A molecular toolbox for fast and convenient diagnosis of emerging and reemerging bacterial pathogens causing fever of intermediate duration.

PURPOSE: Fever of intermediate duration (FID) is defined as a fever in the community without a specific origin or focus, with a duration between 7 and 28 days. FID is often caused by pathogens associated with animal contact or their arthropods parasites, such as ticks, fleas, or lice. The purpose of this work is to design a collection of molecular tools to promptly and accurately detect common bacterial pathogens causing FID, including bacteria belonging to genera Rickettsia, Bartonella, Anaplasma, and Ehrlichia, as well as Coxiella burnetii. METHODS: Reference DNA sequences from a collection of Rickettsia, Bartonella, Anaplasma, and Ehrlichia species were used to design genus-specific primers and FRET probes targeted to conserved genomic regions. For C. burnetii, primers previously described were used, in combination with a newly designed specific probe. Real-time PCR assays were optimized using reference bacterial genomic DNA in a background of human genomic DNA. RESULTS: The four real-time PCR assays can detect as few as ten copies of target DNA from those five genera of FDI-causing bacteria in a background of 300 ng of human genomic DNA, mimicking the low microbial load generally found in patient's blood. CONCLUSION: These assays constitute a fast and convenient "toolbox" that can be easily implemented in diagnostic laboratories to provide timely and accurate detection of bacterial pathogens that are typical etiological causes of febrile syndromes such as FID in humans.

EZH2 Mediates Proliferation, Migration, and Invasion Promoted by Estradiol in Human Glioblastoma Cells.

Glioblastomas (GBM) are the most frequent and aggressive brain tumors. 17ß-estradiol (E2) increases proliferation, migration, and invasion of human GBM cells; however underlying mechanisms are no fully understood. Zeste 2 Enhancer Homologous enzyme (EZH2) is a methyltransferase part of Polycomb 2 repressor complex (PRC2). In GBM, EZH2 is overexpressed and involved in the cell cycle, migration, and invasion processes. We studied the role of EZH2 in the pro-oncogenic actions of E2 in human GBM cells. EZH2 gene silencing and pharmacological inhibition of EZH2 blocked proliferation, migration, and invasion of GBM cells induced by E2. We identified in silico additional putative estrogen response elements (EREs) at the EZH2 promoter, but E2 did not modify EZH2 expression. In silico analysis also revealed that among human GBM samples, EZH2 expression was homogeneous; in contrast, the heterogeneous expression of estrogen receptors (ERs) allowed the classification of the samples into groups. Even in the GBM cluster with high expression of ERs and those of their target genes, the expression of PCR2 target genes did not change. Overall, our data suggest that in GBM cells, pro-oncogenic actions of E2 are mediated by EZH2, without changes in EZH2 expression and by mechanisms that appear to be unrelated to the transcriptional activity of ERs.

Long-Term Antithrombotic Therapy and Clinical Outcomes in Patients with Acute Coronary Syndrome and Renal Impairment: Insights from EPICOR and EPICOR Asia.

BACKGROUND: Information is lacking on long-term management of patients with acute coronary syndrome (ACS) and chronic kidney disease (CKD) (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2). OBJECTIVES: Our objectives were to describe antithrombotic management patterns and outcomes in patients with ACS with varying renal function from the EPICOR (long-tErm follow-uP of antithrombotic management patterns In acute CORonary syndrome patients; NCT01171404) and EPICOR Asia (NCT01361386) studies. METHODS: EPICOR and EPICOR Asia were prospective observational studies of patients who survived hospitalization for ACS and were enrolled at discharge in 28 countries across Europe, Latin America, and Asia. The studies were conducted from 2010 to 2013 and from 2011 to 2014, respectively. This analysis evaluated patient characteristics and oral antithrombotic management patterns and outcomes up to 2 years post-discharge according to admission eGFR: ≥ 90, 60-89, 30-59, or < 30 mL/min/1.73 m2. RESULTS: Among 22,380 patients with available data, eGFR < 60 mL/min/1.73 m2 was observed in 16.7%. Patients with poorer renal function were older, were at greater cardiovascular risk, and had more prior cardiovascular disease and bleeding. Patients with CKD underwent fewer cardiovascular interventions and had more in-hospital cardiovascular and bleeding events. Dual antiplatelet therapy was less likely at discharge in patients with eGFR < 30 (82.3%) than in those with ≥ 90 (91.3%) mL/min/1.73 m2 and declined more sharply during follow-up in patients with low eGFR (p < 0.0001). An adjusted proportional hazards model showed that patients with lower eGFR levels had a higher risk of cardiovascular events and bleeding. CONCLUSIONS: The presence of CKD in patients with ACS was associated with less aggressive cardiovascular management and an increased risk of cardiovascular events.

