RESUMO
BACKGROUND: The objective of this study was to explore the pharmacokinetics of vancomycin and determine an appropriate dosage regimen for vancomycin in adult neurosurgical intensive care unit (ICU) patients. METHODS: First, a 20-month therapeutic drug monitoring database at a medical center was used to retrospectively analyze the pharmacokinetic parameters of vancomycin in adult neurosurgical patients. Significant covariates were selected through Pearson or Spearman correlation tests and multiple linear regressions. Pharmacokinetic models were built using significant covariates to predict vancomycin clearance. Second, a 12-month prospective cohort of neurosurgical ICU patients was recruited to validate the models. Urine and cerebrospinal fluid samples were collected, and vancomycin concentrations were determined using a high-performance liquid chromatography assay. The relation between the model-predicted and observed pharmacokinetic parameters was assessed by Pearson correlation. RESULTS: In the retrospective cohort, 98 sets of peak/trough serum concentrations obtained from 73 patients were analyzed. These patients had a mean age of 54 ± 16 years, an estimated creatinine clearance (eClCr) of 83 ± 29 mL/min, a total vancomycin clearance (ClVan) of 101 ± 41 mL/min, and a volume of distribution (Vd) of 0.93 ± 0.27 L/kg. In a subgroup analysis, the ClVan of ICU patients was higher than the ClVan of non-ICU patients (1.57 ± 0.34-fold versus 1.16 ± 0.32-fold of eClCr, P < 0.05). Fifteen patients enrolled in the prospective cohort had an average age of 67 ± 12 years, an eClCr of 108 ± 44 mL/min, a ClVan of 112 ± 29 mL/min, and a Vd of 1.03 ± 0.55 L/kg. CONCLUSIONS: Adult neurosurgical ICU patients have a significantly elevated ClVan. In this study, 2 dosing equations were derived to achieve optimal serum vancomycin concentrations for this special population.
Assuntos
Antibacterianos/farmacocinética , Vancomicina/farmacocinética , Adulto , Idoso , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Estudos RetrospectivosRESUMO
BACKGROUND/PURPOSE: Combined therapy of sirolimus and cyclosporine has been found to exacerbate cyclosporine-related nephrotoxicity and to imperil graft renal function. We hypothesized that tacrolimus could bring about better renal function than cyclosporine when used in combination with sirolimus and corticosteroids for de novo renal transplantation. METHODS: A two-arm randomized study was conducted to test the hypothesis. Patients who gave written informed consent and received renal transplantation were randomized to take sirolimus in combination with either tacrolimus or cyclosporine. The primary endpoint of this study was renal function, and the secondary endpoints were acute rejection, graft and patient survival, metabolic side effects and infectious complications. RESULTS: A total of 41 Taiwanese renal transplant patients were randomized to receive cyclosporine (CsA group, n = 20) or tacrolimus (TAC group, n = 21) in combination with sirolimus and corticosteroids. The average estimated glomerular filtration rate (eGFR) was 52.77 +/- 3.86 mL per minute for the TAC group at 6 months, and 46.42 +/- 3.95 mL per minute for the CsA group (p > 0.05). At 12 months, the average eGFR was 52.04 +/- 4.38 mL per minute for the TAC group, and 46.79 +/- 4.38 mL per minute for the CsA group (p > 0.05). The biopsy-proven acute rejection rate of the TAC group was 4.76% (1/21), and that of the CsA group was 5.00% (1/20) at 12 months. The 12-month graft survival rates for the TAC and CsA groups were 100% and 90% (p = 0.142), respectively. CONCLUSION: Our study demonstrated that concomitant tacrolimus and sirolimus therapy resulted in a favorable outcome in Taiwanese renal transplant patients at 12 months. Large-scale clinical trials will be needed to further address the issue of which calcineurin inhibitor, cyclosporine or tacrolimus, provides better renal function and graft survival for renal transplant patients.
