Association between type 2 diabetes and depressive symptoms after a 1-year follow-up in an older adult Mediterranean population.

OBJECTIVES: To examine the cross-sectional association between baseline depressive symptoms and the presence of type 2 diabetes (T2D), and its association with glycated hemoglobin (HbA1c) and other metabolic variables, and the prospective association of depressive symptoms and HbA1c after 1 year of follow-up. METHODS: n = 6224 Mediterranean older adults with overweight/obesity and metabolic syndrome (48% females, mean age 64.9 ± 4.9 years) were evaluated in the framework of the PREDIMED-Plus study cohort. Depressive symptoms were assessed using the Beck Depression Inventory-II and HbA1c was used to measure metabolic control. RESULTS: The presence of T2D increased the likelihood of higher levels of depressive symptoms (χ2 = 15.84, p = 0.001). Polynomial contrast revealed a positive linear relationship (χ2 = 13.49, p = 0.001), the higher the depressive symptoms levels, the higher the prevalence of T2D. Longitudinal analyses showed that the higher baseline depressive symptoms levels, the higher the likelihood of being within the HbA1c ≥ 7% at 1-year level (Wald-χ2 = 24.06, df = 3, p < .001, for the full adjusted model). Additionally, depressive levels at baseline and duration of T2D predicted higher HbA1c and body mass index, and lower physical activity and adherence to Mediterranean Diet at 1 year of follow-up. CONCLUSIONS: This study supports an association between T2D and the severity of depressive symptoms, suggesting a worse metabolic control from mild severity levels in the short-medium term, influenced by lifestyle habits related to diabetes care. Screening for depressive symptoms and a multidisciplinary integrative therapeutic approach should be ensured in patients with T2D.

Intensive Weight-Loss Lifestyle Intervention Using Mediterranean Diet and COVID-19 Risk in Older Adults: Secondary Analysis of PREDIMED-Plus Trial.

OBJECTIVES: We tested the effects of a weight-loss intervention encouraging energy-reduced MedDiet and physical activity (PA) in comparison to ad libitum MedDiet on COVID-19 incidence in older adults. DESIGN: Secondary analysis of PREDIMED-Plus, a prospective, ongoing, multicentre randomized controlled trial. SETTING: Community-dwelling, free-living participants in PREDIMED-Plus trial. PARTICIPANTS: 6,874 Spanish older adults (55-75 years, 49% women) with overweight/obesity and metabolic syndrome. INTERVENTION: Participants were randomised to Intervention (IG) or Control (CG) Group. IG received intensive behavioural intervention for weight loss with an energy-reduced MedDiet intervention and PA promotion. CG was encouraged to consume ad libitum MedDiet without PA recommendations. MEASUREMENTS: COVID-19 was ascertained by an independent Event Committee until December 31, 2021. COX regression models compared the effect of PREDIMED-Plus interventions on COVID-19 risk. RESULTS: Overall, 653 COVID-19 incident cases were documented (IG:317; CG:336) over a median (IQR) follow-up of 5.8 (1.3) years (inclusive of 4.0 (1.2) years before community transmission of COVID-19) in both groups. A significantly lowered risk of COVID-19 incidence was not evident in IG, compared to CG (fully-adjusted HR (95% CI): 0.96 (0.81,1.12)). CONCLUSIONS: There was no evidence to show that an intensive weight-loss intervention encouraging energy-reduced MedDiet and PA significantly lowered COVID-19 risk in older adults with overweight/obesity and metabolic syndrome in comparison to ad libitum MedDiet. Recommendations to improve adherence to MedDiet provided with or without lifestyle modification suggestions for weight loss may have similar effects in protecting against COVID-19 risk in older adults with high cardiovascular risks.

Clinical Factors Associated with High Glycemic Variability Defined by Coefficient of Variation in Patients with Type 2 Diabetes.

