Serum fatty acids and progression from dengue fever to dengue haemorrhagic fever/dengue shock syndrome.

PUFA might modulate inflammatory responses involved in the development of severe dengue. We aimed to examine whether serum PUFA concentrations in patients diagnosed with dengue fever (DF) were related to the risk of progression to dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS). A secondary aim was to assess correlations between fatty acids (FA) and inflammatory biomarkers in patients with DF. We conducted a prospective case-control study nested within a cohort of patients who were diagnosed with DF and followed during the acute episode. We compared the distribution of individual FA (% of total FA) at onset of fever between 109 cases who progressed to DHF/DSS and 235 DF non-progressing controls using unconditional logistic regression. We estimated correlations between baseline FA and cytokine concentrations and compared FA concentrations between the acute episode and >1 year post-convalescence in a subgroup. DHA was positively related to progression to DHF/DSS (multivariable adjusted OR (AOR) for DHA in quintile 5 v. 1=5·34, 95 % CI 2·03, 14·1; P trend=0·007). Dihomo-γ-linolenic acid (DGLA) was inversely associated with progression (AOR for quintile 5 v. 1=0·30, 95 % CI 0·13, 0·69; P trend=0·007). Pentadecanoic acid concentrations were inversely related to DHF/DSS. Correlations of PUFA with cytokines at baseline were low. PUFA were lower during the acute episode than in a disease-free period. In conclusion, serum DHA in patients with DF predicts higher odds of progression to DHF/DSS whereas DGLA and pentadecanoic acid predict lower odds.

An assessment of public health surveillance of Zika virus infection and potentially associated outcomes in Latin America.

BACKGROUND: We evaluated whether outbreaks of Zika virus (ZIKV) infection, newborn microcephaly, and Guillain-Barré syndrome (GBS) in Latin America may be detected through current surveillance systems, and how cases detected through surveillance may increase health care burden. METHODS: We estimated the sensitivity and specificity of surveillance case definitions using published data. We assumed a 10% ZIKV infection risk during a non-outbreak period and hypothetical increases in risk during an outbreak period. We used sensitivity and specificity estimates to correct for non-differential misclassification, and calculated a misclassification-corrected relative risk comparing both periods. To identify the smallest hypothetical increase in risk resulting in a detectable outbreak we compared the misclassification-corrected relative risk to the relative risk corresponding to the upper limit of the endemic channel (mean + 2 SD). We also estimated the proportion of false positive cases detected during the outbreak. We followed the same approach for microcephaly and GBS, but assumed the risk of ZIKV infection doubled during the outbreak, and ZIKV infection increased the risk of both diseases. RESULTS: ZIKV infection outbreaks were not detectable through non-serological surveillance. Outbreaks were detectable through serologic surveillance if infection risk increased by at least 10%, but more than 50% of all cases were false positive. Outbreaks of severe microcephaly were detected if ZIKV infection increased prevalence of this condition by at least 24.0 times. When ZIKV infection did not increase the prevalence of severe microcephaly, 34.7 to 82.5% of all cases were false positive, depending on diagnostic accuracy. GBS outbreaks were detected if ZIKV infection increased the GBS risk by at least seven times. For optimal GBS diagnosis accuracy, the proportion of false positive cases ranged from 29 to 54% and from 45 to 56% depending on the incidence of GBS mimics. CONCLUSIONS: Current surveillance systems have a low probability of detecting outbreaks of ZIKV infection, severe microcephaly, and GBS, and could result in significant increases in health care burden, due to the detection of large numbers of false positive cases. In view of these limitations, Latin American countries should consider alternative options for surveillance.

Early warning signal for dengue outbreaks and identification of high risk areas for dengue fever in Colombia using climate and non-climate datasets.

