Diffuse white matter loss in a transgenic rat model of cerebral amyloid angiopathy.

Diffuse white matter (WM) disease is highly prevalent in elderly with cerebral small vessel disease (cSVD). In humans, cSVD such as cerebral amyloid angiopathy (CAA) often coexists with Alzheimer's disease imposing a significant impediment for characterizing their distinct effects on WM. Here we studied the burden of age-related CAA pathology on WM disease in a novel transgenic rat model of CAA type 1 (rTg-DI). A cohort of rTg-DI and wild-type rats was scanned longitudinally using MRI for characterization of morphometry, cerebral microbleeds (CMB) and WM integrity. In rTg-DI rats, a distinct pattern of WM loss was observed at 9 M and 11 M. MRI also revealed manifestation of small CMB in thalamus at 6 M, which preceded WM loss and progressively enlarged until the moribund disease stage. Histology revealed myelin loss in the corpus callosum and thalamic CMB in all rTg-DI rats, the latter of which manifested in close proximity to occluded and calcified microvessels. The quantitation of CAA load in rTg-DI rats revealed that the most extensive microvascular Aß deposition occurred in the thalamus. For the first time using in vivo MRI, we show that CAA type 1 pathology alone is associated with a distinct pattern of WM loss.

Low Omega-3 intake is associated with high rates of depression and preterm birth on the country level.

Low circulating levels of long chain omega-3 polyunsaturated fatty acids (LC omega-3 PUFA) have been linked to major depressive disorder (MDD) and preterm birth (PTB), and prenatal depression associates with PTB. We therefore hypothesized that low Omega-3 intake would associate with higher MDD and PTB rates on the country-level. To test this hypothesis, we obtained country-level estimates for omega-3 intake, MDD prevalence, PTB rate, and per capita income for 184 countries in 2010. We then estimated the LC omega-3 PUFA levels that these intakes produce by accounting for direct consumption and the endogenous conversion of ingested plant-based precursors. Penalized splines indicated that MDD and PTB rates decreased linearly with increasing LC omega-3 PUFA, up to ~ 1000 mg/day for MDD and up to ~ 550 mg/day for PTB. Adjusted linear regression models below these thresholds revealed that a one standard deviation increase in LC omega-3 PUFA (380 mg/day) was associated with an MDD decrease of 5 cases/1000 people and a PTB decrease of 15 cases/1000 livebirths. In light of the extensive prior evidence on the individual-level, these findings indicate that low intake of LC omega-3 PUFA and its precursors may be elevating MDD and PTB rates in 85% of the countries studied.

Estimating the potential impact of behavioral public health interventions nationally while maintaining agreement with global patterns on relative risks.

OBJECTIVE: This paper introduces a novel method to evaluate the local impact of behavioral scenarios on disease prevalence and burden with representative individual level data while ensuring that the model is in agreement with the qualitative patterns of global relative risk (RR) estimates. The method is used to estimate the impact of behavioral scenarios on the burden of disease due to ischemic heart disease (IHD) and diabetes in the Turkish adult population. METHODS: Disease specific Hierarchical Bayes (HB) models estimate the individual disease probability as a function of behaviors, demographics, socio-economics and other controls, where constraints are specified based on the global RR estimates. The simulator combines the counterfactual disease probability estimates with disability adjusted life year (DALY)-per-prevalent-case estimates and rolls up to the targeted population level, thus reflecting the local joint distribution of exposures. The Global Burden of Disease (GBD) 2016 study meta-analysis results guide the analysis of the Turkish National Health Surveys (2008 to 2016) that contain more than 90 thousand observations. FINDINGS: The proposed Qualitative Informative HB models do not sacrifice predictive accuracy versus benchmarks (logistic regression and HB models with non-informative and numerical informative priors) while agreeing with the global patterns. In the Turkish adult population, Increasing Physical Activity reduces the DALYs substantially for both IHD by 8.6% (6.4% 11.2%), and Diabetes by 8.1% (5.8% 10.6%), (90% uncertainty intervals). Eliminating Smoking and Second-hand Smoke predominantly decreases the IHD burden 13.1% (10.4% 15.8%) versus Diabetes 2.8% (1.1% 4.6%). Increasing Fruit and Vegetable Consumption, on the other hand, reduces IHD DALYs by 4.1% (2.8% 5.4%) while not improving the Diabetes burden 0.1% (0% 0.1%). CONCLUSION: While the national RR estimates are in qualitative agreement with the global patterns, the scenario impact estimates are markedly different than the attributable risk estimates from the GBD analysis and allow evaluation of practical scenarios with multiple behaviors.

