Prospective Epidemiological Study Research Articles

Incidence of upper tract urothelial carcinoma in Spain

Introduction and objectivesThe incidence of upper urinary tract tumors is currently unknown. The aim of this study is to determine the real incidence of upper tract urothelial carcinoma (UTUC) in Spain. Material and methodsA descriptive, prospective and multicenter epidemiological study was conducted in 31 Spanish facilities by means of the Platform for Multicenter Studies of the Spanish Association of Urology. Recruitment was opened from May 1st, 2017 to April 30th, 2018. The original database was exported directly from the electronic Data Collection Logbook on December 15th, 2018, with a total of 404 cases registered (402 valid cases after depuration). Statistical analysis was performed using IBM SPSS software v 23 and EPIDAT v 3.4. ResultsThe incidence adjusted to Spanish population from raw data was 3.27 cases per 100.000 inhabitants per year (2.93–3.61 95% CI) and 3,3 cases per 100.000 inhabitants per year (2.96–3.66 95%CI) when adjusted to European population by age.The mean age at diagnosis was 70 years, and 77% of patients were male. Thirty-four percent of patients had an incidental diagnosis. Tumors were most commonly located in the pyelocalyceal system (54%), followed by the distal ureter (22%). Prior ureteroscopy was performed in 114 patients: this technique modified the subsequent treatment indication in 58% of cases.Radical nephroureterectomy was performed in 311 patients. Kidney-sparing surgery was the elected treatment in 76 patients (20%). Complications were found in 69% of cases, most of them classified as Clavien 1 and 2 (86% of all complications). Postoperative mortality rate was 1.7%. ConclusionsUTUC adjusted incidence rate in Spain is 3.27 and 3.3 in Europe. Prior URS modified the treatment indication in 58% of patients. We found a 69% complication rate and a 1.7% mortality rate.

Stroke-Related Visual Impairment; is There an Association with Atrial Fibrillation?

Background/ObjectivesStroke-related visual impairment and atrial fibrillation are both common following stroke. This study explores whether presence of visual impairment following stroke is associated with presence of atrial fibrillation (AF). Subjects/MethodsThe Impact of Visual Impairment after Stroke (IVIS) study is a multi-centre, acute stroke unit, prospective epidemiology study. Standardised visual assessments included visual acuity, reading, visual fields, eye movements and visual perception. AF and blood pressure (BP) were measured on admission. Further data capture included stroke type, age, gender, stroke severity. Analysis included descriptive statistics, independent samples analysis and multivariate analysis for comparison of AF and visual impairment against covariates. Results1500 stroke admissions were recruited of which 1204 stroke survivors had visual assessment. New onset stroke-related visual impairment (n = 703) was significantly associated with older age and stoke severity. AF and BP data were available for 889 stroke survivors. AF was present on admission for 258 stroke survivors and significantly associated with older age, stroke severity and discharge destination. A significant association was found for presence of AF and presence of visual impairment. However, stroke severity was a contributing factor for this association. High systolic BP (>140 mmHg) was present in 62% and high diastolic BP (>90 mmHg) in 29%, but not associated with presence of visual impairment. ConclusionsAF and visual impairment, independently, occur commonly in stroke. Although our results show an association between AF and visual impairment, this appears to be independently influenced by stroke severity. AF was not associated with type of visual impairment or extent of visual recovery. It remains unknown if AF causes more severe visual impairment.

Burn injury in tertiary health facility in South East Nigeria: A 2 year prospective study

Background and ObjectiveBurn injury is one of the severest type of injury known to medicine. The metabolic demand on the body if not well managed can result in varying outcomes. Local practices, early access to health care and extent of injury has been shown to affect outcome. However, the obvious ignorance of /and inability to implement the preventive strategies has made it impossible to reduce the incidence. Inadequate health planning and policy contributes to pressure on the health system. Defining local epidemiology is pertinent for any successful policy planning and implementation at all levels. Methods and resultsThis a prospective epidemiological study of burn injury that presented at Federal Medical Centre Owerri, Imo State over a 24 months period (August 2016–August 2018). A total of 96 cases presented at the facility with a male:female of 1.4:1. The frequency of presentation was 0.92 cases per week. Majority of the injuries presented via the Emergency Room and flame was the most common aetiological agent. Food agents were usually applied on the wounds as first aid. The mortality the study was 14.3%. Most fire injuries occurred at home. The worst affected age group was the economically active (21–40 years). ConclusionThe study is very informative and can guide the centre in predicting its needs and managing resources. It also helps in defining targets for public enlightenment and intervention. We encourage big centres to do such studies so that a national face will be given to burn injury.

