Intestinal P-gp activity is reduced in postmenopausal women under breast cancer therapy.

Intestinal P-glycoprotein (P-gp) activity plays a crucial role in modulating the oral bioavailability of its substrates. Fexofenadine has commonly been used as a P-gp probe, although it is important to note the involvement of other drug transporters like, OATP1B1, OATP1B3, and OATP2B1. In vitro studies demonstrated an upregulation of P-gp protein in response to exposure to pregnancy-related hormones. The objective of this study was to investigate how intestinal P-gp activity is impacted by menopausal status. This study sampled fexofenadine plasma concentrations over 0-12 h after probe drug administration from two groups of patients with breast cancer: premenopausal (n = 20) and postmenopausal (n = 20). Fexofenadine plasma concentrations were quantified using liquid-chromatography tandem mass spectrometry. Area under the plasma concentration-time curve from zero to infinity (AUCinf ) was calculated through limited sampling strategies equation. Multiple linear regression was applied on AUCinf , maximum plasma concentration (Cmax ), and time to Cmax . Postmenopausal patients showed a significant increase in Cmax (geometric mean and 95% confidence interval [CI] 143.54, 110.95-176.13 vs. 223.54 ng/mL, 161.02-286.06 and in AUCinf 685.55, 534.98-878.50 vs. 933.54 ng·h/mL 735.45-1184.99) compared to premenopausal patients. The carriers of the ABCB1 3435 allele T displayed higher Cmax values of 166.59 (95% CI: 129.44-214.39) compared to the wild type at 147.47 ng/mL (95% CI: 111.91-194.34, p = 0.02). In postmenopausal individuals, the decrease in P-gp activity of ~40% may lead to an increased plasma exposure of orally administered P-gp substrates.

Efficacy of a 0.5% Propolis -0.9% Pomegranate Buccal Spray Treatment Compared with 2% Miconazole Gel for Denture Stomatitis Treatment in Elderly Patients: a Randomized Clinical Trial.

Statement of the Problem: Natural products have attracted interest as an alternative to synthetic medi-cations for the treatment of oral diseases due to their efficacy and safety. Propolis and pomegranate extracts have both demonstrated efficacy for the treatment of denture stomatitis. However, use of the two compounds together has not been tested for this purpose. Purpose: A comparison was made of the efficacy of a commercially available propolis-pomegranate buccal spray formulation for the treatment of denture stomatitis, compared with miconazole gel, based on stomatitis lesions and Candida spp. concentrations in mouth rinses. Materials and Method: This was an experimental study, characterized as an open-label, parallel two-armed, non-inferiority randomized clinical trial. Forty elderly adults aged < 60 years with denture stoma-titis were randomly allocated to two groups. The patients applied a buccal spray containing 0.5% propo-lis and 0.9% pomegranate extracts or 2% miconazole gel, a standard treatment recommended in Brazil, to the inner surface of their dentures three times a day for 14 days. They were examined at days 1, 7, 14 and stomatitis lesions were categorized according to Newton's score. Mouth rinses were made with saline solution at days 1 and 14 and then assessed for Candida spp. Results: Both treatments reduced the Newton's score, with clinical cure rates of 75 and 40% for the miconazole and propolis-pomegranate groups, respectively. The Candida concentrations in the mouth rinse decreased significantly only in the miconazole group. Conclusion: The propolis-pomegranate spray was less effective than the miconazole treatment. Howev-er, clinical improvement was also observed in patients treated with the propolis-pomegranate buccal spray.

Meningococcal disease epidemiology in Brazil (2005-2018) and impact of MenC vaccination.

