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2.
Pharm Res ; 36(11): 155, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31485804

RESUMO

PURPOSE: The purpose of this study was to determine the impact of food on gastric pH and the ability of over the counter betaine hydrochloride (BHCl) acid to reacidify gastric pH after food-induced elevations in gastric pH. METHODS: This open-label cross over clinical study (NCT02758015) included 9 subjects who were randomly assigned to one of 16 possible, 4-period cross-over sequences to determine the impact and relationship of food and gastric pH with acid supplementation. Subjects were administered various doses (1500 mg, 3000 mg and 4500 mg) of betaine hydrochloride (BHCl) to determine the ability of acid supplementation to reacidify gastric pH after the elevation of gastric pH caused by the ingestion of food. RESULTS: Following the administration of food and the resulting elevation in gastric pH, time to return to baseline gastric pH levels without acid supplementation was 49.7 ± 14.0 min. Administering 4500 mg of BHCl acid in capsules was able to reacidify gastric pH levels back to baseline following the administration of food in approximately 17.3 ± 5.9 min. AUCpH of each treatment were similar and not statistically different. Mean max pH following the administration of food was 3.20 ± 0.55. CONCLUSION: The ability of food to elevate and maintain gastric pH levels in the presence of acid supplementation was made evident throughout the study. A 4500 mg dose of BHCl was required to reacidify gastric pH after the administration of food. This study details the difficulty faced by clinicians in dosing a poorly soluble, weakly basic drug to patients receiving acid reducing agents where administration with food is recommended to avoid gastric side effects. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02758015.


Assuntos
Betaína/uso terapêutico , Alimentos , Absorção Gástrica , Ácido Gástrico/metabolismo , Fármacos Gastrointestinais/uso terapêutico , Preparações Farmacêuticas/metabolismo , Administração Oral , Adolescente , Adulto , Estudos Cross-Over , Feminino , Interações Alimento-Droga , Determinação da Acidez Gástrica , Humanos , Concentração de Íons de Hidrogênio , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
3.
N Engl J Med ; 381(13): 1227-1239, 2019 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-31553835

RESUMO

BACKGROUND: Morbidity from asthma is disproportionately higher among black patients than among white patients, and black patients constitute the minority of participants in trials informing treatment. Data indicate that patients with inadequately controlled asthma benefit more from addition of a long-acting beta-agonist (LABA) than from increased glucocorticoids; however, these data may not be informative for treatment in black patients. METHODS: We conducted two prospective, randomized, double-blind trials: one involving children and the other involving adolescents and adults. In both trials, the patients had at least one grandparent who identified as black and had asthma that was inadequately controlled with low-dose inhaled glucocorticoids. We compared combinations of therapy, which included the addition of a LABA (salmeterol) to an inhaled glucocorticoid (fluticasone propionate), a step-up to double to quintuple the dose of fluticasone, or both. The treatments were compared with the use of a composite measure that evaluated asthma exacerbations, asthma-control days, and lung function; data were stratified according to genotypic African ancestry. RESULTS: When quintupling the dose of fluticasone (to 250 µg twice a day) was compared with adding salmeterol (50 µg twice a day) and doubling the fluticasone (to 100 µg twice a day), a superior response occurred in 46% of the children with quintupling the fluticasone and in 46% of the children with doubling the fluticasone and adding salmeterol (P = 0.99). In contrast, more adolescents and adults had a superior response to added salmeterol than to an increase in fluticasone (salmeterol-low-dose fluticasone vs. medium-dose fluticasone, 49% vs. 28% [P = 0.003]; salmeterol-medium-dose fluticasone vs. high-dose fluticasone, 49% vs. 31% [P = 0.02]). Neither the degree of African ancestry nor baseline biomarkers predicted a superior response to specific treatments. The increased dose of inhaled glucocorticoids was associated with a decrease in the ratio of urinary cortisol to creatinine in children younger than 8 years of age. CONCLUSIONS: In contrast to black adolescents and adults, almost half the black children with poorly controlled asthma had a superior response to an increase in the dose of an inhaled glucocorticoid and almost half had a superior response to the addition of a LABA. (Funded by the National Heart, Lung, and Blood Institute; BARD ClinicalTrials.gov number, NCT01967173.).


