N = 4133) were included. There were significant effects in favor of the MedSD for waist circumference, triglycerides, blood glucose, systolic blood pressure, and diastolic blood pressure . The MedSD was significantly beneficial when the intervention was longer in duration, was conducted in Europe, used a behavioral technique, and was conducted using small groups. The traditional MedSD had significant beneficial effects on five of the six metabolic risk factors. Results from this study provide support for population specific dietary guideline for metabolic risk reduction.The Mediterranean-style diet (MedSD) has gained attention for its positive effects on health outcomes, including metabolic risk factors. However, it is unknown as to which components of MedSD interventions are most beneficial in reducing risk. The objective of this meta-analysis was to obtain effect sizes for metabolic risk factors and explain the variability across the current literature based on study design, sample, and diet characteristics. Six electronic databases were searched from inception until 9 February 2016. Data from 29 studies ( Metabolic syndrome is defined as a group of interrelated risk factors of metabolic origin that appear to directly promote the development of cardiovascular disease (CVD) . The NatLifestyle therapies such as diet modification and physical activity are currently recommended as first-line interventions to reduce metabolic risk factors . The Medi.e., blood pressure and lipid profiles). Taken together, the findings from the meta-analysis by Kastorini et al. [To our knowledge, only one meta-analysis has evaluated literature on the effects of a MedSD on metabolic syndrome . This mei et al.  noted abi et al.  clearly et al. [The data sources were obtained following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement  guidelinet al.  were scrStudies had to meet the following criteria to be included: (1) report pre-and post-intervention data on waist circumference ; and (2) focus on the MedSD as a whole dietary pattern. Studies were excluded if they (1) did not have pre- and post-intervention data on waist circumference; (2) focused on particular components of the Mediterranean diet, such as only olive oil; (3) included exercise in the intervention; (4) included participants <18 years of age; (5) restricted calorie intake; and (6) did not report the information in a way that would allow effect sizes to be calculated using the published information. The relevance of studies was assessed by two independent researchers (M.G. and J.S.) with a hierarchical approach on the basis of title, abstract, and full manuscript. The original search resulted in 1696 abstracts with relevant key words. After screening and hand-searching articles, 29 articles  that used the traditional MedSD were included in analysis. Refer to A comprehensive and detailed coding form and manual was created by a multidisciplinary team. The coding form includes approximately 330 variables for each study. Various characteristics were extracted from each study: (1) sample characteristics such as ethnicity, number and proportion of females, location of sample, and recruitment details; (2) intervention characteristics such as length of intervention, diet type, distribution of macronutrients, calorie intake, and participation in dietary counseling; and (3) study design characteristics such as number of interventions, type of control group, experimental conditions, and setting. The coding form was pilot-tested by two independent researchers (M.G. and J.S.) and was reviewed by additional experts  before being finalized. The coding form and manual are available upon request to the corresponding author. All 30 studies were independently reviewed and coded by two researchers (M.G. and J.S.) and disagreements were solved by a third-party expert (T.B.H.-M).The Cochrane Collaboration’s tool for assessing risk of bias was used to assess risk of bias within individual studies . In accoMethodological quality (MQ) rankings have been identified as an under-analyzed element of the data reported in meta-analyses . In thisr = 1). We tested for asymmetries by using the Begg [Inter-rater reliability was calculated for all continuous and categorical variables. The kappa (κ) coefficient was used to calculate categorical agreement   were calculated for each outcome by calculating the standardized mean change  for eacheristics ,23. Onlyeristics ,25 and teristics ,27,28.Q [I2 [d+) at meaningful levels of the moderators and their Confidence Intervals (Cis) at different levels of interest. This technique was used to demonstrate results at the maximum and minimum values of significant moderators. Two-sided statistical significance was p < 0.05. Finally, clinical units of measures were included by transforming arithmetically the standardized ES to its unstandardized version [Weighted mean effect size by the inverse of the variance of each study was calculated across all studies under random- and fixed-effects assumptions . To testQ  and I2 [Q [I2  were calQ [I2  was used version .A description of the included studies can be found in +d = −0.54, 95% CI −0.77 to −0.31; +d = −0.46, 95% CI −0.72 to −0.21; +d = −0.50, 95% CI −0.81 to −0.20; +d = −0.72, 95% CI −1.03 to −0.42; +d = −0.94, 95% CI −1.45 to −0.44, respectively), but did not have a significant effect on HDL . There was large heterogeneity between studies with I2 ranging from 92.98% to 98.42%.The traditional MedSD was found to have a significant beneficial effect on five out of six outcomes of interest . OverallAll moderation effects are presented in i.e., a different type of diet) had more beneficial significant effect sizes favoring the MedSD compared to those studies using a traditional pre-/post-design or a crossover design.Significant associations were found for study design waist circumference, HDL cholesterol, triglycerides, fasting blood glucose and systolic blood pressure. Studies that included a comparison intervention group design (Impact per Publication (IPP) value showed more significant beneficial effects for waist circumference, HDL cholesterol, triglycerides, and fasting blood glucose with significant positive associations for each.Studies with a higher The length of the intervention (in weeks) significantly explained between 27.89% and 51.13% of the variability between studies for the following outcomes: waist circumference, HDL cholesterol, triglycerides, fasting blood glucose and systolic blood pressure. There was a significant positive association for length of intervention for all six outcomes of interest . The loni.e., primarily one-on-one or small groups) resulted in significant or trending associations for waist circumference, HDL cholesterol, triglycerides, fasting blood glucose and systolic blood pressure. Interventions consisting of small groups saw significant beneficial effects for all six outcomes, whereas interventions that were primarily one-on-one resulted in only two significant outcomes.The level of intervention or supervision during the study (In regards to specific components of the traditional MedSD interventions, specific macronutrient proportions of the diet, assessment of dietary compliance and participant engagement in dietary counseling did not significantly explain the variability between studies. Participant characteristics, in particular the presence or absence of certain disease states, were also analyzed as moderators. Disease states that were included in this analysis were cardiovascular disease, type II diabetes mellitus, metabolic syndrome, and overweight/obesity. These variables were not considered to be significant moderators.Risk of bias was unclear for random sequence generation, allocation, blinding, incomplete outcome data, selective reporting, and other potential sources of bias . ModeratThe present meta-analysis of 29 intervention trials found that the traditional MedSD has significant beneficial effects for five out of six of the metabolic risk factors: waist circumference, triglycerides, fasting blood glucose, systolic blood pressure and diastolic blood pressure. The significant heterogeneity between studies was partly attributed to the location of the studies, the length of the intervention, and the IPP value of the journal where the study was published. Significant beneficial associations were found for studies conducted in Europe, those of longer duration, studies using a behavioral technique, studies with a comparison intervention group, and studies conducted primarily in groups for most of the metabolic risk factors. To our knowledge, this is the first meta-analysis to evaluate the effects of the Mediterranean diet on metabolic syndrome that meets 100% of the AMSTAR criteria .Our findings that a traditional MedSD is beneficial in reducing the risk of CVD-associated metabolic parameters complements and extends previous work in this area. Several recent systematic reviews and meta-analyses published on the MedSD and CVD risk have reported similar positive effects on HDL cholesterol , triglycet al. [et al. found that the MedSD was associated with reductions in waist circumference, triglycerides and fasting glucose levels. The MedSD was also associated with beneficial effects on HDL cholesterol, whereas there were no association for systolic and diastolic blood pressure [et al. [et al. [To our knowledge, only one meta-analysis has been published on the effects of the Mediterranean diet on metabolic syndrome . The metet al.  includedpressure . However [et al.  differed [et al. . For the [et al. .Our meta-analysis had several limitations. There is significant heterogeneity between studies that could not be explained by the moderators included in our analyses. The data reported in our sample of studies did not allow us to control for baseline physical activity or different types and duration of on-going exercise, and thus, physical activity could not be included as a moderator. Weight loss was not the objective in any of the included studies, however, we did not control for weight change among participants. Lastly, ecological fallacy is a possibility as we did not have access to the raw data from the included studies and should be cautious interpreting the group results as individual effects. There are also multiple strengths for this meta-analysis. We used a comprehensive literature search in six electronic databases and an inclusive and comprehensive coding form and manual were used for data extraction. We performed moderation analysis on all variables with sufficient data provided in the published material. We excluded interventions that included exercise, which we believed would have precluded us from solely evaluating diet-associated effects. To our knowledge, this is the first meta-analysis to find significant beneficial associations for MedSD interventions that use behavioral techniques and small group interventions and metabolic risk factors. Lastly, we were able to use the moving constant technique and a predictive model to calculate effect sizes for each significant moderator and transform that effect size into clinical units of measure.The results of the present meta-analysis suggest that the traditional MedSD can have risk reduction effects on a number of metabolic parameters. In addition, the MedSD was significantly beneficial for different metabolic risk factors when, in general the intervention was longer in duration, the study was conducted in Europe, the report was published in a journal with higher Impact per Publication value, the study included a comparison intervention, a behavioral technique was used, and the study was conducted using small groups. More high-quality intervention studies conducted in non-European countries that control for physical activity and changes in weight, and include objective measures of compliance are warranted and would allow for further moderator analyses.


