Effectiveness and safety of repeat courses of hylan G-F 20 in patients with knee osteoarthritis

Objective: To compare the effectiveness and safety of repeat treatment with hylan G-F 20 based on data from a randomized, controlled trial [Raynauld JP, Torrance GW, Band PA, Goldsmith CH, Tugwell P, Walker V, et al. A prospective, randomized, pragmatic, health outcomes trial evaluating the incorporation of hylan G-F 20 into the treatment paradigm for patients with knee osteoarthritis (Part 1 of 2): clinical results. Osteoarthritis Cartilage 2002;10:506-17]. The hypotheses tested were whether the single-course and repeat-course subgroups would be superior to appropriate care and not different from each other. Method: A total of 255 patients with knee osteoarthritis were randomized to appropriate care with hylan G-F 20 or appropriate care without hylan G-F 20. The hylan G-F 20 group was partitioned into two subgroups: (1) patients who received a single course of hylan G-F 20; and (2) patients who received two or more courses of hylan G-F 20. Results: For the primary effectiveness measure, change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score as a percent of baseline, the single-course subgroup improved by 41%, the repeat-course subgroup by 35%, and the appropriate care group by 14%. Both subgroups improved significantly more than the appropriate care group (P < 0.05), and were not statistically significantly different from each other (70% power to detect a 20% difference). Secondary effectiveness measures showed similar results. In the repeat-course subgroup, no statistically significant differences were found in the number of local adverse events, the number of patients with local adverse events, or arthrocentesis rates between the first and repeat courses of treatment. Conclusions: Although the study was neither designed nor powered to examine repeat treatment, this a posteriori analysis provides support for a favorable effectiveness and safety profile of hylan G-F 20 in repeat course patients. (C) 2004 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Continuous infusion of ticarcillin-clavulanate for home treatment of serious infections: clinical efficacy, safety, pharmacokinetics and pharmacodynamics

Continuous infusion (CI) ticarcillin-clavulanate is a potential therapeutic improvement over conventional intermittent dosing because the major pharmacodynamic (PD) predictor of efficacy of beta-lactams is the time that free drug levels exceed the MIC. This study incorporated a 6-year retrospective arm evaluating efficacy and safety of CI ticarcillin-clavulanate in the home treatment of serious infections and a prospective arm additionally evaluating pharmacokinetics (PK) and PD. In the prospective arm, steady-state serum ticarcillin and clavulanate levels and MIC testing of significant pathogens were performed. One hundred and twelve patients (median age, 56 years) were treated with a CI dose of 9.3-12.4 g/day and mean CI duration of 18.0 days. Infections treated included osteomyelitis (50 patients), septic arthritis (6), cellulitis (17), pulmonary infections (12), febrile neutropenia (7), vascular infections (7), intra-abdominal infections (2), and Gram-negative endocarditis (2); 91/112 (81%) of patients were cured, 14 (13%) had partial response and 7 (6%) failed therapy. Nine patients had PICC line complications and five patients had drug adverse events. Eighteen patients had prospective PK/PD assessment although only four patients had sufficient data for a full PK/PD evaluation (both serum steady-state drug levels and ticarcillin and clavulanate MICs from a bacteriological isolate), as this was difficult to obtain in home-based patients, particularly as serum clavulanate levels were found to deteriorate rapidly on storage. Three of four patients with matched PK/PD assessment had free drug levels exceeding the MIC of the pathogen. Home Cl of ticarcillin-clavulanate is a safe, effective, convenient and practical therapy and is a therapeutic advance over traditional intermittent dosing when used in the home setting. (c) 2005 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

An evaluation of a telephone-based postnatal support intervention for infant feeding in a regional Australian city

Background: Postnatal breastfeeding support in the form of home visits is difficult to accommodate in regional Australia, where hospitals often deal with harsh economic constraints in a context where they are required to provide services to geographically, dispersed consumers. This study evaluated a predominately telephone-based support service called the Infant Feeding Support Service. Methods: A prospective cohort design was used to compare data for 696 women giving birth in two regional hospitals (one public, one private) and participating in the support service between January and July 2003 with data from a cohort of 625 women who gave birth in those hospitals before the introduction of the support service. Each mother participating in the support service was assigned a lactation consultant. First contact occurred 48 hours after discharge, and approximately it weekly thereafter for 4 it weeks. Breastfeeding duration was measured at 3 months postpartum. Results: For women from the private hospital, the support service improved exclusive breastfeeding duration to 4.5 weeks postpartum, but these improvements were not evident at 3 months postpartum. No effects were observed for mothers from the public hospital. Quantitative and qualitative data demonstrated high levels of client satisfaction with the support service. Conclusions: This small-scale, predominately telephone-based intervention provided significant, although apparently context-sensitive, improvements to exclusive breastfeeding duration.

