The role of genetics in the treatment of dystonia with deep brain stimulation: Systematic review and Meta-analysis.

BACKGROUND: Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions that lead to involuntary postures or repetitive movements. Genetic mutations are being increasingly recognized as a cause of dystonia. Deep brain stimulation (DBS) is one of the limited treatment options available. However, there are varying reports on its efficacy in genetic dystonias. This systematic review of the characteristics of genetic dystonias treated with DBS and their outcomes aims to aid in the evaluation of eligibility for such treatment. METHODS: We performed a PUBMED search of all papers related to genetic dystonias and DBS up until April 2022. In addition to performing a systematic review, we also performed a meta-analysis to assess the role of the mutation on DBS response. We included cases that had a confirmed genetic mutation and DBS along with pre-and post-operative BFMDRS. RESULTS: Ninety-one reports met our inclusion criteria and from them, 235 cases were analyzed. Based on our analysis DYT-TOR1A dystonia had the best evidence for DBS response and Rapid-Onset Dystonia Parkinsonism was among the least responsive to DBS. CONCLUSION: While our report supports the role of genetics in DBS selection and response, it is limited by the rarity of the individual genetic conditions, the reliance on case reports and case series, and the limited ability to obtain genetic testing on a large scale in real-time as opposed to retrospectively as in many cases.

Relación entre el Finnish Diabetes Risk Score, glucemia en ayunas y hemoglobina A1c / Relationship between the Finnish Diabetes Risk Score, fasting blood glucose and glycohemoglobin A1c

Introducción: el Finnish Diabetes Risk Score (FINDRISC) mostró alta sensibilidad y especificidad para la detección de personas que evolucionarían a diabetes mellitus (DM) en las poblaciones estudiadas, por lo cual se decidió utilizarlo entre quienes concurrieron por diferentes motivos a realizarse análisis de laboratorio en centros de la Asociación de Laboratorios de Alta Complejidad (ALAC), con el objeto de identificar personas con diferentes niveles de riesgo de presentar alteraciones de la glucemia en ayunas (GA) y de la HbA1c. Objetivos: explorar la asociación entre la puntuación del FINDRISC con GA y HbA1c, estableciendo el punto de corte de mayor sensibilidad y especificidad para encontrar una GA ≥100 mg/dL y una HbA1c ≥5,7% (38,8 mmol/mol), en una población que concurrió a centros de la ALAC. Materiales y métodos: se incluyeron 1.175 individuos de 45 laboratorios de la ALAC, procesamiento local de glucemia y centralizado de HbA1c (high performance liquid chromatography, HPLC). Análisis estadístico: chi-cuadrado, Odds Ratio, ANOVA, test de Tukey, regresión logística binomial y curvas ROC. Resultados: los puntajes totales del FINDRISC se asociaron de manera positiva y estadísticamente significativa, tanto con los valores de GA como con los niveles de HbA1c. Entre sus variables, una edad mayor o igual a 45 años, un perímetro abdominal de alto riesgo, un índice de masa corporal mayor o igual a 25 Kg/m., la presencia de antecedentes familiares de DM (padres, hermanos o hijos) y la existencia de antecedentes de medicación antihipertensiva se asociaron de manera significativa con valores de GA iguales o superiores a 100 mg/dL y/o niveles de HbA1c iguales o mayores a 5,7% (38,8 mmol/mol). No se halló asociación significativa con la realización de actividad física (al menos 30 minutos diarios) ni con el registro de ingesta diario de frutas y verduras. Los valores medios de GA y HbA1c en individuos con puntajes totales del FINDRISC menores o iguales a 11 fueron de 89,9 mg/dL y 5,2% (33,0 mmol/mol), respectivamente, elevándose hasta valores medios de 116,1 mg/dL y 6,1% (43,0 mmol/mol) en los individuos con puntajes iguales o superiores a 21, siguiendo una asociación del tipo "dosis/respuesta". Por curvas ROC, un FINDRISC de 13 presenta una sensibilidad del 81,89%, especificidad del 67,60% y 70,55% de diagnósticos correctos de HbA1c ≥5,7% (38,8 mmol/mol), y una sensibilidad del 72,50%, especificidad del 70,62% y 71,20% de diagnósticos correctos para encontrar personas con una GA ≥100 mg/dL. Conclusiones: el puntaje del FINDRISC se relacionó con niveles crecientes de GA y HbA1c, resultando útil para encontrar personas con GA ≥100 mg/dL y HbA1c ≥5,7% (38,8 mmol/mol) en la población estudiada.

