Stability of tedizolid phosphate-sodium rifampicin and tedizolid phosphate-meropenem admixtures in intravenous infusion bags stored at different temperatures.

This is a report on the chemical stability and physical compatibility of intravenous tedizolid phosphate 0.8 mg/mL-sodium rifampicin 2.4 mg/mL and tedizolid phosphate 0.8 mg/mL-meropenem 4 mg/mL combinations in polypropylene 0.9% sodium chloride infusion bags stored at different storage conditions. Triplicate solutions of both admixtures were prepared in 0.9% sodium chloride polypropylene infusion bags and stored under light protection at room temperature (25±2 °C), refrigeration (2-8 °C) or freezing (-15 - -25 °C) conditions. The study was performed using a validated and stability-indicating liquid chromatography (LC) method. For both admixtures and for all storage conditions, at least 90% of the initial drug concentration of tedizolid phosphate remained unchanged throughout the entire study period. Stability of sodium rifampicin at 25±2 °C was determined to be seven hours and six days when it was stored at 2-8 °C. Under the same storage conditions, meropenem was stable for 12 h or 6 days, respectively. Under freezing conditions, sodium rifampicin was stable throughout all 28 days, while stability of meropenem was only 8 days. Solutions of 0.8 mg/mL tedizolid phosphate admixtured with 2.4 mg/mL rifampicin or 4 mg/mL meropenem, in polypropylene 0.9% sodium chloride infusion bags, are stable for at least 7 or 12 hours, respectively, when stored at 25±2 °C. When stored at 2-8 °C, stability was increased to 6 days for both admixtures.

[Translated article] Efficacy and marginal cost of treatment with tocilizumab in COVID-19 patients.

OBJECTIVE: To describe the marginal cost and survival of patients treated with tocilizumab in a university hospital under real-life conditions and to evaluate factors that could influence costs and health outcomes will be evaluated. METHODS: Observational, single-center, retrospective study of a cohort of adult patients infected with SARS-COV2 treated with tocilizumab. The 1 year restricted mean survival time was analyzed in life-years gained (LYG). The influence of sex, age and severity on patient survival was evaluated. The marginal cost/LYG and marginal cost/survivor ratios were calculated. RESULTS: 508 patients (66 ±â€¯13 years; 32% women) were included. Seventeen percent were admitted to the ICU. Overall survival was 77%. Age older than 71.5 years (HR = 1.08; 95% CI 1.07-1.10; p < 0.001) and ICU admission at initiation of treatment (HR = 2.01; 95% CI 1.30-3.09; p = 0.002) were identified as risk factors. The total budgetary impact of tocilizumab in the period analyzed was 206,466 euros. The patients with the highest cost per unit of health outcome were those admitted to the ICU and those over 71.5 years, with a marginal cost/LYG of €966 and a marginal cost/survivor of €1136. CONCLUSION: The efficiency of treatment with tocilizumab is associated with the age and severity of the patients. The figures are lower in all subgroups than the thresholds usually used in cost-effectiveness evaluations. The results of the present study suggest that early first dose of tocilizumab is an efficient strategy.

[Costs and adherence to antiretroviral treatment]. / Costes y adherencia del tratamiento antirretroviral.

