Remote delivery of a weight management intervention for adults with intellectual disabilities: Results from a randomized non-inferiority trial.

BACKGROUND: Remote delivery of multi-component weight management interventions results in clinically meaningful weight loss in adults without intellectual disabilities (ID), but the effectiveness of remotely delivered weight management interventions in adults with ID has not previously been evaluated. OBJECTIVE: To determine if a weight management intervention delivered remotely could achieve weight loss (kg) at 6 months that is non-inferior to in-person visits in adults with ID and overweight or obesity (BMI ≥25 kg/m2). METHODS: Participants were randomized to a 24-mo. trial (6 mos weight loss,12 mos weight maintenance, 6 mos. no-contact follow up) to compare weight loss achieved with the same multicomponent intervention delivered to individual participants in their home either remotely (RD) or during face-to-face home visits (FTF). RESULTS: One hundred twenty adults with ID (∼32 years of age, 53 % females) were randomized to the RD (n = 60) or the FTF arm (n = 60). Six-month weight loss in the RD arm (-4.9 ± 7.8 kg) was superior to 6-month weight loss achieved in the FTF arm (-2.1 ± 6.7 kg, p = 0.047). However, this may be partially attributed to the COVID-19 pandemic, since weight loss in the FTF arm was greater in participants who completed the intervention entirely pre-COVID (n = 33,-3.2 %) compared to post-COVID (n = 22, -0.61 %). Weight loss across did not differ significantly between intervention arms at 18 (p = 0.33) or 24 months (p = 0.34). CONCLUSION: Our results suggest that remote delivery is a viable option for achieving clinically relevant weight loss and maintenance in adults with ID. NCT REGISTRATION: NCT03291509.

Weight management for adolescents with intellectual and developmental disabilities: Rationale and design for an 18month randomized trial.

Adolescents with intellectual and developmental disabilities (IDD) are an underserved group in need of weight management. However, information regarding effective weight management for this group is limited, and is based primarily on results from small, non-powered, non-randomized trials that were not conducted in accordance with current weight management guidelines. Additionally, the comparative effectiveness of emerging dietary approaches, such as portion-controlled meals (PCMs) or program delivery strategies such as video chat using tablet computers have not been evaluated. Therefore, we will conduct an 18month trial to compare weight loss (6months) and maintenance (7-18months) in 123 overweight/obese adolescents with mild to moderate IDD, and a parent, randomized to a weight management intervention delivered remotely using FaceTime™ on an iPad using either a conventional meal plan diet (RD/CD) or a Stop Light diet enhanced with PCMs (RD/eSLD), or conventional diet delivered during face-to-face home visits (FTF/CD). This design will provide an adequately powered comparison of both diet (CD vs. eSLD) and delivery strategy (FTF vs. RD). Exploratory analyses will examine the influence of behavioral session attendance, compliance with recommendations for diet (energy intake), physical activity (min/day), self-monitoring of diet and physical activity, medications, and parental variables including diet quality, physical activity, baseline weight, weight change, and beliefs and attitudes regarding diet and physical activity on both weight loss and maintenance. We will also complete a cost and contingent valuation analysis to compare costs between RD and FTF delivery.

A virtual reality intervention (Second Life) to improve weight maintenance: Rationale and design for an 18-month randomized trial.

Despite the plethora of weight loss programs available in the US, the prevalence of overweight and obesity (BMI≥25kg/m(2)) among US adults continues to rise at least, in part, due to the high probability of weight regain following weight loss. Thus, the development and evaluation of novel interventions designed to improve weight maintenance are clearly needed. Virtual reality environments offer a promising platform for delivering weight maintenance interventions as they provide rapid feedback, learner experimentation, real-time personalized task selection and exploration. Utilizing virtual reality during weight maintenance allows individuals to engage in repeated experiential learning, practice skills, and participate in real-life scenarios without real-life repercussions, which may diminish weight regain. We will conduct an 18-month effectiveness trial (6 months weight loss, 12 months weight maintenance) in 202 overweight/obese adults (BMI 25-44.9kg/m(2)). Participants who achieve ≥5% weight loss following a 6month weight loss intervention delivered by phone conference call will be randomized to weight maintenance interventions delivered by conference call or conducted in a virtual environment (Second Life®). The primary aim of the study is to compare weight change during maintenance between the phone conference call and virtual groups. Secondarily, potential mediators of weight change including energy and macronutrient intake, physical activity, consumption of fruits and vegetables, self-efficacy for both physical activity and diet, and attendance and completion of experiential learning assignments will also be assessed.

