Analysis of the Postoperative Periarticular Environment and Influence on Sustained Drug Delivery From a Gel Formulation.

Regional intraarticular delivery of local anesthetics is effective in treating postoperative pain following total knee or hip replacement. Recent research efforts have been only partially successful in achieving sustained release of the analgesic agent, in part due to limited understanding of the biological environment into which these formulations are administered. This study aimed to detail the composition and properties of postoperative periarticular fluid (PO-PAF). PO-PAF was collected from 8 patients, and the composition and physicochemical properties were determined. A number of components were identified which are lacking from phosphate buffered saline (PBS) or other synthetic media. The differences in composition led to variation in the physicochemical properties of PO-PAF compared with PBS. Notably, significantly lower surface tension (p <0.05) and higher buffer capacity (p <0.05) were observed in the biological fluid. We demonstrated that the solubility of lidocaine is almost double in PO-PAF compared to PBS (p <0.05) and that lidocaine release from a poloxamer gelling system occurred faster into PO-PAF under both sink and nonsink conditions. Collectively, these data indicate PBS is inappropriate for the in vitro evaluation of intraarticular drug delivery systems. The presented data describe that PO-PAF and will support the future development of biorelevant media to ultimately improve in vivo-in vitro correlation.

The Efficacy of Local Autologous Bone Dust: A Systematic Review.

STUDY DESIGN: A systematic review of bone dust as an autologous bone graft to encourage osseous fusion. OBJECTIVE: To identify and review studies that report on the therapeutic potential of bone dust. The research question was structured as follows: populations-animal and human sources of bone dust harvested using burrs; interventions-autologous bone dust compared with other clinically utilized bone graft options; outcomes assessed-(1) in vitro cell viability, cell differentiation, and osteogenic potential and (2) clinical efficacy in the form of fusion rates as assessed using plain radiographs; study designs-in vitro, preclinical in vivo and clinical studies investigating the therapeutic potential of bone dust, harvested by burring, are included in this systematic review. SUMMARY OF BACKGROUND DATA: Little is known about the efficacy of bone dust, generated during burring of local bone in spine surgery, as a bone graft to encourage osseous union. METHODS: A systematic search was conducted in Medline, PubMed, OVID, Scopus, and Cochrane library. The following key words were used: bone dust, bone burring, bone paste, bone pate. RESULTS: A total of 285 studies were reviewed. Fourteen articles were identified as relevant for inclusion in this systematic review. Current evidence suggests that bone dust retains osteogenic properties, but limited information is available regarding the osteoinductive potential of bone dust. CONCLUSION: Bone dust represents a free source of autologous bone, which can be easily collected during the time of surgery and used as an augment to aid osseous fusion. Further research is required to evaluate the osteoinductive potential of bone dust. The retained growth factors in bone dust may potentially induce local osteoprogenitor cells to proliferate and mineralize to form new bone.

Antidepressants for treatment of depression in primary care: a systematic review and meta-analysis.

INTRODUCTION Evidence for the effectiveness of drug treatment for depression in primary care settings remains limited, with little information on newer antidepressant classes. AIM To update an earlier Cochrane review on the effectiveness of antidepressants in primary care to include newer antidepressant classes, and to examine the efficacy of individual agents. METHODS Selection criteria included antidepressant studies with a randomly assigned placebo group where half or more subjects were recruited from primary care. The Cochrane Collaboration Depression, Anxiety and Neurosis (CCDAN) group searched multiple databases to identify eligible studies. Data extraction was performed independently by two reviewers. Data were analysed using Revman version 5.3.5. RESULTS In total, 17 papers and 22 comparisons were included for analysis. Significant benefits in terms of response were found for tricyclic antidepressants (TCA) with a relative risk (RR) = 1.23 (95% CI, 1.01-1.48), and serotonin selective reuptake inhibitors (SSRI) with a RR = 1.33 (95% CI, 1.20-1.48). Mianserin was effective for continuous outcomes. Numbers needed to treat (NNT) for TCA = 8.5; SSRI = 6.5; and venlafaxine = 6. Most studies were industry-funded and of a brief duration (≤ 8 weeks). There was evidence of publication bias. There were no studies comparing newer antidepressants against placebo. CONCLUSION Antidepressants such as TCA, SSRI, SNRI (serotonin-norepinephrine reuptake inhibitor) and NaSSA (noradrenergic and specific serotonergic antidepressant) classes appear to be effective in primary care when compared with placebo. However, in view of the potential for publication bias and that only four studies were not funded by industry, caution is needed when considering their use in primary care.