OBJECTIVE: To develop a system of data management that allows us to estimate the comparative effectiveness of the various antiretroviral treatment (ART) regimens. METHOD: Retrospective observational study in patients infected with HIV with stable ART. Adherence to treatment and unit cost for each patient's treatment was determined. The cost/patient/day was calculated and, multiplying by an adherence factor (fADH), the (cost/patient/day)(ADH). The comparison of both allowed us to obtain the Δcost/patient, which estimates the additional costs caused by lack of adherence. The incremental cost-effectiveness (iCER), grouping the results by the various coformulated drugs ("combos"). A study of the budgetary impact of these combos was carried out. RESULTS: 468 patients were evaluated (62% adherent). Average adherence was 88±18%. The average value of (cost/patient/day) (ADH) was significantly higher than the cost/patient/day (27.3±9.8€ compared to 24.3±7.6€. p<0.001). Just as with the f(ADH), no differences were found in the Δcost/patient between the different ART combinations. The combo with the least deviation from the cost/patient/day due to lack of adherence was that composed of abacavir/zedovudine/lamivudine (ABC/AZT/3TC,Δcost/patient=8.72±14.18%), and that with the greatest deviation AZT/3TC (Δcost/patient=13.52±17.68%). No significant differences were found in the iCER calculated for any combo. The ART that included abacavir/lamivudine (ABC/3TC) obtained the least budgetary impact. CONCLUSIONS: The greatest cost and percentage of adherent patients associated with the combos composed of Tenovovir/Emtricitabine(TDF/FTC) and ABC/3TC, and the least cost and effectiveness of those composed of AZT/#TC and ABC/AZT/3TC, does not allow us to identify any option as significantly dominant. The regimens with ABC/3TC were shown to be the most favourable from the combined point of view of cost and adherence.

[Design and validation of a dosing algorithm for vancomycin in premature neonates]. / Diseño y validación de un esquema de dosificación de vancomicina en neonatos prematuros.

INTRODUCTION: Inappropriate use of vancomycin contributes to the development of resistant bacteria and jeopardizes the safety and effectiveness of treatment. The aim of this article was to design and validate an empirical dosing algorithm for vancomycin in premature neonates according to their population-based pharmacokinetic characteristics. PATIENTS AND METHODS: We performed a retrospective analysis of 129 serum samples from a cohort of 53 neonates. Homogeneous population groups were identified both from their individual pharmacokinetic parameters and from their biometric characteristics. The design of the dosing algorithm was based on simulation of the serum vancomycin concentration that would be reached with several different doses. The algorithm was validated in another cohort of 30 neonates and 108 serum samples. RESULTS: Introduction of the algorithm significantly increased the percentage initial values obtained with correct minimum and maximum concentrations in the first monitoring round (p<0.05). The mean number of serum samples obtained per patient for treatment monitoring was significantly reduced (3.6+/-2 vs. 4.9+/-3). CONCLUSIONS: The implantation of the dosing algorithm for vancomycin in premature neonates increased the efficiency of treatment, reduced monitoring requirements, and optimized serum vancomycin concentrations from the start of treatment.

[Stability in serum of intravenous busulfan in a polyolefin pack]. / Estabilidad en suero fisiológico del busulfán intravenoso en un envase de poliolefinas.

INTRODUCTION: Although it has been used orally, the variability in its absorption and the risk of causing vomiting has lead to a push towards the intravenous use of bulsulfan. This study looks at the stability of 60 mg of busulfan, in fixed volumes of 250 mL (0.24 mg/mL) and 500 mL (0.12 mg/mL) of serum and different conservation conditions, in a new plastic pack made from polyolefin/polyamide laminates. MATERIAL AND METHODS: High-efficiency liquid chromatography with ultraviolet detection was used to determine the concentration of busulfan derivate with sodium diethyldithiocarbamatetrihydrate. Stability was assessed for both concentrations; refrigerated and at room temperature, using the t(90) of each sample. RESULTS: The percentage of the remaining busulfan concentration at 24 h was always less than 90%. At 25 degrees C and 0.24 mg/mL concentration, the t90 was 8.4 h; at 4 degrees C and a concentration of 0.24 mg/mL it was 16.7 h; at 25 degrees C and a concentration of 0.12 mg/mL it was 12 h and at 4 degrees C and a concentration of 0.12 mg/mL it was 11.5 h. CONCLUSIONS: This study show that busulfan in a concentration of 0.24 mg/mL in serum is stable in the bags tested during a refrigerated storage period of 12 h plus two additional hours of administration of the drug.

[The pharmacokinetics of metronidazole and gentamicin in a single preoperative dose as antibiotic prophylaxis in colorectal surgery]. / Farmacocinética del metronidazol y la gentamicina en dosis única preoperatoria para profilaxis antibiótica quirúrgica en cirugía colorrectal.

