Tumor necrosis factor alpha (TNFalpha) plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA). Blockage of TNFalpha actions by systemic administration of TNF antagonists has recently been shown to ameliorate joint symptoms in RA patients. In the present study, a streptococcal cell wall (SCW)-induced rat arthritis model was used to evaluate the effect of different gene transfer routes of a TNF antagonist on the development and severity of arthritis. Successful delivery of a plasmid DNA encoding a rat TNF receptor-immunoglobulin Fc (TNFR:Fc) fusion gene prompted the subsequent administration of a recombinant adeno-associated virus (rAAV) vector encoding the antagonist, either locally (intraarticular) or systemically (intramuscular). The TNFR:Fc gene, delivered by either route, resulted in profound suppression of the arthritis as reflected in decreased inflammatory cell infiltration, pannus formation, cartilage and bone destruction, and mRNA expression of joint proinflammatory cytokines. Increased bioactive serum TNFR levels were detected as a result of rAAV-ratTNFR:Fc administration, concomitant with a decrease in circulating TNFalpha. Administration of the rAAV-ratTNFR:Fc vector to one joint also suppressed arthritis in the contralateral joint. Importantly, intraarticular administration resulted in significantly lower systemic distribution of the gene product. Hence, the use of rAAV as the delivery vector for TNFR:Fc effectively suppressed SCW-induced arthritis and may provide an approach for local delivery of antiarthritic therapy.
The addition of validated illustrations to pharmaceutical labels can be useful to instruct on how to mask the taste of medication in certain populations. Further studies are needed to assess the clinical impact of providing illustrated information to populations with low health literacy.
Background:Vancomycin is used primarily for Gram-positive infections. Recommended dosage regimens and targeted therapeutic levels vary between institutions.Objectives:This study aims to describe therapeutic levels according to initial vancomycin doses and patient’s age. A secondary objective was to evaluate appropriateness of vancomycin use in our hospital.Methods:A retrospective chart review was conducted at the Children’s Hospital of Eastern Ontario. Patients included in this study were classified by age (neonates, infants, children and adolescents) and categorized into those who received vancomycin ≤5 and >5 days. Initial vancomycin dosing regimens and corresponding initial trough levels obtained were evaluated. Initial trough levels drawn in relation to the third, fourth, or fifth doses corresponding to the first course of therapy were analyzed. Acceptable trough levels ranged from 5-20 mg/L.Results:One-hundred-and-sixty-four patients who received intravenous vancomycin in 2013 were included. Of the 229 courses of vancomycin, 190 (83%) were used 5 days or less (mean 4.9 days). Sixteen infants (88.9%) and 21 adolescents (100%), who received vancomycin empiric dosing of 60 mg/kg/day, had initial trough levels >5mg/L. However, in the children’s group 20 (37.7%) did not reach levels >5 mg/L. None of vancomycin minimum inhibitory concentration (MIC) values were >1mg/L for the four patients who had infections due to methicillin-resistant Staphylococcus aureus strains.Conclusions:In our institution, initial empiric vancomycin dosing of 60 mg/kg/day resulted in levels ≥5mg/L in most infants and adolescents. It remains unclear why some children aged 1-12 years did not achieve these levels.
The aim of this randomized single-blind study is to compare taste and odor disturbances in patients receiving 0.9% sodium chloride flushes from 2 brands. Seventy-five patients from 6 to 18 years of age received intravenous 0.9% sodium chloride infusions, and 50 healthy volunteers who tasted the 2 brands of 0.9% sodium chloride from prefilled syringes were assessed for taste and/or odor disturbances. Taste or odor disturbances were equally present in patients flushed with MedXL and Becton-Dickinson 0.9% sodium chloride. Disturbances are more frequent when 0.9% sodium chloride is flushed through central venous access devices than through peripheral catheters. No difference between the brands was found when healthy volunteers tasted it orally.
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