Introduction: the Finnish Diabetes Risk Score (FINDRISC) has high sensitivity and specificity for the identification of people at risk of diabetes mellitus (DM) in various populations. Therefore, we aimed to use this index to identify individuals at risk of having alterations in fasting glycemia (FG) and HbA1c among those who underwent laboratory analysis at ALAC, Argentina. Objectives: to explore the relationships of the FINDRISC score with the fasting blood glucose (FG) concentration and glycated hemoglobin (HbA1c) level, and to establish appropriate cut-off scores to predict FG ≥100 mg/dL and HbA1c ≥5.7% (38.8 mmol/mol) in this population. Materials and methods: we recruited 1,175 individuals from 45 ALAC laboratories for whom FG and HbA1c had been measured. We analyzed the data using the chi square test, odds ratios, ANOVA plus Tukey's post-hoc test, binomial logistic regression, and receiver operating characteristic (ROC) curves. Results: total FINDRISC score significantly positively correlated with both FG and HbA1c. Of the constituent variables, age ≥45 years, a large waist circumference, a body mass index ≥25 kg/m., a close family history of DM, and the use of antihypertensive medication were significantly associated with FG ≥100 mg/dL and/or HbA1c ≥5.7% (38.8 mmol/mol). However, no significant association was found with physical activity or the daily consumption of fruit and vegetables. The mean FG and HbA1c for individuals with total FINDRISC scores ≤11 were 89.9 mg/dL and 5.2% (33.0 mmol/mol), respectively, which increased to 116.1 mg/dL and 6.1% (43.0 mmol/mol) for individuals with scores ≥21, with a dose/response-type relationship. ROC analysis showed that a FINDRISC of 13 was associated with a sensitivity of 81.89%, a specificity of 67.60%, and a correct diagnosis rate of 70.55% for HbA1c ≥5.7% (38.8 mmol/mol); and a sensitivity of 72.50%, a specificity of 70.62%, and a correct diagnosis rate of 71.20% for FG ≥100 mg/dL. Conclusions: FINDRISC score increases with increasing FG and HbA1c, and is a useful means of identifying people with FG ≥100 mg/dL and HbA1c ≥5.7% (38.8 mmol/mol).

Direct Oral Anticoagulants: An Updated Systematic Review of Their Clinical Pharmacology and Clinical Effectiveness and Safety in Patients With Nonvalvular Atrial Fibrillation.

Direct oral anticoagulants have been an increasingly used class of drugs in the setting of nonvalvular atrial fibrillation, defying vitamin K antagonists' monopoly when it comes to anticoagulation due to its several limitations. Direct oral anticoagulants (DOACs) have entered the market as a noninferior and safer option in comparison with vitamin K antagonists, as their respective phase III clinical trials proved. The aim of this article was to update and summarize data on their clinical pharmacology and to review real-world data to know their comparative effectiveness and safety. We performed a systematic review using PubMed, Google Scholar, Embase, and Web of Science as search engines. Regarding pharmacodynamics, there were no substantial changes reported from their original profile. There were many advances in the knowledge about clinical pharmacokinetics of DOACs that have had a direct impact on their clinical use, mainly related to drug-drug interactions. In a real-world setting, DOACs have shown to be noninferior in preventing thromboembolic events compared to vitamin K antagonists. In regards to safety, DOACs have shown a lower bleeding risk relative to warfarin. Comparison between DOACs has demonstrated rivaroxaban to have the highest bleeding risk. Overall, the evidence gathered showed few changes from the original data presented in phase III clinical trials, concluding that their real-world use coincides greatly with them.

Diagnóstico bacteriológico de la tuberculosis. Estado actual del conocimiento Primera parte / Bacteriologic Diagnosis of Tuberculosis. Current State of Knowledge First part

Uno de los principales desafíos para los Programas de Control de Tuberculosis (PCT) lo constituye la detección temprana de formas abiertas de la enfermedad. La Organización Mundial de la Salud (OMS) ha estimado que el desarrollo de un método de diagnóstico de tuberculosis (TB) que ofreciera un 85% de sensibilidad y un 95% de especificidad sobre muestras de esputo permitiría salvar unas 400000 vidas al año. En condiciones ideales, sería necesario, además, que un método accesible y preciso, aplicado en colectivos de mayor vulnerabilidad, pudiera aportar tanto a la identificación de especie como a su perfil de resistencia, en especial si este implicara un mayor riesgo de fracaso terapéutico. En la última década, el desarrollo del sistema de diagnóstico GeneXpert MTB/RIF ha significado un gran avance en ese sentido. A un costo de USD 9,98 por determinación (en los 145 países subsidiados), el método permitió acercarse a los objetivos mencionados, es decir, la detección precoz de la TB y la detección de resistencia a rifampicina, usualmente tomada como un indicador de fracaso terapéutico.

