Modelling study of the ability to diagnose acute rheumatic fever at different levels of the Ugandan healthcare system.

OBJECTIVE: To determine the ability to accurately diagnose acute rheumatic fever (ARF) given the resources available at three levels of the Ugandan healthcare system. METHODS: Using data obtained from a large epidemiological database on ARF conducted in three districts of Uganda, we selected variables that might positively or negatively predict rheumatic fever based on diagnostic capacity at three levels/tiers of the Ugandan healthcare system. Variables were put into three statistical models that were built sequentially. Multiple logistic regression was used to estimate ORs and 95% CI of predictors of ARF. Performance of the models was determined using Akaike information criterion, adjusted R2, concordance C statistic, Brier score and adequacy index. RESULTS: A model with clinical predictor variables available at a lower-level health centre (tier 1) predicted ARF with an optimism corrected area under the curve (AUC) (c-statistic) of 0.69. Adding tests available at the district level (tier 2, ECG, complete blood count and malaria testing) increased the AUC to 0.76. A model that additionally included diagnostic tests available at the national referral hospital (tier 3, echocardiography, anti-streptolysin O titres, erythrocyte sedimentation rate/C-reactive protein) had the best performance with an AUC of 0.91. CONCLUSIONS: Reducing the burden of rheumatic heart disease in low and middle-income countries requires overcoming challenges of ARF diagnosis. Ensuring that possible cases can be evaluated using electrocardiography and relatively simple blood tests will improve diagnostic accuracy somewhat, but access to echocardiography and tests to confirm recent streptococcal infection will have the greatest impact

Genome-Wide Diet-Gene Interaction Analyses for Risk of Colorectal Cancer

Dietary factors, including meat, fruits, vegetables and fiber, are associated with colorectal cancer; however, there is limited information as to whether these dietary factors interact with genetic variants to modify risk of colorectal cancer. We tested interactions between these dietary factors and approximately 2.7 million genetic variants for colorectal cancer risk among 9,287 cases and 9,117 controls from ten studies. We used logistic regression to investigate multiplicative gene-diet interactions, as well as our recently developed Cocktail method that involves a screening step based on marginal associations and gene-diet correlations and a testing step for multiplicative interactions, while correcting for multiple testing using weighted hypothesis testing. Per quartile increment in the intake of red and processed meat were associated with statistically significant increased risks of colorectal cancer and vegetable, fruit and fiber intake with lower risks. From the case-control analysis, we detected a significant interaction between rs4143094 (10p14/near GATA3) and processed meat consumption (OR = 1.17; p = 8.7E-09), which was consistently observed across studies (p heterogeneity = 0.78). The risk of colorectal cancer associated with processed meat was increased among individuals with the rs4143094-TG and -TT genotypes (OR = 1.20 and OR = 1.39, respectively) and null among those with the GG genotype (OR = 1.03). Our results identify a novel gene-diet interaction with processed meat for colorectal cancer, highlighting that diet may modify the effect of genetic variants on disease risk, which may have important implications for prevention. © 2014

Childhood Exposure to Traffic-Related Air Pollution and the Lower Respiratory Tract Microbiome

This presentation was given at the ISESISIAQ 2019 – Joint Meeting of the International Society of Exposure Science and the International Society of Indoor Air and Climate

Among 4 diet quality indexes, only the alternate mediterranean diet score is associated with better colorectal cancer survival and only in African American women in the multiethnic Cohort

Background: Colorectal cancer (CRC) is the second leading cause of cancer-related death in the United States, with a 5-y survival rate of ~65%. Therefore, the identification of modifiable health factors to improve CRC survival is crucial. Objective: We investigated the association of 4 prediagnostic a priori diet quality indexes with CRC-specific and all-cause mortality in the Multiethnic Cohort (MEC). Methods: The MEC included >215,000 African-American, Native Hawaiian, Japanese-American, Latino, and white adults living in Hawaii and California who completed a validated quantitative food-frequency questionnaire in 1993-1996. CRC cases and deaths were identified through linkages to cancer registries and to state and national vital registries. Sexspecific HRs and 95% CIs were estimated for the Healthy Eating Index (HEI) 2010, the Alternative HEI (AHEI) 2010, the alternate Mediterranean Diet (aMED) score, and the Dietary Approaches to Stop Hypertension (DASH) index with CRC-specific and overall mortality as the primary outcomes. Ethnicity-specific analyses were the secondary outcomes. Results: Among 4204 MEC participants diagnosed with invasive CRC through 2010, 1976 all-cause and 1095 CRC-specific deaths were identified. A higher aMED score was associated with lower CRC-specific mortality in women [HR continuous pattern score divided by its respective SD (HR1SD): 0.86; 95% CI: 0.77, 0.96] but not in men (HR1SD: 1.01; 95% CI: 0.92, 1.11). A higher aMED score was also associated with lower all-cause mortality in women (HR1SD: 0.88; 95% CI: 0.81, 0.96) but not in men (HR1SD: 1.00; 95% CI: 0.93, 1.07). The HEI-2010, AHEI-2010, and DASH index were not significantly associated with CRC-specific or with all-cause mortality. The inverse relation for the aMED score was limited to African Americans and to colon (compared with rectal) cancer. Conclusions: The aMED score was related to lower mortality only in African-American women (1 of 5 ethnic groups studied). The results should be interpreted with caution due to the small numbers of cases within ethnic groups and the issue of multiple testing

Prediagnostic circulating carotenoid levels and the risk of non-Hodgkin lymphoma: the Multiethnic Cohort.

This analysis examined the association of non-Hodgkin lymphoma (NHL) with prediagnostic carotenoid levels, a marker for a diet rich in fruits and vegetables. We conducted a nested case-control study within the Multiethnic Cohort with 271 NHL cases and 538 controls matched on sex, ethnicity, location (Hawaii or Los Angeles), birth year, date and time of blood draw, and hours fasting before blood draw. Serum carotenoid levels were obtained by high-pressure liquid chromatography with photodiode array detection. Conditional logistic regression was used to calculate odds ratios (ORs) according to tertiles of serum carotenoids and trend tests using continuous variables. Higher total serum carotenoids (OR(T3 vs T1) = 0.66 [0.46-0.96]; P(trend) = .02), lycopene (OR = 0.54 [0.38-0.78]; P(trend) = .003), and α-cryptoxanthin (OR = 0.53 [0.36-0.78]; P(trend) = .003) were associated with a lower risk of NHL. For retinol (OR = 0.90 [0.61-1.33]; P(trend) = .04), a statistically significant inverse linear trend was detected. Risk estimates remained unchanged with adjustment for NHL risk factors and were similar in analyses stratified by sex and ethnicity; heterogeneity with NHL subtype was detected only for β-carotene. Other carotenoids, including α-carotene, β-carotene, lutein, β-cryptoxanthin, and zeaxanthin, showed no association with risk. These data provide support for a protective role of carotenoid-rich fruits and vegetables in the etiology of NHL