Healthcare-associated pneumonia: a prospective study in Spain.

ABSTRACTObjectiveThe aim of the study was to describe the epidemiological characteristics and factors related to outcome in Streptococcus pneumoniae and methicillin-resistant Staphylococcus aureus (MRSA) healthcare-associated pneumonia (HCAP).Patients and methodA 3-year prospective observational epidemiological case study of HCAP was conducted in seven Spanish hospitals. Microbiological and patient characteristics and outcomes were collected and classified by causative pathogen into 4 categories: “S. pneumoniae”, “MRSA”, “Others” and “Unknown”. Patients were followed up 30 days after discharge.ResultsA total of 258 (84.6%) patients were enrolled (170 were men [65.9%]). Mean age was 72.4 years ± 15 years (95% CI [70.54-74.25]). The etiology of pneumonia was identified in 73 cases (28.3%):S. pneumoniae in 35 patients (13.6%), MRSA in 8 (3.1%), and other microorganisms in 30 patients (11.6%). Significant differences in rates of chronic obstructive pulmonary disease (p < 0.05), previous antibiotic treatment (p < 0.05), other chronic respiratory diseases, inhaled corticosteroids (p < 0.01), and lymphoma (p < 0.05) were observed among the four groups. Patients with MRSA pneumonia had received more previous antibiotic treatment (87.5%). Thirty-three (12.8%) patients died during hospitalisation; death in 27 (81.2%) was related to pneumonia.ConclusionsThe etiology of HCAP was identified in only one quarter of patients, with S. pneumoniae being the most prevalent microorganism. Patients with chronic respiratory diseases more frequently presented HCAP due to MRSA than to S. pneumoniae. Death at hospital discharge was related in most cases to pneumonia.

Decline in Muscle Strength and Performance Predicts Fracture Risk in Elderly Women and Men.

Muscle strength and performance are associated with fractures. However, the contribution of their rate of decline is unclear. To assess the independent contribution of the rate of decline in muscle strength and performance to fracture risk. Community-dwelling women (n = 811) and men (n = 440) aged 60 years or older from the prospective Dubbo Osteoporosis Epidemiology Study followed from 2000 to 2018 for incident fracture. Clinical data, appendicular lean mass/height2 (ht)2, bone mineral density, quadricep strength/ht (QS), timed get-up-and-go (TGUG), 5 times repeated sit-to-stand (5xSTS), and gait speed (GS) measured biennially. Rates of decline in muscle parameters were calculated using ordinary least squares regression and fracture risk was assessed using Cox's models. Incident low-trauma fracture ascertained by x-ray report. Apart from lean mass in women, all muscle parameters declined over time. Greater rates of decline in physical performance were associated with increased fracture risk in women (Hazard ratios [HRs] ranging from 2.1 (95% CI: 1.5-2.9) for GS to 2.7 (95% CI: 1.9-3.6) for 5xSTS, while in men only the decline in GS was associated with fracture risk (HR: 3.4 [95% CI: 1.8-6.3]). Baseline performance and strength were also associated with increased fracture risk in men (HRs ranging from 1.8 (95% CI: 1.1-3.0) for QS to 2.5 (95% CI: 1.5-4.1) for TGUG, but not in women. Rate of decline in physical performance in both genders, and baseline strength and performance in men, contributed independently to fracture risk. Sit-to-stand and GS were the tests most consistently associated with fractures. Further studies are required to determine whether muscle strength and/or performance improve the predictive accuracy of fracture prediction models.

Correlation of resting heart rate with anthropometric factors and serum biomarkers in a population-based study: Fasa PERSIAN cohort study

