Artificial neural network to predict the effect of obesity on the risk of tuberculosis infection.

BACKGROUND: Body weight has been implicated as a risk factor for latent tuberculosis infection (LTBI) and the active disease. DESIGN AND METHODS: This study aimed to develop artificial neural network (ANN) models for predicting LTBI from body weight and other host-related disease risk factors. We used datasets from participants of the US-National Health and Nutrition Examination Survey (NHANES; 2012; n=5,156; 514 with LTBI and 4,642 controls) to develop three ANNs employing body mass index (BMI, Network I), BMI and HbA1C (as a proxy for diabetes; Network II) and BMI, HbA1C and education (as a proxy for socioeconomic status; Network III). The models were trained on n=1018 age- and sex-matched subjects equally distributed between the control and LTBI groups. The endpoint was the prediction of LTBI. RESULTS: When data was adjusted for age, sex, diabetes and level of education, odds ratio (OR) and 95% confidence intervals (CI) for risk of LTBI with increased BMI was 0.85 (95%CI: 0.77 - 0.96, p=0.01). The three ANNs had a predictive accuracy varied from 75 to 80% with sensitivities ranged from 85% to 94% and specificities of approximately 70%. Areas under the receiver operating characteristic curve (AUC) were between 0.82 and 0.87. Optimal ANN performance was noted using BMI as a risk indicator. CONCLUSION: Body weight can be employed in developing artificial intelligence-based tool to predict LTBI. This can be useful in precise decision making in clinical and public health practices aiming to curb the burden of tuberculosis, e.g., in the management and monitoring of the tuberculosis prevention programs and to evaluate the impact of healthy weight on tuberculosis risk and burden.

Obesity and Prevalence of Latent Tuberculosis: A Population-Based Survey.

OBJECTIVE: Diminution in body weight is a known risk factor that increases the burden of active tuberculosis (TB). However, conflicting evidence exists for the effect of body weight on the risk of latent tuberculosis infection (LTBI). The objective of the present study is to examine the prevalence of LTBI at different body weights, evaluate the extent of association between body mass index (BMI) and LTBI and identify factors mediating this relationship in an adult population. METHODS: We conducted a cross-sectional study to estimate the relationship between BMI and LTBI in participants from the US-National Health and Nutrition Examination Survey (NHANES; 2012, n = 5156; 514 with LTBI and 4642 controls). RESULTS: The association between BMI and levels of cardiometabolic risk markers in both LTBI and control groups had a similar profile. When adjusted for age and sex, BMI was significantly inversely correlated with the prevalence of LTBI (r = -0.147, P < .001). Effect of BMI on the risk of LTBI was evaluated using multivariate logistic regression models adjusted for age, sex, diabetes, and level of education. In this model, increasing BMI was significantly associated with lower risk of LTBI (OR = 0.85; 95%CI: 0.77-0.96, P < .01). CONCLUSION: This study further establishes an inverse relationship between BMI and prevalence of LTBI. Decreased BMI can be considered as a risk factor in LTBI, the reservoir for active TB cases.

Comparative profile for COVID-19 cases from China and North America: Clinical symptoms, comorbidities and disease biomarkers.

BACKGROUND: Large inter-individual and inter-population differences in the susceptibility to and outcome of severe acute respiratory syndrome coronavirus 2 or coronavirus disease 2019 (COVID-19) have been noted. Understanding these differences and how they influence vulnerability to infection and disease severity is critical to public health intervention. AIM: To analyze and compare the profile of COVID-19 cases between China and North America as two regions that differ in many environmental, host and healthcare factors related to disease risk. METHODS: We conducted a meta-analysis to examine and compare demographic information, clinical symptoms, comorbidities, disease severity and levels of disease biomarkers of COVID-19 cases from clinical studies and data from China (105 studies) and North America (19 studies). RESULTS: COVID-19 patients from North America were older than their Chinese counterparts and with higher male: Female ratio. Fever, cough, fatigue and dyspnea were the most common clinical symptoms in both study regions (present in about 30% to 75% of the cases in both regions). Meta-analysis for the prevalence of comorbidities (such as obesity, hypertension, diabetes, cardiovascular diseases, chronic obstructive pulmonary disease, cancer, and chronic kidney diseases) in COVID-19 patients were all significantly more prevalent in North America compared to China. Comorbidities were positively correlated with age but at a significantly younger age range in China compared to North American. The most prevalent infection outcome was acute respiratory distress syndrome which was 2-fold more frequent in North America than in China. Levels of C-reactive protein were 4.5-fold higher in the North American cases than in cases from China. CONCLUSION: The differences in the profile of COVID-19 cases from China and North America may relate to differences in environmental-, host- and healthcare-related factors between the two regions. Such inter-population differences-together with intra-population variability-underline the need to characterize the effect of health inequities and inequalities on public health response to COVID-19 and can assist in preparing for the re-emergence of the epidemic.

