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Nelson J Alvis-Zakzuk,1,2 Diana Díaz-Jiménez,1 Pablo Chaparro-Narváez,1 Juan C Gutiérrez-Clavijo,1 Liliana Castillo-Rodríguez,1 Francisco Edna-Estrada,3 Carlos Castañeda-Orjuela,1 Fernando De La Hoz-Restrepo4 1Observatorio Nacional de Salud, Instituto Nacional de Salud, Bogotá, D.C., Colombia; 2Departamento de Ciencias de la Salud, Universidad de la Costa-CUC, Barranquilla, Colombia; 3Federación Colombiana de Obstetricia y Ginecología, Cartagena, Bolívar, Colombia; 4Grupo de Evaluación en Epidemiología y Salud Pública, Universidad Nacional de Colombia, Bogotá, D.C., ColombiaCorrespondence: Nelson J Alvis-ZakzukDepartamento de Ciencias de la Salud, Universidad de la Costa-CUC, Cl. 58 #55 - 66, Barranquilla, ColombiaEmail nalvis1@cuc.edu.coObjective: We aimed to estimate out-of-pocket (OOP) health expenditures and the indirect costs related to prenatal check-ups in pregnant women seen in a maternity hospital in the Colombian Caribbean region.Methods: We described the economic costs of pregnant women, with no age limits, who attended prenatal check-ups in a maternity hospital. To estimate OOP and indirect costs owing to prenatal check-ups in pregnant women, a survey was constructed, where the woman was asked about some sociodemographic variables, to characterize those attending the prenatal check-ups. Absolute and relative frequencies, averages and confidence intervals were used to characterize the population and estimate OOP and indirect costs in pregnant women. The latter were estimated from the percentile method. A bootstrapping was performed to reduce the bias within the analysis.Results: In total, 56 pregnant women were surveyed, with an average age of 25.9 years (± 6.2). All women surveyed had OOP associated to the prenatal check-up in at least one cost-item, and the OOP ranged between

Objectives: This study aimed to estimate the direct medical costs due to hospitalizations by COVID-19 in Colombia and to identify their cost drivers in Colombia., Methods: This is a retrospective cost-of-illness study of COVID-19 in Colombia. We estimated direct medical costs using data from patients insured to a Benefit Plan Administrator Company, between March 15, 2020 and May 29, 2020. Absolute and relative frequencies, averages, medians, and interquartile ranges (IQRs) were used to characterize the population and estimate the costs of hospitalized patients with COVID-19. We stratified the cost analysis by sex, age groups, comorbidities, and type of hospitalization (general ward and intensive care unit [ICU]). Cost drivers were calculated from a generalized linear model., Results: We studied 113 confirmed patients, 51.3% men. On average, the hospital length of stay was 7.3 (± 6.2) days. A person hospitalized with COVID-19 reported median costs of $1688 (IQR 788-2523). In women, this cost was $1328 (IQR 463-2098); in men, this was 1.4 times greater. The median cost for ICU was $4118 (IQR 2069-5455), 3 times higher than those hospitalized only in the general ward. Admission to the ICU, having 1 comorbidity, length of stay, high blood pressure, having 5 comorbidities, and being treated in the city of Cartagena were statistically significant with direct medical costs., Conclusions: Our study provides an idea of the magnitude of costs needed to hospitalize a COVID-19 case in Colombia. Other studies in Colombia have assessed the costs of hospitalization for infectious diseases such as influenza, costs significantly lower than those described here., (Copyright © 2022 International Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Objective: To estimate the economic burden of Severe Acute Respiratory Infection (SARI) in lab-confirmed influenza patients from a low-income country setting such as Colombia., Methods: A bottom-up costing analysis, from both third payer and social perspectives, was conducted. Direct costs of care were based on the review of 227 clinical records of lab-confirmed influenza inpatients in six facilities from three main Colombian cities. Resources were categorized as: length of stay (LOS), diagnostic and laboratory tests, medications, consultation, procedures, and supplies. A survey was designed to estimate out-of-pocket expenses (OOPE) and indirect costs covered by patients and their families. Cost per patient was estimated with the frequency of use and prices of activities, calculating median and 95% confidence intervals (95% CI) with bootstrapping. Total costs are expressed as the sum of direct medical costs, OOPE and indirect costs in 2018 US dollars., Results: The media direct medical cost per SARI lab-confirmed influenza patient was US$ 700 (95% CI US$ 552-809). Diagnostic and laboratory tests correspond to the highest cost per patient (37%). Median OOPE and indirect costs per patient was US$ 147 (95% CI US$ 94-202), with the highest costs for caregiver expenses (27%). Total costs were US$ 848 (95% CI US$ 646-1,011), OOPE and indirect costs corresponded to 17.4% of the total. The median of direct medical costs per patient was three times higher in elderly patients., Conclusion: SARI influenza costs impose a high economic burden on patients and their families. The results highlight the importance of strengthening preventive strategies nationwide in the age groups with higher occurrence and incurred health costs., Competing Interests: All authors declare no conflicts of interest.