BACKGROUND: High glycemic Variability (HGV) has become a stronger predictor of hypoglycemia. However, clinical factors associate with HGV still are unknown. OBJECTIVE: To determine clinical variables that were associated with a coefficient of variation (CV) above 36% evaluated by continuous glucose monitoring (CGM) in a group of patients with diabetes mellitus. METHODS: A cohort of patients with type 2 diabetes (T2D) was evaluated. Demographic variables, HbA1c, glomerular filtration rate (GFR) and treatment regimen were assessed. A bivariate analysis was performed, to evaluate the association between the outcome variable (CV> 36%) and each of the independent variables. A multivariate model was constructed to evaluate associations after controlling for confounding variables. RESULTS: CGM data from 274 patients were analyzed. CV> 36% was present in 56 patients (20.4%). In the bivariate analysis, demographic and clinical variables were included, such as time since diagnosis, hypoglycemia history, A1c, GFR and treatment established. In the multivariate analysis, GFR <45 mL/min (OR 2.81; CI 1.27,6.23; p:0.01), A1c > 9% (OR 2.81; CI 1.05,7.51; p:0.04) and hypoglycemia history (OR 2.09; CI 1.02,4.32; p:0.04) were associated with HGV. Treatment with iDPP4 (OR 0.39; CI 0.19,0.82; p:0.01) and AGLP1 (OR 0.08; CI 0.01,0.68; p:0.02) was inversely associated with GV. CONCLUSION: Clinical variables such as GFR <45 mL/min, HbA1C>9% and a history of hypoglycemia are associated with a high GV. Our data suggest that the use of technology and treatments able to reduce glycemic variability could be useful in this population to reduce the risk of hypoglycemia and to improve glycemic control.

Health-related quality of life in individuals with metabolic syndrome: A cross-sectional study.

INTRODUCTION AND OBJECTIVES: Metabolic syndrome (MetS) is a combination of various cardiovascular risk factors with a major impact on morbidity and premature mortality. However, the impact of MetS on self-reported health-related quality of life (HRQoL) is unknown. This study evaluated the HRQoL in a Spanish adult population aged 55 years and older with MetS. METHOD: A cross-sectional analysis was performed with baseline data from the PREDIMED-Plus multicentre randomized trial. The participants were 6430 men and women aged 55-75 years with overweight/obesity (body mass index ≥27 and ≤40kg/m2) and MetS. The SF-36 questionnaire was used as a tool to measure HRQoL. Scores were calculated on each scale of the SF-36 by gender and age. RESULTS: Participants showed higher scores in the social function (mean 85.9, 95% CI; 85.4-86.4) and emotional role scales (mean 86.8, 95% CI; 86.0-87.5). By contrast, the worst scores were obtained in the aggregated physical dimensions. In addition, men obtained higher scores than women on all scales. Among men, the worst score was obtained in general health (mean 65.6, 95% CI; 65.0-66.2), and among women, in body pain (mean 54.3, 95%CI; 53.4-55.2). A significant decrease was found in the aggregated physical dimensions score among participants 70-75 years old, but an increased one in the aggregated mental dimensions, compared to younger participants. CONCLUSIONS: Our results reflect that the MetS may negatively affect HRQoL in the aggregated physical dimensions, body pain in women, and general health in men. However, this adverse association was absent for the psychological dimensions of HRQoL, which were less affected.

Abortion and subsequent depressive symptoms: an analysis of the National Longitudinal Study of Adolescent Health.

BACKGROUND: Twenty states currently require that women seeking abortion be counseled on possible psychological responses, with six states stressing negative responses. The majority of research finds that women whose unwanted pregnancies end in abortion do not subsequently have adverse mental health outcomes; scant research examines this relationship for young women. METHODS: Four waves of data from the National Longitudinal Study of Adolescent Health were analyzed. Population-averaged lagged logistic and linear regression models were employed to test the relationship between pregnancy resolution outcome and subsequent depressive symptoms, adjusting for prior depressive symptoms, history of traumatic experiences, and sociodemographic covariates. Depressive symptoms were measured using a nine-item version of the Center for Epidemiologic Studies Depression scale. Analyses were conducted among two subsamples of women whose unwanted first pregnancies were resolved in either abortion or live birth: (1) 856 women with an unwanted first pregnancy between Waves 2 and 3; and (2) 438 women with an unwanted first pregnancy between Waves 3 and 4 (unweighted n's). RESULTS: In unadjusted and adjusted linear and logistic regression analyses for both subsamples, there was no association between having an abortion after an unwanted first pregnancy and subsequent depressive symptoms. In fully adjusted models, the most recent measure of prior depressive symptoms was consistently associated with subsequent depressive symptoms. CONCLUSIONS: In a nationally representative, longitudinal dataset, there was no evidence that young women who had abortions were at increased risk of subsequent depressive symptoms compared with those who give birth after an unwanted first pregnancy.

