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1.
Clin Radiol ; 75(9): 712.e23-712.e31, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32507314

RESUMEN

AIM: To evaluate the clinical and cost implications of using computed tomography colonography (CTC) compared to optical colonoscopy (OC) as the initial colonic investigation in patients with low-to-intermediate risk of colorectal cancer (CRC). MATERIALS AND METHODS: A non-randomised, prospective single-centre study recruited 180 participants to compare the cost implications of two clinical pathways used in the diagnosis of low-to-intermediate risk of CRC that differ in the initial diagnostic test, either CTC or OC. Costs were compared using generalised linear models (GLM) and combined with quality-adjusted life years (QALYs, based on the EQ-5D-5L) to estimate cost-effectiveness at 6 months post-recruitment. Secondary outcomes assessed access to care and patient satisfaction. RESULTS: Mean (SD, n) cost at 6 months post-recruitment per participant was £991 (£316, n=105) for the OC group and £645 (£607, n=68) for the CTC group, leading to an estimated cost difference of -£370 (95% CI: -£554, -£185, p<0.001). Assuming a £20,000 willingness-to-pay per QALY threshold, there was a 91.4% probability of CTC being cost-effective at month 6. The utilisation of CTC led to improved access to care, with a shorter mean time from referral from primary care to results (6.3 days difference, p=0.005). No differences in patient satisfaction were detected between both groups. CONCLUSION: The utilisation of CTC as the first-line investigation for patients with low-to-intermediate risk of CRC has the potential to release OC capacity, of pivotal importance for patients more likely to benefit from an invasive diagnostic approach.


Asunto(s)
Colonografía Tomográfica Computarizada/estadística & datos numéricos , Neoplasias Colorrectales/diagnóstico , Tamizaje Masivo/métodos , Satisfacción del Paciente , Anciano , Colonografía Tomográfica Computarizada/economía , Colonoscopía/economía , Colonoscopía/estadística & datos numéricos , Neoplasias Colorrectales/economía , Análisis Costo-Beneficio , Femenino , Estudios de Seguimiento , Humanos , Masculino , Tamizaje Masivo/economía , Persona de Mediana Edad , Estudios Prospectivos
2.
Anal Chem ; 86(3): 1710-8, 2014 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-24417267

RESUMEN

We propose a label-free biosensor platform to investigate the binding kinetics using antigen-antibody interaction via electrochemical and surface plasmon resonance (SPR) techniques. The L-cysteine in situ capped cadmium sulfide (CdS; size < 7 nm) quantum dots (QDs) self-assembled on gold (Au) coated glass electrode have been covalently functionalized with apolipoprotein B-100 antibodies (AAB). This protein conjugated QDs-based electrode (AAB/CysCdS/Au) has been used to detect lipid (low density lipoprotein, LDL) biomolecules. The electrochemical impedimetric response of the AAB/CysCdS/Au biosensor shows higher sensitivity (32.8 kΩ µM(-1)/cm(2)) in the detection range, 5-120 mg/dL. Besides this, efforts have been made to investigate the kinetics of antigen-antibody interactions at the CysCdS surface. The label-free SPR response of AAB/CysCdS/Au biosensor exhibits highly specific interaction to protein (LDL) with association constant of 33.4 kM(-1) s(-1) indicating higher affinity toward LDL biomolecules and a dissociation constant of 0.896 ms(-1). The results of these studies prove the efficacy of the CysCdS-Au platform as a high throughput compact biosensing device for investigating biomolecular interactions.


Asunto(s)
Apolipoproteína B-100/química , Lípidos/análisis , Puntos Cuánticos , Resonancia por Plasmón de Superficie/métodos , Compuestos de Cadmio/química , Cisteína/química , Espectroscopía Dieléctrica , Electrodos , Oro/química , Cinética , Sulfuros/química
3.
J Nanosci Nanotechnol ; 13(3): 1671-8, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23755572

RESUMEN

We report the application of nano crystalline tin oxide quantum dots (SnO2-QDs) for electrochemical detection of Vibrio cholerae based on DNA hybridization technique. SnO2-QDs (- 1-5 nm) have been synthesized by laser ablation technique in liquid (LAL) and electrophoretically deposited onto hydrolyzed surface of indium tin oxide (ITO) coated glass electrode. A single stranded oligonucleotide probe (23 bases) have been designed form the virulent gene sequence of V. cholerae and has been immobilized onto SnO2-QDs/ITO surface for the fabrication of ssDNA/SnO2-QDs/ITO bioelectrode and these bioelectrode have been further used for DNA hybridization (dsDNA/SnO2-QDs/ITO). The electrochemical response studies have been carried out with different concentration genomic DNA (100-500 ng/microL), which indicated that SnO2 provides an effective surface to bind with the phosphate group of DNA, thus resulting in an enhanced electron transport. The hybridized electrode exhibits linear response with regression coefficient (R) 0.974, high sensitivity 35.20 nA/ng/cm2, low detection limit (31.5 ng/microL), faster response time (3 s) and high stability of 0-120 days when stored under refrigerated conditions.