Assuntos
Imunossupressores/administração & dosagem , Transplante de Rim , Sirolimo/administração & dosagem , Tacrolimo/administração & dosagem , Adulto , Ciclosporina/administração & dosagem , Feminino , Taxa de Filtração Glomerular , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , MasculinoRESUMO
BACKGROUND: The clinical benefits of a combination of statins and ezetimibe in patients with acute coronary syndrome (ACS) were observed in a clinical trial. However, little is known regarding the effectiveness of using statins with or without ezetimibe in patients with ACS and multiple comorbidities in real-world clinical practice. METHODS: This is a nationwide population-based cohort study using Taiwan National Health Insurance Research Database. A total of 212,110 patients with ACS who had been discharged after their first ACS events between 2006 and 2010 were enrolled. A propensity score matching approach was used to create matched cohorts for adjusting potential confounders. Cox proportional hazards regressions were performed to estimate the risk of re-hospitalization for ACS and revascularization. RESULTS: Patients in the statins-plus-ezetimibe group had a significantly lower risk of re-hospitalization for ACS (adjusted hazard ratio [HR]=0.64, 95% confidence interval [CI]: 0.60-0.69) and revascularization (HR=0.69, 95% CI: 0.63-0.76) than those in the statins-alone group. In the statins-plus-ezetimibe group, female patients had a lower risk of re-hospitalization for ACS than male patients did, and patients without diabetes mellitus had a lower risk of re-hospitalization for ACS than did patients with diabetes mellitus. CONCLUSIONS: Patients with ACS and multiple comorbidities receiving a combination therapy of statins and ezetimibe had a lower risk of re-hospitalization for ACS and revascularization than those receiving statins alone. Significant interaction effects were observed between combination with ezetimibe, sex, and diabetes mellitus.
Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Dislipidemias/epidemiologia , Ezetimiba/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Vigilância da População , Síndrome Coronariana Aguda/epidemiologia , Idoso , Anticolesterolemiantes/administração & dosagem , Comorbidade , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Dislipidemias/tratamento farmacológico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Taxa de Sobrevida/tendências , Taiwan/epidemiologia , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: The purpose of this study was to examine the association between statin use by individuals and the risk for incident diabetes mellitus in patients with acute coronary syndrome (ACS) following percutaneous coronary intervention (PCI). METHODS: We conducted a retrospective cohort study of patients who were hospitalized for ACS between January 1, 2006, and December 31, 2010, and who had undergone PCI (n=30,665); the data were retrieved from the Taiwan National Health Insurance Research Database. A propensity score technique was used to establish a 1:1 matched cohort for statin users and non-statin users (n=9043 for each group). The risk for incident diabetes mellitus in statin users compared to non-statin users for patients with ACS after PCI was estimated by the multivariable Cox proportional hazards regression model. RESULTS: Statin use was associated with a significant increase of 27% in the risk for new-onset diabetes mellitus (adjusted hazard ratio [HR] 1.27, 95% CI 1.14 to 1.41) compared to non-statin use in the matched cohort. The matched cohort analysis indicated that almost all individual statins were associated with a statistically significant increase in the risk for new-onset diabetes mellitus compared to those without statin use. CONCLUSIONS: Our study indicated an association between increased risk for new-onset diabetes mellitus and statin use. Because the benefits of statins in prevention of morbidity and mortality in patients with ACS are well-established, clinical decision making should not be changed for patients with existing cardiovascular disease in whom statin therapy is recommended.
Assuntos
Síndrome Coronariana Aguda/complicações , Diabetes Mellitus/epidemiologia , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Idoso , Tomada de Decisões , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Incidência , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Taiwan/epidemiologiaRESUMO
PURPOSE: This study aimed to use the National Health Insurance Research Database, Taiwan for risk analysis of concomitant use of cisapride and erythromycin. METHODS: The sample consisted of subjects identified in the Outpatient Sampling Database (OSD) and Longitudinal Health Insurance Database 2000 (LHID 2000), derived from the original claim data of the National Health Insurance Research Database, Taiwan. RESULTS: According to the LHID 2000, a total of 464 individuals experienced 685 episodes of cisapride-erythromycin co-medication prescribed by 295 physicians, revealing a prevalence of 4.5% concomitant use, with higher prevalence in clinics (9.2%) than in other medical institutes (3.7-5.4%). Among the co-medication episodes, 81.9% and 61.2% were prescribed from the same health institutes and by the same physicians, respectively. No medical record of cardiac arrhythmias was found among these patients in 2001 and 2002, probably due to the fact that 78.9% of the 464 individuals were under age 16, 84.0% had short exposure duration (1-4 days) and 98.0% of the episodes were prescribed with a cisapride dose of less than 0.8 mg/kg/day. CONCLUSIONS: Findings from this study suggest that there exists an urgent need for accreditation in terms of pharmacovigilance of clinical sites and their practicing physicians for the prevention of irrational concomitant prescription in Taiwan. Our findings also indicate that it is necessary to investigate other possible conditions of potentially dangerous co-medication in Taiwan and other developing countries.