Quantitative assessment of the exposure-efficacy relationship of glucocerebrosidase using Markovian elements in Gaucher patients treated with enzyme replacement therapy.

AIMS: The aims of this study are (i) to develop a population pharmacokinetic model of enzyme activity in Gaucher-type 1 (GD1) patients after intravenous administration of enzyme replacement therapy (ERT), and (ii) to establish an exposure-efficacy relationship for bone marrow infiltration to propose dose adjustments according to patient covariate values. METHODS: A prospective follow-up, semi-experimental multi-centre study was conducted in four hospitals to evaluate the pharmacokinetics, efficacy and safety of ERT in GD1 patients. Twenty-five individuals with 266 glucocerebrosidase (GCase) observations in plasma and leukocytes and 14 individuals with 68 Spanish magnetic resonance imaging (S-MRI) observations were enrolled. RESULTS: A two concatenated compartment model with zero-order endogenous production and first-order distribution (CL1 = 3.85 × 10-1 L/d) and elimination (CL2 = 1.25 L/d) allowed GCase observations in plasma and leukocytes to be described, respectively. An exponential time dependency (kT = 6.14 × 10-1 d-1 ) effect on CL1 was incorporated. The final exposure-efficacy model was a longitudinal logistic regression model with a first-order Markov element. An Emax function (EC50 = 15.73 U/L and Emax = 2.33) linked steady-state concentrations of GCase in leukocytes to the probability of transition across the different S-MRI stages. CONCLUSION: A population pharmacokinetic model successfully characterized the leukocyte activity-time profiles of GCase following intravenous administration of ERT in GD1 patients together with an exposure-efficacy relationship in bone marrow using Markovian elements. The information obtained from this study could be of high clinical relevance in individualization of ERT in GD1 patients, as this could lead to anticipative decision-making regarding clinical response in bone and optimal dosing strategy.

Evaluation of ABC gene polymorphisms on the pharmacokinetics and pharmacodynamics of capecitabine in colorectal patients: Implications for dosing recommendations.

AIMS: The aims are to develop a population pharmacokinetic model of capecitabine (CAP) and its main metabolites after the oral administration of CAP in colorectal cancer patients with different polymorphisms of the ATP-binding cassette (ABC) gene and a population pharmacokinetic/pharmacodynamic model capable of accounting for the neutropenic effects, and to optimize the dosing strategy based on the polymorphisms of the ABC gene and/or the administration regimen as a single agent or in combination. METHODS: Forty-eight patients diagnosed with colorectal cancer were included, with 432 plasma levels of CAP, 5'-desoxi-5-fluorouridine (5'-DFUR) and 5-fluorouracil (5-FU), and 370 neutrophil observations. Capecitabine doses ranged from 1250 to 2500 mg/m2 /24 h. Plasma measurements of CAP, 5'-DFUR and 5-FU were obtained at 1, 2 and 3 hours post administration. Neutrophil levels were measured between day 15 and day 24 post administration. RESULTS: The pharmacokinetic model incorporates oxaliplatin as a covariate on absorption lag time, rs6720173 (ABCG5 gene) on clearance of 5'-DFUR (182% increase for mutated rs6720173) and rs2271862 (ABCA2 gene) on clearance of 5-FU (184% increase for mutated rs2271862). System- (Circ0 = 3.54 × 109 cells/mL, MTT = 204 hours and γ = 6.0 × 10-2 ) and drug-related (slope [SLP] = 3.1 × 10-2 mL/mg). Co-administration of oxaliplatin resulted in a 2.84-fold increase in SLP. The predicted exposure thresholds to G3/4 neutropenia in combination and monotherapy were 26 and 70 mg·h/L, respectively. CONCLUSIONS: The population pharmacokinetic/pharmacodynamic model characterized the time course of capecitabine and its metabolites in plasma. Dose recommendations of capecitabine in patients with mutated and wild allele for single nucleotide polymorphisms rs2271862 of ≤3000 and ≤2400 mg/m2 /24 h in monotherapy and ≤1750 and ≤600 mg/m2 /24 h in combination with oxaliplatin, respectively, have been proposed.

Impact of intermediate to high doses of methylprednisolone on mortality rate in patients with COVID-19 pneumonia-induced severe systemic inflammation.