Asunto(s)
ADN Bacteriano/análisis , Puntos Cuánticos , Compuestos de Estaño/química , Vibrio cholerae/aislamiento & purificación , Secuencia de Bases , Sondas de ADN , Microscopía de Fuerza Atómica , Espectroscopía Infrarroja por Transformada de Fourier , Vibrio cholerae/genética , Vibrio cholerae/patogenicidad , Virulencia
4.
Diabetes Res Clin Pract ; 203: 110834, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37478978

RESUMEN

BACKGROUND AND AIMS: The backlog of care in resource stretched healthcare systems requires innovative approaches to aid clinical prioritisation. Our aim was to develop an informatics tool to identify and prioritise people with diabetes who are likely to deteriorate whilst awaiting an appointment to optimise clinical outcomes and resources. MATERIALS AND METHODS: Using data from electronic health care records we identified 6 risk-factors that could be addressed in 4022 people (52% male, 30% non-Caucasian) with diabetes attending a large university hospital in London. The risk-factors were new clinical events/data occurring since their last routine clinic visit. To validate and compare data-led prioritisation tool to a traditional 'clinical approach' a sample of 450 patients were evaluated. RESULTS: Of the 4022 people, 549 (13.6%) were identified as having one or more risk events/factors. People with risk were more likely to be non-Caucasian and had greater socio-economic deprivation. Taking clinical prioritisation as the gold standard, informatics tool identified high risk patients with a sensitivity of 83% and lower risk patients with a specificity of 81%. An operational pilot pathway over 3 months using this approach demonstrated in 101 high risk people that 40% received interventions/care optimisation to prevent deterioration in health. CONCLUSION: A pragmatic data-driven method identifies people with diabetes at highest need for clinical prioritisation within restricted resources. Health informatics systems such as our can enhance care and improve operational efficiency and better healthcare delivery for people with diabetes.


Asunto(s)
Diabetes Mellitus , Informática Médica , Humanos , Masculino , Femenino , Diabetes Mellitus/epidemiología , Diabetes Mellitus/terapia , Atención a la Salud , Factores de Riesgo , Londres/epidemiología
5.
Analyst ; 137(3): 747-53, 2012 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-22132413

RESUMEN

Self-assembled monolayer (SAM) of 4-aminothiophenol (4-ATP) has been investigated for immobilization of bi-enzymes (ChOx and ChEt) towards development of enzyme biosensors for detection of free and total cholesterol. This enzyme immobilized SAM surface has been characterized by scanning electron microscopy and electrochemical measurements. The results of electrochemical response studies reveal fast enzymatic reaction in phosphate buffer saline solution without using any artificial mediator. This may be attributed to the molecular wire type behavior of short 4-ATP molecule that promotes electron transfer between enzyme and the electrode surface due to its conjugated structure. Interference free estimation of free and total cholesterol has been realized at low operating potential of 0.33 V with range of detection as 25 to 400 mg dl(-1), sensitivity of 542.3 nA mM(-1) (for ChOx/4-ATP/Au) and 886.6 nA mM(-1) (for ChEt-ChOx/4-ATP/Au) with a response time of 20 s at pH 7.4.


Asunto(s)
Técnicas Biosensibles , Colesterol/análisis , Enzimas Inmovilizadas , Microscopía Electrónica de Rastreo , Compuestos de Sulfhidrilo/química , Propiedades de Superficie , Temperatura
7.
Biomacromolecules ; 12(3): 540-7, 2011 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-21218766