Insecure maternal attachment is associated with depression in ADHD children.

The objective of this study was to analyze the possible association between maternal attachment style and comorbidity associated with childhood ADHD. We evaluated a total of 103 children with ADHD treated at a Child and Adolescent Mental Health Centre and their mothers. Comorbidity was evaluated using the MINI-KID interview. Maternal attachment was evaluated using the Adult Attachment Questionnaire. We considered child variables that could be associated with the clinical course of ADHD, such as symptom severity, age, gender, evolution time, academic level, and current pharmacological treatment; parental variables, such as the mother's psychiatric history, current psychopathology, marital status, academic level, income, and employment, were also considered. We found an association between maternal insecure attachment and comorbid depressive disorder in childhood ADHD. An insecure maternal attachment style must be considered in the assessment and treatment of childhood ADHD with comorbid depression.

A cardiac mitochondrial cAMP signaling pathway regulates calcium accumulation, permeability transition and cell death.

Although cardiac cytosolic cyclic 3',5'-adenosine monophosphate (cAMP) regulates multiple processes, such as beating, contractility, metabolism and apoptosis, little is known yet on the role of this second messenger within cardiac mitochondria. Using cellular and subcellular approaches, we demonstrate here the local expression of several actors of cAMP signaling within cardiac mitochondria, namely a truncated form of soluble AC (sACt) and the exchange protein directly activated by cAMP 1 (Epac1), and show a protective role for sACt against cell death, apoptosis as well as necrosis in primary cardiomyocytes. Upon stimulation with bicarbonate (HCO3(-)) and Ca(2+), sACt produces cAMP, which in turn stimulates oxygen consumption, increases the mitochondrial membrane potential (ΔΨm) and ATP production. cAMP is rate limiting for matrix Ca(2+) entry via Epac1 and the mitochondrial calcium uniporter and, as a consequence, prevents mitochondrial permeability transition (MPT). The mitochondrial cAMP effects involve neither protein kinase A, Epac2 nor the mitochondrial Na(+)/Ca(2+) exchanger. In addition, in mitochondria isolated from failing rat hearts, stimulation of the mitochondrial cAMP pathway by HCO3(-) rescued the sensitization of mitochondria to Ca(2+)-induced MPT. Thus, our study identifies a link between mitochondrial cAMP, mitochondrial metabolism and cell death in the heart, which is independent of cytosolic cAMP signaling. Our results might have implications for therapeutic prevention of cell death in cardiac pathologies.

A sparse digital signal model for ultrasonic nondestructive evaluation of layered materials.

Signal modeling has been proven to be an useful tool to characterize damaged materials under ultrasonic nondestructive evaluation (NDE). In this paper, we introduce a novel digital signal model for ultrasonic NDE of multilayered materials. This model borrows concepts from lattice filter theory, and bridges them to the physics involved in the wave-material interactions. In particular, the proposed theoretical framework shows that any multilayered material can be characterized by a transfer function with sparse coefficients. The filter coefficients are linked to the physical properties of the material and are analytically obtained from them, whereas a sparse distribution naturally arises and does not rely on heuristic approaches. The developed model is first validated with experimental measurements obtained from multilayered media consisting of homogeneous solids. Then, the sparse structure of the obtained digital filter is exploited through a model-based inverse problem for damage identification in a carbon fiber-reinforced polymer (CFRP) plate.

[Adequacy of urology departments in a health care model of hospitals network]. / Adecuación de Servicios de Urología en un Modelo Asistencial de Red de Hospitales.