Objective: To describe the mortality trends of diabetes mellitus (DM) in Colombia, by sex and age group, from 1979 to 2017., Methods: We carried out an ecological study using mortality data from the Colombian National Administrative Department of Statistics. Crude and age-standardized annual mortality rates per 100 000 people were estimated. Trends of standardized rates were described by sex and age groups. Joinpoint regression models were performed to study mortality trends., Results: Throughout the whole period, the total number of DM recorded deaths in Colombia was 200 650, 58% (116 316) in women (p<0.05). The age-standardized mortality rates (ASMR) by sex increased from 13.2 to 26.6 deaths per 100 000 in women and from 10.1 to 22.7 in men from 1979 to 1999. We observed a decrease from 26.6 to 15.4 per 100 000 in women, and from 22.7 to 15.9 in men for the period 1999-2017. The joinpoint regression analysis showed that the average annual percentage change of the period did not vary in both sexes (men: -0.2%, 95% CI -1.0 to 1.4%; women: 0.7%, 95% CI -0.1 to 1.6%)., Conclusions: The DM mortality showed a decreasing trend after 2000 in women and 2004 in men. Primary and secondary prevention programs must continue to be strengthened for an earlier diagnosis of diabetes.

Four colistin susceptibility testing methods were compared with the standard broth microdilution (BMD) in a collection of 75 colistin-susceptible and 75 mcr -positive E. coli , including ST131 isolates. Taking BMD as reference, all methods showed similar categorical agreement rates (CA) of circa 90%, and a low number of very major errors (VME) (0% for the MicroScan system and Etest ® , 0.7% for UMIC ® ), except for the disc diffusion assay (breakpoint ≤ 11 mm), which yielded false-susceptible results for 8% of isolates. Of note is the number of mcr -positive isolates (17.3%) categorized as susceptible (≤2 mg/L) by the BMD method, but as resistant by the MicroScan system. ST131 mcr -positive E. coli were identified as colistin-resistant by all MIC-based methods. Our results show that applying the current clinical cut-off (>2 mg/L), many mcr -positive E. coli remain undetected, while applying a threshold of >1 mg/L the sensitivity of detection increases significantly without loss of specificity. We propose two possible workflows, both starting with the MicroScan system, since it is automated and, importantly, it categorized all mcr -positive isolates as colistin-resistant. MicroScan should be followed by either BMD or MIC-based commercial methods for colistin resistance detection; or, alternatively, MicroScan, followed by PCR for the mcr screening.

For the first time, this study evaluates consumer exposure via poultry meat to Enterobacteriaceae with capacity to develop severe extraintestinal infections by either bacterial virulence and/or antibiotic resistance traits. The characterization of 256 isolates and the assessment of five parameters, showed that 96 of 100 poultry meat samples from supermarkets of northwest Spain posed ≥ one potential risk: i) 96% carried Enterobacteriaceae resistant to antimicrobials of categories A (64% to monobactams) or B (95% to cephalosporins 3rd and 4rd- generation, quinolones and/or polymixins) of the new categorization of EMA. ii) More than one extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae species were recovered from 28% of poultry meat. iii) High-risk lineages of E. coli, including multidrug-resistant ST131-H22, were present in 62% of samples. iv) E. coli recovered from 25% of samples conformed the ExPEC status. v) E. coli from 17% of samples satisfied the UPEC status. Of note, the recovery from different samples of two E. coli CC10-A (CH11-54) carrying mcr-1.1-bearing IncX4 plasmids, and four E. coli CC10-A (eae-beta1) of the hybrid pathotype aEPEC/ExPEC. (ESBL)-producing K. pneumoniae were isolated from 27% of samples. In summary, poultry meat microbiota is a source of genetically diverse Enterobacteriaceae, resistant to relevant antimicrobials and potentially pathogenic for consumers., Competing Interests: Declaration of competing interest None declared., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The aim of this work was to assess the prevalence of extended spectrum-β-lactamase (ESBL)- and carbapenemase-producing Enterobacteriaceae in fecal samples recovered from rural and urban healthy dogs in Northwest Spain (Galicia) to identify potential high-risk clones and to molecularly characterize positive isolates regarding the genes coding for ESBL/pAmpC resistance and virulence. Thirty-five (19.6%) out of 179 dogs were positive for cephalosporin-resistant Enterobacteriaceae , including Escherichia coli and Klebsiella pneumoniae phylogroups (A, B1, C, D, E, F and clade I) were found. The eight isolates (20.5%) found to conform to the ExPEC status, belonged to clones O1:H45-clade I-ST770 (CH11-552), O18:H11-A-ST93-CC168 (CH11-neg), O23:H16-B1-ST453-CC86 (CH6-31), and O83:H42-F-ST1485-CC648 (CH231-58), with the latter also complying the uropathogenic (UPEC) status. The three E. coli phylogroups (A, B1, C, D, E, F and clade I) were found. The eight isolates (20.5%) found to conform to the ExPEC status, belonged to clones O1:H45-clade I-ST770 (CH11-552), O18:H11-A-ST93-CC168 (CH11-neg), O23:H16-B1-ST453-CC86 (CH6-31), and O83:H42-F-ST1485-CC648 (CH231-58), with the latter also complying the uropathogenic (UPEC) status. The three K. pneumoniae recovered produced CTX-M-15 and belonged to the ST307, a clone previously reported in human clinical isolates. Our study highlights the potential role of both rural and urban dogs as a reservoir of high-risk Enterobacteriaceae clones, such as the CC648 of E. coli and antimicrobial resistance traits. Within a One-Health approach, their surveillance should be a priority in the fight against antimicrobial resistance.

