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1.
ACS Appl Mater Interfaces ; 13(2): 3024-3032, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33404230

RESUMO

A wearable surface-enhanced Raman scattering (SERS) sensor has been developed as a patch type to utilize as a molecular sweat sensor. Here, the SERS patch sensor is designed to comprise a sweat-absorbing layer, which is an interface to the human skin, an SERS active layer, and a dermal protecting layer that prevents damage and contaminations. A silk fibroin protein film (SFF) is a basement layer that absorbs aqueous solutions and filtrates molecules larger than the nanopores created in the ß-sheet matrix of the SFF. On the SFF layer, a plasmonic silver nanowire (AgNW) layer is formed to enhance the Raman signal of the molecules that penetrated through the SERS patch in a label-free method. A transparent dermal protecting layer (DP) allows laser penetration to the AgNW layer enabling Raman measurement through the SERS patch without its detachment from the surface. The molecular detection capability and time-dependent absorption properties of the SERS patch are investigated, and then, the feasibility of its use as a wearable drug detection sweat sensor is demonstrated using 2-fluoro-methamphetamine (2-FMA) on the human cadaver skin. It is believed that the developed SERS patch can be utilized as various flexible and wearable biosensors for healthcare monitoring.


Assuntos
Técnicas Biossensoriais/instrumentação , Análise Espectral Raman/instrumentação , Suor/química , Dispositivos Eletrônicos Vestíveis , Animais , Bombyx/química , Estimulantes do Sistema Nervoso Central/análise , Monitoramento de Medicamentos/instrumentação , Fibroínas/química , Humanos , Metanfetamina/análogos & derivados , Metanfetamina/análise , Nanofios/química , Prata/química , Propriedades de Superfície
2.
Pediatrics ; 147(1)2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33386336

RESUMO

BACKGROUND: Although sensor-based monitoring of daily inhaled corticosteroids (ICSs) and short-acting ß-agonist medications may improve asthma outcomes, the effectiveness of these interventions in diverse pediatric populations remains unclear. METHODS: Caregiver and child dyads were randomly assigned to receive inhaler sensors that allowed for caregiver and clinician electronic monitoring of medications. End points included Asthma Control Test scores (≥19 indicated asthma control) and asthma health care use. Caregiver quality of life (QoL) and child ICS adherence were also assessed. Multilevel models were used to estimate adjusted changes from baseline. RESULTS: Dyads were assigned to the control (n = 127) or intervention (n = 125) arms. At the end line, the mean Asthma Control Test score increased from 19.1 (SE = 0.3) to 21.8 (SE = 0.4) among the intervention and from 19.4 (SE = 0.3) to 19.9 (SE = 0.4) among the control (Δintervention-control = 2.2; SE = 0.6; P < .01). Adjusted rates of emergency department visits and hospitalizations among the intervention were significantly greater (incidence rate ratioemergency department = 2.2; SE = 0.5; P < .01; incidence rate ratiohospital = 3.4; SE = 1.4; P < .01) at endline than the control. Caregiver QoL was greater among the intervention at the endline (Δintervention-control = 0.3; SE = 0.2; P = .1) than the control. CONCLUSIONS: Findings suggest that sensor-based inhaler monitoring with clinical feedback may improve asthma control and caregiver QoL within diverse populations. Higher health care use was observed among the intervention participants relative to the control, indicating further refinement is warranted.


Assuntos
Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Monitoramento de Medicamentos/instrumentação , Adesão à Medicação , Telemetria , Adolescente , Cuidadores/psicologia , Criança , Pré-Escolar , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Monitorização Ambulatorial/instrumentação , Nebulizadores e Vaporizadores , Qualidade de Vida , Smartphone
4.
Proc Natl Acad Sci U S A ; 117(32): 19017-19025, 2020 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-32719130

