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1.
Lancet Haematol ; 7(2): e157-e167, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32004485

RESUMO

Graft-versus-host disease (GVHD) is a major factor contributing to mortality and morbidity after allogeneic stem-cell transplantation. Because of the small number of results from well designed, large-scale, clinical studies there is considerable variability in the prevention and treatment of GVHD worldwide. In 2014, to standardise treatment approaches the European Society of Blood and Marrow Transplantation published recommendations on the management of GVHD in the setting of HLA-identical sibling or unrelated donor transplantation in adult patients with haematological malignancies. Here we update these recommendations including the results of study published after 2014. Evidence was searched in three steps: first, a widespread scan of published trials, meta-analyses, and systematic reviews; second, expert opinion was added for specific issues following several rounds of debate; and third, a refined search to target debated or rapidly updating issues. On the basis of this evidence and the 2014 recommendations, five members of the EBMT Transplant Complications Working Party created 38 statements on GVHD prophylaxis, drug management, and treatment of acute and chronic GVHD. Subsequently, they created the EBMT GVHD management recommendation expert panel by recruiting 20 experts with expertise in GVHD management. An email-based, two-round Delphi panel approach was used to manage the consensus. Modified National Comprehensive Cancer Network categories for evidence and consensus were applied to the approved statements. We reached 100% consensus for 29 recommendations and 95% consensus for nine recommendations. Key updates to these recommendations include a broader use of rabbit anti-T-cell globulin; lower steroid doses for the management of grade 2 acute GVHD with isolated skin or upper gastrointestinal tract manifestations; fluticasone, azithromycin, and montelukast should be used for bronchiolitis obliterans syndrome; and the addition of newer treatment options for resteroid-refractory acute and chronic GVHD. In addition, we discuss specific aspects of GVHD prophylaxis and management in the setting of haploidentical transplantation and in paediatric patients, but no formal recommendations on those procedures have been provided in this Review. The European Society of Blood and Marrow Transplantation proposes to use these recommendations as a basis for the routine management of GVHD during stem-cell transplantation.


Assuntos
Doença Enxerto-Hospedeiro/prevenção & controle , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco/efeitos adversos , Gerenciamento Clínico , Monitoramento de Medicamentos , Resistência a Medicamentos , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia , Humanos , Imunossupressão/métodos , Imunossupressores/administração & dosagem , Imunossupressores/sangue , Imunossupressores/uso terapêutico , Transplante de Células-Tronco/métodos , Condicionamento Pré-Transplante/métodos
3.
J Clin Psychiatry ; 81(2)2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31995677

RESUMO

OBJECTIVE: A nominal group process followed by a modified Delphi method was used to survey expert opinions on best practices for tardive dyskinesia (TD) screening, diagnosis, and treatment and to identify areas lacking in clinical evidence. PARTICIPANTS: A steering committee of 11 TD experts met in nominal group format to prioritize questions to be addressed and identify core bibliographic materials and criteria for survey panelists. Of 60 invited experts, 29 (23 psychiatrists and 6 neurologists) agreed to participate. EVIDENCE: A targeted literature search of PubMed (search term: tardive dyskinesia) and recommendations of the steering committee were used to generate core bibliographic material. Inclusion criteria were as follows: (1) review articles, meta-analyses, guidelines, or clinical trials; (2) publication in English between 2007 and 2017; (3) > 3 pages in length; and (4) publication in key clinical journals with impact factors ≥ 2.0. Of 29 references that met these criteria, 18 achieved a score ≥ 5 (calculated as the number of steering committee votes multiplied by journal impact factor and number of citations divided by years since publication) and were included. CONSENSUS PROCESS: Two survey rounds were conducted anonymously through electronic media from November 2017 to January 2018; responses were collected, collated, and analyzed. Respondent agreement was defined a priori as unanimous (100%), consensus (75%-99%), or majority (50%-74%). For questions using a 5-point Likert scale, agreement was based on percentage of respondents choosing ≥ 4 ("agree completely" or "agree"). Round 1 survey included questions on TD screening, diagnosis, and treatment. Round 2 questions were refined per panelist feedback and excluded Round 1 questions with < 25% agreement and > 75% agreement (unless feedback suggested further investigation). CONCLUSIONS: Consensus was reached that (1) a brief, clinical assessment for TD should be performed at every clinical encounter in patients taking antipsychotics; (2) even mild movements in 1 body area may represent possible TD; (3) management requires an overall evaluation of treatment, including reassessment of antipsychotics and anticholinergics as well as consideration of vesicular monoamine transporter 2 (VMAT2) inhibitors; and (4) informed discussions with patients/caregivers are essential.


