Spatial Cluster Detection for Weighted Outcomes Using Cumulative Geographic Residuals

Spatial cluster detection is an important methodology for identifying regions with excessive numbers of adverse health events without making strong model assumptions on the underlying spatial dependence structure. Previous work has focused on point or individual-level outcome data and few advances have been made when the outcome data are reported at an aggregated level, e.g. at the county- or census tract-level. This paper proposes a new class of spatial cluster detecion methods for point or aggregate data, comprising of continuous, binary, and count data. Compared with the existing spatial cluster detection methods it has the following advantages. First, it readily incorporates region-specific weights, for example, based on a region’s population or a region’s outcome variance, which is key for aggregate data. Second, the established general framework allows for area-level and individual-level covariate adjustment. A simulation study is conducted to evaluate the performance of the method. The proposed method is then applied to assess spatial clustering of high Body Mass Index in a HMO population in the Seattle, Washington USA area

A Randomized, Double-Blind Study of Larazotide Acetate to Prevent the Activation of Celiac Disease During Gluten Challenge

OBJECTIVES: In patients with celiac disease, enteropathy is caused by the entry of gluten peptides into the lamina propria of the intestine, in which their immunogenicity is potentiated by tissue transglutaminase (tTG) and T-helper type 1–mediated immune responses are triggered. Tight junction disassembly and paracellular permeability are believed to have an important role in the transport of gluten peptides to the lamina propria. Larazotide acetate is a tight-junction regulator peptide that, in vitro, prevents the opening of intestinal epithelial tight junctions. The aim of this study was to evaluate the efficacy and tolerability of larazotide acetate in protecting against gluten-induced intestinal permeability and gastrointestinal symptom severity in patients with celiac disease. METHODS: In this dose-ranging, placebo-controlled study, 86 patients with celiac disease controlled through diet were randomly assigned to larazotide acetate (0.25, 1, 4, or 8 mg) or placebo three times per day with or without gluten challenge (2.4 g/day) for 14 days. The primary efficacy outcome was the urinary lactulose/mannitol (LAMA) fractional excretion ratio. Secondary endpoints included gastrointestinal symptom severity, quality-of-life measures, and antibodies to tTG. RESULTS: LAMA measurements were highly variable in the outpatient setting. The increase in LAMA ratio associated with the gluten challenge was not statistically significantly greater than the increase in the gluten-free control. Among patients receiving the gluten challenge, the difference in the LAMA ratios for the larazotide acetate and placebo groups was not statistically significant. However, larazotide acetate appeared to limit gluten-induced worsening of gastrointestinal symptom severity as measured by the Gastrointestinal Symptom Rating Scale at some lower doses but not at the higher dose. Symptoms worsened significantly in the gluten challenge–placebo arm compared with the placebo–placebo arm, suggesting that 2.4 g of gluten per day is sufficient to induce reproducible gluten toxicity. Larazotide acetate was generally well tolerated. No serious adverse events were observed. The most common adverse events were headache and urinary tract infection. CONCLUSIONS: LAMA variability in the outpatient setting precluded accurate assessment of the effect of larazotide acetate on intestinal permeability. However, some lower doses of larazotide acetate appeared to prevent the increase in gastrointestinal symptom severity induced by gluten challenge

Do Health Beliefs and Behaviors Differ According to Severity of Obesity? A Qualitative Study of Australian Adults

Public responses to obesity have focused on providing standardized messages and supports to all obese individuals, but there is limited understanding of the impact of these messages on obese adults. This descriptive qualitative study using in-depth interviews and a thematic method of analysis, compares the health beliefs and behaviors of 141 Australian adults with mild to moderate (BMI 30−39.9) and severe (BMI ≥ 40) obesity. Mildly obese individuals felt little need to change their health behaviors or to lose weight for health reasons. Most believed they could “lose weight” if they needed to, distanced themselves from the word obesity, and stigmatized those “fatter” than themselves. Severely obese individuals felt an urgent need to change their health behaviors, but felt powerless to do so. They blamed themselves for their weight, used stereotypical language to describe their health behaviors, and described being “at war” with their bodies. Further research, particularly about the role of stigma and stereotyping, is needed to fully understand the impact of obesity messaging on the health beliefs, behaviors, and wellbeing of obese and severely obese adults

Microencapsulated foods as a functional delivery vehicle for omega-3 fatty acids: a pilot study

It is well established that the ingestion of the omega-3 (N3) fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) positively benefit a variety of health indices. Despite these benefits the actual intake of fish derived N3 is relatively small in the United States. The primary aim of our study was to examine a technology capable of delivering omega-3 fatty acids in common foods via microencapsulation (MicroN3) in young, healthy, active participants who are at low risk for cardiovascular disease. Accordingly, we randomized 20 participants (25.4 ± 6.2 y; 73.4 ± 5.1 kg) to receive the double blind delivery of a placebo-matched breakfast meal (~2093 kJ) containing MicroN3 (450–550 mg EPA/DHA) during a 2-week pilot trial. Overall, we observed no differences in overall dietary macronutrient intake other than the N3 delivery during our treatment regimen. Post-test ANOVA analysis showed a significant elevation in mean (SE) plasma DHA (91.18 ± 9.3 vs. 125.58 ± 11.3 umol/L; P < 0.05) and a reduction in triacylglycerols (89.89 ± 12.8 vs. 80.78 ± 10.4 mg/dL; P < 0.05) accompanying the MicroN3 treatment that was significantly different from placebo (P < 0.05). In post study interviews, participants reported that the ingested food was well-tolerated, contained no fish taste, odor or gastrointestinal distress accompanying treatment. The use of MicroN3 foods provides a novel delivery system for the delivery of essential fatty acids. Our study demonstrates that MicroN3 foods promote the absorption of essential N3, demonstrate bioactivity within 2 weeks of ingestion and are well tolerated in young, active participants who are at low risk for cardiovascular disease