Asociación entre uricemia y síndrome metabólico en un centro hospitalario de Corrientes / Association between uricemia and metabolic syndrome in a hospital center in Corrientes

Resumen Introducción: en los últimos años numerosa evidencia científica sugiere que la hiperuricemia puede jugar un papel en el desarrollo del síndrome metabólico (SM). En algunos estudios se ha explorado la asociación entre la uricemia y la presencia de SM. Sin embargo, aún no está del todo esclarecido si altos niveles del ácido úrico se relacionan de una manera causal con el desarrollo del SM. Más aún, existen pocos estudios acerca de la presencia del SM y su relación con los niveles de AU en la ciudad de Corrientes. Objetivos: determinar la relación de los niveles séricos de AU y los parámetros que definen el SM en pacientes que concurren al consultorio externo de Clínica Médica y Medicina General del Hospital Ángela I. de Llano, Corrientes, Argentina. Resultados: se incluyó un total de 435 pacientes mayores de 18 años: 312 mujeres (72%) y 123 hombres (28%). El 58% de la población cumplía con el criterio de SM del NCEP-ATP III (60% mujeres y 52% hombres). El 75% presentó hiperuricemia y SM. En este estudio la presencia de SM se asoció significativamente con los valores de uricemia OR: 1.5 (IC 95%: 1,3-1,8). La asociación fue estadísticamente significativa. Conclusiones: los resultados demostraron que el aumento de la frecuencia de los componentes del SM está en relación directa con el incremento de los niveles séricos de AU, y que el valor de corte para esta asociación fue de 4 mg/dl; de ahí la importancia de considerar la determinación de los niveles séricos de AU como posible predictor de SM.

Abstract Introduction: in recent years, numerous scientific evidence suggest that hyperuricemia may play a role in the development of metabolic syndrome (MS). Some studies have explored the association between uricemia and the presence of MS. However, it remains unclear whether high uric acid levels are causally related to the development of MS. Moreover, there are few studies on the presence of metabolic syndrome and its relationship with uric acid (UA) levels in the city of Corrientes, Argentina. Objectives: to determine the relationship between serum UA levels and the parameters that define MS in patients attending the outpatient clinic of Medical Clinic and General Medicine of the Ángela I. de Llano Hospital, Corrientes. Results: a total of 435 patients over 18 years of age were included: 312 (72%) women and 123 (28) men. Fifty-eight percent of the population met the NCEP-ATP III criteria for MS (60% females and 52% males). Seventy-five percent of the population had hyperuricemia and MS. In this study the presence of MS was significantly associated with uricemia values OR:1.5 (95%CI:1.3-1.8). The association is statistically significant. Conclusions: the results show that the increase in the frequency of the components of MS, goes in direct relation with the increase in serum UA levels and that the cut-off value for this association is 4 mg/dl. Hence the importance of considering the determination of serum UA levels as a possible predictor of MS.

Glucemia en ayunas entre 100 y 109 mg/dL versus prediabetes según hemoglobina glicosilada / Fasting blood glucose between 100 and 109 mg/dL versus prediabetes according to glycosylated hemoglobin

Introducción: algunos estudios han señalado que valores de glucemia en ayunas entre 100 y 109 mg/dL se asocian con frecuencias elevadas de prediabetes cuando el criterio de clasificación son los valores de HbA1c. La Sociedad Argentina de Diabetes (SAD) sostiene a 110 mg/dL como valor a partir del cual se clasifica a un paciente como portador de glucemia en ayunas alterada; la frecuencia de individuos posiblemente clasificados en forma incorrecta, según este criterio, aún no se conoce en la población argentina. Objetivos: establecer la frecuencia con que se presenta prediabetes según HbA1c en una población sin diagnóstico de diabetes mellitus (DM) con glucemias en ayunas entre 100 y 109 mg/dL; correlacionar las dos variables y cuantificar la probabilidad de que esto ocurra respecto de otros con glucemias en ayunas <100 mg/dL. Materiales y métodos: se incluyeron 1.002 muestras de igual número de sujetos desde 45 laboratorios de análisis clínicos de la Asociación de Laboratorios de Alta Complejidad (ALAC), con procesamiento local de glucemia y centralizado de HbA1c por high performance liquid chromatography (HPLC). Análisis estadístico: chi cuadrado, odds ratio, coeficiente de correlación y determinación de Pearson, y correlación serial de Durbin-Watson. Resultados: frecuencia de HbA1c ≥5,7% en la población estudiada con glucemias de ayunas entre 100 y 109 mg/dL=29,7%; test de chi cuadrado: p<0,001; odds ratio de tener HbA1c ≥5,7% entre la población con glucemias en ayunas de 100 a 109 mg/dL vs aquella con valores <100 mg/dL=4,328 (IC 95% 2,922-6,411); r=0,852, r2 = 0,727, Durbin-Watson=1,152. Conclusiones: la prediabetes diagnosticada por HbA1c resultó cuatro veces más frecuente en la población estudiada con glucemias en ayunas entre 100 y 109 mg/dL, que en aquella con valores por debajo de 100 mg/dL.