Long-term antithrombotic management patterns in Asian patients with acute coronary syndrome: 2-year observations from the EPICOR Asia study.

BACKGROUND: Despite guideline recommendations, dual antiplatelet therapy (DAPT) is frequently used for longer than 1 year after an acute coronary syndrome (ACS) event. In Asia, information on antithrombotic management patterns (AMPs), including DAPT post discharge, is sparse. This analysis evaluated real-world AMPs up to 2 years post discharge for ACS. HYPOTHESIS: There is wide variability in AMP use for ACS management in Asia. METHODS: EPICOR Asia (NCT01361386) is a prospective observational study of patients discharged after hospitalization for an ACS in eight countries/regions in Asia, followed up for 2 years. Here, we describe AMPs used and present an exploratory analysis of characteristics and outcomes in patients who received DAPT for ≤12 months post discharge compared with >12 months. RESULTS: Data were available for 12 922 patients; of 11 639 patients discharged on DAPT, 2364 (20.3%) received DAPT for ≤12 months and 9275 (79.7%) for >12 months, with approximately 60% still on DAPT at 2 years. Patients who received DAPT for >12 months were more likely to be younger, obese, lower Killip class, resident in India (vs China), and to have received invasive reperfusion. Clinical event rates during year 2 of follow-up were lower in patients with DAPT >12 vs ≤12 months, but no causal association can be implied in this non-randomized study. CONCLUSIONS: Most ACS patients remained on DAPT up to 1 year, in accordance with current guidelines, and over half remained on DAPT at 2 years post discharge. Patients not on DAPT at 12 months are a higher risk group requiring careful monitoring.

Characterization of the immunomodulatory and anti-Helicobacter pylori properties of the human gastric isolate Lactobacillus rhamnosus UCO-25A.

The ability to form biofilms and the potential immunomodulatory properties of the human gastric isolate Lactobacillus rhamnosus UCO-25A were characterized in vitro. It was demonstrated that L. rhamnosus UCO-25A is able to form biofilms on abiotic and cell surfaces, and to modulate the inflammatory response triggered by Helicobacter pylori infection in gastric epithelial cells and THP-1 macrophages. L. rhamnosus UCO-25A exhibited a substantial anti-inflammatory effect in both cell lines and improved IL-10 levels produced by challenged macrophages. Additionally, UCO-25A protected AGS cells against H. pylori infection with a higher pathogen inhibition when a biofilm was formed. Given the importance of inflammation in H. pylori-mediated diseases, the differential modulation of the inflammatory response in the gastric mucosa by an autochthonous strain is an attractive alternative for improving H. pylori eradication and reducing the severity of the diseases that arise from the resulting chronic inflammation.

Predicting two-year mortality from discharge after acute coronary syndrome: An internationally-based risk score.

BACKGROUND: Long-term risk of post-discharge mortality associated with acute coronary syndrome remains a concern. The development of a model to reliably estimate two-year mortality risk from hospital discharge post-acute coronary syndrome will help guide treatment strategies. METHODS: EPICOR (long-tErm follow uP of antithrombotic management patterns In acute CORonary syndrome patients, NCT01171404) and EPICOR Asia (EPICOR Asia, NCT01361386) are prospective observational studies of 23,489 patients hospitalized for an acute coronary syndrome event, who survived to discharge and were then followed up for two years. Patients were enrolled from 28 countries across Europe, Latin America and Asia. Risk scoring for two-year all-cause mortality risk was developed using identified predictive variables and forward stepwise Cox regression. Goodness-of-fit and discriminatory power was estimated. RESULTS: Within two years of discharge 5.5% of patients died. We identified 17 independent mortality predictors: age, low ejection fraction, no coronary revascularization/thrombolysis, elevated serum creatinine, poor EQ-5D score, low haemoglobin, previous cardiac or chronic obstructive pulmonary disease, elevated blood glucose, on diuretics or an aldosterone inhibitor at discharge, male sex, low educational level, in-hospital cardiac complications, low body mass index, ST-segment elevation myocardial infarction diagnosis, and Killip class. Geographic variation in mortality risk was seen following adjustment for other predictive variables. The developed risk-scoring system provided excellent discrimination (c-statistic=0.80, 95% confidence interval=0.79-0.82) with a steep gradient in two-year mortality risk: >25% (top decile) vs. ~1% (bottom quintile). A simplified risk model with 11 predictors gave only slightly weaker discrimination (c-statistic=0.79, 95% confidence interval =0.78-0.81). CONCLUSIONS: This risk score for two-year post-discharge mortality in acute coronary syndrome patients ( www.acsrisk.org ) can facilitate identification of high-risk patients and help guide tailored secondary prevention measures.