Assuntos
Antipsicóticos , Antagonistas Colinérgicos , Programas de Rastreamento/métodos , Conduta do Tratamento Medicamentoso/normas , Exame Neurológico/métodos , Discinesia Tardia , Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Antagonistas Colinérgicos/administração & dosagem , Antagonistas Colinérgicos/efeitos adversos , Consenso , Técnica Delfos , Monitoramento de Medicamentos/métodos , Monitoramento de Medicamentos/normas , Humanos , Guias de Prática Clínica como Assunto , Medição de Risco/métodos , Discinesia Tardia/induzido quimicamente , Discinesia Tardia/diagnóstico , Discinesia Tardia/terapia , Proteínas Vesiculares de Transporte de Monoamina/antagonistas & inibidores
4.
J Clin Psychiatry ; 81(2)2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31995679

RESUMO

Valbenazine and deutetrabenazine are FDA-approved as treatment for tardive dyskinesia (TD). Both medications are vesicular monoamine transporter type 2 (VMAT2) inhibitors, and both are effective for reducing TD symptoms. Clinicians need to be aware of the adverse effects of valbenazine and deutetrabenazine, as well as other key differences between the two, in order to individualize treatment. Using the Abnormal Involuntary Movement Scale assists clinicians in assessing progress for each patient. Treating TD effectively with these new medications will reduce the burden of the condition for patients.


Assuntos
Exame Neurológico/métodos , Discinesia Tardia , Tetrabenazina/análogos & derivados , Valina/análogos & derivados , Proteínas Vesiculares de Transporte de Monoamina/antagonistas & inibidores , Monitoramento de Medicamentos/métodos , Humanos , Conduta do Tratamento Medicamentoso , Moduladores de Transporte de Membrana/administração & dosagem , Moduladores de Transporte de Membrana/efeitos adversos , Administração dos Cuidados ao Paciente/métodos , Administração dos Cuidados ao Paciente/normas , Psiquiatria/educação , Discinesia Tardia/induzido quimicamente , Discinesia Tardia/diagnóstico , Discinesia Tardia/tratamento farmacológico , Tetrabenazina/administração & dosagem , Tetrabenazina/efeitos adversos , Resultado do Tratamento , Valina/administração & dosagem , Valina/efeitos adversos
6.
Expert Opin Drug Saf ; 19(1): 43-57, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31770500

RESUMO

Introduction: Clozapine remains the most effective antipsychotic for treatment-refractory schizophrenia. However, ~40% of the patients respond insufficiently to clozapine. Clozapine's effects, both beneficial and adverse, have been proposed to be partially attributable to its main metabolite, N-desmethylclozapine (NDMC). However, the relation of the clozapine to norclozapine ratio (CLZ:NDMC; optimally defined as ~2) to clinical response and metabolic outcomes is not clear.Areas covered: This narrative review comprehensively examines the clinical utility of the CLZ:NDMC ratio to reduce metabolic risk and increase treatment efficacy. The association of the CLZ:NDMC ratio with changes in psychopathology, cognitive functioning, and cardiometabolic burden will be explored, as well as adjunctive treatments and their effects.Expert opinion: The literature suggests a positive association between the CLZ:NDMC ratio and better cardiometabolic outcomes. Conversely, the CLZ:NDMC ratio appears inversely associated with better cognitive functioning but less consistently with other psychiatric domains. The CLZ:NDMC ratio may be useful for predicting and monitoring cardiometabolic adverse effects and optimizing potential cognitive benefits of clozapine. Future studies are required to replicate these findings, which if substantiated, would encourage examination of adjunctive treatments aiming to alter the CLZ:NDMC ratio to best meet the needs of the individual patient, thereby broadening clozapine's clinical utility.