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Afro-Americanos , Asma/tratamento farmacológico , Broncodilatadores/administração & dosagem , Fluticasona/administração & dosagem , Glucocorticoides/administração & dosagem , Xinafoato de Salmeterol/administração & dosagem , Administração por Inalação , Adolescente , Adulto , Criança , Pré-Escolar , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Humanos , Masculino , Estudos Prospectivos
4.
J Biol Regul Homeost Agents ; 33(3 Suppl. 1): 83-88, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31538453

RESUMO

The aim of this study was to evaluate the adjunctive benefit offers by the administration of a chlorhexidine based local drug deliver (Chlo-SITE) into periodontal socket after a full mouth disinfection session. The study design was a randomized, crossover, clinical trial conducted on 60 non-smokers subjects with chronic periodontitis. Each volunteer was subjected to a one-stage full mouth disinfection session and, immediately after that, test product (Chlo-SITE) was inserted in 1 pocket in 2 quadrant. The 1° and 4° quadrant were used for the study with the application of antiseptic (Test); the 2° and 3° as a control. Periodontal probe (PD), bleeding on probing (BOP) and plaque index (PI) was collected at baseline (T0), after 7 days (T1), after 4 weeks (T2). The results of this study suggest that the application of xanthan-based chlorhexidine gel (Xan-CHX) offers a great benefit in improving of the indices in chronic periodontitis.


Assuntos
Anti-Infecciosos Locais/uso terapêutico , Clorexidina/uso terapêutico , Bolsa Periodontal/tratamento farmacológico , Periodontite/tratamento farmacológico , Estudos Cross-Over , Géis , Humanos , Índice Periodontal
5.
Braz Oral Res ; 33: e078, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31432928

RESUMO

The aim of this study was to assess, correlate, and compare users' perceptions and preference related to maxillary removable retainers. Volunteers were recruited to use four retainer types: conventional wrap-around (CWA), wrap-around with an anterior opening (OWA), "U" wrap-around (UWA), and clear thermoplastic retainer (CT). The main outcomes were the volunteers' perceptions, evaluated with a 100-mm visual analogue scale, and their preferred retainer. The retainers were used for 21 days each (washout intervals of 7 days). Nineteen volunteers (27 ± 4.53 years) were randomly divided into four groups that used the four retainers, but with a different sequence. Perceptions were evaluated immediately after the use of each retainer and the preference at the end of the research. Repeated measures ANOVA and Friedman tests with post-hoc Tukey's test (intergroup comparisons), and Pearson and Spearman analyses (correlations between perceptions) were applied. The WA retainers did not significantly differ among themselves. The CT was rated significantly worse in speech (p ≤ 0.001), discomfort (p < 0.001), and occlusal interference (p < 0.001), and did not significantly differ from the others in esthetics. Users preferred significant more the WA retainers in comparison with the CT retainers. The occlusal interference caused by the CT was positively correlated to other perceptions, such as changes in speech and discomfort. WA retainers presented similar preference and perceptions, but were significantly better than the CT. The CT occlusal coverage appeared to be the primary cause of its rejection.


Assuntos
Desenho de Aparelho Ortodôntico/estatística & dados numéricos , Contenções Ortodônticas/normas , Preferência do Paciente/estatística & dados numéricos , Adulto , Análise de Variância , Estudos Cross-Over , Feminino , Humanos , Masculino , Maxila , Valores de Referência , Estatísticas não Paramétricas , Resultado do Tratamento , Escala Visual Analógica , Adulto Jovem
7.
Arch Endocrinol Metab ; 63(4): 376-384, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31365624

RESUMO

OBJECTIVE: To test the influence of oral fructose and glucose dose-response solutions in blood glucose (BG), glucagon, triglycerides, uricaemia, and malondialdehyde in postprandial states in type 1 diabetes mellitus (T1DM) patients. SUBJECTS AND METHODS: The study had a simple-blind, randomized, two-way crossover design in which T1DM patients were selected to receive fructose and glucose solutions (75g of sugars dissolved in 200 mL of mineral-water) in two separate study days, with 2-7 weeks washout period. In each day, blood samples were drawn after 8h fasting and at 180 min postprandial to obtain glucose, glucagon, triglycerides, uric acid, lactate, and malondialdehyde levels. RESULTS: Sixteen T1DM patients (seven men) were evaluated, with a mean age of 25.19 ± 8.8 years, a mean duration of disease of 14.88 ± 4.73 years, and glycated hemoglobin of 8.13 ± 1.84%. Fructose resulted in lower postprandial BG levels than glucose (4.4 ± 5.5 mmol/L; and 12.9 ± 4.1 mmol/L, respectively; p < 0.01). Uric acid levels increased after fructose (26.1 ± 49.9 µmol/L; p < 0.01) and reduced after glucose (-13.6 ± 9.5 µmol/L; p < 0.01). The malondialdehyde increased after fructose (1.4 ± 1.6 µmol/L; p < 0.01) and did not change after glucose solution (-0.2 ± 1.6 µmol/L; p = 0.40). Other variables did not change. CONCLUSIONS: Fructose and glucose had similar sweetness, flavor and aftertaste characteristics and did not change triglycerides, lactate or glucagon levels. Although fructose resulted in lower postprandial BG than glucose, it increased uric acid and malondialdehyde levels in T1DM patients. Therefore it should be used with caution. ClinicalTrials.gov registration: NCT01713023.