Weight management for individuals with intellectual and developmental disabilities: rationale and design for an 18 month randomized trial.

Weight management for individuals with intellectual and developmental disabilities (IDD) has received limited attention. Studies on weight management in this population have been conducted over short time frames, in small samples with inadequate statistical power, infrequently used a randomized design, and have not evaluated the use of emerging effective dietary strategies such as pre-packaged meals (PMs). Low energy/fat PMs may be useful in individuals with IDD as they simplify meal planning, limit undesirable food choices, teach appropriate portion sizes, are convenient and easy to prepare, and when combined with fruits and vegetables provide a high volume, low energy dense meal. A randomized effectiveness trial will be conducted in 150 overweight/obese adults with mild to moderate IDD, and their study partners to compare weight loss (6 months) and weight maintenance (12 months) between 2 weight management approaches: 1. A Stop Light Diet enhanced with reduced energy/fat PMs (eSLD); and 2. A recommended care reduced energy/fat meal plan diet (RC). The primary aim is to compare weight loss (0-6 months) and weight maintenance (7-18 months) between the eSLD and RC diets. Secondarily, changes in chronic disease risk factors between the eSLD and RC diets including blood pressure, glucose, insulin, LDL-cholesterol, and HDL-cholesterol will be compared during both weight loss and weight maintenance. Finally, potential mediators of weight loss including energy intake, physical activity, data recording, adherence to the diet, study partner self-efficacy and daily stress related to dietary change will be explored.

Is symptom relief associated with reduction in gastric retention after gastric electrical stimulation treatment in patients with gastroparesis? A sensitivity analysis with logistic regression models.

BACKGROUND: Enterra gastric electrical stimulation (GES) is an alternative treatment for gastroparesis (GP) when standard medical therapy fails. The aims of this study were to evaluate the association between total symptom score (TSS) and reduction in gastric retention (GR) after GES by GP etiology and to examine the sensitivity of the association to varying cutpoints used to define GR and TSS improvement. METHODS: Gastric retention assessed with a standardized (99m) Tc radio-labeled egg meal and TSS measured by a five-point Likert scale in 221 GP patients treated with Enterra GES therapy for at least 1 year were analyzed. Bivariate chi-square test and multivariable logistic regression with all possible cutpoints were used to assess the consistency of association and quantitate the relationship across three GP etiologies. KEY RESULTS: Symptom relief in diabetic GP was more likely attributable to GR reduction as indicated by the consistently significant odds ratios (P < 0.01) across all cutpoints. The association in idiopathic GP was inconclusive because odds ratios were sensitive to cutpoints with P-values ranging from 0.01 to 0.47. No association was found for patients with post surgical gastroparesis (P > 0.1 for all cutpoints). Patient age, gender, baseline TSS and baseline GR had no significant effect at 5% level on clinical improvement regardless of cutpoints for GR. CONCLUSIONS & INFERENCES: Association between clinical improvements and GR reduction following GES treatment depends on patient etiology and was able to be demonstrated in diabetic GP. The association for idiopathic GP was inconclusive and no such association was found for post surgical GP across all possible cutpoint combinations.

Effects of long-term aerobic exercise on EPOC.

This study sought to determine the influence of 16 months of progressive aerobic exercise on excess postexercise oxygen consumption (EPOC) and the extent EPOC contributed to weight management. Twenty-five overweight/obese women and 16 overweight/obese men participated in a 16-month exercise program (moderate-intensity treadmill walking) that progressed across the first 26 weeks to 5 days.wk(-1), 45 min.session(-1), and 75% HRR. Three-hour EPOC was measured at baseline, 9 months, and 16 months by indirect calorimetry in response to an exercise session (treadmill walking), in which energy expenditure (EE) was estimated from the participant's previous 10 exercise sessions. For women, EPOC was 7.5 +/- 4.9, 9.6 +/- 7.6, and 6.5 +/- 6.5 L at baseline, 9 months, and 16 months, respectively (p > 0.05). For men, EPOC increased from baseline (11.8 +/- 6.8 L) to 9 months (13.5 +/- 8.6 L) (p < 0.05) with no further increase at 16 months (13.5 +/- 11.0 L). Change in EPOC was correlated with change in EE at 9 months (r = 0.65; p < 0.05) and 16 months (r = 0.58; p < 0.05) for men but not women. Progressive long-term exercise significantly influenced EPOC in overweight/obese men but not women. Change in volume of exercise likely explained the increase in energy expenditure during EPOC in men. EPOC contributed modestly to EE compared to the exercise itself.

