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1.
Ann Pharm Fr ; 81(1): 115-122, 2023 Jan.
Artigo em Francês | MEDLINE | ID: mdl-35952848

RESUMO

Clinical pharmacy procedures are clearly defined by the French society of clinical pharmacy. However, clinical pharmacists do not have efficient tools for their traceability. This need has increased following the publication of the instruction on the day hospital management of patients. Indeed, the action of the clinical pharmacist is included in it. In order to improve our traceability of clinical pharmacy acts and to take advantage of the implementation of the instruction, we worked with the medical information department to integrate our activity into their business software and to model the pathways valued by the intervention of the clinical pharmacist in outpatient care and in day hospital.


Assuntos
Serviço de Farmácia Hospitalar , Farmácia , Humanos , Retroalimentação , Atenção à Saúde , Farmacêuticos , Computadores
2.
Ann Pharm Fr ; 81(6): 1018-1030, 2023 Nov.
Artigo em Francês | MEDLINE | ID: mdl-37391030

RESUMO

Clinical decision support systems (CDSS) are tools that have been used for several years by clinical pharmacy teams to support pharmaceutical analysis, with a perspective of contributing to the quality of care in collaboration with the other health care team members. These tools require both technical, logistical and human resources. The growing use of these systems in different establishments in France and in Europe gave birth to the idea of meeting to share our experiences. The days organized in Lille in September 2021 aimed at proposing a time of exchange and reflection on the use of these CDSS in clinical pharmacy. A first session was devoted to feedback from each establishment. These tools are essentially used to optimize pharmaceutical analysis and to secure patient medication management. This session outlined the clear advantages and common limitations of these CDSS. Two research projects were also presented to put the use of these tools into perspective. The second session of these days, in the form of workshops, addressed 4 themes that surround the implementation of CDSS: their usability, the legal aspect, the creation of rules and their possible valorization. Common problems were raised, the resolution of which requires close collaboration. This is a first step proposing a beginning of harmonization and sharing that should be deepened in order not to lose the dynamics created between the different centers. This event ended with the proposal to set up two working groups around these systems: the creation and structuring of rules for the detection of risk situations and the common valorization of the work.

3.
Ann Pharm Fr ; 80(2): 187-199, 2022 Mar.
Artigo em Francês | MEDLINE | ID: mdl-33992642

RESUMO

OBJECTIVES: To perform an ergonomic intervention using the methodology of the analysis of the activity of the training process of clinical pharmacy residents in the analysis of prescriptions. METHODS: The evaluation was carried out over two semesters: from May to October 2016 (first study) and from November 2016 to April 2017 (second study). The interviews and observations were conducted by an ergonomist who is an expert in this type of evaluation. The first study was based on observations of the training process and interviews at different time. The second study allowed to support pharmacists and evaluate the changes following the recommendations of the previous study. RESULTS: A total of 6 and 9 residents participated in the first and second study, respectively. During the first study, 6 difficulties were raised which allowed implementation decisions. Feedback from residents on the training process was generally positive for the first part of the training but negative for the last part. The average number of fears expressed by the residents was higher at the beginning (2.9 fears) than at the end (1 fear). CONCLUSIONS: The training process has been adapted to the expectations and feelings of the residents. Follow-up at the beginning and throughout the internship was essential. The next stage of this work will be to evaluate the contribution of the dashboards for monitoring clinical pharmacy skills in the new degree for hospital pharmacy.