Reducing the burden of iron deficiency anemia in Cote D'Ivoire through fortification.

BACKGROUND: Iron deficiency anemia (IDA) is highly prevalent in the Cote d'Ivoire and has severe health and economic consequences. In this paper, we apply a health economic model to quantify the burden of IDA, and the contribution of nationwide mandatory iron fortification of wheat flour and voluntary iron fortification of condiments to the reduction of this burden. METHODS: The analysis for the population from 6 months to 64 years builds on published reviews and publicly available datasets and is stratified by age-groups and socioeconomic strata using comparative risk assessment model. RESULTS: Without the impact of these fortification strategies, the annual burden of IDA is estimated at 242,100 disability adjusted life years (DALYs) and 978.1 million USD. Wheat flour and condiment fortification contributed to a reduction of the IDA burden by approximately 5% each. CONCLUSION: In places with high prevalence of malaria and other infectious diseases, such as the Côte D'Ivoire, food fortification as a nutritional intervention should be accompanied with infectious disease prevention and control. The findings of this study provide additional input for policy makers about the magnitude of the impact and can support the conception of future fortification strategies.

Prevalence and predictors of chronic kidney disease among Ghanaian patients with hypertension and diabetes mellitus: A multicenter cross-sectional study.

The burden of chronic kidney disease (CKD) is rapidly rising in developing countries due to astronomical increases in key risk factors including hypertension and diabetes. We sought to assess the burden and predictors of CKD among Ghanaians with hypertension and/or diabetes mellitus in a multicenter hospital-based study. We conducted a cross-sectional study in the Ghana Access and Affordability Program (GAAP) involving adults with hypertension only (HPT), hypertension with diabetes mellitus (HPT + DM), and diabetes mellitus only (DM) in 5 health facilities in Ghana. A structured questionnaire was administered to collect data on demographic variables, medical history, and clinical examination. Serum creatinine and proteinuria were measured, and estimated glomerular filtration rate derived using the CKD-EPI formula. A multivariable logistic regression model was used to identify factors associated with CKD. A total of 2781 (84.4%) of 3294 participants had serum creatinine and proteinuria data available for analysis. The prevalence of CKD was 242 (28.5%) among participants with both DM and HPT, 417 (26.3%) among participants with HPT, and 56 (16.1%) among those with DM alone. Predictors of CKD were increasing age aOR 1.26 (1.17-1.36), low educational level aOR 1.7 (1.23-2.35), duration of HPT OR, 1.02 (1.01-1.04), and use of herbal medications aOR 1.39 (1.10-1.75). Female gender was protective of CKD aOR 0.75 (0.62-0.92). Among patients with DM, increasing age and systolic blood pressure were associated with CKD. There is high prevalence of CKD among DM and hypertension patients in Ghana. Optimizing blood pressure control and limiting the use of herbal preparations may mitigate CKD occurrence in high cardiovascular risk populations in developing countries.

Trend and projection of mortality rate due to non-communicable diseases in Iran: A modeling study.

BACKGROUND: Following the epidemiologic and demographic transition, non-communicable disease mortality is the leading cause of death in Iran. Projecting mortality trend can provide valuable tools for policy makers and planners. In this article, we have estimated the trend of non-communicable disease mortality during 2001-2015 and have projected it until 2030 at national and subnational levels in Iran. METHODS: The data employed was gathered from the Iranian death registration system and using the Spatio-temporal model, the trends of 4 major categories of non-communicable diseases (cancers, cardiovascular diseases, asthma and COPD, and diabetes) by 2030 were projected at the national and subnational levels. RESULTS: The results indicated that age standardized mortality rate for cancers, CVDs, and Asthma and COPD will continue to decrease in both sexes (cancers: from 81.8 in 2015 to 45.2 in 2030, CVDs: 307.3 to 173.0, and Asthma and COPD: from 52.1 to 46.6); however, in terms of diabetes, there is a steady trend in both sexes at national level (from 16.6 to 16.5). Age standardized mortality rates for cancers and CVDs, in males and females, were high in all provinces in 2001. The variation between the provinces is clearer in 2015, and it is expected to significantly decrease in all provinces by 2030. CONCLUSION: Generally, the age standardized mortality rate from NCDs will decrease by 2030. Of course, given the experience of the past two decades in Iran, believing that the mortality rate will decrease may not be an easy notion to understand. However hard to believe, this decrease may be the result of better management of risk factors and early detection of patients due to more comprehensive care in all segments of society, as well as improved literacy and awareness across the country.