A multinational, drug utilization study to investigate the use of dexmedetomidine (Dexdor (R)) in clinical practice in the EU

AIMSDexmedetomidine (dexdor (R)) is approved in the European Union (EU) for sedation of adults in the intensive care unit (ICU). The present observational, retrospective study was requested by the European Medicines Agency to investigate dexmedetomidine use in clinical practice, with a particular focus on off-label use, including the paediatric population.METHODSStudy countries and sites were chosen from those with highest dexmedetomidine use, based on sales. Site selection (blind) was conducted by a multispecialist, independent group. Anonymized data on demographics, treatment indication, dexmedetomidine dosing, concomitant medications and treatment effectiveness were collected retrospectively from records of all dexmedetomidine-treated patients at the site during the enrolment period. Informed consent was waived, to avoid influencing the prescribing of dexmedetomidine. Recruitment was completed within 18 months of first site initiation.RESULTSData from 2000 patients were collected from 16 hospitals in four EU countries (Finland 750, Poland 505, Germany 470, Austria 275). The median age was 62 years, with more males (70.2%) than females. Dexmedetomidine was primarily used in the adult ICU (86.0%) for ICU sedation (78.6%) and mostly dosed according the product label. The intended sedative effect was obtained in 84.9% of administrations. Paediatric use (5.9% of patients, mostly in Austria and Finland) occurred mainly in the adult or paediatric ICU (75.6%) for sedation (67.2%).CONCLUSIONSOverall, most patients were treated with dexmedetomidine according to the product labelling. Use in children was limited but significant and similar in scope to that in adults. Administrations not fully according to the product labelling usually occurred in an ICU environment and reflected extensively investigated clinical uses of dexmedetomidine

Evidence of the Generation of Isosaccharinic Acids and Their Subsequent Degradation by Local Microbial Consortia within Hyper-Alkaline Contaminated Soils, with Relevance to Intermediate Level Radioactive Waste Disposal

The contamination of surface environments with hydroxide rich wastes leads to the formation of high pH (>11.0) soil profiles. One such site is a legacy lime works at Harpur Hill, Derbyshire where soil profile indicated in-situ pH values up to pH 12. Soil and porewater profiles around the site indicated clear evidence of the presence of the α and β stereoisomers of isosaccharinic acid (ISA) resulting from the anoxic, alkaline degradation of cellulosic material. ISAs are of particular interest with regards to the disposal of cellulosic materials contained within the intermediate level waste (ILW) inventory of the United Kingdom, where they may influence radionuclide mobility via complexation events occurring within a geological disposal facility (GDF) concept. The mixing of uncontaminated soils with the alkaline leachate of the site resulted in ISA generation, where the rate of generation in-situ is likely to be dependent upon the prevailing temperature of the soil. Microbial consortia present in the uncontaminated soil were capable of surviving conditions imposed by the alkaline leachate and demonstrated the ability to utilise ISAs as a carbon source. Leachate-contaminated soil was sub-cultured in a cellulose degradation product driven microcosm operating at pH 11, the consortia present were capable of the degradation of ISAs and the generation of methane from the resultant H2/CO2 produced from fermentation processes. Following microbial community analysis, fermentation processes appear to be predominated by Clostridia from the genus Alkaliphilus sp, with methanogenesis being attributed to Methanobacterium and Methanomassiliicoccus sp. The study is the first to identify the generation of ISA within an anthropogenic environment and advocates the notion that microbial activity within an ILW-GDF is likely to influence the impact of ISAs upon radionuclide migration

The association between survey timing and patient-reported experiences with hospitals: results of a national postal survey

<p>Abstract</p> <p>Background</p> <p>Research on the effect of survey timing on patient-reported experiences and patient satisfaction with health services has produced contradictory results. The objective of this study was thus to assess the association between survey timing and patient-reported experiences with hospitals.</p> <p>Methods</p> <p>Secondary analyses of a national inpatient experience survey including 63 hospitals in the 5 health regions in Norway during the autumn of 2006. 10,912 (45%) patients answered a postal questionnaire after their discharge from hospital. Non-respondents were sent a reminder after 4 weeks. Multilevel linear regression analysis was used to assess the association between survey timing and patient-reported experiences, both bivariate analysis and multivariate analysis controlling for other predictors of patient experiences.</p> <p>Results</p> <p>Multivariate multilevel regression analysis revealed that survey time was significantly and negatively related to three of six patient-reported experience scales: doctor services (Beta = -0.424, <it>p</it>< 0.05), information about examinations (Beta = -0.566, <it>p </it>< 0.05) and organization (Beta = -0.528, <it>p </it>< 0.05). Patient age, self-perceived health and type of admission were significantly related to all patient-reported experience scales (better experiences with higher age, better health and routine admission), and all other predictors had at least one significant association with patient-reported experiences.</p> <p>Conclusions</p> <p>Survey time was significantly and negatively related to three of the six scales for patient-reported experiences with hospitals. Large differences in survey time across hospitals could be problematic for between-hospital comparisons, implying that survey time should be considered as a potential adjustment factor. More research is needed on this topic, including studies with other population groups, other data collection modes and a longer time span.</p