Assuntos
Serviço de Farmácia Hospitalar , Farmácia , Ergonomia , Humanos , Farmacêuticos , Prescrições
4.
Ann Pharm Fr ; 77(3): 250-263, 2019 May.
Artigo em Francês | MEDLINE | ID: mdl-30665679

RESUMO

OBJECTIVES: Evaluate the level of knowledge and perceptions of French and Quebec hospital's pharmacists/residents about bibliometrics indicators applied in pharmacy. Identify the determinants associated with this knowledge. METHODS: This is a descriptive cross-sectional study. An anonymous questionnaire of 17 questions answers was developed. The questionnaire was published on the SurveyMonkey site (www.SurveyMonkey.com, SurveyMonkey, Portland, OR, USA) and released from March 19 to April 9, 2018. We calculated and compared the proportion of respondents in Quebec and France by using a Chi2 test. A value less than 0.05 is considered statistically significant. RESULTS: A total of 899 pharmacists (646 in Quebec and 253 in France) and 147 residents (70 in Quebec and 77 in France) were contacted by email. The survey was completed by 401 respondents, e.g., 301 in Quebec (participation rate: 42%) and 100 in France (30%). Overall 26% (106/401) of respondents (67/301 in Quebec vs. 39/100 in France) reported having knowledge or good knowledge of those indicators. These data are corroborated by many other results. CONCLUSIONS: Small proportions are aware of those indicators. A good knowledge is associated with being a French pharmacist, working in a teaching hospital or university, having a professional experience of 10 years or more, be involved in a research project, having a scientific watch or having an online profile on database. It appears necessary to inform pharmacists and residents on notoriety indicators.


Assuntos
Bibliometria , Conhecimentos, Atitudes e Prática em Saúde , Publicações Periódicas como Assunto/normas , Farmacêuticos , Residências em Farmácia , Farmácia/normas , Atitude do Pessoal de Saúde , Estudos Transversais , França , Hospitais Universitários , Quebeque , Estudantes de Farmácia , Inquéritos e Questionários
5.
Ann Pharm Fr ; 76(1): 71-77, 2018 Jan.
Artigo em Francês | MEDLINE | ID: mdl-29145996

RESUMO

OBJECTIVES: The manipulation of drugs from glass ampules can generate particles when the ampule is broken. Several authors recommend the use of filter needle to withdraw the drug content. The main objective is to establish an inventory of the use of filter needles and the perception of pharmacists in Quebec and in France. METHODS: This is a cross-sectional descriptive study. A questionnaire was sent to all health facilities in Quebec (n=30) and a selection of hospitals in France (n=100). Respondents were asked to answer a questionnaire that included policies and procedures on the use of these medical devices and the conditions of their use at the pharmacy and in healthcare services. RESULTS: In total, 27 respondents from Quebec (response rate: 90%) and 41 respondents from France (response rate: 41%) participated in our survey. In Quebec, all exploitable questionnaires except one (42/43) used five micron filter needles at the pharmacy against 28% of utilisation in healthcare services. In France, this practice is nearly ignored. CONCLUSIONS: Action should be taken to decide on the use of filter needles including studies to confirm the consequences of the presence of these particles on an animal model, discussions with regulatory authorities to clarify the situation, incentives for manufacturers to use vials.


Assuntos
Embalagem de Medicamentos , Filtração/estatística & dados numéricos , Agulhas/estatística & dados numéricos , Estudos Transversais , Contaminação de Medicamentos , França , Humanos , Serviço de Farmácia Hospitalar , Quebeque , Inquéritos e Questionários
6.
Ann Pharm Fr ; 76(1): 3-15, 2018 Jan.
Artigo em Francês | MEDLINE | ID: mdl-28800916

RESUMO

OBJECTIVES: The manipulation of drugs from glass ampules can generate particles when the ampule is broken. Several authors recommend the use of filter needle to withdraw the drug content. The aim of this study is to make an assessment of the presence of particles during the manipulation of glass ampules and to discuss the current practices. METHODS: Literature review based on a search strategy (Pubmed, Google Scholar) and a summary table of available data. Analysis to evaluate the efficacy of the filtration when data are available. RESULTS: Eighteen articles have been included. Most of study shows the presence of particles in glass ampules. Important discrepancies reported regarding the number of particles per ampule. Analysis of data from seven studies: decrease of 83% of the total number of particles (>10µm) identified when drugs are removed with filter needle. All studies but two confirm the efficacy of filter needles. CONCLUSIONS: Studies show the presence of particles when drugs are removed from glass ampules. They do not allow to make a conclusion on human clinical consequences associated with the presence of particles. It is necessary to evaluate in human the risks associated with particle contamination to determine the optimal use of filter needle.