Frailty was determined from the presence of three or more ofthe following factors: (i) self-reported unintentional weight loss; (ii) lack ofstrength and energy; (iii) weakness; (iv) slowness; (v) low level of physicalactivity. The association between frailty and socio-demographic, behavioral andhealth factors was measured using the multinomial logistic regression technique. The prevalence of pre-frailty and frailty was 58.7% and 23.8%, respectively. Theadjusted regression model showed that the state of pre-frailty was associated withgender, age group and BMI, and frailty was associated with gender, age group,hospitalization, functional capacity, and self-perceived health.  The evidence presented in this study demonstrates more variables associated withthe frailty condition, reinforcing the concept of a multifactorial clinicalsyndrome that may result in the loss of functionality. The aging process brings changes, which together with the increased prevalence ofchronic diseases can cause the onset of geriatric syndromes, among which the frailtysyndrome is highlighted. Frailty includes factors of different orders, beingcharacterized as a syndrome resulting from the loss of physiological reserves andadaptation to stressors, where the energy deficit, sarcopenia, decreases the musclestrength and tolerance to effort leading to an exacerbated decline in multiple systemsthat places the individual in a condition of greater vulnerability. . There is no defined scientific consensus regarding the term frailty, itsdefinition and its indicators, nor how it can be identified or even evaluated. However,the majority of studies that deal with frailty generally define it as an unstablecondition related to functional decline, from the interaction of the individual with theenvironment, in which, an event considered of minor impact can cause limitations in theperformance of voluntary activities and result in the loss of autonomy and functionalcapacity.Frailty has increasingly emerged as an important concept, both in the clinical care ofolder people, as well as in studies on aging. As a clinical syndrome, it is usuallyassociated with an increased risk of adverse situations such as falls, disabilities,institutionalization, and death. There capacity..The reversal of the installation of advanced frailty frameworks may be linked to theidentification of factors that are considered open to modifications, such associoeconomic conditions, lifestyle, and social support, in which the earlyidentification of signs and symptoms causing the frailty syndrome may indicate theadoption of objective interventions that prevent complications of the frailty andinjuries in the elderly population.. In addition, research into the identification of frailty in the elderly isat an early stage, therefore there are few population-based studies that present factorsinvolved in the process of frailty in the Brazilian population.In Brazil, the majority of municipalities experience an increase in the number ofelderly in the population each year. They present poor health indicators and this maycontribute to the development of early frailty resulting in an unfavorable prognosiswith dependence, hospitalization and severe complications in the subsequentyears. In addWhen studying frailty it is essential to consider the context in which this processtakes place. Since Brazil is a country of continental dimensions it is essential tounderstand how frailty develops in regions marked by pronounced social inequalities.Thus, the aim of this study was to identify the prevalence and the factors associatedwith pre-frailty and frailty of elderly residents in a community with a low humandevelopment index.This is a cross-sectional study that is part of epidemiological study with a communityand populational basis, the title of which is: Nutritional status, risk behaviors andhealth conditions of the elderly people of Lafaiete Coutinho-BA. A census was conductedin January 2011 with elderly people residing in urban areas, registered in the FamilyHealth Strategy, which achieves 100% coverage. All those aged ≥60 years (n=355) werecontacted for interviews and to carry out examinations . Of the 355 elderly people, 316participated in the study (89.0%). There were 17 refusals (4.8%) and 22 (6.2%)individuals were not located in their residences after three visits at differenttimes., with the International Physical Activity Questionnaire (IPAQ), adapted for the elderly(7) added to this, as well as theGeriatric Depression Scale (GDS), used for screening for depression in the elderly andconsisting of 15 questions with yes or no answers, also having been validated for use inBrazil.A specific form was used, based on the questionnaire used in the Health, Welfare andAging Study - SABE (http://hygeia.fsp.usp.br/sabe/quetionario.php), conducted in sevencountries in Latin America and the Caribbean, with te (IPAQ), adaptenBrazil.: 1. Weight Loss: defined by the self-report of unintentional weight loss of≥3 kg during the 12 months preceding the study, as the instrument used was based on the SABE study, which does not make anobjective prediction for weight loss. 2. Muscle weakness: Manual Gripping Force (MGF)was evaluated by means of a hydraulic dynamometer .Frailty was defined according to the gender and body mass index (BMI). For eachcategory, the cutoff points for the MGF (Kgf) were fixed in the 25th percentile, withadjustments for gender and BMI. The cutoff points for men adopted were: 0<BMI<22 -MGF≤19Kgf.; 22≤BMI≤27 - MGF≤21Kgf., BMI>27 - MGF≤22Kgf.; and for women:0<BMI<22 - MGF≤11Kgf.; 22≤BMI<27 - MGF≤15Kgf., BMI>27 - MGF≤14Kgf. 3. Lowresistance and energy: defined based on two questions of the GDS: "Have you put aside many of your activities and interests?" and "Do youfeel full of energy?". A positive answer to the first question and/or a negative answerto the second were considered evidence of low resistance/lack of energy. 4. Slowness inthe walking test: defined through the physical performance of a 2.44m walking test. Theslowness was adjusted according to the gender and height of the elderly person. Theheight was divided into two categories based on the median (50th percentile)men ≤1.61m and women ≤1.49m, below or equal to the median; men >1.61m and women>1.49m, above the median. For each category the cutoff points that considered theindividual slow in the walking test were fixed in the 75th percentile: belowor equal to the median, ≥5s and ≥6s ; above the median,≥4s (for both genders). Low level of physical activity: The instrument used to evaluatethe level of habitual physical activity was the International Physical ActivityQuestionnaire (IPAQ). The individuals who performed less than 150 minutes per week of moderateand/or vigorous physical activity were considered insufficiently active.Frailty (dependent variable) was identified according to the modified version offrailty, considering five components: 1. Weihe study, as the the GDS: "Have . All the individuals who responded to only 3 components and that wereclassified as frail were considered. Individuals who answered at least 4 components forthe classification of frailty were considered eligible for the otherclassifications. Thus, 286 subjects, classified according to frailty phenotype, wereincluded in the analysis.An ordinal variable with scores ranging from zero to five (0-5) was created from the sumof the points of all the components, with the following classification adopted: 0 points= not frail; 1-2 points = pre-frail; ≥3 points = frailications. Thus, 2 =underweight, 22 kg/m2≤BMI≤27kg/m2 = appropriate, andBMI>27kg/m2 = overweight), Fall event in the previous year, Number of self-reported chronic diseases,and Functional capacity (measured through the Basic Activities of Daily Living (BADL)using the Katz scale and Instrumental Activities of Daily Living (IADL), using the Lawtonscale). The explanatory variables were: 1. Sociodemographic: Gender, Age group, Knowledge of howto read and write a message, Family arrangement, Participation in religious activity. 2.Behavioral: Consumption of alcoholic beverage, and Use of tobacco. 3. Health conditions:Hospitalization in the previous year, Body Mass Index BMI: (BMI<22kg/mrweight), Fall etz scale and Insonscale).  to verify the reliability of the answers - score >12 = not compromisedand score ≤12 = compromised). When the cognitive status score was not reached, theinformant was asked to responded to another instrument, which was the FunctionalActivities questionnaire of Pfeffer, with information pertaining to the elderly person, thus evaluating theneed for a substitute informant during the interview. Amount of medications used, Self-perceived health, and Cognitive status  in the crude analysis were included in theadjusted analysis, following the order of a hierarchical model for the determination ofthe outcomes.According to the model established, the variables of the upper levels  interactamong themselves and determine the variables of the lower levels . Regardingthe effect of each explanatory variable on the outcome, the variables of the same leveland upper levels in the model were controlled for, with the statistical criterion forremaining in the model being 20% (p≤0.20).