Model for Early Detection of Breast Cancer in Low-Resource Areas: The Experience in Peru.

PURPOSE: Late-stage breast cancer detection should be something of the past; however, it is still all too common in low-resource areas, including Peru, where 57% of women diagnosed with cancer are diagnosed at stage III or IV disease. Early detection of breast cancer is feasible in low-resource semirural and rural areas where mammography is rarely accessible. METHODS: PATH collaborated with Peruvian health institutions at local, regional, and national levels to design and implement a model of care for the early detection of breast cancer in Peru. The model includes training health promoters for community outreach, professional midwives in clinical breast exam, doctors to perform fine-needle aspiration biopsy sampling with ultrasound to triage, and patient navigators to ensure patients follow through with treatment. RESULTS: In a northern region of Peru, 400 individuals, including health promoters, midwives, doctors, and volunteers, received early-detection training in two phases. In Peru, local health professionals continue to refine and improve methods and materials using locally available resources, and the Peruvian health information system now includes specific breast cancer detection categories. Despite challenges and limited resources, the model is effective, and partnership with government health administrations improves health systems and benefits the population. CONCLUSION: Given the absence of screening mammography, the public health challenge is to bring breast cancer early detection and diagnostic services closer to women's homes and to ensure appropriate follow-up and care. The model is eminently transferable with appropriate adaptation and should now be tested in other settings within and outside of Peru.

Rationale and design of the long-Term rIsk, clinical manaGement, and healthcare Resource utilization of stable coronary artery dISease in post-myocardial infarction patients (TIGRIS) study.

The long-term progression of coronary artery disease as defined by the natural disease course years after a myocardial infarction (MI) is an important but poorly studied area of clinical research. The long-Term rIsk, clinical manaGement, and healthcare Resource utilization of stable coronary artery dISease in post-myocardial infarction patients (TIGRIS) study was designed to address this knowledge gap by evaluating patient management and clinical outcomes following MI in different regions worldwide. TIGRIS (ClinicalTrials.gov Identifier: NCT01866904) is a multicenter, observational, prospective, longitudinal study enrolling patients with history of MI 1 to 3 years previously and high risk of developing atherothrombotic events in a general-practice setting. The primary objective of TIGRIS is to evaluate clinical events (time to first occurrence of any event from the composite cardiovascular endpoint of MI, unstable angina with urgent revascularization, stroke, or death from any cause), and healthcare resource utilization associated with hospitalization for these events (hospitalization duration and procedures) during follow-up. Overall, 9225 patients were enrolled between June 2013 and November 2014 and are being followed in 369 different centers worldwide. This will allow for the description of regional differences in patient characteristics, risk profiles, medical treatment patterns, clinical outcomes, and healthcare resource utilization. Patients will be followed for up to 3 years. Here we report the rationale, design, patient distribution, and selected baseline characteristics of the TIGRIS study. TIGRIS will describe real-world management, quality of life (self-reported health), and healthcare resource utilization for patients with stable coronary artery disease ≥1 year post-MI.

Relación entre las situaciones clínicas que llevan al tratamiento exclusivamente farmacológico del SCASEST y su pronóstico / Association between clinical pathways leading to medical management and prognosis in patients with NSTEACS

Introducción y objetivos: Una proporción importante de pacientes con síndrome coronario agudo sin elevación del segmento ST (SCASEST) se tratan exclusivamente con fármacos (TEF) sin revascularización coronaria inicial. El objetivo del estudio es evaluar las situaciones clínicas que conducen al TEF y su influencia en el pronóstico del SCASEST. Métodos: Se registraron las características basales, las situaciones clínicas que llevaron a TEF y los resultados a 2 años de una cohorte prospectiva de 5.591 pacientes con SCASEST reclutados en 555 hospitales de 20 países de Europa y América Latina. El impacto del TEF en la mortalidad tras el alta se evaluó mediante modelos de surpervivencia de Cox. Resultados: Se utilizó un TEF en 2.306 pacientes (41,2%), de los que 669 (29%) tenían enfermedad coronaria (EC) significativa y 451 (19,6%), EC no significativa y a 1.186 (51,4%) ni siquiera se les practicó una coronariografía. Los pacientes con TEF eran mayores y de más riesgo. La mortalidad a 2 años fue mayor con TEF que con revascularización coronaria (el 11,0 frente al 4,4%; p < 0,001), superior para quienes no se sometieron a coronariografía (14,6%) y aquellos con EC significativa (9,3%). La mortalidad ajustada por riesgo fue superior entre los pacientes a los que no se hizo coronariografía (HR = 1,81; IC95%, 1,23-2,65) o no se revascularizó pese a tener EC significativa (HR = 1,90; IC95%, 1,23-2,95) que con revascularización coronaria. Conclusiones: Los pacientes con SCASEST en TEF constituyen una población heterogénea con perfiles de riesgo y pronóstico diferentes. Se debe considerar estas diferencias al diseñar futuros estudios en esta población (AU)

