Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 473
Filtrar
1.
Mayo Clin Proc ; 95(1): 90-100, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31902433

RESUMO

OBJECTIVE: To compare the safety of metformin vs sulfonylureas in patients with type 2 diabetes by chronic kidney disease (CKD) stage. PATIENTS AND METHODS: This retrospective cohort study included adults in Manitoba, Canada, with type 2 diabetes, an incident monotherapy prescription for metformin or a sulfonylurea, and a serum creatinine measurement from April 1, 2006, to March 31, 2017. Patients were stratified by estimated glomerular filtration rate (eGFR) into the following groups: eGFR of 90 or greater, 60 to 89, 45 to 59, 30 to 44, or less than 30 mL/min/1.73 m2. Outcomes included all-cause mortality, cardiovascular events, and major hypoglycemic episodes. Baseline characteristics were used to calculate propensity scores and perform inverse probability of treatment weights analysis, and eGFR group was examined as an effect modifier for each outcome. RESULTS: The cohort consisted of 21,996 individuals (19,990 metformin users and 2006 sulfonylurea users). Metformin use was associated with lower risk for all-cause mortality (hazard ratio [HR], 0.48; 95% CI, 0.40-0.58; P<.001), cardiovascular events (HR, 0.67; 95% CI, 0.52-0.86; P=.002), and major hypoglycemic episodes (HR, 0.14; 95% CI, 0.09-0.20; P<.001) when compared with sulfonylureas. CKD was a significant effect modifier for all-cause mortality (P=.002), but not for cardiovascular events or major hypoglycemic episodes. CONCLUSION: Sulfonylurea monotherapy is associated with higher risk for all-cause mortality, major hypoglycemic episodes, and cardiovascular events compared with metformin. Although the presence of CKD attenuated the mortality benefit, metformin may be a safer alternative to sulfonylureas in patients with CKD.


Assuntos
Diabetes Mellitus Tipo 2 , Hipoglicemia , Metformina , Insuficiência Renal Crônica , Compostos de Sulfonilureia , Canadá/epidemiologia , Doenças Cardiovasculares/epidemiologia , Creatinina/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Monitoramento de Medicamentos/métodos , Monitoramento de Medicamentos/estatística & dados numéricos , Modificador do Efeito Epidemiológico , Feminino , Taxa de Filtração Glomerular , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Masculino , Conduta do Tratamento Medicamentoso/estatística & dados numéricos , Metformina/administração & dosagem , Metformina/efeitos adversos , Pessoa de Meia-Idade , Mortalidade , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/epidemiologia , Estudos Retrospectivos , Compostos de Sulfonilureia/administração & dosagem , Compostos de Sulfonilureia/efeitos adversos
2.
Am J Health Syst Pharm ; 76(16): 1248-1253, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31369117

RESUMO

PURPOSE: Results of a study to determine the proportion of anticoagulation clinic workload that could be performed by clinical pharmacy technicians (CPTs) and the potential impact on operational efficiency of pharmacist-managed anticoagulation clinics (ACCs) are reported. METHODS: In a quality improvement project involving 11 Veterans Affairs (VA) medical centers, investigators conducted a 3-day time study in pharmacist-managed ACCs followed by scoring of task appropriateness for CPTs via the RAND/UCLA appropriateness method by the VA Anticoagulation Subject Matter Expert (SME) Workgroup. The primary outcome was the percentage of tasks deemed appropriate for a CPT to perform. RESULTS: The Anticoagulation SME Workgroup determined that a wide variety of mainly administrative ACC tasks could be completed by a CPT. At the 11 VA ACCs, an average of 53.4% (range, 39.9-76.1%) of tasks being performed by pharmacists were deemed appropriate for CPTs. The average percentage of total clinic time associated with performing tasks appropriate for a CPT equated to an estimated 1,111 hours per year. Shifting that portion of the annual work hours to a CPT could potentially result in cost avoidance of $55,302. CONCLUSION: At the ACCs evaluated, a significant proportion of tasks (53.4% on average) may be appropriate to assign to CPTs to improve the operational efficiency of these clinics. This finding supports development of business plans for the addition of CPTs in ACCs along with elements to inform crafting of an effective template for ACC structure, including clearly defined CPT roles.


Assuntos
Anticoagulantes/uso terapêutico , Transtornos da Coagulação Sanguínea/prevenção & controle , Hemorragia/prevenção & controle , Ambulatório Hospitalar/organização & administração , Técnicos em Farmácia/organização & administração , Transtornos da Coagulação Sanguínea/sangue , Monitoramento de Medicamentos/métodos , Monitoramento de Medicamentos/estatística & dados numéricos , Eficiência Organizacional , Hemorragia/sangue , Hemorragia/induzido quimicamente , Hospitais de Veteranos/organização & administração , Hospitais de Veteranos/estatística & dados numéricos , Humanos , Coeficiente Internacional Normatizado , Ambulatório Hospitalar/estatística & dados numéricos , Serviço de Farmácia Hospitalar/organização & administração , Serviço de Farmácia Hospitalar/estatística & dados numéricos , Técnicos em Farmácia/estatística & dados numéricos , Papel Profissional , Avaliação de Programas e Projetos de Saúde , Varfarina/uso terapêutico , Carga de Trabalho/estatística & dados numéricos
3.
Am J Health Syst Pharm ; 76(14): 1038-1058, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31361881