(r)), version 16.0program.The study was approved by the Research Ethics Committee of the State University ofSouthwest Bahia (nº 064/2010). Data were tabulated and analyzed using the StatisticalPackage for the Social Sciences for Windows , age group (p<0.001), knows how to read and write a message (p=0.029), hospitalization in the previous year (p=0.003), BMI (p=0.006), fall event(p=0.012), number of chronic diseases (p=0.044), functional capacity (p<0.001),medication use (p=0.002), self-perceived health (p=0.005) and cognitive status (p=0.004).In the first step the variables of the sociodemographic block were analyzed, and thevariables that remained associated with the frail stage were: female gender (p=0.031)and age group ≥80 years (p<0.001) and, with the pre-frail stage, also female gender(p=0.037) and age group ≥80 years (p=0.001).In the second step the variables of the health conditions block were included and thosethat continued to be associated with the frail classification were: hospitalization inthe previous year, one or more times (p=0.033), functional capacity for both dependentin the IADL (p<0.001), as well as in the BADL and IADL (p=0.007), and alsoself-perceived negative health (p=0.007). Only the underweight BMI variable (p=0.015)remained associated with the pre-frail classification.The variables related to behavioral aspects, i.e., consumption of alcoholic beveragesand tobacco use were not included in the adjusted model, as they did not present atleast 20% statistical significance (p≤0.20).. The explanation for the wide variation in the prevalence of frailty in theelderly is probably related to socioeconomic differences among the elderly peoplestudied, as well as the methodological differences in the use of some instruments thatdiffer from those that compose the items used.In the present study 23.8% of the elderly people were frail, 58.7% pre-frail, and 17.5%non-frail. The frailty prevalence values were higher when compared to internationalstudies. The exems used..In the present study women had a higher prevalence in both the pre-frail and frailcategories, corroborating other studies that indicated that elderly women are frailerthan elderly men, and presented a frailty prevalence of over 13% for the men and 17% forthe women. Over three years, the women had twice the pre-frailty incidence ratescompared to the men.In a study conducted in Taiwan, which estimated the prevalence of frailty and identifiedfactors associated with frailty, from the data of the Survey of Health and Living Statusof the Elderly, it was found that the prevalence of frailty increased with age and washigher in women.Fibra), analyzed prevalence characteristics and associated factorsrelated to frailty and, of the sociodemographic variables included in the model, onlyage was associated, even when adjusted for the other variables, thus demonstrating theinfluence of the aging process on the emergence of frailty.Longevity is another aspect that should be taken into consideration. A national study,which is part of the multicentric project Frailty in Elderly Brazilians. Others, however, have reported an association of increased BMI values with thefrail situation, mainly observed in frail elderly women..The findings of the present study were consistent with the results of the study in whichfive Latin American and Caribbean cities were investigated, including São Paulo, Brazil,which verified that higher BMI values for women were related to a greater probability offrailty.. The data obtained are consistent with the literature in that, afteradjustment, an association between the BADL, IADL and frailty was also found.The observation of the association between dependence in performing instrumental andbasic activities and frailty is presented in national and international studies,demonstrating the degree of injury that this impairment generates in the elderly, bydirectly limiting them in their autonomy, resulting in a decrease in the quality oflife. The daso found..However, it is critical to know how the process of functional disability takes place andits relationship to frailty, therefore important adverse factors are interrelated to thetwo events, such as fatigue, low levels of physical activity and decreased musclestrength, which have been suggested as predictors for functional disability.. There are suggestions in the literature that this issue is influenced bythe life trajectory and the experiences of the elderly people and the way they deal withadverse situations, and overcoming these situations has been sustained by the theory thatproposes the relationship between resilience in the elderly and frailty.In this study, self-perceived health was associated with being frail, corroboratingother findings. There tuations, and ov frailty.Some limitations of the study are that this research is characterized as across-sectional type study, in which there is no possibility of establishing cause andeffect, and that some of the instruments used required subjective or self-reportedinformation, which may lead to memory bias. Longitudinal studies and the use of moreobjective instruments are needed to make the inferences about the predictive indicatorsof frailty more robust.The prevalence of pre-frailty and frailty was 58.7% and 23.8%, respectively. Theevidence presented in this study showed that the state of pre-frailty was associatedwith gender, age group and BMI. While the state of frailty was associated with gender,age group, hospitalization, functional capacity and self-perceived health. There weremore variables associated with the frailty condition, which reinforces the concept of amultifactorial clinical syndrome that may result in the loss of functionality.Furthermore, it is worth mentioning once again that the high prevalence of elderlypeople in the pre-frail condition constitutes important information, considering thepossibility of deterioration and becoming frail over a short period, which will resultin more care and spending on the health of these elderly people.Therefore, the results published on the subject should serve to guide and improve thehealthcare policies for the elderly, as well as assist the professionals involved intheir care, whose purpose should be to prevent deterioration and its consequences, andthe development of the preliminary stages of frailty into an advanced situation.


The predisposition, infection, response and organ dysfunction (PIRO) staging system was designed as a stratification tool to deal with the inherent heterogeneity of septic patients. The present study was conducted to assess the performance of PIRO in predicting multiple organ dysfunction (MOD), intensive care unit (ICU) admission, and 28-day mortality in septic patients in the emergency department (ED), and to compare this scoring system with the Mortality in Emergency Department Sepsis (MEDS) and Acute Physiology and Chronic Health Evaluation (APACHE II) scores.n = 680) admitted to the ED of Beijing Chao-Yang Hospital were enrolled. PIRO, MEDS, and APACHE II scores were calculated for each patient on ED arrival. Organ function was reassessed within 3 days of enrollment. All patients were followed up for 28 days. Outcome criteria were the development of MOD within 3 days, ICU admission or death within 28 days after enrollment. The predictive ability of the four components of PIRO was analyzed separately. Receiver operating characteristic (ROC) curve and logistic regression analysis were used to assess the prognostic and risk stratification value of the scoring systems.Consecutive septic patients (P < 0.001). PIRO and APACHE II independently predicted ICU admission and MOD, but MEDS did not. All three systems were independent predictors of 28-day mortality with similar AUC values. The AUC of PIRO was 0.889 for ICU admission, 0.817 for MOD, and 0.744 for 28-day mortality. The AUCs of PIRO were significantly greater than those of APACHE II and MEDS (P < 0.05) in predicting ICU admission and MOD.Organ dysfunction independently predicted ICU admission, MOD, and 28-day mortality, with areas under the ROC curve (AUC) of 0.888, 0.851, and 0.816, respectively. The predictive value of predisposition, infection, and response was weaker than that of organ dysfunction. A negative correlation was found between the response component and MOD, as well as mortality. PIRO, MEDS, and APACHE II scores significantly differed between patients who did and did not meet the outcome criteria (The study indicates that PIRO is helpful for risk stratification and prognostic determinations in septic patients in the ED. Sepsis, which can progress to severe sepsis and septic shock, is becoming a major healthcare problem and affects millions of people around the world each year -5. The eThe concept of the predisposition, infection, response, and organ dysfunction (PIRO) scoring system was recommended at the 2001 International Sepsis Definitions