Assuntos
Diabetes Mellitus Tipo 1/metabolismo , Frutose/metabolismo , Glucose/metabolismo , Período Pós-Prandial/efeitos dos fármacos , Edulcorantes/metabolismo , Adolescente , Adulto , Glicemia/análise , Glicemia/efeitos dos fármacos , Estudos Cross-Over , Relação Dose-Resposta a Droga , Tolerância a Medicamentos , Feminino , Frutose/farmacologia , Glucose/farmacologia , Humanos , Masculino , Malondialdeído/sangue , Pessoa de Meia-Idade , Projetos Piloto , Método Simples-Cego , Soluções/farmacologia , Edulcorantes/farmacologia , Paladar/efeitos dos fármacos , Triglicerídeos/sangue , Ácido Úrico/sangue , Adulto Jovem
8.
Int J Sport Nutr Exerc Metab ; 29(5): 461-465, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31444314

RESUMO

The urinary excretion of hydroxyproline (Hyp), abundant in collagen protein, may serve as a biomarker of habitual collagen intake, assisting with investigations of current interest in the role of dietary collagen intake in supporting the synthesis of collagenous body tissues. This study investigated the time course of urinary Hyp excretion in "free-living," healthy, active males following the ingestion of a standardized bolus (20 g) of collagenous (gelatin and a hydrolyzed collagen powder) and dairy (calcium caseinate and hydrolyzed casein) proteins. The excretion of Hyp was assessed over a 24-hr period, separated into three collection periods: 0-6, 6-12, and 12-24 hr. Hyp was elevated for 0-6 hr after the consumption of collagen-containing supplements (gelatin 31.3 ± 8.8 mmol/mol and hydrolyzed collagen 33.7 ± 22.0 mmol/mol vs. baseline: gelatin 2.4 ± 1.7 mmol/mol and hydrolyzed collagen 2.8 ± 1.5 mmol/mol; p < .05), but not for the dairy protein supplements (calcium caseinate 3.4 ± 1.7 mmol/mol and hydrolyzed casein 4.0 ± 3.7 mmol/mol; p > .05). Therefore, urinary Hyp reflects an acute intake of collagenous protein, but is not suitable as a biomarker for quantifying habitual collagen intake, provided through regular dietary practices in "free-living," healthy, active males.


Assuntos
Colágeno/administração & dosagem , Hidroxiprolina/urina , Fenômenos Fisiológicos da Nutrição Esportiva , Adulto , Biomarcadores/urina , Caseínas , Estudos Cross-Over , Suplementos Nutricionais , Ingestão de Alimentos , Humanos , Masculino
9.
J Int Soc Sports Nutr ; 16(1): 31, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31366352

RESUMO

BACKGROUND: Cashew apple juice (CAJ) was shown to improve immunological mechanisms by regulating a balance between reactive oxygen species and antioxidant concentrations. However, no study exploring the effects of the CAJ and training status on the immune system and oxidative stress induced by exercise. Therefore, we investigated the effects of CAJ supplementation primarily on leukocyte counts and secondary on oxidative stress and cortisol changes after high-intensity exercise in trained and untrained men. METHODS: Ten moderately (endurance) trained (Age = 21.5 ± 0.97 yr., VO2max = 45.6 ± 4.12 mL/kgBM/min) and ten sedentary men (Age = 20.4 ± 2.72 yr., VO2peak = 32.2 ± 7.26 mL/kgBM/min) were randomized to ingest either daily CAJ or a placebo at 3.5 mL/kgBM/day for 4 weeks, with a four-week washout period. Before and after each period, they performed 20-min, high-intensity cycling (85% VO2max), with blood samples collected immediately preceding and the following exercise. Samples were analyzed to determine leukocyte counts, malondialdehyde, 8-isoprostane, and cortisol concentrations. A repeated measures analysis of variance was used to examine the effects of supplement and training status over time with an alpha level of 0.05. RESULTS: There was no interaction between supplement and training status on those variables before and after exercise. However, CAJ raised resting neutrophil counts and exercise-induced leukocyte counts in the trained group (all p < 0.05). Besides, CAJ significantly reduced plasma malondialdehyde concentrations at rest and after exercise and reduced the post-exercise plasma 8-isoprostane concentration in both groups of subjects (p < 0.05). Moreover, CAJ reduced plasma cortisol after exercise in the untrained subjects. CONCLUSIONS: We suggest that 4-week CAJ supplementation can enhance exercise-induced leukocyte and resting neutrophil counts in trained men. The possible mechanism is a reduction in oxidative stress. However, the supplementation did not change the immune responses of untrained men, but it did reduce stress hormone concentrations. TRIAL REGISTRATION NUMBER: TCTR20181127002 Registered 26 November 2018 "retrospectively registered".