Assuntos
Antipsicóticos/administração & dosagem , Clozapina/administração & dosagem , Esquizofrenia/tratamento farmacológico , Antipsicóticos/efeitos adversos , Antipsicóticos/farmacocinética , Clozapina/efeitos adversos , Clozapina/análogos & derivados , Clozapina/sangue , Clozapina/farmacocinética , Cognição/efeitos dos fármacos , Monitoramento de Medicamentos/métodos , Humanos
7.
Biomed Chromatogr ; 34(1): e4742, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31749152

RESUMO

Quantitation of drugs used for the treatment of chronic lymphocytic leukemia in various biological matrices during both pre-clinical and clinical developments is very important, often in routine therapeutic drug monitoring. The first developed methods for quantitation were traditionally done on LC in combination with either UV or fluorescence detection. However, the emergence of LC with mass spectrometry in tandem in early 1990s has revolutionized the quantitation as it has provided better sensitivity and selectivity within a shorter run time; therefore it has become the choice of method for the analysis of various drugs. In this article, an overview of various bioanalytical methods (HPLC or LC-MS/MS) for the quantification of drugs for the treatment of chronic lymphocytic leukemia, along with applicability of these methods, is given.


Assuntos
Antineoplásicos , Cromatografia Líquida , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Antineoplásicos/análise , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Monitoramento de Medicamentos , Humanos , Espectrometria de Massas em Tandem
8.
Clin Biochem ; 75: 40-47, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31669513

RESUMO

OBJECTIVES: Multiple myeloma (MM) is characterized by malignant growth of plasma cells, usually producing a monoclonal antibody (mAb). New treatments for MM include therapeutic monoclonal antibodies (tmAbs), but patients treated with tmAb demonstrate interference on serum electrophoresis (SPE) and immunoprecipitation electrophoresis (IEP). Evaluation of treatment efficacy and determination of MM remission include SPE and IEP which identifies mAb, but cannot differentiate between disease associated mAb and tmAb. We hypothesized that tmAb could be removed from patient sera before testing by SPE and IEP to provide accurate diagnoses for clinicians. DESIGN AND METHODS: We developed the Antigen Specific therapeutic monoclonal Antibody Depletion Assay (ASADA), that utilizes magnetic beads coated with the cognate antigen of the tmAbs, to deplete two different tmAb (daratumumab, elotuzumab) from saline and patient sera and assessed for complete removal of tmAb by SPE and IEP. RESULTS: We found that tmAb could be efficiently removed from saline and patient sera. ASADA demonstrated acceptable analytical specificity and sensitivity in IEP. Recovery of appropriate quantitative values by SPE was demonstrated with clinically acceptable precision. A single bead cocktail could be used to treat both daratumumab and elotuzumab. CONCLUSIONS: This demonstrates proof of principle that ASADA can be used to remove current and future tmAb from patient sera, regardless of platform. This research provides for accurate diagnosis, disease monitoring, and remission status in MM patients being treated with tmAb.


Assuntos
Métodos Analíticos de Preparação de Amostras , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Antineoplásicos/efeitos adversos , Monitoramento de Medicamentos , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/terapia , Anticorpos Monoclonais/sangue , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/sangue , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/sangue , Antineoplásicos/uso terapêutico , Biomarcadores/sangue , Eletroforese das Proteínas Sanguíneas , Humanos , Imunoprecipitação , Mieloma Múltiplo/sangue , Recidiva , Resultado do Tratamento
10.
Biomed Chromatogr ; 34(1): e4623, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31215049

RESUMO

Therapeutic drug monitoring (TDM) has shown to benefit patients treated with drugs of many drug classes, among which is oncology. With an increasing demand for drug monitoring, new assays have to be developed and validated. Guidelines for bioanalytical validation issued by the European Medicines Agency and US Food and Drug Administration are applicable for clinical trials and toxicokinetic studies and demand fully validated bioanalytical methods to yield reliable results. However, for TDM assays a limited validation approach is suggested based on the intended use of these methods. This review presents an overview of publications that describe method validation of assays specifically designed for TDM. In addition to evaluating current practice, we provide recommendations that could serve as a guide for future validations of TDM assays.


