Earl Francis Cook

18F-FDG Metabolic Tumor Volume and Total Glycolytic Activity of Oral Cavity and Oropharyngeal Squamous Cell Cancer: Adding Value to Clinical Staging

18F-FDG metabolic tumor volume (MTV) and total glycolytic activity (TGA) have been proposed as potential prognostic imaging markers for patient outcome in human solid tumors. The purpose of this study was to establish whether MTV and TGA add prognostic information to clinical staging in patients with oral and oropharyngeal squamous cell carcinomas (SCCs). Methods: The Institutional Review Board approved this Health Insurance Portability and Accountability Act–compliant single-institution retrospective study. Forty-five patients with histologically proven oral or oropharyngeal SCC underwent PET/CT for initial cancer staging and were included in the study. MTV was measured using a gradient-based method (PET Edge) and fixed-threshold methods at 38%, 50%, and 60% of maximum standardized uptake value (SUV). The TGA is defined as MTV × mean SUV. Bland–Altman analysis was used to establish the reliability of the methods of segmentation. Outcome endpoints were overall survival (OS) and progression-free survival. Cox proportional hazards univariate and multivariate regression analyses were performed. Results: In Cox regression models, MTV and TGA were the only factors significantly associated with survival outcome after adjusting for all other covariates including American Joint Committee on Cancer (AJCC) stage, with hazards ratio of 1.06 (95% confidence interval, 1.01–1.10; P = 0.006) and 1.00 (95% confidence interval, 1.00–1.01; P = 0.02). The model fit was significantly better when MTV was added to AJCC stage in model I (χ2 value change, 1.16–6.71; P = 0.01) and when TGA was added to AJCC stage in model II (χ2 value change, 1.16–4.37; P = 0.04). The median cutoff point of 7.7 mL for primary tumor MTV was predictive of time to OS (log rank P = 0.04). The median cutoff point of 55 g for PET Edge primary tumor TGA was predictive of time to OS (log rank P = 0.08), though the result was not statistically significant. Conclusion: Gradient-based segmentations of primary tumor MTV and TGA are potential 18F-FDG markers for time to survival in patients with oral and oropharyngeal SCC and may provide prognostic information in addition to AJCC stage. These exploratory imaging markers need validation in larger cohort studies.

Health Literacy not Race Predicts End-of-Life Care Preferences

BACKGROUND Several studies have reported that African Americans are more likely than whites to prefer aggressive treatments at the end of life. OBJECTIVE Since the medical information presented to subjects is frequently complex, we hypothesized that apparent differences in end-of-life preferences and decision making may be due to disparities in health literacy. A video of a patient with advanced dementia may overcome communication barriers associated with low health literacy. DESIGN Before and after oral survey. PARTICIPANTS Subjects presenting to their primary care doctors. METHODS Subjects were asked their preferences for end-of-life care after they heard a verbal description of advanced dementia. Subjects then viewed a 2-minute video of a patient with advanced dementia and were asked again about their preferences. For the analysis, preferences were dichotomized into comfort care and aggressive care. Health literacy was measured using the Rapid Estimate of Adult Literacy in Medicine (REALM) and subjects were divided into three literacy categories: low (0-45, sixth grade and below), marginal (46-60, seventh to eighth grade) and adequate (61-66, ninth grade and above). Unadjusted and adjusted logistic regression models were fit using stepwise algorithms to examine factors related to initial preferences before the video. RESULTS A total of 80 African Americans and 64 whites completed the interview. In unadjusted analyses, African Americans were more likely than whites to have preferences for aggressive care after the verbal description, odds ratio (OR) 4.8 (95% confidence interval [CI] 2.1-10.9). Subjects with low or marginal health literacy were also more likely than subjects with adequate health literacy to have preferences for aggressive care after the verbal description, OR 17.3 (95% CI 6.0-49.9) and OR 11.3 (95% CI 4.2-30.8) respectively. In adjusted analyses, health literacy (low health literacy: OR 7.1, 95% CI 2.1-24.2; marginal health literacy OR 5.1, 95% CI 1.6-16.3) but not race (OR 1.1, 95% CI 0.3-3.2) was an independent predictor of preferences after the verbal description. After watching a video of advanced dementia, there were no significant differences in the distribution of preferences by race or health literacy. CONCLUSIONS Health literacy and not race was an independent predictor of end-of-life preferences after hearing a verbal description of advanced dementia. In addition, after viewing a video of a patient with advanced dementia there were no longer any differences in the distribution of preferences according to race and health literacy. These findings suggest that clinical practice and research relating to end-of-life preferences may need to focus on a patient education model incorporating the use of decision aids such as video to ensure informed decision-making.