BACKGROUND: Dengue has been prevalent in Colombia with high risk of outbreaks in various locations. While the prediction of dengue epidemics will bring significant benefits to the society, accurate forecasts have been a challenge. Given competing health demands in Colombia, it is critical to consider the effective use of the limited healthcare resources by identifying high risk areas for dengue fever. METHODS: The Climate Risk Factor (CRF) index was constructed based upon temperature, precipitation, and humidity. Considering the conditions necessary for vector survival and transmission behavior, elevation and population density were taken into account. An Early Warning Signal (EWS) model was developed by estimating the elasticity of the climate risk factor function to detect dengue epidemics. The climate risk factor index was further estimated at the smaller geographical unit (5 km by 5 km resolution) to identify populations at high risk. RESULTS: From January 2007 to December 2015, the Early Warning Signal model successfully detected 75% of the total number of outbreaks 1 ~ 5 months ahead of time, 12.5% in the same month, and missed 12.5% of all outbreaks. The climate risk factors showed that populations at high risk are concentrated in the Western part of Colombia where more suitable climate conditions for vector mosquitoes and the high population level were observed compared to the East. CONCLUSIONS: This study concludes that it is possible to detect dengue outbreaks ahead of time and identify populations at high risk for various disease prevention activities based upon observed climate and non-climate information. The study outcomes can be used to minimize potential societal losses by prioritizing limited healthcare services and resources, as well as by conducting vector control activities prior to experiencing epidemics.

The trajectory of IGF-1 across age and duration of type 1 diabetes.

BACKGROUND: Individuals with type 1 diabetes may have low IGF-1, related to insulinopenia and insulin resistance. There are few longitudinal studies of IGF-1 levels to establish its pattern in type 1 diabetes with duration and age, and to examine whether IGF-1 tracks within individuals over time. We examine age and duration trends, and the relationship of IGF-1 to gender, glycaemic control, insulin level and other factors. METHODS: Participants in the Wisconsin Diabetes Registry Study, an incident cohort study of type 1 diabetes diagnosed May 1987-April 1992, were followed for up to 18 years with IGF-1 samples up to age 45 for women and age 37 for men. RESULTS: IGF-1 is lower with type 1 diabetes than in normative samples. Although, the pattern across age resembles that in normative samples with a peak in adolescence and slow decline after age 20, the adolescent peak is delayed for women with type 1 diabetes. There was low to moderate tracking of IGF-1 within an individual. Higher insulin dose was associated with higher IGF-1 as was puberty, and female gender. Adjusted for these factors, IGF-1 declined rapidly across early diabetes duration. Lower HbA1c was most strongly related to higher IGF-1 at Tanner stages 1 and 2. CONCLUSIONS: IGF-1 is low in type 1 diabetes, with a delayed adolescent peak in women and is especially influenced by glycaemic control in early and pre-adolescence. High variability within an individual is likely a challenge in investigating associations between IGF-1 and long-term outcomes, and may explain contradictory findings.

Impact of hydrocolloid dressings in the prevention of pressure ulcers in high-risk patients: a randomized controlled trial (PENFUP).

It is uncertain whether hydrocolloid dressings, a more costly intervention than offering standard care with petrolatum, is superior to prevent pressure ulcers among hospitalized high-risk adults. Randomized, parallel-group, open-label, superiority trial with an active control group, blinded for investigators, event validators, and analysts (December 1, 2015 to December 12, 2017). Eligible patients were ≥ 18 years of age with intact skin judged as high-risk for skin ulcers (Braden scale), admitted to surgical or medical wards of two tertiary-level hospitals. Participants were randomized (1:1) to protection with hydrocolloid dressings or petrolatum. The primary outcome was the first occurrence of pressure ulcers (with post-injury photographs adjudicated by three judges) under intention-to-treat analysis. Based on prior cost analysis, and the available resources (assumed incidence of 6 ulcers/1000 patient-days in controls), inclusion of up to 1500 participants allowed to surpass a one-sided superiority threshold > 5% based on a target efficacy > 40% for dressings. We planned an economic analysis using a decision tree model based on the effectiveness of the study results from a perspective of the third payer of health care. After inclusion of 689 patients (69 events), the trial was stopped for futility after a planned interim analysis (conditional power < 0.1 for all scenarios if the trial was completed). Pressure ulcers had occurred in 34 (10.2%) patients in the intervention group [9.6 per 1000 patient-days] and 35 (9.9%) participants in the control group [7.9 per 1000 patient-days], HR = 1.07 [95% CI 0.67 to 1.71]. The estimated incremental cost for dressings (a dominated strategy) was USD 52.11 per patient. Using hydrocolloid dressings was found similar to petrolatum for preventing pressure ulcers among hospitalized high-risk patients. As it conveys additional costs, and in this study was unlikely to demonstrate enough superiority, this strategy did not overcome conventional skin care.Trial registration: ClinicalTrials.gov identifier (NCT number): NCT02565745 registered on December 1, 2015.