Comparative evaluation of microscopic car-following behavior

Microscopic traffic-simulation tools are increasingly being applied to evaluate the impacts of a wide variety of intelligent transport, systems (ITS) applications and other dynamic problems that are difficult to solve using traditional analytical models. The accuracy of a traffic-simulation system depends highly on the quality of the traffic-flow model at its core, with the two main critical components being the car-following and lane-changing models. This paper presents findings from a comparative evaluation of car-following behavior in a number of traffic simulators [advanced interactive microscopic simulator for urban and nonurban networks (AIMSUN), parallel microscopic simulation (PARAMICS), and Verkehr in Statiten-simulation (VISSIM)]. The car-following algorithms used in these simulators have been developed from a variety of theoretical backgrounds and are reported to have been calibrated on a number of different data sets. Very few independent studies have attempted to evaluate the performance of the underlying algorithms based on the same data set. The results reported in this study are based on a car-following experiment that used instrumented vehicles to record the speed and relative distance between follower and leader vehicles on a one-lane road. The experiment was replicated in each tool and the simulated car-following behavior was compared to the field data using a number of error tests. The results showed lower error values for the Gipps-based models implemented in AIMSUN and similar error values for the psychophysical spacing models used in VISSIM and PARAMICS. A qualitative drift and goal-seeking behavior test, which essentially shows how the distance headway between leader and follower vehicles should oscillate around a stable distance, also confirmed the findings.

Community-based programs to promote care seat restraints in children 0-16 years - A systematic review

Study Objective: Community-based models for injury prevention have become an accepted part of the overall injury control strategy. This systematic review of the scientific literature examines the evidence for their effectiveness in reducing injury due to inadequate car seat restraint use in children 0-16 years of age. Methods: A comprehensive search of the literature was performed using the following study selection criteria: community-based intervention study: target population was children aged 0-16 years of age; outcome measure was either injury rates due to motor vehicle crashes or observed changes in child restraint use; and use of community control or historical control in the study design. Quality assessment and data abstraction was guided by a standardized procedure and performed independently by two authors. Data synthesis was in tabular and text form with meta-analysis not being possible due to the discrepancy in methods and measures between the studies. Results: This review found eight studies, that met all the inclusion criteria. In the studies that measured injury outcomes, significant reductions in risk of motor vehicle occupant injury (33-55%) were reported in the study communities. For those studies reporting observed car seat restraint use the community-based programs were successful in increasing toddler restraint use in 1-5 year aged children by up to 11%; child booster seat use in 4-8 year aged children by up to 13%; rear restraint use in children aged 0-15 years by 8%; a 50% increase in restraint use in pre-school aged children in a high-risk community; and a 44% increase in children aged 5-11 years. Conclusion: While this review highlights that there is some evidence to support the effectiveness of community-based programs to promote car restraint use and/or motor vehicle occupant injury, limitations in the evaluation methodologies of the studies requires the results to be interpreted with caution. There is clearly a need for further high quality program evaluation research to develop an evidence base. (C) 2004 Elsevier Ltd. All rights reserved.

An evaluation of potential mechanism-based inactivation of human drug metabolizing cytochromes P450 by monoamine oxidase inhibitors, including isoniazid

To characterize potential mechanism-based inactivation (MBI) of major human drug-metabolizing cytochromes P450 (CYP) by monoamine oxidase (MAO) inhibitors, including the antitubercular drug isoniazid. Human liver microsomal CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A activities were investigated following co- and preincubation with MAO inhibitors. Inactivation kinetic constants (K-I and k(inact)) were determined where a significant preincubation effect was observed. Spectral studies were conducted to elucidate the mechanisms of inactivation. Hydrazine MAO inhibitors generally exhibited greater inhibition of CYP following preincubation, whereas this was less frequent for the propargylamines, and tranylcypromine and moclobemide. Phenelzine and isoniazid inactivated all CYP but were most potent toward CYP3A and CYP2C19. Respective inactivation kinetic constants (K-I and k(inact)) for isoniazid were 48.6 mu M and 0.042 min(-1) and 79.3 mu M and 0.039 min(-1). Clorgyline was a selective inactivator of CYP1A2 (6.8 mu M and 0.15 min(-1)). Inactivation of CYP was irreversible, consistent with metabolite-intermediate complexation for isoniazid and clorgyline, and haeme destruction for phenelzine. With the exception of phenelzine-mediated CYP3A inactivation, glutathione and superoxide dismutase failed to protect CYP from inactivation by isoniazid and phenelzine. Glutathione partially slowed (17%) the inactivation of CYP1A2 by clorgyline. Alternate substrates or inhibitors generally protected against CYP inactivation. These data are consistent with mechanism-based inactivation of human drug-metabolizing CYP enzymes and suggest that impaired metabolic clearance may contribute to clinical drug-drug interactions with some MAO inhibitors.