Fats and Factors: Lipid Profiles Associate with Personality Factors and Suicidal History in Bipolar Subjects

Polyunsaturated fatty acids (PUFA) have shown efficacy in the treatment of bipolar disorder, however their specific role in treating the illness is unclear. Serum PUFA and dietary intakes of PUFA associate with suicidal behavior in epidemiological studies. The objective of this study was to assess serum n-3 and n-6 PUFA levels in bipolar subjects and determine possible associations with suicidal risk, including suicidal history and relevant personality factors that have been associated with suicidality. We studied 27 bipolar subjects using the NEO-PI to assess the big five personality factors, structured interviews to verify diagnosis and assess suicidal history, and lipomics to quantify n-3 and n-6 PUFA in serum. We found positive associations between personality factors and ratios of n-3 PUFA, suggesting that conversion of short chain to long chain n-3s and the activity of enzymes in this pathway may associate with measures of personality. Thus, ratios of docosahexaenoic acid (DHA) to alpha linolenic acid (ALA) and the activity of fatty acid desaturase 2 (FADS2) involved in the conversion of ALA to DHA were positively associated with openness factor scores. Ratios of eicosapentaenoic acid (EPA) to ALA and ratios of EPA to DHA were positively associated with agreeableness factor scores. Finally, serum concentrations of the n-6, arachidonic acid (AA), were significantly lower in subjects with a history of suicide attempt compared to non-attempters. The data suggest that specific lipid profiles, which are controlled by an interaction between diet and genetics, correlate with suicidal history and personality factors related to suicidal risk. This study provides preliminary data for future studies to determine whether manipulation of PUFA profiles (through diet or supplementation) can affect personality measures and disease outcome in bipolar subjects and supports the need for further investigations into individualized specific modulations of lipid profiles to add adjunctive value to treatment paradigms

The development of vegetarian omega-3 oil in water nanoemulsions suitable for integration into functional food products

Global trends show that habitual omega-3 intakes are short of recommended guidelines, particularly among vegetarians and vegans. The potential health implications of low long chain omega-3 polyunsaturated fatty acids (LC3PUFA) intakes coupled with concerns about sustainability of fish stocks call for innovative approaches to provide food based solutions to this problem. Nanoemulsions are systems with extremely small droplet sizes that could provide a solution whilst improving the bioavailability of LC3PUFA. Oil in water nanoemulsion systems were successfully created using ultrasound with oil loads of up to 50 vol % using vegetarian LC3PUFA oils. Nanoemulsions containing 50 vol % flaxseed and algae oil were created with mean droplet size measurements of 192 and 182nm respectively using combinations of the emulsifiers Tween 40 and lecithin. This technique could be applied to create vegetarian LC3PUFA nanoemulsions suitable for integration into enriched functional food products with the potential to increase LC3PUFA intakes and bioavailability

Intravenous mycophenolate mofetil: safety, tolerability, and pharmacokinetics

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72291/1/j.1399-0012.2000.140301.x.pd

Examining the BMI-mortality relationship using fractional polynomials

<p>Abstract</p> <p>Background</p> <p>Many previous studies estimating the relationship between body mass index (BMI) and mortality impose assumptions regarding the functional form for BMI and result in conflicting findings. This study investigated a flexible data driven modelling approach to determine the nonlinear and asymmetric functional form for BMI used to examine the relationship between mortality and obesity. This approach was then compared against other commonly used regression models.</p> <p>Methods</p> <p>This study used data from the National Health Interview Survey, between 1997 and 2000. Respondents were linked to the National Death Index with mortality follow-up through 2005. We estimated 5-year all-cause mortality for adults over age 18 using the logistic regression model adjusting for BMI, age and smoking status. All analyses were stratified by sex. The multivariable fractional polynomials (MFP) procedure was employed to determine the best fitting functional form for BMI and evaluated against the model that includes linear and quadratic terms for BMI and the model that groups BMI into standard weight status categories using a deviance difference test. Estimated BMI-mortality curves across models were then compared graphically.</p> <p>Results</p> <p>The best fitting adjustment model contained the powers -1 and -2 for BMI. The relationship between 5-year mortality and BMI when estimated using the MFP approach exhibited a J-shaped pattern for women and a U-shaped pattern for men. A deviance difference test showed a statistically significant improvement in model fit compared to other BMI functions. We found important differences between the MFP model and other commonly used models with regard to the shape and nadir of the BMI-mortality curve and mortality estimates.</p> <p>Conclusions</p> <p>The MFP approach provides a robust alternative to categorization or conventional linear-quadratic models for BMI, which limit the number of curve shapes. The approach is potentially useful in estimating the relationship between the full spectrum of BMI values and other health outcomes, or costs.</p