An enhanced bunionectomy model as a potential tool for early decision-making in the development of new analgesics

Background

Bunionectomy has been used as a model of postoperative pain for opioids and nonsteroidal anti-inflammatory drugs/cyclooxygenase-2 inhibitors with a fast onset of analgesia. The present study was conducted to assess whether the utility of the model can be broadened in assessing the efficacy of analgesics with diverse mechanisms and pharmacokinetic profiles in drug development and to enhance the sensitivity of a bunionectomy model.

Methods

This was a single center, randomized, double-blind, placebo-controlled, three-arm, parallel group methodology study to evaluate the effects of pregabalin and naproxen sodium on postoperative pain following bunionectomy. Patients (n=100) were randomized 1:1:1 to three treatments (administered 1 hour before and at defined intervals after surgery): pregabalin 300 mg before surgery and 150 mg every 8 hours; naproxen sodium 550 mg before surgery and 550 mg every 12 hours; or placebo in a double-dummy fashion. Primary endpoints were patient-controlled analgesic (PCA) hydromorphone consumption and the time to first PCA hydromorphone use postsurgery over 24 hours.

Results

Of the 100 patients randomized, 96 completed the study. Relative to placebo, pregabalin and naproxen sodium, respectively, reduced PCA hydromorphone consumption by 51% (P=0.005) and 65% (P<0.001) and increased the median time to first use of PCA hydromorphone by 1.5 hours (P=0.004) and 3.7 hours (P<0.001). Both drugs significantly (P<0.050) decreased use of oral opioid rescue medication over 24–48 hours postsurgery relative to placebo. Although there were no statistically significant differences between naproxen sodium and pregabalin in opioid consumption and global evaluation of medication, overall naproxen sodium appeared to be more effective at reducing pain.

Conclusions

The model provided a sensitive method for evaluating efficacy of compounds with diverse mechanisms and pharmacokinetic profiles. The robustness of the enhanced pain model renders bunionectomy pain a valuable tool to assess novel analgesic compounds in small numbers of subjects early in drug development.     

Development and implementation of a performance measure tool in an academic pediatric research network

BackgroundThe Pediatric Emergency Care Applied Research Network (PECARN) is a federally funded multi-center research network. To promote high quality research within the network, it is important to establish evaluation tools to measure performance of the research sites.PurposeTo describe the collaborative development of a site performance measure tool “report card” in an academic pediatric research network. To display report card template information and discuss the successes and challenges of the report cards.Development and implementation of the network performance measure toolThe PECARN Quality Assurance Subcommittee and the PECARN data center were responsible for the development and implementation of the report cards. Using a Balanced Scorecard format, four key metrics were identified to align with PECARN's research goals. Performance indicators were defined for each of these metrics. After two years of development, the final report cards have been implemented annually since 2005. Protocol submission time to the Institutional Review Board (IRB) improved between 2005 and 2007. Mean overall report card scores for site report cards increased during this period with less variance between highest and lowest performing sites indicating overall improvement.ConclusionsReport cards have helped PECARN sites and investigators focus on performance improvement and may have contributed to improved operations and efficiencies within the network.     

Patient-reported outcomes in the Translational Breast Cancer Research Consortium

Members of the Translational Breast Cancer Research Consortium conducted an expert-driven literature review to identify a list of domains and to evaluate potential measures of these domains for inclusion in a list of preferred measures. Measures were included if they were easily available, free of charge, and had acceptable psychometrics based on published peer-reviewed analyses. A total of 22 domains and 52 measures were identified during the selection process. Taken together, these measures form a reliable and validated list of measurement tools that are easily available and used in multiple cancer trials to assess patient-reported outcomes in relevant patients.     

Changes in Immunologic Cell Surface Markers during Cocaine Withdrawal in Pregnant Women

To evaluate the effects of acute cocaine withdrawal on the immune system of pregnant women, we analyzed changes in a panel of cell surface markers and plasma proteins that have immunological importance. The cell surface markers included complement receptors [CR1 (CD35), CR2 (CD21), CR3 (CD11b, CD18)], immunoglobulin Fc receptors [FcγRII (CD32), FcγRIII (CD16)], proteins important for lymphocyte function [CD3, CD4, CD8, CD19, CD25, CD45RA], and the framework antigen HLA-ABC. We also measured levels of the plasma proteins C3, C4, IgG, IgM, and IgA, along with the cytokine interleukin-2, soluble lymphocyte markers sCD25, sCD4, sCD8, IL-2, and soluble immune complexes. While no significant changes were seen in the levels of plasma proteins, changes paralleling the course of acute withdrawal were seen in complement receptors and immunoglobulin Fc receptors on leukocyte subpopulations. By contrast, proteins important for lymphocyte function were relatively unperturbed. There was an increase in receptor expression at the onset of withdrawal that peaked 3–5 days after last cocaine use, followed by a decrease in expression to initial (pre-withdrawal) levels. These changes in cell surface receptors may reflect altered immune function in the women who were withdrawing from cocaine.     

Infant botulism: a review of 12 years' experience at the Children's Hospital of Philadelphia

Fifty-seven patients with infant botulism were cared for at The Children's Hospital of Philadelphia between 1976 and 1987. The ages of the children ranged from 18 days to slightly more than 7 months. The average duration of hospitalization was 44 +/- 34 days, with the average intensive care unit stay lasting 29 +/- 25 days (54 of 57 patients). The majority (77%) of the patients were ultimately intubated and mechanically ventilated (68%). The principal indication for intubation was loss of protective airway reflexes and not hypercarbia or hypoxemia. In those patients who required mechanical ventilation the average duration was 23 +/- 22 days, with the 10 most severely affected patients (greater than or equal to 28 days of mechanical ventilation) averaging 53 +/- 25 days. Excluding patients ventilated for more than a month, those who underwent tracheostomy were hospitalized nearly twice as long as those who were managed by nasotracheal intubation only (33.5 days vs 63.2 days). The use of continuous nasogastric feedings has supplied most infants with sufficient enteral feedings to avoid weight loss and the need for central intravenous alimentation.     

Spontaneous drainage of paravalvular abscess diagnosed by transesophageal echocardiography

Paravalvular abscesses, which occur in up to 30% of cases of native valve endocarditis, are being detected with increasing frequency with the use of transesophageal echocardiography. Abscesses of the mitral aortic intervalvular fibrosa have been described but only in association with native or prosthetic aortic valve endocarditis. We describe a patient with native mitral valve endocarditis complicated by an abscess in the fibrosa. A 51-year-old diabetic man presented with Staphylococcus aureus mitral valve endocarditis. A transesophageal echocardiographic study done 8 days after admission revealed two large masses at the base of the anterior mitral leaflet with extension into the fibrosa consistent with a paravalvular abscess that was not detected by precordial echocardiography. A repeat transesophageal echocardiographic study done 20 days after admission showed spontaneous drainage of the abscess and a subsequent fistula between the left atrium and left ventricle. This case highlights the important role that transesophageal echocardiography has in suspected and known cases of endocarditis. Its major advantage of delineating posterior cardiac structures allowed accurate diagnosis and serial evaluation of this previously unreported complication of endocarditis.