Introduction: some studies have shown that fasting blood glucose values between 100 and 109 mg/dL are associated with high rates of prediabetes when the classification criteria are HbA1c values. The Argentine Diabetes Society still maintains 110 mg/dL as the value from which a patient is classified as having impaired fasting blood glucose; the frequency of individuals possibly incorrectly classified, according to this criterion, is not yet known in any Argentine population. Objectives: to establish the frequency in a population without a diagnosis of diabetes mellitus with fasting blood glucose levels between 100 and 109 mg/dL in which prediabetes occurs according to HbA1c, to correlate both variables and to quantify the probability that this predicts with respect to others with fasting blood glucose levels <100 mg/dL. Materials and methods: 1.002 samples from the same number of subjects from 45 clinical laboratories belonging to ALAC, with local processing of blood glucose and centralized processing of HbA1c by high performance liquid chromatography (HPLC). Statistical analysis: chi square, odds ratio, Pearson correlation coefficient, coefficient of determination and Durbin-Watson serial correlation. Results: frequency of HbA1c ≥5.7% in the studied population with fasting blood glucose levels between 100 and 109 mg/ dL = 29.7%, chi square test: p<0.001; odds ratio of having HbA1c ≥5.7% between the population with fasting blood glucose levels of 100 to 109 mg/dL vs that one with values <100 mg/dL=4.328 (95% CI 2.922-6.411); r=0.852, r2 =0.727, DurbinWatson=1.152. Conclusions: prediabetes diagnosed by HbA1c was four times more frequent in the studied population with fasting glucose values between 100 and 109 mg/dL than in that one with values below 100 mg/dL.

Glycated Hemoglobin Measurement: Comparison of Three Methods Versus High Performance Liquid Chromatography.

BACKGROUND: HbA1c result provide information on metabolic control in diabetes mellitus (DM) and could also be used for its diagnosis. For its determination, the laboratory must be certified by the National Glycohemoglobin Standardization Program (NGSP) or the International Federation of Clinical Chemistry (IFCC) and comply with a strict quality control program. AIMS: To determine the correlation and agreement between HbA1c results measured by three analytical methods (enzymatic, turbidimetric, and capillary electrophoresis) versus HPLC. METHODS: Method comparison-1245 samples from equal number of subjects at 45 Association of High Complexity Laboratories (Asociación de Laboratorios de Alta Complejidad-ALAC) centers, centralizing sample processing and operator. Statistical analysis-analysis of variance (ANOVA) and nonparametric Friedman ANOVA test for related samples, means, and medians. Correlation and concordance-Pearson's correlation and linear regression, intraclass correlation coefficient (Passing and Bablock and Bland and Altman). RESULTS: The comparison of mean values obtained by the four methods showed statistically significant, but clinically irrelevant, differences: HbA1c by HPLC versus Electrophoresis 0.06% (0.42 mmol/mol) P = .000 (± 1.96 DS -0.070 -0.047), Enzymatic 0.087% (1 mmol/mol) P = .000 (± 1.96 DS 0.077 0.098), Turbidimetric 0.056% (0.38 mmol/mol) P = 0.000 (± 1.96 DS -0.067 -0.044). Their concordance showed intraclass correlation of single measures of 0.982 P < .001 (95% CI 0.987 - 0.9838). CONCLUSIONS: The three methods present low variability and high correlation versus the HPLC.

Level of physical activity and barriers to exercise in adults with type 2 diabetes.