Different surveillance studies (2005-2015) in northwest Spain revealed the presence of eae -positive isolates of Escherichia coli O153:H10 in meat for human consumption, poultry farm, wildlife and human diarrheagenic samples. The aim of this study was to explore the genetic and genomic relatedness between human and animal/meat isolates, as well as the mechanism of its persistence. We also wanted to know whether it was a geographically restricted lineage, or whether it was also reported elsewhere. Conventional typing showed that 32 isolates were O153:H10-A-ST10 fim H54, fimAv MT78 , traT and eae -beta1. Amongst these, 21 were CTX-M-32 or SHV-12 producers. The PFGE XbaI -macrorestriction comparison showed high similarity (>85%). The plasmidome analysis revealed a stable combination of IncF (F2:A-:B-), IncI1 (STunknown) and IncX1 plasmid types, together with non-conjugative Col-like plasmids. The core genome investigation based on the cgMLST scheme from EnteroBase proved close relatedness between isolates of human and animal origin. Our results demonstrate that a hybrid MDR aEPEC/ExPEC of the clonal group O153:H10-A-ST10 (CH11-54) is circulating in our region within different hosts, including wildlife. It seems implicated in human diarrhea via meat transmission, and in the spreading of ESBL genes (mainly of CTX-M-32 type). We found genomic evidence of a related hybrid aEPEC/ExPEC in at least one other country.

Porcine Escherichia coli ST131 isolates are scarcely documented. Here, whole genome sequencing and core genome (CG) and plasmidome analysis of seven isolates collected from diarrheic piglets and four from pork meat were performed. All of the 11 ST131 isolates belonged to serotype O25b:H4 and clade B and showed fimH 22 allele or mutational derivatives. The 11 porcine isolates possessed virulence traits that classified the isolates as avian pathogenic, uropathogenic, and extraintestinal pathogenic E. coli -like (APEC-, UPEC-, and ExPEC-like) and constituted virotype D. The CG was performed for all porcine isolates in addition to 73 ST131 reference isolates from different origins. Within clade B, the CG showed nine subclusters, allowing us to describe five new subclades (B6, B6-like, B7, B8, and B9). There was an association between subclade B6, PST43, virotype D2, and food origin, whereas subclade B7 included PST9 isolates with virotype D5 from diarrheic piglets ( p = 0.007). The distance between human and porcine isolates from subclades B6 and B7 had an average of 20 and 15 SNP/Mb, respectively. [F2:A-:B1]-IncF, ColE1-like, and IncX plasmids were the most prevalent. Besides, IncF plasmids harbored a ColV region frequent among APEC isolates. Antimicrobial resistance genes conferring resistance to penicillin, tetracycline, quinolones, and colistin were the most common. The mcr -1.1 gene was detected in 5 of 11 porcine isolates, integrated into the chromosome of one isolate and into plasmids in the remainder isolates (two MOB H 11 /IncHI2-ST4, one MOB P 3 /IncX4, and one MOB F 12 /IncF [F2:A-:B1] supposedly cointegrated with an IncHI2). The surrounding environments of the mcr -1 cassette showed variability. However, there were conserved structures within the same plasmid family. In conclusion, CG analysis defined five new subclades. The ST131 porcine isolates belonged to new subclades B6 and B7. Moreover, porcine and clinical human isolates were strongly related. The 11 porcine ST131 isolates harbored a wide variety of plasmids, virulence, and resistance genes. Furthermore, epidemic plasmids IncX4 and IncHI2 are responsible for the acquisition of mcr -1.1 gene. We hypothesize that the APEC-IncF plasmid acquired the mcr -1.1 gene via cointegrating an IncHI2 plasmid, which is worrying due to combination of virulence and resistance attributes in a single mobile genetic element., (Copyright © 2020 Flament-Simon, de Toro, Mora, García, García-Meniño, Díaz-Jiménez, Herrera and Blanco.)

Introduction: Inequalities in the health field are caused by the differences in the social and economic conditions, that influence the disease risk and the measures taken to treat the disease. Objective: We aimed to estimate the social inequalities in health in Colombia, according to the type of affiliation to the health system as a proxy of socioeconomic status. Materials and methods: We conducted a retrospective descriptive analysis calculating incidence rates age and sex adjusted for all mandatory reporting events using the affiliation regime (subsidized and contributory) as a socioeconomic proxy. Estimates were made at departmental level for 2015. Social inequalities were calculated in terms of absolute and relative gaps. Results: We found social inequalities in the occurrence of mandatory reporting events in population affiliated to the Colombian subsidized regime (poor population). In this population, 82.31 cases of Plasmodium falciparum malaria per 100,000 affiliates were reported more than those reported in the contributory regime. Regarding the relative gap, belonging to the subsidized regime increased by 31.74 times the risk of dying from malnutrition in children under 5 years of age. Other events such as those related to sexual and reproductive health (maternal mortality, gestational syphilis and congenital syphilis); neglected diseases and communicable diseases related to poverty (leprosy and tuberculosis), also showed profound inequalities. Conclusion: In Colombia there are inequalities by regime of affiliation to the health system. Measured socioeconomic status was a predictor of increased morbidity and premature mortality.

