a certain aspect of their life (McFadden et al. 2005). Again, the concept of reliability has been investigated for each group of surveys. The second and the third sections are devoted to empirical works which try, recalling the definition of reliability suggested in the first chapter, to apply this concept to empirical studies

New trajectories of the Hungarian regional development: balanced and rush growth of territorial capital

The basic assumption of the paper is that numerous similarities exist between the patterns of economic growth and territorial capital growth. The rush economic growth and rush growth of territorial capital are compared empirically at Hungarian micro-regional level from 2004 until 2010. After normalizing the dataset, a very novel spatial econometric method is applied, called a penalty for bottleneck. The results show that the constant rush growth of territorial capital is as harmful as economic recession. On the other hand, the decrease of infrastructural and social capital caused the rush growth of territorial capital in this period. Moreover, the key findings of two case studies suggest that the balanced growth of territorial capital will be created by the falling social inequalities and increasing infrastructural capita

Antiepileptic drugs’ tolerability and safety – a systematic review and meta-analysis of adverse effects in dogs

<p>Various anti-epileptic drugs (AEDs) are used for the management of idiopathic epilepsy (IE) in dogs. Their safety profile is an important consideration for regulatory bodies, owners and prescribing clinicians. However, information on their adverse effects still remains limited with most of it derived from non-blinded non-randomized uncontrolled trials and case reports.</p><p><span>This poster won third place, which was presented at the Veterinary Evidence Today conference, Edinburgh November 1-3, 2016. </span></p><br /> <img src="https://www.veterinaryevidence.org/rcvskmod/icons/oa-icon.jpg" alt="Open Access" /

International Veterinary Epilepsy Task Force Consensus Proposal: Outcome of therapeutic interventions in canine and feline epilepsy

Common criteria for the diagnosis of drug resistance and the assessment of outcome are needed urgently as a prerequisite for standardized evaluation and reporting of individual therapeutic responses in canine epilepsy. Thus, we provide a proposal for the definition of drug resistance and partial therapeutic success in canine patients with epilepsy. This consensus statement also suggests a list of factors and aspects of outcome, which should be considered in addition to the impact on seizures. Moreover, these expert recommendations discuss criteria which determine the validity and informative value of a therapeutic trial in an individual patient and also suggest the application of individual outcome criteria. Agreement on common guidelines does not only render a basis for future optimization of individual patient management, but is also a presupposition for the design and implementation of clinical studies with highly standardized inclusion and exclusion criteria. Respective standardization will improve the comparability of findings from different studies and renders an improved basis for multicenter studies. Therefore, this proposal provides an in-depth discussion of the implications of outcome criteria for clinical studies. In particular ethical aspects and the different options for study design and application of individual patient-centered outcome criteria are considered