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Rapid Uptake (rapid + uptake)
Selected AbstractsMethadone maintenance therapy promotes initiation of antiretroviral therapy among injection drug usersADDICTION, Issue 5 2010Sasha Uhlmann ABSTRACT Aims Despite proven benefits of antiretroviral therapy (ART), many human immunodeficiency virus (HIV)-infected injection drug users (IDU) do not access treatment even in settings with free health care. We examined whether methadone maintenance therapy (MMT) increased initiation and adherence to ART among an IDU population with free health care. Design We examined prospectively a cohort of opioid-using antiretroviral-naive HIV-infected IDU and investigated factors associated with initiation of antiretroviral therapy as well as subsequent adherence. Factors associated independently with time to first initiation of antiretroviral therapy were modelled using Cox proportional hazards regression. Findings Between May 1996 and April 2008, 231 antiretroviral-naive HIV-infected opioid-using IDU were enrolled, among whom 152 (65.8%) initiated ART, for an incidence density of 30.5 [95% confidence interval (CI): 25.9,35.6] per 100 person-years. After adjustment for time-updated clinical characteristics and other potential confounders, use of MMT was associated independently with more rapid uptake of antiretroviral therapy [relative hazard = 1.62 (95% CI: 1.15,2.28); P = 0.006]. Those prescribed methadone also had higher rates of ART adherence after first antiretroviral initiation [odds ratio = 1.49 (95% CI: 1.07,2.08); P = 0.019]. Conclusion These results demonstrate that MMT contributes to more rapid initiation and subsequent adherence to ART among opioid-using HIV-infected IDU. Addressing international barriers to the use and availability of methadone may increase dramatically uptake of HIV treatment among this population. [source] Lipophilic cationic drugs increase the permeability of lysosomal membranes in a cell culture system,JOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2010Johannes Kornhuber Lysosomes accumulate many drugs several fold higher compared to their extracellular concentration. This mechanism is believed to be responsible for many pharmacological effects. So far, uptake and release kinetics are largely unknown and interactions between concomitantly administered drugs often provoke mutual interference. In this study, we addressed these questions in a cell culture model. The molecular mechanism for lysosomal uptake kinetics was analyzed by live cell fluorescence microscopy in SY5Y cells using four drugs (amantadine, amitriptyline, cinnarizine, flavoxate) with different physicochemical properties. Drugs with higher lipophilicity accumulated more extensively within lysosomes, whereas a higher pKa value was associated with a more rapid uptake. The drug-induced displacement of LysoTracker was neither caused by elevation of intra-lysosomal pH, nor by increased lysosomal volume. We extended our previously developed numerical single cell model by introducing a dynamic feedback mechanism. The empirical data were in good agreement with the results obtained from the numerical model. The experimental data and results from the numerical model lead to the conclusion that intra-lysosomal accumulation of lipophilic xenobiotics enhances lysosomal membrane permeability. Manipulation of lysosomal membrane permeability might be useful to overcome, for example, multi-drug resistance by altering subcellular drug distribution. J. Cell. Physiol. 224:152,164, 2010 © 2010 Wiley-Liss, Inc. [source] The impact of multiple source feedback on management development: findings from a longitudinal studyJOURNAL OF ORGANIZATIONAL BEHAVIOR, Issue 7 2002Caroline Bailey Despite the rapid uptake of multi-source multi-rater (MSMR) feedback systems by UK organizations, comparatively little research exists describing the actual impact on participant managers, in terms of changes in management competence. Ratings of 104 target managers (by self assessments, bosses-, first- and second-level subordinates) were investigated within the context of a developmental feedback programme in operation within an organization. The study compared ratings over two administrations (with two years between administrations) to determine: (1) changes in co-workers' perceptions of their target manager's competence, (2) changes in target managers' development needs over time, (3) factors influencing a target manager's revised self-assessment and co-workers ratings, (4) changes in congruence between self and co-workers ratings and (5) the relationship of feedback to the organization's formal performance appraisal process. Significant increases in managers' competence were perceived by the managers' themselves and by their subordinates, development needs were seen to reduce and self and co-workers ratings were largely seen to become more congruent. However, polynomial regression analyses revealed co-workers feedback at Time One was not predictive of targets' self-assessments at Time Two. The implications of these findings with regard to the utility of MSMR feedback as a tool for management development are