To estimate the cost-effectiveness of available diagnosis alternatives for Mucosal Leishmaniasis (ML) in Colombian suspected patients. A simulation model of the disease's natural history was built with a decision tree and Markov models. The model´s parameters were identified by systematic review and validated by expert consensus. A bottom-up cost analysis to estimate the costs of diagnostic strategies and treatment per case was performed by reviewing 48 clinical records of patients diagnosed with ML. The diagnostic strategies compared were as follows: 1) no diagnosis; 2) parasite culture, biopsy, indirect immunofluorescence assay (IFA), and Montenegro skin test (MST) combined ; 3) parasite culture, biopsy, and IFA combined; 4) PCR-miniexon; and 5) PCR-kDNA. Three scenarios were modeled in patients with ML clinical suspicion, according to ML prevalence scenarios: high, medium and low. Adjusted sensitivity and specificity parameters of a combination of diagnostic tests were estimated with a discrete event simulation (DES) model. For each alternative, the costs and health outcomes were estimated. The time horizon was life expectancy, considering the average age at diagnosis of 31 years. Incremental cost-effectiveness ratios (ICERs) were calculated per Disability Life Year (DALY) avoided, and deterministic and probabilistic sensitivity analyses were performed. A threshold of willingness to pay (WTP) of three-time gross domestic product per capita (GDPpc) (US$ 15,795) and a discount rate of 3% was considered. The analysis perspective was the third payer (Health System). All costs were reported in American dollars as of 2015. PCR- kDNA was the cost-effective alternative in clinical suspicion levels: low, medium and high with ICERs of US$ 7,909.39, US$ 5,559.33 and US$ 4,458.92 per DALY avoided, respectively. ML diagnostic tests based on PCR are cost-effective strategies, regardless of the level of clinical suspicion. PCR-kDNA was the most cost-effective strategy in the competitive scenario with the parameters included in the present model., Competing Interests: The authors have declared that no competing interests exist.

Antimicrobial agents are crucial for the treatment of many bacterial diseases in pigs, however, the massive use of critically important antibiotics such as colistin, fluoroquinolones and 3rd-4th-generation cephalosporins often selects for co-resistance. Based on a comprehensive characterization of 35 colistin-resistant Escherichia coli from swine enteric colibacillosis, belonging to prevalent Spanish lineages, the aims of the present study were to investigate the characteristics of E. coli clones successfully spread in swine and to assess the correlation of the in vitro results with in silico predictions from WGS data. The resistome analysis showed six different mcr variants: mcr-1.1 ; mcr-1.10 ; mcr-4.1 ; mcr-4.2 ; mcr-4.5; and mcr-5.1 . Additionally, bla CTX-M- 14 , bla CTX-M- 32 and bla SHV- 12 genes were present in seven genomes. PlasmidFinder revealed that mcr-1.1 genes located mainly on IncHI2 and IncX4 types, and mcr-4 on ColE10-like plasmids. Twenty-eight genomes showed a gyrA S83L substitution, and 12 of those 28 harbored double-serine mutations gyrA S83L and parC S80I, correlating with in vitro quinolone-resistances. Notably, 16 of the 35 mcr- bearing genomes showed mutations in the PmrA (S39I) and PmrB (V161G) proteins. The summative presence of mechanisms, associated with high-level of resistance to quinolones/fluoroquinolones and colistin, could be conferring adaptive advantages to prevalent pig E. coli lineages, such as the ST10-A (CH11-24), as presumed for ST131. SerotypeFinder allowed the H-antigen identification of in vitro non-mobile (HNM) isolates, revealing that 15 of the 21 HNM E. coli analyzed were H39. Since the H39 is associated with the most prevalent O antigens worldwide within swine colibacillosis, such as O108 and O157, it would be probably playing a role in porcine colibacillosis to be considered as a valuable subunit antigen in the formulation of a broadly protective Enterotoxigenic E. coli (ETEC) vaccine. Our data show common features with other European countries in relation to a prevalent clonal group (CC10), serotypes (O108:H39, O138:H10, O139:H1, O141:H4), high plasmid content within the isolates and mcr location, which would support global alternatives to the use of antibiotics in pigs. Here, we report for first time a rare finding so far, which is the co-occurrence of double colistin-resistance mechanisms in a significant number of E. coli isolates., (Copyright © 2019 García-Meniño, Díaz-Jiménez, García, de Toro, Flament-Simon, Blanco and Mora.)