Assuntos
Antineoplásicos/análise , Antineoplásicos/farmacocinética , Cromatografia Líquida/métodos , Monitoramento de Medicamentos/métodos , Espectrometria de Massas em Tandem/métodos , Antineoplásicos/uso terapêutico , Humanos , Modelos Lineares , Neoplasias/tratamento farmacológico , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
11.
J Forensic Sci ; 65(1): 288-294, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31454427

RESUMO

Lacosamide is a functionalized amino acid with antiepileptic function. Therapeutic drug monitoring (TDM) in patients for lacosamide is critical as it allows clinicians to control epileptic seizures. A single liquid-liquid extraction step was applied for the extraction of lacosamide from whole blood samples which were thereafter analyzed by GC-MS. Optimum extraction conditions were selected on the basis of experiments with various solvents at different pHs, indicating ethyl acetate at pH 12 as the most efficient parameters for the extraction of lacosamide. Method exhibited linearity from 2 to 100 µg/mL with R2  = 0.998. Accuracy and precision were evaluated at three concentrations and found to be within acceptable limits. LOD and LOQ were determined at 0.1 and 0.5 µg/mL, respectively. Lacosamide was found to be stable at storage conditions. The developed method was applied successfully in clinical samples and postmortem blood sample from an overdose case.


Assuntos
Anticonvulsivantes/sangue , Cromatografia Gasosa-Espectrometria de Massas , Lacosamida/sangue , Anticonvulsivantes/envenenamento , Monitoramento de Medicamentos , Toxicologia Forense , Humanos , Lacosamida/envenenamento , Limite de Detecção , Modelos Lineares , Extração Líquido-Líquido , Envenenamento/diagnóstico
14.
Isr Med Assoc J ; 12(21): 812-816, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31814345

RESUMO

BACKGROUND: The effect of repeated intravenous amantadine (IVAM) in advanced Parkinsonism has not been studied in depth. OBJECTIVES: To report the experience of our medical center with repeated IVAM infusions in patients with advanced Parkinsonism. METHODS: Thirty patients with advanced Parkinsonism of various etiologies were enrolled in an open-label retrospective study. All patients were treated with IVAM infusions in a neurological daycare center. Treatment was initiated with a loading dose of 200/400 mg per day for 5 days followed by a once-daily maintenance dose of 200/400 mg every 1 to 3 weeks. Patients and their caregivers participated in a structured interview and independently completed a clinical global impression of changes scale questionnaire on various motor and non-motor symptoms. RESULTS: Patient mean age was 73.3 ± 9.7 years, average disease duration was 6.2 ± 5.7 years, and mean Hoehn and Yahr score was 3.2 ± 0.84. Mean duration of the IVAM treatment was 15.1 ± 11.6 months. An improvement in general function was reported by 91% of the patients and 89% of the caregivers. Most of the patients reported improvement in tremor and rigidity, as well as in gait stability, freezing of gait, and reduced falls. The treatment was safe with few side effects. CONCLUSIONS: Our data suggest that repeated IVAM infusions could be an effective treatment against various motor symptoms and for improvement of mobility in patients with advanced Parkinsonism. Further randomized clinical trials with a larger sample size using objective measures are warranted to validate our results.


Assuntos
Acidentes por Quedas/prevenção & controle , Amantadina , Destreza Motora/efeitos dos fármacos , Doença de Parkinson , Recuperação de Função Fisiológica/efeitos dos fármacos , Idoso , Amantadina/administração & dosagem , Amantadina/efeitos adversos , Progressão da Doença , Dopaminérgicos/administração & dosagem , Dopaminérgicos/efeitos adversos , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/fisiopatologia , Estudos Retrospectivos , Resultado do Tratamento
15.
J Opioid Manag ; 15(6): 495-498, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31850511

RESUMO

OBJECTIVE: Evaluate the accuracy of the Pennsylvania Prescription Drug Monitoring Program (PA PDMP) in patients undergoing upper extremity procedures. The authors hypothesized that the PA PDMP would provide an accurate account of the prescriptions that were filled. DESIGN: The authors prospectively collected post-operative pain prescription information of patients undergoing outpatient upper extremity surgery over a 2-week period. Patient-reported prescription-filling of opioid was cross-referenced with the PA PDMP information. SETTING: The study was performed at one private institution. PATIENTS: One hundred and thirty-nine consecutive patients undergoing upper extremity procedures. MAIN OUTCOME MEASURE(S): The PA PDMP information was cross-referenced with the post-operative prescription in the medical record to confirm the patient filled the surgeon's prescription. RESULTS: Of the 111 patients who reported filling their prescription, 107 (96.4 percent) of these were confirmed on the PA PDMP Web site (96.4 percent sensitivity; 95% confidence interval [CI]: 91.0-99.0 percent). None of 28 patients who did not fill their prescription appeared in the database search, resulting in 100 percent specificity (95% CI: 87.7-100 percent). Consequently, the overall accuracy of the PA PDMP was shown to be 97.1 percent (95% CI: 92.8-99.2 percent). CONCLUSIONS: The authors' results suggest that the PA PDMP and its many supplementary databases are accurate as it relates to monitoring opioid prescriptions.