Conference to improve the traditional classification of sepsis . The PIRThe PIRO system is theoretically an ideal stratification tool, but it is difficult to translate into clinical practice. In 2008, the first clinical PIRO model was developed , followeThis study was designed to assess the predictive performance of the PIRO system for ICU admission, development of multiple organ dysfunction (MOD), and 28-day mortality in septic patients in the ED, and to compare this scoring system with the Acute Physiology and Chronic Health Evaluation (APACHE) II  and MortWe conducted a prospective observational clinical study in the ED of Beijing Chao-Yang Hospital, a teaching hospital of Capital Medical University with approximately 250,000 ED visits per year. The study was approved by the Beijing Chao-Yang hospital ethics committee, and written informed consent was obtained from every patient.The enrollment criteria were age ≥ 18 years and fulfillment of the sepsis criteria as defined by the International Sepsis Definitions Conference . The excPatients’ basic information, including age, gender, comorbidities, telephone number, and medical record number, was recorded at the time of enrollment. Vital signs, laboratory results, and imaging results obtained on ED arrival were documented, together with diagnoses. The PIRO , APACHE All patients were followed up for 28 days through medical records or by telephone. Organ function was assessed at enrollment and was reassessed when deterioration occurred or on the third day of enrollment if the patient was relatively stable. ICU admission during follow-up, development of MOD within 3 days of enrollment, and 28-day mortality were considered as the outcome criteria. MOD was defined as fulfillment of two or more of the criteria of severe sepsis at any time within 3 days of enrollment, excluding organ dysfunction, which was induced by pre-existing disease.t test. Data with skewed distribution were expressed as the median and quartiles and were analyzed by the Mann–Whitney U test. The chi-square test was used for the comparison of frequencies. Logistic regression analysis was used to determine independent predictors of outcomes. Receiver operating characteristic (ROC) curves were constructed and the area under the ROC curves (AUC) was determined to assess predictive value. All statistical tests were two-tailed, and P < 0.05 was considered statistically significant.All data were analyzed by SPSS version 16.0 . Normally distributed data were expressed as the mean ± standard deviation and were compared using the independent-samples Eight hundred and thirty-seven consecutive septic patients were screened from November 2011 to October 2012. We excluded 153 patients with non-infectious disease and four patients with incomplete data, and thus included 680 septic patients in the study. The characteristics of the study cohort are presented in Table P = 0.012), in patients who developed MOD (75 (66 to 81) years) versus those who did not (71 (51 to 78) years, P < 0.001), and in patients who died within 28 days (74 (65 to 81) years) versus survivors (73 (59 to 79) years, P = 0.012). The percentage of males did not differ between patients with different outcomes.The mean age was much higher in patients subsequently admitted to the ICU  years) versus those who were not (72 (59 to 79) years, The predictive ability of each of the four components of the PIRO system was analyzed separately. The results are presented in Table P < 0.001). The results are shown in Figure The average APACHE II, MEDS, and PIRO scores were significantly different between patients who did and did not meet the outcome criteria (P < 0.01). The PIRO score was also better for predicting the development of MOD (AUC: 0.817) than MEDS (AUC: 0.758) and APACHE II (AUC: 0.764) scores (P < 0.05). The AUC values of the three systems for 28-day mortality were similar.The ROC curves of APACHE II and MEDS scores are shown in Figure It is important for the ED physician to identify high-risk septic patients who are likely to need aggressive resuscitation since significant physiologic changes from sepsis to severe sepsis and septic shock can occur rapidly in the early stages of sepsis. According to the 2012 International Guidelines for Management of Severe Sepsis and Septic Shock, resuscitation should be initiated in patients with sepsis-induced tissue hypoperfusion. In these guidelines, tissue hypoperfusion was defined as hypotension persisting after an initial fluid challenge, or a blood lactate concentration > 4 mmol/l . In factn = 4,618) and an external cohort . In that initial study, the AUCs of the PIRO system in predicting in-hospital mortality were 0.90 in the derivation cohort, 0.86 in the internal validation cohort, and 0.83 in the external validation cohort [The PIRO system assessed in the present investigation was developed from a study of 2,132 patients with suspected infections, and its prognostic value for in-hospital mortality was validated in an internal cohort  reflected established organ dysfunction and may partly account for the superior performance of organ dysfunction in predicting ICU admission and MOD. Another important result of our study is that response negatively correlated with MOD and 28-day mortality. As the criteria of response in the original PIRO were tachycardia, tachypnea, and elevated bands, patients who did not develop these symptoms were prone to adverse outcomes in the present study. Some septic patients manifest hypothermia and leucopenia instead of fever and leukocytosis, and their illness severity is more severe with poorer outcome . This reOur study revealed that APACHE II, MEDS, and PIRO scores were much higher for patients admitted to the ICU than for those who were not. In binary logistic regression analysis, the independent predictors of ICU admission were the APACHE II and PIRO scores, but not the MEDS score. This may be because more organ dysfunction variables are used in the APACHE II and PIRO scores. Most patients were admitted to the ICU because they developed organ dysfunction that needed intensive therapy such as mechanical ventilation or continuous renal replacement therapy. The MEDS score incorporates fewer variables that reflect organ function, so its predictive ability for ICU admission is weaker. The superior predictive performance of the PIRO system for ICU admission may be helpful in establishing the disposition of septic patients in the ED.MOD signals progressive deterioration and is associated with high short-term mortality ,3,4. In The PIRO system was an independent predictor of 28-mortality in the present study. Its prognostic value was similar to that of MEDS and APACHE II scores. A previous study obtained analogous results . The PIROur study was limited by being a single-center study with a relatively small sample size. It is also important to recognize that the present study excluded 48 patients with terminal disease , which significantly influenced the short-term survival rate. Data for these patients were not recorded or analyzed. The absolute scores of MEDS, APACHE II, and PIRO may therefore be a little lower in the present study than in other studies that included terminal patients.The PIRO system is valuable in predicting 28-day mortality, ICU admission, and the development of MOD in septic patients in the ED. The PIRO score is superior to the MEDS and APACHE II scores for risk stratification, and its prognostic value is similar to MEDS and APACHE II scores. Organ dysfunction is the best predictor of ICU admission, MOD, and 28-day mortality among the four components of the PIRO system. The response component negatively correlated with MOD and 28-day mortality.• Organ dysfunction is the best predictor of ICU admission, MOD, and 28-day mortality among the four components of the PIRO system.• The predictive ability of predisposition, infection, and response components is weaker than that of organ dysfunction.• Response negatively correlates with MOD and 28-day mortality.• The PIRO score is superior to the APACHE II and MEDS scores for predicting ICU admission and MOD.• The prognostic performance of the PIRO system for 28-day mortality is similar to that of the MEDS and APACHE II scores.APACHE: Acute Physiology and Chronic Health Evaluation; AUC: area under the receiver operating characteristic curve; ED: emergency department; ICU: Intensive care unit; MEDS: Mortality in Emergency Department Sepsis; MOD: multiple organ dysfunction; PIRO: predisposition, infection, response, and organ dysfunction; ROC: receiver operating characteristic.The authors declare that they have no competing interests.Y-XC conceived and designed the research, acquired, analyzed and interpreted the data, drafted the manuscript and revised it critically for important intellectual content. C-SL conceived and designed the research, analyzed and interpreted the data, gave final approval of the version to be published, and was responsible for the overall content as guarantor. All authors read and approved the final manuscript.


