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1.
Environ Toxicol Pharmacol ; 105: 104344, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38103810

RESUMEN

Two hundred and twenty subjects were recruited while undergoing cardiac catheterization. AHRR cg05575921 methylation was shown to be significantly decreased in ever smokers compared to never smokers (Mean± SD = 64.2 ± 17.2 vs 80.1 ± 11.1 respectively; P < 0.0001). In addition, higher urinary levels of 2-OHNAP and 2-OHFLU were significantly associated with more AHRR cg05575921 hypomethylation, even after correcting for smoking (ß[95%CI]= -4.161[-7.553, -0.769]; P = 0.016 and -5.190[-9.761, -0.618]; P = 0.026, respectively) but not 1-OHPYR (ß[95%CI]= -3.545 [-10.935, 3.845]; P = 0.345). Additionally, hypomethylation of AHRR ROI was significantly associated with obstructive coronary artery disease (CAD) after adjusting for smoking, age, sex, diabetes and dyslipidemia (OR [95%CI] = 1.024[1.000 - 1.048]; P = 0.046). Results of this study necessitate further validation to potentially consider clinical incorporation of AHRR methylation status as an early predictive biomarker for the potential association between ambient air pollution and CAD.


Asunto(s)
Contaminación del Aire , Enfermedad de la Arteria Coronaria , Hidrocarburos Aromáticos , Humanos , Enfermedad de la Arteria Coronaria/genética , Biomarcadores , Metilación de ADN , Proteínas Represoras/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética
2.
PLoS One ; 18(10): e0287844, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37874832

RESUMEN

Cardiovascular diseases are increasing at an alarming rate worldwide, reaching epidemic proportions in countries of the Eastern Mediterranean Region, including Lebanon. Despite the growing number of patients suffering from cardiovascular diseases in Lebanon, there is scarce data on whether cardiac patients adhere to therapeutic dietary guidelines, drug prescriptions, and physical activity recommendations and whether such adherence differs according to sociodemographic, lifestyle, or psychosocial characteristics. A cross-sectional study was conducted among 367 Lebanese adult cardiovascular disease patients admitted for hospitalization at various hospital sites in Lebanon. Electronic medical records and a multi-component questionnaire were used to collect information on patients' characteristics. Dietary assessment was performed using a culture-specific validated food frequency questionnaire, and physical activity levels were assessed using the international physical activity questionnaire (IPAQ). Mental well-being was assessed based on the validated five-item well-being index (WHO-5), and drug adherence was evaluated using the Morisky medication adherence scale (MMAS-8). The majority of the patients were males (67.8%), overweight or obese (74%), smokers (62.1%), and unemployed or retired (54.5%). Almost 35% of the patients were lonely, and nearly one fourth were at a high risk of poor mental health. Approximately 43%, 70%, and 52% of the patients were found to have poor adherence to diet, drug, and physical activity recommendations, respectively. A lower sense of mental well-being was a significant predictor of low dietary and drug adherence. Surprisingly, overweight and obesity were associated with higher odds of dietary adherence. Male gender was positively associated with physical activity while loneliness was inversely associated with physical activity. This study showed that adherence to diet, drug, and physical activity recommendations was low in this patient population and identified several non-clinical characteristics that may affect adherence. These findings highlighted the need for considering patients' psychosocial characteristics in the treatment of patients with cardiovascular diseases.


Asunto(s)
Enfermedades Cardiovasculares , Adulto , Humanos , Masculino , Femenino , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/epidemiología , Sobrepeso/epidemiología , Líbano/epidemiología , Estudios Transversales , Dieta , Obesidad/epidemiología , Ejercicio Físico
3.
Drug Res (Stuttg) ; 73(6): 349-354, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37094796