BackgroundThere is a positive association between raised resting heart rate (RHR), and all causes of mortality and shorter life expectancy. Several serum biomarkers and some anthropometric factors can affect the resting heart rate. This study aimed to investigate the determinants of resting heart rate in a large random sample of the Iranian population.Material and methodsIt is a standardized, retrospective study and the subjects were chosen from the baseline survey of the Prospective Epidemiological Research Study in IrAN (PERSIAN) Fasa non-communicable disease cohort study. It was conducted from winter 2014 to summer 2019 and after obtaining informed consent from a random sample, all the eligible subjects were enrolled. All anthropometric factors and biologic laboratory factors were collected and analyzed by implement smoothly clipped absolute deviation (SCAD) linear regression and SCAD quantile regression. The comparisons between males and females were done via independent T-test.Results & conclusionA total number of 9975 persons from 35 to 90 years old were included. The overall median resting heart rate was 74 (interquartile range:66–80). Mean age has no important difference between males and females (P = 0.79) but, resting heart rate was significantly higher in females (76.6 versus 71.4, P < 0.001). All anthropometric factors except wrist circumference were higher in females (P < 0.05). Age has an adverse effect on resting heart rate and also, there was a direct association between resting heart rate and systolic blood pressure and blood glucose. Alpha-blockers (coefficient = 5.2) and Beta1-blockers (coefficient = − 2.2) were the most effective drugs with positive and negative effects on resting heart rate respectively. Lower hemoglobin, obesity, and more body mass index, and more low-density lipoprotein were associated with more resting heart rate.Continuing the monitoring of this sample via our cohort study and put to action multinational prospective researches with large sample sizes and long follow-ups can lead to more precise results and better scientific judgments.

Incidencia del carcinoma transicional del tracto urinario superior en España

Introduction and objectivesThe incidence of upper urinary tract tumors is currently unknown. The aim of this study is to determine the real incidence of upper tract urothelial carcinoma (UTUC) in Spain. Material and methodsA descriptive, prospective and multicenter epidemiological study was conducted in 31 Spanish facilities by means of the Platform for Multicenter Studies of the Spanish Association of Urology. Recruitment was opened from May 1st, 2017 to April 30th, 2018. The original database was exported directly from the electronic Data Collection Logbook on December 15th, 2018, with a total of 404 cases registered (402 valid cases after depuration). Statistical analysis was performed using IBM SPSS software v 23 and EPIDAT v 3.4. ResultsThe incidence adjusted to Spanish population from raw data was 3.27 cases per 100.000 inhabitants per year (2.93 – 3.61 95% CI) and 3,3 cases per 100.000 inhabitants per year (2.96-3.66 95%CI) when adjusted to European population by age.The mean age at diagnosis was 70 years, and 77% of patients were male. Thirty-four percent of patients had an incidental diagnosis. Tumors were most commonly located in the pyelocalyceal system (54%), followed by the distal ureter (22%). Prior ureteroscopy was performed in 114 patients: this technique modified the subsequent treatment indication in 58% of cases.Radical nephroureterectomy was performed in 311 patients. Kidney-sparing surgery was the elected treatment in 76 patients (20%). Complications were found in 69% of cases, most of them classified as Clavien 1 and 2 (86% of all complications). Postoperative mortality rate was 1.7%. ConclusionsUTUC adjusted incidence rate in Spain is 3.27 and 3.3 in Europe. Prior URS modified the treatment indication in 18% of patients. We found a 69% complication rate and a 1.7% mortality rate.

Testing the role of the timing and chronicity of maternal depressive symptoms in the associations with child behaviour and development.

There is debate regarding whether the association between maternal depressive symptoms (MDS) and child outcomes is due to the timing or chronicity of symptoms. To investigate whether critical periods, sensitive periods, or accumulation models provided the best explanation for the association between MDS and children's behaviour and development. Data on mothers (N=892) were collected from 1996 to 2015 as part of the Australian Longitudinal Study on Women's Health, a prospective longitudinal epidemiological study. Data on children (N=978, 2-12years) were collected in 2016/17 as part of the Mothers and their Children's Health study. Mothers were categorised according to whether they reported MDS (scored≥10 on the CESD-10) before pregnancy, during pregnancy, or in early childhood. Child outcomes were maternal-rated behaviour problems (Strengths and Difficulties Questionnaire; SDQ) and teacher-rated development (Australian Early Development Census; AEDC). We used a structured life course approach to rigorously test critical period, sensitive period, and accumulation (ie chronicity) theories by comparing the fit of a series of models. Most mothers did not report MDS at any time (69.2%), 16.9% reported MDS before pregnancy, 13.2% during pregnancy, and 16.5% in early childhood. High/very high total behaviour problems were reported for 7.0% of children, and developmental vulnerability/risk was reported for 15.9% for social competence and 15.7% for emotional maturity. An accumulation model was the best fit, with each period of MDS associated with an increase of 1.71 points (95% CI 1.26, 2.17) on the SDQ and decreases of 0.31 (95% CI -0.50, -0.12) and 0.29 points (95% CI -0.49, -0.08) on AEDC social competence and emotional maturity, respectively. Chronic MDS were associated with poorer child outcomes than MDS at any single time. Sensitive and critical period models were not supported. This suggests chronicity of symptoms may be more important than timing.