Hypercytokinemia and Pathogen-Host Interaction in COVID-19.

Severe acute respiratory syndrome (SARS) coronavirus (CoV)-2 (SARS-CoV-2) is a novel coronavirus identified as the cause of coronavirus disease-2019 (COVID-19) that began in Wuhan, China in late 2019 and spread now in 210 countries and territories around the world. Many people are asymptomatic or with mild symptoms. However, in some cases (usually the elderly and those with comorbidities) the disease may progress to pneumonia, acute respiratory distress syndrome and multi-organ dysfunction that can lead to death. Such wide interindividual differences in response to SARS-CoV-2 infection may relate to several pathogen- and host-related factors. These include the different levels of the ubiquitously present human angiotensin I converting enzyme 2 (ACE2) receptors gene expression and its variant alleles, the different binding affinities of ACE2 to the virus spike (S) protein given its L- and S-subtypes and the subsequent extent of innate immunity-related hypercytokinemia. The extensive synthesis of cytokines and chemokines in coronavirus diseases was suggested as a major factor in exacerbating lung damage and other fatal complications. The polymorphisms in genes coding for pro-inflammatory cytokines and chemokines have been associated with mediating the response and susceptibility to a wide range of infections and their severe outcomes. Understanding the nature of pathogen-host interaction in COVID-19 symptomatology together with the role of hypercytokinemia in disease severity may permit developing new avenues of approach for prevention and treatment and can delineate public health measures to control the spread of the disease.

Bayesian network modelling study to identify factors influencing the risk of cardiovascular disease in Canadian adults with hepatitis C virus infection.

OBJECTIVES: The present study evaluates the extent of association between hepatitis C virus (HCV) infection and cardiovascular disease (CVD) risk and identifies factors mediating this relationship using Bayesian network (BN) analysis. DESIGN AND SETTING: A population-based cross-sectional survey in Canada. PARTICIPANTS: Adults from the Canadian Health Measures Survey (n=10 115) aged 30 to 74 years. PRIMARY AND SECONDARY OUTCOME MEASURES: The 10-year risk of CVD was determined using the Framingham Risk Score in HCV-positive and HCV-negative subjects. Using BN analysis, variables were modelled to calculate the probability of CVD risk in HCV infection. RESULTS: When the BN is compiled, and no variable has been instantiated, 73%, 17% and 11% of the subjects had low, moderate and high 10-year CVD risk, respectively. The conditional probability of high CVD risk increased to 13.9%±1.6% (p<2.2×10-16) when the HCV variable is instantiated to 'Present' state and decreased to 8.6%±0.2% when HCV was instantiated to 'Absent' (p<2.2×10-16). HCV cases had 1.6-fold higher prevalence of high-CVD risk compared with non-infected individuals (p=0.038). Analysis of the effect modification of the HCV-CVD relationship (using median Kullback-Leibler divergence; DKL ) showed diabetes as a major effect modifier on the joint probability distribution of HCV infection and CVD risk (DKL =0.27, IQR: 0.26 to 0.27), followed by hypertension (0.24, IQR: 0.23 to 0.25), age (0.21, IQR: 0.10 to 0.38) and injection drug use (0.19, IQR: 0.06 to 0.59). CONCLUSIONS: Exploring the relationship between HCV infection and CVD risk using BN modelling analysis revealed that the infection is associated with elevated CVD risk. A number of risk modifiers were identified to play a role in this relationship. Targeting these factors during the course of infection to reduce CVD risk should be studied further.