The aim of the present study was to examine the prevalence and determine the molecular characteristics of extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) causing bacteraemia in a Spanish Hospital over a 12-year period (2000 to 2011). As far as we know, this is the first study which has investigated and compared the serotypes, phylogroups, clonotypes, virotypes, and PFGE profiles of ST131 and non-ST131 clones of bacteraemia ESBL-EC isolates. Of the 2,427 E. coli bloodstream isolates, 96 (4.0%) were positive for ESBL production: 40 for CTX-M-15, 36 for CTX-M-14, eight for CTX-M-1, four for CTX-M-9, CTX-M-32, and SHV-12. The number of ESBL-EC increased from 1.0% during 2000 to 2005 to 5.5% during 2006-2011 ( P < 0.001). The 96 ESBL-EC isolates belonged to 36 different STs. The commonest was ST131 (41 isolates), followed by ST58, ST354, ST393 and ST405 (four isolates each). Most CTX-M-15 isolates (87.5%, 35/40) were ST131, whereas the 36 CTX-M-14 isolates belonged to 23 different STs and only 3 (8.3%) of them were ST131. The 35 ST131 CTX-M-15-producing isolates belonged to the H 30Rx subclone and 29 of them showed the virotype A. A drastic change in ST131 virotypes happened in 2011 due to the emergence of the virotypes E ( sat , papGII , cnf1 , hlyA , and kpsMII-K5 ) and F ( sat , papGII , and kpsMII-K5 ) which displaced virotype A ( afa/draBC , afa operon FM955459, sat , and kpsMII-K2 ). Although the 96 ESBL-EC isolates showed 21 O serogroups and 17 H flagellar antigens, 39 belonged to serotype O25b:H4 (ST131 isolates). The second most prevalent serotype (O15:H1) was found to be associated with another important high-risk clone (ST393). In conclusion, the ST131 was the most frequent sequence type, being the H 30Rx subclone responsible for the significant increase of ESBL-EC isolates since 2006. Here, we report two new virotypes (E and F) of the H 30Rx subclone emerged in 2011. Future molecular studies are needed to understand the dynamics of expansion of this successful high-risk subclone in order to prevent its spread and establish the importance of the two new virotypes.

In colorectal cancer (CRC), cancer-associated fibroblasts (CAFs) are the most abundant component from the tumor microenvironment (TM). CAFs facilitate tumor progression by inducing angiogenesis, immune suppression and invasion, thus altering the organization/composition of the extracellular matrix (i.e., desmoplasia) and/or activating epithelial-mesenchymal transition (EMT). Soluble factors from the TM can also contribute to cell invasion through secretion of cytokines and recently, IL-33/ST2 pathway has gained huge interest as a protumor alarmin, promoting progression to metastasis by inducing changes in TM. Hence, we analyzed IL-33 and ST2 content in tumor and healthy tissue lysates and plasma from CRC patients. Tissue localization and distribution of these molecules was evaluated by immunohistochemistry (using localization reference markers α-smooth muscle actin or α-SMA and E-cadherin), and clinical/histopathological information was obtained from CRC patients. In vitro experiments were conducted in primary cultures of CAFs and normal fibroblasts (NFs) isolated from tumor and healthy tissue taken from CRC patients. Additionally, migration and proliferation analysis were performed in HT29 and HCT116 cell lines. It was found that IL-33 content increases in left-sided CRC patients with lymphatic metastasis, with localization in tumor epithelia associated with abundant desmoplasia. Although ST2 content showed similarities between tumor and healthy tissue, a decreased immunoreactivity was observed in left-sided tumor stroma, associated to metastasis related factors (advanced stages, abundant desmoplasia, and presence of tumor budding). A principal component analysis (including stromal and epithelial IL-33/ST2 and α-SMA immunoreactivity with extent of desmoplasia) allowed us to distinguish clusters of low, intermediate and abundant desmoplasia, with potential to develop a diagnostic signature with benefits for further therapeutic targets. IL-33 transcript levels from CAFs directly correlated with CRC cell line migration induced by CAFs conditioned media, with rhIL-33 inducing a mesenchymal phenotype in HT29 cells. These results indicate a role of IL-33/ST2 in tumor microenvironment, specifically in the interaction between CAFs and epithelial tumor cells, thus contributing to invasion and metastasis in left-sided CRC, most likely by activating desmoplasia.

Introduction: Suicide is a serious social and public health problem that affects the population in most countries in the world. Differences in suicide rates in rural and urban areas have been previously described. Objective: To study the trend of mortality rates by suicide in Colombia, in rural and urban areas by gender, age group, and suicide method during the years 1979-2014. Materials and methods: We conducted a temporal trend ecologic study using death certificates from the Departamento Administrativo Nacional de Estadística, DANE. Specific and adjusted by age and gender mortality rates were calculated. We estimated negative binomial and inflection point regression models to study the trends in mortality rates stratified by gender, age group, and suicide method. Results: A total of 56,448 suicides was reported in Colombia between 1979 and 2014. The risk of suicide was higher in urban areas for men, individuals between 25 and 44 years, and 65 and over; and for those who used hanging as the suicide method. Also, the risk of suicide was higher in the rural area for men between 45 and 64 years old, and those who used firearms, sharp weapons, hanging, and others as suicide methods. The trend of suicide rates in urban areas showed its maximum peak in 1999 and in the rural ones in 2000. Then, in the two areas, there was a gradual decrease. Hanging in both areas presented a tendency to rise in men. Conclusions: Suicide has shown a tendency toward reduction after the year 2000, with differences between urban and rural areas.