Dietary Patterns and Anti-Flavivirus IgG Seroconversion in Colombian Children.

The burden of flaviviral infections, especially dengue and Zika, is high in the Americas. Malnutrition affects the risk and response to infections, but the role of diet on flaviviral infection risk is uncertain. The objective of this study was to investigate the relations between dietary patterns adherence and anti-flavivirus IgG seroconversion in children during a Zika epidemic in a dengue-endemic area of Colombia. In 2015-2016, we followed 424 anti-flavivirus IgG seronegative children aged 2 to 12 years for 1 year. Baseline data included children's sociodemographic, anthropometric, and dietary information collected through a 38-item food frequency questionnaire (FFQ). IgG testing was repeated at the end of follow-up. The primary exposure was adherence to each of four dietary patterns (animal foods, traditional, ultraprocessed foods, and prudent) that were identified from the FFQ through principal component analysis. Secondary exposures were intake frequencies of foods contributing to relevant patterns. We estimated risk of seroconversion by quartiles of adherence scores and compared them using relative risks (RR) and 95% CI from Poisson regression adjusted for sex, age, and socioeconomic status indicators. Seroconversion risk was 32.1%. Adherence to the traditional pattern was positively related to seroconversion. RR comparing fourth versus first quartiles of adherence was 1.52 (95% CI: 1.04-2.21; P trend = 0.02). Of the most representative foods in this pattern, potato and sugarcane water intake frequencies were related to increased seroconversion risk. In conclusion, adherence to a traditional foods pattern, including potatoes and sugarcane water, was positively associated with anti-flavivirus IgG seroconversion.

Using Data-Driven Machine Learning to Predict Unplanned ICU Transfers with Critical Deterioration from Electronic Health Records.

OBJECTIVE: We aimed to develop a data-driven machine learning model for predicting critical deterioration events from routinely collected EHR data in hospitalized children. MATERIALS: This retrospective cohort study included all pediatric inpatients hospitalized on a medical or surgical ward between 2014-2018 at a quaternary children's hospital. METHODS: We developed a large data-driven approach and evaluated three machine learning models to predict pediatric critical deterioration events. We evaluated the models using a nested, stratified 10-fold cross-validation. The evaluation metrics included C-statistic, sensitivity, and positive predictive value. We also compared the machine learning models with patients identified as high-risk Watchers by bedside clinicians. RESULTS: The study included 57,233 inpatient admissions from 34,976 unique patients. 3,943 variables were identified from the EHR data. The XGBoost model performed best (C-statistic=0.951, CI: 0.946 ∼ 0.956). CONCLUSIONS: Our data-driven machine learning models accurately predicted patient deterioration. Future sociotechnical analysis will inform deployment within the clinical setting.

Clinical Indicators of Fatal Dengue in Two Endemic Areas of Colombia: A Hospital-Based Case-Control Study.