UNLABELLED: The traditional health care model is currently facing new health requirements. The implementation of integrated urologic health systems can be one of the possible solutions to these needs. It is mandatory to explore a new health care model, which includes structural and organizational changes. The adequacy of the urology departments of IDCsalud-Madrid network hospitals, creating URORed, is a new system adaptable to constant changes, in order to offer professionalism and quality health care. OBJECTIVE: To describe the administrative/clinic management in the urology service of a health care model of Hospitals network (URORed at IDCsalud. Madrid), that has been included in a model of an Integrated network in a health care service. METHODS: In the period between November 2007 to October 2014, the urology departments of IDCsalud Madrid Group, have been included in a new organizational system, including 4 hospitals, currently with 27 urologists. Each center offers specific urologic services, sharing benefits and human resources. The same directive line leads all centers. RESULTS: The model offers an integrated and uniform urologic service to a specific population of 811.390 habitants (Population Census 2012), with capability to treat specific urologic diseases and to perform a correct clinical follow-up. CONCLUSIONS: Belonging to a health care model in network involves a change of attitude. It creates an organizational change, based on the processes and the results, which enables control of the management analytically, detecting the points that need to be optimized as well as those that are satisfactory. It implies developing a culture of learning and cooperation, so that the processes are fluent and have quality, to create clinical and technological projects in favor of new resource-generating research, based on the needs of the joint management of the hospitals network. The complexity of this model requires a work focused on the human resources, their concerns and their ability to coordinate actions to get results in terms of quality health care and professionalism.

A 50-gene signature is a novel scoring system for tumor-infiltrating immune cells with strong correlation with clinical outcome of stage I/II non-small cell lung cancer.

PURPOSE: To identify a novel system for scoring intratumoral immune response that can improve prognosis and therapy decisions in early stage non-small cell lung cancer (NSCLC). METHODS/PATIENTS: Eighty-four completely resected stage I/II NSCLC without adjuvant therapy were classified by expression profiling using whole genome microarrays. An external cohort of 162 tumors was used to validate the results. Immune cells present in tumor microenvironment were evaluated semiquantitatively by CD20, CD79, CD3, CD8, CD4 and CD57 immunostaining. Univariate and multivariate analyses of variables associated with recurrence-free survival were performed. RESULTS: Initial molecular classification identified three clusters, one with significantly better RFS. A reduced two-subgroup classification and a 50-gene predictor were built and validated in an external dataset: high and low risk of recurrence patients (HR = 3.44; p = 0.001). Analysis of the predictor´s genes showed that the vast majority were related to a B/plasma cell immune response overexpressed in the low-risk subgroup. The predictor includes genes coding for unique B lineage-specific genes, functional elements or other genes that, although non-restricted to this lineage, have strong influence on B-cell homeostasis. Immunostains confirmed increased B-cells in the low-risk subgroup. Gene signature (p < 0.0001) and CD20 (p < 0.05) were predictors for RFS, while CD79 and K-RAS mutations showed a tendency. CONCLUSIONS: Favorable prognosis in completely resected NSCLC is determined by a B-cell-mediated immune response. It can be differently scored by a 50-gene expression profile or by CD20 immunostaining. That prognosis information not reflected by traditional classifications may become a new tool for determining individualized adjuvant therapies.

[Glycemic variability and oxidative stress in children, with type 1 diabetes attending a summer camp]. / Variabilidad glucémica y estrés oxidativo en niños con diabetes tipo 1 asistentes a un campamento.