INTRODUCTION: In addition to respiratory support needs, patients' characteristics to guide indication or timing of corticosteroid treatment in COVID-19 patients are not completely established. This study aimed to evaluate the impact of methylprednisolone on mortality rate in patients with COVID-19 pneumonia-induced severe systemic inflammation (PI-SSI). METHODS: Between 9 March and 5 May 2020 (final follow-up on 2 July 2020), a retrospective cohort study was conducted in hospitalised patients with COVID-19 PI-SSI (≥2 inflammatory biomarkers [IBs]: temperature ≥38℃, lymphocyte ≤800 cell/µL, C-reactive protein ≥100 mg/L, lactate dehydrogenase ≥300 units/L, ferritin ≥1000 mcg/L, D-dimer ≥500 ng/mL). Patients received 0.5-1.0 mg/kg of methylprednisolone for 5-10 days or standard of care. The primary outcome was 28-day all-cause mortality. Secondary outcomes included ≥2 points improvement on a 7-item WHO-scale (Day 14), transfer to intensive care unit (ICU) (Day 28) and adverse effects. Kaplan-Meier method and Cox proportional hazard regression were implemented to analyse the time to event outcomes. RESULTS: A total of 142 patients (corticosteroid group n = 72, control group n = 70) were included. A significant reduction in 28-day all-cause mortality was shown with methylprednisolone in patients with respiratory support (HR: 0.15; 95% CI 0.03-0.71), with ≥3 (HR: 0.17; 95% CI 0.05-0.61) or ≥4 altered IB (HR: 0.15; 95% CI 0.04-0.54) and in patients with both respiratory support and ≥3 (HR: 0.11; 95% CI 0.02-0.53] or ≥4 altered IB (HR: 0.14; 95% CI 0.04-0.51). No significant differences were found in secondary outcomes. CONCLUSION: Intermediate to high doses of methylprednisolone, initiated between 5 and 12 days after symptom onset, was associated with a significant reduction in 28-day all-cause mortality in patients with COVID-19 pneumonia and ≥3 o ≥ 4 altered IB, independently of the need of respiratory support.

Quantitative and qualitative control of antineoplastic preparations: Gravimetry versus HPLC.

This article compares gravimetry vs. high-performance liquid chromatography (HPLC) as quality control (QC) methods for paclitaxel, docetaxel and oxaliplatin preparations. We aimed at assessing the preparation method reliability in our hospital, evaluating compounding accuracy and estimating the influence of personnel training and standardized homogenization on compounding accuracy. Agreement, correlation, concordance, accuracy and precision between methods were evaluated for each drug. Conforming preparation percentages (CPs) at different tolerance limits (TLs) and compounding accuracy were calculated for each method and drug. Compounding accuracy was compared before and after personnel training and standardized homogenization implantation. SPSS v 20.0 and Ene v 2.0 were used. A total of 222 samples (58 docetaxel, 95 paclitaxel and 69 oxaliplatin) were analyzed. Gravimetry and HPLC are comparable methods. Overall CP was 81% for gravimetry at 10% TL and 85% for HPLC at 15% TL. Compounding accuracy is shown to be good for all methods and drugs. Homogenization optimization and personnel training make measurements more accurate for docetaxel and paclitaxel HPLC, but seem to worsen accuracy for docetaxel gravimetry. Gravimetry has shown to be a good alternative to HPLC for routine QC. Coupling with electronic methods should be considered in the future.

Effectiveness, toxicity, and economic evaluation of ipilimumab for the treatment of patients with metastatic melanoma in the Spanish outpatient setting.

To evaluate the effectiveness and toxicity profile of ipilimumab treatment and to examine the cost-effectiveness relation in a real-world sample of patients with metastasic melanoma. This was a multicenter, observational, retrospective cohorts study. To assess the effectiveness and safety of ipilimumab treatment progression-free survival (PFS), overall survival (OS) and adverse events were registered. An economic evaluation was performed and cost-effectiveness ratios (CERs) were calculated. Eleven patients were included, mean age 59 (SD=11) years. The median PFS was 3.83 months (95% confidence interval 0.98-9.80) and the median OS was 5.15 months (95% confidence interval 1.70-8.48). None of the patients included in the study achieved an objective response. A stable disease was achieved in four (36%) patients. The most commonly reported analytical adverse event was anemia, with all patients developing anemia in any grade. The most severe adverse event was neutropenia (n=6; 55%), with three patients developing grade 4 neutropenia (3/11; 27%). The total cost of ipilimumab treatment was &OV0556;483 397, with a median of 43 033 (interquartile range=9555) euros per patient. The median-based CER was 136 675 (28 539-474 865) euros per progression-free year gained and the median-based CER was 100 112 (23 107-374 893) euros per life-year gained. PFS observed in real-world patients was higher than that reported in clinical trials and OS was lower. The incidence of adverse events was higher. The additional cost per progression-free year gained was ∼&OV0556;136 675. The data from this study fill an important need for information on the relative value of this treatment in terms of cost-effectiveness.