Objective: The aim of the present study was to estimate the economic impact of chikungunya virus (CHIKV) infection in Colombia from a societal perspective., Methods: We conducted a retrospective, bottom-up cost-of-illness study in clinically confirmed cases during the first chikungunya (CHIK) outbreak in Colombia in 2014. Direct and indirect costs were estimated per patient. Economic costs were calculated by the addition of direct costs (direct medical costs and out-of-pocket heath expenditures) and indirect cost as a result of loss of productivity., Results: A total of 126 patients (67 children and 59 adults) with CHIK were included. The median of the direct medical cost in children was US$257.9 (interquartile range [IQR] 121.7-563.8), and US$66.6 (IQR 26.5-317.3) for adults. The productivity loss median expenditures reached US$81.3 (IQR 72.2-203.2) per adult patient. The median economic cost in adults as a result of CHIK was US$152.9 (IQR 101.0-539.6), of which 53.2% was a result of indirect costs. Out-of-pocket expenditures comprised 3.3% of all economic costs., Conclusions: Our study can help health decision makers to properly assess the burden of disease caused by CHIK in Colombia, an endemic tropical country. We recommend to strength the health information systems and to continue investing in public health measures to prevent CHIK., (Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

This is a wide epidemiological study of 499 E. coli isolates recovered from 179 outbreaks of enteric colibacillosis from pig production farms in Spain during a period of 10 years. Most samples were of diarrheagenic cases occurred during the post-wean period (PWD) which showed to be significantly associated with ETEC (67%) followed by aEPEC (21.7%). On the contrary, aEPEC was more prevalent (60.3%) among diarrheas of suckling piglets, followed by ETEC (38.8%). STEC/ETEC or STEC were recovered in 11.3 and 0.9% of PWD and neonatal diarrhea, respectively. Detection of the F4 colonization factor was not significantly different between isolates recovered from neonatal pigs and those recovered post wean (40.5 versus 27.7%) while F18 was only present among PWD isolates (51.5% of ETEC, STEC, and STEC/ETEC isolates). We also found a high prevalence of resistance to colistin related to the presence of the mcr-1 gene (25.6% of the diarreagenic isolates). The characterization of 65 representative mcr-1 isolates showed that all were phenotypically resistant to colistin (>2 μg/ml), and most (61 of 65) multidrug-resistant (MDR). Six ETEC and one STEC mcr-1 isolates were also carriers of ESBL genes. In addition, other seven mcr-1 isolates harbored mcr-4 (three ETEC) and mcr-5 (two ETEC and two aEPEC) genes. In the phylogenetic analysis of the 65 mcr-1 diarrheagenic isolates we found that more than 50% (38 out of 65) belonged to A-ST10 Cplx and from those, 29 isolates showed the clonotype CH11-24. In this study, we also recovered 18 ST131 isolates including seven mcr-1 carriers. To the best of our knowledge, this would be the first report of ST131 mcr-1 isolation in pigs. Worryingly, the swine mcr-1 ST131 carriers also showed MDR, including to trimethoprim-sulfamethoxazole, tobramycin, gentamicin and ciprofloxacin. In the PFGE-macrorestriction comparison of clinical swine and human ST131, we found high similarities (≥85%) between two pig and two human ST131 isolates of virotype D5. Acquisition of mcr-1 by this specific clone means an increased risk due to its special feature of congregating virulence and resistance traits, together with its spread capability. Here we show a potential zoonotic swine source of ST131.

We present a clinical case of a premature birth from a mother of 33+5 weeks gestation where the newborn was admitted to the neonatal unit due to her low weight, chest retraction and prematurity, despite an Apgar score of 8/9/10 and birth weight of 1.300 g. The team of midwives that attended the woman from her arrival performed an assessment according to Virginia Henderson's Needs. Nursing diagnoses for the mother of Situational low self- esteem and Deficient Knowledge were established, and of Ineffective thermoregulation for the newborn infant. The care plan was based in great measure on the Kangaroo-mother care method which was started in the neonatal unit, and adapted to the needs and care required by the newborn infant. The method enabled the parents to cope with the situation in a better way and the vital signs of the infant to be maintained., (Copyright © 2018 Elsevier España, S.L.U. All rights reserved.)

Colistin is an antimicrobial polypeptide commonly employed for controlling and treating neonatal and post-weaning diarrhoea (PWD) diseases caused by Enterotoxigenic and Shiga toxin-producing Escherichia coli (ETEC and STEC). The plasmid-mediated colistin resistance gene, mcr-1 was first described in late 2015 and, since then, multiple studies have reported its global distribution. In addition, five different mcr genes have been identified. The aim of this study was to characterise the colistin-resistant E. coli clonal groups implicated in PWD in farms of intensive pig production. Of 186 ETEC and STEC isolated in Spain from 2006 to 2017, 76.9% showed resistance to colistin. Of those, 102 were mcr-4 carriers, 37 mcr-1 and 5 mcr-5, with co-occurrence of mcr-1/mcr-4, mcr-1/mcr-5 and mcr-4/mcr-5 in five isolates. Three different mcr-4 variants were detected, including the new mcr-4.4 and mcr-4.5 described here. Interestingly, the clonal group ST10-A (CH11-24) appears to be primarily responsible for the spread of mcr-4. In summary, our results show that the pig industry is an important reservoir of colistin-resistant E. coli, carriers of other additional risk genes, such as bla ESBL . These food-producing animals might be spreading a cocktail of multiple resistances, posing a worrisome threat to human health., (Copyright © 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

Female genital mutilation, condemned by all UN member countries has spread throughout the world as a result of migratory flows and is practiced under the guise of a custom, tradition or culture. In Spain, it is punishable as a personal injury offence under the current penal code. A clinical case study reviewedthe main actions of the midwife in this kind of injury in a pregnant woman during labour. The data collected from the physical examination and the midwife's assessment according to the Virginia Henderson model are presented and a complete care plan developed. From the case it can be concluded that in the hospital area, midwives can and should reinforce and complete the work with these women and their families, of informing, educating and reinforcing the decision not to mutilate. This work should have been started in, the health centre., (Copyright © 2017 Elsevier España, S.L.U. All rights reserved.)