RESUMO

To achieve the mission of personalized medicine, centering on delivering the right drug to the right patient at the right dose, therapeutic drug monitoring solutions are necessary. In that regard, wearable biosensing technologies, capable of tracking drug pharmacokinetics in noninvasively retrievable biofluids (e.g., sweat), play a critical role, because they can be deployed at a large scale to monitor the individuals' drug transcourse profiles (semi)continuously and longitudinally. To this end, voltammetry-based sensing modalities are suitable, as in principle they can detect and quantify electroactive drugs on the basis of the target's redox signature. However, the target's redox signature in complex biofluid matrices can be confounded by the immediate biofouling effects and distorted/buried by the interfering voltammetric responses of endogenous electroactive species. Here, we devise a wearable voltammetric sensor development strategy-centering on engineering the molecule-surface interactions-to simultaneously mitigate biofouling and create an "undistorted potential window" within which the target drug's voltammetric response is dominant and interference is eliminated. To inform its clinical utility, our strategy was adopted to track the temporal profile of circulating acetaminophen (a widely used analgesic and antipyretic) in saliva and sweat, using a surface-modified boron-doped diamond sensing interface (cross-validated with laboratory-based assays, R 2 ∼ 0.94). Through integration of the engineered sensing interface within a custom-developed smartwatch, and augmentation with a dedicated analytical framework (for redox peak extraction), we realized a wearable solution to seamlessly render drug readouts with minute-level temporal resolution. Leveraging this solution, we demonstrated the pharmacokinetic correlation and significance of sweat readings.


Assuntos
Acetaminofen/análise , Monitoramento de Medicamentos/métodos , Saliva/química , Suor/química , Acetaminofen/administração & dosagem , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Monitoramento de Medicamentos/instrumentação , Humanos , Medicina de Precisão , Dispositivos Eletrônicos Vestíveis
5.
Clin Pharmacol Ther ; 108(5): 1090-1097, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32588427

RESUMO

Association between Hydroxychloroquine (HCQ) and Azithromycin (AZT) is under evaluation for patients with lower respiratory tract infection (LRTI) caused by the Severe Acute Respiratory Syndrome (SARS-CoV-2). Both drugs have a known torsadogenic potential, but sparse data are available concerning QT prolongation induced by this association. Our objective was to assess for COVID-19 LRTI variations of QT interval under HCQ/AZT in patients hospitalized, and to compare manual versus automated QT measurements. Before therapy initiation, a baseline 12 lead-ECG was electronically sent to our cardiology department for automated and manual QT analysis (Bazett and Fridericia's correction), repeated 2 days after initiation. According to our institutional protocol (Pasteur University Hospital), HCQ/AZT was initiated only if baseline QTc ≤ 480ms and potassium level> 4.0 mmol/L. From March 24th to April 20th 2020, 73 patients were included (mean age 62 ± 14 years, male 67%). Two patients out of 73 (2.7%) were not eligible for drug initiation (QTc ≥ 500 ms). Baseline average automated QTc was 415 ± 29 ms and lengthened to 438 ± 40 ms after 48 hours of combined therapy. The treatment had to be stopped because of significant QTc prolongation in two out of 71 patients (2.8%). No drug-induced life-threatening arrhythmia, nor death was observed. Automated QTc measurements revealed accurate in comparison with manual QTc measurements. In this specific population of inpatients with COVID-19 LRTI, HCQ/AZT could not be initiated or had to be interrupted in less than 6% of the cases.


Assuntos
Azitromicina , Infecções por Coronavirus , Monitoramento de Medicamentos , Eletrocardiografia/métodos , Hidroxicloroquina , Síndrome do QT Longo , Pandemias , Pneumonia Viral/tratamento farmacológico , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/efeitos adversos , Anti-Infecciosos/farmacocinética , Azitromicina/administração & dosagem , Azitromicina/efeitos adversos , Azitromicina/farmacocinética , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/fisiopatologia , Precisão da Medição Dimensional , Monitoramento de Medicamentos/instrumentação , Monitoramento de Medicamentos/métodos , Monitoramento de Medicamentos/normas , Feminino , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/farmacocinética , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/diagnóstico , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Pneumonia Viral/diagnóstico , Pneumonia Viral/fisiopatologia , Torsades de Pointes/induzido quimicamente , Torsades de Pointes/prevenção & controle
6.
Ann Biol Clin (Paris) ; 78(2): 147-155, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32319943

RESUMO

OBJECTIVE: The aim of this study was to evaluate the analytical performance of the Alinity®c Abbott compared to the Architect® immunoassay system for the determination of drugs having a narrow therapeutic index. METHODS: Valproic acid, amikacin, gentamicin, phenobarbital and vancomycin were analyzed using Particle-Enhanced Turbidimetric Inhibitor Immunoassay (Petinia), phenytoin and theophylline were analyzed using an immunoenzymatic method and a colorimetric method was performed to quantify lithium. The methods were validated according to the total error approach. Seven validation standards were analyzed in quintuplet during four days to establish the limits of the methods. Dilution integrity and interferences (hemolysis and high concentrations of bilirubin and lipids) were also tested. Depending on the analyte, the results obtained for twenty to forty patients on the Alinity® were compared to those obtained on the Architect®. RESULTS: The bias and the coefficients of variation for repeatability and for intermediate precision were lower than 15% for all drugs. Accuracy profiles were acceptable (acceptance limits fixed at 30%) in the validated ranges. The lower limits of quantification (LLOQ) were similar to those determined by Abbott except for gentamicin for which we determined a LLOQ at 1.22 mg/L while Abbott determined it at 0.5 mg/L. All assays diluted linear and analyte concentrations were not affected by interferences. Concentrations obtained for real samples on the Alinity®c are comparable to those obtained on the Architect®ci. CONCLUSIONS: The analytical validation of a method suitable for therapeutic drug monitoring of drugs on the Alinity®c meets the requirements of European Medicines Agency.