Effectiveness, toxicity, and economic evaluation of vinflunine for the treatment of patients with transitional cell carcinoma in the Spanish outpatient setting.

The aim of this study was to evaluate the effectiveness and toxicity profile of the vinflunine chemotherapy regimen and to examine the cost-effectiveness relation in a real-world sample of patients with transitional cell carcinoma of the bladder. This is a multicenter, observational, retrospective cohort study. To assess the effectiveness and safety of vinflunine treatment, progression-free survival, overall survival, and adverse events were registered. An economic evaluation was performed and cost-effectiveness ratios were calculated. A total of 37 patients were included in the study, with a mean age of 67 (SD=9) years. The median progression-free survival was 2.61 months (95% confidence interval 1.79-4.23) and the median overall survival was 5.72 months (95% confidence interval 3.34-10.35). An objective response was achieved in eight (22%) patients. Statistically significant differences were found between patients treated with vinflunine as a second-line therapy and those treated with vinflunine as a third-line therapy (P=0.036). The most commonly reported analytical adverse event was anemia (n=34; 92%), and the most severe was neutropenia (n=19; 51%), with nine patients developing grade 4 neutropenia (9/19; 47%). The total cost of vinflunine treatment was &OV0556;553 873, with a median of &OV0556;8524 (interquartile range, &OV0556;9220) per patient. The median-based cost-effectiveness ratio was &OV0556;44 789 (&OV0556;31 706-58 022) per progression-free year gained and &OV0556;22 750 (&OV0556;14 526-34 085) per life-year gained. The data from this study fill an important need for information on the relative value of this treatment in terms of cost-effectiveness and might help achieve an optimal quality healthcare system.

[Incidence, management and costs of adverse effects in chronic hepatitis C patients on triple therapy with telaprevir or boceprevir: first 12 weeks of treatment]. / Incidencia, manejo y coste de los efectos adversos hematológicos y dermatológicos durante las 12primeras semanas de tratamiento con triple terapia para hepatitisC.

INTRODUCTION: The aim of the study was to analyze the incidence, management and cost associated to hematological and dermatological adverse effects (AE) in chronic hepatitis C patients on triple therapy (TT) with telaprevir (TVR) or boceprevir (BOC). METHODS: An analysis was made on the data recorded on patients who started treatment with TVR or BOC associated with peginterferon alfa and ribavirin in a 12-week follow-up period. RESULTS: Fifty-three patients were included (TVR n=36; BOC n=17). Thrombocytopenia (83% TVR vs. 88% BOC) followed by neutropenia (89% TVR vs. 82% BOC) were the most common AE. Dermatological AE were observed in 32% of patients. Eleven patients required treatment discontinuation (all of them received TVR), and toxicity was the main reason for discontinuation (64%). The percentage of patients who required supportive treatment for management of AE was 66%. The most used supportive treatment was erythropoietin. Eight patients required emergency health care, and 2 were hospitalized due to AE. Total cost of additional supportive resources was 32,522€ (625 [SD=876]€/patient) (TVR 759 [SD=1,022]€/patient vs. BOC 349 [SD=327]€/patient; P>.05). Patients with gradeiii-iv toxicity required greater supportive care with higher costs, compared to patients with gradei-ii toxicity (849 [SD=1,143]€/patient vs. 387 [SD=397]€/patient; P=.053). CONCLUSION: The addition of new protease inhibitors to conventional treatment leads to a higher incidence of hematological AE in our study, compared to data described in clinical trials. The elevated incidence of AE involves the use of supportive care, increasing total costs of therapy.

Effectiveness and safety of liposomal rapamycin for the treatment of facial angiofibromas in tuberous sclerosis.