INTRODUCTION: Physical activity (PA) is an important element in type 2 diabetes mellitus (T2DM) management. The aims of this study were to assess the percentage of adults with T2DM who perform PA, according to the intensity level and to describe barriers to exercise and the association between metabolic control and other clinical variables. METHODS: Multicenter, observational, cross-sectional study. Data were collected through the International PA Questionnaire (IPAQ) and the PA Barrier Questionnaire. Adults (18-65 years old) with T2DM from 17 Argentine diabetes centers were included, from May to July 2018. RESULTS: A total of 270 men (54.9 ± 9.8 years) and 225 women (55.3 ± 9.6 years) were included. Duration of diabetes: 8.2 ± 6.3 years. The BMI in men was 32 ± 10.6 kg/m2, whereas that in women was 32.5 ± 7.2 kg/m2. The last two HbA1c values were 7.6 ± 1.7% and 7.5 ± 1.6. Results also showed that 12.7% had clinical heart disease, 13.7% had nephropathy, 20.8% had neuropathy, 6.1% had diabetic foot and 14.1% had retinopathy. The level of PA was low in 52.3% of the patients studied and moderate in 30.5%. The most frequent barriers were: "lack of will" (59.6%) and "lack of energy" (37.2%). The low level of PA was associated with age (OR: 1.05 per year of age; p < 0.001), HbA1c (OR: 1.16 per 1%; p < 0.05), BMI (OR: 1.06 per kg/m2; p < 0.001) and sex (OR: 1.69 for women; p < 0.01). CONCLUSIONS: PA in a cornerstone in management T2DM. Nevertheless, in this study, 52.3% of T2DM adults showed low level of PA. The main barriers reported were related to low personal motivation. These factors should be taken into account to implement programs to promote physical activity.

Pregnancy Complicated by the Most Frequent Forms of Maturity Onset Diabetes of the Young: A Narrative Review on Its Pharmacological Implications.

BACKGROUND: Monogenic Diabetes (MFD) represents close to 2% of all the cases of diabetes diagnosed in people younger than 45 years old. Maturity-Onset Diabetes of the Young (MODY), neonatal diabetes, and several syndromic forms of diabetes are included among the most accounts for about typical forms of MDF. MODY is the most frequent type of MFD, with MODY 1, 2, 3, and 5 being the most prevalent forms. The aim of this narrative review is to describe pregnancy associated changes in the pharmacological profile of the antidiabetic drugs used in women with the most frequent MODY subtypes. METHODS: A comprehensive literature search was carried out to identify eligible studies from MEDLINE/ PubMed, EMBASE, and SCIELO databases from 1970 to 2019 first semester. RESULTS: Pregnancy introduces changes in the pharmacodynamic and pharmacokinetic profile of some of the treatments used in MODY. MODY 3 (also known as HNF1-A MODY) is the most frequent MDF. MODY 3 patients are highly sensitive to Sulfonylureas (SU). This is also the case for MODY pregnant women. This high sensitivity to SU is also registered in patients with MODY 1 (HNF4-A MODY). Pharmacodynamic changes have been proposed to explain this behavior (Epac2 hyperactivity). However, changes in expression/activity of the metabolizing CYP2C9 cytochrome and/or alterations in the drug transporters oatp1 (Slc21a1), Lst-1 (Slc21a6), OATPD (SLC21A11), and oat2 may better explain, at least in part, this phenomenon by an increase in the concentration of the active drug. CONCLUSION: The impact of changes in the pharmacological behavior of drugs like SU and other metabolized/transported by mechanisms altered in a pregnancy complicated by MODY is unknown. However, switching-to-insulin recommendation formulated for MODY 1 and 3 seems to be justified. Further research in this field is needed for a better understanding of changes in drug activity associated with this particular subset of patients with MFD.

Secretory Autophagy and Its Relevance in Metabolic and Degenerative Disease.

Proteins to be secreted through so-called "conventional mechanisms" are characterized by the presence of an N-terminal peptide that is a leader or signal peptide, needed for access to the endoplasmic reticulum and the Golgi apparatus for further secretion. However, some relevant cytosolic proteins lack of this signal peptides and should be secreted by different unconventional or "non-canonical" processes. One form of this unconventional secretion was named secretory autophagy (SA) because it is specifically associated with the autophagy pathway. It is defined by ATG proteins that regulate the biogenesis of the autophagosome, its representative organelle. The canonical macroautophagy involves the fusion of the autophagosomes with lysosomes for content degradation, whereas the SA pathway bypasses this degradative process to allow the secretion. ATG5, as well as other factors involved in autophagy such as BCN1, are also activated as part of the secretory pathway. SA has been recognized as a new mechanism that is becoming of increasing relevance to explain the unconventional secretion of a series of cytosolic proteins that have critical biological importance. Also, SA may play a role in the release of aggregation-prone protein since it has been related to the autophagosome biogenesis machinery. SA requires the autophagic pathway and both, secretory autophagy and canonical degradative autophagy are at the same time, integrated and highly regulated processes that interact in ultimate cross-talking molecular mechanisms. The potential implications of alterations in SA, its cargos, pathways, and regulation in human diseases such as metabolic/aging pathological processes are predictable. Further research of SA as potential target of therapeutic intervention is deserved.