Assuntos
Monitoramento de Medicamentos/instrumentação , Monitoramento de Medicamentos/métodos , Nefelometria e Turbidimetria/instrumentação , Nefelometria e Turbidimetria/métodos , Amicacina/análise , Amicacina/sangue , Automação Laboratorial/instrumentação , Automação Laboratorial/métodos , Colorimetria/instrumentação , Colorimetria/métodos , Gentamicinas/análise , Gentamicinas/sangue , Humanos , Imunoensaio/instrumentação , Imunoensaio/métodos , Fenobarbital/análise , Fenobarbital/sangue , Fenitoína/análise , Fenitoína/sangue , Reprodutibilidade dos Testes , Teofilina/análise , Teofilina/sangue , Ácido Valproico/análise , Ácido Valproico/sangue , Vancomicina/análise , Vancomicina/sangue
7.
Proc Natl Acad Sci U S A ; 117(7): 3509-3517, 2020 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-32019879

RESUMO

Personalized medicine offers great potential benefits for disease management but requires continuous monitoring of drugs and drug targets. For instance, the therapeutic window for lithium therapy of bipolar disorder is very narrow, and more frequent monitoring of sodium levels could avoid toxicity. In this work, we developed and validated a platform for long-term, continuous monitoring of systemic analyte concentrations in vivo. First, we developed sodium microsensors that circulate directly in the bloodstream. We used "red blood cell mimicry" to achieve long sensor circulation times of up to 2 wk, while being stable, reversible, and sensitive to sodium over physiologically relevant concentration ranges. Second, we developed an external optical reader to detect and quantify the fluorescence activity of the sensors directly in circulation without having to draw blood samples and correlate the measurement with a phantom calibration curve to measure in vivo sodium. The reader design is inherently scalable to larger limbs, species, and potentially even humans. In combination, this platform represents a paradigm for in vivo drug monitoring that we anticipate will have many applications in the future.


Assuntos
Monitoramento de Medicamentos/métodos , Eritrócitos/química , Sódio/sangue , Animais , Circulação Sanguínea , Monitoramento de Medicamentos/instrumentação , Fluorescência , Camundongos , Camundongos Nus , Mimetismo Molecular , Ratos
8.
J Cardiovasc Pharmacol ; 75(4): 314-320, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32040035

RESUMO

BACKGROUND: The current light transmission aggregation method is a recognized conventional method for platelet function evaluation, but it is time-consuming and poor in parallelism and cannot simultaneously monitor multiple inducers at multiple levels. The microtiter plate method has been established because of the high-throughput characteristic, but it needs more practical applications. OBJECTIVES: To evaluate the microtiter plate method by using aspirin and clopidogrel in vivo and in vitro. METHODS: In vitro, the platelet aggregations inhibited by aspirin (0.3, 1, 3, 10, 30, 90 µM) and clopidogrel (1, 3, 10, 30, 100, 300 µM) were evaluated with the presence of arachidonic acid (AA) and adenosine diphosphate (ADP) agonists. Using the combination index (CI), the effect of the combination of aspirin and clopidogrel on platelet aggregation was evaluated. In vivo, New Zealand rabbits (n = 18) were randomly divided into 3 groups, aspirin group (5 mg/kg, intragastrical gavage [i.g.]), clopidogrel group (14 mg/kg at the first day, followed by 4 mg/kg, i.g.), and the combination of these two drugs, administered (i.g.) continuously for 7 days. Then, the blood was collected to measure platelet aggregation. RESULTS: Different concentrations of AA (12.5, 25, 50, 100 µM) and ADP (1.25, 2.5, 5, 10 µM) could promote platelet aggregation in concentration-dependent manner, and the most stable induction concentrations of AA and ADP were 50 and 5 µM. In vitro, with the above optimized detection system, aspirin and clopidogrel alone or in combination had concentration-dependent antiplatelet aggregation. The combination of aspirin and clopidogrel also showed synergistic inhibition effect within the concentration range studied. In vivo, aspirin and clopidogrel alone or in combination inhibited platelet aggregation induced by multiple concentrations of AA and ADP agonists, and the combined inhibition was more significant during the administration than aspirin or clopidogrel alone. CONCLUSIONS: The improved microtiter plate method combining the use of multiple levels of multiple agonists avoids the variation of the effective inducer concentrations due to individual different response of platelets to agonists. It may be a potential approach in the detection of platelet aggregation.