AIM: Topical rapamycin is the pharmacological treatment of choice for facial angiofibromas in rare tuberous sclerosis disease. A new, more advanced, and complex formula was developed in our pharmacy service: rapamycin 0.4% liposomal formulation, with better organoleptic characteristics and a more favorable release profile of the active ingredient. The purpose of this study is to evaluate the effectiveness and safety of liposomal topical rapamycin for the treatment of facial injuries in this rare disease. METHOD: This was an observational, prospective, and multicenter study. Effectiveness was evaluated mainly through facial angiofibromas severity index (FASI), investigator's global assessment (IGA) scores, and dermatology life quality index (DLQI) questionnaire. To assess the safety profile of rapamycin, adverse reactions were reported, and blood tests and blood rapamycin levels were performed during treatment. RESULTS: Eleven patients were included, of which 8/11 (73%) patients obtained successful treatment according to FASI and IGA scores after 24 weeks of treatment. Statistical analysis demonstrated a significant improvement (p<.05) in FASI and IGA scores, erythema, and FA size after treatment with rapamycin liposomal formulation (FASI before treatment, median (interquartile range): 6.0 (2.0), FASI after treatment: 3.5 (2.0), p=.0063). Five patients also improved their quality of life after treatment. Regarding safety profile of rapamycin, the most common adverse reaction was mild pruritus and 2 patients reported erythema, who discontinued treatment prematurely. All hematological tests were normal, and blood rapamycin levels were undetectable. CONCLUSIONS: After galenic improvements and clinical evaluations, the rapamycin liposomal formulation proved to be effective and safe for this therapeutic indication. This new formulation was included as a magistral formula in our hospital pharmacy service, now accessible for prescribing by dermatologists. Drug development in hospital pharmacy is often the only pharmacological alternative available to treat the symptoms of rare diseases, when treatment options are limited or inadequate.

Chemical stability and physical compatibility of meropenem in admixtures for continuous and extended intravenous infusions.

INTRODUCTION: Prolonged intravenous infusion of beta-lactams increase the clinical cure rate compared to conventional administration in critical or septic patients. This study aimed to determine chemical stability and physical compatibility of meropenem at conditions used in clinical practice to evaluate the stability of the preparation during its administration and the possibility of anticipated preparation. METHODS: Admixtures in study were: (i) meropenem 6g in 0.9% sodium chloride (NS) in infusor of 2mL/h 50mL or 10mL/h 240mL; (ii) meropenem 1 or 2g in NS in infusion bag of 250mL. Temperatures of study were: (i) infusor: 4.5°C, 32°C or 12h at 4.5°C followed by 32°C; (ii) Infusion bag: 4.5°C, 24.5°C or 6h at 4.5°C followed by 24.5°C. Time of study was 5-6 days in infusor and 1 day in infusion bag. Chemical stability was evaluated by high performance liquid chromatography and physical compatibility by measuring pH and visual inspection. RESULTS: Chemical stability and physical compatibility of meropenem in admixtures in infusors were reduced at high meropenem concentration and high temperature. Admixtures in infusion bag show chemical stability and physical compatibility for at least 1 day. CONCLUSION: Administration of meropenem 6g in infusion of 24h in 240mL of 0.9% NaCl in infusor of 10mL/h could be possible if the admixture is infused at 4.5°C. Extended infusion of meropenem 1 or 2g in 0.9% NaCl in infusion bag (250mL) in 3-4h is also feasible. Anticipated preparation of the admixtures in infusion bag is possible with a stability of 24h.

[Translated article] Advances in the work of multidisciplinary teams for the care of patients with severe uncontrolled asthma. A post-COVID vision (TEAM 2.0 project).

Asthma is a chronic respiratory disease with a high health, social and economic impact, particularly in the case of Severe Uncontrolled Asthma (SUA). For this reason, new strategies are especially necessary to improve its approach, with a personalized approach to each patient and from a multidisciplinary perspective, in addition to integrating the new telemedicine and telepharmacy practices promoted as a result of the COVID-19 pandemic. In this context, the TEAM 2.0 project ("Work in Multidisciplinary Asthma Teams") has been developed, following the TEAM project carried out in 2019, with the aim of updating and prioritizing good multidisciplinary work practices in SUA in a post pandemic context and analyze the progress made. A coordinating group, made up of eight multidisciplinary teams of hospital pharmacists, pulmonologists, and allergists, carried out an updated bibliographic review, sharing of good multidisciplinary practices, and analysis of advances. Through five regional meetings with other experts with experience in SUA, the good practices identified were shared and subjected to debate, evaluation and prioritization. In total, 23 good multidisciplinary work practices in SUA, grouped into five work areas: 1) Organization of work in multidisciplinary teams, 2) Patient education, self-management and adherence, 3) Health results, data monitoring and persistence, 4) Telepharmacy and experiences implemented during the COVID-19 pandemic and 5) Training and research, were evaluated and prioritized by 57 professionals from the field of Hospital Pharmacy, Pulmonology, Allergology and Nursing. This work has made it possible to update the roadmap of priority actions to continue advancing in optimal models of care for patients with AGNC in a post-COVID-19 context.

Advances in the work of multidisciplinary teams for the care of patients with severe uncontrolled asthma. A post-COVID vision (TEAM 2.0 project). / Avances en el trabajo de equipos multidisciplinares para la atención al paciente con asma grave no controlada. Una visión post-COVID (Proyecto TEAM 2.0).

Asthma is a chronic respiratory disease with a high health, social and economic impact, particularly in the case of Severe Uncontrolled Asthma (SUA). For this reason, new strategies are especially necessary to improve its approach, with a personalized approach to each patient and from a multidisciplinary perspective, in addition to integrating the new telemedicine and telepharmacy practices promoted as a result of the COVID-19 pandemic. In this context, the TEAM 2.0 project ("Work in Multidisciplinary Asthma Teams") has been developed, following the TEAM project carried out in 2019, with the aim of updating and prioritizing good multidisciplinary work practices in SUA in a post pandemic context and analyze the progress made. A coordinating group, made up of eight multidisciplinary teams of hospital pharmacists, pulmonologists, and allergists, carried out an updated bibliographic review, sharing of good multidisciplinary practices, and analysis of advances. Through five regional meetings with other experts with experience in SUA, the good practices identified were shared and subjected to debate, evaluation and prioritization. In total, 23 good multidisciplinary work practices in SUA, grouped into five work areas: 1) Organization of work in multidisciplinary teams, 2) Patient education, self-management and adherence, 3) Health results, data monitoring and persistence, 4) Telepharmacy and experiences implemented during the COVID-19 pandemic and 5) Training and research, were evaluated and prioritized by 57 professionals from the field of Hospital Pharmacy, Pulmonology, Allergology and Nursing. This work has made it possible to update the roadmap of priority actions to continue advancing in optimal models of care for patients with AGNC in a post-COVID-19 context.

Pharmacometric characterization of entero-hepatic circulation processes of orally administered formulations of amiodarone under complex binding kinetics.

AIMS: The aims of this work are (i) to characterize the absorption properties of orally administered formulations at different dose levels, and (ii) to evaluate the impact of entero-hepatic circulation on the time-course of amiodarone (AM) in rats in order to optimize the development of new oral (OR) formulations. METHODS: Intravenous (IV) formulation consisted on a solution of a commercial injectable of AM chlorhydrate. OR formulations included the IV commercial formulation (Trangorex®) (Solution I), an aqueous supramicellar solution of AM chlorhydrate with Polysorbate at 5% (Solution II) and a suspension from Trangorex® tablets (Tablet). Data from 96 male Wistar rats, including 985 AM observations, were analyzed using NONMEM v7.4. RESULTS: The population pharmacokinetic (PK) model assumes linear absorption processes, showing ka of AM from Solution II (Polysorbate 80, 5%) and Solution I increased by 2.5- and 1.62-fold compared to Tablet formulation. OR bioavailability of AM from Tablet, Solution I and Solution II was 37%, 40%, and 50%, respectively. The structural model of AM disposition was adapted from a previously population PK model and expanded by incorporating entero-hepatic reabsorption (EHR) processes, which estimated a 12.3% biliary excretion of AM and complete re-absorption from lumen. CONCLUSIONS: The current population PK model of AM demonstrated the absorption rate enhancement when AM is formulated with supramicellar concentrations of Polysorbate 80. The study design allowed to characterize the EHR of AM and its contribution in the overall AM disposition.

Impact of Pharmacokinetic and Pharmacodynamic Properties of Monoclonal Antibodies in the Management of Psoriasis.

The treatment of psoriasis has been revolutionized by the emergence of biological therapies. Monoclonal antibodies (mAb) generally have complex pharmacokinetic (PK) properties with nonlinear distribution and elimination. In recent years, several population pharmacokinetic/pharmacodynamic (PK/PD) models capable of describing different types of mAb have been published. This study aims to summarize the findings of a literature search about population PK/PD modeling and therapeutic drug monitoring (TDM) of mAb in psoriasis. A total of 22 articles corresponding to population PK/PD models of tumor necrosis factor (TNF)-α inhibitors (adalimumab and golimumab), interleukin (IL)-23 inhibitors (guselkumab, tildrakizumab, and risankizumab), IL-23/IL-12 inhibitor (ustekinumab), and IL-17 inhibitors (secukinumab, ixekizumab, and brodalumab) were collected. A summary of the clinical trials conducted so far in psoriasis was included, together with the current structural population PK and PD models. The most significant and clinical covariates were body weight (BW) and the presence of immunogenicity on clearance (CL). The lack of consensus on PK/PD relationships has prevented establishing an adequate dosage and, therefore, accentuates the need for TDM in psoriasis.

Machine-learning-derived predictive score for early estimation of COVID-19 mortality risk in hospitalized patients.

The clinical course of COVID-19 is highly variable. It is therefore essential to predict as early and accurately as possible the severity level of the disease in a COVID-19 patient who is admitted to the hospital. This means identifying the contributing factors of mortality and developing an easy-to-use score that could enable a fast assessment of the mortality risk using only information recorded at the hospitalization. A large database of adult patients with a confirmed diagnosis of COVID-19 (n = 15,628; with 2,846 deceased) admitted to Spanish hospitals between December 2019 and July 2020 was analyzed. By means of multiple machine learning algorithms, we developed models that could accurately predict their mortality. We used the information about classifiers' performance metrics and about importance and coherence among the predictors to define a mortality score that can be easily calculated using a minimal number of mortality predictors and yielded accurate estimates of the patient severity status. The optimal predictive model encompassed five predictors (age, oxygen saturation, platelets, lactate dehydrogenase, and creatinine) and yielded a satisfactory classification of survived and deceased patients (area under the curve: 0.8454 with validation set). These five predictors were additionally used to define a mortality score for COVID-19 patients at their hospitalization. This score is not only easy to calculate but also to interpret since it ranges from zero to eight, along with a linear increase in the mortality risk from 0% to 80%. A simple risk score based on five commonly available clinical variables of adult COVID-19 patients admitted to hospital is able to accurately discriminate their mortality probability, and its interpretation is straightforward and useful.

Topical rapamycin in the treatment of facial angiofibromas in tuberous sclerosis: a systematic review based on evidence.

INTRODUCTION: facial angiofibromas of tuberous sclerosis are the most prevalent cutaneous manifestation, affecting 80% of patients, which cause facial lesions with negative psychosocial consequences. Newly, topical rapamycin has been established as an effective and safe therapy for this skin condition. PURPOSE: to analyze the available scientific evidence about the effectiveness and safety of topical sirolimus in the treatment of facial angiofibromas in tuberous sclerosis. METHODS: a literature search was conducted in PubMed and Cochrane. Effectiveness and safety were analyzed along with the main characteristics of each formulation in all included studies. RESULTS: thirty studies were included involving a total of 508 patients, developed in the last 20 years. Four randomized clinical trial, 17 case series and 9 single case reports were founded. Multiple topical rapamycin concentrations (0.003-1%) and formulations (gel, ointment, solution) were found in literature. Rapamycin demonstrated its effectiveness in all studies included, except for 5 patients in a 1 b study. Rapamycin was shown to be safe for the treatment of FA. CONCLUSIONS: Topical sirolimus can be considered an effective and safety option for the treatment of facial angiofibromas in tuberous sclerosis. However, further long-term studies need to establish an evidence-based therapeutic protocol.KEY MESSAGEUpdated review to date in topical rapamycin for facial angiofibromas, allowing support in therapeutic decisions.

Physico-Chemical Stability of Admixtures of Vinflunine Used in Clinical Practice.

Procedure of administration of vinflunine is complex and consists of an Y-site injection with fluid at different speeds. Dose is diluted with 100 mL of 0.9% sodium chloride or 5% glucose and infused with half of the 500 mL bag of the fluid over 20 min; after that, the remaining fluid is administered at 300 mL/h. In this study, chemical stability and physical compatibility of vinflunine diluted with in 500 mL of both fluids were evaluated to simplify the administration procedure (infusion of mixture on 20 min followed by 250 mL of fluid at 300 mL/h). Physical compatibility and chemical stability were evaluated at two temperatures and protected from and exposed to light. Physical compatibility was evaluated by visual inspection, gravimetric control and measure of pH. A chromatographic method was developed to evaluate chemical stability. The dilution of vinflunine with 500 mL of fluid to final concentrations of 0.75 and 1.54 mg/mL is viable at doses used in clinical practice since admixtures are stable for 2 days at room temperature and at least 7 days under refrigeration. These results extend the expiration date of mixtures of vinflunine administered by the usual procedure and confirm the viability of the proposed procedure since administration is simplified and stability of vinflunine is guaranteed.

Potential risk of medication discrepancies and reconciliation errors at admission and discharge from an inpatient medical service.

BACKGROUND: Medication discrepancies, defined as unexplained variations among drug regimens at care transitions, are common. Some are unintended and cause reconciliation errors that are potentially detrimental for patients. OBJECTIVE: To determine the prevalence of medication discrepancies and reconciliation errors at admission and discharge in hospitalized patients and explore risk factors for reconciliation errors and their potential clinical impact. METHODS: An observational prospective study was conducted at a general teaching hospital. Patients who were admitted to the internal medicine service and were receiving chronic preadmission treatment were included in the study. Preadmission treatment was compared with the treatment prescribed on admission (first 48 hours) and at hospital discharge, and discrepancies and reconciliation errors were identified. The primary endpoint was the presence of reconciliation errors at admission and/or discharge. Potential risk factors (patient-, medication-, and system-related) for reconciliation errors were analyzed using a multivariate logistic regression model. RESULTS: Of the 120 patients enrolled in the study between April and August 2009, 109 (90.8%) showed 513 discrepancies. The prevalence of patients with reconciliation errors was 20.8% (95% CI 13.6 to 28.1). Intended medication discrepancies were more frequent at admission (96.6%) than at discharge (75.5%), while reconciliation errors were more frequent at discharge (24.5%) than at admission (3.4%). The prevalence ratio (admission vs discharge) was 2.4 (95% CI 1.9 to 3.0) for discrepancies and 0.65 (95% CI 0.32 to 1.32) for reconciliation errors. The logistic regression analysis revealed an association between the number of discrepancies at admission (OR 1.21; 95% CI 1.01 to 1.44) and age (OR 1.05; 95% CI 0.99 to 1.10) and an increased risk of reconciliation errors. CONCLUSIONS: Medication reconciliation strategies should focus primarily on avoiding errors at discharge. Since medication discrepancies at admission may predispose patients to reconciliation errors, early detection of such discrepancies would logically reduce the risk of reconciliation errors. Medication reconciliation programs must implement a process for gathering accurate preadmission drug histories and must submit this information to a critical assessment of patients' needs.

Best practices for interdisciplinary care of uncontrolled severe asthma patients (TEAM project).

As one of the most prevalent chronic respiratory diseases, asthma imposes a heavy health and socioeconomic burden on society,  particularly in the case of patients who fail to appropriately control the  disease. For this reason, improving the clinical management of patients  with severe uncontrolled asthma should be a priority for any healthcare  system.At a time when healthcare models for chronic disease management and  personalized medicine are undergoing a major overhaul, the project presented in this study seeks to lay the foundations for an  interdisciplinary care model for patients with severe uncontrolled asthma. The work carried out reinforces the general perception that it is  paramount to optimize coordination between different levels of care,  encourage collaboration and an interdisciplinary approach, and promote  an integrated care model that makes it possible to adapt the care of  patients with severe uncontrolled asthma in a more personalized manner. Under this project, a series of interdisciplinary working groups were  created, made up of specialist hospital pharmacists, pneumologists and  allergists, to identify and prioritize a number of best practices, and  classify them in terms of their potential impact on the improvement of  the quality of care and the health outcomes of patients with severe  uncontrolled asthma, and their feasibility. The authors' ambition is that  the conclusions drawn from this study should help other interdisciplinary  teams improve the care provided to patients suffering from severe  uncontrolled asthma.

El asma es una de las enfermedades crónicas respiratorias de mayor prevalencia e impacto sanitario y socioeconómico, especialmente  en el caso de pacientes que no alcanzan un adecuado control de la  enfermedad.Por ello, mejorar el manejo clínico de los pacientes con asma grave no  controlada debe ser una prioridad sanitaria. En un contexto de  redefinición general de los modelos de atención orientados al abordaje de la cronicidad y la personalización se ha desarrollado un proyecto para  definir las bases del modelo de atención multidisciplinar del paciente con  asma grave no controlada. El trabajo realizado refuerza la percepción de  la necesidad de optimizar la coordinación entre niveles asistenciales,  fomentar la colaboración y el abordaje multidisciplinar, y promover un  modelo integral asistencial que permita adaptar la atención a los  pacientes con asma grave no controlada de manera más personalizada.  El trabajo ha permitido la identificación y priorización de buenas  prácticas, por parte de equipos de trabajo multidisciplinares constituidos  por médicos especialistas en alergología, neumología y farmacéuticos  especialistas en farmacia hospitalaria, en base a su potencial impacto en  la mejora de la calidad asistencial, resultados en salud del paciente con  asma grave no controlada y la factibilidad de su implementación. Las  conclusiones de este proyecto pretenden servir de ayuda a otros equipos  de trabajo multidisciplinar con interés en mejorar la asistencia a esta  patología.

Clinical utility of serum concentrations of adalimumab as predictor of treatment adherence. / Utilidad de las concentraciones séricas de adalimumab como predictores de adherencia al tratamiento.

OBJECTIVE: to evaluate the usefulness of serum concentrations (Sc) of adalimumab (ADA) as a predictor of medication adherence using the medication possession ratio (MPR) and Morisky Green test (MGT) in patients with chronic inflammatory diseases. MATERIAL AND METHOD: Design a prospective descriptive cohort study. INCLUSION CRITERIA: adult patients diagnosed with inflammatory arthropathy (IA) or inflammatory bowel disease (IBD) treated with ADA. EXCLUSION CRITERIA: positive anti-adalimumab antibody. VARIABLES: sex, age, diagnosis, dosage regimen, Sc (mg/mL), MPR (MPR ≥ 80% adherent) and MGT (non-adherent or adherent). Statistical analysis was performed using STATA v13.0. RESULTS: Forty-five patients (23 women) with an age of 52.22 (14.39) years, 17 IBD (37.78%), 26 IA (57.78%) and 2 with both conditions (4.44%) treated with 40mg ADA every 14 days (42/45; 93.33%) or every 7 days (3/45; 6.67%). We detected subtherapeutic Sc in 22.22% of patients (10/45); 10% (1/10) were classified as non-adherent and 90% (9/10) as adherent according to MGT and MPR. The quantification of Sc shows weak agreement with MPR, as was the case with the indirect methods of each (MPR and MGT). The association was slightly greater when the indirect methods were compared to each other (0.244 vs. 0.378). CONCLUSION: the determination of Sc of ADA alone has limited utility in the detection of non-adherent patients.

Quality Improvement Project to Evaluate Discharge Prescriptions in Children With Cystic Fibrosis.

Cystic Fibrosis (CF) requires multiple pharmaceutical treatments, elevating the risk of medication errors (ME), which may compromise patient safety. This study aimed to improve the quality of discharge prescriptions (DPs) using indicators following admissions for IV antibiotics in pediatric CF patients. METHODS: This project involved a longitudinal observational retrospective descriptive study followed by a longitudinal quasi-experimental prospective phase between January 2013 and December 2016 in CF patients admitted to a London Children's Hospital. The CF pharmacist reviewed DPs. Six rights of medication administration were defined (6R): dose, drug, frequency, duration of treatment, pharmaceutical form, and route of administration. We classified ME according to 6R, including subtype of error: committed/omitted. We calculated quality indicators by dividing the number of each correct parameter defined by 6R by number of DPs. Retrospective results were used prospectively to describe and implement improvement strategies and safety actions. RESULTS: The retrospective study phase included 42 CF children (100 hospital admissions and 1,343 drugs). The prospective phase included thirty-five children (55 admissions and 822 drugs). The total number of ME identified was 148 (78 committed; 70 omitted) in retrospective phase and 135 (19 committed; 116 omitted) in prospective phase. Quality indicators for drug and dose showed significant improvement after implementing safety strategies. The global quality indicator increased from 22% (retrospective) to 41.82% (prospective), but we did not achieve the previously defined quality standard value (50%). CONCLUSIONS: A retrospective review of DP by a CF Pharmacist identified failures in DP quality. Implementing improvement strategies improved prescribing. Integrating pharmacist within multidisciplinary team improves DP reducing errors.