RESUMO

PURPOSE: The results of the 2018 ASHP national survey of pharmacy practice in hospital settings are presented. METHODS: Pharmacy directors at 4,897 general and children's medical-surgical hospitals in the United States were surveyed using a mixed-mode method of contact by mail and email. Survey completion was online using Qualtrics. IMS Health supplied data on hospital characteristics; the survey sample was drawn from IMS's hospital database. RESULTS: The response rate was 16.6%. The percentage of hospitals that routinely have pharmacists assigned to provide drug therapy management has increased. Transitions-of-care processes have generally increased over the last 6 years. The percentage of hospitals with pharmacists in a wide variety of clinic types and clinical practice areas has increased over the last 2 years. Opioid stewardship programs are emerging in many U.S. hospitals, with pharmacists participating or taking the lead in program implementation. Outsourcing of compounded sterile product preparation is common. The proportion of hospitals not using any technology when compounding sterile preparations has declined. Pharmacy departments commonly track and monitor trends for administrative, operational, quality, and outcome metrics. CONCLUSION: Pharmacists continue to improve drug therapy monitoring for patients in U.S. hospitals. They are also responding to public health issues related to medication use. These advancements include taking an active role in opioid stewardship programs, safe compounding of sterile medications for patients, and reducing the need for hospital-based care.


Assuntos
Educação de Pacientes como Assunto/organização & administração , Serviço de Farmácia Hospitalar/organização & administração , Monitoramento de Medicamentos/estatística & dados numéricos , Humanos , Sistemas de Medicação no Hospital/organização & administração , Sistemas de Medicação no Hospital/estatística & dados numéricos , Conduta do Tratamento Medicamentoso/organização & administração , Conduta do Tratamento Medicamentoso/estatística & dados numéricos , Educação de Pacientes como Assunto/estatística & dados numéricos , Transferência de Pacientes/organização & administração , Serviço de Farmácia Hospitalar/estatística & dados numéricos , Avaliação de Programas e Projetos de Saúde , Sociedades Farmacêuticas , Inquéritos e Questionários/estatística & dados numéricos , Estados Unidos
4.
Eur J Clin Pharmacol ; 75(8): 1069-1075, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31139866

RESUMO

BACKGROUND: Routine laboratory monitoring of rivaroxaban and dose adjustment relating to exposure is currently not recommended. However, in certain clinical situations, assessment of rivaroxaban levels is desirable. OBJECTIVES: To examine inter- and intra-subject plasma rivaroxaban variability in patients with atrial fibrillation (AF) and to correlate these results to clinical outcomes. PATIENTS/METHODS: We included 60 patients with AF treated with rivaroxaban: half on 20 mg daily (R20) and half on 15 mg daily (R15). Three trough and peak blood samples were collected with an interval of 6-8 weeks apart. Plasma rivaroxaban concentration was measured directly by liquid chromatography-tandem mass-spectrometry (LC-MS/MS) and indirectly by anti-Xa for rivaroxaban, prothrombin time (PT), and activated partial thromboplastin time (APTT). RESULTS: Patients on R15 were older (76 ± 6 vs 71 ± 6 years), had lower creatinine clearance (60 ± 26 vs 99 ± 32 mL/min), higher CHADS2 (2.5 ± 1.2 vs 1.8 ± 1.3), all p < 0.01, but had similar rivaroxaban concentrations in trough samples to patients on R20. There was no significant intra-individual variability for trough or peak rivaroxaban concentration assessed by LC-MS/MS, anti-Xa, or PT. Trough rivaroxaban levels determined by LC-MS/MS (48 ± 30 vs 34 ± 26, p = 0.02) and anti-Xa, but not with PT and APTT, were higher in patients with bleeding than in patients without it. CONCLUSIONS: There is a pronounced inter-, but not intra-individual variability in the rivaroxaban trough levels in patients with AF. Assessment of trough rivaroxaban concentration with LC-MS/MS or anti-Xa, but not with APTT or PT, may help to identify patients at increased risk of bleeding.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Variação Biológica Individual , Variação Biológica da População , Inibidores do Fator Xa/farmacologia , Hemorragia/epidemiologia , Rivaroxabana/farmacologia , Idoso , Idoso de 80 Anos ou mais , Testes de Coagulação Sanguínea/estatística & dados numéricos , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos/estatística & dados numéricos , Inibidores do Fator Xa/uso terapêutico , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Medição de Risco , Rivaroxabana/uso terapêutico
5.
BMC Med ; 17(1): 89, 2019 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-31064370

RESUMO

BACKGROUND: Therapeutic drug monitoring involves therapeutic modifications based on the measurement of drug levels and antidrug antibodies. The viability of therapeutic drug monitoring in vedolizumab-treated patients with inflammatory bowel disease remains questioned. MAIN BODY: Accumulating evidence from clinical trials and real-world data suggests that an exposure-efficacy relationship may exist for vedolizumab in inflammatory bowel disease, but results are not as straightforward as they are for anti-tumour necrosis factor-α therapy. Robust target vedolizumab trough levels are currently missing, since available data are heterogenous and prospective, interventional pharmacokinetic-pharmacodynamic studies are lacking. The positioning of vedolizumab drug monitoring in therapeutic algorithms is yet to be defined. CONCLUSION: Therapeutic drug monitoring has the potential to improve the outcome parameters of vedolizumab-treated patients with inflammatory bowel disease. Before the therapeutic drug monitoring of vedolizumab can be implemented in a widespread fashion, prospective studies are needed to evaluate the effect of vedolizumab dose optimisation. These studies should focus on objective disease markers and vedolizumab drug levels, and define thresholds for optimal drug exposure.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Monitoramento de Medicamentos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Anticorpos Monoclonais Humanizados/sangue , Anticorpos Monoclonais Humanizados/farmacocinética , Ensaios Clínicos como Assunto/estatística & dados numéricos , Monitoramento de Medicamentos/estatística & dados numéricos , Humanos , Doenças Inflamatórias Intestinais/sangue , Estudos Prospectivos , Resultado do Tratamento
6.
S Afr Med J ; 109(3): 174-177, 2019 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-30834874