Assuntos
Aspirina/farmacologia , Clopidogrel/farmacologia , Monitoramento de Medicamentos/instrumentação , Ensaios de Triagem em Larga Escala/instrumentação , Inibidores da Agregação Plaquetária/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Testes de Função Plaquetária/instrumentação , Animais , Relação Dose-Resposta a Droga , Terapia Antiplaquetária Dupla , Humanos , Masculino , Valor Preditivo dos Testes , Coelhos , Fatores de Tempo
9.
Talanta ; 209: 120560, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31892051

RESUMO

Antipsychotic clozapine is the most effective medication currently available for schizophrenia. However, clozapine is dramatically underutilized due to its harsh side effects that are not effectively monitored. By continuously monitoring clozapine blood levels, such as use of an implantable glucometer, which has transformed diabetes management, the treatment can be optimized and side effects will be minimized. Currently, none of the methods for clozapine detection show the ability to repeatedly measure clozapine in whole blood without pretreatment steps. Here we propose using a microelectrode modified with reduced graphene oxide-a material that was used for repeatable measurements in implantable electrochemical devices. We present the successful direct electrodeposition of reduced-graphene oxide coating onto microelectrodes. Systematic characterization of the electrodeposition technique parameters (i.e., the technique scan rate and the number of cycles) revealed their effect on the electrochemical activity and the structural properties (the film thickness and roughness) of the films. The developed reduced-graphene oxide-modified microelectrode exhibited the feasibility to detect clozapine in microliters-volume-samples of whole blood with a limit-of-detection and a sensitivity of 0.64 ±â€¯0.04 µM and 19.6 ±â€¯1.3 µA/cm2µM, respectively. Moreover, the reduced graphene oxide-modified microelectrodes exhibited high repeatability (retaining 94.6% of the electrochemical signal after 10 repeats), reproducibility (3.6% relative standard deviation), and storage stability (retaining 89% of the electrochemical signal after 4 weeks). Finally, relative recovery studies of 0.5, 1, and 2 µM clozapine concentrations resulted in 108 ±â€¯4.0%, 112 ±â€¯3.5%, and 103 ±â€¯2.2%, respectively. Future studies should investigate the microelectrode fouling mechanisms in whole blood and explore methods to overcome fouling.


Assuntos
Antipsicóticos/sangue , Clozapina/sangue , Técnicas Eletroquímicas/instrumentação , Grafite/química , Monitoramento de Medicamentos/instrumentação , Desenho de Equipamento , Humanos , Limite de Detecção , Microeletrodos , Oxirredução
10.
J Pharm Biomed Anal ; 180: 113076, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-31896523

RESUMO

With the increased cases of multidrug- or rifampicin-resistant tuberculosis and co-infection with HIV globally, it is difficult to achieve ideal clinical responses because of poor drug absorption and drug-drug interactions. Herein, a bioanalytical UPLC-MS/MS method was developed and validated to quantify five anti-TB agents in human plasma samples for detecting blood drug concentrations to improve therapeutic effects. To overcome the matrix effects, stable isotope labeled analogue of each analyte was used for internal standardization. A simple single-step protein precipitation by acetonitrile was employed for the sample preparation, then the analytes including rifampicin, rifabutin, pyrazinamid, ethambutol, isoniazid and their isotope labeled internal standards (ILISs) were implemented on an HILIC silica column with a gradient mode. The linear range for each analyte was covering the peak drug concentration (Cmax) in the 20 times diluted plasma samples. The coefficient of variation of intra- and inter-day precision was less than 17.0 %, and the accuracy ranged between 91.5 and 110.0 %. The extraction recoveries of all agents were ≥90.2 %, and the matrix effects with internal standard-normalization for all agents were 97.1-110.0 %. The optimal blood sampling time was designed basing on the results of stability validation. This UPLC-MS/MS method with a run time of 3.5 min was successfully applied to routine therapeutic monitoring of the five anti-TB agents in patient plasma.