A study of the whole spectrum of biopsied head and neck (HN) diseases in Taiwan has not yet been performed. Therefore, the current study aimed to provide updated information about HN lesions in a cohort of referral Taiwanese patients for histopathological examination.HN lesions (2000–2011) in patients with records of age, sex, and histological diagnoses were retrieved from the Oral Pathology Department of the institution. These lesions were classified into four main categories: tumor/tumor-like reactive lesions, cystic/pseudocystic lesions, inflammatory/infective lesions, and others/miscellaneous lesions.A total of 37,210 HN lesions were included in the current study. Most of these lesions were distributed in the group of tumor/tumor-like reactive lesions, followed by the groups of inflammatory/infective lesions, cystic/pseudocystic lesions, and others/miscellaneous lesions. Squamous cell carcinoma was the most common HN lesion, and was also the most frequent malignant lesion among the referral patients.It was worthy of note that squamous cell carcinoma and oral potentially malignant disorders comprised high percentages of all HN lesions for the present cohort of referral patients. Reviewing the English literature, to our knowledge, most of the previous studies of HN lesions analyzed specific diseases, such as odontogenic cysts or tumors ,2, in ceThe Oral Pathology Department of the institution is the department providing a histopathological service encompassed by HN surgery specialty in southern Taiwan, receiving specimens mainly from the surgeons of the OMF Surgery Department, ENT Department, and Plastic Surgery Department of the hospital as well as other nearby regional hospitals and local dental clinics. Three experienced board-certified HN pathologists make the histological diagnosis for each biopsy independently, based mostly on paraffin embedded sections of hematoxylin-eosin staining and sometimes conjunction with immunohistochemical and/or histochemical staining. The histological diagnoses are established by peer slide review; however, if disagreement exists amongst the pathologists, a consensus is reached upon mutual discussion.This study complied with the Helsinki Declaration with the data collected after the approval of the Institutional Review Board of the hospital (KMUH-IRB-2014-73). A total of 39,503 diagnosed cases in the HN region between 2000 and 2011 were retrieved from the database of the Oral Pathology Department. With the exclusion of normal tissues and lesions without specific findings, a pool of 37,210 cases was included for analyses. Age, sex, and histological diagnoses were recorded for these HN lesions, which were classified into four main categories: tumor/tumor-like reactive lesions, cystic/pseudocystic lesions, inflammatory/infective lesions, and others/miscellaneous lesions.0/N, p0 = 0.05, N = 50 items) for multiple testing-adjusted corrections. Hence, the results were considered significant when the p value was < 0.001 (i.e. 0.05/50). If p < 0.0001, the research findings were very highly significant.Statistical analyses  for prevalence rates of the lesions, age and sex distributions of the patients were performed using SAS Statistical Package . Since the number of the items of some tables was as large as approximately 50, we employed the Bonferroni method .The data of benign odontogenic tumors are listed in Table Most of the HN lesions in the current study were distributed in the group of benign non-odontogenic tumor/tumor-like reactive lesions Table . The mosFive of the seven types of lesions in the epithelial subgroup were potentially malignant disorders, and all these five lesions belonged to the top 12 diseases. The most common lesion of the potentially malignant disorders was HK, followed by ED and OSF. The number of male patients was almost ten times that of the female patients in all the lesions of potentially malignant disorders (p < 0.0001).= 0.9045). Hemangioma was the second most common lesion, which was mostly found in the sixth decade of life. In the hemangioma, the percentage of sixth decade of life was observed no significantly difference than the age 40–49 (p = 0.0550). The 50–59 age group compared with other groups, the p value was < 0.0001, except for 30–39 age group (p = 0.0080), and 60–69 age group (p = 0.0001).Fibroma, comprising about 50% of the lesions, was the most common lesion in the soft tissue subgroup, significantly higher than the other groups (p < 0.0001), with the number of male patients almost equal to that of female patients . Compared with fibrous dysplasia, cemento-ossifying fibroma had higher percentage than fibrous dysplasia (p = 0.0019). There were no difference of percentage between cemento-osseous dysplasia and fibrous dysplasia (p = 0.4533). In cemento-ossifying fibroma, the percentage of males was significantly lower than females (p = 0.0039). In cemento-osseous dysplasia, the percentage of males was significantly lower than females (p < 0.0001). In fibrous dysplasia, the percentage of males and females was similar (p = 0.1936).Pleomorphic adenoma was the most common lesion in the salivary gland subgroup compared with the other type (p < 0.0001), with an almost equal sex distribution (p = 0.9013); this comprised about 67.0% of the lesions and was mostly noted in the fourth to the sixth decades of life. Warthin’s tumor was the second most common lesion, in which the number of males was much higher than that of females (p = 0.0209).The data of malignant non-odontogenic tumor/tumor-like reactive lesions are shown in Table The second greatest number of HN lesions was noted in the inflammatory/infective group Table , which cThe data of the others/miscellaneous lesions are shown in Table The Oral Pathology Department not only provides services for nearly all the biopsied HN lesions , but is also the most heavily used referral center for patients with these lesions in southern Taiwan. Therefore, the various types of lesions in the current study are representative of the occurrence of such lesions among the cohort of referral patients for a biopsy procedure in this geographical region.In the current study, a total of 37,210 cases of HN lesions from 2000–2011 was documented in a cohort of Taiwanese patients referred for histopathological examination. SCC was the most common lesion in this cohort 13.3%), which was in contrast to the findings of Franklin & Jones  and Ali .3%, whicMost lesions in the current study were distributed in the benign non-odontogenic tumor group (43.1%), followed by the inflammatory/infective group 31.6%), which was compatible with the findings of Jones & Franklin %, which ,10,11. MThe overall male to female ratio (3.4:1) in the current study was higher than the studies of Ali (1.1:1) , Ali & SThe lesions in the odontogenic cystic group were mostly distributed in the third to the sixth decade of life, and the number of males was slightly higher than the number of females; this result was compatible with the study of Avelar et al. . RadiculEpidermoid cyst was the most common lesion in the group of non-odontogenic cyst/pseudocyst in the current cohort, which was in contrast to the studies of Ali , BhaskerOdontoma was the most common lesion in the group of benign odontogenic tumor, constituting about 43.0% of the lesions, which was in contrast to the study of Ali . The ratPleomorphic adenoma (67.0%) and Warthin’s tumor (12.5%) were the two most common lesions in the salivary gland subgroup, which was compatible with the results of Jaafari-Ashkavandi et al.   and WangFibroma was the most common lesion 69.4%) in the soft tissue subgroup, which was compatible with the studies of Ali & Sundaram .4% in th-11.In the current study, the number of female patients was about three times higher than that of male patients (1 : 3) in the bone subgroup, which was similar to the result of Ali (1:8) . CementoThe lesions within the epithelial subgroup comprised about 39.0% of all HN lesions in the present cohort, which was much higher than the result of Amarasinghe et al. (11.3%) in Sri Lanka . FurtherCompatible with the study of Ali , the numMucoepidermoid carcinoma and adenoid cystic carcinoma were the two most common malignant lesions in the salivary gland subgroup, which was similar to the results of Bradley & McGurk  and WangSCC was the most common HN lesion (13.3%) and also the most frequent lesion in the epithelial subgroup of malignant non-odontogenic tumors, which was appeared to be higher than the findings of Jones & Franklin  and Tay Candidiasis comprised 6.8% of all HN lesions, which was appeared to be higher than the result of Jones & Franklin (1.0%) . InflammThe present study described in detail the frequency, age and sex distribution in a cohort of Taiwanese patients referred for histopathological examination. It showed trends similar to previous reports from other countries; however, some detailed information was different, perhaps due to the different criteria and different geographic distribution. Moreover, oral SCC and oral potentially malignant disorders comprised high percentages of all HN lesions in the cohort; nevertheless it should be cautioned that the sample being non-epidemiologic and would probably be greatly askew to a high rate of malignant/potentially malignant lesions when compared to an epidemiological sample.HN: Head & neck; OMF: Oral and maxillofacial; SCC: Squamous cell carcinoma; HK: Hyperkeratosis; ED: Epithelial dysplasia; OSF: Oral submucous fibrosis; EH: Epithelial hyperplasia; ENT: Ear, nose & throat.The authors declare that they have no competing interests.FL, KYH, and YKC are the primary writers of the manuscript and participated in the study implementing. YKC conceived of the study, and had made substantial contributions to conception and design, and revised the manuscript critically for important intellectual content. PHC implements all the required statistical analyses. WCW, LML, HCH, and JYC assisted in interpretation of data. CHC, and YKC are the principal investigators of clinical studies in this project. All authors read and approved the final manuscript.