Assuntos
Suplementos Nutricionais , Exercício , Sucos de Frutas e Vegetais , Contagem de Leucócitos , Estresse Oxidativo , Anacardium , Estudos Cross-Over , Dinoprosta/análogos & derivados , Dinoprosta/sangue , Método Duplo-Cego , Humanos , Hidrocortisona/sangue , Masculino , Malondialdeído/sangue , Malus , Neutrófilos/citologia , Espécies Reativas de Oxigênio/metabolismo , Fenômenos Fisiológicos da Nutrição Esportiva , Adulto Jovem
10.
J Int Soc Sports Nutr ; 16(1): 32, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31370896

RESUMO

BACKGROUND: The efficacy of sodium citrate supplementation (SC) in exercise performance is unclear. Therefore, the aim of this study was to investigate the effect of SC on skilled tennis performance. METHODS: Ten Brazilian nationally-ranked young male tennis players (age: 17 ± 1 yrs.; stature: 176.7 ± 5.2 cm; body mass: 68.4 ± 7.9 kg) participated in this crossover, placebo-controlled, double-blind study. Upon arrival, at baseline, in both experimental sessions blood was collected, then subjects ingested either sodium citrate (SC - 0.5 g.kg-1BM in capsules of 500 mg) or a placebo (PLA). Two hours later, pre-match blood was collected then skills tests (skill tennis performance test - STPT, repeated-sprint ability shuttle test - RSA) were performed followed by a 1-h simulated match. Immediately following the match, blood was again collected, and STPT, and RSA were administered. RESULTS: All metabolic parameters (i.e. base excess, pH, bicarbonate, and blood lactate) increased (p < 0.001) from baseline to pre-match and post-match in SC condition. Each metabolic parameter was greater (p < 0.001) in SC compared to PLA condition at both pre- and post-match. The SC condition elicited a greater (p < 0.01) shot consistency at post-match in the STPT vs. PLA condition (SC: 58.5 ± 14.8% vs. PLA: 40.4 ± 10.4%). A greater (p < 0.001) amount of games won was observed in the simulated match for SC condition vs. PLA condition (SC: 8.0 ± 1.6 vs. PLA: 6.0 ± 1.7). Additionally, the games won during the simulated match in SC condition was positively correlated with percentage shot consistency (r = 0.67, p < 0.001). CONCLUSIONS: The current findings suggest that SC supplementation is an effective ergogenic aid to enhance skilled tennis performance.


Assuntos
Desempenho Atlético , Substâncias para Melhoria do Desempenho/administração & dosagem , Citrato de Sódio/administração & dosagem , Tênis , Adolescente , Bicarbonatos/sangue , Estudos Cross-Over , Método Duplo-Cego , Teste de Esforço , Humanos , Ácido Láctico/sangue , Masculino , Fenômenos Fisiológicos da Nutrição Esportiva
11.
Int J Clin Pharmacol Ther ; 57(10): 506-519, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31397274

RESUMO

OBJECTIVE: Mycophenolate mofetil (MMF) is widely used as an immunosuppressant for the prophylaxis of acute organ rejection in recipients of solid organ transplants. MATERIALS AND METHODS: We have compared, in healthy subjects, the pharmacokinetics of mycophenolic acid when MMF was administered in the form of the innovator product CellCept (F. Hoffmann-La Roche Ltd.) or one of three commercially available generics, Renodapt (Biocon Ltd.), Mycept (Panacea Biotec), or Cellmune (Cipla Ltd.). The study was powered to detect a 20% difference in mean formulation performance measures, but not to formally evaluate bioequivalence. Geometric mean ratios of maximum concentrations (Cmax) and areas under plasma concentration-time curves were calculated. RESULTS: Comparing generics against each other, the differences in point estimates of the geometric mean ratios of Cmax of two of the comparisons were either borderline within (Renodapt/Cellmune) or clearly outside (Mycept/Cellmune) a region of 80 - 125% around the reference mean, indicating that bioequivalence between these generics may be difficult to show. CONCLUSION: Physicians in the field of transplantation should be aware of the potential risk of altering the therapeutic outcome when switching from one preparation of MMF to another. ClinicalTrials.gov identifier: NCT02981290.


Assuntos
Medicamentos Genéricos/farmacocinética , Imunossupressores/farmacocinética , Ácido Micofenólico/farmacocinética , Equivalência Terapêutica , Estudos Cross-Over , Rejeição de Enxerto , Humanos
12.
J Int Soc Sports Nutr ; 16(1): 34, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31409363