A Simple Validated Gluten-Free Diet Adherence Survey for Adults With Celiac Disease

BACKGROUND & AIMS Celiac disease is an increasingly prevalent disorder. To monitor response to treatment in clinical and research settings, it is essential to accurately measure gluten-free diet (GFD) adherence in a standardized manner. The aim of this study was to develop a valid and reliable Celiac Dietary Adherence Test (CDAT). METHODS Items and domains believed to be essential for successful GFD adherence were used to develop an 85-item survey with input from patient focus groups. The survey was administered to 200 individuals with biopsy-proven celiac disease who underwent standardized dietician evaluation (SDE) and serologic testing. RESULTS Of the initial 85 items, 41 were correlated highly with the SDE (P < .01). Responses for all 200 participants for the 41 items were entered into a single database. Computer-generated randomization produced a derivation cohort of 120 subjects and a validation cohort of 80. By using the derivation cohort, a 7-item questionnaire was developed using logistic regression. The additive score based on these items was correlated highly with the SDE in both the derivation and validation cohorts (P < .001) and performed significantly better than immunoglobulin A tissue transglutaminase titers in receiver operating characteristic curve analysis with areas under the curve of 0.830 and 0.652, respectively. CONCLUSIONS The CDAT is a clinically relevant, easily administered, 7-item instrument that allows for standardized evaluation of GFD adherence and is superior to tissue transglutaminase serology. The CDAT may be useful in both research and clinical settings.

A prospective comparative study of five measures of gluten‐free diet adherence in adults with coeliac disease

Background  Increasing numbers of individuals are now being diagnosed with coeliac disease. The only accepted treatment for coeliac disease is lifelong adherence to a strict gluten‐free diet (GFD). Individuals’ ability to adhere to the GFD varies, but systematic studies guiding the assessment of adherence are currently lacking.

Development and Validation of a Colon Cancer Risk Assessment Tool for Patients Undergoing Colonoscopy

OBJECTIVES:Diagnostic criteria for hereditary colorectal cancer (CRC) are complex. “Open-access” colonoscopy makes it challenging to identify who needs genetic evaluation, intensive surveillance, and screening for extracolonic tumors. Our aim was to develop a simple, preprocedural risk assessment tool to identify who may be at highest risk for CRC.METHODS:A total of 631 outpatients undergoing colonoscopy at two academic practices completed a questionnaire assessing personal and family histories of CRC, polyps, and Lynch syndrome (LS)-associated malignancies. Subjects were considered to be high-risk if one of the nine prespecified characteristics of hereditary CRC syndromes was met. Through recursive partitioning analysis, an algorithm of fewest questions needed to capture the most high-risk individuals was developed. The results were validated in 5,335 individuals undergoing colonoscopy at five private endoscopy centers and tested in 285 carriers of mismatch repair mutations associated with LS.RESULTS:About 17.7% and 20.0% of individuals were classified as high-risk in the development and validation cohorts, respectively. Recursive partitioning revealed three questions that were most informative for identifying high-risk patients: (i) “Do you have a first-degree relative with CRC or LS-related cancer diagnosed before age 50?” (ii) “Have you had CRC or polyps diagnosed before age 50?” (iii) “Do you have ≥3 relatives with CRC?” When asked successively, these questions identified 77% of high-risk individuals in both cohorts and 271 of 285 (95%) of mutation carriers.CONCLUSIONS:Approximately one in five individuals undergoing colonoscopy would benefit from further risk assessment. We developed a simple, three-question CRC Risk Assessment Tool to identify the majority of patients who require additional assessment and possible genetic evaluation.

Liver transplantation in the critically ill: a multicenter Canadian retrospective cohort study

IntroductionCritically ill cirrhosis patients awaiting liver transplantation (LT) often receive prioritization for organ allocation. Identification of patients most likely to benefit is essential. The purpose of this study was to examine whether the Sequential Organ Failure Assessment (SOFA) score can predict 90-day mortality in critically ill recipients of LT and whether it can predict receipt of LT among critically ill cirrhosis listed awaiting LT.MethodsWe performed a multicenter retrospective cohort study consisting of two datasets: (a) all critically-ill cirrhosis patients requiring intensive care unit (ICU) admission before LT at five transplant centers in Canada from 2000 through 2009 (one site, 1990 through 2009), and (b) critically ill cirrhosis patients receiving LT from ICU (n = 115) and those listed but not receiving LT before death (n = 106) from two centers where complete data were available.ResultsIn the first dataset, 198 critically ill cirrhosis patients receiving LT (mean (SD) age 53 (10) years, 66% male, median (IQR) model for end-stage liver disease (MELD) 34 (26-39)) were included. Mean (SD) SOFA scores at ICU admission, at 48 hours, and at LT were 12.5 (4), 13.0 (5), and 14.0 (4). Survival at 90 days was 84% (n = 166). In multivariable analysis, only older age was independently associated with reduced 90-day survival (odds ratio (OR), 1.07; 95% CI, 1.01 to 1.14; P = 0.013). SOFA score did not predict 90-day mortality at any time. In the second dataset, 47.9% (n = 106) of cirrhosis patients listed for LT died in the ICU waiting for LT. In multivariable analysis, higher SOFA at 48 hours after admission was independently associated with lower probability of receiving LT (OR, 0.89; 95% CI, 0.82 to 0.97; P = 0.006). When including serum lactate and SOFA at 48 hours in the final model, elevated lactate (at 48 hours) was also significantly associated with lower likelihood of receiving LT (0.32; 0.17 to 0.61; P = 0.001).ConclusionsSOFA appears poor at predicting 90-day survival in critically ill cirrhosis patients after LT, but higher SOFA score and elevated lactate 48 hours after ICU admission are associated with a lower probability receiving LT. Older critically ill cirrhosis patients (older than 60) receiving LT have worse 90-day survival and should be considered for LT with caution.