Assuntos
Antituberculosos/sangue , Monitoramento de Medicamentos/métodos , Etambutol/sangue , Isoniazida/sangue , Pirazinamida/sangue , Rifabutina/sangue , Rifampina/sangue , Infecções Oportunistas Relacionadas com a AIDS/sangue , Calibragem , Cromatografia Líquida de Alta Pressão/métodos , Monitoramento de Medicamentos/instrumentação , Humanos , Padrões de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrometria de Massas em Tandem/métodos , Tuberculose/sangue
11.
AIDS Behav ; 24(1): 284-290, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31758349

RESUMO

There is no gold standard for estimating antiretroviral therapy (ART) adherence. Feasible, acceptable, and objective measures that are cost- and time-effective are needed. US adults (N = 93) on ART for ≥ 3 months, having access to a mobile phone and internet, and willing to mail in self-collected hair samples, were recruited into a pilot study of remote adherence data collection methods. We examined the correlation of self-reported adherence and three objective remotely collected adherence measures: text-messaged photographs of pharmacy refill dates for pharmacy-refill-based adherence, text-messaged photographs of pills for pill-count-based adherence, and assays of home-collected hair samples for pharmacologic-based adherence. All measures were positively correlated. The strongest correlation was between pill-count- and pharmacy-refill-based adherence (r = 0.68; p < 0.001), and the weakest correlation was between self-reported adherence and hair drug concentrations (r = 0.14, p = 0.34). The three measures provide objective adherence data, are easy to collect, and are viable candidates for future HIV treatment and prevention research.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Monitoramento de Medicamentos/instrumentação , Prescrições de Medicamentos/estatística & dados numéricos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/psicologia , Cabelo/química , Adesão à Medicação/estatística & dados numéricos , Adolescente , Adulto , Feminino , Infecções por HIV/prevenção & controle , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Valor Preditivo dos Testes
12.
Anal Chim Acta ; 1096: 76-88, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31883594

RESUMO

In this work, we developed cerium oxide/tin oxide (CeO2/SnO2) nanocatalyst with the assistance of urea by a simple sonochemical method and utilized as an efficient electrode material for electrochemical sensing of anti-inflammatory drug 5-aminosalicylic acid (Mesalamine, MES). The CeO2/SnO2 nanoparticles (NPs) were systematically characterized in terms of their crystal structure, morphologies, and physicochemical properties using XRD, Raman, FESEM, HR-TEM, EDX, mapping, and XPS analysis. The characterization results clearly confirmed that the prepared NPs was formed in the phase of CeO2/SnO2 without any other impurities. The electrochemical properties of CeO2/SnO2 NPs were investigated by EIS, CV, and DPV techniques. The CeO2/SnO2 NPs (9.6 µA) modified GCE demonstrated an excellent and improved electrocatalytic activity in terms of higher anodic peak current and lower peak potential when compared to bare GCE (6.7 µA) and CeO2 NPs/GCE (8.2 µA) for the sensing of MES. The CeO2/SnO2 NPs/GCE shows broader linear response range and lower detection limit of 0.02-1572 µM and 0.006 µM, respectively. Moreover, other potentially interfering compounds such as a similar functional group containing biological substances and inorganic species have no interference effect towards MES sensing. In addition, the practicability of the CeO2/SnO2 NPs/GCE was tested by real sample analysis in commercial MES tablet, human urine, and serum samples with the appreciable recovery results.


Assuntos
Anti-Inflamatórios não Esteroides/sangue , Anti-Inflamatórios não Esteroides/urina , Cério/química , Mesalamina/sangue , Mesalamina/urina , Compostos de Estanho/química , Catálise , Monitoramento de Medicamentos/instrumentação , Técnicas Eletroquímicas/instrumentação , Eletrodos , Humanos , Limite de Detecção , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Sonicação
13.
Biosens Bioelectron ; 150: 111897, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31786018

RESUMO

Flexible wearable chemical sensors are emerging tools which target diagnosis and monitoring of medical conditions. One of the potential applications of wearable chemical sensors is therapeutic drug monitoring for drugs that have a narrow therapeutic range such as lithium. We have investigated the possibility of developing a fibre-based device for non-invasive lithium drug monitoring in interstitial fluid. A flexible cotton-based lithium sensor was coupled with a carbon fibre-based reference electrode to obtain a potentiometric device. In vitro reverse iontophoresis experiments were performed to extract Li+ from under porcine skin by applying a current density of 0.4 mA cm-2 via two electrodes. Carbon fibre-based reverse iontophoresis electrodes were fabricated and used instead of a conventional silver wire-based version and comparable results were obtained. The fibre-based Li+ sensor and reference electrodes were capable of determining the Li+ concentration in samples collected via reverse iontophoresis and the results compared well to those obtained by ion chromatography. Additionally, biocompatibility of the materials used have been tested. Promising results were obtained which confirm the possibility of monitoring lithium in interstitial fluid using a wearable sensor.