Assuntos
Contaminação de Medicamentos , Embalagem de Medicamentos , Material Particulado/análise , Filtração , Vidro , Humanos
7.
Acta Anaesthesiol Scand ; 59(2): 197-204, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25476454

RESUMO

BACKGROUND: International guidelines recommend noradrenaline (NA) as the vasopressor of choice to treat septic shock. The aim of this study was to determine the best way to infuse patients with NA. METHODS: The in vitro study was designed to measure NA concentration at the end of each studied assembly line. Three infusion systems used the double pump method and three single pumps, which differed as regards NA concentrations (0,2 - 0,5 - 1 mg/h), dead space volume of the devices and the use of saline. Infusion systems were compared according to the time necessary to reach an NA mass flow rate steady-state plateau after the onset of infusion or after a flow change. RESULTS: Times were significantly different between the six methods for infusing NA. The system using the double syringe method with a standard extension set was the longest to reach the steady state after the onset of infusion [40.00 min (19.57 - 49.22)]. The steady-state plateau was obtained most rapidly with the double-syringe pump systems using very low dead-space volume extension sets and single-syringe pump systems containing diluted noradrenaline at the beginning of NA infusion. CONCLUSION: A combination of a low dead-space volume extension set and a double pump method with a constant saline flow rate at 5 ml/h might be the solution to provide the most reliable NA infusion delivery.


Assuntos
Sistemas de Liberação de Medicamentos/instrumentação , Bombas de Infusão , Norepinefrina/administração & dosagem , Vasoconstritores/administração & dosagem , Desenho de Equipamento , Humanos , Técnicas In Vitro , Infusões Intravenosas/instrumentação , Seringas , Fatores de Tempo
8.
Ann Pharm Fr ; 73(4): 277-80, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25863599

RESUMO

An in vitro study was carried out to determine the anti-Xa activity of heparin in binary parenteral nutrition (BPN) admixtures for premature neonates in our neonatal intensive care unit (NICU) after a 24-hour infusion, as well as to assess drug interaction with a 50% glucose solution. Two types of bags were prepared: (1) BPN admixtures (composition defined in the NICU) including sodium heparin at 77 UI/mL and (2) bags containing only G50% with sodium heparin at 193 UI/mL. The anti-Xa activity of heparin was measured in bags at T0, after the 24-hour infusion and in eluates at the outlet of the infusion line after 24hours, using a validated chromogenic anti-Xa method. Comparisons of the mean concentration observed with the theoretical value for anti-Xa activity were performed with the Student t-test. Mean values of anti-Xa activity do not differ significantly from the values expected for all conditions. We found a slight variation in anti-Xa activity when infused over 24hours for both types of bags, with and without in-line filtration, showing that heparin remains stable during this infusion period in both BPN admixtures and G50%.


Assuntos
Anticoagulantes/farmacologia , Fator Xa/metabolismo , Alimentos Formulados/análise , Heparina/farmacologia , Nutrição Parenteral , Testes de Coagulação Sanguínea , Filtração , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal
9.
Anaesthesia ; 69(2): 131-6, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24387829

RESUMO

The aim of our in-vitro study was to assess the impact of infusion set characteristics on the accuracy of morphine doses in patient-controlled analgesia. Two infusion sets differing in conception and dead-space volume were assessed: a standard set and a low dead-space volume Y-set. The patient-controlled analgesia programme parameters were as follows: bolus equal to 1 ml at 100 ml.h(-1) ; lockout intervals equal to 5 and 10 min; and carrier fluid flow rate equal to 10 and 50 ml.h(-1) . Morphine concentration was determined by an ultraviolet spectrophotometric method. The morphine doses were significantly different from one set to the other during bolus and lockout intervals, whatever the patient-controlled analgesia programme. The average doses were approximately 1.3-6.0 times higher with the low dead-space volume Y-set during bolus. Our study underlines the impact of infusion set characteristics on the accuracy of morphine patient-controlled analgesia doses.