RESUMEN

The present work describes electrophoretic fabrication of nanostructured chitosan-zirconium-oxide composite (CHIT-NanoZrO(2)) film (180 nm) onto indium-tin-oxide (ITO)-coated glass plate. This nanobiocomposite film has been explored as immobilization platform for probe DNA specific to M. Tuberculosis as model biomolecule to investigate its sensing characteristics. It is revealed that pH-responsive behavior of CHIT and its cationic skeleton is responsible for the movement of CHIT-NanoZrO(2) colloids toward cathode during electrophoretic deposition. The FT-IR, SEM, TEM, and EDX techniques have been employed for the structural, morphological, and composition analysis of the fabricated electrodes. The morphological studies clearly reveal uniform inter-linking and dispersion of hexagonal nanograins of ZrO(2) (30-50 nm) into the chitosan matrix, resulting in homogeneous nanobiocomposite formation. Electrochemical response measurements of DNA/CHIT-NanoZrO(2)/ITO bioelectrode, carried out using cyclic voltammetry and differential pulse voltammetry, reveal that this bioelectrode can specifically detect complementary target DNA up to 0.00078 µM with sensitivity of 6.38 × 10(-6) AµM(-1).


Asunto(s)
Quitosano/química , ADN Bacteriano/análisis , Electroforesis/métodos , Nanocompuestos/química , Ácidos Nucleicos/análisis , Circonio/química , Sondas de ADN , Mycobacterium tuberculosis/aislamiento & purificación
8.
J Healthc Qual Res ; 36(3): 168-175, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33487584

RESUMEN

INTRODUCTION AND OBJECTIVES: Surgical patients are at risk of hospital-acquired venous thromboembolisms (VTEs), and preventative measures such as thromboembolism deterrent stockings (TEDs) and low molecular weight heparin (LMWH) are proven to be beneficial. The National Quality Requirement in the NHS Standard Contract 2017/19 in England mandates that 95% of inpatients undergo VTE risk assessments. As hospitals transition to Electronic Patient Records (EPR), it is important to observe the impact on vital safety indicators such as VTE risk. The aim of this study is to observe the effect of implementing EPR in a tertiary centre on adherence to national guidelines, including VTE assessment rates and prophylaxis administration in surgical patients. MATERIALS AND METHODS: Using consecutive sampling, all acute surgical admissions at the hospital from 26/02/2018 to 18/03/2018 (n=154) pre-EPR and 31/10/2018 to 25/11/2018 (n=151) post-EPR were observed for VTE risk assessment, 24-h re-assessment, prophylaxis prescriptions, administration, and patient compliance. Data was compared using a two-tailed Z-test. RESULTS: Pre-EPR, 96% of patients had completed VTE assessments, which increased after EPR implementation to 97% (p=0.39). LWMH prescription rates decreased from 82% to 77% following EPR (p=0.14). Moreover, TED prescriptions decreased from 84% to 64% post-EPR (p<0.01). Administration rates of prophylaxis generally improved post-EPR. The 24-h re-assessment rate decreased from 62% to 54% of patients (p=0.08). CONCLUSION: The study demonstrated that EPR is non-inferior to paper records. Transitioning to an EPR system did not interfere with the completion of VTE risk assessments, hence did not negatively impact the ability to achieve national targets.


Asunto(s)
Tromboembolia Venosa , Anticoagulantes/uso terapéutico , Registros Electrónicos de Salud , Heparina de Bajo-Peso-Molecular , Humanos , Prescripciones , Tromboembolia Venosa/prevención & control
9.
J Nanosci Nanotechnol ; 10(10): 6479-88, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21137750

RESUMEN

Cholesterol oxidase (ChOx) has been covalently immobilized onto polyaniline-carboxymethyl cellulose (PANI-CMC) nanocomposite film deposited onto indium-tin-oxide (ITO) coated glass plate using glutaraldehyde as a cross-linker. Fourier transform infrared (FTIR) spectroscopic and electrochemical studies have been used to characterize the PANI-CMC/ITO nanocomposite electrode and ChOx/PANI-CMC/ITO bioelectrode. Scanning electron microscopy (SEM) studies reveal the formation of PANI-CMC nanocomposite fibers of size approximately 150 nm in diameter. The ChOx/PANI-CMC/ITO bioelectrode exhibits linearity as 0.5-22 mM, detection limit as 1.31 mM, sensitivity as 0.14 mA/mM cm2, response time as 10 s and shelf-life of about 10 weeks when bioelectrode is stored at 4 degrees C. The low value of Michaelis-Menten constant (K(m)) obtained as 2.71 mM reveals high affinity of immobilized ChOx for PANI-CMC/ITO nanocomposite electrode.