Manejo de la Hiperuricemia en Pacientes en Argentina. Una Encuesta Mediante Cuestionario / Hyperuricemia Management in Patients from Argentina. A Questionnaire Survey

Resumen Introducción: Durante muchos años el ácido úrico se ha considerado como un producto metabólico inerte del metabolismo de las purinas, sin embargo, ha sido recientemente asociado a una serie de estados de enfermedad crónica. No hay hallazgos concluyentes disponibles en la actualidad para tomar una conducta activa clara respecto al tratamiento de ácido úrico sérico, y cuál sería su objetivo terapéutico. Material y métodos: Debido a esta controversia, se decidió llevar a cabo una encuesta para evaluar cuáles son las decisiones que se toman en este contexto, en el ámbito médico de la Argentina. Se consultó en qué pacientes se evaluaba en forma rutinaria el ácido úrico sérico, resultando en un 53.2% de todos los pacientes, sin diferenciar patologías, y un 11.5% refirió que no lo realiza rutinariamente. Con respecto al tratamiento sólo refirieron tratarlo con enfermedad renal un 62.5%; con diabetes 61.7%; con síndrome metabólico 60.4%; con enfermedad cardiovascular un 50.3%; con gota, cálculos renales o dolor articular, un 91.3%, 74% y 36.1% respectivamente. Resultados: Los datos de la encuesta confirman la falta de evidencia en el criterio para la selección de pacientes, a los fines de evaluar los niveles de ácido úrico sérico y su tratamiento. Conclusiones: De esta forma, se concluye que prima la necesidad de realizar estudios prospectivos y randomizados de las patologías con alta incidencia de uricemia elevada, para poder determinar normativas que orienten una conducta a los especialistas según los resultados obtenidos, y que dicha decisión no esté basada solo en la opinión de los expertos.

Abstract Introduction: For many years, uric acid was considered to be an inert product of purine metabolism; however, it has recently been associated with a number of chronic diseases. Nowadays, there are no conclusive findings available regarding a clear action plan to treat serum uric acid or which specific therapeutic goals it would have. Methods: Given this controversy, a survey was conducted in order to evaluate which decisions are taken regarding this situation within the Argentinian medical community. The question was in which cases serum uric acid was routinely assessed and the result was 53.2% no matter the pathology; 11,5% of physicians did not assess it routinely. Regarding its treatment, 62.5% of them reported to have treated it as part of kidney disease; 61.7 % as part of diabetes; 60.4% as part of metabolic syndrome; 50.3% as part of cardiovascular disease; 91.3 % as part of gout; 74% as part of renal stones, and 36.1% as part of joint pain. Results: The data collected by means of the survey show a lack of evidence for establishing the patient selection criteria when evaluating levels of serum uric acid and its treatment. Conclusions: Therefore, it is concluded that it is necessary to conduct prospective and randomized studies of conditions with a high incidence of elevated uricemia in order to develop guidelines for specialists according to results; this decision should not be based on experts' opinion alone.

Long-term pharmacotherapy of obesity in patients that have undergone bariatric surgery: pharmacological prevention and management of body weight regain.

INTRODUCTION: The obesity epidemic continues to grow. Bariatric surgery is part of the arsenal to treat the disease. Surgery results in an effective option for patients with severe obesity but also when obesity is associated with significant comorbidities. Weight regain is frequent after bariatric surgery. Consequently, the addition of anti-obesity drugs to prevent and manage weight regain are commonly recommended even when the quality of the evidence supporting this recommendation is relatively weak. cfsda65 AREAS COVERED: The aim of this review is to summarize the available evidence concerning long-term pharmacotherapy of obesity in patients that have undergone bariatric surgery with a focus on pharmacological prevention and management of weight regain. The etiology and epidemiology of weight regain are summarized, as well as the available information about the benefits and risks of long-term pharmacotherapy in the prevention and management of recidivism. EXPERT OPINION: The available information, mainly obtained from observational studies and small trials, is encouraging but calls for a prudent approach in the selection of appropriate agents for each individual patient and a careful follow-up to detect adverse reactions or drug interactions. Results from well-designed trials are upcoming. In the meantime, a cautious, individualized approach is advisable.

Vitamin D Levels and Cardiometabolic Markers in Indigenous Argentinean Children Living at Different Altitudes.