Assuntos
Antidepressivos/análise , Fibra de Algodão , Monitoramento de Medicamentos/instrumentação , Compostos de Lítio/análise , Técnicas Biossensoriais/instrumentação , Linhagem Celular , Fibra de Algodão/análise , Eletrodos , Estudos de Viabilidade , Humanos , Lítio/análise , Dispositivos Eletrônicos Vestíveis
14.
J Pharm Biomed Anal ; 177: 112853, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31499431

RESUMO

Tacrolimus (TAC) is an immunosuppressant for preventing solid-organ transplant rejection. Because of its narrow therapeutic window, analytical methods which can detect TAC in serum samples with high accuracy and reliability are required. In this study, specific aptamers (Apt122 and Apt125) for TAC were isolated via systematic evolution of ligands by exponential enrichment method using magnetic beads to immobilize the target. After determination of binding constants of aptamers by flow cytometry analysis, Apt122 was selected and labeled with ATTO 647 N as a fluorophore to develop a fluorescent sensing platform for detection of TAC using graphene oxide (GO) as a fluorescence quencher. The designed aptasensor could detect TAC in phosphate buffer saline (10 mM PBS) and serum samples with detection limits as low as 1.4 and 2.5 nM, respectively.


Assuntos
Aptâmeros de Nucleotídeos/química , Monitoramento de Medicamentos/métodos , Imunossupressores/sangue , Técnica de Seleção de Aptâmeros/métodos , Tacrolimo/sangue , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Monitoramento de Medicamentos/instrumentação , Estudos de Viabilidade , Corantes Fluorescentes/química , Grafite/química , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/química , Ligantes , Limite de Detecção , Reprodutibilidade dos Testes , Tacrolimo/administração & dosagem , Tacrolimo/química
15.
J Pharm Biomed Anal ; 177: 112842, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31526960

RESUMO

BACKGROUND: Anti-drug-antibodies (ADA) against infliximab are frequently measured in patients receiving infliximab treatment with loss of response and undetectable infliximab concentrations. Different ADA bridging assays (1st generation, 2nd generation and ready-to-use kit) have been developed successively and were applied over the last 10 years, making comparison between ADA concentrations very challenging. A cutoff of 8 µg/ml was established to discriminate low from high ADA concentrations using the 1st generation ADA bridging assay. The objective of this study was to enable comparison of ADA concentrations determined with the different assays that were developed over the years. METHODS: 166 serum samples were collected from patients with inflammatory bowel disease treated with infliximab. 98 samples were measured simultaneously with the 1st and 2nd generation ADA assay, 67 serum samples were measured with the 2nd generation assay and the ready-to-use kit. RESULTS: From our ADA concentration comparison experiments, we deduced that the previously established cutoff of 8 µg/ml with the 1st generation ELISA has a similar impact as the cutoff of 374 ng/ml with the 2nd generation ELISA and a cutoff of 119 ng/ml in the ready-to-use ELISA kit. CONCLUSION: ADA concentrations measured with the different assays were compared and a cutoff concentration was determined for each of them to distinguish between low and high ADA concentrations. These cutoff concentrations may serve as a tool for clinicians to make treatment decisions for patients with a loss of response to infliximab and undetectable infliximab serum concentrations.


Assuntos
Anticorpos/sangue , Monitoramento de Medicamentos/métodos , Fármacos Gastrointestinais/imunologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/imunologia , Anticorpos/imunologia , Calibragem , Tomada de Decisão Clínica/métodos , Monitoramento de Medicamentos/instrumentação , Monitoramento de Medicamentos/normas , Resistência a Medicamentos , Ensaio de Imunoadsorção Enzimática/instrumentação , Ensaio de Imunoadsorção Enzimática/métodos , Ensaio de Imunoadsorção Enzimática/normas , Estudos de Viabilidade , Fármacos Gastrointestinais/administração & dosagem , Humanos , Doenças Inflamatórias Intestinais/sangue , Doenças Inflamatórias Intestinais/imunologia , Infliximab/administração & dosagem , Sensibilidade e Especificidade
16.
Am J Emerg Med ; 38(3): 503-507, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31221474