A randomized trial of targeted educational materials for smoking cessation in African Americans using transdermal nicotine

This study examines the efficacy of targeted versus standard care smoking cessation materials among urban African American smokers. Five hundred smokers (250 to each group) are randomized to receive a culturally targeted or standard care videotape and print guide. Both groups receive 8 weeks of nicotine patches and reminder telephone calls at Weeks 1 and 3. Process outcomes include material use and salience at 1 and 4 weeks postbaseline. Smoking outcomes include 7-day abstinence, smoking reduction, and readiness to quit at 4 weeks and 6 months postbaseline. Despite greater use of the targeted guide (68.8 per cent vs. 59.6 per cent, p < .05), intervention participants do not perceive the targeted materials as more salient, and no significant differences are found between groups on the smoking outcomes. Findings point to the importance of greater audience segmentation and individual tailoring to better match intervention materials to the needs of the priority population. (AU)

Peripheral insulin and brain structure in early Alzheimer disease.

OBJECTIVE: Accumulating evidence suggests insulin and insulin signaling may be involved in the pathophysiology of Alzheimer disease (AD). The relationship between insulin-mediated glucoregulation and brain structure has not been assessed in individuals with AD. METHODS: Nondemented (Clinical Dementia Rating [CDR] 0, n = 31) and early stage AD (CDR 0.5 and 1, n = 31) participants aged 65 years and older had brain MRI to determine whole brain and hippocampal volume and 3-hour IV glucose tolerance tests to determine glucose and insulin area under the curve (AUC). Linear regression models were used to assess the relationship of insulin and glucose with brain volume, cognition, and dementia severity. RESULTS: In early AD, insulin and glucose AUCs were related to whole brain (insulin beta = 0.66, p < 0.001; glucose beta = 0.45, p < 0.01) and hippocampal volume (insulin beta = 0.42, p < 0.05; glucose beta = 0.46, p < 0.05). These relationships were independent of age, sex, body mass index, body fat, cardiorespiratory fitness, physical activity, cholesterol, and triglycerides. Insulin AUC, but not glucose, was associated with cognitive performance in early AD (beta = 0.40, p = 0.04). Insulin AUC was associated with dementia severity (Pearson r = -0.40, p = 0.03). Glucose and insulin were not related to brain volume or cognitive performance in nondemented individuals. CONCLUSIONS: Increased peripheral insulin is associated with reduced Alzheimer disease (AD)-related brain atrophy, cognitive dysfunction, and dementia severity, suggesting that insulin signaling may play a role in the pathophysiology of AD.

Breast-tissue sampling for risk assessment and prevention.

Breast tissue and duct fluid provide a rich source of biomarkers to both aid in the assessment of short-term risk of developing breast cancer and predict and assess responses to prevention interventions. There are three methods currently being utilized to sample breast tissue in asymptomatic women for risk assessment: nipple-aspirate fluid (NAF), random periareolar fine-needle aspiration (RPFNA) and ductal lavage. Prospective single-institution trials have shown that the presence of atypical cells in NAF fluid or RPFNA specimens is associated with an increased risk of breast cancer. Furthermore, RPFNA-detected atypia has been observed to further stratify risk based on the commonly used Gail risk-assessment model. A prospective trial evaluating risk prediction on the basis of atypical cells in ductal-lavage fluid is ongoing. The ability of other established non-genetic biomarkers (mammographic breast density; serum levels of bioavailable estradiol, testosterone, insulin-like growth factor-1 and its insulin like growth factor binding protein-3) to stratify risk based on the Gail model is as yet incompletely defined. Modulation of breast intra-epithelial neoplasia (i.e. hyperplasia with or without atypia) with or without associated breast-tissue molecular markers, such as proliferation, is currently being used to evaluate response in Phase II chemoprevention trials. RPFNA has been the method most frequently used for Phase II studies of 6-12 months duration. However, ductal lavage, RPFNA and random and directed core needle biopsies are all being utilized in ongoing multi-institutional Phase II studies. The strengths and weaknesses of each method are reviewed.

Active commuting to and from school and BMI in elementary school children-preliminary data.