The objective of this study was to assess the association between vitamin D and cardiometabolic markers in 2 indigenous communities from similar ethnic backgrounds, but living at different altitudes. A cross-sectional study compared 152 (72 females) indigenous schoolchildren from San Antonio de los Cobres (SAC), 3750 m above sea level, with 175 (86 females) from Chicoana (CH), 1400 m above sea level, mean age 9 years. Anthropometry, blood pressure, lipids, glucose, insulin, and vitamin D were assessed in spring season. The prevalence of children's overweight/obesity was significantly lower in SAC, 9.2% (13), than in CH, 41.5% (71). There was a significantly higher prevalence of vitamin D deficiency (<20 ng/mL) in SAC (n = 103, 67.7%) than in CH (n = 62, 36.3%). SAC showed an inverse correlation between vitamin D and insulinemia (r = -0.17, P < .05), whereas CH showed an inverse correlation between vitamin D and systolic blood pressure (r = -0.19, P < .05), z-BMI (body mass index; r = -0.25, P < .01), triglycerides (r = -0.15, P < .05), glucose (r = -0.35, P < .05), and insulinemia (r = -0.24, P < .01). Multiple linear regression analysis showed that vitamin D (ß = -.47; R 2 = .21) was significantly associated with SAC location, adjusted for confounding variables. Vitamin D levels were significantly and directly associated with altitude and inversely with metabolic markers, suggesting that populations living at high altitudes are at higher risk for future cardiovascular diseases.

Blood pressure levels among Indigenous children living at different altitudes.

The objective was to compare blood pressure (BP) levels in 2 groups of Indigenous Argentine school children from similar ethnic backgrounds but living at different altitudes. One hundred and fifty-two (46.3%) children (age, 4-14 years) from San Antonio de los Cobres (SAC), at 3750 m above sea level, and 176 children (53.7%) from Chicoana (CH), at 1400 m above sea level, participated in this cross-sectional study. Data for children's anthropometry, BP, glucose, lipids, vitamin D, and insulin, as well as mothers' height and weight were assessed. Hypertension was defined as BP ≥ 95th percentile. The prevalence of overweight/obesity among children was significantly lower in SAC (n = 17, 11.2%) than in CH (n = 74, 42%) (body mass index (BMI) > 85th percentile per US Centers for Disease Control and Prevention norms). However, the prevalence of hypertension was significantly higher among children in SAC (n = 15, 9.9%) than among those in CH (n = 2, 1.1%). Children were divided into 4 groups by mean arterial BP quartiles for comparison by ANOVA. As mean arterial BP increased, age, BMI, glucose, triglycerides, triglycerides/high-density lipoprotein cholesterol, and insulin levels increased significantly. Multiple linear regression analyses showed that children's mean arterial BP was significantly associated with altitude adjusted for confounding variables (R2 = 0.42). Furthermore, when mean arterial BP was replaced by systolic BP (R2 = 0.51) or diastolic BP (R2 = 0.33), similar results were obtained. Our results suggest that Indigenous children who live permanently at high altitude have higher levels of BP, adjusted for confounding variables. Routine BP measurements conducted in the SAC community could be essential for the prevention of cardiovascular disease.

Incidencia de diabetes mellitus tipo 1 en personas menores de 15 años, entre los años 2009 y 2016, en la provincia de Corrientes / Incidence of type 1 diabetes mellitus in persons under 15 years old, betwenn the years 2009 and 2016, in the province of Corrientes

Introducción: la incidencia de diabetes mellitus tipo 1 (DM1) aumentó en los últimos años en varias regiones del mundo. Los Estudios Diabetes Mondiale (DiaMond), Europa y Diabetes (EURODIAB) fueron fundamentales para monitorizar el desarrollo de incidencia de DM1 en niños al propiciar pruebas sobre tendencias y prevalencia mundiales. En el Estudio DiaMond, en la provincia de Corrientes, se halló una incidencia de 4,3/100.000 (2,21-7,51) entre los años 1990 a 1999. Objetivos: determinar la incidencia de DM1 en niños <15 años en la provincia de Corrientes entre el 1º de enero de 2009 y el 31 de diciembre de 2016, según edad, sexo y residencia; comparar con el período 1990-1999; calcular la tasa de incidencia 2009-2016; analizar la presencia de factores de riesgo económicos, psicosociales y ambientales. Materiales y métodos: registro de casos de DM1 con población <15 años, que debutó con DM1, entre el 1º de enero de 2009 y el 31 de diciembre de 2016, a través de una ficha epidemiológica. La fuente primaria fueron datos de registros de médicos especializados en diabetes, endocrinólogos y pediatras, y las fuentes secundarias se tomaron de los registros de entrega de insulinas de hospitales, obras sociales y de la Asociación Correntina de Ayuda al Diabético. El método de captura-recaptura se empleó para establecer el grado de eficiencia y estimar el número de casos incidentes. Se calculó la incidencia anual cada 100.000 habitantes en riesgo, agrupados en tres categorías por edad (0-4, 5-9, 10-14). Resultados: casos estimados 104 (IC95% 100-108). Incidencias 6,0/100.000 2009; 2,3/100.000 2010; 3,71/100.000 2011; 3,75/100.000 2012; 5,82/100.000 2013; 5,2/100.000 2014; 2,7/100.000 2015; 5,5/100.000 2016; incidencia general por año 4,4/100.000. Conclusiones: la tasa calculada entre 2009-2016 de 4,4/100.000 fue similar al período 1990-1999 de 6/100.000 y se mantuvo en el rango de tasa intermedia 5-9,99 por 100.000/año