Introduction and objectives: A large proportion of patients with non—ST-segment elevation acute coronary syndrome (NSTEACS) are initially selected for medical management (MM) and do not undergo coronary revascularization during or immediately after the index event. The aim of this study was to explore the clinical pathways leading to MM in NSTEACS patients and their influence on prognosis. Methods: Patient characteristics, pathways leading to MM, and 2-year outcomes were recorded in a prospective cohort of 5591 NSTEACS patients enrolled in 555 hospitals in 20 countries across Europe and Latin America. Cox models were used to assess the impact of hospital management on postdischarge mortality. Results: Medical management was the selected strategy in 2306 (41.2%) patients, of whom 669 (29%) had significant coronary artery disease (CAD), 451 (19.6%) had nonsignificant disease, and 1186 (51.4%) did not undergo coronary angiography. Medically managed patients were older and had higher risk features than revascularized patients. Two-year mortality was higher in medically managed patients than in revascularized patients (11.0% vs 4.4%; P < .001), with higher mortality rates in patients who did not undergo angiography (14.6%) and in those with significant CAD (9.3%). Risk-adjusted mortality was highest for patients who did not undergo angiography (HR = 1.81; 95%CI, 1.23-2.65), or were not revascularized in the presence of significant CAD (HR = 1.90; 95%CI, 1.23-2.95) compared with revascularized patients. Conclusions: Medically managed NSTEACS patients represent a heterogeneous population with distinct risk profiles and outcomes. These differences should be considered when designing future studies in this population (AU)

Metabolic syndrome and cardiovascular risk in diabetic population of El Hierro, Canary Islands / Síndrome metabólico y riesgo cardiovascular en la población diabética de El Hierro, Islas Canarias

Introduction: In the Canary Islands there is a high prevalence of vascular risk factors. Objective: To analyze the clinical characteristics of 300 patients with type 2 diabetes in El Hierro, in the Canary Islands. Methods: Patients were assessed at the Internal Medicine Unit of the hospital from 1982 to 2010, and followed up until December 2014 or until death. The sample is composed of 154 women and 156 men (52%). Results: mean age was 66.40 ± 11.60 years, with an average follow-up time of 11.04 ± 4.93 years, and 80.3% were diagnosed of metabolic syndrome, signifi cantly more frequent among women (86.43% vs74.67%, χ2 = 5.62, p = 0.018). During the follow-up period, 51 patients died and a signifi cant proportion developed new cardiovascular complications, such as heart failure (6.7%), ischemic heart disease (17.3%), atrial fi brillation (14.3%), stroke 7%), or peripheral arterial disease (6.9%). Cox regression analysis showed that, although advanced age was the major factor involved in the development of all these complications and in mortality, low cholesterol levels were related to the development of ischemic heart disease and mortality, results that were not dependent on the consumption of statins (as in other examples of inverse epidemiology). Ethanol consumption was related to the incidence of peripheral arterial disease. Conclusions: Old age was the main factor involved in the development of complications and mortality. In addition, low cholesterol levels were related to the development of ischemic heart disease and mortality.

