Publications

BACKGROUND

Biological pathways are a useful abstraction of biological concepts, and software tools to deal with pathway diagrams can help biological research. PathVisio is a new visualization tool for biological pathways that mimics the popular GenMAPP tool with a completely new Java implementation that allows better integration with other open source projects. The GenMAPP MAPP file format is replaced by GPML, a new XML file format that provides seamless exchange of graphical pathway information among multiple programs.

RESULTS

PathVisio can be combined with other bioinformatics tools to open up three possible uses: visual compilation of biological knowledge, interpretation of high-throughput expression datasets, and computational augmentation of pathways with interaction information. PathVisio is open source software and available at http://www.pathvisio.org.

CONCLUSION

PathVisio is a graphical editor for biological pathways, with flexibility and ease of use as primary goals.

BACKGROUND

Individuals with end-stage renal disease (ESRD) manifest a chronic inflammatory state. Serum albumin, C-reactive protein (CRP), interleukin-6 (IL-6) and serum amyloid A (SAA) have been associated with mortality in ESRD, although reports vary as to whether they are true independent markers of mortality. We undertook a prospective study to determine whether these markers could predict mortality in ESRD.

METHODS

A cohort of individuals on haemodialysis was followed prospectively for a mean of 2.1 years. Albumin, CRP, IL-6 and SAA were drawn at enrollment. Association between mortality and serum markers was assessed using Cox proportional hazards regression. A trend analysis was undertaken to establish the functional form of the association between serum markers and outcome.

RESULTS

After multivariable adjustment, IL-6 was most strongly associated with mortality, followed closely by albumin (P = 0.0002 and P = 0.0005, respectively). CRP was marginally associated with mortality (P = 0.046), and SAA was not independently associated with mortality. In the final model adjusting for the effects of both IL-6 and albumin simultaneously, both markers remained associated with mortality (P = 0.003 and P = 0.011).

CONCLUSION

IL-6 had the strongest independent association with mortality, followed closely by albumin. CRP and SAA were not associated with mortality when measured at single time points. Increasing levels of IL-6 and decreasing levels of albumin were associated with increased mortality. IL-6 and albumin may be capturing different aspects of the inflammatory burden observed in haemodialysis patients.

AIMS

Given the selectivity of clinical trial patients and meager representation of elderly in the major implantable cardioverter defibrillator (ICD) randomized trials (<25%), whether such data apply to elderly patients overall is unclear. The purpose of our study is to understand the influence of age on mortality after ICD implantation.

METHODS AND RESULTS

We performed a retrospective cohort study of 502 consecutive patients receiving ICDs from 1993 to 2003 at a single university hospital. The primary predictor was patient age, categorized as <65, 65-75, and >75 years at ICD implantation. The primary outcome was time to death. Mean follow-up was 4 years. Median survival after ICD implantation was 5.3 years among subjects >75 years, less than half that of the youngest group. After adjusting for potential confounders, compared with subjects <65 years of age, patients >75 years [hazard ratio (HR), 4.7; 95% confidence interval (CI), 2.8-7.9; P < 0.001] and those 65-75 years (HR, 2.8; 95% CI, 1.7-4.8; P < 0.001) were at greater risk of death. Increased age was associated with higher total, cardiac, and non-cardiac mortality (all P

CONCLUSION

Age at ICD implantation is strongly and independently associated with mortality. Age should be considered among potential co-morbidities in anticipating survival of the elderly patient prior to ICD implantation.