According to the World Health Organization, 98% of fatal dengue cases can be prevented; however, endemic countries such as Colombia have recorded higher case fatality rates during recent epidemics. We aimed to identify the predictors of mortality that allow risk stratification and timely intervention in patients with dengue. We conducted a hospital-based, case-control (1:2) study in two endemic areas of Colombia (2009-2015). Fatal cases were defined as having either 1) positive serological test (IgM or NS1), 2) positive virological test (RT-PCR or viral isolation), or 3) autopsy findings compatible with death from dengue. Controls (matched by state and year) were hospitalized nonfatal patients and had a positive serological or virological dengue test. Exposure data were extracted from medical records by trained staff. We used conditional logistic regression (adjusting for age, gender, disease's duration, and health-care provider) in the context of multiple imputation to estimate exposure to case-control associations. We evaluated 110 cases and 217 controls (mean age: 35.0 versus 18.9; disease's duration pre-admission: 4.9 versus 5.0 days). In multivariable analysis, retro-ocular pain (odds ratios [OR] = 0.23), nausea (OR = 0.29), and diarrhea (OR = 0.19) were less prevalent among fatal than nonfatal cases, whereas increased age (OR = 2.46 per 10 years), respiratory distress (OR = 16.3), impaired consciousness (OR = 15.9), jaundice (OR = 32.2), and increased heart rate (OR = 2.01 per 10 beats per minute) increased the likelihood of death (AUC: 0.97, 95% confidence interval: 0.96, 0.99). These results provide evidence that features of severe dengue are associated with higher mortality, which strengthens the recommendations related to triaging patients in dengue-endemic areas.

Lipid profile, plasma apolipoproteins, and pre-eclampsia risk in the GenPE case-control study.

BACKGROUND AND AIMS: Pre-eclampsia constitutes a leading cause of maternal and perinatal morbidity and mortality. Pre-eclampsia susceptibility is believed to be associated with altered lipid profiles and abnormal lipid metabolism via lipid peroxidation that leads to endothelial dysfunction. The goal of this study was to evaluate the association of maternal blood lipid and apolipoprotein levels with pre-eclampsia in a large-scale study. METHODS: Using data from a large case-control study (1366 cases of pre-eclampsia and 1741 normotensive controls), the association between the distributions of eight lipid fractions and pre-eclampsia risk was evaluated using adjusted logistic regression models. Pre-eclampsia was defined as blood pressure ≥140/90 mmHg and proteinuria ≥300 mg/24 h (>1 + dipstick). Sub-group analyses were conducted for early (<34 weeks) and late (≥37 weeks) pre-eclampsia, estimating the effect of 1 standard deviation increase in log-transformed lipid fraction levels in adjusted multinomial regression models. RESULTS: After adjustment for potential confounders, concentrations of triglycerides, apolipoprotein E (ApoE) and the relationship between apolipoprotein B and A1 (ApoB/ApoA1) showed the strongest associations with pre-eclampsia, particularly for those cases with an early onset. CONCLUSIONS: Higher levels of triglycerides, ApoE and the ApoB/ApoA1 ratio are associated with an increased risk of pre-eclampsia. Further studies that allow for a causal inference are needed to confirm or refute the aetiological role of blood lipids in pre-eclampsia.

Vitamin D deficiency and pre-eclampsia in Colombia: PREVitD study.

PURPOSE: Pre-eclampsia is a multisystem disorder characterized by new-onset hypertension and proteinuria during pregnancy. Pre-eclampsia remains a major cause of maternal death in low-income countries. Vitamin D has a very diverse biological role in cardiovascular diseases. This study will evaluate the association of vitamin D levels and relevance to pre-eclampsia. METHODS: We conducted a case-control study of women recruited from the GenPE (Genetics and Pre-eclampsia) Colombian registry. This is a multicenter case-control study conducted in eight Colombian cities. 25-Hydroxyvitamin D (25(OH)D) concentration was measured using liquid-chromatography-tandem mass spectrometry from 1013 women with pre-eclampsia and 1015 mothers without pre-eclampsia (controls). RESULTS: Fifty-two percent of women with pre-eclampsia were vitamin D deficient. The 25(OH)D concentrations were significantly lower in the pre-eclampsia (mean 29.99 ng/mL; 95% CI: 29.40-30.58 ng/mL) group compared to controls (mean 33.7 ng/mL; 95% CI: 33.20-34.30 ng/mL). In the unadjusted model, maternal vitamin D deficiency, defined by maternal 25(OH)D concentration <30 ng/mL, was associated with an increased probability of suffering from pre-eclampsia (OR 2.10; 95% CI, 1.75-2.51). After adjusting for covariates, a similarly increased probability of having pre-eclampsia was observed (OR 2.18; 95% CI, 1.80-2.64) among women with vitamin D deficiency, relative to controls. CONCLUSION: Although the results suggest that low maternal concentrations of 25(OH)D increase pre-eclampsia risk, this evidence may not be indicative of a causal association. Future studies are needed to confirm a definite causal relationship between concentrations of vitamin D and the risk of pre-eclampsia, by means of powered clinical trials.