The modifying effect of nutritional factors on the association between IL1-ß single nucleotide polymorphism and serum CXCL10 levels in young Canadian adults.

BACKGROUND: Genetic and nutritional factors play an important role in inflammatory response and diseases. CXCL10 is a critical biomarker that is involved in multiple inflammatory diseases, and elevated levels of CXCL10 have been associated with the development of several chronic and infectious diseases. In contrast, micronutrients can attenuate inflammatory responses. Single nucleotide polymorphisms in the pro-inflammatory cytokine genes such as IL-1ß at rs16944 contributed to a number of inflammatory disorders and may substantiate the convergance between chronic and infectious diseases. AIM: This study aims to identify the modifying effect of nutritional factors on the association between IL-1ß genotypes and CXCL10 levels. METHODS: Participants (N = 386) were healthy males and females from the Toronto Nutrigenomics and Health study recruited from the University of Toronto. Levels of micronutrients and inflammatory markers were measured in plasma. IL-1ß genotypes were extracted from the Affymetrix 6.0 SNP chip. RESULTS: CXCL10 levels were not different across different IL-1ß genotypes. Among those with the GA genotype, elevated CXCL10 levels were observed with higher than median ascorbic acid (ß = 0.004 ± 0.002, P = 0.047) or higher than median vitamin D status (ß = 0.003 ± 0.002, P = 0.044). Among participants with the AA genotype, subjects with low α-tocopherol status had elevated levels of CXCL10 (ß = -0.016 ± 0.007, P = 0.012). CONCLUSION: The association between IL-1ß rs16944 genotype and CXCL10 levels was modified by the levels of ascorbic acid, α-tocopherol and vitamin D. These findings may aid in understanding the combined effect of genetic and dietary factors in the development of various infectious and chronic diseases in which IL-1ß and CXCL10 may play an etiological role.

Morbidity and mortality from road injuries: results from the Global Burden of Disease Study 2017.

BACKGROUND: The global burden of road injuries is known to follow complex geographical, temporal and demographic patterns. While health loss from road injuries is a major topic of global importance, there has been no recent comprehensive assessment that includes estimates for every age group, sex and country over recent years. METHODS: We used results from the Global Burden of Disease (GBD) 2017 study to report incidence, prevalence, years lived with disability, deaths, years of life lost and disability-adjusted life years for all locations in the GBD 2017 hierarchy from 1990 to 2017 for road injuries. Second, we measured mortality-to-incidence ratios by location. Third, we assessed the distribution of the natures of injury (eg, traumatic brain injury) that result from each road injury. RESULTS: Globally, 1 243 068 (95% uncertainty interval 1 191 889 to 1 276 940) people died from road injuries in 2017 out of 54 192 330 (47 381 583 to 61 645 891) new cases of road injuries. Age-standardised incidence rates of road injuries increased between 1990 and 2017, while mortality rates decreased. Regionally, age-standardised mortality rates decreased in all but two regions, South Asia and Southern Latin America, where rates did not change significantly. Nine of 21 GBD regions experienced significant increases in age-standardised incidence rates, while 10 experienced significant decreases and two experienced no significant change. CONCLUSIONS: While road injury mortality has improved in recent decades, there are worsening rates of incidence and significant geographical heterogeneity. These findings indicate that more research is needed to better understand how road injuries can be prevented.

Maternal infection with Zika virus and prevalence of congenital disorders in infants: systematic review and meta-analysis.

