Validation of RT-qPCR test for SARS-CoV-2 in saliva specimens.

BACKGROUND: Saliva samples may be an easier, faster, safer, and cost-saving alternative to NPS samples, and can be self-collected by the patient. Whether SARS-CoV-2 RT-qPCR in saliva is more accurate than in nasopharyngeal swaps (NPS) is uncertain. We evaluated the accuracy of the RT-qPCR in both types of samples, assuming both approaches were imperfect. METHODS: We assessed the limit of detection (LoD) of RT-qPCR in each type of sample. We collected paired NPS and saliva samples and tested them using the Berlin Protocol to detect SARS-CoV-2 envelope protein (E). We used a Bayesian latent class analysis (BLCA) to estimate the sensitivity and specificity of each test, while accounting for their conditional dependence. RESULTS: The LoD were 10 copies/mL in saliva and 100 copies/mL in NPS. Paired samples of saliva and NPS were collected in 412 participants. Out of 68 infected cases, 14 were positive only in saliva. RT-qPCR sensitivity ranged from 82.7 % (95 % CrI: 54.8, 94.8) in NPS to 84.5 % (50.9, 96.5) in saliva. Corresponding specificities were 99.1 % (95 % CrI: 95.3, 99.8) and 98.4 %(95 % CrI: 92.8, 99.7). CONCLUSIONS: SARS-CoV-2 RT-qPCR test in saliva specimens has a similar or better accuracy than RT-qPCR test in NPS. Saliva specimens may be ideal for surveillance in general population, particularly in children, and in healthcare or other personnel in need of serial testing.

Zika virus infection and risk of Guillain-Barré syndrome: A meta-analysis.

OBJECTIVE: Findings from studies of the association between Zika virus (ZIKV) infection and Guillain-Barré syndrome (GBS) are inconsistent. I conducted a systematic review and meta-analysis to clarify the nature of this association. METHODS: I searched PubMed, Scopus, Cochrane, CINAHL, Web of Science, Scielo, and DOAJ for case report, ecological, and analytic studies with "Zika" and "Guillain-Barré syndrome" as keywords, published up to July 1stth 2018. I evaluated if ZIKV infection status influenced the diagnosis of GBS (detection bias) in case-report and analytic studies; assessed if changes in weekly number of cases of ZIKV infection during outbreaks were followed by changes in number of GBS cases 1-8 weeks later; gauged the likelihood of selection, confounding, information, sparse data, and time-dependent bias (i.e. when ZIKV infection was ascertained after GBS onset) in analytic studies; and calculated the average ZIKV-GBS odds ratio (OR) in studies without time-dependent bias. RESULTS: In case reports, ZIKV infection prevalence in GBS cases was 2.4 to 25 times higher than expected. Changes in the number of ZIKV-infection cases during outbreaks were not consequentially followed by changes in the number of GBS cases (OR: 1.01; 95% CI: 0.99-1.03). Major biases were likely in all but one analytic study, which showed a non-significant ZIKV-GBS association. The average ZIKV-GBS OR in studies without time-dependent bias was 1.57 (95% CI: 0.86-2.86). INTERPRETATION: These findings indicate the available evidence is insufficient to claim ZIKV infection causes GBS. Therefore, stakeholders may want to reconsider current ZIKV-GBS public health and patient care recommendations.

Inflammation markers and risk of developing hypertension: a meta-analysis of cohort studies.

OBJECTIVE: To systematically assess the association of circulating inflammation markers with the future risk of hypertension. METHODS: We did a systematic literature search of PubMed and Scopus, from database inception to July 10, 2018. Prospective and retrospective cohort studies evaluating the association of circulating C reactive protein (CRP), high-sensitive CRP (hs-CRP), interleukin 6 (IL-6) and IL-1ß to the risk of developing hypertension in the general population were included. The relative risks (RRs) for the top versus bottom tertiles of circulating biomarkers were calculated using a fixed-effects/random-effects model. A potential non-linear dose-response association was tested. RESULTS: Fourteen prospective cohort studies, two retrospective cohort studies and five nested case-control studies involving 142 640 participants and 20 676 cases were identified. The RR for the third versus first tertiles of circulating CRP was 1.23 (95% CI 1.11 to 1.35; I2=59%, n=12). The association remained unchanged after adjustment for body mass index. The RRs for other biomarkers were as follows: hs-CRP (RR 1.20, 95% CI 1.02 to 1.37; I2=74%, n=7), IL-6 (RR 1.51, 95% CI 1.30 to 1.71; I2=0%, n=5), and IL-1ß (RR 1.22, 95% CI 0.92 to 1.51; I2=0%, n=3). A non-linear dose-response meta-analysis demonstrated that the risk of hypertension increased linearly with increasing circulating inflammation markers, even within the low-risk and intermediate-risk categories. CONCLUSIONS: Higher levels of circulating CRP, hs-CRP and IL-6, but not IL-1ß, were associated with the risk of developing hypertension. The association persisted in subgroups of studies defined by major sources of heterogeneity.