Clinico-electrographic characteristics and classification of genetic generalized epilepsy in Oman

PurposeThere is a lack of information on the annual incidence of genetic generalized epilepsy (GGE) in the Arab countries, especially Oman. Ascertaining the true burden of illness has crucial implications for health policies and priorities. We aim to study the clinico-electrographic characteristics, classification, and annual incidence of GGE in Oman. MethodUsing the cross-sectional data of EEGs obtained from all patients with GGE who presented to Sultan Qaboos University hospital (major referral center for epilepsy in Oman) from January 2007 to June 2014. Analyses were performed using univariate statistics. ResultsApproximately 10,423 patients had EEG studies during the study period of which 376 patients (3.6 %) had EEG abnormalities suggestive of GGE. Forty two percent of the 376 GGE patients were male with ages ranging from 3 to 58 years. We were able to classify 273 patients to one of the GGE syndromes. Forty-three percent of 130 patients had a positive family history of epilepsy in their first or second-degree relatives. The generalized tonic-clonic seizure was the most common seizure type observed in 242 patients (64 %; 95 %CI: 59.2 %–68.9 %). Juvenile myoclonic epilepsy was the most common epilepsy syndrome (41 % of the total GGE patients) encountered in our region. A significant female predominance (9.7 % vs 2.5 %; p = 0.016) was observed in juvenile absence epilepsy. Certain interictal focal EEG abnormalities did not exclude a diagnosis of GGE. An average annual GGE incidence of 2.9 % (95 % CI: 2.6 %–3.2 %) was observed during the study period. ConclusionThis hospital-based study is the first of its kind in the Arabian Gulf region, classifying the different subcategories of GGE. Our results indicate that GGE is a common epilepsy subtype in Oman. A prospective population-based epidemiological study is required to estimate the precise frequency of GGE in Oman.

Remarkable Factors in the Etiology of Monosymptomatic Enuresis Nocturna in Primary School Children

Objective: Monosymptomatic enuresis nocturna is a common clinical problem in childhood. The aim of this study is to determine the frequency of monosymptomatic enuresis nocturna in primary school children and to evaluate related factors and families' approach to enuretic child. Methods: A primary school was chosen in the center of Diyarbakır between January 2019 and February 2019 for a prospective cross-sectional epidemiological study. Total 535 cases aged 6-10 years included in the study. Data collection forms consisting of three parts were given to 1000 students. In the first part, age, gender, height, weight, betwetting frequency, functional constipation were evaluated. In the second part maternal education level, family economic level, the bed wetting history in the family, and the number of individuals in the family were questioned. In the third section, families' approach to enuretic child was evaluated. Results: Frequency of monosymptomatic enuresis nocturna was 17.5 %. No statistically significant relationship was determined in respect of age, gender, body mass index, large family and monosymptomatic enuresis nocturna (p&gt;0.05). There was a statistically significant relationship between maternal education level, family economic level, the bed wetting history in the family, functional constipation and monosymptomatic enuresis nocturna (p&lt;0.05). 26.7% of families punished their children for bedwetting. Conclusions: Prevalance of monosymptomatic enuresis nocturna were higher among the primary school children living in low socioeconomic conditions, those with mothers with a low education level, those with a positive familial history and those with constipation. Key words: enuresis nocturna in primary school children; monosymptomatic enuresis nocturna; etiology of enuresıs nocturna. DOI: 10.7176/JHMN/75-04

1438-P: The Novel Extracellular Matrix Hormone Endotrophin, a Fragment of Collagen Type VI, Is Associated with Diabetes and Is a Risk Factor for Mortality in Elderly Women