OBJECTIVE: To assess glycemic variability, oxidative stress and their relationship in children and adolescents with type 1 diabetes (T1DM) attending a summer camp. PATIENTS AND METHOD: Cross-sectional study that included 54 children and adolescents with T1DM aged 7-16, attending a 7 day summer camp. Sociodemographic information, clinical data, and blood glucose values measured using an Accu-Chek Nano® glucose meter were recorded. Glucose variability markers (standard deviation [SD], low blood glucose index [LBGI], high blood glucose index [HBGI], mean amplitude of glycemic excursions [MAGE] and mean of daily differences [MODD]) were calculated. Oxidative stress was assessed by the measurement of 8-iso-prostaglandin F2 alpha (PGF2α) in a 24-hour urine sample collected at the end of the camp in 14 children. RESULTS: The Median SD, MAGE and MODD indexes were in the high range (61, 131 and 58 mg/dl, respectively), LBGI in the moderate range (3.3), and HBGI in the low range (4.5). The mean HbA1c was 7.6% and the median urinary excretion rate of 8-iso-PGF2α was 864.39 pg/mg creatinine. The Spearman correlation coefficients between markers of glycemic variability (SD, HBGI, MAGE, MODD) were significant. Non-significant correlations were found between markers of glycemic variability and urinary 8-iso-PGF2α. CONCLUSIONS: High glycemic variability was observed in children and adolescents attending a summer camp. However, no correlations were found between markers of glycemic variability and oxidative stress measured by urinary 8-iso-PGF2α. Further studies are needed to address the relationship between oxidative stress and glycemic variability in children with T1DM.

[Analysis of the implementation of safety practices in the automated medication dispensing cabinets]. / Análisis de la implantación de prácticas seguras en los sistemas automatizados de dispensación de medicamentos.

OBJECTIVE: To determine the degree of implementation of recommended safety practices in the design and use of automated medication dispensing cabinets (ADCs) in Spanish hospitals. METHODS: A descriptive study based on completion of the "Self- Evaluation Survey on the Safety of Automated Medication Dispensing Systems" from 10/10/2012 to 4/10/2013, at voluntarily participating hospitals. The survey contained 93 items grouped into 14 core processes. RESULTS: In the 36 participating hospitals the average score for the completed survey was 307.8 points (66.2% of the highest possible score [LC 95% CI: 63.2-69.2]). The lowest scores were obtained for core processes 9, 12, 13, 8, 3, 4 and 11 referring to the establishment of guidelines for medication removed using the override function (28.4%), training for healthcare professionals (52%), risk management (53%), defining removal procedures (55.3%), use of ADCs in connection with electronic prescribing (60.9%), information that appears on ADC screens (61.8%) and eliminating medications being returned to ADCs (63.9%), respectively. The hospitals that used ADCs in connection with electronic prescribing as their principal system for distribution presented a higher level of implantation of safety practices than those that used ADCs as a complementary distribution system. CONCLUSIONS: ADC installation has been accompanied by the implementation of various safety practices, but there are still numerous areas of risk for which technical, organizational, and system monitoring safety practices must be added in order to minimize errors with this technology.

Objetivo: Conocer el grado de implantación de las prácticas seguras recomendadas para el diseño y utilización de los sistemas automatizados de dispensación (SAD) de medicamentos en los hospitales españoles. Método: Estudio descriptivo que se basó en la cumplimentación voluntaria del "Cuestionario de autoevaluación de la seguridad de los sistemas automatizados de dispensación de medicamentos", entre el 10-10-2012 y el 10-4-2013. El cuestionario contiene 93 puntos de evaluación agrupados en 14 procedimientos esenciales. Resultados: En los 36 hospitales participantes la puntuación media del cuestionario fue de 307,8 puntos (66,2% del valor máximo posible [LC 95%: 63,2-69,2]). Los valores porcentuales más bajos se obtuvieron de menor a mayor en los procedimientos esenciales 9, 12, 13, 8, 3, 4 y 11, referentes al establecimiento de directrices para las retiradas excepcionales de medicamentos (28,4%), formación a los profesionales (52%), gestión de riesgos (53%), definición de los procedimientos de retirada (55,3%), uso de SAD conectados a prescripción electrónica (60,9%), información que aparece en pantalla (61,8%) y eliminación de la devolución de medicamentos a los SAD (63,9%), respectivamente. Los hospitales que utilizaban SAD con conexión a prescripción electrónica como sistema principal de distribución presentaron un mayor grado de implantación de prácticas seguras que los que usaban SAD como sistema complementario. Conclusiones: La instalación de los SAD se ha acompañado de la implantación de varias prácticas seguras, pero existen numerosas áreas de riesgo en las que es necesario establecer prácticas de tipo técnico, organizativo y de monitorización del sistema para minimizar los errores con esta tecnología.

PP078. Total antioxidant capacity in patients with pregnancy induced hypertension: Its relation to maternal and/or perinatal complications.