Asunto(s)
Compuestos de Anilina/química , Técnicas Biosensibles/métodos , Carboximetilcelulosa de Sodio/química , Colesterol/análisis , Nanocompuestos/química , Colesterol/metabolismo , Colesterol Oxidasa/química , Colesterol Oxidasa/metabolismo , Espectroscopía Dieléctrica , Enzimas Inmovilizadas/química , Enzimas Inmovilizadas/metabolismo , Concentración de Iones de Hidrógeno , Modelos Lineales , Microscopía Electrónica de Rastreo , Tamaño de la Partícula , Polimerizacion , Sensibilidad y Especificidad , Espectroscopía Infrarroja por Transformada de Fourier , Compuestos de Estaño/química
10.
Int J Clin Pharmacol Ther ; 48(5): 309-18, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-20420787

RESUMEN

OBJECTIVE: Fesoterodine 4 mg and 8 mg once daily are indicated for the treatment of overactive bladder. A thorough QT study was conducted to investigate the effects of fesoterodine on cardiac repolarization. MATERIALS AND METHODS: In this parallel-group study, subjects were randomly assigned to receive double-blind fesoterodine 4 mg, fesoterodine 28 mg, or placebo or open-label moxifloxacin 400 mg (positive control) for 3 days. Electrocardiograms (ECGs) were obtained on Days -1 (baseline), 1, and 3. The primary analysis was the time-averaged changes from baseline for Fridericia's-corrected QT interval (QTcF) on Day 3. RESULTS: Among 261 subjects randomized to fesoterodine 4 mg (n = 64), fesoterodine 28 mg (n = 68), placebo (n = 65), or moxifloxacin 400 mg (n = 64), 256 completed the trial. The least squares mean changes in QTcF from baseline were 21.1, 20.5, 18.5, and 31.3 ms (maximum), and -5.1, -4.2, -5.2, and 7.6 ms (time-averaged at Day 3) for placebo, fesoterodine 4 mg, fesoterodine 28 mg, and moxifloxacin, respectively. The lower limit of the 95% confidence interval exceeded 5 ms for moxifloxacin. CONCLUSIONS: The results indicate that fesoterodine is not associated with QTc prolongation or other ECG abnormalities at either therapeutic or supratherapeutic doses.


Asunto(s)
Compuestos de Bencidrilo/toxicidad , Electrocardiografía , Antagonistas Muscarínicos/toxicidad , Compuestos Aza/toxicidad , Compuestos de Bencidrilo/administración & dosificación , Compuestos de Bencidrilo/uso terapéutico , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Fluoroquinolonas , Humanos , Análisis de los Mínimos Cuadrados , Síndrome de QT Prolongado/inducido químicamente , Masculino , Persona de Mediana Edad , Moxifloxacino , Antagonistas Muscarínicos/administración & dosificación , Antagonistas Muscarínicos/uso terapéutico , Quinolinas/toxicidad , Vejiga Urinaria Hiperactiva/tratamiento farmacológico
11.
Artículo en Inglés | MEDLINE | ID: mdl-20367113

RESUMEN

A highly sensitive, amperometric uric acid biosensor possessing unique physical, electro-conductive properties of carbon nanotubes is described for determination of uric acid level in serum. A uric acid biosensor was constructed after immobilization of uricase onto a polyaniline/CNT matrix by carbonamide linkage. The scanning electron micrographs confirmed the immobilization of globular enzyme onto the electroploymerized polyaniline/CNT composite. Employment of carbon nanotubes composite in the present electrode leads to a very quick response time of 8 sec with the minimum detection limit of 5 microM along with an increase in shelf-life of electrode system to >180 days with slight loss of enzyme activity. Efficiency of the present amperometric uric acid biosensor was validated by quantitative estimation of uric acid level in biological serum of healthy individuals and the persons suffering from hyperuricemia and gout.


Asunto(s)
Compuestos de Anilina/química , Técnicas Biosensibles/métodos , Enzimas Inmovilizadas/metabolismo , Nanocompuestos/química , Nanotubos de Carbono/química , Urato Oxidasa/metabolismo , Ácido Úrico/análisis , Bacillus/enzimología , Técnicas Biosensibles/instrumentación , Electroquímica , Electrodos , Enzimas Inmovilizadas/química , Equipo Reutilizado , Concentración de Iones de Hidrógeno , Microscopía Electrónica de Rastreo , Reproducibilidad de los Resultados , Factores de Tiempo , Compuestos de Estaño/química , Urato Oxidasa/química , Ácido Úrico/sangre , Ácido Úrico/metabolismo
12.
Lab Chip ; 20(4): 760-777, 2020 02 21.
Artículo en Inglés | MEDLINE | ID: mdl-31951241