Lipodystrophy (LD) is a frequent adverse event of combination antiretroviral therapy (ART) and occurs mainly in patients exposed to first-generation antiretroviral drugs. The aim of this study was to explore and measure the interaction between LD, mental health, and quality of life of human immunodeficiency virus (HIV) positive individuals seen in a metabolic clinic.LIPO group and metabolism day clinic at the University Hospitals of Geneva, Switzerland between January 31, 2008 and November 28, 2013. Data on LD were prospectively collected using the HIV Outpatient Study (HOPS) score, the Lipodystrophy Case Definition (LDCD), ART regimens, anthropometric measures, imaging, and standardized questionnaires. Quality of life was evaluated using a visual analog scale of 0–100. Depression and anxiety were assessed using the Beck Depression Inventory and the State Trait Anxiety Inventory scales, respectively.We conducted a single-site cross-sectional study including all HIV-infected patients attending the 3; median viral load, 20 copies/mL) were evaluated. Among these, 62.7, 63.5 and 35.5% of patients reported at least one body site affected by fat hypertrophy, atrophy or both, respectively. Using the LDCD score conservative definition, including imaging and biological values, 57.8% were diagnosed with LD. Of these, 39.7% suffered from severe/very severe LD. Depression was reported by 35.6% of individuals; 51.9% had anxiety symptoms and 49.5% reported poor quality of life . LD  1.07–25.37, p-value: 0.040), depression , and anxiety  all affected significantly the quality of life.One hundred ninety-four patients  on successful ART  contains supplementary material, which is available to authorized users. Since the description of the first case of acquired immune deficiency syndrome (AIDS) in 1981, human immunodeficiency virus (HIV) infection has reached pandemic proportions and has continued to expand in worldwide; in 2012 an estimated of 35.3 million of peoples were infected by HIV . HoweverThere is currently no universal definition of LD. This implies significant variation in the prevalence rate, incidence, severity, and risk factors, which makes difficult any comparison between studies and across countries and ethnicities . DiagnosSystematic reviews have discussed the impact of ARV agents and regimens on LD, but with discordant conclusions. If a clear relationship between NRTIs  and LA has been demonstrated, the causal role of specific drugs in the development of fat accumulation remains to be clarified , 12. WitSeveral research groups have focused on the impact of LD on quality of life –23. In aLIPO group and metabolism day clinic at the University Hospitals of Geneva, Switzerland.This study aimed to identify the complex relationships between LD, mental health disorders, and the quality of life in patients attending the LIPO group and metabolism) at the University Hospitals of Geneva between January 31, 2008 and November 28, 2013 were included in the study. This multidisciplinary consultation  is held once monthly and patients are referred to the clinic by their treating physician for several reasons, such as the evaluation of HIV-related or unrelated multiple medical co-morbidities, or LD management. A complete medical check-up is coordinated by the infectious diseases team and includes blood analyses, imaging , and psychological, plastic surgery, dermatology, endocrinology, bone diseases and dietary consultations. Physicians from other medical specialties are available upon request e.g., nephrologist, endocrinologist, bone specialist, cardiologist, hepatologist. All patients provided written informed consent and the study protocol was approved by the clinical ethics committee of the University Hospitals of Geneva (CER #09017).All patients participating to the metabolic clinic  grading by a questionnaire with 20 items regarding the trait anxiety developed by Spielberger in 1983 ; 88 (45.4%) were female and 108 (72.5%) were Caucasians  Table . AlthougAmong the 188 patients who completed the questionnaire, 93 49.5%) described a poor quality of life (median (IQR): 40.0 (30.0–50.0) with a visual score of <50% . Althoug9.5% descLIPO group and metabolism day clinic. Almost half of all patients considered themselves as suffering from a poor quality of life. Severe LD, depression, and anxiety were all associated with poor quality of life. This high level of LD frequency is partly due because the patients are referred to the day clinic by their treating physician.Results of our study indicate a high frequency of LD and mental health disorders among HIV-infected men and women on successful ART presenting at the Through these findings, we demonstrate that the objective signs of LD, based on a validated score (LDCD) and including morphologic data and metabolic values, are associated with a decreased quality of life and with the presence of mental health disorders. Fat loss observed by the patient and the physician (HOPS score) was also associated with a poor quality of life, but only in the univariate analysis.Our results are consistent with several previous studies. First, some authors have highlighted a poor quality of life, severe stigma, and lower values in social and psychological scores regarding HIV-infected patients with or without reported LD , 34. Of Other studies show discordant results. Quality of life scales and psychological questionnaire often change from one study to another  , 16, 18;LD remains a prevalent adverse event, despite the advent of new generation ARV drugs . A recenIn a recent analysis of 15,275 participants to the Swiss HIV Cohort Study, Keiser et al. describe the suicide rate in HIV patients from 1998 to 2008. Despite a significant decrease rate of suicide between the pre era ARV drugs and the late era, suicides are more frequent in HIV population compared to general population . In 62% This study shows a complex interplay between quality of life, mental health disorders, and signs of LD. Severe LD and mental health disorders were all associated with a subjective impairment of quality of life. Moreover, individuals with a more recent diagnosis (<10 years) or those with a detectable viral load (≥40 copy/mL), more likely due to insufficient adherence to treatment, had also a poor quality of life. Therefore, psychological issues in HIV chronic infection is of major importance for daily constraints associated with the disease, adherence to therapy, and quality of life.Women were more likely to express signs of depression and anxiety as found in other studies , 50. DepOur study has some limitations. First, we used a modified quality of life score. This scale registers the self-estimation of the patient within a very specific timeframe. For this reason, a various number of independent variables can interfere with this estimate. We arbitrarily defined poor quality of life as between 0–50 and good quality of life between 51–100 and these thresholds could be challenged. However, this measure is simple to evaluate, and easily repeatable. Moreover, the QoL score that we used in our study has the advantage to be used directly during the clinical interview and measure synthetically the psychic pain in a biopsychosocial situation. As the validated Visual Analog Scale (VAS) largely used for pain appreciation, our QoL scale measure a subjective definition. Secondly, LD assessment remains difficult because of the lack of a gold standard definition. However, we consider that the use of two different scores, one based on the physician and patient perceptions and the other based on objective features, allowed us to capture with sufficient precision the prevalence and the severity of LD in this population. We were able to assess LD with great precision, using multiple and routinely-performed tools during the patient one-day visits to the day hospital. These included 191 of validated questionnaires, representing 98.5% of the patients included in the cohort, and 135 imaging (69.6%) (CT and DXA scans), as well as biological values, which are all features related to the LD. Regarding the HOPS score, there was good concordance between physician and patient assessments for fat atrophy and hypertrophy. Moreover, although the study population represented selected individuals referred by their practicing physician, it included both men and women of diverse ethnicity, thus making our results more consistent.The majority of the HIV-infected patients seen in the metabolic clinic in Geneva describe, at least, one body site affected by LA or LH and are diagnosed with LD regarding the LDCD score. Depression as well as anxiety feature are also very frequent in our studied population, and, with the presence of LD, are related to a poor quality of life, leading to psycho-social consequences. Mental health and a simple score for quality of life should be routinely assessed among HIV-infected individuals, including those on effective ART, in order to recognize early signs and symptoms of psychological distress and to help patients have better outcomes in their daily life.