OBJECTIVE: Zika virus (ZIKV) infection is a vector-borne disease that can be transmitted sexually and vertically. The vertical transmission of the virus may lead to congenital Zika syndrome in infants. The aim of this study is to conduct a systematic review and meta-analysis of published reports documenting the prevalence of congenital Zika-related disorders in infants of mothers infected with ZIKV during pregnancy. METHODS: We conducted a comprehensive search in Ovid MEDLINE, Ovid MEDLINE (R) Epub ahead of print, Embase, Embase Classic and Web of Science databases to identify human studies reporting prevalence of congenital disorders in infants of ZIKV-infected mothers. RESULTS: We identified 25 reports selected for inclusion in the current study (n = 4683 subjects). The majority of the studies were from South American high-risk countries. Only one third of the identified studies were conducted in the United States. Clinical maternal symptoms included maculopapular rash (76.9%), arthralgia (46.4%), fever (45.5%) and headache (31.8%) with myalgia and conjunctivitis only presented in 25% of the cases. The most prevalent congenital disorder in the newborns was brain calcifications (42.6; 95% CI, 30.8-54.4), followed by ventriculomegaly (21.8; 95% CI, 15.2-28.4), joint abnormalities (13.2; 95% CI, 9.4-18.2), ocular abnormalities (4.2; 95% CI, 1.0-7.5) and microcephaly (3.9; 95% CI, 2.4-5.4). CONCLUSION: The current study highlights the high prevalence of a range of congenital disorders in newborns of mothers infected with ZIKV. It warrants developing studies to further clarify the mechanisms by which each of these disorders occurs in response to the viral infection during pregnancy and its vertical transmission to the infants.

The Association between Plasma Omega-6/Omega-3 Ratio and Anthropometric Traits Differs by Racial/Ethnic Groups and NFKB1 Genotypes in Healthy Young Adults.

Evidence for a relationship between omega-6/omega-3 (n-6/n-3) polyunsaturated fatty acid (PUFA) ratio and obesity in humans is inconsistent, perhaps due to differences in dietary intake or metabolism of PUFAs between different subsets of the population. Since chronic inflammation is central to obesity and inflammatory pathways are regulated by PUFAs, the objective of this study was to examine whether variants in the NFKB1 gene, an upstream regulator of the inflammatory response, modify the association between the n-6/n-3 ratio (from diet and plasma) and anthropometric traits in a multiethnic/multiracial population of young adults. Participants' (n = 898) dietary PUFA intake was assessed using a food frequency questionnaire and plasma PUFA concentrations by gas chromatography. Nine tag single nucleotide polymorphisms (SNP) in NFKB1 were genotyped. Significant interactions were found between racial/ethnic groups and plasma n-6/n-3 ratio for body mass index (BMI) (p = 0.02) and waist circumference (WC) (p = 0.007). Significant interactions were also observed between racial/ethnic groups and three NFKB1 genotypes (rs11722146, rs1609798, and rs230511) for BMI and WC (all p ≤ 0.04). Significant interactions were found between two NFKB1 genotypes and plasma n-6/n-3 ratio for BMI and WC (rs4648090 p = 0.02 and 0.03; rs4648022 p = 0.06 and 0.04, respectively). Our findings suggest that anthropometric traits may be influenced by a unique combination of n-6/n-3 ratio, racial/ethnic background, and NFKB1 genotypes.

Metabolites of prostaglandin synthases as potential biomarkers of Lyme disease severity and symptom resolution.

BACKGROUND: Lyme disease or Lyme borreliosis (LB) is the commonest vector-borne disease in the North America. It is an inflammatory disease caused by the bacterium Borrelia burgdorferi. The role of the inflammatory processes mediated by prostaglandins (PGs), thromboxanes and leukotrienes (LTs) in LB severity and symptoms resolution is yet to be elucidated. OBJECTIVES: We aim to systematically review and evaluate the role of PGs and related lipid mediators in the induction and resolution of inflammation in LB. METHODS: We conducted a comprehensive search in PubMed, Ovid MEDLINE(R), Embase and Embase Classic to identify cell-culture, animal and human studies reporting the changes in PGs and related lipid mediators of inflammation during the course of LB. RESULTS: We identified 18 studies to be included into this systematic review. The selected reports consisted of seven cell-culture studies, seven animal studies, and four human studies (from three patient populations). Results from cell-culture and animal studies suggest that PGs and other lipid mediators of inflammation are elevated in LB and may contribute to disease development. The limited number of human studies showed that subjects with Lyme meningitis, Lyme arthritis (LA) and antibiotic-refractory LA had increased levels of an array of PGs and lipid mediators (e.g., LTB4, 8-isoPGF2α, and phospholipases A2 activity). Levels of these markers were significantly reduced following the treatment with antibiotics or non-steroidal anti-inflammatory drugs. CONCLUSION: Dysregulation of prostaglandins and related lipid mediators may play a role in the etiology of LB and persistence of inflammation that may lead to long-term complications. Further investigation into the precise levels of a wide range of PGs and related factors is critical as it may propose novel markers that can be used for early diagnosis.