RESUMEN

A dual-modality microfluidic biosensor is fabricated using a mesoporous nanostructured cysteine-graphene hydrogel for the quantification of human cardiac myoglobin (cMb). In this device, the nanoengineered mesoporous l-cysteine-graphene (Cys-RGO) hydrogel performs the role of a dual-modality sensing electrode for the measurements conducted using differential pulse voltammetry and surface plasmon resonance (SPR) techniques. High surface reactivity, mesoporous structure and fast electron transfer combined with good reaction kinetics of the graphene hydrogel in this device indicate excellent performance for the detection of human cardiac myoglobin in serum samples. In electrochemical modality, this microfluidic chip exhibits a high sensitivity of 196.66 µA ng-1 mL cm-2 for a linear range of concentrations (0.004-1000 ng mL-1) with a low limit of detection (LOD) of 4 pg mL-1 while the SPR technique shows a LOD of 10 pg mL-1 for cMb monitoring in the range 0.01-1000 ng mL-1. The intra-assay coefficient of variation was less than 8% for standard samples and 9% for real serum samples, respectively. This Cys-RGO hydrogel-based microfluidic SPR chip allows real-time dynamic tracking of cMb molecules with a high association constant of 4.93 ± 0.2 × 105 M-1 s-1 and a dissociation constant of 1.37 ± 0.08 × 10-4 s-1, self-verification, reduced false readout, and improved detection reliability.


Asunto(s)
Técnicas Biosensibles , Grafito , Humanos , Hidrogeles , Microfluídica , Reproducibilidad de los Resultados
13.
Analyst ; 134(5): 997-1002, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-19381396

RESUMEN

A 20-mer thiolated oligonucleotide probe (th-ssDNA) specific to Neisseria gonorrhoeae immobilized onto a sol-gel derived nano-structured zinc oxide (ZnO) film dip-coated onto an indium-tin-oxide (ITO) glass substrate has been used for the fabrication of a DNA biosensor for sexually transmitted disease (gonorrhoea) detection using hybridization technique. The results of characterization studies carried out on this th-ssDNA-ZnO/ITO bioelectrode using X-ray diffraction, UV-Visible, Fourier-transform infrared, scanning electron microscopy and electrochemical techniques reveal the linearity as 0.000524 fmol-0.524 nmol, with a detection limit of 0.000704 fmol within 60 s.


Asunto(s)
Gonorrea/diagnóstico , Nanoestructuras/química , Transición de Fase , Óxido de Zinc/química , Técnicas Electroquímicas/instrumentación , Técnicas Electroquímicas/métodos , Electrodos , Humanos , Neisseria gonorrhoeae/aislamiento & purificación
14.
J Nanosci Nanotechnol ; 9(8): 4679-85, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19928134

RESUMEN

Hydrogen peroxide (H2O2) sensor has been fabricated by immobilizing horse radish peroxidase (HRP) onto polyaniline(PANI)-cerium oxide (CeO2) nano-composite film onto indium-tin-oxide (ITO) coated glass substrate using electrochemical technique. The HRP/PANI-CeO2/ITO bioelectrode has been characterized using scanning electron microscopy (SEM), Fourier Transform Infrared spectroscopy, UV-visible spectroscopy and electrochemical analysis, respectively. This electrode shows improved sensitivity (159.6 nA/mM) and detection limit (50 mM). Further this H2O2 sensor shows high HRP affinity to the PANI-CeO2 matrix as indicated by low value (2.9) mM of Michaelis-Menten constant (K(m)). This bioelectrode exhibits maximum response current at pH 7.0 and retains 90% of its initial response current after about 8 weeks.

15.
J Nanosci Nanotechnol ; 9(3): 1792-6, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19435041

RESUMEN

Nanocomposite thin film of cross-linked polyaniline [CLPANI, derived from polyaniline and aniline formaldehyde condensate (AFC)] and WO3 has been fabricated using vacuum thermal evaporation technique. X-ray diffraction pattern of as-grown film shows broad reflections of polymer along with mixed reflection of nonhydrated and hydrated WO3 nanoparticles. The scanning electron microscopy studies reveal uniform dispersion of WO3 nanoparticles in CLPANI network. The broadening of the absorption band at 320 nm corresponding to PANI and AFC-WO3 nanocomposite is attributed to cross-linking between the polymeric units. The NO(x) gas sensing characteristics of vacuum deposited CLPANI-WO3 thin film have been studied by measuring the change in resistance with respect to time. The sensor can be operated at room temperature, resulting in extended shelf life of the sensor. The response time and recovery time of the sensor operated at room temperature have been experimentally determined as 30 s and 11 minutes respectively.