RESUMO

BACKGROUND: The Joint United Nations Programme on HIV/AIDS (UNAIDS) third 90-90-90 target requires 90% of patients on antiretroviral treatment (ART) to be virally suppressed (<1 000 copies/mL). In Khayelitsha, Cape Town, South Africa viral load (VL) suppression of <400 copies/mL was reported as 89% in 2016, but only 56% of patients had a result recorded in routine data. We conceived a VL 'cascade' to represent the steps required for an expected VL to be reported as complete in routine data and thus contribute to reported VL suppression: among those for whom a VL is 'expected', a sample must be collected and tested ('done'), a result must be 'filed' in the patient folder, 'noted' by a clinician and electronically 'captured'. The low reported completion suggested gaps along the VL cascade and cast doubt on the validity of reported suppression. OBJECTIVES: To assess the validity of routinely reported VL suppression and identify barriers to VL completion. METHODS: A retrospective cohort study between 1 July 2015 and 30 June 2016, which included all Khayelitsha patients receiving ART, with a routine VL expected, was conducted. We obtained data routinely captured on site and VL data from the laboratory system. A sample of 1 035 patient folders was reviewed. VL suppression was calculated using laboratory data, including all tests done, and compared with reported suppression based on on-site captured electronic data. Successful progression through each step on the VL cascade was estimated. We used logistic regression to identify factors associated with laboratory data and reported VL testing. RESULTS: Of 22 991 patients for whom a routine VL test was due, 84% were done, 79% filed, 76% noted and 55% captured. Using all laboratory data, VL suppression was  estimated as 82%, 87%, 89% and 91% at the 50, 200, 400 and 1 000 copies/mL thresholds, respectively, but reported suppression using captured results was 80%, 86%, 88% and 89% at those thresholds. Routine VL testing is more likely to be done in children <15 years old (adjusted odds ratio (aOR) 1.89, 95% confidence interval (CI) 1.45 - 2.48) and pregnant women (aOR 1.90, 95% CI 1.28 - 2.81) than in men, adjusted for facility. CONCLUSIONS: Despite a low reported completion, VL testing completion was high. Reported suppression using captured data was similar to suppression calculated using all laboratory data, which provided an accurate measure of progress towards the 90-90-90 target. More work is needed to reach the 16% of patients missed by routine testing.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Monitoramento de Medicamentos/normas , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Indicadores de Qualidade em Assistência à Saúde/estatística & dados numéricos , Carga Viral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Criança , Monitoramento de Medicamentos/estatística & dados numéricos , Feminino , Fidelidade a Diretrizes/estatística & dados numéricos , Infecções por HIV/sangue , Acesso aos Serviços de Saúde/estatística & dados numéricos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Garantia da Qualidade dos Cuidados de Saúde , Reprodutibilidade dos Testes , Estudos Retrospectivos , África do Sul , Resultado do Tratamento , Adulto Jovem
7.
Ther Drug Monit ; 41(2): 107-110, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30883503

RESUMO

This article presents 3 cases of immunocompromised patients for whom therapeutic drug monitoring of ganciclovir in combination with cytomegalovirus viral load measurement was used to guide treatment. The first patient is diagnosed with thymoma A, the second is a heart transplant recipient, and the third is an HIV-positive patient. These patients were all diagnosed with cytomegalovirus and treated with ganciclovir. Our case studies illustrate how therapeutic drug monitoring-guided dosing can be helpful in the management of these complex cases.


Assuntos
Infecções por Citomegalovirus/tratamento farmacológico , Monitoramento de Medicamentos/estatística & dados numéricos , Ganciclovir/uso terapêutico , Adulto , Antivirais/uso terapêutico , Infecções por Citomegalovirus/sangue , Esquema de Medicação , Ganciclovir/sangue , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Carga Viral
8.
Infect Control Hosp Epidemiol ; 40(3): 375-379, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30729904

RESUMO

Underestimating antimicrobial use based on days of therapy (DOT) is recognized for certain antimicrobial agents. We investigated the difference between DOT and therapeutic drug monitoring (TDM)-based exposure days in estimating vancomycin use and demonstrated that DOT may underestimate vancomycin exposure by ∼10%.


Assuntos
Antibacterianos/administração & dosagem , Monitoramento de Medicamentos/métodos , Vancomicina/administração & dosagem , Antibacterianos/uso terapêutico , Monitoramento de Medicamentos/estatística & dados numéricos , Humanos , Pacientes Internados/estatística & dados numéricos , Estudos Retrospectivos , Vancomicina/uso terapêutico
9.
Eur J Heart Fail ; 21(3): 337-341, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30741494