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.

Maternal Zika virus infection and newborn microcephaly-an analysis of the epidemiological evidence.

PURPOSE: To evaluate whether existing data and evidence support a causal link between maternal Zika virus (ZIKV) infection and newborn microcephaly. METHODS: I quantified and compared the prevalence of all and severe microcephaly in Brazil, during and before 2015-2016, to assess whether an outbreak has occurred, used time series analysis to evaluate if the presumed outbreak was linked to a previous outbreak of ZIKV infections, and quantitatively synthesized published data from observational studies testing this association. RESULTS: The prevalences of microcephaly in 2015-2016 were similar or lower than background levels (prevalence ratio [PR] for all microcephaly: 0.19; 95% confidence intervals [CI]: 0.17, 0.20). Changes in the number of cases of ZIKV infections at times matching 11-18 weeks of pregnancy were not followed by changes in the number of microcephaly cases (PR for infection at 12 weeks: 1.02; 95% CI: 0.99, 1.05). In observational studies, the prevalence of microcephaly was not significantly increased in newborns of Zika-infected mothers (average PR: 1.30; 95% CI: 0.84, 2.02). CONCLUSIONS: Existing evidence is insufficient to claim maternal ZIKV infection causes microcephaly. Although a public health response seems sensible, it should be consistent with existing knowledge and consider risks, potential benefits and harm, and competing priorities.

Cardiovascular Disease Risk Factors in Hispanic Adolescents in South Texas.

OBJECTIVES: Despite a national crisis of increased prevalence of obesity and type 2 diabetes mellitus in adolescents, especially among Hispanics, there is a paucity of data on health indicators among farmworker adolescents and their peers. The main aim of this study was to estimate the prevalence of cardiovascular disease risk factors in a population of Hispanic adolescent students in south Texas. The study also aimed to compare the prevalence of these risk factors between students enrolled in the Migrant Education Program (MEP) and other students, and between boys and girls. METHODS: In partnership with the Weslaco (Texas) Independent School District and the Migrant Education Department, a cohort study was conducted from 2007 to 2010 to estimate the prevalence of overall obesity (body mass index ≥85th percentile for age and sex), abdominal obesity (waist circumference ≥75th percentile for age, sex, and ethnicity), acanthosis nigricans (AN), and high blood pressure (HBP; ≥90th percentile for age, height, and sex or systolic/diastolic BP ≥120/80 mm Hg) among MEP students compared with other students from two south Texas high schools. Multilevel logistic regression was used to assess the relation between sex and our main outcomes of interest while accounting for within-school nesting of participants. RESULTS: Among 628 sampled students, 508 (80.9%) completed the consent procedure and participated in the study. Of these, 257 were MEP students and 251 were non-MEP peers. Approximately 96.7% of participants were Hispanic and 50.0% were boys. Analyses of data across the years comparing MEP students and non-MEP students show an average prevalence of 44.8% versus 47.7% for overall obesity, 43.2% versus 43.7% for abdominal obesity, 24.7% versus 24.7% for AN, and 29.2% versus 32.8% for HBP. Across recruitment and follow-up years, the prevalence of overall obesity, abdominal obesity, and HBP was 1.3 to 1.5, 1.2 to 1.8, and 2.9 to 4.6 times higher in boys than in girls, respectively. In contrast, the prevalence of AN varied little by sex. CONCLUSIONS: The high prevalence of cardiovascular risk factors in both groups suggests a compelling need for comprehensive, culturally targeted interventions to prevent future cardiovascular diseases in these high-risk Hispanic adolescents, especially among boys. There were not, however, substantial differences between MEP students and other students. These findings also support the feasibility of conducting future epidemiologic studies among adolescent farmworkers and their families, as well as culturally appropriate school or community-based interventions.

Drug Side Effect Symptoms and Adherence to Antihypertensive Medication.