BACKGROUND: Meningococcal disease (MD) presents a substantial public health problem in Brazil. Meningococcal C conjugate (MenC) vaccination was introduced into the routine infant immunization program in 2010, followed by adolescent vaccination in 2017. We evaluated changes in national and regional MD incidence and mortality between 2005 and 2018, serogroup distribution and vaccine coverage. METHODS: Data were obtained from national surveillance systems from 2005 to 2018. Age-stratified incidence and mortality rates were calculated and a descriptive time-series analysis was performed comparing rates in the pre-(2005-2009) and post-vaccination (2011-2018) periods; MD due to specific meningococcal serogroups were analyzed in the pre-(2007-2009) and post-vaccination (2011-2018) periods. RESULTS: From 2005 to 2018, 31,108 MD cases were reported with 6496 deaths; 35% of cases and deaths occurred in children < 5 years. Incidence and mortality rates declined steadily since 2012 in all age-strata, with significantly lower incidence and mortality in the post-vaccine introduction period in children aged < 1-year, 1-4 years, 5-9 years and 10-14 years. A significant decline in MenC disease in children < 5 years was observed following MenC vaccine introduction; infants < 1 year, from 3.30/100,000 (2007-2009) to 1.08/100,000 (2011-2018) and from 1.44/100,000 to 0.42/100,000 in 1-4-year-olds for these periods. Reductions in MenB disease was also observed. MenW remains an important cause of MD with 748 cases reported across 2005-2018. While initial infant vaccination coverage was high (>95% nationwide), this has since declined (to 83% in 2018); adolescent uptake was < 20% in 2017/18). Regional variations in outcomes and vaccine coverage were observed. CONCLUSION: A substantial decline in incidence and mortality rates due to MD was seen following MenC vaccine introduction in Brazil, especially among children < 5 years chiefly driven by reductions in MenC serogroup. While these benefits are considerable, the prevalence of MD due to other serogroups such as MenW and MenB remains a concern. A video summary linked to this article can be found on Figshare: https://doi.org/10.6084/m9.figshare.13379612.v1.

Effect of Lercanidipine on the Pharmacokinetics-Pharmacodynamics of Carvedilol Enantiomers in Patients With Chronic Kidney Disease.

This study evaluates the carvedilol-lercanidipine drug interaction, and the influence of chronic kidney disease (CKD) on both drugs. Patients with high blood pressure (8 with normal renal function [control] and 8 with CKD with estimated glomerular filtration rate categories of G3b to G5 [12-38 mL/min/1.73 m2 ]) were included and prescribed 3 different treatment regimens, a single oral dose of racemic carvedilol 25 mg (CAR), a single oral dose of racemic lercanidipine 20 mg (LER), and single oral doses of CAR plus LER. Blood samples were collected and variations in heart rate were assessed (using isometric exercise with handgrip) for up to 32 hours. Lercanidipine pharmacokinetics were not enantioselective, and were not affected by carvedilol and CKD. Carvedilol pharmacokinetics (data presented as median) were enantioselective with higher plasma exposure of (R)-(+)-carvedilol in both control (103.5 vs 46.0 ng ∙ h/mL) and CKD (190.6 vs 98.9 ng ∙ h/mL) groups. Lercanidipine increased the area under the plasma concentration-time curve of only (R)-(+)-carvedilol in the CKD group (190.6 vs 242.2 ng ∙ h/mL) but not in the control group (103.5 vs 98.7 ng ∙ h/mL). CKD increased plasma exposure (46.0 vs 98.9 ng ∙ h/mL) and effect-compartment exposure (5.5 vs 20.9 ng ∙ h/mL) to (S)-(-)-carvedilol, resulting in higher ß-adrenergic inhibition (10.0 vs 6.1 bpm). Therefore, carvedilol dose titration in CKD patients with estimated glomerular filtration rate categories of G3b to G5 should be initiated, with no more than half the dose used for patients with normal renal function.

Analyses of Budget Impact Considering the Use of the Picture Archiving and Communication System.

OBJECTIVE: To analyze the budget impact of using the picture archiving and communication system (PACS) in comparison to the screen/film system. METHODS: The budget impact analysis was conducted on the basis of registry data from the Clinics Hospital of the Faculty of Medicine, University of São Paulo, Ribeirão Preto, Brazil. The budget impacts were compared between the PACS, with high- and low-cost PACS architectures, and the screen/film system by considering reference and alternative scenarios over the course of 5 years. RESULTS: The budget impact associated with the use of PACS was lower than that associated with the use of the screen/film system in all the evaluated scenarios. The low-cost PACS architecture (mini-PACS) had an even lower budget impact, especially in the scenario in which a simulation of lower numbers of medical examinations was performed. CONCLUSIONS: The screen/film system had a high budget impact in all the scenarios evaluated, wherein its costs were higher than the available budget. In contrast, the PACS (high- and low-cost architectures) showed a budget impact that allowed for savings in resources, especially the mini-PACS. Therefore, we recommend the implementation and use of the PACS in health services with any volume of examinations performed.

Influence of experimental diabetes and insulin treatment on the enantioselective pharmacokinetics of mexiletine and its metabolites.