Inflammatory bowel diseases (IBDs), such as ulcerative colitis and Crohn's disease, are chronic pathologies associated with a deregulated immune response in the intestinal mucosa, and they are triggered by environmental factors in genetically susceptible individuals. Exogenous glucocorticoids (GCs) are widely used as anti-inflammatory therapy in IBDs. In the past, patients with moderate or severe states of inflammation received GCs as a first line therapy with an important effectiveness in terms of reduction of the disease activity and the induction of remission. However, this treatment often results in detrimental side effects. This downside drove the development of second generation GCs and more precise (non-systemic) drug-delivery methods. Recent clinical trials show that most of these new treatments have similar effectiveness to first generation GCs with fewer adverse effects. The remaining challenge in successful treatment of IBDs concerns the refractoriness and dependency that some patients encounter during GCs treatment. A deeper understanding of the molecular mechanisms underlying GC response is key to personalizing drug choice for IBDs patients to optimize their response to treatment. In this review, we examine the clinical characteristics of treatment with GCs, followed by an in depth analysis of the proposed molecular mechanisms involved in its resistance and dependence associated with IBDs. This thorough analysis of current clinical and biomedical literature may help guide physicians in determining a course of treatment for IBDs patients and identifies important areas needing further study., Competing Interests: Conflict-of-interest statement: No potential conflicts of interest.

Background: Different strains of invasive Escherichia coli (E. coli), isolated from intestinal mucosa of patients, are related to the pathogenesis of inflammatory bowel diseases (IBD)., Aim: To evaluate an association between intracellular E. coli and IBD; its clinical characteristics and use of steroids., Material and Methods: Sixty one patients with Crohn's disease and 83 with ulcerative colitis were studied. To determine the intracellular E. coli content, colonoscopy biopsies of these patients and 29 control subjects were processed using the gentamicin protection assay. Differences in the bacterial content between patient groups were evaluated using Mann-Whitney test, while the association between presence of E. coli with endoscopic activity, location/extension and use of corticosteroid as anti-inflammatory treatment were evaluated with Fisher's exact test or Chi-square test., Results: E. coli strains were detected in 36.1, 39.3 and 10.3% of patients with ulcerative colitis, Crohn's disease and controls, respectively. The number of bacteria per biopsy in Crohn's disease and ulcerative colitis was significantly higher than in controls (p < 0.01 between patients and controls). In ulcerative colitis, significant associations were found between the presence of bacteria and disease location and use of corticosteroids. In Crohn's disease, no association was found., Conclusions: IBD are associated with the presence of intracellular E. coli strains in the intestinal mucosa, suggesting an alteration in the microbiota or loss of integrity of the epithelial barrier. The association of intracellular E. coli with clinical features and the use of corticosteroids in ulcerative colitis suggests that different factors could promote colonization or proliferation of these bacteria.

The ST2/IL33 signalling pathway has been associated with ulcerative colitis (UC). ST2, encoded by the IL1RL1 gene, is expressed as both a membrane-anchored receptor (ST2L) activated by IL33 and as a soluble receptor (sST2) with anti-inflammatory properties. In UC patients, sST2 is further increased by corticosteroid treatment; however, the glucocorticoid-mediated molecular regulation remains unknown. We therefore tested whether genetic variants in the IL1RL1 distal promoter are involved in UC and affect glucocorticoid-mediated ST2 expression. Serum ST2 levels and genetic variants in the IL1RL1 distal promoter were examined by ELISA and PCR sequencing in UC patients receiving corticosteroids. Glucocorticoid-mediated ST2 production was evaluated in intestinal mucosa cultures. Molecular regulation of glucocorticoid-mediated ST2 was assessed by RT-qPCR, ChIP assay and luciferase reporter assay. Dexamethasone effect on ST2 transcript expression was analyzed in leukocytes and related to IL1RL1 variants. Sequencing of a distal IL1RL1 promoter region demonstrated that SNPs rs6543115(C) and rs6543116(A) are associated with increased sST2 in UC patients on corticosteroids. Dexamethasone up-regulated sST2 transcription through interaction with the glucocorticoid-response element (GRE) carrying rs6543115(C) variant. Our data indicate that IL1RL1 SNPs rs6543115(C) confer susceptibility to UC and is contained in the GRE, which may modulate glucocorticoid-induced sST2 expression.

