Assessing a therapeutic exchange protocol for second-generation antidepressants: clinical results.

OBJECTIVE: To design a therapeutic exchange protocol for antidepressants and clinically assess variables, such as: compliance level, frequency of cases with clinically significant increase on the Udvalg-für-Kliniske-Undersogelser (UKU) psychopharmacological scale, adverse effects analysis, overall analysis of UKU rating development and patients' level of acceptance. Secondary objectives were to correlate psychopharmacological treatment aspects with the pharmacological morbidity level, and evaluate the clinical impact of pharmacotherapeutic optimisation measures. METHOD: The protocol is designed in accordance with a bibliographical review, which was approved by the Pharmacy and Therapeutics Commission. Sequential study was carried out with a sample of 30 patients. Three measurements were taken (base line, at 48-72 hours and at 1-3 weeks) to calculate the pharmacotherapeutic morbidity with the UKU rating scale and the Global Clinical Impression. Pharmacotherapeutic optimisation measures were used for those patients with high pharmacotherapeutic morbidity levels. RESULTS: The compliance level was 73.3%. One patient experienced ≥25% increase on the UKU rating scale and another patient suffered from an adverse effect. The final UKU rating reached statistical significance compared with the measurements taken at 48-72 hours (P=.032) and with the base line measurement (P=.007). Patient acceptance was 90%. The impact of optimisation measurements on the pharmacotherapeutic morbidity level was clinically and statistically significant (P<.001). CONCLUSIONS: The proposed protocol has been widely accepted and it is quite certain that it is to be introduced in at a general hospital level.

[Assessment of a pharmaceutical interventional programme in patients on medications with renal risk]. / Evaluación de un programa de intervención farmacéutica en pacientes con medicamentos de riesgo renal.

OBJECTIVE: To compare the adaptation of medical prescriptions according to the dosage guides in patients with renal disease, before and after applying a pharmaceutical intervention programme. The secondary objectives were to prepare a guide to dosing in renal disease and to measure the prevalence of prescription of drugs with renal risk. METHOD: Non-randomised, experimental interventional study (before/after) conducted in a general hospital with 800 beds, including hospitalised patients, over the age of 18, with kidney disease and drugs with renal risk prescribed in their pharmacotherapeutic profile. The study was designed to be carried out in two descriptive cross-cutting phases (control group) and a prospective interventional cohort study (intervention group). The primary variable was the percentage non-adaptation according to the stage of renal disease. RESULTS: The study included 185 patients, 88 in the control group and 97 in the intervention group. In the intervention group, the prevalence of non-compliance before and after the intervention was 18.7 % and 2.1 %, representing a statistically significant reduction in non-adaptation of the dose. The costs saved with the pharmaceutical intervention programme were 1,939.63 euro over two months, the average saving per medication intervened amounting to 62.57 euro (CI 95 %, 23.99-101.14 euro; p = 0.02). CONCLUSIONS: The results of the study indicate that the application of a pharmaceutical care model based on the prospective validation of drugs with renal risk, very significantly improved the adaptation of dosing regimens in kidney disease.

[Use and cost of biological disease-modifying anti-rheumatic drugs in Spain (PRAXIS study)]. / Utilización y coste de los modificadores biológicos de la artritis reumatoide en España (estudio PRAXIS).

