Cooneyscott1034

BACKGROUND Washout periods (WPs) are increasingly shortened due to concerns of disease rebound when patients on natalizumab are switched to alternative disease-modifying therapies (DMTs). OBJECTIVE To characterize disease activity outcomes with different WPs when switching from natalizumab. METHODS We conducted a retrospective review of patients switching from natalizumab in our MS clinics. Disease activity (relapse, new T2 lesions and/or gadolinium enhancing lesions) between different WPs (days) 0-30, 31-60, and 61-180 were compared, during the first year after switching from natalizumab. To determine predictors of disease activity when switching to any DMT, multivariate logistic regression analysis was used. Post hoc analyses were performed to evaluate the impact of individual DMTs on disease activity. RESULTS 335 patients discontinued natalizumab with WP 0-30 (n = 104), 31-60 (n = 113), and 61-180 (n = 136). Disease activity occurred in 44.2% of patients in the 0-30 WP group, 18.6% in the 31-60 WP group, and 27.2% in the 61-180 WP group. There was a significant decrease in odds of disease activity with longer WP when compared to the 0-30 group 31-60 (OR 0.241, 95% CI 0.108-0.514, p value  less then  0.001), and 61-180 (OR 0.439, 95% CI 0.218-0.871, p value  less then  0.05). CONCLUSIONS Unexpectedly, in our study, patients who had the shortest WP 0-30 days had the most disease activity. Shortening WPs may not be enough to suppress disease activity post-natalizumab switch.Quality indicators are vital for monitoring the transformation of institution-based mental health services towards the provision of person-centered mental healthcare. While several mental healthcare quality indicators have been identified as relevant and valid, their actual usability and utility for routine monitoring healthcare quality over time is significantly determined by the availability and trustworthiness of the underlying data. In this feasibility study, quality indicators that have been systematically identified for use in the Danube region countries of Bulgaria, the Czech Republic, Hungary, and Serbia were measured on the basis of existing mental healthcare data in the four countries. Data were collected retrospectively by means of the best available, most standardized, trustworthy, and up-to-date data in each country. Out of 21 proposed quality indicators, 18 could be measured in Hungary, 17 could be measured in Bulgaria and in the Czech Republic, and 8 could be measured in Serbia. The results demonstrate that a majority of quality indicators can be measured in most of the countries by means of already existing data, thereby demonstrating the feasibility of quality measurement and regular quality monitoring. However, data availability and usability are scattered across countries and care sectors, which leads to variations in the quality of the quality indicators themselves. Making the planning and outputs of national mental healthcare reforms more transparent and evidence-based requires (trans-)national standardization of healthcare quality data, their routine availability and standardized assessment, and the regular reporting of quality indicators.In this study, a switchable solvent-based liquid-phase microextraction method was developed to preconcentrate selected pesticides from tap water and wastewater matrices for determination by gas chromatography-mass spectrometry. A thorough optimization process was performed for prominent extraction parameters such as switchable solvent amount, concentration/amount of sodium hydroxide, salt type and mixing period. Optimum parameters obtained at the end of the optimization process were applied to aqueous standard solutions to validate the method. The linear dynamic ranges of all four analytes were appreciably wide with coefficient of determination values greater than 0.9997. The limits of detection and quantification (LOD and LOQ) were calculated for the analytes in the ranges of 0.38-2.0 ng/mL and 1.3-6.5 ng/mL, respectively. Spiked recovery experiments were used to validate the accuracy of the developed method and to determine the performance of the method in different sample matrices. Tap water, municipal wastewater and medical wastewater were spiked at three different concentrations and analyzed under the method's optimum conditions. The percent recovery results calculated for the samples were in the range of 79-107%, and this validated the method's accuracy and applicability to complex matrices such as municipal and medical wastewater samples.PURPOSE Appetitive behaviours have been associated with body mass index (BMI). However, existing data were largely derived from cross-sectional studies and cannot provide insight into the direction of associations. We aimed to explore the bidirectionality of these associations in school-age children. METHODS Participants are from the Generation XXI birth cohort, assessed at both 7 and 10 years of age (n = 4264; twins excluded). The Children's Eating Behaviour Questionnaire (CEBQ) was used to measure appetitive behaviours (8 subscales). Anthropometrics were measured and WHO BMI z-score was calculated. Cross-lagged analyses were performed to compare the magnitude and direction of the associations (behaviours at 7 years to BMI z-score at 10 years and the reverse) (covariates child's sex, physical exercise, maternal age and education; plus BMI z-score at age 7 or, in the reverse direction, the subscale score). RESULTS In cross-lagged analyses, appetitive behaviours at 10 years of age (apart from emotional undereating) were shown to be reactive to the child BMI z-score at 7 years of age. Only slowness in eating was significantly related to subsequent BMI. However, the strongest association was from the