RESUMEN

Favipiravir is an antiviral drug used to treat influenza and is also being investigated for the treatment of SARS-CoV-2. Its pharmacokinetic profile varies depending on ethnic group. The present research examines the pharmacokinetic features of favipiravir in healthy male Egyptian volunteers. Another goal of this research is to determine the optimum dissolution testing conditions for immediate release tablets. In vitro dissolution testing was investigated for favipiravir tablets in three different pH media. The pharmacokinetic features of favipiravir were examined in 27 healthy male Egyptian volunteers. The parameter "AUC0-t" vs. percent dissolved was used to develop level C in vitro in vivo correlation (IVIVC) to set the optimum dissolution medium to achieve accurate dissolution profile for favipiravir (IR) tablets. The in vitro release results revealed significant difference among the three different dissolution media. The Pk parameters of twenty-seven human subjects showed mean value of Cpmax of 5966.45 ng/mL at median tmax of 0.75 h with AUC0-∞ equals 13325.54 ng.h/mL, showing half-life of 1.25 h. Level C IVIVC was developed successfully. It was concluded that Egyptian volunteers had comparable Pk values to American and Caucasian volunteers, however they were considerably different from Japanese subjects. AUC0-t vs. % dissolved was used to develop level C IVIVC to set the optimum dissolution medium. Phosphate buffer medium (pH 6.8) was found to be the optimum dissolution medium for in vitro dissolution testing for Favipiravir IR tablets.


Asunto(s)
COVID-19 , Humanos , Masculino , Egipto , Área Bajo la Curva , SARS-CoV-2 , Comprimidos , Voluntarios , Solubilidad , Voluntarios Sanos
4.
Sci Rep ; 12(1): 21563, 2022 12 13.
Artículo en Inglés | MEDLINE | ID: mdl-36513746

RESUMEN

Urinary podocin and nephrin mRNAs (podocyturia), as candidate biomarkers of endothelial/podocyte injury, were measured by quantitative PCR in Type II diabetics with normal albumin excretion rates (AER) at baseline, at 3-4 years, and at 7 years. Development of cardiovascular disease (CVD) was collected as outcome. Visit 1 podocyturia was significantly higher in subjects who subsequently developed CVD versus those who did not. Visit 1 AER terciles exhibited similar time to CVD, in contrast with stepwise and substantial increases in CVD events predicted by Visit 1 podocyturia terciles. Covariate-adjusted hazard ratios were highest for podocin, intermediate for nephrin mRNAs, and lowest for AER. Podocyturia was also measured in patients with and without significant coronary obstruction, and in 480 normoalbuminuric subjects at the enrolment visit to the Multi-Ethnic Study of Atherosclerosis (MESA). Podocyturia > 3 × 106 copies was associated with presence of obstructive coronary artery disease. In the MESA population, Visit 1 podocyturia was significantly higher in men, subjects with elevated BMI, and those with Type II DM. Conclusions: Podocyturia may be an earlier predictor of cardiovascular events than moderate albuminuria; it is significantly higher in patients with obstructive coronary artery disease, and in subjects with established risk factors for CVD.


Asunto(s)
Aterosclerosis , Enfermedades Cardiovasculares , Enfermedad de la Arteria Coronaria , Podocitos , Masculino , Humanos , Biomarcadores , Factores de Riesgo
6.
BMJ Open ; 11(10): e050957, 2021 10 19.
Artículo en Inglés | MEDLINE | ID: mdl-34667007

RESUMEN

INTRODUCTION: Alterations in linear and non-linear parameters of beat-to-beat blood pressure variability (BPV) have been shown to predict disease prognosis and distinguish between risk categories in various pathological conditions, independently of average blood pressure levels. Obesity places subjects at elevated risk of vascular diseases, including hypertension, resulting in serious cardiac, respiratory and cerebral events. However, little is known about the status of vascular dynamics in obese and morbidly obese adults. METHODS AND ANALYSIS: In this present quasi-experimental longitudinal study, changes in beat-to-beat BPV, using continuous, non-invasive blood pressure monitoring, in obese subjects undergoing bariatric surgery are characterised. The capacity of linear and non-linear measures of BPV to detect differences between hypertensive, prehypertensive and normotensive obese subjects prebariatric and postbariatric surgery are tested. Additionally, potential correlations between beat-to-beat BPV and age, body mass index, gender and comorbidities will be investigated. In parallel, the impact of the unsteady fluctuations of beat-to-beat blood pressure on the dynamic stresses imparted by blood flow on blood vessel walls will be explored. We expect to find altered BPV profiles in hypertensive and prehypertensive subjects as compared with normotensive subjects. We also expect to see differential normalisation in BPV profiles between hypertensive, prehypertensive and normotensive subjects over time. ETHICS AND DISSEMINATION: The study has been approved by the Institutional Review Board at the American University of Beirut (IRB ID: BIO-2018-0040). Study results will be made available to the public through publications in peer-reviewed journals and conference papers and/or presentations.


