Supporting the use of a coagulometric method for rivaroxaban control: a hypothesis-generating study to define the safety cut-offs.

AIMS: Although quantitative anti-FXa assays can be used to measure rivaroxaban plasma levels, they are not widely performed or available. We aimed to tentatively determine the cut-off for thromboembolism and bleeding prevention based on the clotting effect of non-rivaroxaban conjugate-activated FX plasma levels in patients with rivaroxaban using a coagulometric method. METHODS AND RESULTS: Rivaroxaban was added in vitro to normal plasma at a range of 0 to 241 µg/L to cover expected peak and trough levels. Rivaroxaban chromogenic (µg/L) and RVV-confirm as a ratio were determined. Patient plasma samples were assayed with the RVV-confirm reagent. The appropriate rivaroxaban plasma concentration to inhibit clotting mechanisms was based on the remaining FXa in plasma, which was expressed as the ratio of patients/normal, R-C. There is a high correlation between R-C in vitro and spiked normal plasma rivaroxaban concentration (R-Square 0.910, linear equation; 0.971 quadratic equation, p < 0.0001 for both) but not with plasma rivaroxaban chromogenic assays. We propose a cut-off R-C value of 1.65 and 4.5 for safety. Based on the proposed therapeutic range, in 158 assays performed in 58 patients, 6.3 % assays were above the level of bleeding tendency at the peak (R-C 5.39 ± 1.01, median 5.13) and 42 % assays were below the prevention cut-off at the trough (R-C 1.31 ± 0.18, median 1.35). CONCLUSIONS: RVVconfirm® is fast and sensitive to measure the effect of rivaroxaban. Clinical studies are needed to establish whether this cut-off is useful for identifying patients at increased risk of hemorrhage or those who exhibit a low level of anticoagulation.

Simple and rapid assay for effect of the new oral anticoagulant (NOAC) rivaroxaban: preliminary results support further tests with all NOACs.

BACKGROUND: New oral anticoagulant (NOAC) drugs are known to influence the results of some routine hemostasis tests. Further data are needed to enable routine assessment of the effects of NOAC on clotting parameters in some special circumstances. METHODS: Following administration of rivaroxaban to patients, at the likely peak and trough activity times, we assessed the effects on prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and clotting time using Russell's viper venom, and in the presence of phospholipids and calcium reagent available as DVVreagent® and DVVconfirm®. The data were used to determine an adequate NOAC plasma level based on anticoagulant activities expressed as a ratio (patients/normal, R-C). RESULTS: DVVconfirm as R-C could be rapidly performed, and the results were reasonably sensitive for rivaroxaban and probably for other FX inhibitors. This assay is not influenced by lupus anticoagulant and heparin, does not require purified NOAC as control, and will measure whole-plasma clotting activity. CONCLUSIONS: We propose a cut-off R-C value of 4.52 ± 0.33 for safety, but clinical studies are needed to establish whether this cut-off is useful for identifying patients at increased risk of hemorrhage or exhibiting low anticoagulation effect. It also seems possible that normal R-C could indicate an absence of anticoagulant activity when rivaroxaban is discontinued due to episodes of uncontrolled bleeding during anticoagulation or for emergency surgery.

Age-distribution and genotype-phenotype correlation for N-acetyltransferase in Argentine children under isoniazid treatment.

INTRODUCTION: Metabolic clearance of isoniazid (INH) may be up to 10 times faster in individuals who are rapid acetylators compared with slow acetylators. In addition, the acetylation phenotype has been suggested to change with age. A better knowledge of the age distribution of the acetylation genotype and phenotype in children requiring INH for tuberculosis treatment or prevention could be important to optimize safety and efficacy of INH use. OBJECTIVES: The aim of the present study was to evaluate the genotype and phenotype of NAT2 in an Argentinean pediatric population rom Buenos Aires. In addition, we wanted to describe genotype-phenotype correlation, as well as its distribution at different ages. METHODOLOGY: NAT2 genotyping was performed by RFLP technique, searching for common polymorphisms. Acetylisoniazid and isoniazid concentrations were measured by HPLC and NAT2 phenotype was defined from the ratio of both concentrations (Metabolic Ratio, MR). RESULTS: Almost half of the patients (46.02%) possessed wild-type haplotype, with 17.05% of individuals having two fully functional alleles, 57.95% one fully functional allele and 25% with no fully functional allele. According to phenotype, most children (96.59%) were classified as fast acetylators, whereas 1.14% of the cases were intermediate and 2.27% slow acetylators. There was a positive association between age and MR (R = 0.52985, p < 0.000001) with a significant MR difference between age categories (p < 0.001). CONCLUSIONS: We found a high proportion of rapid acetylators compared with other populations. Acetylator phenotype showed a positive correlation with age, with a significant change around the 4th year of life.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

Association of the C-344T aldosterone synthase gene variant with essential hypertension: a meta-analysis.