RESUMO

BACKGROUND: We previously reported that consuming a food bar (FB) containing whey protein and the plant fiber isomalto-oligosaccharides [IMO] had a lower glycemic (GI) but similar insulinemic response as a high GI carbohydrate. Therefore, we hypothesized that ingestion of this FB before, during, and following intense exercise would better maintain glucose homeostasis and performance while hastening recovery in comparison to the common practice of ingesting carbohydrate alone. METHODS: Twelve resistance-trained males participated in an open label, randomized, counterbalanced, crossover trial with a 7-d washout period. Participants consumed a carbohydrate matched dextrose comparitor (CHO) or a FB containing 20 g of whey, 25 g of IMO, and 7 g of fat 30-min before, mid-way, and following intense exercise. Participants performed 11 resistance-exercises (3 sets of 10 repetitions at 70% of 1RM) followed by agility and sprint conditioning drills for time. Participants donated blood to assess catabolic and inflammatory markers, performed isokinetic strength tests, and rated perceptions of muscle soreness, hypoglycemia before, and following exercise and after 48 h of recovery. Data were analyzed using general linear models (GLM) for repeated measures and mean changes from baseline with 95% confidence intervals (CI) with a one-way analysis of variance. Data are reported as mean change from baseline with 95% CI. RESULTS: GLM analysis demonstrated that blood glucose was significantly higher 30-min post-ingestion for CHO (3.1 [2.0, 4.3 mmol/L,] and FB (0.8 [0.2, 1.5, mmol/L, p = 0.001) while the post-exercise ratio of insulin to glucose was greater with FB (CHO 0.04 [0.00, 0.08], FB 0.11 [0.07, 0.15], p = 0.013, η2 = 0.25). GLM analysis revealed no significant interaction effects between treatments in lifting volume of each resistance-exercise or total lifting volume. However, analysis of mean changes from baseline with 95% CI's revealed that leg press lifting volume (CHO -130.79 [- 235.02, - 26.55]; FB -7.94 [- 112.17, 96.30] kg, p = 0.09, η2 = 0.12) and total lifting volume (CHO -198.26 [- 320.1, - 76.4], FB -81.7 [- 203.6, 40.1] kg, p = 0.175, η2 = 0.08) from set 1 to 3 was significantly reduced for CHO, but not for the FB. No significant interaction effects were observed in ratings of muscle soreness. However, mean change analysis revealed that ratings of soreness of the distal vastus medialis significantly increased from baseline with CHO while being unchanged with FB (CHO 1.88 [0.60, 3.17]; FB 0.29 [- 0.99, 1.57] cm, p = 0.083, η2 = 0.13). No significant GLM interaction or mean change analysis effects were seen between treatments in sprint performance, isokinetic strength, markers of catabolism, stress and sex hormones, or inflammatory markers. CONCLUSION: Pilot study results provide some evidence that ingestion of this FB can positively affect glucose homeostasis, help maintain workout performance, and lessen perceptions of muscle soreness. TRIAL REGISTRATION: clinicaltrials.gov, # NCT03704337 . Retrospectively registered 12, July 2018.


Assuntos
Carboidratos da Dieta/administração & dosagem , Suplementos Nutricionais , Treinamento de Resistência , Proteínas do Soro do Leite/administração & dosagem , Glicemia , Estudos Cross-Over , Ingestão de Alimentos , Teste de Esforço , Humanos , Insulina/sangue , Contração Isométrica , Masculino , Mialgia , Oligossacarídeos/administração & dosagem , Projetos Piloto , Fenômenos Fisiológicos da Nutrição Esportiva , Adulto Jovem
13.
Int J Clin Pharmacol Ther ; 57(9): 478-482, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31272528

RESUMO

AIM: To compare the bioequivalence of two 10-mg memantine tablet formulations. MATERIALS AND METHODS: 19 subjects were included in this single-dose, open-label, randomized, two-way crossover study following an overnight fast. A 5-week washout period was applied. Blood samples were collected up to 72 hours following drug administrations. Plasma memantine concentrations were determined by LC-MS/MS. The pharmacokinetic parameters AUC0-72h and Cmax were calculated and used for bioequivalence evaluation after log-transformation. RESULTS: The point estimates and 90% confidence intervals for AUC0-72h and CCmax for memantine were 100.72% (97.43 - 104.13%) and 101.46% (97.15 - 105.96%), respectively. CONCLUSION: These results indicated that the two formulations of memantine were bioequivalent; therefore, they may be prescribed interchangeably.


Assuntos
Memantina/farmacologia , Área Sob a Curva , Cromatografia Líquida , Estudos Cross-Over , Humanos , Indonésia , Comprimidos , Espectrometria de Massas em Tandem , Equivalência Terapêutica
14.
DNA Cell Biol ; 38(8): 814-823, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31314552