Synthesis and immunological evaluation of M protein targeted tetra-valent and tri-valent group A streptococcal vaccine candidates based on the lipid-core peptide system

Group A streptococcus (GAS) is responsible for causing many clinical complications including the relatively benign streptococcal pharyngitis and impetigo. However. if left untreated. these conditions may lead to more severe diseases such as rheumatic fever (RF) and rheumatic heart disease (RHD). These diseases exhibit high morbidity and mortality, Particularly in developing countries and in indigenous populations of affluent countries. Only ever occur following GAS infection, a vaccine offers Promise for their Prevention. As stich, we have investigated the Use of the lipid-core peptide (LCP) system for the development of multi-valent Prophylactic GAS vaccines. The current study has investigated the capacity of this system to adjuvant LIP to four different GAS peptide epitopes. Presented are the synthesis and immunological assessment of tetra-valent and tri-valent GAS LCP systems. We demonstrated their capacity to elicit systemic IgG antibody responses in B10.BR mice to all GAS peptide epitopes. The data also showed that the LCP systems Were self-adjuvanting. These findings are particularly encouraging for the development of multi-valent LCP-based GAS vaccines.

Leadership Attributes and Cultural Values in Australia and New Zealand Compared: An Initial Report Based on GLOBE Data.

This paper reports a comparative study of Australian and New Zealand leadership attributes, based on the GLOBE (Global Leadership and Organizational Behavior Effectiveness) program. Responses from 344 Australian managers and 184 New Zealand managers in three industries were analyzed using exploratory and confirmatory factor analysis. Results supported some of the etic leadership dimensions identified in the GLOBE study, but also found some emic dimensions of leadership for each country. An interesting finding of the study was that the New Zealand data fitted the Australian model, but not vice versa, suggesting asymmetric perceptions of leadership in the two countries.

Using household survey data to inform policy decisions regarding the delivery of evidence-based parenting interventions.

Background: This study used household survey data on the prevalence of child, parent and family variables to establish potential targets for a population-level intervention to strengthen parenting skills in the community. The goals of the intervention include decreasing child conduct problems, increasing parental self-efficacy, use of positive parenting strategies, decreasing coercive parenting and increasing help-seeking, social support and participation in positive parenting programmes. Methods: A total of 4010 parents with a child under the age of 12 years completed a statewide telephone survey on parenting. Results: One in three parents reported that their child had a behavioural or emotional problem in the previous 6 months. Furthermore, 9% of children aged 2–12 years meet criteria for oppositional defiant disorder. Parents who reported their child's behaviour to be difficult were more likely to perceive parenting as a negative experience (i.e. demanding, stressful and depressing). Parents with greatest difficulties were mothers without partners and who had low levels of confidence in their parenting roles. About 20% of parents reported being stressed and 5% reported being depressed in the 2 weeks prior to the survey. Parents with personal adjustment problems had lower levels of parenting confidence and their child was more difficult to manage. Only one in four parents had participated in a parent education programme. Conclusions: Implications for the setting of population-level goals and targets for strengthening parenting skills are discussed.

Evaluation of multifrequency bioelectrical impedance data for predicting lean tissue mass in beef cattle

Multifrequency bioimpedance analysis has the potential to provide a non-invasive technique for determining body composition in live cattle. A bioimpedance meter developed for use in clinical medicine was adapted and evaluated in 2 experiments using a total of 31 cattle. Prediction equations were obtained for total body water, extracellular body water, intracellular body water, carcass water and carcass protein. There were strong correlations between the results obtained through chemical markers and bioimpedance analysis when determined in cattle that had a wide range of liveweights and conditions. The r(2) values obtained were 0.87 and 0.91 for total body water and extracellular body water respectively. Bioimpedance also correlated with carcass water, measured by chemical analysis (r(2) = 0.72), but less well with carcass protein (r(2) = 0.46). These correlations were improved by inclusion of liveweight and sex as variables in multiple regression analysis. However, the resultant equations were poor predictors of protein and water content in the carcasses of a group of small underfed beef cattle, that had a narrow range of liveweights. In this case, although there was no statistical difference between the predicted and measured values overall, bioimpedance analysis did not detect the differences in carcass protein between the 2 groups that were apparent following chemical analysis. Further work is required to determine the sensitivity of the technique in small underfed cattle, and its potential use in heavier well fed cattle close to slaughter weight.