Temporal variation of Trypanosoma cruzi discrete typing units in asymptomatic Chagas disease patients.

Chagas disease caused by Trypanosoma cruzi is a public health problem in Latin America. This parasite displays a high genetic diversity evidenced in six Discrete Typing Units (DTUs) namely TcI-TcVI. The aim of this study was to observe the temporal variation of the DTUs in asymptomatic patients at three different times (10 days interval). The results showed that intermittence is the rule in the bloodstream of Chagas disease patients. The patients showed different detectable DTUs with short time intervals, which favors the clonal histiotropic model and the multiclonality structure of this parasite.

A 'polypill' aimed at preventing cardiovascular disease could prove highly cost-effective for use in Latin America.

We evaluated the cost-effectiveness of administering a daily "polypill" consisting of three antihypertensive drugs, a statin, and aspirin to prevent cardiovascular disease among high-risk patients in Latin America. We found that the lifetime risk of cardiovascular disease could be reduced by 15 percent in women and by 21 percent in men if the polypill were used by people with a risk of cardiovascular disease equal to or greater than 15 percent over ten years. Attaining this goal would require treating 26 percent of the population at a cost of $34-$36 per quality-adjusted life-year. Offering the polypill to women at high risk and to men age fifty-five or older would be the best approach and would yield acceptable incremental cost-effectiveness ratios. The polypill would be very cost-effective even in the country with the lowest gross national income in our study. However, policy makers must weigh the value of intervention with the polypill against other interventions, as well as their country's willingness and ability to pay for the intervention.

Major cardiovascular risk factors in Latin America: a comparison with the United States. The Latin American Consortium of Studies in Obesity (LASO).

BACKGROUND: Limited knowledge on the prevalence and distribution of risk factors impairs the planning and implementation of cardiovascular prevention programs in the Latin American and Caribbean (LAC) region. METHODS AND FINDINGS: Prevalence of hypertension, diabetes mellitus, abnormal lipoprotein levels, obesity, and smoking were estimated from individual-level patient data pooled from population-based surveys (1998-2007, n=31,009) from eight LAC countries and from a national survey of the United States (US) population (1999-2004) Age and gender specific prevalence were estimated and age-gender adjusted comparisons between both populations were conducted. Prevalence of diabetes mellitus, hypertension, and low high-density lipoprotein (HDL)-cholesterol in LAC were 5% (95% confidence interval [95% CI]: 3.4, 7.9), 20.2% (95% CI: 12.5, 31), and 53.3% (95% CI: 47, 63.4), respectively. Compared to LAC region's average, the prevalence of each risk factor tended to be lower in Peru and higher in Chile. LAC women had higher prevalence of obesity and low HDL-cholesterol than men. Obesity, hypercholesterolemia, and hypertriglyceridemia were more prevalent in the US population than in LAC population (31 vs. 16.1%, 16.8 vs. 8.9%, and 36.2 vs. 26.5%, respectively). However, the prevalence of low HDL-cholesterol was higher in LAC than in the US (53.3 vs. 33.7%). CONCLUSIONS: Major cardiovascular risk factors are highly prevalent in LAC region, in particular low HDL-cholesterol. In addition, marked differences do exist in this prevalence profile between LAC and the US. The observed patterns of obesity-related risk factors and their current and future impact on the burden of cardiovascular diseases remain to be explained.