Epoxyeicosatrienoic acids (EETs) are derived from cytochrome P450-catalyzed epoxygenation of arachidonic acid and have emerged as important mediators of numerous biological effects. The major elimination pathway for EETs is through soluble epoxide hydrolase (sEH)-catalyzed metabolism to dihydroxyeicosatrienoic acids (DHETs). Based on previous studies showing that EETs have anti-inflammatory effects, we hypothesized that chronic inhibition of sEH would attenuate a lipopolysaccharide (LPS)-induced inflammatory response in vivo. Continuous dosing of the sEH inhibitors 12-(3-adamantan-1-ylureido)-dodecanoic acid (AUDA), a polyethylene glycol ester of AUDA, and 1-adamantan-1-yl-3-(5-(2-(2-ethoxyethoxy)ethoxy)-pentyl)urea resulted in robust exposure to the inhibitor and target engagement, as evidenced by significant increases in plasma EET/DHET ratios following 6 days of inhibitor treatment. However, sEH inhibitor treatment was not associated with an attenuation of LPS-induced inflammatory gene expression in the liver, and AUDA did not protect from LPS-induced neutrophil infiltration. Furthermore, Ephx2-/-mice that lack sEH expression and have significantly increased plasma EET/DHET ratios were not protected from LPS-induced inflammatory gene expression or neutrophil accumulation in the liver. LPS did have an effect on sEH expression and function, as evident from a significant down-regulation of Ephx2 mRNA and a significant shift in plasma EET/DHET ratios 4 h after LPS treatment. In conclusion, there was no evidence that increasing EET levels in vivo could modulate an LPS-induced inflammatory response in the liver. However, LPS did have significant effects on plasma eicosanoid levels and hepatic Ephx2 expression, suggesting that in vivo EET levels are modulated in response to an inflammatory signal.

BACKGROUND

Neck pain is a common presentation to the Emergency Department (ED), requiring appropriate evaluation to exclude serious pathology.

OBJECTIVES

To review an atypical clinical presentation of neck pain and to distinguish this case and its associated radiographic features from more common clinical entities.

CASE REPORT

We present an ED case of calcific tendonitis of the longus coli muscle.

SUMMARY

Acute calcific retropharyngeal tendinitis is a rare, benign etiology of non-traumatic neck pain that is poorly recognized and often mistaken for other conditions secondary to infection or trauma. The importance of this disorder, as well as a review of the literature on the subject, is presented.

BACKGROUND

The United States (US) Food and Drug Administration (FDA) approves new drugs based on sponsor-submitted clinical trials. The publication status of these trials in the medical literature and factors associated with publication have not been evaluated. We sought to determine the proportion of trials submitted to the FDA in support of newly approved drugs that are published in biomedical journals that a typical clinician, consumer, or policy maker living in the US would reasonably search.

METHODS AND FINDINGS

We conducted a cohort study of trials supporting new drugs approved between 1998 and 2000, as described in FDA medical and statistical review documents and the FDA approved drug label. We determined publication status and time from approval to full publication in the medical literature at 2 and 5 y by searching PubMed and other databases through 01 August 2006. We then evaluated trial characteristics associated with publication. We identified 909 trials supporting 90 approved drugs in the FDA reviews, of which 43% (394/909) were published. Among the subset of trials described in the FDA-approved drug label and classified as "pivotal trials" for our analysis, 76% (257/340) were published. In multivariable logistic regression for all trials 5 y postapproval, likelihood of publication correlated with statistically significant results (odds ratio [OR] 3.03, 95% confidence interval [CI] 1.78-5.17); larger sample sizes (OR 1.33 per 2-fold increase in sample size, 95% CI 1.17-1.52); and pivotal status (OR 5.31, 95% CI 3.30-8.55). In multivariable logistic regression for only the pivotal trials 5 y postapproval, likelihood of publication correlated with statistically significant results (OR 2.96, 95% CI 1.24-7.06) and larger sample sizes (OR 1.47 per 2-fold increase in sample size, 95% CI 1.15-1.88). Statistically significant results and larger sample sizes were also predictive of publication at 2 y postapproval and in multivariable Cox proportional models for all trials and the subset of pivotal trials.

CONCLUSIONS

Over half of all supporting trials for FDA-approved drugs remained unpublished >/= 5 y after approval. Pivotal trials and trials with statistically significant results and larger sample sizes are more likely to be published. Selective reporting of trial results exists for commonly marketed drugs. Our data provide a baseline for evaluating publication bias as the new FDA Amendments Act comes into force mandating basic results reporting of clinical trials.