Introducción: en Canarias existe una elevada prevalencia de factores de riesgo vascular, superior a la del resto de España.Objetivo: analizar las características clínicas de 300 adultos diabéticos tipo II de El Hierro, en el Archipiélago Canario. Métodos: los pacientes fueron valorados en la Unidad de Medicina Interna del hospital entre 1982 a 2010, y seguidos hasta diciembre de 2014 o hasta su fallecimiento. La muestra se compone de 154 mujeres y 156 hombres (52%). Resultados: la edad media fue de 66.40 ± 11,60 años, con un tiempo medio de seguimiento de 11,04 ± 4,93 años, y el 80,3% fue diagnosticados de síndrome metabólico, significativamente más frecuente entre las mujeres (86,43% vs.74,67%; χ2 = 5,62, p = 0,018). Durante el periodo de seguimiento 51 pacientes murieron, y una proporción significativa desarrolló nuevas complicaciones cardiovasculares, como insuficiencia cardiaca (6,7%), cardiopatía isquémica (17,3%), fibrilación auricular (14,3%), ictus (4,7%), o enfermedad arterial periférica (6,9%). Mediante análisis de regresión de Cox observamos que, aunque la edad avanzada fue el factor principal implicado en el desarrollo de todas estas complicaciones y en la mortalidad, los niveles bajos de colesterol se relacionaron con el desarrollo de cardiopatía isquémica y de mortalidad, resultados que no eran dependientes del consumo de estatinas (como en otros ejemplos de epidemiología inversa). El consumo de etanol se relacionó con la incidencia de la enfermedad arterial periférica. Conclusiones: la edad avanzada fue el factor principal implicado en el desarrollo de complicaciones y mortalidad. Además, los niveles bajos de colesterol se relacionaron con el desarrollo de cardiopatía isquémica y mortalidad.

Síndrome metabólico y riesgo cardiovascular en la población diabética de El Hierro, Islas Canarias / Metabolic syndrome and cardiovascular risk in diabetic population of El Hierro, Canary Islands

Introducción: en Canarias existe una elevada prevalencia de factores de riesgo vascular, superior a la del resto de España. Objetivo: analizar las características clínicas de 300 adultos diabéticos tipo II de El Hierro, en el Archipiélago Canario. Métodos: los pacientes fueron valorados en la Unidad de Medicina Interna del hospital entre 1982 a 2010, y seguidos hasta diciembre de 2014 o hasta su fallecimiento. La muestra se compone de 154 mujeres y 156 hombres (52%). Resultados: la edad media fue de 66.40 ± 11,60 años, con un tiempo medio de seguimiento de 11,04 ± 4,93 años, y el 80,3% fue diagnosticados de síndrome metabólico, significativamente más frecuente entre las mujeres (86,43% vs. 74,67%; χ2 = 5,62, p = 0,018). Durante el periodo de seguimiento 51 pacientes murieron, y una proporción significativa desarrolló nuevas complicaciones cardiovasculares, como insuficiencia cardiaca (6,7%), cardiopatía isquémica (17,3%), fibrilación auricular (14,3%), ictus (4,7%), o enfermedad arterial periférica (6,9%). Mediante análisis de regresión de Cox observamos que, aunque la edad avanzada fue el factor principal implicado en el desarrollo de todas estas complicaciones y en la mortalidad, los niveles bajos de colesterol se relacionaron con el desarrollo de cardiopatía isquémica y de mortalidad, resultados que no eran dependientes del consumo de estatinas (como en otros ejemplos de epidemiología inversa). El consumo de etanol se relacionó con la incidencia de la enfermedad arterial periférica. Conclusiones: la edad avanzada fue el factor principal implicado en el desarrollo de complicaciones y mortalidad. Además, los niveles bajos de colesterol se relacionaron con el desarrollo de cardiopatía isquémica y mortalidad (AU)

Introduction: In the Canary Islands there is a high prevalence of vascular risk factors. Objective: To analyze the clinical characteristics of 300 patients with type 2 diabetes in El Hierro, in the Canary Islands. Methods: Patients were assessed at the Internal Medicine Unit of the hospital from 1982 to 2010, and followed up until December 2014 or until death. The sample is composed of 154 women and 156 men (52%). Results: mean age was 66.40 ± 11.60 years, with an average follow-up time of 11.04 ± 4.93 years, and 80.3% were diagnosed of metabolic syndrome, significantly more frequent among women (86.43% vs 74.67%, χ2 = 5.62, p = 0.018). During the follow-up period, 51 patients died and a significant proportion developed new cardiovascular complications, such as heart failure (6.7%), ischemic heart disease (17.3%), atrial fibrillation (14.3%), stroke 7%), or peripheral arterial disease (6.9%). Cox regression analysis showed that, although advanced age was the major factor involved in the development of all these complications and in mortality, low cholesterol levels were related to the development of ischemic heart disease and mortality, results that were not dependent on the consumption of statins (as in other examples of inverse epidemiology). Ethanol consumption was related to the incidence of peripheral arterial disease. Conclusions: Old age was the main factor involved in the development of complications and mortality. In addition, low cholesterol levels were related to the development of ischemic heart disease and mortality (AU)

Association of Previous Clinical Breast Examination With Reduced Delays and Earlier-Stage Breast Cancer Diagnosis Among Women in Peru.

