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Wei's urn design was proposed in 1987 for subject randomization in trials comparing m ≥ 2 treatments with equal allocation. In this manuscript, two modified versions of Wei's urn design are presented to accommodate unequal allocations. First one uses a provisional allocation of [Formula: see text] to achieve the target allocation r1 : r2, and the second one uses equal allocation for r1 + r2 arms to achieve an unequal allocation r1 : r2 based on the concept Kaiser presented in his recent paper. The properties of these two designs are evaluated based on treatment imbalance and allocation predictability under different sample sizes and unequal allocation ratios. Simulations are performed to compare the two designs to other designs used for unequal allocations, include the complete randomization, permuted block randomization, block urn design, maximal procedure, and the mass weighted urn design.

Current clinical classifications of chronic rhinosinusitis (CRS) have weak prognostic utility regarding treatment outcomes. Simplified discriminant analysis based on unsupervised clustering has identified novel phenotypic subgroups of CRS, but prognostic utility is unknown.We sought to determine whether discriminant analysis allows prognostication in patients choosing surgery versus continued medical management.A multi-institutional prospective study of patients with CRS in whom initial medical therapy failed who then self-selected continued medical management or surgical treatment was used to separate patients into 5 clusters based on a previously described discriminant analysis using total Sino-Nasal Outcome Test-22 (SNOT-22) score, age, and missed productivity. Patients completed the SNOT-22 at baseline and for 18 months of follow-up. Baseline demographic and objective measures included olfactory testing, computed tomography, and endoscopy scoring. SNOT-22 outcomes for surgical versus continued medical treatment were compared across clusters.Data were available on 690 patients. Baseline differences in demographics, comorbidities, objective disease measures, and patient-reported outcomes were similar to previous clustering reports. Three of 5 clusters identified by means of discriminant analysis had improved SNOT-22 outcomes with surgical intervention when compared with continued medical management (surgery was a mean of 21.2 points better across these 3 clusters at 6 months, P.05). These differences were sustained at 18 months of follow-up. Two of 5 clusters had similar outcomes when comparing surgery with continued medical management.A simplified discriminant analysis based on 3 common clinical variables is able to cluster patients and provide prognostic information regarding surgical treatment versus continued medical management in patients with CRS.

Context. Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting and persistent consequence of numerous classes of antineoplastic agents, affecting up to 30%e40% of patients. To date, there is no effective prevention or therapy. An evolving hypothesis for reducing CIPN pain involves direct nerve stimulation to reduce the pain impulse. Objectives. To evaluate the impact on CIPN associated with the MC5-A Calmare therapy device (Competitive Technologies, Inc. Fairfield, CT). Methods. The MC5-A Calmare therapy device is designed to generate a patient-specific cutaneous electrostimulation to reduce the abnormal pain intensity. Sixteen patients from one center received one-hour interventions daily over 10 working days. Results. Of 18 patients, 16 were evaluable. The mean age of the patients was 58.6 yearsdfour men and 14 womendand the duration of CIPN was three months to eight years. The most common drugs were taxanes, platinums, and bortezomib (Velcade, Millenium Pharmaceuticals, Cambridge MA). At the end of the study (Day 10), a 20% reduction in numeric pain scores was achieved in 15 of 16 patients. The pain score fell 59% from 5.81 � 1.11 before treatment to 2.38 � 1.82 at the end of 10 days (P < 0.0001 by paired t-test). A daily treatment benefit was seen with a strong statistically significant difference between the preand post-daily pain scores (P < 0.001). Four patients had their CIPN reduced to zero. A repeated-measures analysis using the scores from all 10 days confirmed these results. No toxicity was seen. Some responses have been durable without maintenance. Conclusions. Patient-specific cutaneous electrostimulation with the MC5-A Calmare device appears to dramatically reduce pain in refractory CIPN patients with no toxicity. Further studies are underway to define the benefit, mechanisms of action, and optimal schedule. J Pain Symptom Manage 2010;-:-e-. 2010 Published by Elsevier Inc on behalf of U.S. Cancer Pain Relief Committee.