RESUMO

AIMS: To assess differences in diuretic dose requirements in patients treated with sacubitril/valsartan compared with enalapril in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM-HF) trial. METHODS AND RESULTS: Overall, 8399 patients with New York Heart Association class II-IV heart failure and reduced LVEF were randomized to sacubitril/valsartan 200 mg bid or enalapril 10 mg twice daily. Loop diuretic doses were assessed at baseline, 6, 12, and 24 months, and furosemide dose equivalents were calculated via multiplication factors (2x for torsemide and 40x for bumetanide). Percentages of participants with reductions or increases in loop diuretic dose were determined. At baseline, 80.8% of participants were taking any diuretics (n = 6290 for loop diuretics, n = 496 for other diuretics); of those, recorded dosage data for loop diuretics were available on 5487 participants. Mean baseline furosemide equivalent doses were 48.2 mg for sacubitril/valsartan and 49.6 mg for enalapril (P = 0.25). Patients treated with sacubitril/valsartan were more likely to reduce diuretic dose and less likely to increase diuretic dose relative to those randomized to enalapril at 6, 12, 24 months post-randomization, with an overall decreased diuretic use of 2.0% (P = 0.02), 4.1% (P < 0.001), and 6.1% (P < 0.001) at 6, 12, and 24 months, respectively, with similar findings in an on-treatment analysis. CONCLUSION: Treatment with sacubitril/valsartan was associated with more loop diuretic dose reductions and fewer dose increases compared with enalapril, suggesting that treatment with sacubitril/valsartan may reduce the requirement for loop diuretics relative to enalapril in patients with heart failure with reduced ejection fraction.


Assuntos
Aminobutiratos , Enalapril , Furosemida , Insuficiência Cardíaca , Volume Sistólico , Tetrazóis , Idoso , Aminobutiratos/administração & dosagem , Aminobutiratos/farmacocinética , Antagonistas de Receptores de Angiotensina/administração & dosagem , Antagonistas de Receptores de Angiotensina/farmacocinética , Disponibilidade Biológica , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos/métodos , Monitoramento de Medicamentos/estatística & dados numéricos , Enalapril/administração & dosagem , Enalapril/farmacocinética , Feminino , Furosemida/administração & dosagem , Furosemida/farmacocinética , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Conduta do Tratamento Medicamentoso/estatística & dados numéricos , Pessoa de Meia-Idade , Inibidores de Simportadores de Cloreto de Sódio e Potássio/administração & dosagem , Inibidores de Simportadores de Cloreto de Sódio e Potássio/farmacocinética , Tetrazóis/administração & dosagem , Tetrazóis/farmacocinética
10.
Clin Biochem ; 66: 91-94, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30731069

RESUMO

INTRODUCTION: Treatment with vancomycin and gentamycin requires strict monitoring of its serum concentration for proper dosage optimization. This study aimed to assess the quality and the harmonization of antibiotics assays in Polish laboratories. MATERIALS AND METHODS: 413 results of vancomycin and 148 results of gentamycin assays obtained from Polish laboratories in 30 international external quality assessment (EQA) surveys carried out from March 2011 to May 2018 were analyzed. RESULTS: Interlaboratory robust coefficients of variation (rCVs) in particular surveys comprised between 1.3 and 47.2% for vancomycin, and between 1.8 and 34.2% for gentamycin. The percentage of the results with the difference above acceptable limit ±10% from the target value established for own method group was 25.7% for vancomycin and 25.6% for gentamycin. When the difference was established according to target value for all methods, the percentage of results outside the acceptable limit was 2-fold higher on average (54.8% for vancomycin and 43.2% for gentamycin). The comparison of target values for methods revealed statistically significant differences between analytical systems used (p < .0001). The highest difference was 40% for vancomycin and 12% for gentamycin. CONCLUSIONS: The present analysis revealed high dispersion of the antibiotics assays results in Polish laboratories. Moreover, vancomycin and gentamycin results differed significantly in a way dependent on the analytical system used. There appear to be an urgent need for harmonization of methods used for vancomycin and gentamycin measurement.


Assuntos
Antibacterianos/análise , Bioensaio/estatística & dados numéricos , Monitoramento de Medicamentos/estatística & dados numéricos , Gentamicinas/análise , Garantia da Qualidade dos Cuidados de Saúde/normas , Vancomicina/análise , Confiabilidade dos Dados , Humanos , Laboratórios/estatística & dados numéricos , Polônia , Fatores de Tempo
11.
J Med Econ ; 22(5): 471-477, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30744455

RESUMO

OBJECTIVES: To determine how overall cost of anticoagulation therapy for warfarin compares with that of Novel Oral Anticoagulants (NOACs). Also, to demonstrate a scientific, comprehensive, and an analytical approach to estimate direct costs involved in monitoring and management of anticoagulation therapy for outpatients in an academic primary care clinic setting, post-initiation of therapy. METHODS: A population-based cross-sectional study was conducted in conjunction with observations of patient care processes between August 2014 and January 2015. The study was conducted in an academic primary care outpatient setting at Mayo Clinic's warfarin anticoagulation clinic, Rochester, MN. The anticoagulation clinic serves patients 18 years of age or older in Warfarin therapy management, for any indication, after referral from the patient's primary care provider. The study included anticoagulation clinic enrollment data on a population of 5,526 patients. Time-Driven Activity-Based Costing (TDABC) technique was applied. Detailed process flow maps which showed process steps for all the anticoagulation program components and care continuum phases were created. Staff roles associated with each of the process steps were identified and displayed on the maps. Process times and costs were captured and analyzed. The main outcome was direct cost of monitoring and management of anticoagulation therapy, post-initiation of therapy. RESULTS: The cost of warfarin management for patients who display unstable International Normalized Ratio (INR) is more than three times those who display stable INR over time. (Comparator to distinguish stability: Frequency of point-of-care visits needed by patients.) For complex anticoagulation patients, total cost of medication and monitoring for warfarin anticoagulation therapy is similar to that for NOACs. CONCLUSION: Despite warfarin being significantly less expensive to purchase than NOACs, overall warfarin management incurs higher costs due to laboratory monitoring and provider time than NOACs. NOAC treatment, therefore, may not be more expensive than warfarin therapy management for complex anticoagulation patients.