Asunto(s)
Compuestos de Anilina/química , Técnicas de Sonda Molecular/instrumentación , Nanocompuestos/química , Óxido Nítrico/análisis , Óxidos/química , Tungsteno/química , Contaminantes Atmosféricos/análisis , Monitoreo del Ambiente/instrumentación , Microscopía Electrónica de Rastreo , Fenómenos Ópticos , Análisis Espectral , Temperatura , Factores de Tiempo
16.
Int J Clin Pharmacol Ther ; 47(6): 384-90, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19473600

RESUMEN

OBJECTIVE: Fesoterodine is a new, once-daily, oral, antimuscarinic agent indicated for the treatment of overactive bladder. It undergoes rapid and extensive metabolism by plasma esterases to form its principal active moiety, 5-hydroxymethyl tolterodine (5-HMT). The sustained-release formulation of fesoterodine delivers 5-HMT with linear, dose-proportional pharmacokinetics (PK) suitable for once-daily dosing. This study was designed for the definitive assessment of the effect of food on 5-HMT PK using the commercial formulation of fesoterodine. METHODS: In this randomized, open-label, single-dose, 2-way, crossover study, fesoterodine 8 mg was administered orally to healthy subjects in either a fed (after a high-fat, high-calorie breakfast) or fasted state. Blood samples for PK were drawn up to 36 hours after dosing. Primary endpoints for food effect assessment were area under the concentration-versus-time curve up to the last sample (AUC(0-tz)), and maximum plasma concentration (C(max)) for 5-HMT. Adverse events, vital signs, hematology, clinical chemistry, and electrocardiograms were monitored for safety assessment. RESULTS: A total of 16 healthy male subjects enrolled and completed the study. Mean values of both primary PK parameters of 5-HMT (AUC(0-tz) and C(max)) were approximately 19% higher after fesoterodine administration in the fed versus the fasted state. The upper limits of the corresponding 90% confidence intervals for the "fed/fasted" ratios of AUC(0-tz) (104%, 137%) and C(max) (94%, 149%) were not included in the prespecified acceptance range (80%, 125%) for concluding "no food effect." Secondary PK variables, (i.e. time to maximum plasma concentration terminal elimination half-life and mean residence time), did not differ markedly between the fed and fasted states. Fesoterodine was well tolerated, and adverse events were mild, with no apparent difference in frequency between fed and fasted states. CONCLUSIONS: The hypothesis of "no food effect" could not be statistically confirmed; however, only modest increases of approximately 19% were observed for C(max) and AUC(0-tz) of 5-HMT. This magnitude of PK effects is unlikely to be of clinical relevance based on Phase 2 and 3 clinical experience with fesoterodine, supporting its administration without regard to meals.


Asunto(s)
Compuestos de Bencidrilo/farmacocinética , Interacciones Alimento-Droga , Alimentos , Antagonistas Muscarínicos/farmacocinética , Adolescente , Adulto , Compuestos de Bencidrilo/efectos adversos , Compuestos de Bencidrilo/sangre , Estudios Cruzados , Ayuno , Humanos , Masculino , Persona de Mediana Edad , Antagonistas Muscarínicos/efectos adversos , Antagonistas Muscarínicos/sangre
17.
Int J Clin Pharmacol Ther ; 47(9): 570-8, 2009 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-19761716