OBJECTIVE: To analyse the use of health care resources and the associated costs in patients with rheumatoid arthritis (RA) treated with three biological disease-modifying anti-rheumatic drugs (bDMARDs): etanercept, infliximab and adalimumab. DESIGN: observational, retrospective, multicentre study. Length of study: 6 months. TARGET POPULATION: patients with RA, who have been undergoing treatment for at least one year. SCOPE: Spanish National Health System hospitals. Use of resources: review of the patient records of all patients included in the study by the Hospital Pharmacy Departments. Health care costs: the unit costs were obtained from Spanish databases; disease costs per patient were estimated from the use of resources results (euro in July 2006). Sensitivity analysis: univariate of base case. Budget impact analysis: replacement of infliximab and adalimumab by etanercept for three hospital populations. RESULTS: 1,111 patient records from 41 Spanish hospitals were reviewed, 432 patients were treated with etanercept, 396 were treated with infliximab and 283 with adalimumab. Mean doses: etanercept: 48.90 mg per week; infliximab: 4.14 mg/kg every 8 weeks; adalimumab: 41.58 mg every two weeks (97.8, 138 and 104% respectively, of recommended doses). Treatment with etanercept led to fewer costs. Compared to infliximab, six-monthly costs per patient were reduced with etanercept as follows: bDMARD treatment (232.23 euro), treatment failure (163.42 euro), consultations (54.88 euro), tests (22.52 euro) and costs associated to bDMARD administration (euro 474.42). The saving per patient treated with etanercept compared to infliximab for six months was 577.94 euro. With respect to adalimumab, the savings with etanercept were mainly related to bDMARDs (1,111.74 euro) and test costs (10.16 euro), obtaining a six-monthly saving of euro 906.68 per patient treated with etanercept. Sensitivity analysis confirmed the robustness of the base case in the majority of cases, with six-monthly savings of 395.79-644.32 euro per patient compared to infliximab and of 672.09-1.159.46 euro compared to adalimumab. Infliximab treatment was less expensive than etanercept and adalimumab treatment when taking into consideration the minimum possible number of doses of infliximab (3 doses for six months). Hospital budget savings could be obtained as a consequence of a reduction in costs due to use of etanercept, ranging from 14,500-231,100 euro when replacing infliximab with etanercept and from 22,600-362,600 euro when replacing adalimumab with etanercept, according to the hospital population included (50 to 200 patients). CONCLUSIONS: Our results showed that in most cases, the treatment of rheumatoid arthritis with etanercept compared to infliximab and adalimumab reduced hospital costs.

[ST segment elevation acute coronary syndrome during pregnancy: a case report and review of therapeutic options]. / Síndrome coronario agudo con elevación de ST durante el embarazo: descripción de un caso y revisión de las opciones terapéuticas.

ST segment elevation acute coronary syndrome is a clinical condition that is rarely observed in pregnant women. However, its manifestation is a situation of high maternal-fetal risk. Pharmacotherapeutical management of these patients is difficult and requires individualized care by a multidisciplinary team since many of the standard treatments are included within the categories of teratogencity C or D of the Food and Drug Administration and experience with techniques such as coronary angioplasty with stent placement is scarce. The case of a 32-year woman who was 11 weeks pregnant and diagnosed of acute coronary syndrome with ST segment and its therapeutic approach are described. Furthermore, the information available on epidemiology, etiology and pathophysiology of acute coronary syndrome with ST segment during pregnancy and the specific role of the currently available treatment options are reviewed.

[Replacement therapy with protein C for meningococcal sepsis and fulminant purpura in pediatric patients]. / Tratamiento sustitutivo con proteína C en sepsis meningocócica y púrpura fulminante en pacientes pediátricos.

Disseminated intravascular coagulation as associated to sepsis contributes to the development of clinical multiple organ failure by extensive thrombosis in microcirculation vessels. This condition commonly manifests itself in severe meningococcal sepsis. On the skin, its clinical manifestation is extensive purpura with necrotic lesions that usually progress to serious distal ischemia and may call for amputation. A common denominator in these events regarding hemostasis is a depletion of so-called natural anticoagulant proteins, particularly protein C. According to clinical observations replacement therapy with human plasma-derived protein C concentrates has been associated with significantly improved clinical outcome in patients with meningococcal sepsis and fulminant purpura. This paper reports a case of acquired protein C deficiency in a girl with meningococcal sepsis, fulminant purpura, disseminated intravascular coagulation, and septic shock. Fresh plasma therapy was intended to increase consumption coagulopathy-depleted coagulation factors and to provide small amounts of protein C. The inability to restore protein C concentrations above 30%, and the presence of severe thrombopenia in the setting of disseminated intravascular coagulation led to the onset of replacement therapy using a human protein C concentrate (Ceprotin), which increased plasma protein C concentrations and contributed to revert the existing hypercoagulability status. Finally, evidence available in the literature regarding fulminant meningococcal sepsis management using human protein C concentrates and recombinant activated protein C is discussed.