MMP-28 as a regulator of myelination

<p>Abstract</p> <p>Background</p> <p>Matrix metalloproteinase-28 (MMP-28) is a poorly understood member of the matrix metalloproteinase family. Metalloproteinases are important mediators in the development of the nervous system and can contribute to the maturation of the neural micro-environment.</p> <p>Results</p> <p>MMP-28 added to myelinating rat dorsal root ganglion (DRG) co-cultures reduces myelination and two antibodies targeted to MMP-28 (pAb180 and pAb183) are capable of binding MMP-28 and inhibiting its activity in a dose-dependent manner. Addition of 30 nM pAb180 or pAb183 to rat DRG cultures resulted in the 2.6 and 4.8 fold enhancement of myelination respectively while addition of MMP-28 to DRG co-cultures resulted in enhanced MAPK, ErbB2 and ErbB3 phosphorylation. MMP-28 protein expression was increased within demyelinated lesions of mouse experimental autoimmune encephalitis (EAE) and human multiple sclerosis lesions compared to surrounding normal tissue.</p> <p>Conclusion</p> <p>MMP-28 is upregulated in conditions of demyelination in vivo, induces signaling in vitro consistent with myelination inhibition and, neutralization of MMP-28 activity can enhance myelination in vitro. These results suggest inhibition of MMP-28 may be beneficial under conditions of dysmyelination.</p

Knee complaints vary with age and gender in the adult population. Population-based reference data for the Knee injury and Osteoarthritis Outcome Score (KOOS)

BACKGROUND: Self-reported knee complaints may vary with age and gender. Reference data from the adult population would help to better interpret the outcome of interventions due to knee complaints. The objectives of the present study were to describe the variation of self-reported knee pain, function and quality of life with age and gender in the adult population and to establish population-based reference data for the Knee injury and Osteoarthritis Outcome Score (KOOS). METHODS: Population-based cohort retrieved from the national population register. The knee-specific Knee injury and Osteoarthritis Outcome Score (KOOS) was mailed to 840 subjects aged 18–84 yrs. RESULTS: 68% response rate. Women in the age group 55–74 reported more knee-related complaints in all the KOOS subscales than age-matched men. The differences were significant for the subscales Pain (p = 0.027), Symptoms (p = 0.003) and ADL function (p = 0.046). In men, worse ADL and Sport and Recreation function was seen in the oldest age group 75–84 years compared to the younger age groups (p < 0.030). In women, worse Pain (p < 0.007), ADL (p < 0.030), Sport and Recreation (p < 0.001) and QOL (p < 0.002) were seen already in the age group 55–74 compared to the younger age groups. CONCLUSION: We found pain and other symptoms, physical function, and knee-related quality of life to vary with age and gender implying the use of age- and gender matched reference values for improved understanding of the outcome after interventions due to knee injury and knee OA

Self-rated health and factors influencing responses among young Egyptian type 1 diabetes patients