Assuntos
Analgesia Controlada pelo Paciente/instrumentação , Analgésicos Opioides/administração & dosagem , Morfina/administração & dosagem , Analgesia Controlada pelo Paciente/métodos , Esquema de Medicação , Desenho de Equipamento , Humanos , Bombas de Infusão , Infusões Intravenosas , Reprodutibilidade dos Testes , Espectrofotometria Ultravioleta/métodos
10.
Ann Pharm Fr ; 71(4): 243-8, 2013 Jul.
Artigo em Francês | MEDLINE | ID: mdl-23835022

RESUMO

INTRODUCTION: For 1 year, our unit has been equipped with portable H2O2 Dräger detectors contributing to protect the staff from a possible exposure to this odourless and toxic gas. This work shows the current available data about H2O2 toxicity, describes the organization of the implementation and the analysis of the values measured over 12 months. MATERIAL AND METHODS: Data about H2O2 toxicity have been obtained through a literature review. The measured values are presented in instantaneous value and occupational exposure limit (OEL) over 8 h. RESULTS: Over six technicians, the average percentage, of detected values superior to zero reached 1.06% in August. The detected maximum instantaneous value reached 2.2 ppm in May. These isolated exposures have little incidence when related to the 8-h exposure with an occupational exposure limit (OEL) of 0.072 ppm over 12 months. DISCUSSION AND CONCLUSION: The implementation of this tool has allowed to highlight a technical problem of the sterilization airlock that could be resolved. This measuring device of H2O2 concentration in the air in real time allows to secure everyday working conditions and to alert the staff of a possible technical failure. However, literature data regarding chronic toxicity are limited and restrict the analysis of the measured values.


Assuntos
Antineoplásicos , Composição de Medicamentos , Peróxido de Hidrogênio/análise , Poluição do Ar em Ambientes Fechados/análise , Animais , Cães , Monitoramento Ambiental , Humanos , Exposição Ocupacional/prevenção & controle , Ratos , Esterilização
11.
Eur J Drug Metab Pharmacokinet ; 36(4): 197-203, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21842319

RESUMO

Gravity-fed infusion (GFI) systems are acknowledged as being unable to keep their flow-rate constant. This may affect drug plasma levels such as aminoglycosides. Numerous factors have previously been cited, but their relative importance has never been quantified so far. The objective of this work is to identify the main factors that influence GFI in vitro outflow and to propose a mathematical model of flow-rate evolution as a function of time. In this model, pressure loss and infusion device creep have been considered as the main variation factors. Concomitantly, two experiments were undertaken. Firstly, the flow-rate evolution of an in vitro infusion of 250 mL of dextrose 5% was assessed. Secondly, the creep occurring on an infusion device was measured through a stress relaxation experiment. The experimental infusion flow-rate decreased by as much as 28.5% over 1 h. Simulated and experimental data are well correlated (r = 0.987; P < 0.0001). The maximum creep effect happens during the first 15 min of infusion. In this work, height of the liquid in the bag and tube creep were found to be the main variation factors in GFI flow-rate. This new mathematical model should help to explain the differences observed in drug plasma levels with gravity-fed devices.