BACKGROUND: Non-adherence to antihypertensive medication increases the risk of uncontrolled hypertension. Antihypertensive drug-related symptoms (side effects) are frequently cited as a main cause of non-adherence, but with little support from prospective studies. We evaluated the association between drug side effects and prospective adherence to treatment. METHODS: We collected data on the number and dose of antihypertensive drugs at enrollment and at 3, 6, 9, and 12 months of follow-up in a cohort of 175 hypertensive patients starting or restarting antihypertensive treatment (mean age: 50 years; 58% women). During the follow-up visits, we gathered data on 24 side effects during the last month and the pill count adherence ratio (PCAR = pills taken out of number prescribed × 100) since the previous visit. The association between side effects at a visit and adherence through the next visit was estimated using mixed effect models. RESULTS: Eighty-five percent of the participants experienced side effects, and 34.5% became non-adherent (PCAR <80%). After adjusting for confounders, PCAR was 6.0 percentage points lower (P = 0.04) among individuals with number of side effects above the median value (4 symptoms). Also, in individuals with genitourinary side effects, PCAR was 7.1 percentage points lower (P = 0.02) than in those without such side effects. Specifically, PCAR was 6.5 (P = 0.06) and 7.6 (P = 0.01) percentage points lower among individuals with excessive urination and decrease in sexual drive, respectively. CONCLUSION: Antihypertensive drug side effects was associated with drug adherence but only excessive urination and decrease in sexual drive significantly predicted lower adherence. These symptoms could be used as markers to screen out patients at high risk of non-adherence.

Environmental and occupational health research and training needs in Colombia: A Delphi study.

INTRODUCTION: Environmental factors contribute with 16% of the burden of disease in Colombia. A main obstacle in implementing national and regional environmental and occupational health policies is the limited knowledge on the local ability to study and control the impact of harmful exposures on health. OBJECTIVE: To identify needs for research and training in environmental and occupational health in Colombia. MATERIALS AND METHODS: We conducted a three-round hybrid Delphi study. A group of environmental and occupational health Colombian experts (n=16) from government agencies, universities, and research centers was recruited to participate in the study. Expert´s opinions on research and training needs were gathered through online questionnaires, followed by an in-person meeting. The percentage of agreement and the coefficient of variation were used to measure consensus. RESULTS: Air pollution and chemical products were considered the most important environmental and occupational exposures, due to their significant impact on chronic non-communicable diseases, such as respiratory diseases, cardiovascular diseases, and cancer. Research on the effects of outdoor air pollution on cardiovascular and respiratory diseases was considered of the greatest importance. Priority training areas included environmental and occupational health risk assessment, exposure modeling, advanced statistical methods, urban planning, occupational safety and hygiene, and epidemiology and toxicology. CONCLUSIONS: These findings provide a valuable input for the definition and implementation of national environmental and occupational health policies and for the development of a regional hub aimed at strengthening the capacity for research and training in Colombia.

Environmental and occupational health research and training needs in Colombia: A Delphi study / Necesidades de investigación y formación en salud ambiental y ocupacional en Colombia: un estudio Delphi

Introduction: E nvironmental factors contribute with 16% of the burden of disease in Colombia. A main obstacle in implementing national and regional environmental and occupational health policies is the limited knowledge on the local ability to study and control the impact of harmful exposures on health. Objective: To identify needs for research and training in environmental and occupational health in Colombia. Materials and methods: We conducted a three-round hybrid Delphi study. A group of environmental and occupational health Colombian experts (n=16) from government agencies, universities, and research centers was recruited to participate in the study. Expert´s opinions on research and training needs were gathered through online questionnaires, followed by an in-person meeting. The percentage of agreement and the coefficient of variation were used to measure consensus. Results: Air pollution and chemical products were considered the most important environmental and occupational exposures, due to their significant impact on chronic non-communicable diseases, such as respiratory diseases, cardiovascular diseases, and cancer. Research on the effects of outdoor air pollution on cardiovascular and respiratory diseases was considered of the greatest importance. Priority training areas included environmental and occupational health risk assessment, exposure modeling, advanced statistical methods, urban planning, occupational safety and hygiene, and epidemiology and toxicology. Conclusions: These findings provide a valuable input for the definition and implementation of national environmental and occupational health policies and for the development of a regional hub aimed at strengthening the capacity for research and training in Colombia.