RESUMEN

OBJECTIVE: Fesoterodine, a new antimuscarinic agent for overactive bladder, undergoes immediate and extensive hydrolysis by nonspecific esterases to 5-hydroxymethyl tolterodine (5-HMT), the metabolite principally responsible for its antimuscarinic activity. Formation of 5-HMT does not require cytochrome P450 (CYP)-mediated metabolism, but its further metabolism and inactivation involves CYP3A4 and CYP2D6 isoenzymes. Subject age, gender, and race can play a key role in inter-subject variability in pharmacokinetics and thus efficacy and safety of drugs. This article examines the effects of age, gender, and race on the pharmacokinetics and pharmacodynamics of fesoterodine. METHODS: Data from two randomized, double-blind, placebo-controlled, parallel-group trials in healthy subjects are presented: Study 1 investigated the effects of race (white vs. black men) and Study 2 investigated the effects of age (young vs. old men) and gender (elderly men vs. elderly women) on the pharmacokinetics and pharmacodynamics of single doses of fesoterodine 8 mg. In both studies, the primary endpoints were area under the concentration-time curve up to the last sample (AUC0-tz) and maximum concentration (Cmax) of 5-HMT in plasma. Pharmacodynamic variables included spontaneous salivary secretion (Studies 1 and 2) and residual urine volume (Study 2 only). The two studies included 5 groups of 16 subjects each (randomized 3 : 1 to fesoterodine or placebo): white men aged 18 - 45 years, black men aged 18 - 45 years (Study 1); young white men aged 18 - 40 years, elderly white men aged > 65 years, and elderly white women aged > 65 years (Study 2). RESULTS: There were no clinically meaningful differences in the primary endpoints between white and black subjects or between young white men, elderly white men, and elderly white women. Mean AUC0-tz was 70.7 ng/ml x h in whites and 64.1 ng/ml x h in blacks; mean Cmax was 6.1 and 5.5 ng/ml in whites and blacks, respectively. Mean AUC0-tz in young white men, elderly white men, and elderly white women was 49, 48, and 54 ng/ml x h, respectively; mean Cmax in young white men, elderly white men, and elderly white women was 4.1, 3.8, and 4.6 ng/ml, respectively. Consistent with the anticholinergic pharmacology of fesoterodine, declines in salivary volume were observed in both studies, and elevations in residual urinary volume were observed, especially in elderly subjects, in Study 2. Fesoterodine was well tolerated, with common adverse events such as headache and dry mouth recognized as antimuscarinic class effects. CONCLUSIONS: Subject demographics, such as age, gender, and race, do not have a clinically meaningful effect on 5-HMT pharmacokinetics or pharmacodynamics after single-dose administration of fesoterodine 8 mg; thus, no dosage adjustment is required for fesoterodine based on age, gender, or race.


Asunto(s)
Envejecimiento/fisiología , Compuestos de Bencidrilo/farmacología , Compuestos de Bencidrilo/farmacocinética , Antagonistas Muscarínicos/farmacología , Antagonistas Muscarínicos/farmacocinética , Adolescente , Adulto , Anciano , Área Bajo la Curva , Compuestos de Bencidrilo/efectos adversos , Población Negra , Método Doble Ciego , Etnicidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antagonistas Muscarínicos/efectos adversos , Salivación/efectos de los fármacos , Caracteres Sexuales , Urodinámica/efectos de los fármacos , Población Blanca , Adulto Joven
18.
Int J Tuberc Lung Dis ; 23(12): 1257-1262, 2019 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-31931908

RESUMEN

SETTING: Patients with presumed multidrug-resistant tuberculosis (MDR-TB) and undergoing MDR-TB treatment from Rajasthan, India.OBJECTIVE: To compare the GenoType® MTBDRsl v.1.0 (MTBDRsl) assay capacity to detect resistance to ofloxacin, amikacin, capreomycin, kanamycin and ethambutol in Mycobacterium tuberculosis with phenotypic drug susceptibility testing (DST) using MGIT™960™ in sputum samples and isolates.DESIGN: Fifty-three smear-positive sputum samples were tested directly by MTBDRsl and 205 MDR-TB isolates were processed using MTBDRsl and DST for five drugs on MGIT960. DNA sequencing was performed in isolates with discordance in the results between the two methods for the gyrA, gyrB and rrs genes.RESULT: Sensitivity and specificity of MTBDRsl was found to be respectively 93.1% and 100% for fluoroquinoline, respectively 75-78% and 100% for aminoglycosides/cyclopeptides, respectively 70% and 92% for ethambutol and respectively 92.3% and 100% for extensively drug-resistant (XDR) TB detection. On sequencing eight discordant isolates for quinolones, mutations were seen in 12.5% of the gyrB gene and among 20 discordant isolates for aminoglycosides/cyclopeptides in the rrs gene in 15% isolates. The turnaround time was 2 days for MTBDRsl vs. 10 days for MGIT960.CONCLUSIONS: MTBDRsl can be used as an initial rapid test for detecting XDR-TB, resistance to quinolones and aminogycosides/cyclopeptides in smear-positive sputum samples.