Biologic Markers of Antibiotic-Refractory Lyme Arthritis in Human: A Systematic Review.

INTRODUCTION: Lyme disease-also known as Lyme borreliosis (LB)-is the most common vector-borne disease in North America and Europe. It may result in substantial morbidity, primarily from persistent Lyme arthritis (LA) that-although treatable-can develop into antibiotic-refractory LA (A-RLA). The aim of this study is to systematically review and evaluate a range of biomarkers for their potential predictive value in the development of A-RLA. METHODS: We conducted a systematic review of studies examining biomarkers among patients with A-RLA from MEDLINE via OVID, EMBASE and Web of Science databases and identified a total of 26 studies for qualitative analysis. RESULTS: All studies were of patient populations from the USA, with the exception of one from Europe. We identified an array of biomarkers that are commonly modulated in the A-RLA compared with subjects with antibiotic-responsive LA. These included a range of inflammatory markers (IL-6, IL-8, IL-10, IL-1ß, IL-23, IL-17F, TNFα, IFNγ, CXCL9, CXCL10, CCL2, CCL3 and CCL4, CRP), factors along the innate and adaptive immune response pathways (e.g., CD4+ T cells, GITR receptors, OX40 receptors, IL-4+CD4+Th2 cells, IL-17+CD4+ T cells) and an array of miRNA species (e.g., miR-142, miR-17, miR-20a, let-7c and miR-30fam). CONCLUSION: The evidence base of biologic markers for A-RLA is limited. However, a range of promising biomarkers have been identified. Cytokines and chemokines related to Th17 pathway together with a number of miRNAs species (miR-146a, miR-155 and let-7a) may be promising candidates in the prediction of A-RLA. A panel of multiple biomarkers may yield clinically relevant prediction of the possible resistance at the time of LA first diagnosis. FUNDING: Public Health Agency of Canada.

C-reactive protein as a biomarker of severe H1N1 influenza.

BACKGROUND: C-reactive protein (CRP) is an acute-phase reactant downstream of the pro-inflammatory cytokines released during influenza infection. However, the role of this inflammatory marker in influenza severity and complications is yet to be elucidated. OBJECTIVES: We aim to systematically review and evaluate the levels of CRP in severe and non-severe H1N1 influenza cases and assess its utility as a biomarker in predicting the severity of infection. METHODS: We conducted a comprehensive search in Ovid MEDLINE, Ovid MEDLINE (R) Epub ahead of Print, Embase and Embase Classic to identify human studies reporting measurements of CRP levels in patients infected with H1N1 influenza at various levels of disease severity. RESULTS: Our search identified ten studies eligible for inclusion in this systematic review. The results of the data analysis show that the average CRP levels upon diagnosis were significantly higher (P < 0.05) in patients who developed severe H1N1 influenza compared to their counterparts with a no severe disease. Furthermore, levels of CRP were associated with the degree of H1N1 severity. Subjects with H1N1-related pneumonia and patients who were hospitalized or died of the disease complications, respectively, had 1.4- and 2.5-fold significantly higher CRP levels (P < 0.05) than those with no severe disease outcome. CONCLUSION: CRP levels have been consistently shown to be significantly higher in H1N1 influenza patients who develop a severe disease outcome. The resuts of the present study suggest that serum CRP can be employed-in combination with other biomarkers-to predict the complications of H1N1 influenza.

Cardiovascular disease risk in patients with hepatitis C infection: Results from two general population health surveys in Canada and the United States (2007-2017).