Lu. longipalpis distribution in an urban scenario, discriminating micro-scale landscape variables at microhabitat and macrohabitat scales and the presence from the abundance of the vector. For this objective, we studied vectors and domestic reservoirs and evaluated different environmental variables simultaneously, so we constructed a set of 13 models to account for micro-habitats, macro-habitats and mixed-habitats. We captured a total of 853 sandflies, of which 98.35% were Lu. longipalpis. We sampled a total of 197 dogs; 177 of which were associated with households where insects were sampled. Positive rK39 dogs represented 16.75% of the total, of which 47% were asymptomatic. Distance to the border of the city and high to medium density vegetation cover ended to be the explanatory variables, all positive, for the presence of sandflies in the city. All variables in the abundance model ended to be explanatory, trees around the trap, distance to the stream and its quadratic, being the last one the only one with negative coefficient indicating that the maximum abundance was associated with medium values of distance to the stream. The spatial distribution of dogs infected with L. infantum showed a heterogeneous pattern throughout the city; however, we could not confirm an association of the distribution with the variables assessed. In relation to Lu. longipalpis distribution, the strategy to discriminate the micro-spatial scales at which the environmental variables were recorded allowed us to associate presence with macrohabitat variables and abundance with microhabitat and macrohabitat variables. Based on the variables associated with Lu. longipalpis, the model will be validated in other cities and environmental surveillance, and control interventions will be proposed and evaluated in the microscale level and integrated with socio-cultural approaches and programmatic and village  strategies.The principal objective of this study was to assess a modeling approach to  Leishmania infantum (syn. chagasi) that is transmitted by insects belonging to Diptera:Phlebotominae, Lutzomyia longipalpis being the principal vector in urban areas. Therefore, the prevention and control of this vector is a sound objective, so as to reduce the probability of contact human-vector and reducing the probability of infection. Therefore, knowing the variables that have an impact and the spatial scale at which these act will allow us to approach an understanding of the dynamic population of the vector and allow us to develop more appropriate strategies of control. Thus, the aim of this study was to assess a modeling approach to Lu. longipalpis distribution in an urban scenario, discriminating micro-scale landscape variables at microhabitat and macrohabitat scales. For this, we worked in Santo Tomé, Corrientes, Argentina. We observed that the presence of Lu. longipalpis is defined only by the macrohabitat variables tested, but the abundance is defined by variables of both scales, microhabitat and macrohabitat.Visceral leishmaniasis in America is caused by an unicellular organism,  Leishmania infantum (syn. chagasi). The sandfly Lutzomyia longipalpis was incriminated as the most important vector [Visceral leishmaniasis (VL) in America is caused by t vector  and the t vector –5.Lu. longipalpis was recorded in Argentina at forest-rural sites in 1951 and 2000 with very few individuals per capture, since 2006 this species has been found in VL urban foci in captures with more than 100 insects per trap in the first focus at the city of Posadas, Province of Misiones, and also present in other cities of northeastern Argentina (provinces of Formosa and Chaco), [Lu. longipalpis in the province of Corrientes (contiguous to Misiones where Posadas is close to the border between both provinces) to assess the possibility of autochthonous transmission of L. infantum. This province has an active transmission scenario with canine leishmaniasis cases and vector presence since 2008 [th epidemiological week of 2015 . Despite canine leishmaniasis was diagnosed in numerous dogs, no systematic rate of infected dogs was performed until this study.Although  Chaco),  studied Dynamic epidemiological patterns of transmission are the result of the simultaneous and multi-scale interaction of biotic factors that coexist in heterogeneous epidemiological landscapes ,13. In tLu. longipalpis abundance in urban scenarios with the presence of chickens, dogs and/or fruit trees, or Normalized Difference Vegetation Index (NDVI) ranges, which can offer suitable conditions for reproductive success of the vector [surface of bare soil or covered with grass, distance from house to watercourse, number of plant-pots, and number of tree species as possible contributors to the abundance of vectors in an urban environment [Lu. longipalpis in urban environments are only partially understood [Lu. longipalpis abundance in Posadas city at this scale, the vector showed different associations between variables recorded at micro-habitat (trap site) and macro-habitat variables . Further, in this urban setting more than 30%-40% of the sites sampled had Lu. longipalpis presence while less than 5% had high abundance of the vector, suggesting that the presence and the abundance are modulated by different variables [Lu. longipalpis distribution in an urban scenario different from Posadas, discriminating micro-scale landscape variables at microhabitat and macrohabitat scales, and the presence from the abundance of the vector, in order to try to improve the explanatory power of the model, and so to contribute to the design of integrated intervention strategies based on the associated variables. The visceral canine leishmaniasis distribution was also analyzed as it was proposed as indicator of transmission or human risk [Previous studies on leishmaniasis associated e vector –22. A stironment . Despitederstood , and thederstood . The micderstood ,26. But ariables . Therefoman risk –29.2.This study was carried out in Santo Tomé City, Corrientes, Argentina . This city belongs to the ‘Espinal’ ecoregion, Neotropical ecozone , and it th February 2013. We studied vectors and domestic reservoirs simultaneously. In order to sample the entire urban area, the city was divided into a grid of 600 m2 squares (patch), except for the neighborhood ‘Estación’ on the West, where high vector abundance had been reported by a previous study [2 squares. One domestic unit was selected within each patch using the ‘worst scenario’ criterion [2 patches, minimum and maximum distances between traps settled in different patches were 145 and 472 m respectively; whereas in the 200 m2 patches, minimum and maximum distances between traps were 110 and 270 m respectively. The geographic coordinates of all the sites sampled were registered with a Global Positioning System (Garmin eTrex10).The study was conducted from 25 to 27us study , and wasriterion . The ‘woSandflies were captured with automatic CDC-like light traps, used for the sampling of Phlebotominae in peridomestic environments. Traps were active from approximately 5:30 p.m. to 7:30 a.m., for 3 consecutive rainless nights. Traps were placed 1.5 m above the ground.Evandromyia cortelezzii and Ev. sallesi females cannot be distinguished by their morphology, so specimens collected were included within the Ev. cortelezzii-sallesi complex.All Phlebotominae sandflies were dried and preserved prior to processing. The specimens were cleared with lacto-phenol and identified according to  under a Lu. longipalpis individuals summed up to the 10–15 percentile, we operatively classified the domestic units into low (<30) and high abundance (>30) [According to previous studies in urban areas where traps with more than 30 ce (>30) .Maximum (max) and minimum (min) temperatures (T) and relative humidity (RH) were registered during sampling in the trap active period with digital thermo-hygrometers  in 17 randomly selected domestic units. During the capture period mean climatic variables were: Tmin mean: 15.42, SE: 1.75; Tmax mean: 31.43, SE: 1.02; RH min mean: 39.46, SE: 5.59; RH max mean: 92.28, SE: 6.55.Dogs house. We also sampled all dogs in neighboring houses within a 25 m radius, Dogs neighbours. The presence of antibodies against L. infantum by means of the immunochromatographic rK39 technique was done in situ . For each dog, 11 variables were gathered: breed (yes/no), gender, age (years), size , sterilization (yes/no), night resting place (interior/exterior), unleashed , moving history (yes/no), repellent use (yes/no), repellent periodicity (months), symptoms (yes/no).Dogs from the houses with sandfly traps were blood-sampled by veterinarians, The study was conducted according to the ethical regulations for research established by the World Organization for Animal Health (OIE)  and withSatellite information to generate the environmental stratification of the city was obtained from a Spot 5 HRG1 J image . The synthetic image was digitally processed in order to convert digital values into reflectance values for each of the pixels of the cropped image. Land cover spectral responses were determined by band math in the Red and Near-Infrared spectra, giving a normalized difference vegetation index (NDVI) raster image as a result. The NDVI image was subjected to an unsupervised classification by the Isodata method so as to obtain the different classes resulting from the spectral responses of the land cover present in the area of study ,36. The Trees, Fruit trees, Plant pots, Dogs, Hens and UnMat)  . VariablLu. longipalpis during the 3-night trapping period. Pearson correlation coefficients for the 13 variables were below 0.5, except for Urban cover with LDenVegC and HMDenVegC (-0.79 and -0.8 respectively). Also, variance inflation factors (VIF) were calculated with package car for R [Urban cover. When this variable was set aside, all VIF values were between 1 and 3 units. Therefore, Urban cover was not included in the models.We calculated the accumulated abundance of ar for R  showing NB full, Hurdle full). Ten models set aside the ‘animal’ variables , because of its moving nature in contrast with the other ‘sessile’ things measured. As it was stated in the introduction, according to a conceptual framework that discriminates instrumentally spatial scales, conceptually the presence from the abundance phenomena, and allow to introduce the expert knowledge in the final models, 2 Hurdle models were constructed as an abundance part with 6–4 variables, and a presence part with 6 variables . Two models took into account a possible quadratic relationship of Stream with sandfly abundance, and the number of trees at the trap to represent shade and humidity at the microscale. Two other hurdle models were constructed only with biotic