Assuntos
Anticoagulantes/economia , Fibrilação Atrial/tratamento farmacológico , Monitoramento de Medicamentos/economia , Monitoramento de Medicamentos/estatística & dados numéricos , Centros Médicos Acadêmicos/economia , Centros Médicos Acadêmicos/estatística & dados numéricos , Instituições de Assistência Ambulatorial/economia , Instituições de Assistência Ambulatorial/estatística & dados numéricos , Anticoagulantes/uso terapêutico , Custos e Análise de Custo , Estudos Transversais , Feminino , Pessoal de Saúde/economia , Humanos , Coeficiente Internacional Normatizado/economia , Coeficiente Internacional Normatizado/estatística & dados numéricos , Masculino , Varfarina/economia , Varfarina/uso terapêutico
12.
J Infect Chemother ; 25(6): 437-443, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30782427

RESUMO

The objective of this study was to explore the optimal dosage regimen of daptomycin and to determine the necessity and validity of a high-dose regimen from the perspectives of PK/PD parameters using Monte Carlo Simulation (MCS) and therapeutic drug monitoring (TDM) in a Japanese clinical setting. The volume of distribution (0.13 ± 0.012 L/kg) in this study was greater than that in healthy volunteers reported in Japan. The range of half-lives was between 8.9 and 34.9 h, which were gradually prolonged as creatinine clearance decreased. In MCS, the cumulative fractions of response (CFR) of the peak/MIC â‰§ 60 and the AUC/MIC â‰§ 666 at the 6 mg/kg q 24 h were 72.0% and 78.8% but at the 10 mg/kg q 24 h, the CFRs improved to both 99%. In TDM with 6 mg/kg q 24 h regimen, the patients who reached the peak and AUC target were 40% (2 out of 5 patients), respectively. The intraindividual variability in daptomycin PK may indicate the necessity of TDM and high-dose regimen, such as over 8 mg/kg, may be needed to ensure the effectiveness especially on Japanese patients with normal renal function.


Assuntos
Antibacterianos/farmacologia , Daptomicina/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Área Sob a Curva , Creatinina/sangue , Creatinina/metabolismo , Creatinina/urina , Daptomicina/uso terapêutico , Relação Dose-Resposta a Droga , Esquema de Medicação , Monitoramento de Medicamentos/estatística & dados numéricos , Feminino , Meia-Vida , Humanos , Infusões Intravenosas , Japão , Rim/efeitos dos fármacos , Rim/fisiologia , Masculino , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Método de Monte Carlo , Eliminação Renal/efeitos dos fármacos , Infecções Estafilocócicas/sangue , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/urina , Resultado do Tratamento
13.
Farm. hosp ; 43(1): 19-23, ene.-feb. 2019. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-182582

RESUMO

Objetivo: El objetivo de nuestro estudio fue analizar las características de los medicamentos sujetos a seguimiento adicional. Para ello, estudiamos: los criterios aplicados para su designación, los criterios de dispensación autorizados, los grupos farmacológicos a los que pertenecen y su seguridad postcomercialización. Método: Se analizó la lista publicada por la Agencia Europea de Medicamentos en enero de 2017 (EMA/245297/2013 Rev.41). La información para el análisis se extrajo de las páginas web de la Agencia Europea de Medicamentos y la Agencia Española de Medicamentos y Productos Sanitarios. Resultados: Se estudiaron 316 medicamentos sujetos a seguimiento adicional. El criterio de designación más común fue ser un nuevo principio activo (n = 197 [62,3%]). Otros criterios de designación comunes fueron: requerir un estudio postautorización de seguridad (n = 52 [16,5%]) y ser un medicamento biológico, aunque no un nuevo principio activo (n = 49 [15,5%]). Con respecto a las condiciones de dispensación, casi el 66% de estos medicamentos se autorizaron con criterios de dispensación restringidos. Hasta enero de 2017, la Agencia Española de Medicamentos y Productos Sanitarios había publicado 14 notas informativas de seguridad referidas a los medicamentos sujetos a seguimiento adicional. Conclusiones: Los medicamentos sujetos a seguimiento adicional incluyen mayoritariamente nuevas sustancias activas. El grupo farmacológico más frecuente es el de los fármacos antineoplásicos e inmunomoduladores. La revisión postcomercialización de su seguridad ha generado ya alguna información publicada por la Agencia Española de Medicamentos y Productos Sanitarios


Objective: The objective of this study was to analyse the characteristics of medicines subject to additional monitoring. We assessed the following aspects: the criteria applied to approve a medicine as being subject to additional monitoring; the authorized dispensing conditions; the pharmacological groups to which they belong; and their post-authorisation safety. Method: We analysed the list published by the European Medicines Agency in January 2017 (EMA/245297/2013 Rev.41). Information for the analysis was obtained from the web sites of the European Medicines Agency and the Spanish Agency of Medicines and Medical Devices. Results: We assessed 316 medicines subject to additional monitoring. The most common criterion used to assign a medicine as being subject to additional monitoring was it being a new active substance (n = 197 [62.3%]). Other common criteria were requiring a post-authorisation safety study (n = 52 [16.5%]) and being a biologic medicine but not a new active substance (n = 49 [15.5%]). Regarding dispensing conditions, nearly 66% of these medicines were authorized under restricted conditions. Until January 2017, the Spanish Agency of Medicines and Medical Device published 14 safety reports related to medicines subject to additional monitoring. Conclusions: The group of medicines subject to additional monitoring mainly includes new active substances. The most common pharmacological group is antineoplastic and immunomodulating agents. The postauthorisation safety study has already produced information published by the Spanish Agency of Medicines and Medical Devices