As a result of the aging population and obesity, diabetes is a major, increasing public health issue approaching global epidemic proportions. It is well known that patients with diabetes have higher levels of inflammation and that the underlying pathology contributes to blood vessel damage resulting in cardiovascular complications. Recently it was suggested that a fragment of collagen type VI (COL VI), released during deposition, is in fact a novel hormone (endotrophin; ETP), suggesting the extracellular matrix (ECM) to be involved in the regulation of type 2 diabetes. In this study, we investigated the association of ETP (measured by the PRO-C6 ELISA) with diabetes and mortality in a large prospective cohort. From 1999-2001, 5855 postmenopausal women with a mean±SD age of 71±6.5 were included in the Prospective Epidemiological Risk Factor study, and visits were planned according to a pre-defined protocol. The diagnoses for diabetes and mortality were extracted from the Danish Health Registries. We measured ETP in serum of 5608 women at baseline (samples collected from 1999-2001). ETP levels were measured in 2016. ETP levels were significantly elevated in women who died (p&amp;lt;0.0001). Additionally, we found that ETP levels were higher in women diagnosed with diabetes prior to baseline visit (n=206) compared to women diagnosed with diabetes after baseline (n=515, p=0.017), that ETP were higher in women with diabetes prior to baseline compared to healthy women (p&amp;lt;0.0001), and a trend of higher levels of ETP in women diagnosed with diabetes after baseline compared to healthy women (p=0.10). In conclusion, we demonstrate that the hormone ETP, a biomarker also reflecting COL VI deposition, was increased in serum of postmenopausal women with diabetes compared to healthy women. In addition, we show that ETP was associated with mortality, suggesting that turnover of the ECM is very important in metabolic disorders. Disclosure A. Møller: None. D.G.K. Rasmussen: Employee; Self; Nordic Bioscience. M.A. Karsdal: Stock/Shareholder; Self; Nordic Bioscience. C. Christiansen: None. L.M. Staunstrup: None. C.L. Bager: None. Funding Danish Research Foundation

Prenatal Mercury Exposure in Pregnant Women from Suriname's Interior and Its Effects on Birth Outcomes.

Prenatal mercury (Hg) exposure was determined in a sub-cohort of the Caribbean Consortium for Environmental and Occupational Health’s environmental epidemiologic prospective cohort study of pregnant women living in Suriname’s interior. The associations between Hg exposure, low birth weight (LBW, <2500 g) and preterm birth (PTB, <37 weeks) were explored. Correlation analysis, Fisher’s exact test and logistic regression analyses were conducted to evaluate the associations between maternal hair Hg levels and birth weight, LBW and PTB, and between potential confounders, LBW and PTB, respectively. Among 204 singleton births were 198 live births, five stillbirths and one miscarriage. The mean participant age was 26 years; 15.7% of participants had PTBs and 8.1% delivered a child with a LBW. The median hair Hg level was 3.48 μg/g hair. Low hair Hg exposure, based on lowest tertile < 2.34 μg/g, was associated with LBW (OR = 7.2; 95% CI 1.5–35.6; p = 0.015); this association was independent of maternal age, ethnic background, household income and village location, and no correlation was found between hair Hg and PTB. Young maternal age was associated with PTB (RR = 5.09, 95% CI: 1.92–13.85; p = 0.0004) while maternal age was not associated with hair Hg or LBW. The impact of prenatal Hg exposure on pediatric neurodevelopment is currently being evaluated in the infant sub-cohort.

Assessing Human Molybdenum Nutritional Status by Analyzing Frequency distribution Properties in the Hair and Whole Blood with a Median Derivatives Bioassay

Abstract Objectives Molybdenum is the essential trace element in human nutrition since it is a part of a pterin coenzyme which is essential for the activity of various oxidases. High doses of Mo are neurotoxic to the human brain. The safe adequate intake of Mo is set at 75–200 µg·g−1, but there is no available long-term biological indicator tissue to assess the Mo nutritional status. The aim of this study was to assess human Mo nutritional status with a median derivatives bioassay. Methods We analyzed frequency distribution of hair Mo (HMo) in a prospective, observational, cross sectional and exploratory epidemiological study of 1073 apparently healthy adults (339 men, M and 734 women, W) from Zagreb, CROATIA. Whole blood Mo (WBMo) was assessed in a population subsample of 143 W and 91 M. Both hair and whole blood, a long- and short-term biological indicator, respectively were analyzed for Mo with the ICP MS at the Center for Biotic Medicine, Moscow, Russia: an ISO certified bioelement (electrolytes, trace- and ultra-trace elements) analytical laboratory. Hair Mo natural frequency distribution was analyzed with the aid of median derivatives bioassay logistic sigmoid curve for men and women separately. The range of values below the linear segment of the sigmoid curve (the adequate Mo intake) was considered to reflect Mo deficiency, whereas the values above that linear range indicate Mo dietary excess. The adequate linear range may be further subdivided into marginal (subclinical), true adequate, and ample region with a 30:60:10 ratio, respectively. Results The linear segment of the hair Mo deposition was distinctly different (ng·g−1) and higher in M (34–75) than W (27–57) with the observed median ♀/♂ ratio 0.82. The marginal (subclinical) interval ranges are M 34–46.3, W 27–36). However, there were no difference in the WBMo confidence intervals between M (455–1380) and W (480–1145); the Median ♀/♂ observed ratio is 0.93. Conclusions Adequate human population Mo nutritional status may be accurately assessed by analyzing hair Mo frequency distribution with the median derivatives bioassay. Apparently, there is gender dependent delay of Mo hair saturation in the men hair. For the first time it was possible to differentiate the subclinical levels of sparsely adequate dietary Mo. Funding Sources Institute for Research and Development of Sustainable Eco Systems, 10,000 Zagreb, Croatia.