INTRODUCTION: Pregnancy-induced hypertension (PIH) is a major cause of maternal and perinatal mortality and morbidity, particularly in under-resourced countries, like Mexico. Studies on PIH have shown increased oxidative stress products such as malondialdehyde and decrease of total antioxidant capacity (TAC). In this research we measured one marker of oxidative stress (OS) the TAC in patients with PIH and we associated it with the development of maternal and/or fetal complications. OBJECTIVES: Determine whether the plasma level of total antioxidant capacity (as a marker of oxidative stress) influences the development of maternal and/or perinatal complications in patients with PIH. METHODS: A observational, analytical, clinical study was conducted in patients with gestational hypertension (GH), mild preeclampsia (MP), severe preeclampsia (SP) and normal pregnancy (NP) > or = 28weeks gestational age. Serum samples were collected and stored at -70°C until use for the determination of total antioxidant capacity. It was associated with the development of maternal and/or perinatal complications. RESULTS: TAC level in normotensive patients (NP) was mean of 2679 +/- 2014mEq/L while in hypertensive patients (GH, MP, SP) was on mean of 1502 +/-1340mEq/L (p<0.05), in the GH group was 1620 +/-1042mEq/L, in the MP group was 1977 +/-1865mEq/L, in the SP was 819 +/-305meq/L The mean TAC level in the 29 patients who had maternal and/or perinatal complications was 1521mEq/L, while in the 38 patients who showed no maternal and/or perinatal complications the mean was 2355mEq/L (p<0.05). Of the 29 patients who had complications 15 (52%) had greatly diminished TAC levels (less than 1000mEq/L), 9 (31%) had between 1000 and 2500mEq/L and only 5 (17%)>2500mEq/L. 72% (28/39) of PIH group had one or more maternal and/or perinatal complications, while only 1 patient (3.6%) of 28 patients with NP had one or more maternal and/or perinatal complications (p<0.05). CONCLUSION: Patients with decreased TAC level had a higher percentage of maternal and/or perinatal complications. Patients with PIH classified as mild preeclampsia, showing reduced TAC level should be in close observation as they have the risk of developing life-threatening complications since management is usually as outpatient.

[The course of attention deficit/hyperactivity disorder in an outpatient sample]. / Curso del trastorno por déficit de atención y/o hiperactividad en una muestra ambulatoria.

INTRODUCTION: Attention Deficit Hyperactivity Disorder may be a disorder of with a poor prognosis and more so when associated with psychosocial risk factors. The aim of this study is to identify clinical and psychosocial risk factors associated with poor prognosis of this disorder. PATIENTS AND METHODS: In a sample of 88 patients was followed up at our Child and Adolescent Mental Health Centres for two or more years. We classified subjects using the Clinical Global Impression Scale of Improvement following the clinical course in three categories (improved, worsened and unchanged). We performed bivariate and univariate logistic regressions to study the association between the variables and outcome. RESULTS: Worsened and unchanged groups (30% of the sample) had more psychiatric comorbidity, a higher percentage of individuals with no drug treatment, and presence of the following social risk factors: inadequate parenting, adverse social and family environment and psychosocial stress. The highest degree of association is related to the absence of drug treatment (OR=15.8, 95% CI 2.71 to 92.19, P=.002) and the presence of two comorbidities (OR=4.8, 95% CI 1.02 to 22.64, P=.047). CONCLUSIONS: In our sample of ADHD outpatients, there was a subgroup that was unchanged or worsened. Drug therapy, psychological treatment, detection and clinical management of comorbidity and some of the psychosocial risk factors can influence the course and outcome of ADHD and therefore the standard treatment of these patients needs to be considered.

Exercise training and cytokines in breast cancer survivors.