IMPORTANCE: Mammographic screening is impractical in most of the world where breast cancers are first identified based on clinical signs and symptoms. Clinical breast examination may improve early diagnosis directly by finding breast cancers at earlier stages or indirectly by heightening women's awareness of breast health concerns. OBJECTIVE: To investigate factors that influence time to presentation and stage at diagnosis among patients with breast cancer to determine whether history of previous clinical breast examination is associated with earlier presentation and/or earlier cancer stage at diagnosis. DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional analysis of individual patient interviews using a validated Breast Cancer Delay Questionnaire, 113 (71.1%) of 159 women with breast cancer treated at a federally funded tertiary care referral cancer center in Trujillo, Peru, from February 1 through May 31, 2015, were studied. MAIN OUTCOMES AND MEASURES: Method of breast cancer detection and factors that influence time to and stage at diagnosis. RESULTS: Of 113 women with diagnosed cancer (mean [SD] age, 54 [10.8] years; age range, 32-82 years), 105 (92.9%) had self-detected disease. Of the 93 women for whom stage was documented, 45 (48.4%) were diagnosed with early-stage disease (American Joint Committee on Cancer [AJCC] stage 0, I, or II), and 48 (51.6%) were diagnosed with late-stage disease (AJCC stage III or IV). Mean (SD) total delay from symptom onset to initiation of treatment was 407 (665) days because of patient (mean [SD], 198 [449] days) and health care system (mean [SD], 241 [556] days) delay. Fifty-two women (46.0%) had a history of clinical breast examination, and 23 (20.4%) had undergone previous mammography. Women who underwent a previous clinical breast examination were more likely to have shorter delays from symptom development to presentation compared with women who had never undergone a previous clinical breast examination (odds ratio, 2.92; 95% CI, 1.30-6.60; P = .01). Women diagnosed with shorter patient delay were more likely to be diagnosed with early-stage disease (AJCC stage 0, I, or II) than those with longer patient delay (31 [58.5%] vs 11 [30.6%], P = .01). Women who underwent a previous clinical breast examination were more likely to be diagnosed with early-stage disease compared with women who had never undergone previous clinical breast examination; this relationship remained significant after controlling for insurance and household income (odds ratio, 2.44; 95% CI, 1.01-5.95; P = .048). CONCLUSIONS AND RELEVANCE: In a population in which most breast cancers are self-detected, previous clinical breast examination was associated with shorter patient delay and earlier stage at breast cancer diagnosis. In regions of the world that lack mammographic screening, the routine use of clinical breast examination may provide a resource-appropriate strategy for improving breast cancer early diagnosis.

Longer-term oral antiplatelet use in stable post-myocardial infarction patients: Insights from the long Term rIsk, clinical manaGement and healthcare Resource utilization of stable coronary artery dISease (TIGRIS) observational study.

OBJECTIVE: To describe contemporary patient characteristics and treatment patterns, including antithrombotic management, of post-myocardial infarction (MI) stable coronary artery disease (CAD) patients at high atherothrombotic risk from different geographical regions. METHODS: Patients ≥50years with prior MI 1-3years ago and ≥1 risk factor (age ≥65years, diabetes, 2nd prior MI >1yr ago, multivessel CAD, creatinine clearance 15-<60ml/min) were enrolled by 369 physicians (96% cardiologists) in 25 countries (2013-14) in the prospective TIGRIS study (NCT01866904). RESULTS: 9225 patients were enrolled (median 1.8years) post-MI: 52% with prior ST-elevation MI, median age 67years, 24% women, 67% Caucasian, 55% had ≥2 additional qualifying risk factors, 14% current smokers, 67% overweight/obese, 34% with blood pressure ≥140/90mmHg. 81% underwent percutaneous coronary intervention (PCI; 66% with drug-eluting stents) for the index MI. 75% of patients had been discharged on dual antiplatelet therapy (DAPT; acetylsalicylic acid [ASA]+ADP receptor inhibitor [ADPri]), mainly clopidogrel (75%). 63% had discontinued antiplatelet treatment (60% ADPri) around 1year, most commonly by physician recommendation (90%). At enrolment, 97% were taking an antithrombotic drug, most commonly ASA (88%), with 27% on DAPT (median duration 1.6years); continued DAPT >1year was highest (39%) in Asia-Pacific and lowest (12%) in Europe. CONCLUSIONS: Despite guideline recommendations, 1 in 4 post-MI patients did not receive DAPT for ~1year. In contrast to guideline recommendations supporting newer ADPris, clopidogrel was mainly prescribed. Prior to recent RCT data supporting DAPT >1year post-MI/PCI, >1 in 4 patients have continued on DAPT, though with substantial international variability.