Variations between women and men in risk factors, treatments, cardiovascular disease incidence, and death in 27 high-income, middle-income, and low-income countries (PURE): a prospective cohort study

Some studies, mainly from high-income countries (HICs), report that women receive less care (investigations and treatments) for cardiovascular disease than do men and might have a higher risk of death. However, very few studies systematically report risk factors, use of primary or secondary prevention medications, incidence of cardiovascular disease, or death in populations drawn from the community. Given that most cardiovascular disease occurs in low-income and middle-income countries (LMICs), there is a need for comprehensive information comparing treatments and outcomes between women and men in HICs, middle-income countries, and low-income countries from community-based population studies. In the Prospective Urban Rural Epidemiological study (PURE), individuals aged 35-70 years from urban and rural communities in 27 countries were considered for inclusion. We recorded information on participants' sociodemographic characteristics, risk factors, medication use, cardiac investigations, and interventions. 168 490 participants who enrolled in the first two of the three phases of PURE were followed up prospectively for incident cardiovascular disease and death. From Jan 6, 2005 to May 6, 2019, 202 072 individuals were recruited to the study. The mean age of women included in the study was 50·8 (SD 9·9) years compared with 51·7 (10) years for men. Participants were followed up for a median of 9·5 (IQR 8·5-10·9) years. Women had a lower cardiovascular disease risk factor burden using two different risk scores (INTERHEART and Framingham). Primary prevention strategies, such as adoption of several healthy lifestyle behaviours and use of proven medicines, were more frequent in women than men. Incidence of cardiovascular disease (4·1 [95% CI 4·0-4·2] for women vs 6·4 [6·2-6·6] for men per 1000 person-years; adjusted hazard ratio [aHR] 0·75 [95% CI 0·72-0·79]) and all-cause death (4·5 [95% CI 4·4-4·7] for women vs 7·4 [7·2-7·7] for men per 1000 person-years; aHR 0·62 [95% CI 0·60-0·65]) were also lower in women. By contrast, secondary prevention treatments, cardiac investigations, and coronary revascularisation were less frequent in women than men with coronary artery disease in all groups of countries. Despite this, women had lower risk of recurrent cardiovascular disease events (20·0 [95% CI 18·2-21·7] versus 27·7 [95% CI 25·6-29·8] per 1000 person-years in men, adjusted hazard ratio 0·73 [95% CI 0·64-0·83]) and women had lower 30-day mortality after a new cardiovascular disease event compared with men (22% in women versus 28% in men; p<0·0001). Differences between women and men in treatments and outcomes were more marked in LMICs with little differences in HICs in those with or without previous cardiovascular disease. Treatments for cardiovascular disease are more common in women than men in primary prevention, but the reverse is seen in secondary prevention. However, consistently better outcomes are observed in women than in men, both in those with and without previous cardiovascular disease. Improving cardiovascular disease prevention and treatment, especially in LMICs, should be vigorously pursued in both women and men. Full funding sources are listed at the end of the paper (see Acknowledgments).

The impact of estrogen receptor status on EGFR/TP53/CTNNB1 axis in the evolution of non-small cell lung cancer.