Assuntos
Infusões Intravenosas/métodos , Gravitação , Humanos , Modelos Teóricos , Farmacocinética , Soluções
12.
Int J Med Inform ; 155: 104568, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34537687

RESUMO

BACKGROUND: Clinical decision support systems (CDSSs) can improve the quality of patient care by helping physicians to review their prescriptions and thus to optimize drug treatments. Nevertheless, the "alert fatigue" brought on by a large number of irrelevant alerts can decrease a CDSS's effectiveness and thus clinical value. Involving a clinical pharmacist in the development and management of a CDSS can reduce the number of irrelevant alerts presented to physicians. Clinical pharmacists screen alerts and suggest PIs for physicians, corresponding to any proposed therapeutic change about health products, only for relevant alerts could improve the relevance and the acceptance of the information given to physicians about the risks faced by their patients. OBJECTIVE: To assess the value of involving clinical pharmacists in the development and maintenance of decision support rules for generating alerts and pharmaceutical interventions (PIs) and to describe the level of acceptance of these PIs by the physicians. METHOD: In a retrospective, single-centre study, we evaluated the number of PIs accepted from alerts generated by the CDSS when a clinical pharmacist had developed and managed this tool. During the first 7 months of development of the CDSS, a clinical pharmacist analyzed alerts triggered by the CDSS according to its technical validity and pharmaceutical relevance. Lastly, for alerts that led to a PI, the level of acceptance by physicians was documented. RESULTS: During the study, 1430 alerts were analysed: 186 (13%) were considered to be technically invalid - mainly due to the characteristics of the interface. Of the 1244 (87.0%) technically valid alerts, 353 (24.6%) were pharmaceutically relevant and led to a PI. The three main causes of pharmaceutical irrelevance were a lack of specificity in the CDSS (70.8%), lack of relevance with regard to the ward's habits (15.6%), and the pharmacist's decision to recommend monitoring for the patient rather than sending a PI immediately (10.8%). 64.6% of the submitted PIs were accepted by the physicians. CONCLUSION: The standardized analysis of alerts by a clinical pharmacist appears to be a good way of improving the development of CDSS by limiting the generation of irrelevant alerts and the latter's transmission to physicians. The involvement of a clinical pharmacist in the development and implementation of a CDSS appears to be novel and may help to optimize drug treatment.


Assuntos
Sistemas de Apoio a Decisões Clínicas , Médicos , Humanos , Farmacêuticos , Estudos Retrospectivos
13.
Pulm Pharmacol Ther ; 23(4): 324-6, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20307680

RESUMO

Aminoglycosides are broad-spectrum antibiotics with peak-dependent bactericidal activity, administered by gravity infusion or for more accuracy by electronic pump infusion. The aim of this study was to assess the difference between the two systems and its pharmacokinetic impact. Twenty-four patients hospitalised for community-acquired pulmonary infections received amikacin by IV route over 1 h with a targeted peak concentration of 35 mg/L. They were randomly distributed into two groups, one receiving infusion through a pump system, the other by gravity. Amikacin serum levels were determined at the end of infusion and 24 h later. C(max) values were significantly lower with gravity than pump (40.2 +/- 12.3 vs. 50.6 +/- 17.6 mg/L, respectively; p = 0.04). Elimination half-life time, volume of distribution and clearance did not differ significantly from one group to the other. The percentage of patients who failed to achieve the targeted peak concentration was significantly higher with gravity than pump (41.7% vs. 16.7%, respectively; p < 0.001). Improving infusion flow-rate provides better control over amikacin C(max). This study underlines the fact that infusion device characteristics should be added to the physiopathological information of a patient if we are to make a better estimation of pharmacokinetic parameters.


Assuntos
Amicacina/farmacocinética , Antibacterianos/farmacocinética , Infecções Bacterianas/tratamento farmacológico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Amicacina/administração & dosagem , Antibacterianos/administração & dosagem , Feminino , Meia-Vida , Humanos , Bombas de Infusão , Infusões Intravenosas , Pneumopatias/tratamento farmacológico , Pneumopatias/microbiologia , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Distribuição Tecidual
14.
J Clin Pharm Ther ; 35(4): 395-400, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20831542