Assuntos
Analgésicos Opioides/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Programas de Monitoramento de Prescrição de Medicamentos , Bases de Dados Factuais , Monitoramento de Medicamentos , Humanos , Programas de Monitoramento de Prescrição de Medicamentos/normas
16.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(10): 1252-1257, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31771724

RESUMO

OBJECTIVE: To evaluate cerebrospinal fluid (CSF) vancomycin concentrations and identify factors influencing CSF vancomycin concentrations in critically ill neurosurgical patients. METHODS: A retrospective study was conducted. Adult patients who received vancomycin treatment and CSF vancomycin concentrations monitoring admitted to neurosurgical intensive care unit (ICU) of the First Affiliated Hospital of Sun Yat-sen University from January 2016 to June 2019 were enrolled. General information, vancomycin dosing regimens, CSF vancomycin concentrations, CSF drainage methods and volume of the previous day, and concurrent medications, etc. were collected for analysis. CSF vancomycin concentrations of patients with definite or indefinite central nervous system (CNS) infection, different vancomycin dosing regimens and their influencing factors were analyzed. RESULTS: A total of 22 patients were included. 168 CSF specimens were collected for culture, 20 specimens of which were culture positive, with a positive rate of 11.9%. Sixty cases of CSF vancomycin concentration were obtained. Among the 22 patients, 7 patients (31.8%) were diagnosed with proven CNS infection, 11 patients (50.0%) clinically diagnosed, 2 patients (9.1%) diagnosed with uncertain CNS infection, and 2 patients (9.1%) diagnosed without CNS infection. Intravenous (IV) administration of vancomycin alone was used in 15 cases (25.0%), intrathecal injection in 17 cases (28.3%), IV+intrathecal injection in 23 cases (38.3%), and IV+intraventricular administration in 5 cases (8.3%). The CSF vancomycin concentrations ranged from < 0.24 to > 100 mg/L, with an average level of 14.40 (4.79, 42.34) mg/L. (1) Administration methods of vancomycin affected CSF vancomycin concentrations. The CSF vancomycin concentration with intrathecal injection or intraventricular administration was higher than that of IV administration alone [mg/L: 25.91 (11.28, 58.17) vs. 2.71 (0.54, 5.33), U = 42.000, P < 0.01]. (2) When vancomycin was administered by IV treatment alone, CSF vancomycin concentrations were low in both groups with definite CNS infection (proven+probable) and indefinite CNS infection (possible+non-infection), the CSF vancomycin concentrations of which were 4.14 (1.40, 6.36) mg/L and 1.27 (0.24, 3.33) mg/L respectively, with no significant difference (U = 11.000, P = 0.086). (3) CSF vancomycin concentrations rose with the increased dose of vancomycin delivered by intrathecal injection or intraventricular administration. According to the dose of vancomycin administered locally on the day before therapeutic drug monitoring (TDM), cases were divided into the following groups: 0-15 mg group (n = 22), 20-35 mg group (n = 33), and 40-50 mg group (n = 5), the CSF vancomycin concentrations of which were 4.14 (1.09, 8.45), 30.52 (14.31, 59.61) and 59.43 (25.51, 92.45) mg/L respectively, with significant difference (H = 33.399, P < 0.01). Moreover, the cases of CSF vancomycin concentration of ≥ 10 mg/L accounted for 18.2%, 84.8% and 100% of these three groups, respectively. CSF vancomycin concentrations mostly reached target level when dose of vancomycin administered locally were 20 mg/L or more. CONCLUSIONS: It is difficult to reach target CSF vancomycin concentration for critically ill neurosurgical patients with or without CNS infection by IV treatment. Local administration is an effective treatment regimen to increase CSF vancomycin concentration.