Asunto(s)
Cirugía Bariátrica , Hipertensión , Obesidad Mórbida , Adulto , Presión Sanguínea , Humanos , Estudios Longitudinales , Obesidad Mórbida/cirugía , Pérdida de Peso
7.
Biomed Chromatogr ; 35(7): e5098, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33606892

RESUMEN

A novel, simple and rapid UPLC-MS/MS method was developed and validated for determination of favipiravir (FAV) in human plasma. Lamivudine was used as an internal standard (IS). The Xevo TQD LC-MS/MS was operated under the multiple-reaction monitoring mode using electrospray ionization. Precipitation with acetonitrile was used in sample preparation as it gives relatively cleaner plasma samples. The prepared samples were chromatographed using an Acquity UPLC® HSS C18 (100 × 2.1 mm, 1.8 µm) column. The mobile phase was composed of ammonium formate and methanol in a gradient mode that was pumped at a flow rate of 0.35 ml/min. The developed method was validated as per the FDA guidelines and linearity was in the range of 0.25-16 µg/ml for FAV. The intra- and inter-day precision and accuracy results were within the acceptable limits. A run time of 4.5 min and a low quantification limit of FAV allowed the application of the developed method for the determination of FAV in a bioequivalence study in healthy human volunteers.


Asunto(s)
Amidas/sangre , Cromatografía Líquida de Alta Presión/métodos , Pirazinas/sangre , Espectrometría de Masas en Tándem/métodos , Adulto , Amidas/química , Amidas/farmacocinética , Femenino , Humanos , Límite de Detección , Masculino , Persona de Mediana Edad , Pirazinas/química , Pirazinas/farmacocinética , Reproducibilidad de los Resultados , Equivalencia Terapéutica , Adulto Joven
8.
Biomed Chromatogr ; 35(5): e5048, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33314205

RESUMEN

A robust and rapid UPLC-MS/MS method has been developed, optimized and validated for determination of amlodipine (AML), indapamide (IND) and perindopril (PRN) in human plasma. A positive electrospray ionization mode was used in a Xevo TQD LC-MS/MS instrument. A single sample preparation step using extraction technique was applied to extract the three analytes from plasma samples. There was no need to extract indapamide from blood samples in a further step. Extraction of the three drugs and internal standards was done using a solvent mixture composed of methyl tertiary butyl ether, dichloromethane and ethyl acetate. The prepared samples were analyzed using an Acquity UPLC HSS C18 (100 × 2.1 mm, 1.7 µm) column. Ammonium acetate and methanol, pumped at a flow rate of 0.3 ml/min, were used as a mobile phase. Method validation was done as per the US Food and Drug Administration guidelines. Linearity was achieved in the range of 0.2-15 ng/ml for AML, 0.5-50 ng/ml for IND and 0.5-120 ng/ml for PRN. Accuracy and precision were estimated and found to be within the acceptable ranges. The rapid chromatography permits analysis of many samples per batch, making the method suitable for clinical and pharmacokinetic investigations. The developed and validated method was applied to estimate AML, IND, and PRN in a fasting bioequivalence study in healthy human volunteers.