RESUMO

BACKGROUND: Treatment of anaemia in renal-insufficient patients relies on the use of an erythropoiesis-stimulating agent (ESA). This study aimed to compare the impact of two different strategies of ESA prescribing on variation in haemoglobin (Hb) concentration in end-stage renal disease (ESRD) patients. METHODS: Patients with ESRD, on haemodialysis, and who had received ESA for >3 months were recruited. Different parameters were analysed: demographics, Hb level the last day of the year before dialysis, the most recent weekly ESA dose, risk factors for resistance and cost. Each institution continued its local practice for achieving the desired Hb level: increasing the ESA dose to overcome resistance in one centre and defining an upper ESA-dose limit in the other. RESULTS: A total of 185 patients were recruited. No significant differences in the biological parameters were found between the two populations. In both centres, Hb levels were comparable and mean levels exceeded 11 g/dL, despite the higher ESA doses given in one centre to achieve this target. This finding also held true for the subgroups with greater than or equal to two resistance factors. These two strategies led to large between-centre differences in treatment costs. CONCLUSION: The ESA-use strategy difference probably indicates that erythropoietin-resistance was not overcome with increased dosing. The Hb concentrations remained stable even when ESA doses were increased. On current evidence, the cheaper ESA-dose limitation strategy is preferable but randomized controlled studies, including comparisons of alternative ESA formulations are necessary.


Assuntos
Anemia/tratamento farmacológico , Hematínicos/uso terapêutico , Falência Renal Crônica/terapia , Idoso , Anemia/economia , Anemia/etiologia , Darbepoetina alfa , Relação Dose-Resposta a Droga , Esquema de Medicação , Epoetina alfa , Eritropoetina/administração & dosagem , Eritropoetina/análogos & derivados , Eritropoetina/economia , Eritropoetina/uso terapêutico , Feminino , França , Hematínicos/administração & dosagem , Hematínicos/economia , Humanos , Pacientes Internados , Falência Renal Crônica/economia , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes , Diálise Renal/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento
15.
Data Brief ; 33: 106474, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33251299

RESUMO

The dataset displays the pharmacokinetics data obtained from the TRACES pilot study. The nine patients included were undergoing haemorrhagic caesarean section (blood loss > 800 mL) and receiving a single i.v dose of tranexamic acid (0.5, 1 or 2 g over 1 min). The dataset gathers the tranexamic acid blood and urinary concentrations. With these first elements, a pharmacokinetic compartment model was built as described in Gilliot et al. and the individual pharmacokinetic parameters were estimated. In parallel, the patients anthropometric, biological, and clinical characteristics were collected. The correlation between the patient data and the estimated individual pharmacokinetic parameters were tested. The correlation tests revealed that the dose, the height, the body weight, and the ideal bodyweight had and impact on the volume of distribution of tranexamic acid. According to these results, these latter covariates were explored using a multi-regression analysis in Gilliot et al.

16.
Eur J Pharm Sci ; 153: 105486, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32717429

RESUMO

BACKGROUND: In previous studies, the choice of doses of tranexamic acid was empirically defined as no pharmacokinetic study had been conducted in haemorrhagic caesarean section. OBJECTIVE: The objective was to build a pharmacokinetic model in patients receiving a single 0.5, 1 or 2 g intravenous bolus. METHOD: A preliminary monocentric open study was performed in the Lille centre. Blood samples and one urinary sample were collected in the 6 h following the injection. Nine patients were included. Tranexamic acid concentration was measured using liquid chromatography system coupled with tandem mass spectrometry. We used Monolix 2019R1 for population pharmacokinetic modelling. A structural model was constructed followed by the investigation of potential covariates. RESULTS: Data were best described with a two-compartment model with a double first-order elimination from the central compartment. The model was improved when the variable ideal weight per dose was affected as a covariate for the apparent volume of distribution. Assuming a dose of 1 g and a height of 160 cm, the pharmacokinetic parameters were estimated at 10.26 L.h-1 for total clearance, 11.5 L for the volume of the central compartment, 15.8 L for the volume of the second compartment, a diffusional clearance of 30.36 L.h-1 , and a urinary excretion fraction of 25.8%. CONCLUSIONS: The population pharmacokinetic model of tranexamic acid in haemorrhagic caesarean section was successfully established in our tiny sample of patients. The results of this preliminary TRACES pharmacokinetic study suggested that elimination of tranexamic acid is partially non urinary in contrast with healthy patients.