Assuntos
Humanos , Monitoramento de Medicamentos/normas , Medicamentos de Venda Assistida/normas , Medicamentos Biossimilares , Aprovação de Drogas , Monitoramento de Medicamentos/estatística & dados numéricos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , União Europeia , Farmacovigilância
14.
Farm Hosp ; 43(1): 19-23, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30624169

RESUMO

OBJECTIVE: The objective of this study was to analyse the characteristics of  medicines subject to additional monitoring. We assessed the following aspects:  the criteria applied to approve a medicine as being subject to additional  monitoring; the authorized dispensing conditions; the pharmacological groups to which they belong; and their post-authorisation safety. METHOD: We analysed the list published by the European Medicines Agency in  January 2017 (EMA/245297/2013 Rev.41). Information for the analysis was  obtained from the web sites of the European Medicines Agency and the Spanish  Agency of Medicines and Medical Devices. RESULTS: We assessed 316 medicines subject to additional monitoring. The most  common criterion used to assign a medicine as being subject to additional  monitoring was it being a new active substance (n = 197 [62.3%]). Other  common criteria were requiring a post-authorisation safety study (n = 52  [16.5%]) and being a biologic medicine but not a new active substance (n = 49  [15.5%]). Regarding dispensing conditions, nearly 66% of these medicines were authorized under restricted conditions. Until January 2017, the Spanish Agency  of Medicines and Medical Device published 14 safety reports related to medicines subject to additional monitoring. CONCLUSIONS: The group of medicines subject to additional monitoring mainly  includes new active substances. The most common pharmacological group is antineoplastic and immunomodulating agents. The postauthorisation safety  study has already produced information published by the Spanish Agency of  Medicines and Medical Devices.


Assuntos
Monitoramento de Medicamentos/tendências , Medicamentos Biossimilares , Aprovação de Drogas , Monitoramento de Medicamentos/estatística & dados numéricos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , União Europeia , Humanos , Farmacovigilância
15.
Eur J Heart Fail ; 21(3): 352-359, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30632656

RESUMO

AIMS: Patients with pulmonary arterial hypertension associated with congenital heart disease (CHD-PAH) after defect correction have a poor prognosis compared with other CHD-PAH patients. Therefore, it is important that these patients are treated as early and effectively as possible. Evidence supporting the use of PAH therapies in patients with corrected CHD-PAH from randomised controlled trials is limited. The purpose of these analyses was to characterise the corrected CHD-PAH patients from the GRIPHON study and examine the response to selexipag. METHODS AND RESULTS: Out of the 110 patients diagnosed with corrected CHD-PAH, 55 had atrial septal defects, 38 had ventricular septal defects, 14 had persistent ducti arteriosus, and 3 had defects not further specified. Hazard ratios (HR) and 95% confidence intervals (CI) for the primary composite endpoint were calculated using Cox proportional hazard models. Compared with the non-CHD patients from GRIPHON, patients with corrected CHD-PAH were slightly younger, with a greater proportion being treatment-naive and in World Health Organization functional class I/II. The rate of the primary composite endpoint of morbidity/mortality was lower in patients with corrected CHD-PAH who were treated with selexipag compared with those treated with placebo (HR 0.58; 95% CI 0.25, 1.37). The most common adverse events were those known to be related to selexipag. CONCLUSIONS: These post-hoc analyses of GRIPHON provide valuable information about a large population of patients with corrected CHD-PAH, and suggest that selexipag may delay disease progression and was well-tolerated in patients with corrected CHD-PAH.


Assuntos
Acetamidas , Procedimentos Cirúrgicos Cardíacos , Cardiopatias Congênitas , Hipertensão Pulmonar , Pirazinas , Acetamidas/administração & dosagem , Acetamidas/efeitos adversos , Adulto , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/métodos , Progressão da Doença , Método Duplo-Cego , Monitoramento de Medicamentos/métodos , Monitoramento de Medicamentos/estatística & dados numéricos , Intervenção Médica Precoce/métodos , Feminino , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/mortalidade , Cardiopatias Congênitas/cirurgia , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/etiologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Pirazinas/administração & dosagem , Pirazinas/efeitos adversos , Resultado do Tratamento
16.
BMJ ; 364: l67, 2019 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-30679233

RESUMO

OBJECTIVE: To compare the effectiveness and safety of three non-tumour necrosis factor (TNF) α inhibitors (rituximab, abatacept, and tocilizumab) in the treatment of rheumatoid arthritis. DESIGN: Population based prospective study. SETTING: 53 university and 54 non-university clinical centres in France. PARTICIPANTS: 3162 adults (>18 years) with rheumatoid arthritis according to 1987 American College of Rheumatology criteria, enrolled in one of the three French Society of Rheumatology registries; who had no severe cardiovascular disease, active or severe infections, or severe immunodeficiency, with follow-up of at least 24 months. INTERVENTION: Initiation of intravenous rituximab, abatacept, or tocilizumab for rheumatoid arthritis. MAIN OUTCOME MEASURE: The primary outcome was drug retention without failure at 24 months. Failure was defined as all cause death; discontinuation of rituximab, abatacept, or tocilizumab; initiation of a new biologic or a combination of conventional disease modifying antirheumatic drugs; or increase in corticosteroid dose >10 mg/d compared with baseline at two successive visits. Because of non-proportional hazards, treatment effects are presented as life expectancy difference without failure (LEDwf), which measures the difference between average duration of survival without failure. RESULTS: Average durations of survival without failure were 19.8 months for rituximab, 15.6 months for abatacept, and 19.1 months for tocilizumab. Average durations were greater with rituximab (LEDwf 4.1, 95% confidence interval 3.1 to 5.2) and tocilizumab (3.5, 2.1 to 5.0) than with abatacept, and uncertainty about tocilizumab compared with rituximab was substantial (-0.7, -1.9 to 0.5). No evidence was found of difference between treatments for mean duration of survival without death, presence of cancer or serious infections, or major adverse cardiovascular events. CONCLUSION: Among adults with refractory rheumatoid arthritis followed-up in routine practice, rituximab and tocilizumab were associated with greater improvements in outcomes at two years compared with abatacept.