variables, excluding Unused materials, Altitude, Border and Stream . Bare soil was not considered in Hurdle Biotic 2 since Bare Soil class had very low cover values in the entire city and could have a low influence in vector abundance/presence.We constructed a set of 13 models to account for micro- (2), macro- (2) and mixed-habitats effects (9) . Two modLu. longipalpis accumulated abundance and the environmental characteristics related to each domestic unit was analyzed by a multiple regression procedure using GLM with a logarithm link function. The nature of the variable indicated a Poisson error structure, but to account also for high over dispersion we applied a Negative Binomial error structure [theta using package MASS for R [The association between tructure . Model pSS for R –41.log link), and a hurdle component for zero counts . With this approach, we can model simultaneously both the probability of occurrence and the abundance of sandflies, and search for environmental variables that may determine the presence and absence of the vector and/or the number of sandflies observed at each site.We used a hurdle count regression model to predict the presence and the accumulated abundance of sandflies in a site as a function of explanatory variables measured at micro and macrohabitat ,43. The Akaike weights  and ΔAICc [wi were considered the best models in the set. Spatial autocorrelation in the raw variable and models residuals were checked by Moran’s I and semivariograms with SAM software [boot for R [The final set of candidate models was selected by means of the AICc criterion and taking into account the nd ΔAICc –47. Modesoftware . Parametot for R .PresenceAbsence for R [To evaluate the predictive ability of the final model for the “presence part” we calculated: Kappa index, proportion of correct classifications (PCC), area under the curve (AUC), sensitivity and specificity with package ce for R . As a thk39 positivity  by means of a generalized linear mixed model taking into account the clusters (random factor) made up of Dogs house plus Dogs neighbors. We constructed 5 models with binomial family and logit link using package lme4 for R [Model 1 took into account individual dog characteristics such as: breed, gender, age, size, and sterilization; Model 2 accounted for dogs habits: night resting place, unleashed, moving history, repellent use, repellent periodicity. Model 3 included all the variables. Model 4 was similar to model 1 but incorporating two interactions: gender*sterilization, and breed*sterilization. Models were compared by AICc.In first place, we analyzed the variable re4 for R . Model 1(Proportion of Positives) and the centered environmental variables, including also the accumulated abundance of phlebotomines. Due to over dispersion, we constructed 5 GLM models with negative binomial family and log link  using the same variables as the ones listed as NB models in Lu. longipalpis at each house, using package MASS for R [In second place, we analyzed the association between the proportion of dog positivity in each trapped house and its neighbours SS for R .Lu. longipalpis, Migonemyia migonei, Nyssomyia whitmani, Brumptomyia sp., Ny. neivai and Ev. cortelezzii-sallesi , of which 51% were positive for Lu. longipalpis  and Stream2 (p = 0.008) but the effect could not be confirmed due to computational issues during bootstrapping.As for the Urban cover, 31.15% of Low density vegetation cover, 17.91% of Medium to high density vegetation cover, and 4.25% of Bare soil cover  of AICc from the others. After removing two non-significant terms from the presence part , Altitude and Stream2, AICc diminished 4 units and this model was retained.After model selection, one NB model and three hurdle count regression models were responsible for 99% of the collective model weight . But theThe Kappa index calculates the agreement between model predicted values and observed data, indicating how much better from a random classification the model is. The reduced final model had an intermediate Kappa value of 0.43 . The reduced model improved the sensitivity from 0.55 (SD = 0.09) to 0.71 (SD = 0.08) but reduced the specificity from 0.91 (SD = 0.06) to 0.73 (SD = 0.1). The reduced final model correctly classified 72% (SD = 0.06) of the data (AUC = 0.75 (SD = 0.07)) .Border) and high to medium density vegetation cover (HMDenVegC) ended to be explanatory, all positive, of the presence of sandflies in the city (Trees), distance to the stream and its quadratic , being the last one the only one with negative coefficient indicating that the maximum abundance was associated to medium values of distance to the stream.After calculating BCa confidence intervals for each estimate, only distance to the border of the city , transit or traffic within the locality or with other endemic locations [presence of green areas adjacent to the house), individual variables such as short hair and pure breed, and individual management variables (peri-domestic/domestic restricted dogs), but the authors also highlighted design and analysis limitations of the reviewed articles [positive association with the number of cats in the households, protective presence of chickens and pigs) [In Santo Tomé, the spatial distribution of dogs infected with ocations ,52. Indeocations –56. Howearticles . Also, bnd pigs) .This lack of strong or consistent associations in the literature could be related mainly to: a) design limitations due to work with: reported cases vs. actual incidence of infection, prevalence of past transmission vs. current environmental variables, individual factors of susceptibility-vulnerability-exposition mixed with environmental variables, dogs with different roaming area; b) inconsistencies between the spatial scales of dependent and explanatory variables; c) diagnosis limitations, in our study the majority of the rK39+ dogs were clinically asymptomatic, and it is known the relative low sensitivity of rK39 test in asymptomatic dogs ,59; and Ny. whitmani for the first time in the study area. This species has been incriminated in the cutaneous leishmaniasis outbreaks due to Leishmania braziliensis of the Argentinean northeastern border both by natural infection and environment-time-space association with human cases, though observed abundances in the study area are still far from epidemic risk and this species has usually been associated to primary vegetation in Argentina [We report rgentina ,61. Howergentina .Lu. longipalpis distribution, the strategy to discriminate the micro-spatial scales at which the environmental variables were recorded allowed us to associate presence with macrohabitat variables, and abundance with microhabitat and macrohabitat variables.In relation to Lu. longipalpis was positively affected by the variables Distance to the city border and High density vegetation cover. As the distance to the city border increased, the probability of Lu. longipalpis presence tend to be higher. The variable High density vegetation cover showed also a positive relation with the vector presence. It can be explained by the generation of enabling environments for the presence of Lu. longipalpis. Though these variables seem to be contradictory, the city under study has a not uniform physiognomy presenting centric areas with high proportion of green surface, offering small breeding and resting conditions for the vector  and NDVI no correlation was observed with Lu. longipalpis abundance [The abundance of g places  by meansg places ; and treg places . Other te larvae ), or mig [et al.  found asbundance , showingLu. longipalpis presence or abundance did not show association in our study. The attractiveness of mammals and birds, mainly chickens, and its capacity to enhance breeding sites  was proposed [Lu. longipalpis in urban settings [Lu. longipalpis even this; therefore the homogeneity of this variable between trapping points at micro-scale could have masked the results, and the effect at the macrohabitat level was not measured. Low socio-economic level and poor sanitation (sewage system and rubbish collection) were associated with VL incidence and these associations were explained by vector suitability [Other variables once reported as associated with proposed ,69, whilsettings . The hentability , althougLu. longipalpis could act as source populations in a metapopulation structure within a ‘city network’ of connected patches. Therefore, to identify the sites in each scale and the variables associated with presence and abundance could contribute to assess the significance of particular habitat patches [Lu. longipalpis distribution could contribute to propose environmental management control interventions. From individual practices to county planning (microhabitat to macrohabitat) the recommendations on density and species of trees, and potential breeding sites could be assessed experimentally. On the other hand, finding areas more suitable for Lu. longipalpis (hosting the populations with highest abundances in the village (distance to stream) by itself or as surrogate of socio-economic conditions or related practices (chicken breeding)), may be used to focus the allocation of resources, or to select the sites to evaluate the interventions.Considering the low temperatures registered during the sampling nights, sites with high trap positivity could reveal stable vector hot spots as the ones described at the city of Posadas in the 2007 and 2009 ,25,64, w patches , with im patches ,72. At mLu. longipalpis presence and abundance as different components, allowed to explain 70% of the vector presence. Based on the variables associated with Lu. longipalpis, the model will be validated in other cities and environmental surveillance and control interventions will be proposed and evaluated in the microscale level. In this sense, programmatic and village strategies integrated with socio-cultural approaches could be incorporated in city, neighborhood and individual environmental management, according to each mesoscale and microscale scenarios, based on participatory action methodologies, so the actual intervention will be defined together with community [In conclusion, discriminating environmental spatial based variables recorded at mesohabitat and microhabitat buffers and modeling ommunity .S1 TableModel selection metrics for NB and hurdle count regression models fit to presence and/or abundance data for Phlebotominae sandflies at 53 sites. Model results are ranked by AICc from best to worst.(DOC)Click here for additional data file.S1 FigEstimated probability of sandfly presence (dots and smoothed line) in terms of increasing proportion of vegetation cover (Low + Medium/High density vegetation cover proportion). ID: trap/site.(TIF)Click here for additional data file.