This study evaluates the influence of streptozotocin-induced diabetes on the kinetic disposition and metabolism of mexiletine (MEX) enantiomers in rats. Animals in the control (n = 6 for each blood collection time), diabetic (single intravenous dosage of 45 mg·(kg body mass)(-1) of streptozotocin), and insulin-treated groups (diabetic rats treated daily with 2 IU insulin) received by gavage a single dose of 10 mg·(kg body mass)(-1) racemic MEX. MEX enantiomers and the metabolites hydroxymethylmexiletine (HMM) and p-hydroxymexiletine PHM) were analyzed by LC-MS/MS. Statistical analysis was based on a serial sacrifice design, and parameter estimation was performed using a Bayesian modeling procedure. Area under the curve (AUC) for the (-)-(R) enantiomers of MEX, HMM, and PHM did not differ between the control and diabetic groups. However, AUC for (+)-(S)-MEX and (+)-(S)-HMM were lower in the diabetic than in the control group. Insulin treatment recovered glucose levels to normal and the (+)-(S)-MEX AUC and (+)-(S)-HMM AUC became similar to the AUCs observed in the nondiabetic animals.

Late referral for chronic kidney disease patients: nutritional point of view.

UNLABELLED: The prevalence of late referral of patients with chronic kidney disease (CKD) is high and has been associated with a worse CKD prognosis, however few studies have been conducted from a nutritional perspective. OBJECTIVE: Characterize the nutritional status of patients with CKD at first attendance in a nephrology service, with early (ER) and late referral (LR). METHODOLOGY: It was a cross-sectional study with patients older than 18 years referred to the Nephrology service of a University Hospital. The referral groups were classified according to estimated glomerular filtration rate (eGFR) as: LR (eGFR15 ml/min/1.73m2) based on the Kidney Disease Outcomes Quality Initiative. Nutritional evaluation included subjective global assessment (SGA), anthropometric, laboratory and bioelectrical impedance data. The SAS software was used for statistical analysis. RESULTS: Seventy-five patients were evaluated, 29% of them belonging to the LR group. This group showed a greater previous weight loss (-7.0 ± 3.5 versus -2.8 ± 7.0 Kg) and lower values for all anthropometric and body composition variables. In general, the laboratory results of the LR group also were worse. According to the SGA, all LR patients had some degree of malnutrition (50% with severe malnutrition against 28.8% in ER), showing significantly lower results for GFR (21.4 + 12.2 ml/ min/1.73 m2), albumin (3.9 + 0.3 g/dL), serum bicarbonate (22.8 + 5.1 mmol/L) and phase angle (5.3+ 0.6 θ). Renal function was positively correlated with percent adequacy of arm circumference (r=0,40; p<0,01) and albumin (r=0,45; p<0,01). CONCLUSION: The LR group showed a worse nutritional status showing that, for the nutritional point of view, the delayed referral brings substantial losses that can make difference in future treatment, thus demonstrating the importance of early nutritional monitoring for this population.

La prevalencia de la referencia tardía de los pacientes con enfermedad renal crónica (ERC) es alta y se ha asociado con un pronóstico peor ERC, sin embargo pocos estudios se han llevado a cabo desde una perspectiva nutricional. Objetivo: Caracterizar el estado nutricional de los pacientes con ERC con la primera cita en un servicio de nefrología, con temprana (ER) y la remisión tardía (LR). Metodología: Se realizó un estudio transversal con pacientes mayores de 18 años a que se refiere el servicio de Nefrología del Hospital Universitario. Los grupos de referencia se clasificaron de acuerdo a la tasa estimada de filtración glomerular (TFG) como: LR (TFG 15 ml / min / 1.73m2), basado en la Kidney Disease Outcomes Quality Initiative. Evaluación nutricional incluyó la evaluación subjetiva global (SGA), antropométricas, de laboratorio y los datos de impedancia bioeléctrica. El software de SAS ® se utilizó para el análisis estadístico. Resultados: Fueron evaluados setenta y cinco pacientes, el 29% de ellos pertenece al grupo LR. Este grupo mostró una pérdida mayor de peso anterior (-7,0 ± 3,5 frente a -2,8 ± 7,0 Kg) y los valores más bajos para todas las variables antropométricas y de composición corporal. En general, los resultados de laboratorio del grupo LR también eran peores. De acuerdo con el SGA, todos los pacientes tenían LR algún grado de desnutrición (50% con desnutrición severa contra 28,8% en ER), que muestra resultados significativamente más bajos de la TFG (21,4 + 12,2 ml / min / 1,73 m2), albúmina (3,9 + 0,3 g / dL), bicarbonato sérico (22,8 + 5,1 mmol / L) y ángulo de fase (5.3+ 0,6 ). La función renal se correlacionó positivamente con el porcentaje de adecuación de la circunferencia del brazo (r=0,40; p.