BACKGROUND: The CYP11B2 gene (CYP11B2) encoding aldosterone synthase has been associated with essential hypertension and some, but not all, studies have reported that the C-344T variant may influence the risk of the disease. OBJECTIVE: We performed a systematic review of the literature by means of a meta-analysis to evaluate the influence of the C-344T CYP11B2 polymorphism on arterial hypertension and intermediate phenotypes. METHODS: From 485 reports, we included 42 observational studies, case-control and cohort at baseline. Fixed and random effect models were used to pool data from individual studies. RESULTS: From 19 heterogeneous studies including 5343 essential hypertensive and 5882 control subjects, we found a significant association between hypertension and the C-344T variant in fixed but not in random effect models [for homozygous CC: odds ratio (OR), 0.834; 95% confidence interval (CI), 0.760-0.914; P < 0.0001, n = 11 225]. Besides, homozygous CC subjects had lower plasma renin activity (D, -0.161; 95% CI, -0.279 to -0.043; P < 0.01, n = 1428) but no difference in plasma aldosterone levels (D, -0.006; 95% CI, -0.081 to 0.07; P = 0.88, n = 2872). Limiting the quantitative analysis of blood pressure to 13 studies including only untreated individuals, no significant association was found for systolic arterial blood pressure (D, 0.042; 95% CI, -0.057 to 0.141; P = 0.41, n = 1775) and diastolic arterial blood pressure (D, 0.026; 95% CI, -0.073 to 0.125; P = 0.61, n = 1775). CONCLUSION: Homozygous individuals for the -344C CYP11B2 allele are at 17% lower risk of hypertension with respect to homozygous TT subjects.

Serotonin and serotonin transporter gene variant in rotating shift workers.

STUDY OBJECTIVES: Because serotonin (5-HT) is a neurotransmitter associated with circadian rhythm regulation, we explored a possible relation among 5-HT, serotonin metabolite, 5-hydroxyindolacetic acid (5HIAA), and the functional polymorphism of the serotonin transporter gene (SLC6A4) promoter with rotating shift work. DESIGN AND PARTICIPANTS: 683 men were included in this study: 437 day workers were compared with 246 rotating shift workers. RESULTS: Platelet 5-HT content differed significantly (P = 0.002) between day workers (41.28+/-1.99 pg/mg) and rotating shift workers (37.91+/-4.16 pg/mg); 5-HIAA content was also significantly (P = 0.00004) higher in day workers (11.40+/-0.82 pg/mg) than in rotating shift workers (9.33+/-1.02 pg/ mg). We looked for further differences in SLC6A4 promoter (5-HTTLPR, 44 bp insertion: long (L)/deletion: short (S) alleles). We found a significant (P = 0.016) difference in genotype distribution between day workers LL: 126 (28.8%), LS: 202 (46.2%), and SS: 109 (24.9%), and rotating shift workers LL: 47 (19.1%), LS: 124 (50.4%), and SS: 75 (30.5%). When we divided the subjects between workers with less and more than 60 month rotating shift-work exposure, the difference in SLC6A4 genotypes frequency was only significant in the group with > or =60 months (P = 0.011). In addition, there was a significantly lower content of platelet 5-HIAA in S allele carriers in comparison with the other genotypes (SS: 9.2+/-1.0 pg/mg vs. SL/LL: 11.0+/-0.8 pg/mg, P <0.02). CONCLUSIONS: Platelet 5-HT and 5-HIAA contents were significantly lower in rotating shift workers than day workers, and there was a significant association between the S variant of SLC6A4 promoter and shift work. These findings may be important for targeting effective therapeutic strategies to ameliorate the associated comorbidities and behavioral problems in rotating shift workers.

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.