BACKGROUND: United States National Health Objectives include increasing the proportion of trips made by walking to and from school for children who live within 1.6 km to 50%. The purpose of this objective is to increase the level of physical activity among children. However, the impact of walking, bicycling or skating (active commuting) to and from school on the prevalence of overweight is unknown. METHODS: Body mass index (BMI) was measured for 320 children (age 10.2+/-0.7 years) in September. Over 5 months, an active commuting index (SI) and daily physical activity were estimated via questionnaire. In April, BMI and body fat were measured. RESULTS: A significant positive association was found between April BMI and SI adjusting for September BMI (partial r=0.03, P<0.05). Positive associations were found between SI and physical activity before school (r=0.17, P<0.05) and daily moderate intensity physical activity (r=0.13, P<0.05). There were no significant association between SI and BF (P>0.05). CONCLUSIONS: This preliminary data suggests that active commuting does not appear to provide sufficient amounts of physical activity to attenuate BMI; however, it may contribute to the attainment of physical activity recommendations. Future research is needed to objectively measure the impact of active commuting on the prevalence of overweight.

A comparison of three methods of analyzing post-exercise oxygen consumption.

Oxygen consumption after exercise is frequently plotted as a function of time and then the area under the curve (AUC) is calculated. Subsequently, this AUC is further manipulated and thus, differences between these manipulations may impact the interpretation of changes in oxygen consumption after exercise. The purpose of this study was to determine if the method of calculating AUC influences the interpretation of changes in post-exercise oxygen consumption in response to long-term aerobic exercise. Forty-three moderately obese, sedentary participants volunteered to participate in this study (26 women and 17 men). All participants performed verified supervised exercise during the study. Supervised treadmill exercise was initially conducted for 3 d/week at 60 % of heart rate reserve (HRR) for 30 min and progressed to 5 d/week at 75 % of HRR for 45 min across the first 4 months. Pre-exercise, exercise, and post-exercise oxygen consumption was measured at baseline and 9 months. AUC was calculated by three methods; total, incremental, and positive incremental. Descriptive statistics and dependent T-tests were calculated for each method of calculating the AUC. In addition, the intra-individual coefficient of variation was determined for each individual for each AUC method. A pearson product moment correlation was calculated for each method to determine the strength of the relationship between pre- and post-training values. The change in post-exercise oxygen AUC after nine months of training was 5.36+/-10.90 L, 2.17+/-7.61 L, and 1.74+/-9.10 L for the total, incremental, and positive incremental methods, respectively. There was significant change in post-exercise total AUC from baseline to 9-months (5.36 +/- 10.90 L), while there was no significant change in incremental or positive incremental AUC. There was a moderately high correlation (r=0.67, p <0.05) between baseline and 9-months for the total AUC method, while there was no significant correlation for incremental and positive incremental AUC methods. These results suggest that the method used to calculate AUC can lead to a different interpretation of the effects of training on post-exercise oxygen consumption. From this data, it appears that analyzing post exercise oxygen consumption with the total area under the curve method has a greater ability to detect a change from aerobic training, than either the positive or incremental area under the curve methods.

Smoking in urban African Americans: behaviors, gender differences, and motivation to quit.

OBJECTIVE: This study describes smoking behaviors and gender differences, and correlates these factors with motivation to quit smoking among African-American smokers at a community-based health center. DESIGN: A 62-item survey assessed depression, hassles, readiness to change, and demographics. METHODS: Participants (N = 81) were interviewed in an adult clinic waiting room. RESULTS: On average, participants smoked 13 cigarettes per day. Many reported attempts to reduce smoking-related health risks: 46% switched brands, 57% reduced their smoking, and 19% smoked only on some days. Fifty-nine percent indicated depressive symptoms. For women vs men, noteworthy differences were: reduction in number of cigarettes smoked (66.7% vs 40.0%; P = .023), switching brands (58.8% vs 23.3%; P = .003), number of attempts to quit in the past year (2.7 vs 1.2; P = .034), and high concern about weight gain (52.9% vs 26.7%; P = .047). Cigarettes smoked per day was negatively correlated with motivation to quit (P = .022). Variables positively correlated with motivation to quit included: harm reduction strategies (P = .002), intention to quit in 30 days (P<.0001), and intention to quit in 6 months (P<.0001). CONCLUSIONS: Women showed more potential indications of readiness to quit, including more attempts to quit, reductions in number of cigarette smoked, and brand switching. Knowledge of cessation barriers, gender differences, and correlates to motivation may prove useful for investigators conducting research in this population.