The role of hepatitis C virus (HCV) infection in increasing the risk of cardiovascular disease (CVD) is controversial. The objective of the present study is to estimate the 10-year risk of CVD in HCV- positive subjects and describe their profile of cardiometabolic risk markers compared to HCV-negative subjects. We conducted a cross-sectional study to estimate 10-year CVD risk, calculated using the Framingham Risk Score (FRS), in participants from the Canadian Health Measures Survey (CHMS; 2007-2015, n = 10,115) and the US-National Health and Nutrition Examination Survey (NHANES; 2007-2016, n = 16,668). Subjects included in our analysis were aged 30 to 74 years with no prior history of CVD. FRS estimates, sociodemographic and cardiometabolic risk factors were compared between HCV- positive and -negative subjects in the two surveys. HCV-positive subjects had a distinct sociodemographic profile compared to their HCV-negative counterparts. Cardiometabolic risk factors, inflammatory markers and serum levels of micronutrients were comparable between the two survey populations, both in HCV-positive and -negative subjects. The average FRS in HCV-positive patients was in the range of "intermediate" 10-year CVD risk (i.e., 10-20%) and was significantly higher (P<0.01) than their HCV-negative counterparts who were within the "low" 10-year CVD risk range (i.e., ≤10%). Using a multivariable linear regression model adjusted for ethnicity, number of metabolic syndrome components and BMI, HCV infection was significantly associated with a 2.5-3.5% absolute risk increase of 10-year CVD (P<0.01). The results of the present study suggest a potential association between HCV infection and risk of subclinical and clinical CVD. The expansion of anti-HCV therapy may also contribute to reduced CVD risk and burden in patients with chronic HCV infection and should be explored further in other datasets and population modelling studies.

Prevalence of chronic comorbidities in dengue fever and West Nile virus: A systematic review and meta-analysis.

BACKGROUND: Flavivirus diseases such as dengue fever (DENV), West Nile virus (WNV), Zika and yellow fever represent a substantial global public health concern. Preexisting chronic conditions such as cardiovascular diseases, diabetes, obesity, and asthma were thought to predict risk of progression to severe infections. OBJECTIVE: We aimed to quantify the frequency of chronic comorbidities in flavivirus diseases to provide an estimate for their prevalence in severe and non-severe infections and examine whether chronic diseases contribute to the increased risk of severe viral expression. METHODS: We conducted a comprehensive search in PubMed, Ovid MEDLINE(R), Embase and Embase Classic and grey literature databases to identify studies reporting prevalence estimates of comorbidities in flavivirus diseases. Study quality was assessed with the risk of bias tool. Age-adjusted odds ratios (ORs) were estimated for severe infection in the presence of chronic comorbidities. RESULTS: We identified 65 studies as eligible for inclusion for DENV (47 studies) and WNV (18 studies). Obesity and overweight (i.e., BMI> 25 kg/m2, prevalence: 24.5%, 95% CI: 18.6-31.6%), hypertension (17.1%, 13.3-21.8%) and diabetes (13.3%, 9.3-18.8%) were the most prevalent comorbidities in DENV. However, hypertension (45.0%, 39.1-51.0%), diabetes (24.7%, 20.2-29.8%) and heart diseases (25.6%, 19.5-32.7%) were the most prevalent in WNV. ORs of severe flavivirus diseases were about 2 to 4 in infected patients with comorbidities such as diabetes, hypertension and heart diseases. The small number of studies in JEV, YFV and Zika did not permit estimating the prevalence of comorbidities in these infections. CONCLUSION: Higher prevalence of chronic comorbidities was found in severe cases of flavivirus diseases compared to non-severe cases. Findings of the present study may guide public health practitioners and clinicians to evaluate infection severity based on the presence of comorbidity, a critical public health measure that may avert severe disease outcome given the current dearth of clear prevention practices for some flavivirus diseases.

Prevalence of chronic comorbidities in chikungunya: A systematic review and meta-analysis.