child BMI z-score to the behaviour (βstandardized = - 0.028 compared with βstandardized = - 0.103, likelihood ratio test p  less then  0.001). CONCLUSIONS BMI at age 7 was related to appetitive behaviours at 10 years of age, rather than the reverse. This suggests that children with a higher BMI in middle childhood are at increased risk of developing an avid appetite over time.PURPOSE To identify key factors for the best practice of knowledge transfer from high-income settings to low- and middle-income settings. RESULTS Interactive sessions led to the identification of European learnings that can and should be shared beyond Europe. Furthermore, methods were characterised which may lead to successful knowledge transfer with subsequent quality improvement. CONCLUSION To ensure successful implementation of knowledge and new methods, political support is extremely important. A strong focus should be an improvement of collaboration and network development. Rehabilitation, early and late pallative care, cost effectiveness and long-term follow-up are priorities. Limitations are budget constraints which limit the execution of NCCPs.PURPOSE To review recent pharmacogenomics studies on breast cancer patients undergoing tamoxifen therapy, highlighting how our knowledge on cytochrome P450 2D6 (CYP2D6) can help to guide the development of adjuvant therapies for these patients. METHODS A comprehensive literature search was conducted. Articles reporting findings pertaining to the effect of CYP2D6 on the therapeutic efficacy of tamoxifen, those reporting how targeting CYP2D6 could inform tamoxifen-based therapy development, and those on the tamoxifen effects on cell lines and animal models were included in the review. RESULTS With CYP2D6 being the primary enzyme for tamoxifen metabolism, single-nucleotide polymorphisms (SNPs) in this gene were one of the determinants in the rate of tamoxifen metabolism, thereby potentially having an effect on the efficacy of tamoxifen-based therapies. Our review indicates the potential effectiveness of targeting these SNPs, including those for the CYP2D6*10 allele (c. 100C > T), in modifying the level of tamoxifen metabolism. These findings suggest the importance of pharmacogenomics research in our understanding of the efficacy of adjuvant therapies. However, the involvement of multiple enzymes in tamoxifen metabolism, dietary factors, ethnic differences in gene frequencies, and patients' compliance to tamoxifen therapies in studies do present challenges in pharmacogenomics research. CONCLUSIONS Pharmacogenomics could play important roles in mediating the advancement of tamoxifen-based adjuvant therapies. Research efforts should be directed towards the exploration of further SNPs of CYP2D6 that affect tamoxifen metabolism, as well as epigenetic changes in CYP2D6, enabling the design of precision medicine and confirming clinical validity in the use of pharmacogenomics for tamoxifen.An SIS model is analyzed to consider the contribution of community structure to the risk of the spread of a transmissible disease. We focus on the human day-to-day activity introduced by commuting to a central place for the social activity. We assume that the community is classified into two subpopulations commuter and non-commuter, of which the commuter has two phases of the day-to-day activity private and social. Further we take account of the combination of contact patterns in two phases, making use of mass-action and ratio-dependent types for the infection force. We investigate the dependence of the basic reproduction number on the commuter ratio and the daily expected duration at the social phase as essential factors characterizing the community structure, and show that the dependence is significantly affected by the combination of contact patterns, and that the difference in the commuter ratio could make the risk of the spread of a transmissible disease significantly different.Extensive improvements in executive functions and language abilities are accompanied by changes in functional connections within the brain and in gray and white matter during the first few years of life. Diffusion tensor imaging provides a unique look into pediatric brain anatomy and critical information regarding white-matter development. The aims of the current study were to investigate the variability in diffusion indices in language and cognitive white-matter tracts, hemispheric lateralization, and how diffusion measures are related to age, language and cognitive abilities from early toddler age to early childhood. Diffusion tensor imaging data were acquired from seventy-four 17-107 month-old typically developing children (mean = 69 months; females = 39). Effects of hemisphere and age on diffusion properties (mean diffusivity, radial diffusivity, axial diffusivity and fractional anisotropy) were measured at 100 points along the length of white-matter tracts related to expressive language and cognitive abilities, including the cingulum bundle, superior longitudinal fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, arcuate fasciculus and corpus callosum (forceps major and forceps minor). Diffusion properties exhibited variability along the length of the tracts, with hemispheric effect and age differences in specific segments of the tracts. Significant positive correlation was found between fractional anisotropy and expressive language and cognitive abilities. Our results provide a detailed examination of the effect of age and hemisphere on diffusion properties. Furthermore, the results delineate the neural correlates of white-matter microstructure to behavioral language and cognitive performance in white-matter tracts related to language and cognitive abilities at the tract level along with development.