Assuntos
Obstetrícia , Ácido Tranexâmico , Cesárea , Feminino , Humanos , Injeções Intravenosas , Gravidez
18.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1093-1094: 158-166, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30029202

RESUMO

Ibrutinib is an orally administered first-in-class irreversible Bruton's tyrosine kinase (BTK) covalent inhibitor for the treatment of patients with B-cell malignancies. Several isolated clinical observations reported its efficacy in central nervous system dissemination. Herein, we described the development and validation of an ultra-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) procedure for the quantification of ibrutinib and its active metabolite PCI-45227 in cerebrospinal fluid (CSF). This is the first complete validated method for quantification of ibrutinib and PCI-45227 in CSF. The compounds were eluted on a Waters BEH C18 column (50.0 × 2.1 mm; 1.7 µm) using a gradient elution with a mobile phase composed of ammonium formate buffer 5 mM pH 3.2 and acetonitrile +0.1% formic acid with a flow rate of 400 µL·min-1. Two deuterated internal standards were used to obtain the most accurate quantification. The CSF samples were prepared by a simple and rapid dilution. The method was validated by testing the selectivity, response function, intra-day and inter-day precisions, trueness, limits of detection (LOD) and lower limits of quantification (LLOQ). The validation results proved that the methods were suitable to quantify ibrutinib and PCI-45227 in real biological CSF samples from 0.50 (ibrutinib) or 1.00 (PCI-45227) to 30.00 ng·mL-1. Furthermore, the developed method was adapted to allow the quantification of both compounds in plasma and the results were compared to those reported in literature. The plasmatic samples were treated by protein precipitation and the method was validated to quantify ibrutinib and PCI-45227 in real biological plasmatic samples from 5.00 to 491 ng·mL-1. Lastly, for both matrices, accuracy profiles were plotted from the trueness and precision results using a 20% α-risk (ß = 80%) and the tolerance intervals were comprised within the acceptance limits fixed at ±25% for the LLOQ and ±15% for the other concentrations. Finally, these methods were successfully applied to quantify ibrutinib and PCI-45227 in real human CSF and plasma samples.


Assuntos
Adenina/análogos & derivados , Cromatografia Líquida de Alta Pressão/métodos , Pirazóis/líquido cefalorraquidiano , Pirimidinas/líquido cefalorraquidiano , Espectrometria de Massas em Tandem/métodos , Adenina/sangue , Adenina/líquido cefalorraquidiano , Adenina/química , Adenina/uso terapêutico , Humanos , Limite de Detecção , Linfoma de Células B/tratamento farmacológico , Piperidinas , Pirazóis/sangue , Pirazóis/química , Pirazóis/uso terapêutico , Pirimidinas/sangue , Pirimidinas/química , Pirimidinas/uso terapêutico , Reprodutibilidade dos Testes
19.
Sci Rep ; 8(1): 14860, 2018 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-30291297

RESUMO

Monoclonal antibodies (mAbs) are key components in several therapies for cancer and inflammatory diseases but current knowledge of their clinical pharmacokinetics and distribution in human tissues remains incomplete. Consequently, optimal dosing and scheduling in clinics are affected. With sequential radiolabeled mAb-based imaging, radiation dosing in tissues/organs can be calculated to provide a better assessment of mAb concentrations in tissues. This is the first pharmacokinetic model of 90Y-Ibritumomab tiuxetan (90Y-IT) in humans to be described, based on three-dimensional (3D) dosimetry using single-photon emission computed-tomography coupled with computed-tomography. 19 patients with follicular lymphoma were treated initially with 90Y-IT in the FIZZ trial. Based on a compartmental approach individualising the vascular compartment within studied organs, this study proposes a reliable pharmacokinetic (PK) five-compartment model replacing the currently used two-compartment model and constitutes a new direction for further research. This model provides exchange constants between the different tissues, Area Under the Curve of 111In-IT in blood (AUC) and Mean Residence Time (MRT) that have not been reported so far for IT. Finally, the elimination process appears to occur in a compartment other than the liver or the spleen and suggests the metabolism of mAbs may take place mainly on the vascular compartment level.