Background: The ST2/IL-33 pathway has been related to ulcerative colitis (UC), and soluble ST2 (sST2), to disease severity. We tested the potential usefulness of sST2 as a predictive marker of treatment response and patients' outcome., Methods: Twenty-six patients with active UC were prospectively recruited and grouped according to an endoscopic score and therapy response. Colonoscopic biopsies were collected at baseline and 6 months or when patients showed clinical activity. The protocol was reinitiated in patients requiring rescue therapy. Blood and stool were collected at baseline, 1, 3, 6 and 12 months. Serum and mucosal ST2, and fecal calprotectin (FC) content were determined by ELISA and correlated to Mayo clinical and endoscopic subscore. Intestinal ST2 was evaluated by immunofluorescence. Wilcoxon signed rank test and Spearman correlations (Rs) were applied (p <0.05)., Results: Follow-up was completed in 24 patients. sST2 levels (median and range) varied from 173.5 [136.6-274.0] to 86.5 [54.6-133.2] in responders (p < 0.05), and 336.3 [211.0-403.2] to 385.3 pg/mL [283.4-517.3] in non-responders at baseline and 6 months, respectively. sST2 levels correlated with Mayo clinical and endoscopic subscore, mucosal ST2 and FC (Rs = 0.57, 0.66, 0.74 and 0.42, respectively; p < 0.0001) and showed a trend similar to that of FC in responders. Non-responders revealed an increased ST2 content, restricted to the lamina propria's cellular infiltrate., Conclusions: Consecutive sST2 measurement to follow changes in inflammatory activity of UC patients who respond or not to treatment identifies sST2, like FC, as a useful biomarker in predicting clinical outcome of UC patients.

Objective: To estimate the economic costs of avoidable mortality (AM) in Colombia during the period 1998 to 2011, with the human capital perspective valuing the productivity lost., Methods: The information of cases of avoidable death was identified from the Colombian official general mortality database, and we estimated the potential productivity years of life lost, assuming a productive life span between 18 years and 57 years and 18 years and 62 years in women and men, respectively. Two scenarios were built: lower loss with the minimum wage, and higher loss with the per capita gross domestic product. Total costs for the period were reported by sex and health event. Average cost per 1000 people was also estimated. All costs were adjusted and reported in 2012 US dollars., Results: Sixty-eight percent of the total AM in Colombia during the period 1998 to 2011 occurred during or before the productivity age. The total AM costs were estimated to range between US $80.5 million and US $150.4 million. Higher costs of AM were incurred in men. Events from the injuries group caused the higher productivity lost., Conclusions: All the avoidable deaths in Colombia have a huge economic impact from the productivity lost perspective, equivalent to between 1.6% and 3.0% of the annual gross domestic product. The cost analyses in public health are an additional input for decision making and prioritization of intervention., (Copyright © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Objectives: A hallmark characteristic of SS patients is the ectopic presence of the mucins MUC5B and MUC7 in the extracellular matrix of salivary glands that have lost apical-basolateral acinar-cell polarity. This study aims to determine whether exogenous salivary mucins induce gene expression of pro-inflammatory cytokines, as well as to evaluate whether the Toll-like receptor-4 (TLR4) pathway is involved in this response., Methods: Differentiated human submandibular gland (HSG) cells were stimulated with mucins or oligosaccharide residues at different concentrations and for different periods of time. The expression of pro-inflammatory cytokines and their receptors was determined by semi-quantitative real time PCR (sqPCR). TLR4-mediated responses induced by mucin were evaluated with the Toll-IL-1 receptor domain containing adaptor protein (TIRAP) inhibitory peptide or using anti-hTLR4 blocking antibody. TLR4-receptor expression was also determined in SS patients, controls and HSG cells., Results: Mucins induced a significant increase in CXCL8, TNF-α, IFN-α, IFN-β, IL-6 and IL-1β, but not B cell activating factor (BAFF). Cytokine induction was mediated by TLR4, as shown using TIRAP or using anti-hTLR4 antibody. Sugar residues present in MUC5B, such as sulpho-Lewis (SO3-3Galβ1-3GlcNAc), also induced cytokines. Unexpectedly, mucins induced MUC5B, but not MUC7 expression., Conclusion: Salivary mucins were recognized by TLR4 in epithelial cells initiating a pro-inflammatory response that could attract inflammatory cells to amplify and perpetuate inflammation and thereby contribute to the development of a chronic state characteristic of SS. The ectopic localization of MUC5B and MUC7 in the salivary gland extracellular matrix from SS patients and the current results reveal the importance of salivary epithelial cells in innate immunity, as well as in SS pathogenesis., (© The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: Estimate the Years of Life Lost (YLL) for overall and avoidable causes of death (CoD) in Colombia for the period 1998-2011., Methods: From the reported deaths to the Colombian mortality database during 1998-2011, we classified deaths from avoidable causes. With the reference life table of the Global Burden of Disease (GBD) 2010 study, we estimated the overall YLL and YLL due to avoidable causes. Calculations were performed with the difference between life expectancy and the age of death. Results are reported by group of cause of death, events, sex, year and department. Comparative analysis between number of deaths and YLL was carried out., Results: A total of 83,856,080 YLL were calculated in Colombia during period 1998-2011, 75.9% of them due to avoidable CoD. The year 2000 reported the highest number of missed YLL by both overall and avoidable CoD. The departments with the highest YLL rates were Caquetá, Guaviare, Arauca, Meta, and Risaralda. In men, intentional injuries and cardiovascular and circulatory diseases had the higher losses, while in women YLL were mainly due to cardiovascular and circulatory diseases., Conclusions: The public health priorities should focus on preventing the loss of YLL due to premature death and differentiated interventions by sex.