Background: To investigate the existence of a selection bias using a virtual radiotherapy dose-escalation trial. In dose-escalation trials, normal tissue constraints generally remain constant while the tumor dose is increased. Since tumor dose and normal tissue constraints are competing demands, a point will be reached at which the tumor dose cannot be increased without exceeding normal tissue constraints. Methods and Materials: In 9 patients with non–small-cell lung cancer, the tumor dose was escalated from 66 Gy to 78 Gy in 4-Gy dose levels using intensity-modulated radiotherapy planning, while the limiting normal tissue dose contraints remained constant. Dosimetric, radiobiologic, and other planning parameters were compared at the 66-Gy dose level for patients eligible for all dose levels and for those eligible only for lower dose levels. Results: Seven of 9 patients were eligible for all dose levels (Group E). Two of 9 patients ("ineligible" or Group I) qualified only for lower total doses (95% confidence interval, 0.075–0.6, significant). In Group E, mean planning target volumes were smaller (132 vs. 404 cm 3 , nonsignificant), monitor units per fraction were significantly lower (448 vs. 802, p = 0.0008), and the average composite score for plan quality was better than in Group I (0.012 vs. 0.068, nonsignificant). Average tumor-control probabilities were higher (0.33 vs. 0.23, nonsignificant), and normal tissue-complication probabilities were lower for Group E than for Group I. Conclusions: Patients eligible for higher dose levels had significantly superior estimated outcome parameters. A method to eliminate this source of error in the interpretation of dose-escalation trials is suggested.

Objective. To use a meta-analysis on all reported cases of deep brain stimulation (DBS) for dystonia to determine which factors significantly influence outcome. The Burke-Fahn-Marsden (BFM) movement scale, the most reported measure, was chosen as the primary outcome measure for this analysis. Methods. A MEDLINE search identified 137 patients who underwent DBS for dystonia in 24 studies that had individual BFM scores. Individual patient data, including age at onset of dystonia, age at surgery, gender, distribution of dystonia, etiology of dystonia, presence of associated features, abnormality of preoperative imaging, prior stereotactic surgeries, nucleus stimulated, type of anesthesia used, use of physiologic monitoring, type of imaging used for localization, stimulation parameters used, time of response to stimulation, and timing of outcome assessment were entered into an SPSS database for statistical analysis. Results. The mean BFM percentage change (improvement in postoperative score from baseline) was 51.8% (range −34% to 100%). Significantly better outcomes were achieved with stimulation of the globus pallidus internus (GPi) than with stimulation of the posterior portion of the ventral lateral (VLp) nucleus of the thalamus (p = 0.0001). The etiology of the dystonia also had a significant effect on outcomes. Statistically significant improvements in outcomes were seen for all etiologic categories, except encephalitis. Dystonia due to birth injury and encephalitis had significantly worse outcomes when compared to other etiologies. However, there were no significant differences in the outcomes of patients who were DYT1 (DYT1 is the gene associated with the disorder Dystonia Musculorum Deformans) gene positive, DYT1 gene negative, or had pantothenate kinase-associated neurodegeneration (PKAN), tardive dyskinesia, and idiopathic and posttraumatic dystonias. Longer duration of dystonia symptoms correlated negatively with surgical outcome. A regression model using the three variables—stimulation site, etiology of dystonia, and duration of dystonia symptoms—explained 51% of the variance in outcomes. Conclusion. Deep brain stimulation of the GPi provides significant improvement in BFM scores in a variety of dystonic conditions.

Objective The purpose of this study was to determine the rate of new bowel symptoms and anal sphincter defects in primiparous women with and without recognized anal sphincter (AS) injury. Study design One hundred seventeen primiparous women classified with increasing degrees of perineal trauma and 21 controls delivered by cesarean section were enrolled immediately postpartum and demographic and delivery data were collected. At 6 weeks' postpartum, subjects completed a bowel function questionnaire and endoanal ultrasonography was performed. Logistic regression, chi-square, and 2-sample t tests were used for statistical analysis. Results A significant difference in new bowel symptoms was reported in women with (39%) and without (11%) recognized AS injury (P = .002). AS defects were present in 0%, 15%, 23%, 37%, and 67% of women with C/S, first-, second-, third-, and fourth-degree lacerations, respectively. Combined defects of the internal and external AS were associated with the greatest risk of new bowel symptoms (OR 32.1 [95% CI 9.6-107], P Conclusion In women with and without recognized AS trauma, new bowel symptoms were strongly correlated with the presence of anatomic AS defects postpartum.