RESUMO

Lung cancer is known to cause high mortality and morbidity. The study aimed to explore the association between rs3733845 and rs3733846 polymorphisms in the promoter region of miR-143/145 and the risk of lung cancer among 575 nonsmoking cases and 575 cancer-free controls in a Chinese female population. We genotyped two single nucleotide polymorphisms (SNPs) in the promoter region of miR-143/145 in 575 cases and 575 controls using TaqMan allelic discrimination method. Logistic regression analysis was conducted to assess the association between polymorphisms in the promoter of miR-143/miR-145 and risk of lung cancer females. Crossover analysis was used to explore the interaction between the two SNPs and environmental risk factors (cooking oil fume exposure and passive smoking exposure). The results showed that both rs3733845 and rs3733846 polymorphisms were associated with an increased lung adenocarcinoma risk in dominant model (adjusted odds ratio [OR] = 1.329, 95% confidence intervals [CIs] = 1.026-1.723, p = 0.031 and adjusted OR = 1.450, 95% CI = 1.112-1.890, p = 0.006, respectively). The results of crossover analysis revealed that rs3733845 and rs3733846 risk genotypes along with cooking oil exposure increased lung cancer risk by 1.862-fold and 2.260-fold, respectively (adjusted OR = 1.862, 95% CI = 1.105-3.138, p = 0.020 for rs3733845; adjusted OR = 2.260, 95% CI = 1.354-3.769, p = 0.002 for rs3733846). There was positive multiplicative interaction between the two SNPs and cooking oil fume exposure (adjusted OR = 1.362, 95% CI = 1.078-1.719, p = 0.009 for oil × rs3733845; adjusted OR = 1.399, 95% CI = 1.122-1.745, p = 0.003 for oil × rs3733846). In nonsmoking females, rs3733845 and rs3733846 polymorphisms might be associated with lung adenocarcinoma risk. Moreover, the interactions between the two SNPs and cooking oil fume exposure were statistically significant on a multiplicative scale rather than an addictive scale.


Assuntos
Neoplasias Pulmonares/genética , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Idoso , Estudos de Casos e Controles , Culinária , Estudos Cross-Over , Feminino , Interação Gene-Ambiente , Predisposição Genética para Doença , Humanos , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Fumar
15.
JAMA ; 322(3): 216-228, 2019 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-31310297

RESUMO

Importance: The effects of intensive care unit (ICU) visiting hours remain uncertain. Objective: To determine whether a flexible family visitation policy in the ICU reduces the incidence of delirium. Design, Setting and Participants: Cluster-crossover randomized clinical trial involving patients, family members, and clinicians from 36 adult ICUs with restricted visiting hours (<4.5 hours per day) in Brazil. Participants were recruited from April 2017 to June 2018, with follow-up until July 2018. Interventions: Flexible visitation (up to 12 hours per day) supported by family education (n = 837 patients, 652 family members, and 435 clinicians) or usual restricted visitation (median, 1.5 hours per day; n = 848 patients, 643 family members, and 391 clinicians). Nineteen ICUs started with flexible visitation, and 17 started with restricted visitation. Main Outcomes and Measures: Primary outcome was incidence of delirium during ICU stay, assessed using the CAM-ICU. Secondary outcomes included ICU-acquired infections for patients; symptoms of anxiety and depression assessed using the HADS (range, 0 [best] to 21 [worst]) for family members; and burnout for ICU staff (Maslach Burnout Inventory). Results: Among 1685 patients, 1295 family members, and 826 clinicians enrolled, 1685 patients (100%) (mean age, 58.5 years; 47.2% women), 1060 family members (81.8%) (mean age, 45.2 years; 70.3% women), and 737 clinicians (89.2%) (mean age, 35.5 years; 72.9% women) completed the trial. The mean daily duration of visits was significantly higher with flexible visitation (4.8 vs 1.4 hours; adjusted difference, 3.4 hours [95% CI, 2.8 to 3.9]; P < .001). The incidence of delirium during ICU stay was not significantly different between flexible and restricted visitation (18.9% vs 20.1%; adjusted difference, -1.7% [95% CI, -6.1% to 2.7%]; P = .44). Among 9 prespecified secondary outcomes, 6 did not differ significantly between flexible and restricted visitation, including ICU-acquired infections (3.7% vs 4.5%; adjusted difference, -0.8% [95% CI, -2.1% to 1.0%]; P = .38) and staff burnout (22.0% vs 24.8%; adjusted difference, -3.8% [95% CI, -4.8% to 12.5%]; P = .36). For family members, median anxiety (6.0 vs 7.0; adjusted difference, -1.6 [95% CI, -2.3 to -0.9]; P < .001) and depression scores (4.0 vs 5.0; adjusted difference, -1.2 [95% CI, -2.0 to -0.4]; P = .003) were significantly better with flexible visitation. Conclusions and Relevance: Among patients in the ICU, a flexible family visitation policy, vs standard restricted visiting hours, did not significantly reduce the incidence of delirium. Trial Registration: ClinicalTrials.gov Identifier: NCT02932358.