<p>Abstract</p> <p>Background</p> <p>Patients diagnosed with type 1 diabetes mellitus (T1DM) face major daily challenges. Self-rated health (SRH) is a global measure of an individual's health related quality of life (HRQoL) and is based on the question, "In general, how would you rate your health?" Subjects rate their health as excellent, very good, good, poor or very poor. Our objective was to determine the HRQoL using the SRH measure and determine factors influencing responses. We hypothesized that better SRH responses were associated with shorter diabetes duration, better compliance and better glycemic control.</p> <p>Methods</p> <p>The standardized SRH measure was the instrument used for health related quality of life assessment. Logistic regression analysis was used to examine the association between SRH responses and selected variables.</p> <p>Results</p> <p>124 subjects, 64 females (51.6%) and 60 males (48.4%) were included. Average age was 13.08 (±3.19) and average diabetes duration was 5.82 (±1.60), while the mean HbA₁C was 8.02 (±1.60). The majority rated their health as good (31%), 29% rated it as excellent, 11% as very good, 14% as poor and 15% as very poor. Regression analysis showed that regular exercise was the only predictor that was independently and significantly associated with a "better" self-health rating, with an OR of 12.84, CI of 1.425-115.727 and a <it>p </it>value of 0.023.</p> <p>Conclusion</p> <p>Regular exercise among Egyptian children with T1DM is strongly associated with a "better" overall health related quality of life and should be repeatedly encouraged.</p

Employment Is Associated with the Health-Related Quality of Life of Morbidly Obese Persons

Published version of an article in the journal: Obesity Surgery. The original publication is available at Springerlink. http://dx.doi.org/10.1007/s11695-010-0289-6. Open AccessBackground&nbsp;&nbsp;We aimed to investigate whether employment status was associated with health-related quality of life (HRQoL) in a population of morbidly obese subjects. Methods&nbsp;&nbsp;A total of 143 treatment-seeking morbidly obese patients completed the Medical Outcome Study 36-Item Short-Form Health Survey (SF-36) and the Obesity and Weight-Loss Quality of Life (OWLQOL) questionnaires. The former (SF-36) is a generic measure of physical and mental health status and the latter (OWLQOL) an obesity-specific measure of emotional status. Multiple linear regression analyses included various measures of the HRQoL as dependent variables and employment status, education, marital status, gender, age, body mass index (BMI), type 2 diabetes, hypertension, obstructive sleep apnea, and treatment choice as independent variables. Results&nbsp;&nbsp;The patients (74% women, 56% employed) had a mean (SD, range) age of 44 (11, 19–66) years and a mean BMI of 44.3 (5.4) kg/m2. The employed patients reported significantly higher HRQoL scores within all eight subscales of SF-36, while the OWLQOL scores were comparable between the two groups. Multiple linear regression confirmed that employment was a strong independent predictor of HRQoL according to the SF-36. Based on part correlation coefficients, employment explained 16% of the variation in the physical and 9% in the mental component summaries of SF-36, while gender explained 22% of the variation in the OWLQOL scores. Conclusion&nbsp;&nbsp;Employment is associated with the physical and mental HRQoL of morbidly obese subjects, but is not associated with the emotional aspects of quality of life

Anti-erbB2 treatment induces cardiotoxicity by interfering with cell survival pathways

INTRODUCTION: Cardiac dysfunction is among the serious side effects of therapy with recombinant humanized anti-erbB2 monoclonal antibody. The antibody blocks ErbB-2, a receptor tyrosine kinase and co-receptor for other members of the ErbB and epidermal growth factor families, which is over-expressed on the surface of many malignant cells. ErbB-2 and its ligands neuregulin and ErbB-3/ErbB-4 are involved in survival and growth of cardiomyocytes in both postnatal and adult hearts, and therefore the drug may interrupt the correct functioning of the ErbB-2 pathway. METHODS: The effect of the rat-anti-erbB2 monoclonal antibody B-10 was studied in spontaneously beating primary myocyte cultures from rat neonatal hearts. Gene expression was determined by RT-PCR (reverse transcription polymerase chain reaction) and by rat stress-specific microarray analysis, protein levels by Western blot, cell contractility by video motion analysis, calcium transients by the FURA fluorescent method, and apoptosis using the TUNEL (terminal uridine nick-end labelling) assay. RESULTS: B-10 treatment induces significant changes in expression of 24 out of 207 stress genes analyzed using the microarray technique. Protein levels of ErbB-2, ErbB-3, ErbB-4 and neuregulin decreased after 1 day. However, both transcription and protein levels of ErbB-4 and gp130 increased several fold. Calreticulin and calsequestrin were overexpressed after three days, inducing a decrease in calcium transients, thereby influencing cell contractility. Apoptosis was induced in 20% cells after 24 hours. CONCLUSION: Blocking ErbB-2 in cultured rat cardiomyocytes leads to changes that may influence the cell cycle and affects genes involved in heart functions. B-10 inhibits pro-survival pathways and reduces cellular contractility. Thus, it is conceivable that this process may impair the stress response of the heart