e21035 Background: The role of estrogen receptor status in the carcinogenesis of lung cancer remains elusive. A census of clonal and sub-clonal mutations has been defined through the analyses of evolutionary histories of cancers. We previously reported a prospective multicenter molecular epidemiology study (JME study; Kawaguchi T, J Clin Oncol 2016), which included the expression levels of estrogen receptors β (ER) using immunohistochemistry(IHC) and the mutational profile using next generation sequencing as well as solid smoking information and reproductive/ hormonal risk factors from the detailed questionnaire. Methods: Utilizing the data of the JME study, the impact of ER in lung cancer development was explored. All the patients underwent surgery. In 441 ever- and 435 never-smokers, ER were observed in 46.4% and 53.5%, respectively. The cancer-associated 72 gene mutations and 5 gene amplifications examined in this study included EGFR, SMAD4, APC, FBXW7, BRAF, STK11, PIK3CA, TP53, PTEN, KRAS, CTNNB1, NFE2L2, NF1, and MET. ALK fusion was detected by IHC. Patients were enrolled between July 2012 and December 2013, with follow up until November 30th, 2017.Cox proportional hazards models were used to assess the ER expression on relapse free survival (RFS) and overall survival (OS). A logistic regression model was applied to assess the impact of ER (positive vs. negative) on gene alterations, using sex, smoking history, age and stage as independent variables. Results: ER expression was significantly higher in never smokers (vs. ever smokers; p = 0.022) and earlier stage (stage I vs. II-IV; p = 0.002). Patients with ER positive tumors had a longer RFS than those with negative tumors (RFS rate at 4 years: 33.7 vs. 26.5%; p = 0.021), however, there was no significant difference in OS between the two groups (p = 0.108). In the impact of ER status on the gene alterations, mutations in EGFR (p = 0.003), TP53 (p = 0.007) and CTNNB1 (p = 0.027) were significantly associated with ER expression. Multivariate analysis showed that EGFR mutations (OR = 1.394, 95%CI: 1.029-1.890, p = 0.032) and CTNNB1 mutations (OR = 0.272, 95%CI: 0.087-0.853, p = 0.026) were significantly associated with ER expression, while there was a trend for significance with TP53 mutations (OR = 0.737, 95%CI: 0.537-1.011, p = 0.059). Conclusions: ER positive status triggered the clonal EGFR mutations and suppressed the sub-clonal mutations of TP53 and CTNNB1. It is suggested that ER plays a critical role in the alterations of EGFR/TP53/ CTNNB1 axis in lung cancer evolution.

Results from the European Union MAPEC_LIFE cohort study on air pollution and chromosomal damage in children: are public health policies sufficiently protective?

BackgroundChildren are at high risk of suffering health consequences of air pollution and childhood exposure can increase the risk of developing chronic diseases in adulthood. This study, part of the MAPEC_LIFE project (LIFE12 ENV/IT/000614), aimed to investigate the associations between exposure to urban air pollutants and micronucleus (MN) frequency, as a biomarker of chromosomal damage, in buccal cells of children for supporting implementation and updating of environmental policy and legislation.MethodsThis prospective epidemiological cohort study was carried out on 6- to 8-year-old children living in five Italian towns with different levels and features of air pollution. Exfoliated buccal cells of the children were sampled twice, in winter and spring, obtaining 2139 biological samples for genotoxicological investigation. Micronucleus (MN) frequency was investigated in buccal cells of children and its association with air pollution exposure was assessed applying multiple Poisson regression mixed models, including socio-demographic and lifestyle factors as confounders. We also dichotomize air pollutants’ concentration according to the EU Ambient Air Quality Directives and WHO Air Quality Guidelines in all Poisson regression models to assess their risk predictive capacity.ResultsPositive and statistically significant associations were found between MN frequency and PM10, PM2.5, benzene, SO2 and ozone. The increment of the risk of having MN in buccal cells for each μg/m3 increase of pollutant concentration was maximum for benzene (18.9%, 95% CIs 2.2–38.4%) and modest for the other pollutants (between 0.2 and 1.4%). An increased risk (between 17.9% and 59.8%) was found also for exposure to PM10, benzene and benzo(a)pyrene levels higher than the threshold limits.ConclusionsSome air pollutants are able to induce chromosomal damage in buccal cells of children even at concentrations below present EU/WHO limits. This type of biological effects may be indicative of the environmental pressure which populations are exposed to in urban areas.

Association between overall fruit and vegetable intake, and fruit and vegetable sub-types and blood pressure: the PRIME study (Prospective Epidemiological Study of Myocardial Infarction).