Identifying the components of asthma health status in children with mild to moderate asthma.

BACKGROUND Weak and inconsistent correlations between measurements of asthma health status suggest that the disease is composed of nonoverlapping components. OBJECTIVE Factor analysis was used to explore the relationships between measures of asthma morbidity and to identify heterogeneous components of asthma health status in children 5 to 12 years old. Results were compared across time (baseline and 48-month visit) and treatment arms. METHODS Analyses were conducted in 7 different study windows in a database from a large clinical trial of children with mild to moderate asthma (n = 1041). Measurements of lung function, symptoms, and health care utilization from daily diary cards, serum IgE levels, total eosinophil count, skin test positivity, and airway hyperresponsiveness were included. Data on fractional exhaled nitric oxide and sputum eosinophil cationic protein were included in a subgroup of patients. RESULTS In each of the study windows, factor analysis identified 5 factors that explained between 50% and 60% of the common variance. Factors identified included (1) inflammatory markers, (2) symptoms/medication use, (3) asthma exacerbations, and measures of lung function, which subdivided into (4) FEV(1) and forced vital capacity, and (5) bronchodilator response and the FEV(1)/forced vital capacity ratio. Exploratory analyses suggest that fractional exhaled nitric oxide account for the atopy/inflammatory marker factor, and sputum measurements account for a sixth, separate factor. CONCLUSION The consistent identification of a 5-factor structure across time and treatment arms suggests that each of these factors provides independent information in the assessment of asthma.

Development of a breast reconstruction satisfaction questionnaire (BRECON): dimensionality and clinical importance of breast symptoms, donor site issues, patient expectations, and relationships.

To develop a valid, reliable and responsive, self‐administered questionnaire to assess womens satisfaction with breast reconstruction.

The breast reconstruction satisfaction questionnaire (BRECON‐31): An affirmative analysis

To verify the subscale structure of the BRECON‐31 using a test sample of women naïve to the questionnaire.

Treatment interruptions among patients with tuberculosis in Russian TB hospitals

OBJECTIVE To evaluate risk factors for in-patient treatment interruptions (TIs) in Russian tuberculosis (TB) hospitals. METHODS The regional case-based registers for all TB patients registered in the main regional TB hospitals were analyzed for the period 1993-2002. Multivariable analysis of risk factors for TIs was performed using logistic regression. The prediction rule was developed based on the final multivariable model coefficients obtained from analysis of the largest (Lipetsk) database. RESULTS During the study period, 18-50% of new cases and 36-56% of retreatment cases had interrupted in-patient treatment. In multivariate analysis, independent predictors of treatment interruption included: male gender (odds ratios (ORs) 1.5-2.3), age group 25-50 years (ORs 1.5-1.7), alcohol abuse (ORs 1.8-4.0), imprisonment history (ORs 1.3-2.5), unemployment (ORs 1.1-2.8), being a retreatment case (ORs 1.3-2.5), and having severe forms of TB (1.4-4.0); factors protective from interruption included urban residence (ORs 0.7-0.9) and having concomitant diseases (ORs 0.6-0.8). Based on the Lipeck model, new TB cases from the four regions were divided into low, high, and very high risk groups. Proportions of TI were approximately 20-35% in the low risk group, approximately 60-75% in the high risk group, and approximately 75-85% in the very high risk group (except Orel). CONCLUSIONS We have described the independent predictors of patient TI, and a predictive rule for the in-patient TB treatment phase interruptions has been developed. Treatment interruption is a significant obstacle in the success of the National Tuberculosis Control Program in Russia. Interventions targeted at the high risk groups should be implemented in order to prevent in-patient treatment interruption.