Asunto(s)
Amlodipino , Antihipertensivos , Cromatografía Líquida de Alta Presión/métodos , Indapamida , Perindopril , Espectrometría de Masas en Tándem/métodos , Adulto , Amlodipino/sangre , Amlodipino/farmacocinética , Antihipertensivos/sangre , Antihipertensivos/farmacocinética , Humanos , Indapamida/sangre , Indapamida/farmacocinética , Límite de Detección , Persona de Mediana Edad , Perindopril/sangre , Perindopril/farmacocinética , Manejo de Especímenes , Equivalencia Terapéutica
9.
Environ Pollut ; 272: 115967, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33176945

RESUMEN

In Lebanon, previous studies have indicated an onset of cardiovascular diseases 12 years earlier than in other parts of the world, suggesting the presence of additional risk factors specific to Lebanon. Measurements of airborne particles in Lebanon surpass the recommendations of the World Health Organization by over 150%. This study examined the association between obstructive coronary artery disease (CAD), assessed by a novel marker calculated from coronary catheterization, and markers of air pollution, specifically polycyclic aromatic hydrocarbons (PAHs), in a cohort of 258 patients seen at the American University of Beirut Medical Center since 2014. The concentrations of four types of hydroxylated polycyclic aromatic hydrocarbons (OHPAHs), 2-OHNAP, 2-OHFLU, 3-OHPHE, and 1-OHPYR, were measured in the urine samples of these patients using high performance liquid chromatography coupled with fluorescence detector. Results showed that the OHPAH concentrations were higher than what was reported in high-income countries and, most notably, the levels for non-smokers in this study were higher than those of smokers and some occupational workers in other countries. This implies that patients were exposed to high levels of PAHs, which originate from combustion sources. In particular, 1-OHPYR showed a significant association with presence of obstructive CAD, even after adjusting for covariates like age, sex, and diabetes. Smokers or not, this association has implications for public health and calls for urgent need to pass regulations to reduce the emissions of PAH sources, such as cars, diesel generators, and incinerators.


Asunto(s)
Enfermedad de la Arteria Coronaria , Hidrocarburos Policíclicos Aromáticos , Biomarcadores , Cromatografía Líquida de Alta Presión , Enfermedad de la Arteria Coronaria/epidemiología , Humanos , Líbano
10.
J Med Educ Curric Dev ; 7: 2382120520953106, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32923674

RESUMEN

OBJECTIVE: The American University of Beirut Faculty of Medicine follows the American model of medical education. In 2013-2014, a carefully designed new curriculum replaced the previous, largely traditional curriculum, and aimed to improve student wellbeing, upgrade the learning environment, enhance student empathy, and counter the negative influences of the hidden curriculum. This longitudinal study assessed the effectiveness of the new curriculum in those domains over a period of 7 years. METHODS: Three cohorts of medical students anonymously filled a paper-based survey at the end of years 1, 2, 3, and 4 of the 4-year curriculum. These included the Class of 2016, the last batch of students who followed the old curriculum, and 2 cohorts that followed the new curriculum (Class of 2017 and Class of 2019). The perceived learning environment was assessed by the Dundee Ready Education Environment Measurement survey; the student's empathy was assessed by the Jefferson Scale of Physician Empathy-Student version; and the hidden curriculum was examined using a locally developed survey. RESULTS: The scores on the learning environment survey were significantly higher among the cohorts following the new curriculum relative to those following the old curriculum. Similar significant results appeared when looking at each of the subscales for the learning environment. The students' empathy scores were also significantly higher in both cohorts of the new curriculum when compared with the old curriculum. Nevertheless, there was a significant decrease in empathy in both third and fourth years relative to second year. The new curriculum also improved aspects of the students' perceptions and responses to the hidden curriculum. CONCLUSION: In conclusion, a well-planned and well-researched curricular intervention, based on sound educational theories, practices, and standards can indeed transform the learning environment, as well as the attitudes, values, and experiences of medical students.