Assuntos
Anticorpos Monoclonais/farmacocinética , Radioisótopos de Ítrio/farmacocinética , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/uso terapêutico , Feminino , Humanos , Linfoma Folicular/terapia , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Radiometria , Distribuição Tecidual , Tomografia Computadorizada de Emissão de Fóton Único , Radioisótopos de Ítrio/uso terapêutico
20.
Orthop Traumatol Surg Res ; 103(8): 1161-1167, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28964919

RESUMO

BACKGROUND: Patients are playing an increasingly large role in their own management and must therefore receive clear, complete, and comprehensible information. In the field of hip and knee arthroplasty, little is known about the level of patient knowledge and effectiveness of surgeon-to-patient information transfer. We therefore designed a prospective observational study with the objective of assessing four factors: patient knowledge during management, quality of information transfer, informational needs, and factors associated with the level of knowledge. HYPOTHESIS: The level of patient knowledge changes during the management process. PATIENTS AND METHODS: A prospective single-centre study was conducted between January 2014 and March 2015 during the outpatient visits and inpatient stays of 63 patients who underwent arthroplasty of the hip (n=36) or knee (n=27). A single observer attended all patient visits and recorded the information provided by the surgeon. Each patient completed a self-questionnaire after the outpatient visit (T1), at admission (T2), and at discharge after surgery (T3). Semi-quantitative scores were used to assess knowledge and informational needs. The effectiveness of information transfer was evaluated by comparing the information provided by the surgeon to the replies made by the patients. RESULTS: The mean overall knowledge score (on a 0-42 scale) increased from 17.22±6.33 at T1 to 19.44±6.89 at T3 (P=0.0028). In contrast, knowledge about complications was better at T1 than at T3 (2.67±1.98 vs. 2.19±1.91; P<0.05). Agreement between information given by the surgeon and replies made by patients varied across items from 23% to 100%. The mean informational needs score (on a scale from 0 to 21) ranged from 3.67 to 4.83 and was higher at T3 than at T2 (4.83±3.77 vs. 3.67±4.86; P=0.03). The proportion of patients who wanted written information was higher at T3. Most patients sought information before the outpatient visit. At each step of the management process, the main areas about which the patients wanted information were the surgical procedure, the rehabilitation programme, and the prosthesis. Several socio-demographic or management-related factors influenced the level of knowledge. Thus, older age and lower educational attainment were associated with lower knowledge scores, whereas previous lower-limb orthopaedic surgery and amount of information provided by the surgeon were associated with higher knowledge scores. Knowledge scores were not associated with being employed vs. retired, gender, replacement of a hip vs. a knee, the surgeon, or being accompanied by another person. DISCUSSION: Our study is original in that we assessed changes in patient knowledge during the management process for hip or knee arthroplasty. The level of patient knowledge was fairly low and varied considerably across individuals and time points in the management process. These data highlight the importance of providing patients with information throughout their management and particularly at discharge, when the desire for information seems greatest. LEVEL OF EVIDENCE: IV, prospective observational study with no control group.


Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Conhecimentos, Atitudes e Prática em Saúde , Educação de Pacientes como Assunto , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Quadril/efeitos adversos , Artroplastia de Quadril/reabilitação , Artroplastia do Joelho/efeitos adversos , Artroplastia do Joelho/reabilitação , Comunicação , Escolaridade , Feminino , Humanos , Comportamento de Busca de Informação , Masculino , Pessoa de Meia-Idade , Avaliação das Necessidades , Relações Médico-Paciente , Estudos Prospectivos , Inquéritos e Questionários
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