Assuntos
Abatacepte , Anticorpos Monoclonais Humanizados , Artrite Reumatoide , Rituximab , Abatacepte/administração & dosagem , Abatacepte/efeitos adversos , Adulto , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Fatores Biológicos/uso terapêutico , Estudos de Coortes , Monitoramento de Medicamentos/métodos , Monitoramento de Medicamentos/estatística & dados numéricos , Resistência a Medicamentos , Quimioterapia Combinada/métodos , Quimioterapia Combinada/estatística & dados numéricos , Feminino , França/epidemiologia , Humanos , Masculino , Estudos Prospectivos , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Análise de Sobrevida , Fator de Necrose Tumoral alfa/antagonistas & inibidores
17.
J Pediatric Infect Dis Soc ; 8(2): 97-104, 2019 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-29294072

RESUMO

BACKGROUND: Vancomycin dosing in neonates is challenging because of the large variation in pharmacokinetics. Existing empiric dosing recommendations use table-based formats, within which a neonate is categorized on the basis of underlying characteristics. The ability to individualize dosing is limited because of the small number of "dose categories," and achieving narrow exposure targets is difficult. Our objective was to evaluate a model-based dosing approach (which we designated Neo-Vanco) designed to individualize empiric vancomycin dosing in neonates. METHODS: Neo-Vanco was developed on the basis of a published, externally validated population pharmacokinetic model. Using a simulation-based methodology, individualized empiric doses that maximize the probability of attaining a 24-hour area under the curve/minimum inhibitory concentration ratio (AUC24/MIC) of >400 while minimizing troughs >20 mg/L are calculated. To evaluate the Neo-Vanco strategy, retrospective data from neonates treated with vancomycin at 2 healthcare systems were used, and empiric dose recommendations from the following 4 sources were examined: Neo-Vanco, Neofax, Red Book, and Lexicomp. Predicted AUC24 and troughs were calculated and compared. RESULTS: Overall, 492 neonates were evaluated (median postmenstrual age, 36 weeks [5th-95th percentiles (90% range), 25-47 weeks]; median weight, 2.4 kg [90% range, 0.6-4.8 kg]). The percentage of neonates predicted to achieve an AUC24/MIC of >400 was 94% with Neo-Vanco, 18% with Neofax, 23% with Red Book, and 55% with Lexicomp (all P < .0001 vs Neo-Vanco). Predicted troughs of >20 mg/L were infrequent and similar across the dosing approaches (Neo-Vanco, 2.8%; Neofax, 1.0% [P = .03]; Red Book, 2.6% [P = .99]; and Lexicomp, 4.1% [P = .27]. CONCLUSION: A model-based dosing approach that individualizes empiric vancomycin dosing was predicted to improve achievement of target exposure levels in neonates. Prospective clinical evaluation is warranted.


Assuntos
Idade Gestacional , Recém-Nascido Prematuro/sangue , Vancomicina/administração & dosagem , Vancomicina/sangue , Antibacterianos/administração & dosagem , Antibacterianos/sangue , Relação Dose-Resposta a Droga , Esquema de Medicação , Monitoramento de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Testes de Sensibilidade Microbiana , Estudos Retrospectivos
18.
Br J Clin Pharmacol ; 85(1): 194-201, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30312494

RESUMO

AIMS: CYP2D6*9, CYP2D6*10 and CYP2D6*41 are the most frequent reduced-function CYP2D6 alleles in Caucasians. Despite lacking in vivo evidence, they are collectively classified with an enzyme activity score of 0.5. Thus, the aim of this study was to compare the functional impact of CYP2D6*9, CYP2D6*10 and CYP2D6*41 on CYP2D6 metabolism in a large patient population. METHODS: A total of 1003 patients (mainly Caucasians) with data on CYP2D6 genotype and serum concentrations of venlafaxine and metabolites were included from a therapeutic drug monitoring service in Oslo, Norway. The O-desmethyl-to-N-desmethyl-venlafaxine metabolic ratio (MR) was applied as CYP2D6 biomarker and compared (Mann-Whitney) between carriers of CYP2D6*9-10 (merged) and CYP2D6*41, either combined with CYP2D6*1 or non-coding (null) alleles. MR subgroup estimates were obtained by multiple linear regression for calculations of CYP2D6*9-10 and CYP2D6*41 activity scores. RESULTS: MR was significantly lower in carriers of CYP2D6*41 than CYP2D6*9-10 (P < 0.002). The majority of CYP2D6*41/null carriers (86.7%) had MR in the observed range of CYP2D6null/null carriers compared with the minority of CYP2D6*9-10/null carriers (17.4%). CYP2D6 genotype explained 60.7% of MR variability in the multivariate analysis providing subgroup estimates of 9.54 (95% CI; 7.45-12.20), 3.55 (2.06-6.10), 1.33 (0.87-2.05) and 0.47 (0.35-0.61) in carriers of CYP2D6*1/null (n = 269), CYP2D6*9-10/null (n = 17), CYP2D6*41/null (n = 30) and CYP2D6null/null (n = 95), respectively. Based on these estimates, the calculated activity score of CYP2D6*41 was 0.095 compared to 0.34 for CYP2D6*9-10. CONCLUSIONS: CYP2D6 metabolism measured as the O/N-desmethylvenlafaxine ratio is significantly lower in Scandinavian carriers of CYP2D6*41 vs. CYP2D6*9-10. Thus, these alleles should be differentiated when classifying CYP2D6 phenotype from genotype.