Increased fruit and vegetable (FV) intake is associated with reduced blood pressure (BP). However, it is not clear whether the effect of FV on BP depends on the type of FV consumed. Furthermore, there is limited research regarding the comparative effect of juices or whole FV on BP. Baseline data from a prospective cohort study of 10 660 men aged 50-59 years examined not only the cross-sectional association between total FV intake but also specific types of FV and BP in France and Northern Ireland. BP was measured, and dietary intake assessed using FFQ. After adjusting for confounders, both systolic BP (SBP) and diastolic BP (DBP) were significantly inversely associated with total fruit, vegetable and fruit juice intake; however, when examined according to fruit or vegetable sub-type (citrus fruit, other fruit, fruit juices, cooked vegetables and raw vegetables), only the other fruit and raw vegetable categories were consistently associated with reduced SBP and DBP. In relation to the risk of hypertension based on SBP >140 mmHg, the OR for total fruit, vegetable and fruit juice intake (per fourth) was 0·95 (95 % CI 0·91, 1·00), with the same estimates being 0·98 (95 % CI 0·94, 1·02) for citrus fruit (per fourth), 1·02 (95 % CI 0·98, 1·06) for fruit juice (per fourth), 0·93 (95 % CI 0·89, 0·98) for other fruit (per fourth), 1·05 (95 % CI 0·99, 1·10) for cooked vegetable (per fourth) and 0·86 (95 % CI 0·80, 0·91) for raw vegetable intakes (per fourth). Similar results were obtained for DBP. In conclusion, a high overall intake of fruit, vegetables and fruit juice was inversely associated with SBP, DBP and risk of hypertension, but this differed by FV sub-type, suggesting that the strength of the association between FV sub-types and BP might be related to the type consumed, or to processing or cooking-related factors.

Descriptive Epidemiology of Traumatic Injuries During the First Lockdown Period of COVID-19 Crisis in Iran: A Multicenter Study

Background: The study of alterations in the epidemiological pattern of traumatic injuries during the COVID-19 crisis can provide estimates in the planning of healthcare resources. In a prospective epidemiological study during the first 45 days of lockdown legislation in Iran and by comparing the results with previously published large population-based studies in Iran, we sought changes in the epidemiology of traumas. Methods: Data were obtained prospectively from the orthopedic emergency departments of two tertiary orthopedic trauma centers in Iran form Feb 20 to Apr 3 2020 for 45 days. Both centers were active in giving care for COVID-19 patients, and they were major referral orthopedic trauma centers. Results: A total of 628 patients with a mean age of 38.9 ± 19.9 (range 1 to 96) years consisting of 640 limb injuries were recruited. There were 387 (60.5%) fractures, 176 (27.5%) lacerations, and only 13 (2%) ligamentous injuries due to sports activities. Low-energy trauma was the most common mechanism of injury (38.3%), and its rate was specifically high as the mechanism of injury among women (69 %). In men, sharp injuries had the highest frequency (33%). Sharp injuries and blunt trauma during labor were 6.6 times and 19.5 times more prevalent in men, respectively. Most injuries were seen in 21 - 40-year-old patients. Distal radius/ulna fracture was the most common site of fracture. There were 233 (36.4%) patients with self-discharge. Conclusions: There were important epidemiological changes during the COVID-19 crisis in trauma patients. The cessation of sports activities resulted in a reduction in ligamentous injuries of sports origin. Women better implemented the stay-at-home strategies shown by a sudden increase in the men to women ratio of risk-taking traumatic injuries. The decreased number of patients with soft-tissue injuries and a high rate of self-discharge must inform the authorities of the fear of in-hospital contamination.

Manifestaciones cardiovasculares en pacientes hospitalizados con dengue

IntroductionCardiac complications in dengue patients are not uncommon and are not diagnosed, since they are usually mild and self-limiting. ObjectivesTo characterize the cardiovascular manifestations in hospitalized patients with dengue infection. MethodsWe conducted an observational, analytical, longitudinal, prospective epidemiological study, which included 427 patients treated at Manuel Fajardo Clinical-Surgical Teaching Hospital with diagnosis of dengue infection since April 2017 to April 2018. ResultsCardiovascular manifestations (19.7%), mainly heart rate disorders (sinus bradycardia [13.8%], atrial [4.9%] and ventricular [4.0%] extrasystoles) were frequent in dengue infection patients. Pericarditis and myocarditis were diagnosed in 1.6% and 0.2% respectively. These disorders were self-limiting in 83.3% of cases and occurred in the first days of the onset of fever in 75.0%. Advanced age (OR=1.70), male sex (OR=1.94), decreased platelet count (OR=1.13) and dengue with warning signs (OR=3.29) were related to a higher probability of presenting cardiovascular disorders in the course of a dengue infection. ConclusionsCardiovascular manifestations in dengue patients are frequent, and are related to advanced age, male sex, as well as severe forms of the disease.

Association of dairy consumption with metabolic syndrome, hypertension and diabetes in 147 812 individuals from 21 countries

ObjectiveOur aims were to assess the association of dairy intake with prevalence of metabolic syndrome (MetS) (cross-sectionally) and with incident hypertension and incident diabetes (prospectively) in a large multinational cohort...