Objectives. To assess the effectiveness of salvage radiotherapy (RT) for a persistent or rising prostate-specific antigen (PSA) level after radical prostatectomy, and to identify the pretreatment factors that may predict for patients likely to benefit from this treatment. Methods. Seventy-three consecutive patients were treated during a 10-year period (1989 to 1999) with RT after radical prostatectomy. Twelve patients were excluded from analysis because of either an undetectable PSA level before RT or lack of follow-up data. No patients had clinical or radiographic evidence of distant disease. An undetectable PSA level (less than 0.1 ng/mL) was required to be considered disease free. Results. The median PSA level before RT was 0.8 ng/mL (range 0.1 to 63). The median radiation dose prescribed was 66.6 Gy. The actuarial PSA-free survival rate at 4 years was 39%. Failure was uncommon in patients followed up beyond 4 years. Univariate analysis revealed that a pre-RT PSA level of less than 1.0 ng/mL ( P = 0.001), Gleason score less than 8 ( P = 0.003), and achievement of an undetectable PSA level after prostatectomy ( P = 0.018) were significant predictors of improved disease-free survival. On multivariate analysis, both a pre-RT PSA level of less than 1.0 ng/mL and a Gleason score less than 8 maintained statistical significance. Conclusions. Salvage RT provides a reasonable chance of intermediate-term disease-free survival in patients with PSA persistence or relapse after radical prostatectomy. Patients with a higher PSA level (greater than 1 ng/mL) and Gleason score of 8 or more are less likely to benefit from this treatment, and improved therapies are needed for this subset of patients. Patients should be referred promptly for salvage RT after detection of relapse.

Objectives To estimate the prevalence and severity of asthma in an adolescent population by sex and race. Methods Cross-sectional, population-based survey of school children. Setting Midwestern city experiencing damage from the 1993 Mississippi River flood. Participants: 2,693 children attending grades 7 to 12. Measurements Questions from the International Study of Asthma and Allergies in Childhood (ISAAC). Results Two thousand six hundred ninety-three children were surveyed, for a response rate of 90%. In this population, 16.4% reported having ever been diagnosed with asthma; 25% reported wheezing in the last 12 months; 32% reported symptoms of rhinitis in the last 12 months; and 22% reported ever having hay fever. The prevalence rate for current asthma was 12.6%. Female students had significantly greater prevalence rates for current asthma (16.4% vs 9.0%, OR=1.85); ever-diagnosed asthma (18.5% vs 14.3%, OR=1.36); wheezing ≥ 4 times in the last 12 months (12.0% vs 5.6%, OR=1.95); current rhinitis (38.7% vs 25.4%, OR=1.73); and hay fever (26.4% vs 18.4%, OR=1.57). All associations with sex remained significant, except ever-diagnosed asthma, after controlling for other known risk factors in logistic regression. African-Americans had higher prevalence rates than other races with differences reaching statistical significance for ever-diagnosed asthma and current asthma; however, these relationships did not remain significant after controlling for other known risk factors in logistic regression. Conclusions Our prevalence rates were similar to those reported by other studies that used the ISAAC questionnaire. Female students reported significantly more asthma, wheezing, rhinitis, and hay fever than male students. Female students also reported more severe symptoms and a greater number of emergency room and hospital admissions.

Themost effective means of educating children with asthma and theirfamilies has not been clearly demonstrated in previous studies. Peereducation is uniquely suited to the complex problems encountered inunderserved populations. The purpose of this study was to show thefeasibility of delivering a peer education program for children withasthma and the effect of the program on indoor allergen levels in aninner-city population in Chicago. Overall, the program was wellreceived. Baseline allergen levels were consistent with some previousstudies in showing low levels of mite allergens and high levels ofcockroach allergens, with 79.6% of samples having levels > 8 U/g. Atotal of 28.2% of samples had cat allergen levels > 2 μg/g, although only 9.7% of homes had cats, confirming previous reports thatcat allergen is ubiquitous. Mold levels were seasonal, with the highestlevels in the summer. Results from this study suggest that interventionprograms should focus more on elimination of cockroaches than waspreviously appreciated, while minimizing the use of pesticides, and onidentification of the sources of cat allergen. Structural andpsychosocial issues in homes need to be addressed in future studies. This study has demonstrated the feasibility of delivering peereducation in a inner-city population and highlighted the need forcomprehensive intervention strategies addressing complex issues facingunderservedneighborhoods.

Background Asthma mortality rates in Chicago are among the highest in the United States, with substantially greater rates in poor and minority populations. How much of the differential can be attributed to differences in prevalence versus severity or access to care has not been determined. Objective To examine rates of asthma prevalence, severity, and symptoms and to explore the relationships of these rates to race and socioeconomic status in a random sample of Chicago school children. Methods Self-administered survey. Results Overall, rates of asthma were higher than previously reported, with 16% of students in the stratified cluster random sample of 3,670 children in the 7th and 8th grades having had asthma. Prevalence rates were significantly higher in schools with >98% African Americans than in other schools, with the highest prevalence rates seen in African American schools in low income neighborhoods. Rates were associated with the percent of African American children in the school and with median income of the school's census tract. Relationships were most consistent with indices of more severe disease. Conclusions Asthma prevalence is higher than previously noted, with rates greatest in minority and low income populations. Differences are more striking for measures of severity than for symptoms of wheezing, but are far less than previously reported differences in mortality, suggesting that additional factors, such as differential access to continuous health care, may be affecting high death rates from asthma in Chicago.