Assuntos
Delírio/prevenção & controle , Família/psicologia , Unidades de Terapia Intensiva/organização & administração , Visitas a Pacientes , Ansiedade , Brasil , Esgotamento Profissional , Cuidados Críticos/psicologia , Estudos Cross-Over , Depressão , Feminino , Educação em Saúde , Hospitalização , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
16.
Anticancer Res ; 39(7): 3937-3944, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262924

RESUMO

BACKGROUND: The study aim was to evaluate the efficacy of wrapping oblate for prevention of everolimus-associated stomatitis in metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: Patients with mRCC prescribed everolimus after failure of vascular endothelial growth factor-tyrosine kinase inhibitor were enrolled. Patients were consecutively assigned to take everolimus covered with or without oblate. The primary end-points were the incidence of and time to grade 2 or more stomatitis. Additionally, we assessed whether grade 2 or more stomatitis that occurred in the non-oblate group could be prevented with crossover application of oblate. RESULTS: This study included 79 patients [oblate group: 42(53%); non-oblate group: 37(47%)]. Thirty (38%) patients developed grade 2 or more stomatitis [incidence: oblate group, 31% (13/42); non-oblate group, 46% (17/37), p=0.245; median time to grade 2 or more stomatitis: oblate group, not reached; non-oblate group, 6.0 months, p=0.251]. Among 10 patients who developed grade 2 or more stomatitis in the non-oblate group and received oblate-covered everolimus, nine (90%) showed complete recovery or improved to grade 1, which persisted until discontinuation of everolimus. CONCLUSION: Oblate-covered everolimus improved the incidence of and time to grade 2 or more stomatitis, although it was not statistically significantly different compared to the non-oblate group. Oblate wrapping prevented recurrence of grade 2 or more stomatitis in patients who took uncovered everolimus and developed significant stomatitis.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma de Células Renais/tratamento farmacológico , Everolimo/administração & dosagem , Imunossupressores/administração & dosagem , Neoplasias Renais/tratamento farmacológico , Estomatite/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Carcinoma de Células Renais/patologia , Estudos Cross-Over , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/efeitos adversos , Everolimo/efeitos adversos , Feminino , Humanos , Imunossupressores/efeitos adversos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Estomatite/induzido quimicamente
17.
Int J Clin Pharmacol Ther ; 57(10): 520-530, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31262398

RESUMO

OBJECTIVE: To characterize the pharmacokinetics of trazodone hydrochloride (HCl) sustained-release tablets (TSR) and trazodone immediate-release formulation (TIR) and investigate the effects of food on the pharmacokinetics of the drug in healthy subjects. MATERIALS AND METHODS: Three open-label, randomized crossover trials of single-dose, multiple-dose, and food-drug interaction testing were conducted. A validated high-performance liquid chromatography-fluorescence method was used to measure the plasma concentration of trazodone, and a non-compartment model was used to obtain the pharmacokinetic parameters. AUC and Cmax dose proportionality were analyzed using a power model. RESULTS: TSR lacked dose proportionality over a dose range of 25 - 150 mg. In the food-drug interaction study, no significant changes in the pharmacokinetic parameters of the drug under the fed conditions were observed. Multiple dosage of TSR and TIR reached steady state after 7 days, with no accumulation phenomenon observed. The peak time and peak concentrations of TSR were significantly longer and lower, respectively, than those of TIR. CONCLUSION: TSR showed clear sustained-release characteristics, and food exhibited no significant effects on the pharmacokinetic parameters of trazodone. TSR and TIR reached steady state levels after 7 consecutive days of administration, with no accumulation phenomenon observed.


Assuntos
Preparações de Ação Retardada/farmacocinética , Trazodona/farmacocinética , Área Sob a Curva , Estudos Cross-Over , Interações Alimento-Droga , Humanos , Comprimidos
18.
Am J Dent ; 32(3): 138-142, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31295395

RESUMO

PURPOSE: To compare the enamel protection efficacy of a stabilized stannous fluoride dentifrice to a triclosan-containing sodium fluoride dentifrice using a 10-day in situ erosion model, in accordance with the American Dental Association Seal of Acceptance guidelines for enamel erosion control. METHODS: In this single-center, double-blind, randomized, supervised-usage, two-treatment, four-period, crossover study, healthy adult subjects were randomized to a treatment sequence involving the following products: a 0.454% stannous fluoride (1,100 ppm F) dentifrice (Procter & Gamble) and a control dentifrice containing 0.243% sodium fluoride (1,100 ppm F) and 0.3% triclosan (Colgate-Palmolive). Each study period consisted of 10 treatment days. Subjects wore an intra-oral appliance fitted with two polished human enamel samples for 6 hours per treatment day. While wearing the appliance, subjects swished with their assigned dentifrice slurry for 60 seconds twice daily and with 250 ml orange juice over a 10-minute period four times daily. After 10 days, enamel specimens were removed and measured for surface loss using contact profilometry. RESULTS: 36 subjects were enrolled and 33 completed the study (mean age = 41.8 years). The stannous fluoride dentifrice demonstrated 90.3% less enamel loss than the NaF/triclosan dentifrice (P < 0.001) at Day 10, with median enamel loss of 0.279 µm and 2.877 µm, respectively. Both products were well tolerated. CLINICAL SIGNIFICANCE: The stannous fluoride dentifrice provided significantly greater protection against dental erosion relative to the NaF/triclosan dentifrice.