OBJECTIVE: To describe, in patients undergoing colorectal surgery (CRS), the pharmacokinetics of a single, prophylactic preoperative dose of 1,500 mg of metronidazole plus 240 mg gentamicin and measure its efficacy in accordance with the accepted pharmacodynamic and microbiological parameters. METHOD: Thirty-six patients undergoing CRS agreed to participate in the study. Three blood samples were taken from each. Cmax 15 minutes after finishing the infusion of the mixture, CfinIQ on finishing the surgery, and Cmin between 12 and 24 hours post-administration. The concentrations of metronidazole and gentamicin in each simple were measured and the pharmacokinetic parameters were estimated (dV- distribution volume , Cl-plasma clearance). For the metronidazole, concentrations in excess of 8 microg/ml were considered effective, and for gentamicin, C(max) in excess of 9 microg/ml and inhibition quotients above 8. RESULTS: All the concentrations of metronidazole, both CmaxMTZ and CfinIQMTZ were above 8 microg/ml and all the CmaxGEN in excess of 9 microg/ml. The CIGEN was 13.8+/-3.8, with no individual value below 8. For the metronidazole, a dV of 0.68+/-0.2 l/kg was estimated and a Cl of 3.15+/-1.20 l/h and for the gentamicin, the dV as 0.23+/-0.06 l/kg and the Cl was 4.71+/-1.95 l/h. CONCLUSION: In patients undergoing CRS, surgical intervention did not significantly modify the pharmacokinetics of metronidazole or gentamicin in comparison with other groups of patients. The prophylaxis using a single, pre-surgical dose enables the achievement, for both antimicrobial agents, concentrations of a sufficient size to guarantee clinical efficacy.

[Simplified scale for medication adherence related problems in anti-retroviral therapy]. / Escala simplificada para detectar problemas de adherencia (ESPA) al tratamiento antirretroviral.

OBJECTIVE: The purpose is to describe an own-developed scale for medication adherence evaluation of HIV patients under antiretroviral therapy, and to compare it with other previously described methods. METHODS: The six-item scale was compared with a pharmacy record about the delivery of medication. Accordance between scale and a four-item Morisky-type scale (measure 1) and a percentage of doses taken as prescribed during the past two weeks (measure 2) was computed. RESULTS: The own-scale showed 93% sensitivity, 70% specificity, a likelihood ratio of 3.08 and good agreement compared with the pharmacy record (k = 0.62, p < 0.001). Agreement between the scale and measure 1 and measure 2 was very weak (k = 0.12, p = 0.446 and k = 0.10, p = 0.273 respectively). 39.7% of patients was considered as adherent according with the own-scale and was observed correlation between adherence and clinical outcomes. CONCLUSION: The scale appears to be a valid instrument to check and detect adherence related problems compared with the pharmacy medication record. Easiness to use make feasible to consider as an adequate tool to detect non-adherent patients or patients with adherence related problems into the daily clinical practice.

[Pharmacoeconomic assessment of two tocolysis protocols for the inhibition of premature delivery]. / Evaluación farmacoeconómica de dos protocolos de tocolisis para la inhibición del parto prematuro.

OBJECTIVE: Pharmacoeconomic assessment of two tocolysis protocols alternatively using atosiban or ritodrine as first-choice tocolytic agent able to delay birth for 48 hours in the acute management of premature birth risk in gravid women. METHODS: The modeling technique used for the selection of the most efficient protocol was the decision analysis. A search for controlled clinical trials comparing the effectiveness and/or safety of atosiban versus ritodrine was performed in Medline and the Cochrane Library. Only differential costs were considered for cost analysis. RESULTS: Cost-effectiveness obtained with the protocol including ritodrine as first-choice drug was Euros 194/effectiveness unit, and Euros 632/effectiveness unit when atosiban is used. The sensitivity analysis shows sensitivity only for an incidence of acute lung edema greater than 8% or a cost of at least Euros 50,000. CONCLUSION: A tocolysis protocol using ritodrine as first-choice agent and atosiban as rescue drug is the most efficient option based on available evidence. In pregnant women where the likelihood of developing acute pulmonary edema is high, or when therapy cost is high, atosiban may be an appropriate alternative option.

[HIV-infected patients' perceived satisfaction with an outpatient pharmaceutical care unit (OPCU)]. / Originales Breves Satisfacción percibida por pacientes infectados por el VIH con la unidad de atención farmacéutica a pacientes externos (UFPE).

INTRODUCTION: Satisfaction measurements attempt to establish patient views regarding health care. In the setting of pharmaceutical care, the measurements of the generically called "h umanistic"variables is scarce, and the number of validated instruments is inadequate. The goal of this study is to present a specifically-developed satisfaction survey regarding outpatient pharmaceutical care units, and to prove its applicability and inner consistency in a HIV-infected patient population on antiretroviral therapy. METHODS: The survey includes 19 questions within four groups - A. The unit's physical space, location, and organization; B. Dispensation; C. Pharmaceutical consultation, and D. Overall satisfaction with the unit. Each question is scored from 1 to 5. The study was carried out by administering 250 surveys to consecutive patients arriving at the OPCU, Castell6n General Hospital. RESULTS: Responses show a high degree of patient satisfaction with questions posed, with mean values oscillating between 3.0 and 4.8. The highest means corresponded to pharmacist valuation, and the lowest values corresponded to questions within the organizational module. All questions considered, the mean score obtained was 3.96 + 0.95 (median of 4). The survey exhibited high internal reproducibility both for each group and all questions. CONCLUSION: The satisfaction survey discussed here is an accessible, easy-to-use instrument that may be rapidly completed and used in pharmaceutical care units with outpatients as a measurement of patient satisfaction. The high scores HIV-infected patients assign to questions included in the survey suggest a benefit from standardized pharmaceutical care.

Effectiveness and safety of once-daily aminoglycosides: a meta-analysis.

The effectiveness and safety of once-daily versus several-times-daily aminoglycosides were studied in a meta-analysis. MEDLINE for 1988 to 1995 was searched, and additional studies were identified from review articles and references in retrieved articles. Studies selected for meta-analysis were randomized controlled clinical trials in nonneutropenic adult patients comparing the clinical effectiveness or nephrotoxicity or ototoxicity of once-daily with several-times-daily aminoglycosides. Differences between groups were expressed as odds ratios. The results were combined by the procedure of Mantel and Haenszel, and 95% confidence intervals and exact confidence intervals were computed. An odds ratio smaller than 1 would indicate a lesser likelihood of a given endpoint in the once-daily group, and an odds ratio greater than 1 would indicate a greater likelihood. Eighteen studies involving 2317 patients were included in the meta-analysis. Summary odds ratios were 1.47 for effectiveness (95% CI = 1.13-1.94), 0.56 for ototoxicity (95% CI = 0.26-1.16), and 0.60 for nephrotoxicity (95% CI = 0.40-0.86). A meta-analysis showed that treatment with single daily doses of aminoglycosides seems to be more effective, less nephrotoxic, and as ototoxic as multiple doses daily.

[Miliary tuberculosis and cerebral tuberculomas. Apropos a case]. / Tuberculosis miliar y tuberculomas cerebrales. A propósito de un caso.

We present a case of a 45-year-old patient with miliary tuberculosis (MI), whose initial clinical symptomatology was uncertain. A few weeks after the beginning of chemotherapy, and in the face a Jacksonian crisis, cerebral tuberculomas were detected with CAT. The interesting thing in this case is to highlight that the diagnosis of MT anatomopathologic after pulmonary biopsy with mini-thoracotomy and that the cerebral complication could be classified within the so-called "paradoxical worsening" as it has been documented in the literature.

[Pharmaceutical care program in HIV patients under antiretroviral treatment: methodology and documentation]. / Programa de atención farmacéutica a pacientes VIH con tratamiento antirretroviral: metodología y documentación.

Most hospital pharmacy services in Spain have increased pharmaceutical care activities for HIV-patients under antiretroviral therapy during last years. So, it is necessary the establishment of work methods to secure the best quality of care. The pharmacy service of the general hospital of Castellón has developed a global pharmaceutical care program for these patients characterized by the systematic and individualized strategy or basic pharmaceutical care record which can be completed with additional proceedings. The basic record includes complete drug therapy registry, clinical evolution data and detection of drug related problems (DRP), evaluation and promotion of patient adherence, individualized counselling and nutritional evaluation. Additional proceedings include exhaustive DRP monitoring, additional patient adherence to treatments measurements, SOAP methodology, quality of life and perceived patient satisfaction. Our purpose integrate patient status with pharmaceutical care provided and the expected or obtained outcomes, either clinical or economic as well as activity outcomes, quality of life and satisfaction related results. The main characteristics of the purposed methodology are: clinical orientation, it permits the registry and the establishment of a systematic work methodology, is designed as a cross structure and variables are coded. According to our experience, our model can be considered useful in clinical practice and could be applied in different hospital outpatient units.

[Managing methotrexate toxicity: a case report]. / Manejo de la intoxicación por metotrexato: a propósito de un caso.

High-dose methotrexate is included in chemotherapy regimens used to treat a number of malignant neoplasms. Methotrexate plasma concentration is considered the best toxicity predictor. Monitoring methotrexate plasma concentrations is standard practice in the identification of at-risk patients, the titration of folinic acid doses, and the establishment of corrective measures. Methotrexate is a kidney-cleared weak acid, and renal function impairment may retard methotrexate clearance. A case of severe methotrexate-induced toxicity secondary to renal failure is reported in a patient with non-Hodgkin s lymphoma receiving methotrexate at a dose of 1 g/m2. Corrective measures included folinic acid rescue therapy, cholestyramine resin administration, hydration and urine alkalinization, urine pH monitoring, and extracorporeal clearance techniques.

[Pharmacokinetic monitoring of 24-hour infusion of methotrexate in an adult population with non-Hodgkin lymphoma]. / Monitorización farmacocinética del metotrexato en infusión de 24 horas en una población adulta afectada de linforma no Hodgkin.

OBJECTIVES: To describe the behavior and variability of methotrexate (MTX) pharmacokinetic parameters in patients with non-Hodgkin lymphoma (NHL) and to suggest a monitoring system to optimize sample collection using a bayesian method. METHOD: Two adult patient groups diagnosed with different NHL types were studied. Group I was made up of 9 patients aged 53 +/- 16 years who received MTX at a mean dose of 1.652 +/- 327 mg per course. Group II was made up of 7 patients aged 53 +/- 14 years who received MTX at a mean dose of 1.862 +/- 220 mg per course. No statistically significant differences between groups were seen. Serum MTX measurements were performed using polarized immunofluorescence (TDx system). The pharmacokinetic analysis was performed using Abbottbase Pharmacokinetics Systems (PKS) software, adjusting experimental data according to a bicompartmental linear model for intravenous delivery using non-linear regression in Group I and Bayesian estimates in Group II. By estimating mean square error and linear regression between predicted and experimental concentrations, the capability of the Bayesian method implemented in PKS to predict plasma MTX concentration at 48 hours post-infusion was evaluated. The safety of MTX therapy was assessed using patient medical histories and then scoring toxicity using the WHO scale. RESULTS: Pharmacokinetic parameters obtained for group I included: alpha (h(-1)) = 0.38 +/- 0.12; beta (h(-1)) = 0.07 +/- 0.03; K12 (h(-1)) = 0.02 +/- 0.02; K21 (h(-1)) = 0.09 +/- 0.09; K13 (h(-1)) = 0.34 +/- 0.12; Vc (l/kg) = 0.53 +/- 0.23; Vss (l/kg) = 0.62 +/- 0.26; Cl (l/kg.h) = 0.16 +/- 0.06. The error for the PKS population model in measuring plasma MTX concentration at 48 hours post-infusion in Group II was calculated in accordance with three sampling schemes -12 h, 24 h, and both. It was -14.58 x 10(-3), -15.70 x 10(-3) and -14.67 x 10(-3), respectively. Eqm was 9.58 x 10(-3), 2.39 x 10(-3), and 1.02 x 10(-3), respectively. CONCLUSION: An MTX monitoring scheme is suggested based on a Bayesian method implementing pharmacokinetic parameters obtained from an adult population with NHL, which allows therapy safety and the clearance profile of MTX to be predicted from a single sample collected at 24 hours post-infusion.

[Acute renal failure probably associated with topiramate]. / Fallo renal agudo probablemente asociado a topiramato.

A case of acute renal failure probably associated with topiramate is discussed. The patient showed a significant, progressive increase in creatinine and serum urea values 5 days after topiramate treatment onset, as well as diminished creatinine clearance and non-oliguric acute renal failure requiring haemodialysis initiation. Upon topiramate discontinuance altered parameters became normal. No significant alterations were revealed by ultrasonography and renal biopsy. Coincidence in time and the absence of other factors suggest topiramate as likely cause of renal failure.

[Monitoring of intraperitoneal administration of vancomycin in patients on continuous ambulatory peritoneal dialysis]. / Monitorización de la vacomicina en administración intraperitoneal en pacientes sometidos a diálisis peritoneal continua ambulatoria.

OBJECTIVE: To validate a pharmacokinetic model of the treatments with intraperitoneal vancomycin applied to patients on continuous ambulatory peritoneal dialysis with bacterial peritonitis. METHODS: To carry out a prospective study divided in 2 cohorts: the first one including ten patients of 56±14 years and 65±5 kg, and the second one with 10 patients (12 episodes of peritonitis) aged 52±13 years and 64±8 kg. The treatment consists of administering and retaining for 6 h in the peritoneal cavity a solution containing 2 g of vancomycin and 1 g of ceftazidime into 2 l of "dialysis solution". After the antibiotic administration, blood samples were obtained at 4, 6, 8, 10, 24, 48 and 168 h in the first cohort and at 6 and 120 h (C(VAN)(120)) in the second. The pharmacokinetic model was developed from the parameters obtained from the first cohort and was validated by the second cohort, calculating the mean error (ME) and the mean squared prediction error (MSPE) of the C(VAN)(120). RESULTS: Vancomycin serum concentrations fell from 39.63±7.62 mcg/ml at 4h to 8.55±2.87 mcg/ml at 168 h for the first cohort, and from 37.65±6.84 mcg/ml at 6h to 10.82±2.66 mcg/ml at 120 h (C(VAN)(120)) for the second cohort. The pharmacokinetics parameters were: C1=0.006 1/h/kg and Vd:=0.52 1/kg for the first cohort, and C1=0.006 1/h/kg and Vd:=0.53 1/kg for the second. The predictive ME and MSPE of the C(VAN)(120). were 0.59 mcg/ml ([EM*100/C(VAN)(120)=5.5%) and 10.38 mcg(2)/ml(2) ([MES*100/(C(VAN)(120))(2)]) respectively. CONCLUSION: The presented model shows an adequate exactitude and precision for the monitoring of intraperitoneal vancomycin in patients submitted to continuous ambulatory peritoneal dialysis with peritonitis.

Comparing the digoxin test with the Architect® i1000sr system with respect to the AxSYM® system.

OBJECTIVE: To assess the technique employed by the autoanalyser Architect® i1000sr to determine digoxin in serum samples, compared with the assay developed for AsSYM® using microparticle enzyme immunoassay (DigoxinII). METHOD: A prospective analysis of the samples from 100 requests to monitor patients being treated with digoxin. The samples were processed in AxSYM® and Architect®. The techniques were assessed using the linear regression coefficient, determination coefficient, mean absolute error, mean squared prediction error and the Bland-Altman method. RESULTS: The serum levels showed a correlation coefficient of 0.93. There was nearly a 40% difference for the concentrations between 0.8 and 2 ng/ml and nearly 20% in the rest of the samples analysed. CONCLUSIONS: The Architect® system is precise; however, from a clinical monitoring point of view, it is unacceptably inaccurate when compared with the AxSYM®.