A nomogram to predict radiation pneumonitis, derived from a combined analysis of RTOG 9311 and institutional data

PURPOSE: To test the Washington University (WU) patient dataset, analysis of which suggested that superior-to-inferior tumor position, maximum dose, and D35 (minimum dose to the hottest 35% of the lung volume) were valuable to predict radiation pneumonitis (RP), against the patient database from Radiation Therapy Oncology Group (RTOG) trial 9311. METHODS AND MATERIALS: The entire dataset consisted of 324 patients receiving definitive conformal radiotherapy for non-small-cell lung cancer (WU = 219, RTOG 9311 = 129). Clinical, dosimetric, and tumor location parameters were modeled to predict RP in the individual datasets and in a combined dataset. Association quality with RP was assessed using Spearman's rank correlation (r) for univariate analysis and multivariate analysis; comparison between subgroups was tested using the Wilcoxon rank sum test. RESULTS: The WU model to predict RP performed poorly for the RTOG 9311 data. The most predictive model in the RTOG 9311 dataset was a single-parameter model, D15 (r = 0.28). Combining the datasets, the best derived model was a two-parameter model consisting of mean lung dose and superior-to-inferior gross tumor volume position (r = 0.303). An equation and nomogram to predict the probability of RP was derived using the combined patient population. CONCLUSIONS: Statistical models derived from a large pool of candidate models resulted in well-tuned models for each subset (WU or RTOG 9311), which did not perform well when applied to the other dataset. However, when the data were combined, a model was generated that performed well on each data subset. The final model incorporates two effects: greater risk due to inferior lung irradiation, and greater risk for increasing normal lung mean dose. This formula and nomogram may aid clinicians during radiation treatment planning for lung cancer.     

Small molecules in stem cell self-renewal and differentiation

The use of stem cells in regenerative medicine is a promising approach to the treatment of disease and injury. Natural and synthetic small molecules have been shown to be useful chemical tools for controlling and manipulating the fates of cells. Small molecules can target signaling transduction pathways (for example, tyrosine kinase receptors) and affect DNA replication, cell differentiation, tumor metastasis and apoptosis. Stem cells share many properties with cancer cells and these similarities can provide insights to control and direct cell behavior; small molecules are already standard chemotherapeutics in the treatment of cancer. Libraries of small molecules have been examined for anticancer behavior (especially apoptosis), and, more recently, for stem cell self-renewal and differentiation capabilities in potential approaches to regenerative medicine. Differentiation therapy for cancer is based on the idea that cancer cells are undifferentiated embryonic-like cells and proposes to promote the differentiation and hence block cell proliferation. For example, retinoids have a role in stem cell differentiation to several lineages and have also been used to promote differentiation of acute promyeloic leukemic cells. Small molecules are also important tools for understanding mechanistic and developmental processes. Strategies for generating functional small molecule libraries have been outlined previously. In this review, we will look at several small molecules that have been described in the recent literature as effectors of stem cell self-renewal or differentiation as associated with the Wnt, Hedgehog or NF-kappaB pathways.     

Consent Administrator Training to Reduce Disparities in Research Participation

Purpose: The aims for this paper are to summarize the current state of disparities in clinical research participation, discuss regulatory and interpersonal causes for these disparities, and to suggest an approach to address this problem by standardized training for consent administrators.
Organizing Construct: A program based on the Precede-Proceed model for training consent administrators is proposed and described.
Conclusions: The current process for informed consent for research is unstandardized and inadequate, and may contribute to racial and ethnic disparities. Researchers are urged to consider a formal training program for members of their research teams who will be obtaining participants' consent.
Clinical Relevance: An educational program for consent administrators may help to reduce disparities in research participation by improving communication between research staff and potential participants.     

Visual acuity in an Australian Aboriginal population

Background: Australia is a developed country, However; Aboriginal Australians have rates of blindness comparable to Third World countries. There have been well-funded eye health programs for 15 years in Central Australia. This paper examines if there has been an improvement in visual disability of one traditional group of Aboriginal Australians. Methods: Results from an eye health survey of the Anangu Pitjantjatjara of South Australia in 1990 are presented. These data are compared with results for ‘blindness’ and ‘poor vision’ from a national survey undertaken in 1976. The two surveys were comparable in design, both were cross-sectional population-based prevalence surveys. Prevalence rates were adjusted for the size of the source population. Results: Young rural Aboriginal Australians have good visual acuity. Low vision and blindness (WHO definitions) occur in 19.6% and 10.4% of 60+ year olds, respectively. Women were more likely than men to be blind or have low vision (OR= 1.93; 1.06-3.58). There was a decline in ‘poor vision’ between surveys (OR=2.86; 1.86-4.75) but not in ‘blindness’. Conclusion: Although there has been a reduction in the prevalence of visual disability in rural Aboriginal Australians, improvements in the provision of eye care for the elderly need to occur.     

Improvements in pelvic exenteration: Factors responsible for reducing morbidity and mortality

Background: Since pelvic exenteration for the treatment of recurrent gynecologic malignancy first was described, reported rates of morbidity and mortality have declined steadily. However, the factors responsible for this decline have never been clearly delineated. Methods: We reviewed the charts of 154 patients who underwent pelvic exenteration for gynecologic malignancy between 1954 and 1994. Charts were abstracted for details of the surgical procedure, pathologic findings, postoperative management, short- and long-term complications, time to recurrence, and overall survival. Results: Seventy-two patients (47%) experienced 95 identifiable postoperative complications, resulting in death in 22 patients (14%). The rate of infectious complications declined to a statistically significant degree between the first two decades and latter two decades of the study (odds ratio [OR] 0.28, 95% CI 0.11–0.69). The use of routine prophylactic antibiotics was associated with this decline in infectious complications (OR 0.25, 95% CI 0.07–0.83). The use of preoperative subcutaneous heparin was associated with a reduction in thrombotic complications from 5 of 100 patients to 0 of 54 patients (P=.11), as well as a significant reduction in overall risk of complications (OR 0.53, 95% CI 0.33–0.85) and risk of postoperative mortality (OR 0.19, 95% CI 0.05–0.80). There was a significant reduction in overall risk of postoperative complications with both intensive care unit monitoring postoperatively (OR 0.65, 95% CI 0.43–0.99) and routine postoperative monitoring with a pulmonary artery catheter (OR 0.61, 95% CI 0.38–0.98). Conclusions: Routine use of prophylactic antibiotics, prophylactic subcutaneous heparin, and intensive postoperative monitoring appear to have reduced morbidity from pelvic exenteration.