Monitoring trough plasma concentrations of mycophenolate mofetil in patients with uveitis.

BACKGROUND: Mycophenolate mofetil (MMF) has been used successfully in patients with various forms of uveitis not responsive to other immunosuppressants. Nevertheless, for these patients neither recommendations for optimal dosage of MMF nor data concerning drug exposure of MMF are available. OBJECTIVE: To describe the results of the therapeutic drug monitoring (TDM) of MMF trough concentrations in a cohort of patients with uveitis, with the aim of optimizing the dosage of this drug, by maintaining a target concentration to achieve adequate immunosuppression with a minimal risk of therapeutic failure or toxicity. PATIENTS AND METHODS: This study describes the results of monitoring trough plasma concentrations of MMF in 12 patients with uveitis during a mean period of 21.4 months. Patients included one with Stevens-Johnson syndrome, one with Graves-Basedow's disease, one with Behcet's disease, one with idiopathic thrombocytopenic purpura and the rest with idiopathic uveitis. All patients were treated with steroids and additional therapy prior to treatment with MMF. RESULTS: Pharmacokinetic monitoring of mycophenolic acid (MPA) was performed with 108 trough plasma samples using an EMIT assay. Mean daily MMF dose was 24.5 +/- 6.3 mg/kg and mean trough MPA concentration was 2.9 +/- 1.9 microg/mL. Therapy was effective in 10 patients (83%). There were few side-effects: diarrhoea, excitement, agitation and cough that disappeared with daily dose reduction of MMF. CONCLUSIONS: MMF was effective in the majority of patients with uveitis with an acceptable profile of side-effects. TDM of MMF in patients with uveitis is clinically practicable and may help to optimize individual immunosuppressive therapy. We estimated that MMF dosages in the range of 0.5-1.5 g/day might be sufficient for treating uveitis and we recommend an initial target range of 2-4 microg/mL, which included 50% of our results. Randomized controlled trials are essential to confirm the efficacy of MMF in uveitis.

[Pharmacokinetic interaction between valproic acid and carbapenem-like antibiotics: a discussion of three cases]. / Interacción farmacocinética entre ácido valproico y antibióticos carbapenémicos: descripción de tres casos.

A number of literature references suggest that carbapenem-like antibiotics decrease plasma concentrations of valproic acid in epileptic patients. This interaction may result in a recurrence of epileptic seizures in these patients. To clarify the possible mechanism of such carbapenem-valproic acid interaction several experimental studies have been carried out in animals. However, the mechanism of this drug-drug interaction is as yet uncertain. in this article we report three new cases that were observed in our hospital within three months. One of these patients developed seizures. We also review the different mechanisms proposed, as well as cases published to this day. All these data demonstrate that care should be taken in using these potent antibiotics in patients receiving valproic acid.

High-dose methotrexate-doxycycline interaction.

OBJECTIVE: To report a case in which an interaction occurred between doxycycline and high-dose methotrexate (HD-MTX) and discuss its clinical, quality of life, and economic repercussions. CASE SUMMARY: A 17-year-old girl diagnosed with high-degree osteosarcoma in her left femur was admitted to our hospital to receive her eleventh postoperative cycle of HD-MTX, according to the clinical protocol approved at our hospital. Simultaneously, due to a palpebral abscess in her left eye, the patient received systemic treatment with doxycycline 100 mg every 12 hours. As in previous cycles, pharmacokinetic monitoring of methotrexate (MTX) plasma concentrations was performed to improve leucovorin calcium rescue. The biological half-life 12 and 24 hours after infusion showed that the patient was at high risk of intoxication. She then developed hematologic as well as gastrointestinal toxicity and remained hospitalized for 11 days. The patient was readmitted 48 hours after hospital discharge because of a febrile episode that required an additional hospital stay of 12 days, and the twelfth cycle of HD-MTX had to be postponed 18 days because of the results of the previous cycle. DISCUSSION: Significant differences (p < 0.05) were observed in the eleventh HD-MTX cycle for plasma concentrations and pharmacokinetic parameters compared with the previous 10 cycles. The interaction resulted in clinical, quality of life, and economic repercussions. CONCLUSIONS: The potential interaction between MTX and doxycycline may cause pharmacokinetic changes, and its clinical repercussions on the quality of life of the patient and associated costs should be considered.