Methylene blue chromoendoscopy for detection of short-segment Barrett's esophagus.

BACKGROUND: The yield of intestinal metaplasia (IM) with randomly obtained biopsy specimens in patients with short lengths of columnar-appearing mucosa in the distal esophagus is low (30%-50%). Vital staining would be beneficial if it identified more patients with short-segment Barrett's esophagus (SSBE). Our aim was to compare the confirmation of IM in patients with suspected SSBE (columnar-appearing mucosa <3 cm in length) by using methylene blue (MB)-directed versus random biopsies. METHODS: Consecutive patients undergoing EGD in whom columnar-appearing mucosa less than 3 cm in length was visualized underwent MB staining. Stained areas within suspected SSBE segments were targeted for biopsies. All biopsy specimens were stained with H & E with alcian blue at pH 2.5 and evaluated by a single pathologist. A historical control group (different from patients undergoing MB staining) consisted of patients with less than 3 cm of columnar-appearing mucosa in whom biopsy specimens were obtained randomly without MB staining. RESULTS: The MB group included 75 patients (mean age 63.8 +/- 10.9 years) with a mean length of columnar-appearing mucosa of 1.2 cm (range 0.5-2.5 cm). The control group included 83 patients (mean age 60.5 +/- 12.9 years) with a mean length of columnar-appearing mucosa of 1.16 cm (range 0.5-2.5 cm). IM (i.e., confirmed SSBE) was detected in 61% of the MB group versus 42% of the control group (p = 0.0237). Patients in the MB group required significantly fewer biopsies (4.3 +/- 1.5 vs. 5.1 +/- 12.3, p = 0.0162). Confirmation of IM by length was as follows: less than 1 cm (irregular Z line), MB 17.4% versus control 25% (p = 0.73); 1 to less than 2 cm, MB 77% versus control 45% (p = 0.03); 2 to less than 3 cm, MB 90% versus control 58% (p = 0.02). CONCLUSIONS: MB chromoendoscopy significantly increases the detection of IM and requires fewer biopsies in patients with suspected SSBE with greater than 1 cm of columnar-appearing mucosa. It does not appear to be beneficial in patients with irregular Z lines (<1 cm).

Differences among African American light, moderate, and heavy smokers.

This study examined differences in demography, behavior, attitude, and physician intervention among African American light, moderate, and heavy smokers. Data were derived from an intervention study designed to assess whether a smoking status stamp would increase screening for smoking status and cessation counseling by physicians. Current analysis included 879 African American smokers categorized into three groups: light (<10 cigarettes/day), moderate (10-19 cigarettes/day), or heavy (> or =20 cigarettes/day) smokers based on number of cigarettes per day smoked. Light smokers constituted 40% of study sample, 33% were moderate smokers, and 27% were heavy smokers. Light smokers were more likely to be female (p<0.001) and have a shorter smoking history (p<0.001). Light smokers were not different in age (p=0.334), or the number of previous quit attempts (p=0.551). Although light smokers were more likely than moderate and heavy smokers to be preparing to quit (p<0.001), they were less likely to be asked their smoking status (p=0.031) or told to arrange follow-up for smoking cessation (p=0.034) by their physicians. Many African American smokers are light smokers. Light smokers are more likely to be female and have a shorter smoking history. Despite their readiness to quit, compared to heavier smokers, African American light smokers are asked about smoking less often by their physicians. Programs are needed to enhance physician intervention in this understudied population of smokers.

Helicobacter pylori eradication dramatically improves inflammation in the gastric cardia.