Introduction: Diabetes Mondiale, Europe and Diabetes studies were fundamental to monitor the development of incidence of type 1 diabetes mellitus (DM1) in children, providing evidence on global trends and prevalence, in the Province of Corrientes was found an incidence 4.3/100,000 (2.21-7.51). Objectives: to determine the incidence of DM1 in children <15 years old in the Province of Corrientes between January 1, 2009 and December 31, 2016, according to age, sex and residence; compare with the period 1990-1999, calculate incidence rate 2009 and 2016; analyze the presence of economic, psychosocial and environmental risk factors. Materials and methods: registry of cases of DM1 with population <15 years, which debuted with DM1, between January 1, 2009 and December 31, 2016 through an epidemiological record, being primary source of data records of diabetologists, endocrinologists and pediatricians; secondary sources records of delivery of insulins from hospitals, social eorks and Correntina Association of Diabetic Aid. The capture-recapture method was used to establish the degree of efficiency and estimate the number of incident cases. The annual incidence per 100,000 inhabitants at risk was calculated, grouped into three age categories (0-4, 5-9, 10-14). Results: estimated cases 104 (95%CI 100-108). Incidences 6.0/100,000 2009; 2.3/100,000 2010; 3.71/100,000 2011; 3.75/100,000 2012; 5.82/100,000 2013; 5.2/100,000 2014; 2.7/100,000 2015; 5.5/100,000 2016; general incidence per year 4.4/100,000. Conclusions: the calculated rate between 2009-2016 of 4.4/100,000 was similar to the period 1990-1999 of 6/100,000, keeping in the range of intermediate rate 5-9.99 per 100,000/year

Hepatic Elimination of Drugs in Gestational Diabetes.

BACKGROUND: The liver is the major metabolic clearance organ for chemical agents from the human body. Pregnancy is associated with several physiological changes that may affect one or more of these factors, and also induces changes in the hepatic clearance of certain drugs. The aim of this paper was to review some of the currently available information in the field to provide some insights about the relevance of these changes on the clearance of some drugs. METHODS: A comprehensive literature search was carried out to identify eligible studies from MEDLINE/PubMed, EMBASE and SCIELO databases through 1970 first semester. RESULTS: Gestational Diabetes Mellitus (GDM) is a frequent disease commonly associated with other entities as obesity, hypertension, dyslipidemia, non-alcoholic fatty liver disease, prothrombotic conditions, changes in intestinal microbiome. These entities, together with the glycemic fluctuations associated with GDM might affect the determinants of the hepatic clearance (hepatic blood flow, the unbound fraction of drugs, and the hepatic intrinsic clearance). GDM is frequently associated with multi-drug treatments. While many of these drugs are cleared by the liver, little is known about the clinical relevance of these GDM associated pharmacokinetic changes. CONCLUSION: Considering the frequency of the disease and the effects that these pharmacokinetic changes might have on the mother and child, the need for further research seems advisable. In the meantime, cautious clinical judgment in the management of drug administration in women affected by this disease is recommended.

Pharmacotherapy and motor recovery after stroke.

INTRODUCTION: Stroke is one of the most prevalent neurological diseases worldwide, especially among the elderly population. There are various mechanisms that enhance motor recovery after a stroke. In clinical practice, we have the opportunity to enhance plasticity by designing specific rehabilitation programs. Areas covered: There are a variety of drugs commonly administered to people after the acute phase of a stroke. These drugs may modify motor performance. Herein reviewed is the evidence concerning motor enhancement or decline in stroke patients, produced by drugs commonly used in rehabilitation settings. An extensive review of animal and human studies is performed. Expert commentary: Many of the clinical trials carried out were underpowered. Modest evidence supports the claim that there are agents that can affect motor rehabilitation after a stroke. Amphetamine-like agents, serotonin reuptake inhibitors, and levodopa might improve motor outcomes, while antipsychotics, some antiepileptic drugs, and GABAmimetic drugs could impair the recovery process. To draw definite recommendations, more comprehensive knowledge about the efficacy, long-term effects, and safety of these drugs is required. There are also other interesting molecules that open a promising field for basic and clinical research, in the search for new therapeutic options.