Association Between Clinical Pathways Leading to Medical Management and Prognosis in Patients With NSTEACS.

INTRODUCTION AND OBJECTIVES: A large proportion of patients with non-ST-segment elevation acute coronary syndrome (NSTEACS) are initially selected for medical management (MM) and do not undergo coronary revascularization during or immediately after the index event. The aim of this study was to explore the clinical pathways leading to MM in NSTEACS patients and their influence on prognosis. METHODS: Patient characteristics, pathways leading to MM, and 2-year outcomes were recorded in a prospective cohort of 5591 NSTEACS patients enrolled in 555 hospitals in 20 countries across Europe and Latin America. Cox models were used to assess the impact of hospital management on postdischarge mortality. RESULTS: Medical management was the selected strategy in 2306 (41.2%) patients, of whom 669 (29%) had significant coronary artery disease (CAD), 451 (19.6%) had nonsignificant disease, and 1186 (51.4%) did not undergo coronary angiography. Medically managed patients were older and had higher risk features than revascularized patients. Two-year mortality was higher in medically managed patients than in revascularized patients (11.0% vs 4.4%; P < .001), with higher mortality rates in patients who did not undergo angiography (14.6%) and in those with significant CAD (9.3%). Risk-adjusted mortality was highest for patients who did not undergo angiography (HR = 1.81; 95%CI, 1.23-2.65), or were not revascularized in the presence of significant CAD (HR = 1.90; 95%CI, 1.23-2.95) compared with revascularized patients. CONCLUSIONS: Medically managed NSTEACS patients represent a heterogeneous population with distinct risk profiles and outcomes. These differences should be considered when designing future studies in this population.

Rationale, Design, and Baseline Characteristics of the EPICOR Asia Study (Long-tErm follow-uP of antithrombotic management patterns In Acute CORonary Syndrome patients in Asia).

BACKGROUND: In-hospital and postdischarge mortality for acute coronary syndromes (ACS) vary across Asia and remain generally poorer than globally. The relationship between real-life antithrombotic management patterns (AMPs) and ACS-related outcomes in Asia is unclear. METHODS: EPICOR Asia (Long-tErm follow-uP of antithrombotic management patterns In acute CORonary syndrome patients in Asia) (NCT01361386) is a prospective, multinational, observational study of patients discharged after hospitalization for an ACS, with 2-year follow-up. The aim is to describe short- and long-term (up to 2 years post-index event) AMPs in patients hospitalized for ACS and to record clinical outcomes, healthcare resource use, and self-reported health status. Pre- and in-hospital management, AMPs, and associated outcomes, with particular focus on ischemic and bleeding events, will be recorded during the 2-year follow up. RESULTS: Between June 2011 and May 2012, 13 005 patients were enrolled. From these, 12 922 patients surviving an ACS (6616 with STEMI, 2570 with NSTEMI, and 3736 with UA) were eligible for inclusion from 219 hospitals across 8 countries and regions in Asia: China (n = 8214), Hong Kong (n = 177), India (n = 2468), Malaysia (n = 100), Singapore (n = 93), South Korea (n = 705), Thailand (n = 957), and Vietnam (n = 208). CONCLUSIONS: EPICOR Asia will provide information regarding clinical management and AMPs for ACS patients in Asia. Impact of AMPs on clinical outcomes, healthcare resource use, and self-reported health status both during hospitalization and up to 2 years after discharge will also be described.

Discapacidad del adulto mayor como impacto del proceso de envejecimiento en la población peruana, 2007 / Disability in older people as impact of aging population in Peru, 2007

La presente investigación pretende exponer la evolución del deterioro de las capacidades físicas de la población adulta mayor y como ésta es impactada por el avance de la edad. Se ha tomado como fuente de datos el Censo Nacional de Población y Vivienda 2007 habiendo llegado a resultados que permiten explicar funcionalmente como se produce este deterioro funcional del adulto mayor. Que este proceso no es diferenciable por sexo ni por ámbito de residencia. Se alcanzan recomendaciones para la formulación de políticas regionales a favor del adulto mayor.

The present investigation seeks to expose the evolution of the deterioration of the biggest mature population's physical capacities and i eat this is impacted by the advance of the age. He/she has taken as source of data Population's National Census and Housing 2007 having arrived to results that they allow to explain functionally like the biggest adult's functional deterioration takes place. That this process is not diferenciable for sex neither for residence environment. Recommendations are reached for the formulation of political regional in favor of the biggest adult.