OBJECTIVES: Inflammation of the gastric cardia, i.e., "carditis," has been associated with Helicobacter pylori (H. pylori) infection; however, some investigators believe carditis to be a histological marker for gastroesophageal reflux disease. The aim of this study was to investigate the role of H. pylori eradication on the grade of carditis scored according to the updated Sydney classification. METHODS: Consecutive patients presenting for upper endoscopy underwent systematic gastric biopsies (eight antral, 12 corpus, and four cardia). Patients with H. pylori infection and carditis were identified and followed prospectively before and after H. pylori treatment. At pretreatment and, on average, 2 yr after eradication of H. pylori, the degree of inflammation in the gastric cardia and H. pylori status were blindly assessed by a single pathologist. RESULTS: A total of 31 patients with H. pylori infection and carditis were identified. The mean age was 70 yr (range: 37-81 yr); all were male. Four were African-American and 27 were Caucasian. All patients were treated with standard anti-H. pylori therapy, including a proton pump inhibitor in combination with two antibiotics for 2 wk. Eradication of H. pylori was successful in 23 patients (group I), whereas eight patients had persistent infection (group II). Patients were followed after eradication therapy for a mean of 23.2 months (range: 6-48 months). After eradication therapy, there was a significant decrease (p < 0.0001) in the carditis scores (activity and inflammation scores) in group I, whereas the scores remained unchanged in group II patients. In both groups, there were no significant changes in the degree of intestinal metaplasia or atrophy. There were four patients with intestinal metaplasia, and one with atrophy. CONCLUSIONS: There is a dramatic improvement in the degree of inflammation and activity scores in the gastric cardia of patients with successful H. pylori eradication compared to those with persistent infection. By fulfilling one of Koch's postulates (i.e., improvement in the disease after cure of the possible etiological organism), these data support H. pylori as being the etiological agent for carditis in this group of patients.

Homocysteine elevation in sickle cell disease.

OBJECTIVE: Ischemic complications are common in patients with sickle cell disease. Hyperhomocysteinemia is a risk factor for arteriosclerosis and venous thrombosis, and given the propensity of patients with sickle cell disease to develop ischemic complications, we hypothesized that they might have elevated plasma homocysteine concentrations. METHODS: Plasma concentrations of homocysteine, vitamin B12 and folate were measured in 49 adults with sickle cell disease and 16 normotensive Black controls. All subjects with sickle cell disease had been prescribed folic acid 1 mg by mouth daily. RESULTS: The median plasma concentration of homocysteine of subjects with sickle cell disease was approximately 1.5-fold higher than that of controls (p=0.0008). This difference persisted, even when subjects with renal insufficiency were excluded. Plasma folate levels were 1.5-fold higher in subjects with sickle cell disease than in controls (p=0.0498). There was no significant difference in plasma vitamin B12 concentrations between the two groups. There was no difference in plasma homocysteine concentrations between transfused and non-transfused sickle cell subjects. CONCLUSIONS: Patients with sickle cell disease have elevated plasma concentrations of homocysteine in spite of elevated plasma folate levels and vitamin B12 concentrations similar to those observed in controls. Based on these data, we hypothesize that the concentration of folate required to normalize plasma homocysteine levels in patients with sickle cell disease may be higher than that of normal controls and that patients with sickle cell disease have a higher nutritional requirement for folic acid than the general population.

Short-term breast cancer prediction by random periareolar fine-needle aspiration cytology and the Gail risk model.

BACKGROUND: : Biomarkers are needed to refine short-term breast cancer risk estimates from epidemiologic models and to measure response to prevention interventions. The purpose of our study was to determine whether the cytologic appearance of epithelial cells obtained from breast random periareolar fine-needle aspirates or molecular marker expression in these cells was associated with later breast cancer development. METHODS: : Four hundred eighty women who were eligible on the basis of a family history of breast cancer, prior precancerous biopsy, and/or prior invasive cancer were enrolled in a single-institution, prospective trial. Their risk of breast cancer according to the Gail model was calculated, and random periareolar fine-needle aspiration was performed at study entry. Cells were characterized morphologically and analyzed for DNA aneuploidy by image analysis and for the expression of epidermal growth factor receptor, estrogen receptor, p53 protein, and HER2/NEU protein by immunocytochemistry. All statistical tests are two-sided. RESULTS: : At a median follow-up time of 45 months after initial aspiration, 20 women have developed breast cancer (invasive disease in 13 and ductal carcinoma in situ in seven). With the use of multiple logistic regression and Cox proportional hazards analysis, subsequent cancer was predicted by evidence of hyperplasia with atypia in the initial fine-needle aspirate and a 10-year Gail projected probability of developing breast cancer. Although expression of epidermal growth factor receptor, estrogen receptor, p53, and HER2/NEU was statistically significantly associated with hyperplasia with atypia, it did not predict the development of breast cancer in multivariable analysis. CONCLUSION: : Cytomorphology from breast random periareolar fine-needle aspirates can be used with the Gail risk model to identify a cohort of women at very high short-term risk for developing breast cancer. We recommend that cytomorphology be studied for use as a potential surrogate end point in prevention trials.