11.
Biomed Chromatogr ; 32(11): e4347, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30047564

RESUMEN

A novel and sensitive LC-MS/MS method was developed, optimized and validated for quantification of sofosbuvir (SOF) and velpatasvir (VEL) in human plasma using ledipasvir as an internal standard (IS). Sample preparation was done using acetonitrile for precipitation of plasma proteins. Chromatographic analysis was done on an Acquity UPLC BEH C18 column using 0.1% formic acid and acetonitrile as a mobile phase. The Xevo TQD LC-MS/MS system was run with electrospray ionization mode. The developed method was optimized and then validated according to the US Food and Drug Administration guidelines. Linearity was found to be in the range of 0.25-3500 ng/mL for SOF and 1-1000 ng/mL for VEL. A short run time of 1.5 min allows swift analysis of many plasma samples per day. The developed method was successfully utilized for estimating both SOF and VEL in the plasma of healthy human volunteers participated in a bioequivalence study.


Asunto(s)
Carbamatos/sangre , Cromatografía Líquida de Alta Presión/métodos , Compuestos Heterocíclicos de 4 o más Anillos/sangre , Sofosbuvir/sangre , Espectrometría de Masas en Tándem/métodos , Adulto , Carbamatos/farmacocinética , Femenino , Compuestos Heterocíclicos de 4 o más Anillos/farmacocinética , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Sofosbuvir/farmacocinética , Equivalencia Terapéutica , Adulto Joven
12.
Biomed Chromatogr ; 32(7): e4224, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29498757

RESUMEN

A robust, rapid and sensitive UPLC-MS/MS method has been developed, optimized and validated for the determination of amlodipine (AML) and atorvastatin (ATO) in human plasma using eplerenone as an internal standard (IS). Multiple-reaction monitoring in positive electrospray ionization mode was utilized in Xevo TQD LC-MS/MS. Double extraction was used in sample preparation using diethyl ether and ethyl acetate. The prepared samples were analyzed using an Acquity UPLC BEH C18 (50 × 2.1 mm, 1.7 µm) column. Ammonium formate and acetonitrile, pumped isocraticaly at a flow rate of 0.25 mL/min, were used as a mobile phase. Method validation was done as per the US Food and Drug Administration guidelines. Linearity was achieved in the range of 0.1-10 ng/mL for AML and 0.05-50 ng/mL for ATO. Intra-day and inter-day accuracy and precision were calculated and found to be within the acceptable range. A short run time, of <1.5 min, permits analysis of a large number of plasma samples per batch. The developed and validated method was applied to estimate AML and ATO in a bioequivalence study in healthy human volunteers.


Asunto(s)
Amlodipino/sangre , Atorvastatina/sangre , Cromatografía Líquida de Alta Presión/métodos , Espectrometría de Masas en Tándem/métodos , Adolescente , Adulto , Amlodipino/química , Amlodipino/farmacocinética , Atorvastatina/química , Atorvastatina/farmacocinética , Humanos , Modelos Lineales , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Equivalencia Terapéutica , Adulto Joven
13.
Clin Drug Investig ; 38(5): 439-448, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29417463

RESUMEN

BACKGROUND AND OBJECTIVES: The purpose of this study was to apply the reference-scaled average bioequivalence (RSABE) approach to evaluate the bioequivalence and to investigate the pharmacokinetic properties of two formulations of fixed dose combination (FDC) tablet of sofosbuvir (SOF) and ledipasvir (LED) (400/90 mg) in 36 healthy Egyptian volunteers. METHODS: The study was performed in single-dose, randomized-sequence, open-label, reference-replicated, 3-period crossover design (RTR, TRR, RRT), with a washout period of 2 weeks. A rapid and simple LC-MS/MS method was developed and validated for the simultaneous estimation of SOF and LED using eplerenone as an internal standard (IS). RESULTS: The results showed that the 90% confidence intervals (CIs) for natural log-transformed ratios of Cmax, AUClast and AUC∞ of SOF (89.95-115.31, 98.77-109.75 and 98.79-109.75) were within the RSABE acceptance limits. The 90% CIs for natural log-transformed ratios of Cmax and AUClast of LED (87.33-115.15 and 83.82-112.26) were within the FDA bioequivalence limits (80.00-125.00). In addition, the in vitro dissolution study was done and both formulations released > 85% of drug within 15 min in the proposed dissolution medium. CONCLUSIONS: In conclusion, bioequivalence between the two fixed-dose combination products was demonstrated for both active ingredients.