BACKGROUND: Epidemiologic evidence suggests that patients with chikungunya virus (CHIKV) infection may be at risk of severe disease complications when they also have comorbidities such as obesity, diabetes, cardiac diseases, and/or asthma. However, the prevalence of these co-existing medical conditions in severe CHIKV cases has not been systematically reported. OBJECTIVE: The aim of the present study is to conduct a systematic review and meta-analysis to describe the prevalence of chronic comorbidities in CHIKV and evaluate their possible contributions to disease severity. METHODS: A search strategy was developed for online databases. Search terms used were "Chikungunya" AND "Diabetes, Hypertension, Stroke, Cardiovascular Diseases, Coronary Artery Diseases, Obesity, OR Asthma". Only 11 articles documenting the frequency of comorbidities in CHIKV were included. Meta-analyses were conducted to evaluate the overall prevalence of comorbidities in the CHIKV infection and stratify the estimates by severity. RESULTS: Among 2,773 CHIKV patients, hypertension was the most prevalent comorbidity (31.3%; 95%CI: 17.9-48.8%) followed by diabetes (20.5%; 95%CI: 12.7-31.3%), cardiac diseases (14.8%; 95%CI: 8.1-25.5%) and asthma (7.9%; 95%CI: 3.3-17.7). There was 4- to 5-fold significant increased prevalence of diabetes, hypertension and cardiac diseases in CHIKV patients over 50 years of age compared to their younger counterparts. Severe CHIKV cases had a significantly higher proportion of diabetes than non-severe cases (p<0.05). CHIKV patients with diabetes had OR of 1.2 (95%CI: 1.05-1.48; p=0.0135) for developing severe infection outcome compared to those with no diabetes. CONCLUSION: Hypertension, diabetes and cardiac diseases may contribute to the severe outcome of CHIKV. Diabetic subjects may be at higher risk of severe infection. These findings may be relevant in developing public health measures and practices targeting CHIKV patients with comorbidities to avert the severe outcome of the infectious disease.

Circulating concentrations and relative percent composition of trans fatty acids in healthy Canadian young adults between 2004 and 2010: a cross-sectional study.

BACKGROUND: Trans fatty acids (TFAs) produced from industrial partial hydrogenation of vegetable oils have been the subject of much research regarding their negative effect on the development of chronic diseases, and recommendations to label foods with partially hydrogenated vegetable oils and limit their levels were introduced in Canada in 2003 and 2007, respectively. Our aim was to determine temporal changes in circulating plasma TFAs in a population of young healthy Canadian adults after the introduction of the guidelines. METHODS: In this study, circulating plasma concentrations and relative percent composition of individual TFAs over time (2004-2010) were determined in a cross-sectional cohort of young healthy Canadian adults as part of the Toronto Nutrigenomics study. RESULTS: A total of 1294 participants were included in the cohort. Relative to 2004, total TFA levels were significantly lower in 2005-2009 (p < 0.05), but not in 2010. Although levels of 16:1t9 and 18:1t11 declined after 2004, levels of 18:1t9 and 18:1t10 were significantly lower in 2005-2009 (p < 0.05), but not in 2010. INTERPRETATION: Trans fatty acids were lower in 2009 relative to 2004, but not different in 2010, suggesting that young Canadians may remain vulnerable to partially hydrogenated vegetable oil exposure and that there is a need for further monitoring of specific food categories and vulnerable populations.

Global Cardiovascular and Renal Outcomes of Reduced GFR.

The burden of premature death and health loss from ESRD is well described. Less is known regarding the burden of cardiovascular disease attributable to reduced GFR. We estimated the prevalence of reduced GFR categories 3, 4, and 5 (not on RRT) for 188 countries at six time points from 1990 to 2013. Relative risks of cardiovascular outcomes by three categories of reduced GFR were calculated by pooled random effects meta-analysis. Results are presented as deaths for outcomes of cardiovascular disease and ESRD and as disability-adjusted life years for outcomes of cardiovascular disease, GFR categories 3, 4, and 5, and ESRD. In 2013, reduced GFR was associated with 4% of deaths worldwide, or 2.2 million deaths (95% uncertainty interval [95% UI], 2.0 to 2.4 million). More than half of these attributable deaths were cardiovascular deaths (1.2 million; 95% UI, 1.1 to 1.4 million), whereas 0.96 million (95% UI, 0.81 to 1.0 million) were ESRD-related deaths. Compared with metabolic risk factors, reduced GFR ranked below high systolic BP, high body mass index, and high fasting plasma glucose, and similarly with high total cholesterol as a risk factor for disability-adjusted life years in both developed and developing world regions. In conclusion, by 2013, cardiovascular deaths attributed to reduced GFR outnumbered ESRD deaths throughout the world. Studies are needed to evaluate the benefit of early detection of CKD and treatment to decrease these deaths.

