Publications

OBJECTIVE

To assess the contribution of workplace exposures to chronic obstructive pulmonary disease (COPD) risk in a community with a heavy burden of past industrial employment.

METHODS

A random population sample of Sheffield, U.K. residents aged over 55 years (n=4000), enriched with a hospital-based supplemental sample (n=209), was approached for study. A comprehensive self-completed questionnaire elicited physician-made diagnoses, current symptoms, and past workplace exposures. The latter were defined in three ways: self-reported exposure to vapours, gases, dusts and fumes (VGDF); response to a specific exposure checklist; and through a job exposure matrix (JEM) assigning exposure risk likelihood based on job history independent of respondent-reported exposure. A subset of the study group underwent lung function testing. Population attributable risk fractions (PAR%), adjusted for age, sex and smoking, were calculated for association between workplace exposure and COPD.

RESULTS

2001 (50%) questionnaires were returned from the general population sample and 60 (29%) by the hospital supplement. Among 1754 with complete occupational data, any past occupational exposure to VGDF carried an adjusted excess risk for report of a physician's diagnosis of COPD, emphysema, or chronic bronchitis (ORs 3.9; 95% CI 2.7 to 5.8), with a corresponding PAR% value of 58.7% (95% CI 45.6% to 68.7%). The PAR% estimate based on JEM exposure was 31%. From within the subgroup of 571 that underwent lung function testing, VGDF exposure was associated with a PAR% of 20.0% (95% CI -7.2 to 40.3%) for Global initiative for chronic obstructive lung disease (GOLD) 1 (or greater) level of COPD.

CONCLUSION

This heavy industrial community-based population study has confirmed significant associations between reported COPD and both generic VGDF and JEM-defined exposures. This study supports the predominantly international evidence-based notion that workplace conditions are important when considering the current and future respiratory health of the workforce.

UNLABELLED

We introduce GO-Elite, a flexible and powerful pathway analysis tool for a wide array of species, identifiers (IDs), pathways, ontologies and gene sets. In addition to the Gene Ontology (GO), GO-Elite allows the user to perform over-representation analysis on any structured ontology annotations, pathway database or biological IDs (e.g. gene, protein or metabolite). GO-Elite exploits the structured nature of biological ontologies to report a minimal set of non-overlapping terms. The results can be visualized on WikiPathways or as networks. Built-in support is provided for over 60 species and 50 ID systems, covering gene, disease and phenotype ontologies, multiple pathway databases, biomarkers, and transcription factor and microRNA targets. GO-Elite is available as a web interface, GenMAPP-CS plugin and as a cross-platform application.

AVAILABILITY

http://www.genmapp.org/go_elite

A majority of the novel orally administered, molecularly targeted anticancer therapies are weak bases that exhibit pH-dependent solubility, and suppression of gastric acidity with acid-reducing agents could impair their absorption. In addition, a majority of cancer patients frequently take acid-reducing agents to alleviate symptoms of gastroesophageal reflux disease, thereby raising the potential for a common but underappreciated drug-drug interaction (DDI) that could decrease the exposure of anticancer medication and result in subsequent failure of therapy. This article is a review of the available clinical literature describing the extent of the interaction between 15 orally administered, small-molecule targeted anticancer therapies and acid-reducing agents. The currently available clinical data suggest that the magnitude of this DDI is largest for compounds whose in vitro solubility varies over the pH range 1-4. This range represents the normal physiological gastric acidity (pH ~1) and gastric acidity while on an acid-reducing agent (pH ~4).

Primary testicular lymphoma (PTL) is a rare testicular tumor representing less than 9% of all testicular cancers. PTL usually tends to spread to or relapse at nodal structures or extra-nodal sites such as contralateral testes, central nervous system, skin, lung, pleura, waldeyer's ring and soft tissues. We present a case of PTL with huge left atrial mass, an extremely unusual site of involvement. Early disease usually carries a good prognosis, whereas advanced stage carries an extremely poor prognosis. Herein, we report the complete remission to date in a patient with advanced stage PTL with huge left atrial mass, treated with systemic rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone and intrathecal methotrexate. A brief review of literature focusing on various aspects of management of primary testicular lymphoma and lymphomatous involvement of heart is also discussed.

BACKGROUND

Studies document increasing rates of hospitalization among patients with inflammatory bowel disease, but temporal trends for in-hospital mortality among patients with inflammatory bowel disease are not characterized. We sought to determine whether in-hospital mortality changed over a 13-year period among nationwide hospitalizations associated with inflammatory bowel disease. We additionally sought to identify factors correlated with mortality.

METHODS

We used the National Hospital Discharge Survey, a large nationally representative database, for the years 1994 through 2006. Age- and mortality-adjusted rates of in-hospital mortality and standardized mortality ratios were calculated for four time periods. Logistic regression analysis was used to assess associations between advancing time and mortality in adjusted analyses.

RESULTS

150 (0.9%) of 17,393 hospitalizations for patients with inflammatory bowel disease ended in death. Age-adjusted in-hospital mortality decreased from 3.6 deaths per 1,000 hospital days in 1994-96 to 2.4 per 1,000 in 2003-06; standardized mortality ratio decreased from 0.33 to 0.27. Similar trends were seen for patients with ulcerative colitis, but mortality did not change over time among patients with Crohn's disease. Multivariable logistic regression analysis confirmed the significance of these changes in mortality, with 17% decreased odds of in-hospital death per three-year period (P=0.012). Subject age (OR 1.06 per year, P<0.001), Charlson comorbidity index (OR 1.29 per 1-point increase, P<0.001), and diagnosis of ulcerative colitis (versus Crohn's disease, OR 1.41, P= .042) were also associated with in-hospital mortality.

CONCLUSIONS

The odds of in-hospital mortality among hospitalized patients with inflammatory bowel disease decreased by 17% per 3-year period from 1994 to 2006 in analysis adjusted for age and comorbidity status, in this large, nationally representative database. Multiple factors likely contribute to these trends.