Asunto(s)
Bencimidazoles/administración & dosificación , Bencimidazoles/farmacocinética , Medicamentos Genéricos/administración & dosificación , Medicamentos Genéricos/farmacocinética , Fluorenos/administración & dosificación , Fluorenos/farmacocinética , Sofosbuvir/administración & dosificación , Sofosbuvir/farmacocinética , Adolescente , Adulto , Área Bajo la Curva , Cromatografía Liquida , Estudios Cruzados , Composición de Medicamentos , Quimioterapia Combinada , Egipto/epidemiología , Femenino , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Estándares de Referencia , Comprimidos , Espectrometría de Masas en Tándem , Equivalencia Terapéutica , Adulto Joven
14.
Cardiovasc Revasc Med ; 18(4): 265-273, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28314676

RESUMEN

BACKGROUND/PURPOSE: Diabetes portends an increased risk of adverse early and late outcomes in patients undergoing PCI. In this study, we aimed to investigate if the adverse effect of diabetes mellitus (DM) on early and late PCI outcomes is reduced with drug-eluting (DES) compared to bare-metal (BMS) stents. METHODS/MATERIALS: We reviewed the Mount Sinai Beth Israel Hospital first PCI experience for multivessel coronary artery disease (CAD, 1998-2009). Patients were excluded if they had single-vessel CAD, emergency, no stent, prior bypass graft or myocardial infarction <24h. Diabetes-effect was derived from 9-year all-cause mortality and re-intervention risk-adjusted hazard ratios [AHR (95% confidence intervals)] for DES (N=2679; 48% three-vessel; 39% DM) and BMS (N=2651; 40% three-vessel; 33% DM) and then stratified based on stent (DES/BMS) and vessel disease (two/three). RESULTS: Diabetes-effect on mortality was lower for DES (AHRDM/NoDM=1.41 [1.14-1.74]) versus BMS (AHRDM/NoDM=1.71 [1.50-2.01]), but this was predominantly driven by two-vessel patients. This diabetes effect was similar for first (DES1: AHRDM/NoDM=1.43 [1.14-1.79]) and second (DES2: AHRDM/NoDM=1.53 [0.77-3.07]) generation DES. Re-intervention comparisons were similarly increased by diabetes in all sub-cohorts. CONCLUSIONS: Our analysis of a large real-world PCI series indicates that diabetes is associated with worse 9-year mortality irrespective of stent type, albeit this is mitigated to varying degrees with DES, particularly in DES2 and in case of 2-vessel disease. A complementary stent-effect analysis confirmed DES-to-BMS and DES2-to-DES1 superiority in both diabetics and non-diabetics.


Asunto(s)
Enfermedad de la Arteria Coronaria/terapia , Diabetes Mellitus/epidemiología , Stents Liberadores de Fármacos , Intervención Coronaria Percutánea/instrumentación , Anciano , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/mortalidad , Bases de Datos Factuales , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/mortalidad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Ciudad de Nueva York/epidemiología , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , Modelos de Riesgos Proporcionales , Diseño de Prótesis , Retratamiento , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento
15.
Physiol Rep ; 4(11)2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27288061