The purpose of this randomized controlled trial was to determine the effects of an 8-week (aerobic+strength) exercise training program (3 sessions/week) on the circulating cytokine levels of breast cancer survivors. We randomly allocated 16 female survivors of breast cancer (mean±SD age: 50±5 years) to an intervention or usual care (control) group (N=8 in each group). The intervention group followed an 8-week exercise program consisting of 3 sessions/week (session duration: 90 min). We measured the levels of the following cytokines before and after the intervention: beta-NGF, CTACK, eotaxin, FGF basic, G-CSF, gmCSFα, HGF, ICAM1, IFNα2, IFNγ, IL1α, IL1ß, IL1ra, IL2, IL2ra, IL3, IL4, IL6, IL7, IL8, IL9, IL10, IL12, IL13, IL15, IL16, IL17, IL18, IP10, LIF, MCS-F, MIP1α, MIP1ß, MIF, MCP1, MCP3, MIG, PDGF bb, SCF, SCGFß, SDF1α, TRAIL, TNFα, TNFß, VCAM1, and VEGF. We only observed a significant interaction (group*time) effect for CTACK ( P=0.016), with mean values remaining stable in the intervention group but increasing over time in controls. The intervention program did not induce a significant decrease in the main breast cancer-related cytokines such as IL6 and IL8. A combined (aerobic+strength) 8-week exercise training intervention did not induce major changes in the basal cytokine levels of breast cancer survivors.

Robust anti-arrhythmic efficacy of verapamil and flunarizine against dofetilide-induced TdP arrhythmias is based upon a shared and a different mode of action.

BACKGROUND AND PURPOSE: The high predisposition to Torsade de Pointes (TdP) in dogs with chronic AV-block (CAVB) is well documented. The anti-arrhythmic efficacy and mode of action of Ca(2+) channel antagonists, flunarizine and verapamil against TdP were investigated. EXPERIMENTAL APPROACH: Mongrel dogs with CAVB were selected based on the inducibility of TdP with dofetilide. The effects of flunarizine and verapamil were assessed after TdP and in different experiments to prevent dofetilide-induced TdP. Electrocardiogram and ventricular monophasic action potentials were recorded. Electrophysiological parameters and short-term variability of repolarization (STV) were determined. In vitro, flunarizine and verapamil were added to determine their effect on (i) dofetilide-induced early after depolarizations (EADs) in canine ventricular myocytes (VM); (ii) diastolic Ca(2+) sparks in RyR2(R4496+/+) mouse myocytes; and (iii) peak and late I(Na) in SCN5A-HEK 293 cells. KEY RESULTS: Dofetilide increased STV prior to TdP and in VM prior to EADs. Both flunarizine and verapamil completely suppressed TdP and reversed STV to baseline values. Complete prevention of TdP was achieved with both drugs, accompanied by the prevention of an increase in STV. Suppression of EADs was confirmed after flunarizine. Only flunarizine blocked late I(Na). Ca(2+) sparks were reduced with verapamil. CONCLUSIONS AND IMPLICATIONS: Robust anti-arrhythmic efficacy was seen with both Ca(2+) channel antagonists. Their divergent electrophysiological actions may be related to different additional effects of the two drugs.

Substance use among university students at the St Augustine campus of the University of the West Indies.

OBJECTIVE: Substance use and abuse is a well known public health risk that peaks in persons between 18 and 25 years of age and is prevalent among university students. While this has been repeatedly documented in developed nations, there have been limited studies in the English-speaking Caribbean. This study therefore sought to assess the prevalence of alcohol, tobacco and marijuana use among university students in the English-speaking Caribbean and any associated risk factors. METHODS: The study was designed as a descriptive, cross-sectional study to assess substance use in full-time, undergraduate students of The University of the West Indies (UWI), Trinidad and Tobago, over a six-month period. Questionnaires were distributed and students asked to self-report on their use of alcohol, tobacco and marijuana during the preceding six months. RESULTS: The six-month prevalence rate for alcohol was 70% and 28% of students were identified as regular users. Binge drinking was estimated at 31%. Muslims were least likely to have used alcohol when compared to other religious groupings. The prevalence rate for tobacco and marijuana was 17% and 13%, respectively Ten per cent used all three substances. The use of all three substances was associated with multiple problems. CONCLUSION: We conclude that substance use is common among many students of the UWI but generally lower than reports from other regions of the world. Despite this, substance use is associated with a number of problems and immediate educational interventions may be necessary to assist students in making informed and responsible choices.