[An analysis of patient information sheets for obtaining informed consent in clinical trials]. / Análisis de las hojas de información al paciente para la obtención de su consentimiento informado en ensayos clínicos.

BACKGROUND: The written information provided to the potential participants in a clinical trial must have certain qualitative and quantitative characteristics to reach the ethical requirements governing the theory of the informed consent. MATERIAL AND METHODS: In a sample of 101 clinical trial protocols approved in two Spanish university general hospitals, the following items were evaluated: a) the amount and quality of the written information given to the patient, in accordance with the established in the Spanish legislation; b) the formal readability of this written forms, by means of the Flesch method, and c) the level of complexity of the vocabulary, by means of the number of non-comprehensible words for two volunteers unaware of the health professions, with high studies. RESULTS: The balance of benefits and risks, the identification and the way of contact with the main investigator, the description of the alternative treatments and the specification of the compensations in case of lesions were the items with highest noncompliance. The mean global readability by means of the index of Flesch was of -12.7 (text with a high level of complexity). The mean percentage of words non-comprehensible for the volunteers that analyzed the texts was 0.3%. CONCLUSIONS: The written form of information provided to the patient in the clinical trials developed in Spain has serious deficiencies, either in their formal readability (complexity of the linguistic structure) or in the amount and quality of the information that provides. These deficiencies could have a wrong influence in the appropriate obtention of the informed consent from the patients.

Vigabatrin-associated reversible acute psychosis in a child.

OBJECTIVE: To describe a child with vigabatrin-associated reversible acute psychosis and review the literature reports on this adverse effect. CASE SUMMARY: A 7-year-old boy with intractable epilepsy developed acute psychosis 3 days after initiating a rapid vigabatrin dosage escalation. All symptoms resolved within 48 hours after vigabatrin therapy was withdrawn. Two months later, reinitiation of vigabatrin therapy using a slower dosage escalation was well-tolerated by the patient, and he currently is being treated with vigabatrin successfully. DISCUSSION: Although vigabatrin-associated psychosis is rare, a few cases have been reported in predisposed adult patients, especially in the early stages of treatment. The mechanism of this reaction remains unclear and its incidence is unknown. To our knowledge, there has been no previous report of this adverse effect in children. CONCLUSIONS: Caution must be taken in children with predisposing factors at the beginning of vigabatrin therapy.

[The participation of pharmacy services in evaluating parenteral nutrition programs]. / Participación de los Servicios de Farmacia en la valoración de los programas de nutrición parenteral.

The situation of parenteral nutrition practised in our hospital over one year was analyzed from the standpoint of Pharmacy Services, with a random sample of 26 patients with 322 days on parenteral nutrition. The most important results showed that the degree of compliance of the application sheets was 85.3%. The protocolized nutrient units were used in 80.1% of total days on parenteral nutrition, with an average of 0.97 +/- 0.60 modifications per day 855.0% electrolytes and 39.9% insulin). During the follow-up of parenteral nutrition, analytical determinations were performed every 2.3 +/- 1.8 and 4.2 +/- 2.6 days in blood and urine respectively. 30 biochemical alterations were observed, in particular hyperglycaemia (26.7%), hypoglycaemia (10%), hyperpotassemia (13.3%) and hyponatraemia (13.3%). In 70% of cases, corrective action was taken within 24 hours. The average number of multidisciplinary communications was 4.5 per patient. The initiative was taken by the pharmacist in 75.8% of cases, and the most frequent reason for communication was analysis of biochemical situation of patient and proposal for modification in daily intake.