RESUMEN

Blood pressure exhibits substantial short- and long-term variability (BPV). We assessed the hypothesis that the complexity of beat-to-beat BPV will be differentially altered in salt-sensitive hypertensive Dahl rats (SS) versus rats protected from salt-induced hypertension (SSBN13) maintained on high-salt versus low-salt diet. Beat-to-beat systolic and diastolic BP series from nine SS and six SSBN13 rats (http://www.physionet.org) were analyzed following 9 weeks on low salt and repeated after 2 weeks on high salt. BP complexity was quantified by detrended fluctuation analysis (DFA), short- and long-range scaling exponents (αS and αL), sample entropy (SampEn), and traditional standard deviation (SD) and coefficient of variation (CV(%)). Mean systolic and diastolic BP increased on high-salt diet (P < 0.01) particularly for SS rats. SD and CV(%) were similar across groups irrespective of diet. Salt-sensitive and -protected rats exhibited similar complexity indices on low-salt diet. On high salt, (1) SS rats showed increased scaling exponents or smoother, systolic (P = 0.007 [αL]) and diastolic (P = 0.008 [αL]) BP series; (2) salt-protected rats showed lower SampEn (less complex) systolic and diastolic BP (P = 0.046); and (3) compared to protected SSBN13 rats, SS showed higher αL for systolic (P = 0.01) and diastolic (P = 0.005) BP Hypertensive SS rats are more susceptible to high salt with a greater rise in mean BP and reduced complexity. Comparable mean pressures in sensitive and protective rats when on low-salt diet coupled with similar BPV dynamics suggest a protective role of low-salt intake in hypertensive rats. This effect likely reflects better coupling of biologic oscillators.


Asunto(s)
Presión Sanguínea/efectos de los fármacos , Dieta Hiposódica , Cloruro de Sodio Dietético/administración & dosificación , Animales , Determinación de la Presión Sanguínea , Entropía , Masculino , Dinámicas no Lineales , Ratas , Ratas Endogámicas Dahl
16.
Med Teach ; 38(10): 1017-1024, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27008548

RESUMEN

BACKGROUND: The Faculty of Medicine at the American University of Beirut implemented a new medical curriculum, which included 90 team-based learning (TBL) sessions in years 1 and 2 of medical school. METHODS: A validated team performance scale (TPS) and peer evaluation of communication skills, professionalism and personal development were collected at different time points during the two years. Grades on the individual and group readiness assurance tests and an evaluation form were collected after every TBL session. RESULTS: Students generally positively evaluated most TBL sessions as promoters of critical thinking and appreciated the self-learning experience, though they preferred and had better individual grades on those that entailed preparation of didactic lectures. There was a sustained and cumulative improvement in teamwork skills over time. Similar improvement was noted with peer evaluations of communication skills, professionalism, and personal development over time. CONCLUSIONS: This is the first report about such a longitudinal follow-up of medical students who were exposed to a large number of TBL sessions over two years. The results support the suggestion that TBL improves medical students' team dynamics and their perceived self-learning, problem solving and communication skills, as well as their professionalism and personal development.


Asunto(s)
Actitud , Educación de Pregrado en Medicina/métodos , Procesos de Grupo , Aprendizaje , Aprendizaje Basado en Problemas/métodos , Estudiantes de Medicina/psicología , Conducta Cooperativa , Curriculum , Evaluación Educacional , Femenino , Humanos , Líbano , Masculino , Modelos Educacionales , Grupo Paritario , Facultades de Medicina
18.
BMJ Open ; 4(7): e004880, 2014 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-24989618

RESUMEN

BACKGROUND: Pharmaceutical company representatives likely influence the prescribing habits and professional behaviour of physicians. OBJECTIVE: The objective of this study was to systematically review the effects of interventions targeting practising physicians' interactions with pharmaceutical companies. ELIGIBILITY CRITERIA: We included observational studies, non-randomised controlled trials (non-RCTs) and RCTs evaluating legislative, educational, policy or other interventions targeting the interactions between physicians and pharmaceutical companies. DATA SOURCES: The search strategy included an electronic search of MEDLINE and EMBASE. Two reviewers performed duplicate and independent study selection, data abstraction and assessment of risk of bias. APPRAISAL AND SYNTHESIS METHODS: We assessed the risk of bias in each included study. We summarised the findings narratively because the nature of the data did not allow a meta-analysis to be conducted. We assessed the quality of evidence by outcome using the GRADE methodology. RESULTS: Of 11 189 identified citations, one RCT and three observational studies met the eligibility criteria. All four studies specifically targeted one type of interaction with pharmaceutical companies, that is, interactions with drug representatives. The RCT provided moderate quality evidence of no effect of a 'collaborative approach' between the pharmaceutical industry and a health authority. The three observational studies provided low quality evidence suggesting a positive effect of policies aiming to reduce interaction between physicians and pharmaceutical companies (by restricting free samples, promotional material, and meetings with pharmaceutical company representatives) on prescription behaviour. LIMITATIONS: We identified too few studies to allow strong conclusions. CONCLUSIONS: Available evidence suggests a potential impact of policies aiming to reduce interaction between physicians and drug representatives on physicians' prescription behaviour. We found no evidence concerning interventions affecting other types of interaction with pharmaceutical companies.