Prevalence and correlates of preventive care among adults with diabetes in Kansas.

OBJECTIVE: To assess the prevalence and correlates of recommended preventive care among adults with diabetes in Kansas. RESEARCH DESIGN AND METHODS: A cross-sectional telephone survey was conducted among a sample of adults (> or = 18 years of age) with self-reported diabetes. Recommended preventive care was defined based on four criteria: number of health-care provider (HCP) visits per year (> or = 4 for insulin users and > or = 2 for nonusers), number of foot examinations per year (> or = 4 for insulin users and > or = 2 for nonusers), an annual dilated eye examination, and a blood pressure measurement in the past 6 months. RESULTS: The mean age of the 640 respondents was 61 years, 58% were women, and 86% were white. In the preceding year, 62% of respondents reported the appropriate number of visits to a HCP 27% the appropriate number of foot examinations, 65% an annual dilated eye examination, and 89% a blood pressure measurement in the preceding 6 months. Only 17% (95% CI 14-20) met all four criteria for recommended care. The adjusted odds of receiving recommended care were higher for males than for females (odds ratio [OR] 1.6; 95% CI 1.1-2.5), higher for people whose HCP scheduled follow-up appointments than for those who self-initiated follow-up (OR 2.7; 95% CI 1.6-4.8), and higher for former smokers than for current smokers (OR 3.1; 95% CI 1.6-6.9). CONCLUSIONS: Preventive care for people with diabetes is not being delivered in compliance with current guidelines, especially for women and current smokers. Scheduling follow-up visits for patients, targeting certain high-risk populations, and developing protocols to improve foot care may be effective in improving care.

Fractionated radiation therapy in combination with adenoviral delivery of the cytosine deaminase gene and 5-fluorocytosine enhances cytotoxic and antitumor effects in human colorectal and cholangiocarcinoma models.

Radiosensitization of human gastrointestinal tumors by 5-fluorouracil (5-FU) has been studied in vitro and clinically in human cancer therapy trials. The bacterial enzyme cytosine deaminase (CD) converts the nontoxic prodrug 5-fluorocytosine (5-FC) into 5-FU. Human colon cancer cells stably expressing CD have been shown by other investigators to be sensitized to radiation following treatment with 5-FC. We previously used an adenoviral vector under control of the cytomegalovirus promoter (AdCMVCD) encoding the CD gene in combination with 5-FC and a single fraction of radiation exposure to enhance cytotoxicity to human cholangiocarcinoma cells in vitro and in vivo. The purpose of this study was to determine whether AdCMVCD infection and 5-FC with multiple fraction low-dose radiotherapy results in enhanced cytotoxicity. In the present study, we utilized AdCMVCD and 5-FC with single fraction radiotherapy to demonstrate enhanced cytotoxicity to WiDr human colon carcinoma cells in vitro. Additionally, we tested this gene therapy/prodrug treatment strategy employing a fractionated radiation dosing schema in animal models of WiDr colon carcinoma and SK-ChA-1 cholangiocarcinoma. A prolonged WiDr tumor regrowth delay was obtained with AdCMVCD infection in combination with systemic delivery of 5-FC and fractionated external beam radiation therapy compared with control animals treated without radiation, without 5-FC, or without AdCMVCD. The results of treatment with AdCMVCD + 5-FC + radiation therapy to cholangiocarcinoma xenografts were equivalent to those obtained with systemic 5-FU administration + radiation. Thus, the use of AdCMVCD can be effectively combined with clinically relevant 5-FC and radiation administration schemes to achieve enhanced tumor cell killing and increased control of established tumors of human gastrointestinal malignancies.

A robust summarize-regress procedure for tissue-specific pharmacokinetics.

The destructive sampling necessary to obtain tissue-specific pharmacokinetics of radiolabeled ligands does not permit true time-dependent models to be estimated. To adjust for this, small groups of animals are sacrificed at varying time points and the percent injected dose per gram (PID) of radiolabeled ligands is summarized for each tissue of interest. Usually the average PID at each time point is modeled to obtain estimates of pharmacokinetic parameters for each tissue when utilizing summarize-regress procedures. In this paper, it is recommended that the median should be the summary measure at each time point to be modeled in these circumstances. The discrepancy that exists between modeling the average and median PID is demonstrated by an actual experiment. Finally, simulation studies are performed and the results are compared when using these two summary measures.