Comparación de trazos cefalométricos computarizados y manuales midiendo el error de reproducibilidad / A comparison between computerized cephalometric drawing and hand-made cephalometric drawing measuring errors of reproduction

ANTECEDENTES: Las investigaciones sobre la precisión y la reproducibilidad en la ubicación de puntos, ángulos y medidas cefalométricas muestran que varían considerablemente en cuanto a la localización. OBJETIVO: analizar el error de reproducibilidad en los trazos cefalométricos obtenidos en forma manual y computarizada. MÉTODO: se realizó un estudio descriptivo de diseño observacional analítico. Se seleccionaron 10 radiografías de perfil, tomadas a pacientes mayores de 15 años, con buena nitidez y resolución de la imagen, y se excluyeron aquellas que presentaban distorsión del tamaño, de la forma de la imagen y donde no había contacto oclusal. Sobre éstas se realizó el cálculo, ubicando los puntos cefalométricos, empleando el análisis de Steiner; para el trazado manual, se tomaron 5 fotocopias donde se realizaron las medidas angulares y lineales. Para el trazo computarizado, se utilizó el programa Span-6 que se realizó 5 veces. Se aplicaron las pruebas estadísticas para error de reproducibilidad de DÁhlberg, y el coeficiente de correlación para comparar los dos métodos. RESULTADOS: en la técnica manual, en lo que respecta a las medidas angulares, el error fue < 0,5520, y en las medidas lineales error fue < 0,1220, excepto para I-I: NB que fue de 1.732 mm. En la técnica computarizada, el error de reproducibilidad fue <1.80, siendo mayor en Go-Gn:SN. CONCLUSIONES: el método computarizado presentó mayor error de reproducibilidad en la mayoría de las medidas, excepto para la medida angular y lineal de I-I: NB.

Producción de bacillus thuringiensis H-14 var. israelensis utilizando espárrago (Asparagus officinalis) y su uso potencial para el control de la malaria en la Libertad - Perú / Bacillus thuringiensis H-14 var israelensis production using asparagus (Asparagus officinalis) and its potential use for Malaria control in la Libertad - Perú

Objetivo. Estandarizar un medio de cultivo utilizando la infusión de espárrago (Asparagus officinalis) para la producción masiva de bacillus thurningiensis (Bti) H-14 bvar. israelensis y determinar el efecto biolarvicida del Bti sobre Anopheles sp en criaderos naturales del distrito Laredo durante los meses de enero a diciembre del 2000. Materiales y métodos: Se ensayaron 3 medios a base de infusión de espárragos blanco: M1: 100 mL de la infusión, pH 9; M2: 50 mL de la infusión con 50 mL de buffer fosfato, pH 7; y M3: 25 mL de la infusión con 75 mL de agua destilada, pH 9. Como control se utilizó biolarvicidad a través del LC50 y LC90. El medio de cultivo óptimo (menor LC50 y LC90) sirvió para la producción masiva del Bti, el cual se sometió a bioensayo de laboratorio y aplicaciones en criaderos naturales. La efectividad fue determinada mediante la densidad larvaria pre y post aplicación del Bti. Resultados: El medio de cultivo óptimo para la producción de Bti fue M1, mostrando alta efectividad, con 100 por ciento de mortalidad en condiciones de laboratorio y 71-97 por ciento de mortalidad en el campo a las 24 horas de exposición con 3 aplicaciones realizadas semanalmente. Conclusiones: M1 es el medio óptimo para cultivar Bti, con alta efectividad para controlar larvas de Anopheles en el laboratorio y en el campo.

Objective: To standardize a culture medium using asparagus infusion (Asparagus officinalis) for the massive production of Bacillus thurigiensis (Bti) H-14 var. israelensis and to determine Bti bio-larvicide effect upon Anopheles sp. in natural breeding sites in Laredo district from January to December, 2000. Materials and methods: Three media based on white asparagus infusion were tested: M1: 100-mL infusion, pH: 9; M 2: 50-mL infusion plus 50-mL buffer phosphate, pH: 7, and M 3: 25-mL infusion plus 75-mL distilled water, pH: 9. The standard TPH medium was used as a control. Bti production in the different culture media was assessed in order to determine the bio-larvicide effectiveness using LC50 and LC90 The optimum culture medium (lower values for LC 50 and LC90) served for Bti production, and it was evaluated in laboratory and natural breeding sites. Effectiveness was determined measuring larval density prior and after Bti application. Results: The optimum medium for Bti production was M,. It showed high effectiveness, with 100% mortality under laboratory conditions, and 71-97% mortality in the field after 24 hours of exposition with three weekly applications. Conclusions: M1 is the optimum medium for culturing Bti, with high effectiveness for controlling Anopheles larvae both under laboratory and field conditions.