A systematic review and meta-analysis for the adverse effects, immunogenicity and efficacy of Lyme disease vaccines: Guiding novel vaccine development.

BACKGROUND: Lyme borreliosis (LB) is the most prevalent arthropod-borne infectious disease in North America. Currently, no vaccine is available to prevent LB in humans, although monovalent and multivalent vaccines have been developed in the past. OBJECTIVE: The aim of the current study is to conduct a systematic review and meta-analysis to evaluate and compare the findings from these two classes of vaccines for their reactogenicity, immunogenicity and efficacy, in the hope this may assist in the development of future vaccines. METHODS: A search strategy was developed for online databases (PubMed, Ovid MEDLINE, and Embase). Search terms used were "vaccine/vaccination", "Lyme disease/Borreliosis", "clinical trial(s)" and "efficacy". Only seven clinical trials were included to compare the results of the monovalent vaccines to those of the multivalent one. Meta-analyses were conducted to evaluate the reactogenicity and immunogenicity of the two vaccine classes. Odds ratio (OR) for LB (and 95% confidence intervals; 95% CI) were calculated for the efficacy of the monovalent vaccine from three different clinical trials at different dose schedules. RESULTS: Incidence of redness (local adverse effect) and fever (systemic side effect) were, respectively, 6.8- and 2.9-fold significantly lower (p < 0.05) in individuals who received multivalent vaccines compared to those receiving the monovalent one. Incidences of all other local and systemic adverse effects were non-significantly lower in the multivalent vaccine compared to the monovalent vaccines. Seroprotection was comparable among individuals who received the two vaccine classes at the 30 µg dose level. Efficacy in the prevention of LB was only evaluated for the monovalent vaccines. OR of LB ranged from 0.49 (95% CI: 0.14-0.70; p < 0.005, vs. placebo) to 0.31 (95% CI: 0.26-0.63; p < 0.005) for the initial and final doses respectively, with an overall OR of 0.4 (95% CI: 0.26-0.63, p < 0.001). CONCLUSION: The current study further validates that the monovalent and multivalent LB vaccines result in mild local side effects and self-limiting systemic adverse effects, with the multivalent vaccine slightly more tolerable than the monovalent one. Both vaccine classes were similarly highly immunogenic. A new vaccine with high safety standards, better efficacy, low cost, and public acceptance is yet to be developed. Meanwhile, personal protection limiting exposure to ticks is recommended.

Burden of musculoskeletal disorders in the Eastern Mediterranean Region, 1990-2013: findings from the Global Burden of Disease Study 2013.

OBJECTIVES: We used findings from the Global Burden of Disease Study 2013 to report the burden of musculoskeletal disorders in the Eastern Mediterranean Region (EMR). METHODS: The burden of musculoskeletal disorders was calculated for the EMR's 22 countries between 1990 and 2013. A systematic analysis was performed on mortality and morbidity data to estimate prevalence, death, years of live lost, years lived with disability and disability-adjusted life years (DALYs). RESULTS: For musculoskeletal disorders, the crude DALYs rate per 100 000 increased from 1297.1 (95% uncertainty interval (UI) 924.3-1703.4) in 1990 to 1606.0 (95% UI 1141.2-2130.4) in 2013. During 1990-2013, the total DALYs of musculoskeletal disorders increased by 105.2% in the EMR compared with a 58.0% increase in the rest of the world. The burden of musculoskeletal disorders as a proportion of total DALYs increased from 2.4% (95% UI 1.7-3.0) in 1990 to 4.7% (95% UI 3.6-5.8) in 2013. The range of point prevalence (per 1000) among the EMR countries was 28.2-136.0 for low back pain, 27.3-49.7 for neck pain, 9.7-37.3 for osteoarthritis (OA), 0.6-2.2 for rheumatoid arthritis and 0.1-0.8 for gout. Low back pain and neck pain had the highest burden in EMR countries. CONCLUSIONS: This study shows a high burden of musculoskeletal disorders, with a faster increase in EMR compared with the rest of the world. The reasons for this faster increase need to be explored. Our findings call for incorporating prevention and control programmes that should include improving health data, addressing risk factors, providing evidence-based care and community programmes to increase awareness.