RESUMO

BACKGROUND: The most recent guidelines on prescribing opioids from the United States Centers for Disease Control recommend that clinicians not prescribe opioids as first-line therapy for chronic non-cancer pain. If an opioid prescription is considered for a patient already on opioids, prescribers are encouraged to check the statewide prescription drug monitoring database (PDMP). Some additional guidelines recommend screening tools such as the Current Opioid Misuse Measure (COMM) which may also help identify drug-aberrant behaviors. OBJECTIVE: To compare the PDMP and the Current Opioid Misuse Measure (COMM), a commonly-recommended screening tool for patients on opioids, in detecting drug-aberrant behaviors in patients already taking opioids at the time of ED presentation. METHODS: Patients on opioids were enrolled prospectively in a mixed urban-suburban ED seeing approximately 65,000 patients per year. The sensitivity, specificity, likelihood ratios, and diagnostic odds ratios of the PDMP and COMM were compared against objective criteria of drug-aberrant behaviors as documented in the electronic medical record (EMR) and medical examiner databases. RESULTS: Compared to the COMM, the PDMP had similar sensitivity (36% vs 45%) and similar specificity (79% vs 55%), but better positive predictive value, better negative predictive value, and better diagnostic odds ratio. The combination of the PDMP and the COMM did not improve the detection of drug-aberrant behaviors. CONCLUSIONS: The PDMP alone is a more useful as a screening instrument than either the COMM or the combination of the PDMP plus COMM in patients already taking opioids at time of ED presentation. However, the PDMP misses a majority of patients with documented drug-aberrant behaviors in the EMR, and should not be used in isolation to justify whether a particular opioid prescription is appropriate.


Assuntos
Analgésicos Opioides/administração & dosagem , Bases de Dados Factuais/normas , Monitoramento de Medicamentos/instrumentação , Transtornos Relacionados ao Uso de Opioides/diagnóstico , Uso Indevido de Medicamentos sob Prescrição/prevenção & controle , Adulto , Dor Crônica , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica , Valor Preditivo dos Testes , Estudos Prospectivos , Medição de Risco , Inquéritos e Questionários
17.
Rev. Pesqui. (Univ. Fed. Estado Rio J., Online) ; 12: 468-475, jan.-dez. 2020. ilus, tab
Artigo em Inglês, Português | LILACS, BDENF - Enfermagem | ID: biblio-1087433

RESUMO

Objetivo: a avaliação da cultura de segurança do paciente permite aos hospitais identificar e gerir prospectivamente questões relevantes de segurança em suas rotinas de trabalho. Método: estudo quantitativo, transversal e descritivo, ocorrida no ano de 2017 na Unidade de Terapia Intensiva Adulta em um hospital privado, localizado em Niterói/RJ. A população foram os profissionais médicos e equipe de enfermagem, utilizando análise estatística por meio de programa R, com a interface Rcmdr. Resultados: baseados nas respostas às perguntas sobre notificação de eventos aplicada com a Pesquisa de Cultura de Segurança do Paciente a 97 profissionais, com uma taxa de resposta de 85,6%, correspondendo a 83 profissionais. Menos de 45% dos participantes da pesquisa sempre notificam um erro, engano ou falha, que afete ou não o paciente, 59,0% não fizeram nenhuma notificação nos últimos 12 meses antecedentes à pesquisa e não houve diferença significativa na quantidade de notificação que destacasse uma categoria profissional, graduados ou não. Discussão: houve maior adesão à notificação de eventos pelos com maior tempo de hospital e com maior tempo naquela terapia intensiva. Não se encontrou correlação do número de notificações relatadas com o tempo de profissão e com a carga horária de trabalho. Conclusão: no que tange à conscientização de incrementar a adesão à notificação de eventos, a análise realizada contribuiu para a melhoria da segurança do paciente


Objective: ealuating the patient's safety culture allows hospitals to identify and manage relevant safety issues prospectively in their work routines. Method: a quantitative, transversal and descriptive study, carried out in 2017 at the Adult Intensive Care Unit in a private hospital, located in Niterói / RJ. The population were medical professionals and nursing staff, using statistical analysis through program R, with the Rcmdr interface. Results: based on responses to questions about event notification applied with the Patient Safety Culture Survey to 97 professionals, with a response rate of 85.6%, corresponding to 83 professionals. Less than 45% of respondents report an error, deception, or failure, affecting the patient, 59.0% did not report in the last 12 months prior to the survey, and there was no significant difference in the amount of notification that stood out a professional category, graduates or not. Discussion: there was greater adherence to the notification of events by those with longer hospital time and with more time in that intensive therapy. There was no correlation between the number of reports reported with the time of profession and the workload. Conclusion: with regard to the awareness of increasing adherence to event notification, the analysis performed contributed to the improvement of patient safety