Assuntos
Antidepressivos de Segunda Geração/farmacocinética , Citocromo P-450 CYP2D6/metabolismo , Monitoramento de Medicamentos/estatística & dados numéricos , Cloridrato de Venlafaxina/farmacocinética , Idoso , Alelos , Antidepressivos de Segunda Geração/administração & dosagem , Antidepressivos de Segunda Geração/sangue , Cicloexanóis/administração & dosagem , Cicloexanóis/sangue , Cicloexanóis/farmacocinética , Citocromo P-450 CYP2D6/genética , Succinato de Desvenlafaxina/administração & dosagem , Succinato de Desvenlafaxina/sangue , Succinato de Desvenlafaxina/farmacocinética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Noruega , Estudos Retrospectivos , Cloridrato de Venlafaxina/administração & dosagem , Cloridrato de Venlafaxina/sangue
19.
Med Mal Infect ; 49(3): 187-193, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30420165

RESUMO

OBJECTIVES: To assess the documentation of the 72-hour antibiotic therapy reassessment in medical records. METHODS: One-day prevalence evaluation of curative antibiotic therapies≥72hours. The documentation of the reassessment was defined according to three criteria: (1) "clear" documentation (clinical or microbiological comment associated with a comment on the need to adjust the antibiotic therapy or on the lack of need); (2) "tacit" documentation (only based on a clinical or microbiological comment); (3) no documentation. RESULTS: We assessed 114 antibiotic therapies in 26 hospital departments. A clear reassessment at 72hours was observed in only 45 (39%) records and 31 (27%) records had no reassessment. The planned duration of treatment was written in 63 (55%) records. At 72hours, among the 71 antibiotic therapies with a microbiological documentation, 69 (97%) were active and 44 (62%) had a narrow spectrum. Among the 48 antibiotic therapies with a broad spectrum on day 1, only 21 (44%) benefited from a de-escalation at 72hours. A clearly recorded reassessment at 72hours was associated with de-escalation (P=0.025) and the prescription of a planned duration of treatment was associated with antibiotic therapy compliance with local or national guidelines (P=0.018). CONCLUSION: Although reassessment was observed in 73% of records, it was correctly recorded at 72hours in only 39% of cases. The documentation of the reassessment and the prescription of a planned duration were associated with a better quality of antibiotic prescription (de-escalation, compliance with guidelines) and are relevant indicators for monitoring the proper use of antibiotics.


Assuntos
Antibacterianos/administração & dosagem , Documentação , Monitoramento de Medicamentos/métodos , Registros Médicos , Antibacterianos/efeitos adversos , Gestão de Antimicrobianos/métodos , Gestão de Antimicrobianos/organização & administração , Gestão de Antimicrobianos/normas , Estudos Transversais , Documentação/normas , Documentação/estatística & dados numéricos , Esquema de Medicação , Monitoramento de Medicamentos/normas , Monitoramento de Medicamentos/estatística & dados numéricos , França/epidemiologia , Hospitais/normas , Hospitais/estatística & dados numéricos , Humanos , Registros Médicos/normas , Registros Médicos/estatística & dados numéricos , Prevalência , Avaliação de Programas e Projetos de Saúde , Medição de Risco , Fatores de Tempo
20.
Nephrol Dial Transplant ; 34(1): 83-89, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29548021

RESUMO

Background: Monitoring of mycophenolic acid (MPA) levels may be useful for effective mycophenolate mofetil (MMF) dosing. However, whether commonly obtained trough levels are an acceptable method of surveillance remains debatable. We hypothesized that trough levels of MPA would be a poor predictor of area under the curve (AUC) for MPA. Methods: A total of 51 patients with lupus nephritis who were on MMF 1500 mg twice a day and had a 4-h AUC done were included in this study. MPA levels were measured prior to (C0) and at 1 (C1), 2 (C2) and 4 (C4) h, followed by 1500 mg of MMF. The MPA AUC values were calculated using the linear trapezoidal rule. Regression analysis was used to examine the relationship between the MPA trough and AUC. Differences in the MPA trough and AUC between different clinical and demographic categories were compared using t-tests. Results: When grouped by tertiles there was significant overlap in MPA, AUC 0-4 and MPA trough in all tertiles. Although there was a statistically significant correlation between MPA trough levels and AUC, this association was weak and accounted for only 30% of the variability in MPA trough levels. This relationship might be even more unreliable in men than women. The use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers was associated with increased MPA trough levels and AUC at 0-4 h (AUC0-4). Conclusion: Trough levels of MPA do not show a strong correlation with AUC. In clinical situations where MPA levels are essential to guide therapy, an AUC0-4 would be a better indicator of the adequacy of treatment.


Assuntos
Antibióticos Antineoplásicos/sangue , Monitoramento de Medicamentos/estatística & dados numéricos , Nefrite Lúpica/sangue , Nefrite Lúpica/tratamento farmacológico , Ácido Micofenólico/sangue , Adolescente , Adulto , Antibióticos Antineoplásicos/administração & dosagem , Área Sob a Curva , Gerenciamento Clínico , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Prognóstico , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA