Riesgo de enfermedades cardiovasculares según categorías de presión arterial en una cohorte argentina

SummaryBackground: Hypertension is a recognized strong risk factor for cardiovascular disease. However, no data was available in our country to quantify the relationship between blood pressure and cardiovascular event.Objective: to quantify the risk of cardiovascular events according to blood pressure categories.Methods: A prospective epidemiological study was conducted in 1526 inhabitants from Rauch City, (Buenos Aires, Argentina) between 1997 and 2012. Subjects were classified into one of these blood-pressure categories: 1-optimal, 2-normal, 3-high-normal, 4-grade 1 hypertension, 5-grade 2 hypertension and 6-grade 3 hypertension. The first CVD event, including unstable angina pectoris, fatal and non-fatal myocardial infarction, myocardial revascularization, and fatal or non-fatal stroke, was defined as the primary endpoint. Multivariable Cox proportional-hazards regression models were used to estimate the relative risk (HR) of CVD according to base-line blood-pressure categories.Results: In 2012, 1124 individuals (73.7% of the baseline sample), 719 women and 405 men (in 1997, aged 45±16 and 46±16 respectively) or their relatives in case of death, could be surveyed again in order to obtain information concerning incident CVD events. Cardiovascular event rates and  HR values increased in a stepwise manner across the blood pressure categories (p for trend across categories &lt;0.001 in both sex); however, in subjects aged ?55 years a j-curve phenomenon was observed, showing the lowest incidence in the high-normal category. In all categories CVD events rates were higher for men.Conclusion: This study quantified relationships between BP and CVD starting from high-normal blood pressure in Argentina.   Resumen Antecedentes: La hipertensión arterial es un reconocido factor de riesgo de enfermedad cardiovascular (ECV). Sin embargo, no hay información en Argentina que cuantifique la relación entre la presión arterial (PA) y ECV.Objetivo: Cuantificar el riesgo de ECV de acuerdo a categorías de PA.Método: Se realizó un estudio epidemiológico prospectivo en 1526 habitantes de la ciudad de Rauch (Buenos Aires, Argentina) entre octubre de 1997 y febrero de 2012. Los individuos fueron clasificados en las categorías de PA: 1-óptima, 2-normal, 3-normal-alta, 4-hipertensión grado 1, 5-hipertensión grado 2 y 6-hipertensión grado 3. Fue definido como punto final el primer evento de ECV (angina de pecho inestable, infarto fatal y no fatal, revascularización, y accidente cerebrovascular fatal y no fatal). El riesgo relativo (HR) de tener un evento fue estimado usando modelos de regresión multivariable de Cox.Resultados: En 2012, fueron re-encuestados 1124 individuos (73,7% de la muestra basal), 719 mujeres y 405 hombres, o sus parientes en caso de muerte (edad en 1997 45±16 y 46±16 años, respectivamente). Las tasas de ECV y los HR se incrementaron para cada categoría de PA por encima de la óptima (p &lt; 0.001 en ambos sexos); sin embargo, en sujetos mayores de 55 años se observó un fenómeno de curva en J, con la incidencia más baja en la categoría normal-alto. En todas las categorías la tasa de eventos fue mayor en hombres.Conclusión: Este estudio demostró y cuantificó la relación entre de PA y ECV a partir de PA normal alta en una población de Argentina. </p

Impact of common cardio-metabolic risk factors on fatal and non-fatal cardiovascular disease in Latin America and the Caribbean: An individual-level pooled analysis of 31 cohort studies

Background: Estimates of the burden of cardio-metabolic risk factors in Latin America and the Caribbean (LAC) rely on relative risks (RRs) from non-LAC countries. Whether these RRs apply to LAC remains unknown. Methods: We pooled LAC cohorts. We estimated RRs per unit of exposure to body mass index (BMI), systolic blood pressure (SBP), fasting plasma glucose (FPG), total cholesterol (TC) and non-HDL cholesterol on fatal (31 cohorts, n=168,287) and non-fatal (13 cohorts, n=27,554) cardiovascular diseases, adjusting for regression dilution bias. We used these RRs and national data on mean risk factor levels to estimate the number of cardiovascular deaths attributable to non-optimal levels of each risk factor. Results: Our RRs for SBP, FPG and TC were like those observed in cohorts conducted in high-income countries; however, for BMI, our RRs were consistently smaller in people below 75 years of age. Across risk factors, we observed smaller RRs among older ages. Non-optimal SBP was responsible for the largest number of attributable cardiovascular deaths ranging from 38 per 100,000 women and 54 men in Peru, to 261 (Dominica, women) and 282 (Guyana, men). For non-HDL cholesterol, the lowest attributable rate was for women in Peru (21) and men in Guatemala (25), and the largest in men (158) and women (142) from Guyana. Interpretation: RRs for BMI from studies conducted in high-income countries may overestimate disease burden metrics in LAC; conversely, RRs for SBP, FPG and TC from LAC cohorts are similar to those estimated from cohorts in high-income countries. Funding: Wellcome Trust (214185/Z/18/Z)Fil: Carrillo Larco, Rodrigo M.. Imperial College London; Reino UnidoFil: Stern, Dalia. Instituto Nacional de Salud Publica (insp);Fil: Hambleton, Ian R.. The University Of The West Indies; BarbadosFil: Hennis, Anselm. Pan American Health Organization; Estados UnidosFil: Cesare, Mariachiara Di. Middlesex University; Reino UnidoFil: Lotufo, Paulo. Universidade de Sao Paulo; BrasilFil: Ferreccio, Catterina. Pontificia Universidad Católica de Chile; ChileFil: Irazola, Vilma. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Perel, Pablo. London School of Hygiene and Tropical Medicine; Reino UnidoFil: Gregg, Edward W. Imperial College London; Reino UnidoFil: Miranda, J. Jaime. Universidad Peruana Cayetano Heredia; PerúFil: Ezzati, Majid. Imperial College London; Reino UnidoFil: Danaei, Goodarz. Harvard Medical School; Estados UnidosFil: Aguilar Salinas, Carlos A.. Instituto Nacional de Ciencias Médicas y Nutrición; MéxicoFil: Alvarez Váz, Ramón. Universidad de la República; UruguayFil: Amadio, Marselle B.. Centro Universitario Senac Santo Amaro; BrasilFil: Baccino, Cecilia. Universidad de la República; UruguayFil: Bambs, Claudia. Pontificia Universidad Católica de Chile; ChileFil: Bastos, João Luiz. Universidade Federal de Santa Catarina; BrasilFil: Beckles, Gloria. Centers for Disease Control and Prevention; Estados UnidosFil: Bernabe Ortiz, Antonio. Universidad Peruana Cayetano Heredia; PerúFil: Bernardo, Carla DO. University of Adelaide; AustraliaFil: Bloch, Katia V.. Universidade Federal do Rio de Janeiro; BrasilFil: Blümel, Juan E.. Universidad de Chile; ChileFil: Boggia, Jose G.. Universidad de la República; UruguayFil: Borges, Pollyanna K.. Universidade Estadual do Ponta Grossa; BrasilFil: Bravo, Miguel. MELISA Institute; ChileFil: Brenes Camacho, Gilbert. Universidad de Costa Rica; Costa RicaFil: Carbajal, Horacio A.. Universidad Nacional de La Plata; ArgentinaFil: Castillo Rascón, María Susana. Universidad Nacional de Misiones; Argentin

Dendritic cell deficiencies persist seven months after SARS-CoV-2 infection

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection induces an exacerbated inflammation driven by innate immunity components. Dendritic cells (DCs) play a key role in the defense against viral infections, for instance plasmacytoid DCs (pDCs), have the capacity to produce vast amounts of interferon-alpha (IFN-α). In COVID-19 there is a deficit in DC numbers and IFN-α production, which has been associated with disease severity. In this work, we described that in addition to the DC deficiency, several DC activation and homing markers were altered in acute COVID-19 patients, which were associated with multiple inflammatory markers. Remarkably, previously hospitalized and nonhospitalized patients remained with decreased numbers of CD1c+ myeloid DCs and pDCs seven months after SARS-CoV-2 infection. Moreover, the expression of DC markers such as CD86 and CD4 were only restored in previously nonhospitalized patients, while no restoration of integrin β7 and indoleamine 2,3-dyoxigenase (IDO) levels were observed. These findings contribute to a better understanding of the immunological sequelae of COVID-19

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Impact of common cardio-metabolic risk factors on fatal and non-fatal cardiovascular disease in Latin America and the Caribbean: an individual-level pooled analysis of 31 cohort studies

Background: Estimates of the burden of cardio-metabolic risk factors in Latin America and the Caribbean (LAC) rely on relative risks (RRs) from non-LAC countries. Whether these RRs apply to LAC remains un- known. Methods: We pooled LAC cohorts. We estimated RRs per unit of exposure to body mass index (BMI), systolic blood pressure (SBP), fasting plasma glucose (FPG), total cholesterol (TC) and non-HDL cholesterol on fatal (31 cohorts, n = 168,287) and non-fatal (13 cohorts, n = 27,554) cardiovascular diseases, adjusting for regression dilution bias. We used these RRs and national data on mean risk factor levels to estimate the number of cardiovascular deaths attributable to non-optimal levels of each risk factor. Results: Our RRs for SBP, FPG and TC were like those observed in cohorts conducted in high-income countries; however, for BMI, our RRs were consistently smaller in people below 75 years of age. Across risk factors, we observed smaller RRs among older ages. Non-optimal SBP was responsible for the largest number of attributable cardiovascular deaths ranging from 38 per 10 0,0 0 0 women and 54 men in Peru, to 261 (Dominica, women) and 282 (Guyana, men). For non-HDL cholesterol, the lowest attributable rate was for women in Peru (21) and men in Guatemala (25), and the largest in men (158) and women (142) from Guyana. Interpretation: RRs for BMI from studies conducted in high-income countries may overestimate disease burden metrics in LAC; conversely, RRs for SBP, FPG and TC from LAC cohorts are similar to those esti- mated from cohorts in high-income countries

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

BLOOD PRESSURE AND COMMUNITY-BASED STRATEGIES 507 DECREASE OF BLOOD PRESSURE BY COMMUNITY-BASED STRATEGIES

Abstract In a cross section study performed in Rauch in 1997 we found a high prevalence of hypertension and low levels of treatment and control. To evaluate the impact of the community-based intervention activities on blood pressure (BP), we made a cohort study in 1526 inhabitants aged between 15 and 75 years in 2003. The initial study, the advice to consult the family doctor when alterations were found, the free provision of antihypertensive drugs, the press diffusion of the study results and a healthy lifestyle were included among the intervention activities. BP was measured in the subjects&apos; residence by especially trained nurses, considering systolic BP (SBP) and diastolic BP (DBP) as the average of three measurements in one occasion. A total of 1307 subjects (85.65%) were re-interviewed. SBP decreased from 137.98 ± 0.57 to 132.49 ± 0.53 mm Hg (p&lt;0.01) and DBP from 88.73 ± 0.38 to 81.87 ± 0.33 mm Hg (p&lt;0.01). Pressure decrease was observed in all the age groups, in both sexes and in the subgroup without receiving antihypertensive drugs. The percentage with antihypertensive drugs increased from 12.2 to 20.4 (p&lt;0.01). A significant relationship was observed between the percentiles of the BP changes and weight changes in subjects with and without antihypertensive drugs. Community-based intervention strategies were effective to BP control and, probably, to decrease the cardiovascular risk in a community with high prevalence of hypertension. Key words: high blood pressure, community-based strategies, hypertension treatment and control Resumen Descenso de la presión arterial por estrategias comunitarias. La ciudad de Rauch presentaba en 1997 alta prevalencia de hipertensión arterial (HA) y bajos niveles de tratamiento y control. Para evaluar el impacto de actividades de intervención comunitarias sobre la presión arterial (PA) reencuestamos en el año 2003 a una cohorte de 1526 habitantes de 15-75 años. Las actividades de intervención fueron el estudio inicial, la indicación de concurrir a su médico cuando se hallaban alteraciones, la provisión gratuita de antihipertensivos y la difusión por medios masivos de los resultados del estudio y de hábitos saludables de vida. La PA fue medida en el domicilio por enfermeras especialmente entrenadas, considerando PA sistólica y diastólica (PAS y PAD) a los promedios de tres registros en una ocasión. Se reencuestaron 1307 individuos (85.65%). La PAS descendió de 137.98 ± 0.57 a 132.49 ± 0.53 mm Hg (p&lt;0.01) y la PAD de 88.73 ± 0.38 a 81.87 ± 0.33 mm Hg (p&lt;0.01). La PA disminuyó en ambos sexos, en todos los grupos etáreos y en el subgrupo sin antihipertensivos. El porcentaje de sujetos con antihipertensivos aumentó de 12.2 a 20.4 (p&lt;0.01) y se observó una relación significativa entre los percentilos de los cambios de la PA y los cambios del peso en sujetos con y sin antihipertensivos. Las estrategias de intervención comunitaria fueron efectivas para controlar la PA y, probablemente, para disminuir el riesgo cardiovascular en una comunidad con alta prevalencia de HA. Palabras clave: hipertensión arterial, estrategias comunitarias, tratamiento y control de la hipertensión arterial Received: 4-IV-2005 Accepted-3-VIII-2005 Postal address: Dr. Martín R. Salazar, 14 N° 320, 1900 La Plata, Argentina. Fax (54-221) 425-0811 e-mail: [email protected] Studies carried out in Argentina on urban population showed a high prevalence of hypertension 1-3 , a high increase of blood pressure (BP) in a ten-year period, and an incidence of hypertension during that period of 64% in men with high normal BP 4 . It is known that systolic BP (SBP) increases with age and that the relationship between BP and cardiovascular risk is linear 5 . Hypertension and other health-risk factors trigger the development of cardiovascular diseases and in our country they are the leading death causes (34.2%

Adherence to antihypertensive drug treatment in Argentina: a multicenter study.Adherence to antihypertensive drugs in Argentina.

Adherence to antihypertensive medication is an important challenge that doctors often face in the treatment of hypertension. Good adherence is crucial to prevent cardiovascular complications. In consequence, the present study aimed at determining the prevalence of adherence to antihypertensive treatment and identifying associated clinical variables. A multicenter cross-sectional study was conducted in 12 cities of Argentina. A systematic sampling was performed in order to select patients with hypertension and under pharmacological treatment for at least 6 months. Physicians took three BP measurements, and the level of adherence was assessed using the self-administered Morisky questionnaire (MMAS-8). Participants were classified into three levels of adherence: high adherence—MMAS score of 8; medium adherence—MMAS scores of 6 to <8; and low adherence—MMAS scores of <6. A total of 1111 individuals (62 ± 12 years old, women 49.4%) were included in the present analysis; 159 (14.3%), 329 (29.6%) and 623 (56.1%) patients had low, medium, and high adherence, respectively. The prevalence of controlled hypertension increased only in high adherent patients: 42.8%, 42.2%, and 64.5% for low, medium, and high adherence groups, respectively. Similarly, systolic BP was lower only in the high adherence group. High educational level (OR 3.47, 95% CI 2.68-4.49) and diuretic treatment (OR 0.64, 95% CI 0.47-0.88) were independent predictors of high adherence. In conclusion, more than a half of treated hypertensive patients had a high level of adherence. These patients had lower BP values and higher control levels. A high educational level predicts high adherence.Fil: Espeche, Walter. Hospital San Martin de la Plata; Argentina. Universidad Nacional de La Plata; ArgentinaFil: Salazar, Martin. Universidad Nacional de La Plata; Argentina. Hospital San Martin de la Plata; ArgentinaFil: Sabio, Rodrigo. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Diaz, Alberto Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Leiva Sisnieguez, Carlos Enrique. Universidad Nacional de La Plata; Argentina. Hospital San Martin de la Plata; ArgentinaFil: Olano, Daniel. Hospital San Martin de la Plata; ArgentinaFil: Balbin, Eduardo. Hospital San Martin de la Plata; ArgentinaFil: Renna, Nicolas Federico. Universidad Nacional de Cuyo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Grosse, Pedro. No especifíca;Fil: Flores, Roberto A.. Universidad Nacional de Santiago del Estero. Facultad de Ciencias Medicas.; ArgentinaFil: Lagos, Ana C.. No especifíca;Fil: Ferrero, Pablo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Poppe, Silvia. Hospital Nacional Profesor Alejandro Posadas.; ArgentinaFil: Risso Patron, Facundo. No especifíca;Fil: Sotnieczuk Stasiuk, Victor D.. No especifíca;Fil: Valentini, Elina. No especifíca;Fil: Cardozo, Jose Ricardo. Hospital Justo Pereyra Aristóbulo del Valle; ArgentinaFil: Romano, Jose R.. Hospital de Formosa; ArgentinaFil: Parodi, Roberto. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; ArgentinaFil: Carbajal, Horacio. Universidad Nacional de La Plata; Argentin