Objetivo: la evaluación de la cultura de seguridad del paciente permite a los hospitales identificar y gestionar prospectivamente cuestiones relevantes de seguridad en sus rutinas de trabajo. Método: estudio cuantitativo, transversal y descriptivo, ocurrido en el año 2017 en la Unidad de Terapia Intensiva Adulta en un hospital privado, ubicado en Niterói / RJ. La población fueron los profesionales médicos y equipo de enfermería, utilizando análisis estadístico por medio del programa R, con la interfaz Rcmdr. Resultados: basados en las respuestas a las preguntas sobre notificación de eventos aplicada con la Encuesta de Cultura de Seguridad del Paciente a 97 profesionales, con una tasa de respuesta del 85,6%, correspondiendo a 83 profesionales. En la mayoría de los casos, la mayoría de las personas que sufren de la enfermedad de Alzheimer, una categoría profesional, graduados o no. Discusión: hubo mayor adhesión a la notificación de eventos por los con mayor tiempo de hospital y con mayor tiempo en aquella terapia intensiva. No se encontró correlación del número de notificaciones relatadas con el tiempo de profesión y con la carga horaria de trabajo. Conclusión: en lo que concierne a la concientización de incrementar la adhesión a la notificación de eventos, el análisis realizado contribuyó a la mejora de la seguridad del paciente


Assuntos
Humanos , Monitoramento de Medicamentos/instrumentação , Segurança do Paciente/estatística & dados numéricos , Estudos Transversais , Fatores de Risco , Sistemas de Notificação de Reações Adversas a Medicamentos/tendências , Medição de Risco , Unidades de Terapia Intensiva
18.
PLoS One ; 14(11): e0224751, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31738773

RESUMO

BACKGROUND: The COBAS AmpliPrep/COBAS TaqMan assay HCV (CAP/CTM) is widely used in clinical routine for HCV testing. Recently, the new cobas HCV test was established for high throughput testing with minimal operator intervention. As different assays may yield different quantitative/qualitative results that possibly impact treatment decisions, the aim of this study was to externally evaluate the cobas HCV test performance in comparison to CAP/CTM in a clinically relevant setting. METHODS: Serum samples were obtained from 270 patients who received direct acting antiviral therapy with different treatment regimens at two study sites (Hannover and Frankfurt) in 2016. Overall, 1545 samples (baseline, on-treatment and follow-up) were tested in parallel by both assays. RESULTS: The mean difference between cobas HCV and CAP/CTM for the quantification of HCV RNA was 0.008 log10 IU/ml HCV RNA (95% limits of agreement: -0.02-0.036) showing excellent agreement of both assays. With respect to clinical cut offs (HCV RNA detectable vs. target not detected and HCV RNA above the lower limit of quantification (LLOQ) vs.

Assuntos
Antivirais/administração & dosagem , Monitoramento de Medicamentos/instrumentação , Hepacivirus/isolamento & purificação , Hepatite C Crônica/tratamento farmacológico , Carga Viral/efeitos dos fármacos , Adulto , Hepacivirus/genética , Hepatite C Crônica/sangue , Hepatite C Crônica/virologia , Ensaios de Triagem em Larga Escala/instrumentação , Humanos , Técnicas de Diagnóstico Molecular/instrumentação , RNA Viral/genética , RNA Viral/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real/instrumentação
20.
Methods Enzymol ; 629: 151-176, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31727238

RESUMO

Over the past two decades there have been tremendous advances in our understanding of tumor immunology, which have in turn led to new and exciting immunology-based therapeutics. However, further research is needed into the dynamics and regulation of the immune response in the tumor microenvironment in order to achieve the full potential of these agents in treating all cancer patients. Defining the role of cytokines, chemokines, and other soluble mediators will be essential to this endeavor. This chapter describes, in detail, the technical protocol and applicability of LEGENDplex™ bead-based multiplex assays in quantifying these critical signaling molecules.


Assuntos
Biomarcadores Tumorais/análise , Quimiocinas/análise , Citometria de Fluxo/métodos , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/imunologia , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Quimiocinas/imunologia , Quimiocinas/metabolismo , Monitoramento de Medicamentos/instrumentação , Monitoramento de Medicamentos/métodos , Citometria de Fluxo/instrumentação , Humanos , Imunoensaio/instrumentação , Imunoensaio/métodos , Neoplasias/sangue , Neoplasias/imunologia , Neoplasias/patologia , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia
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