Assuntos
Antibacterianos/líquido cefalorraquidiano , Unidades de Terapia Intensiva , Vancomicina/líquido cefalorraquidiano , Adulto , Monitoramento de Medicamentos , Humanos , Estudos Retrospectivos
17.
Expert Rev Clin Pharmacol ; 12(12): 1099-1106, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31760892

RESUMO

Introduction: Pharmacokinetic-pharmacodynamic (PK-PD) studies of antibiotics in pediatrics are limited. Pediatric dosing regimens for many antimicrobial drugs have been historically derived from adult pharmacokinetic data. Most pediatric formularies and dosing guidelines globally are expert-based and provide no rationale for the recommended doses, leading to heterogeneous guidance.Areas covered: We systematically reviewed the current dosing for 28 antibiotics listed in the Access and Watch groups of the 2019 World Health Organization (WHO) Essential Medicines List for children (EMLc). PubMed and EMBASE were searched for all PK-PD and pharmacological studies in pediatrics up to May 2018. In total, 262 pediatric related articles were deemed eligible. The most studied drugs were those where therapeutic drug monitoring is routine (aminoglycosides, glycopeptides) and study reporting detail was variable, with only 60.0% using the PK-PD results in make dosing recommendations. Based on this evidence, dose recommendations for each antibiotic were made.Expert opinion: We provide an up-to-date review of the limited available evidence on pediatric dosing for the 28 commonly prescribed antibiotics in the 2019 WHO EMLc. We propose synthesized dosing recommendations for those antibiotics administered systemically for the treatment of serious infections. Further PK-PD studies in children, particularly with underlying conditions, are needed.


Assuntos
Antibacterianos/administração & dosagem , Infecções Bacterianas/tratamento farmacológico , Monitoramento de Medicamentos/métodos , Fatores Etários , Antibacterianos/farmacocinética , Antibacterianos/farmacologia , Criança , Relação Dose-Resposta a Droga , Medicamentos Essenciais , Humanos , Guias de Prática Clínica como Assunto , Organização Mundial da Saúde
18.
Lancet ; 394(10209): 1668-1684, 2019 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-31668410

RESUMO

The rapid emergence since the mid-2000s of a large and diverse range of substances originally designed as legal alternatives to more established illicit drugs (pragmatically clustered and termed new psychoactive substances; [NPS]) has challenged traditional approaches to drug monitoring, surveillance, control, and public health responses. In this section of the Series, we describe the emergence of NPS and consider opportunities for strengthening the detection, identification, and responses to future substances of concern. First, we explore the definitional complexity of the term NPS. Second, we describe the origins and drivers surrounding NPS, including motivations for use. Third, we summarise evidence on NPS availability, use, and associated harms. Finally, we use NPS as a case example to explore challenges and opportunities for future drug monitoring, surveillance, control, and public health responses. We posit that the current means of responding to emerging substances might no longer be fit for purpose in a world in which different substances can be rapidly introduced, and where people who use drugs can change preferences on the basis of market availability.


Assuntos
Monitoramento de Medicamentos/métodos , Controle de Medicamentos e Entorpecentes/legislação & jurisprudência , Psicotrópicos/efeitos adversos , Saúde Pública/legislação & jurisprudência , Adolescente , Adulto , Comércio/legislação & jurisprudência , Coleta de Dados , Controle de Medicamentos e Entorpecentes/métodos , Feminino , Humanos , /legislação & jurisprudência , Masculino , Pessoa de Meia-Idade , Motivação , Psicotrópicos/classificação , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adulto Jovem
19.
Clin Biochem ; 74: 24-30, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31672648