Asunto(s)
Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis/aislamiento & purificación , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , ADN Bacteriano/genética , Farmacorresistencia Bacteriana Múltiple , Genotipo , Humanos , Mycobacterium tuberculosis/genética , Sensibilidad y Especificidad , Esputo/microbiología , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/microbiología
19.
Bone Joint J ; 101-B(8): 984-994, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31362557

RESUMEN

AIMS: The aim of the Scaphoid Magnetic Resonance Imaging in Trauma (SMaRT) trial was to evaluate the clinical and cost implications of using immediate MRI in the acute management of patients with a suspected fracture of the scaphoid with negative radiographs. PATIENTS AND METHODS: Patients who presented to the emergency department (ED) with a suspected fracture of the scaphoid and negative radiographs were randomized to a control group, who did not undergo further imaging in the ED, or an intervention group, who had an MRI of the wrist as an additional test during the initial ED attendance. Most participants were male (52% control, 61% intervention), with a mean age of 36.2 years (18 to 73) in the control group and 38.2 years (20 to 71) in the intervention group. The primary outcome was total cost impact at three months post-recruitment. Secondary outcomes included total costs at six months, the assessment of clinical findings, diagnostic accuracy, and the participants' self-reported level of satisfaction. Differences in cost were estimated using generalized linear models with gamma errors. RESULTS: The mean cost up to three months post-recruitment per participant was £542.40 (sd £855.20, n = 65) for the control group and £368.40 (sd £338.60, n = 67) for the intervention group, leading to an estimated cost difference of £174 (95% confidence interval (CI) -£30 to £378; p = 0.094). The cost difference per participant increased to £266 (95% CI £3.30 to £528; p = 0.047) at six months. Overall, 6.2% of participants (4/65, control group) and 10.4% of participants (7/67, intervention group) had sustained a fracture of the scaphoid (p = 0.37). In addition, 7.7% of participants (5/65, control group) and 22.4% of participants (15/67, intervention group) had other fractures diagnosed (p = 0.019). The use of MRI was associated with higher diagnostic accuracy both in the diagnosis of a fracture of the scaphoid (100.0% vs 93.8%) and of any other fracture (98.5% vs 84.6%). CONCLUSION: The use of immediate MRI in the management of participants with a suspected fracture of the scaphoid and negative radiographs led to cost savings while improving the pathway's diagnostic accuracy and patient satisfaction. Cite this article: Bone Joint J 2019;101-B:984-994.


Asunto(s)
Análisis Costo-Beneficio , Fracturas Óseas/diagnóstico por imagen , Costos de la Atención en Salud/estadística & datos numéricos , Imagen por Resonancia Magnética/economía , Hueso Escafoides/lesiones , Traumatismos de la Muñeca/diagnóstico por imagen , Adolescente , Adulto , Anciano , Ahorro de Costo/estadística & datos numéricos , Servicio de Urgencia en Hospital , Femenino , Estudios de Seguimiento , Fracturas Óseas/economía , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Satisfacción del Paciente/estadística & datos numéricos , Estudios Prospectivos , Radiografía , Hueso Escafoides/diagnóstico por imagen , Reino Unido , Traumatismos de la Muñeca/economía , Adulto Joven
20.
Anal Biochem ; 383(2): 194-9, 2008 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-18817744

RESUMEN

Nanocomposite film composed of polyaniline (PANI) and multiwalled carbon nanotubes (MWCNT), prepared electrophoretically onto indium tin oxide (ITO)-coated glass plate, was used for covalent immobilization of cholesterol oxidase (ChOx) via N-ethyl-N'-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) chemistry. Results of linear sweep voltammetric measurements reveal that ChOx/PANI-MWCNT/ITO bioelectrode can detect cholesterol in the range of 1.29 to 12.93 mM with high sensitivity of 6800 nA mM(-1) and a fast response time of 10 s. Photometric studies for ChOx/PANI-MWCNT/ITO bioelectrode indicate that it is thermally stable up to 45 degrees C and has a shelf life of approximately 12 weeks when stored at 4 degrees C. The results of these studies have implications for the application of this interesting matrix (PANI-MWCNT) toward the development of other biosensors.


Asunto(s)
Compuestos de Anilina/química , Técnicas Biosensibles/instrumentación , Técnicas Biosensibles/métodos , Colesterol/análisis , Nanocompuestos/química , Nanotubos de Carbono/química , Colesterol/metabolismo , Colesterol Oxidasa/metabolismo , Impedancia Eléctrica , Electroquímica , Electrodos , Electroforesis , Vidrio/química , Concentración de Iones de Hidrógeno , Pseudomonas fluorescens/enzimología , Sensibilidad y Especificidad , Espectroscopía Infrarroja por Transformada de Fourier , Propiedades de Superficie , Temperatura , Factores de Tiempo , Compuestos de Estaño/química
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