Introducción. Los factores ambientales contribuyen con el 16 % de la carga de enfermedad en Colombia. Un obstáculo importante para la implementación de políticas en salud ambiental y ocupacional es el conocimiento limitado sobre la capacidad local para estudiar y controlar el impacto de exposiciones ambientales y ocupacionales. Objetivo. Identificar necesidades de investigación y formación en salud ambiental y ocupacional en Colombia. Materiales y métodos. Se hizo un estudio Delphi híbrido en tres rondas. Se reclutó a un grupo de expertos en salud ambiental y ocupacional (n=16) de instituciones gubernamentales, universidades y centros de investigación. Las opiniones de los expertos sobre necesidades de investigación y formación se recolectaron mediante cuestionarios electrónicos, seguidos de una reunión presencial. El porcentaje de acuerdo y el coeficiente de variación se usaron para cuantificar el consenso del grupo. Resultados. La contaminación del aire y los productos químicos fueron considerados por los expertos como las exposiciones más importantes, dado su gran efecto en las enfermedades crónicas no transmisibles. La investigación de los efectos de la contaminación del aire ambiental sobre las enfermedades cardiovasculares y respiratorias, se consideró de importancia máxima. Las áreas prioritarias de formación fueron la evaluación del riesgo, el modelado de la exposición, los métodos estadísticos avanzados, la planeación urbana, la higiene y la seguridad industrial, y la epidemiología y la toxicología aplicadas a la salud ambiental y ocupacional. Conclusiones. Estos resultados son un insumo importante para la implementación de políticas nacionales en salud ambiental y ocupacional, y para el desarrollo de un nodo regional que fortalezca la capacidad de investigación y formación en Colombia.

Food insecurity and dyslipidemia in a representative population-based sample in the US.

OBJECTIVE: The association of food insecurity with dyslipidemia has not been firmly established. The main objective of this study was to assess whether food insecurity was associated with dyslipidemia. METHOD: A population-based sample of 1,663 adults from the 2008-2011 Survey of the Health of Wisconsin was used. Food insecurity was defined as an affirmative response to either of the questions: (1) "In the last 12months, have you been concerned about having enough food for you or your family?" (2) "In the last 12months, have your food choices been limited because there wasn't enough money?" High total cholesterol was defined as total cholesterol (TC) >240mg/dL or taking prescribed lipid-lowering medication. Low high-density lipoprotein cholesterol (HDL-C) was defined as <40mg/dL in men and <50mg/dL in women. RESULTS: Food insecurity was not associated with high TC either among men or women. Food insecurity was associated with a higher likelihood of low HDL-C among women (adjusted odds ratio [AOR]: 2.31 {95% confidence interval [CI]: 1.42, 3.76}), but not among men. Obesity appears to be a partial mediator of the association among women (P from the Sobel test=0.01). CONCLUSION: These findings suggest that food insecurity may contribute to an increased risk of low HDL-C in women.

Serum bilirubin and the risk of hypertension.

BACKGROUND: Experimental studies suggest oxidative stress could lead to the development of hypertension. Serum bilirubin is a major contributor to the antioxidant capacity in blood plasma and has been identified as an independent cardiovascular risk factor in cohort studies. However, data on the relationship between bilirubin and blood pressure are scarce and inconclusive. METHODS: We analysed data from the National Health and Nutrition Examination Surveys (NHANES) 1999-2012 (N=31069). Fifty multiple imputed data sets were generated and analysed to avoid selection/confounding bias due to excluding individuals/variables with missing values. A minimal sufficient adjustment set of variables (MSAS) needed to estimate the unconfounded effect of bilirubin on blood pressure and hypertension (systolic/diastolic blood pressure ≥ 140/90 mmHg or using antihypertensive medication) was identified using the back-door criterion and included in all regression models. RESULTS: After adjustment for the MSAS variables, systolic blood pressure decreased progressively up to -2.5 mmHg (p<0.001) and the prevalence of hypertension was up to 25% lower (P<0.001) in those with bilirubin ≥ 1.0 mg/dl-the highest two deciles-compared with those with 0.1-0.4 mg/dl-the lowest decile. Sensitivity analyses showed these results were unlikely to be explained by residual confounding or selection bias. CONCLUSIONS: High serum bilirubin may decrease the risk of hypertension by inactivating and inhibiting the synthesis of reactive oxygen species in vascular cells. Strategies to boost the bioavailability of circulating and tissue bilirubin or to mimic bilirubin's antioxidant properties could have a significant impact on prevention and control of hypertension as well as coronary heart disease.

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.

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.