discussed. Copyright © 2002 John Wiley & Sons, Ltd. [source] Pharmacokinetic and pharmacodynamic properties of metomidate in turbot (Scophthalmus maximus) and halibut (Hippoglossus hippoglossus)JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2003M. K. Hansen Metomidate was administered to halibut (Hippoglossus hippoglossus) and turbot (Scophthalmus maximus) intravenously at a dose of 3 mg/kg bodyweight, as a bath treatment at a dose of 9 mg/L water for 5 min to study the disposition of metomidate, and as bath treatment (9 mg/L) for 10 min to study the absorption and effect of metomidate on respiration and balance/motor control. Additionally, turbot were given metomidate orally at a dose of 7 mg/kg. The studies were performed in seawater at a temperature of 10.3 ± 0.4 °C (halibut) and 18.0 ± 0.3 °C (turbot). Pharmacokinetic modeling of the data showed that metomidate had shorter elimination half-life and higher plasma concentrations in turbot compared with halibut, both species displaying a rapid uptake, distribution and excretion. Following intravenous administration, the volumes of distribution at steady state (Vd(ss)) were 0.21 L/kg (halibut) and 0.44 L/kg (turbot). Plasma clearances (Cl) were 0.099 L/h·kg in halibut and 0.26 L/h·kg in turbot and the elimination half-lives (t½,z) were calculated to be 5.8 h and 2.2 h in halibut and turbot, respectively. Mean residence times (MRT) were 2.2 h in halibut and 1.7 h in turbot. Following oral administration, the t½,z was 3.5 h in turbot. The maximum plasma concentration (Cmax) was 7.8 mg/L in turbot 1 h after administration. The oral bioavailability (F) was calculated to 100% in turbot. Following 5 min bath the maximum plasma concentrations (Cmax), which were observed immediately after end of the bath, were 9.5 mg/L and 13.3 mg/L in halibut and turbot, respectively. Metomidate rapidly immobilized the fish, with respiratory depression, reduced heart rate, and loss of balance/motor control within 1 min (mean). Recovery was slow, with resumed balance/motor control after 26.4 min. Opercular respiration movements were resumed more rapidly with a recorded mean of 1.7 min. Oral administration was demonstrated to be a way of immobilizing fish, for example in large aquariums, without exposing them to unwanted stress. [source] Comparison of nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 (COX-2) inhibitors use in Australia and Nova Scotia (Canada)BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 1 2009Nadia Barozzi WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Cyclo-oxygenase-2 (COX-2) inhibitors were marketed aggressively and their rapid uptake caused safety concerns and budgetary challenges in Canada and Australia. WHAT THIS STUDY ADDS , The study showed that there were similarities in the anti-inflammatory prescribing pattern between Australia and Nova Scotia; however, volumes of both ns-NSAIDs and COX-2 inhibitors prescribed were higher in Australia in the study period. The remarkable increase observed in Australia in NSAIDs use was essentially due to the much higher COX-2 inhibitor use. Differences in regulatory and marketing practices, as well as cultural and historical differences might be some of the reasons for differences in the NSAID prescribing between Australia and Nova Scotia. AIMS Cyclooxygenase-2 (COX-2) inhibitors were marketed aggressively and their rapid uptake caused safety concerns and budgetary challenges in Canada and Australia. The objectives of this study were to compare and contrast COX-2 inhibitors and nonselective nonsteroidal anti-inflammatory drug (ns-NSAID) use in Nova Scotia (Canada) and Australia and to identify lessons learned from the two jurisdictions. METHODS Ns-NSAID and COX-2 inhibitor Australian prescription data (concession beneficiaries) were downloaded from the Medicare Australia website (2001,2006). Similar Pharmacare data were obtained for Nova Scotia (seniors and those receiving Community services). Defined daily doses per 1000 beneficiaries day,1 were calculated. COX-2 inhibitors/all NSAIDs ratios were calculated for Australia and Nova Scotia. Ns-NSAIDs were divided into low, moderate and high risk for gastrointestinal side-effects and the proportions of use in each group were determined. Which drugs accounted for 90% of use was also calculated. RESULTS Overall NSAID use was different in Australia and Nova Scotia. However, ns-NSAID use was similar. COX-2 inhibitor dispensing was higher in Australia. The percentage of COX-2 inhibitor prescriptions over the total NSAID use was different in the two countries. High-risk NSAID use was much higher in Australia. Low-risk NSAID prescribing increased in Nova Scotia over time. The low-risk/high-risk ratio was constant throughout over the period in Australia and increased in Nova Scotia. CONCLUSIONS There are significant differences in Australia and Nova Scotia in use of NSAIDs, mainly due to COX-2 prescribing. Nova Scotia has a higher proportion of low-risk NSAID use. Interventions to provide physicians with information on relative benefits and risks of prescribing specific NSAIDs are needed, including determining their impact. [source] | ||||||||||