Assuntos
Esmalte Dentário , Dentifrícios , Fluoretos de Estanho , Adulto , Estudos Cross-Over , Dentifrícios/uso terapêutico , Método Duplo-Cego , Humanos , Fosfatos , Fluoretos de Estanho/uso terapêutico , Estados Unidos
19.
BMC Vet Res ; 15(1): 181, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31146740

RESUMO

BACKGROUND: Epilepsy is the most common brain disease in dogs. Recently, diets have been reported to have a positive impact on seizure activity and behaviour in various species including dogs with idiopathic epilepsy (IE). Historically, classic high fat ketogenic diets (KD) and medium chain triglycerides (MCT) KD have been successfully used to manage drug-resistant epilepsy. Similarly, an MCT enriched diet has been shown to improve seizure control and behavioural comorbidities in some dogs with IE. However, it is unknown whether an MCT dietary supplement (DS) may provide similar positive effects. METHODS: A 6-month prospective, randomised, double-blinded, placebo-controlled, crossover, multicentre dietary trial is designed comparing a 9% metabolic energy based calculated medium-chain triglyceride (MCT) oil supplement to a conventional 'control' DS. Only dogs which will have an International Veterinary Epilepsy Task Force Tier II level like diagnosis of IE which satisfied the following inclusion criteria are included: age between 6 months and ≤ 12 years; weighing between 4 and ≤ 65 kg; unremarkable interictal neurological examinations; no clinically significant findings on routine laboratory diagnostics; unremarkable brain MRI scan; have had at least 3 seizures in the previous 3 months prior to enrolment; treated with at least one ASD and being classified as resistant. All dogs are fed initially for 90 ± 2 days with either the control oil or the MCT oil alongside their normal diet, followed by 97 ± 2 days with the other supplement including a 7-day washout period. Overall, the aim is to recruit thirty-six patients at five different centres and to investigate the effect of MCTs as DS on seizure activity, tolerability, behavioural comorbidities and quality of life (QoL). DISCUSSION: Dietary interventions are rarely studied in a standardised form in veterinary medicine. The background diet, the cohort of animals and ASD received is standardised in this prospective diet trial to ensure representative data about the potential effect of MCT DS. If the study data confirms former findings, this would provide further evidence for the efficacy of MCTs as a management option for canine epilepsy. This publication should offer a repository of trial conditions and variable description with forecasted statistical analysis.


Assuntos
Ração Animal , Suplementos Nutricionais , Doenças do Cão/dietoterapia , Epilepsia/veterinária , Triglicerídeos/uso terapêutico , Animais , Protocolos Clínicos , Estudos Cross-Over , Cães , Método Duplo-Cego , Epilepsia/dietoterapia , Estudos Prospectivos , Distribuição Aleatória
20.
Am J Vet Res ; 80(7): 631-636, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31246120

RESUMO

OBJECTIVE: To assess effects of nitrogen and helium on efficacy of an alveolar recruitment maneuver (ARM) for improving pulmonary mechanics and oxygen exchange in anesthetized horses. ANIMALS: 6 healthy adult horses. PROCEDURES: Horses were anesthetized twice in a randomized crossover study. Isoflurane-anesthetized horses in dorsal recumbency were ventilated with 30% oxygen and 70% nitrogen (treatment N) or heliox (30% oxygen and 70% helium; treatment H) as carrier gas. After 60 minutes, an ARM was performed. Optimal positive end-expiratory pressure was identified and maintained for 120 minutes. Throughout the experiment, arterial blood pressures, heart rate, peak inspiratory pressure, dynamic compliance (Cdyn), and Pao2 were measured. Variables were compared with baseline values and between treatments by use of an ANOVA. RESULTS: The ARM resulted in significant increases in Pao2 and Cdyn and decreases in the alveolar-arterial gradient in the partial pressure of oxygen in all horses. After the ARM and during the subsequent 120-minute phase, mean values were significantly lower for treatment N than treatment H for Pao2 and Cdyn. Optimal positive end-expiratory pressure was consistently 15 cm H2O for treatment N, but it was 10 cm H2O (4 horses) and 15 cm H2O (2 horses) for treatment H. CONCLUSIONS AND CLINICAL RELEVANCE: An ARM in anesthetized horses might be more efficacious in improving Pao2 and Cdyn when animals breathe helium instead of nitrogen as the inert gas.


Assuntos
Anestesia Geral/veterinária , Hélio/administração & dosagem , Cavalos/fisiologia , Nitrogênio/administração & dosagem , Oxigênio/administração & dosagem , Alvéolos Pulmonares/fisiologia , Anestesia Geral/métodos , Animais , Estudos Cross-Over , Feminino , Isoflurano/administração & dosagem , Masculino , Posicionamento do Paciente/métodos , Posicionamento do Paciente/veterinária , Distribuição Aleatória
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