RESUMO

BACKGROUND: In some clinical situations (pregnancy, aging, drug resistance, toxicity), measurements of lamotrigine plasma levels may be reliable. Limited studies indicate that saliva and hair could be alternative sources for monitoring lamotrigine therapy. The drug content in hair can also be used to assess the history of drug therapy and to ascertain long-term patient compliance. The aims of this study were to 1) determine the correlations among plasma, saliva, and hair lamotrigine concentrations, 2) evaluate saliva as an alternative matrix for monitoring drug levels and 3) evaluate hair as a source of information on adherence to antiepileptic treatment and on the correlation of hair concentrations with clinical outcomes in patients with epilepsy. METHODS: Plasma, saliva, and hair lamotrigine concentrations were measured by liquid chromatography-tandem mass spectrometry in positive ionization mode. The study group (n = 85) was recruited among the epileptic patients at the Institute of Psychiatry and Neurology, Warsaw, Poland. RESULTS: Plasma concentrations were not influenced by sex, age, or the concomitant use of other antiepileptic drugs. Lamotrigine saliva and plasma concentrations were strongly correlated (r = 0.82, p < 0.001). Lamotrigine hair concentrations were correlated with the plasma concentrations (r = 0.53, p < 0.001) and daily dose in mg/kg (r = 0.23, p = 0.024). The analysis revealed no significant correlation between lamotrigine hair levels and the number of seizures in the previous 3 months (r = -0.1, p > 0.05). CONCLUSIONS: The lamotrigine saliva concentration is strongly correlated with its plasma level, and saliva can be used as an alternative matrix to plasma for monitoring. Lamotrigine can also be successfully measured in hair, and the drug levels in hair tend to be correlated with the levels in plasma. However, lamotrigine levels in hair may not correspond to clinical outcomes (i.e., seizure episodes).


Assuntos
Anticonvulsivantes/análise , Monitoramento de Medicamentos/métodos , Cabelo/química , Lamotrigina/análise , Saliva/química , Adolescente , Adulto , Idoso , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/sangue , Anticonvulsivantes/uso terapêutico , Cromatografia Líquida , Epilepsia/sangue , Epilepsia/tratamento farmacológico , Feminino , Humanos , Lamotrigina/administração & dosagem , Lamotrigina/sangue , Lamotrigina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Polônia , Convulsões/sangue , Convulsões/tratamento farmacológico , Espectrometria de Massas em Tandem , Adulto Jovem
20.
Clin Biochem ; 74: 31-35, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31672652

RESUMO

BACKGROUND: In the chronic inflammation process in the course of rheumatoid arthritis (RA), many alterations in the expression of plasma proteins, as well as their posttranslational modifications (including glycosylation) can occur. Taking into account the disturbances in protein glycosylation and the emerging new treatment regimens, the aim of this study was to assess the serum profile of transferrin isoforms in RA patients treated with biological drugs. METHODS: The study included 20 patients (16 females and 4 males; mean age: 53.4 years; range: 24-67) with rheumatoid arthritis treated with rituximab. Serum samples were taken 3 times: before and 3 and 6 months during treatment. The isoforms of transferrin were separated by capillary electrophoresis (MINICAP electrophoretic system, Sebia, France) into five major fractions: asialo-, disialo-, trisialo-, tetrasialo- and pentasialotransferrin. The results were calculated as relative concentrations of each fraction. RESULTS: The median trisialotransferrin relative concentrations after 3 and 6 months treatment (4.40% and 4.10%, respectively) were significantly higher (p = 0.013, p = 0.009, respectively) than before treatment (3.50%). The levels of serum pentasialotransferrin were also increased 3 and 6 months following treatment (16.5% and 17.7%, p = 0.005 and p = 0.006, respectively) as compared to those before therapy (14.5%), while tetrasialotransferrin concentrations were lower (80.3% and 78.4%, p = 0.009 and p = 0.008, respectively) than before treatment (81.5%). Trisialotransferrin relative concentration correlated with Hb (p = 0.019), whereas pentasialotransferrin with PLT (p = 0.036) after treatment. CONCLUSIONS: This study indicates that treatment with rituximab of RA patients alters the serum profile of transferrin isoforms. Tri-, tetra- and pentasialotransferrin relative concentrations measurements can be a useful tool to monitor therapy.


Assuntos
Artrite Reumatoide/sangue , Artrite Reumatoide/terapia , Produtos Biológicos/uso terapêutico , Fatores Imunológicos/uso terapêutico , Rituximab/uso terapêutico , Transferrina/análise , Adulto , Idoso , Biomarcadores/sangue , Monitoramento de Medicamentos/métodos , Eletroforese Capilar , Feminino , Seguimentos , Glicosilação , Humanos , Masculino , Pessoa de Meia-Idade , Isoformas de Proteínas/sangue , Índice de Gravidade de Doença , Transferrina/química , Resultado do Tratamento , Adulto Jovem
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