Asunto(s)
Industria Farmacéutica , Relaciones Interprofesionales , Médicos , Políticas , Industria Farmacéutica/educación , Industria Farmacéutica/legislación & jurisprudencia
19.
J Pharm Biomed Anal ; 98: 1-8, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24863555

RESUMEN

A rapid, simple, sensitive and specific LC-MS/MS method has been developed and validated for the simultaneous estimation of amlodipine (AML), benazepril (BEN) and benazeprilat (BNT) using eplerenone and torsemide as internal standards (IS). The Xevo TQD LC-MS/MS was operated under the multiple-reaction monitoring mode using electrospray ionization. Sample preparation involves both extraction and precipitation techniques. The reconstituted samples were chromatographed on Acquity UPLC BEH C18 (50mm×2.1mm, 1.7µm) column by pumping 0.1% formic acid and acetonitrile in a gradient mode at a flow rate of 0.45ml/min. A detailed validation of the method was performed as per the FDA guidelines and the standard curves were found to be linear in the range of 0.1-5ng/ml for AML; 5-1200ng/ml for both BEN and BNT. The intra-day and inter-day precision and accuracy results were within the acceptable limits. A run time of 2.5min for each sample made it possible to analyze more than 300 human plasma samples per day. The developed assay method was successfully applied to a bioequivalence study in human volunteers.


Asunto(s)
Amlodipino/sangre , Benzazepinas/sangre , Plasma/química , Cromatografía Líquida de Alta Presión/métodos , Humanos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Espectrometría de Masa por Ionización de Electrospray/métodos , Espectrometría de Masas en Tándem/métodos , Equivalencia Terapéutica
20.
Cardiovasc Diagn Ther ; 3(3): 129-36, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24282761

RESUMEN

BACKGROUND: In deciding on optimal interventions for cardiovascular disease (CVD) prevention, more than one set of guidelines are available. HYPOTHESIS: The aim of the study was to assess the agreement between the European Society of Cardiology (ESC) 2011 Guidelines for CVD Prevention and the Canadian Cardiovascular Society (CCS) 2009 Guidelines in recommending lipid lowering interventions in a seemingly healthy cohort of Lebanese persons. METHODS: A nationally representative cohort of Lebanon was identified according to the World Health Organization (WHO) Steps Criteria. From this cohort, a group of 283 adult individuals not known to have chronic illnesses was selected. Using the algorithms present in each guideline, lipid lowering recommendations for each individual were determined. Agreement between the two guideline recommendations was determined using the Kappa test. RESULTS: As per ESC, 3.9% of the participants required immediate drug therapy, 15.5% should be considered for drug therapy, and 80.1% required lifestyle intervention. As per the CCS, however, 19.4% required drug therapy. The overall level of agreement between the ESC and CCS for recommending lipid lowering was moderate (Kappa 0.77), and better in males (Kappa 0.82). In contrast, 37.5% of females recommended drug therapy as per the CCS guidelines would not be per the ESC guidelines (Kappa 0.63). CONCLUSIONS: Significant discrepancies exist in recommendations for lipid-lowering therapy between CCS and ESC guidelines when applied to Lebanese individuals, particularly for women. Local healthcare authorities and the WHO should attend to this issue in order to unify treatment approaches and limit disparities in care.

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