Assessment of the implementation of safe medication practices in Intensive Medicine Units.

OBJECTIVE: To assess the level of implementation of medication safety practices in Intensive Care Units (ICUs) and to identify opportunities for improvement. DESIGN: A descriptive multicenter study was carried out. SETTING: Intensive Care Units. PARTICIPANTS/PROCEDURE: A total of 40 ICUs voluntarily completed the "Medication use-system safety self-assessment for Intensive Care Units" between March and September 2020. The survey comprised 147 items for evaluation grouped into 10 key elements. MAIN VARIABLES: Calculation was made of the mean scores and mean percentages based on the maximum possible values for the overall survey, referred to the key elements and to each individual item for evaluation. RESULTS: The mean score of the overall questionnaire among the participating ICUs was 436.8 (49.2% of the maximum possible score). No differences were found according to functional dependence, size of the hospital or type of ICU. The key elements referred to the incorporation of clinical pharmacists in these Units, as well as the competence and training of the professionals in safety practices yielded the lowest values (31.2% and 33.2%, respectively). Three other key elements related to accessibility to information about patients and medicines; to the standardization, storage and distribution of medicines; and to the quality and risk management programs, yielded percentages <50%. CONCLUSIONS: Numerous effective safety medication practices have been identified with a low level of implementation in ICUs. This situation must be addressed in order to reduce medication errors in critically ill patients.

Assessment of the implementation of safe medication practices in Intensive Medicine Units. / Evaluación de la implantación de prácticas seguras con los medicamentos en los Servicios de Medicina Intensiva.

OBJECTIVE: To assess the level of implementation of medication safety practices in Intensive Care Units (ICUs) and to identify opportunities for improvement. DESIGN: A descriptive multicenter study was carried out. SETTING: Intensive Care Units. PARTICIPANTS/PROCEDURE: A total of 40 ICUs voluntarily completed the "Medication use-system safety self-assessment for Intensive Care Units" between March and September 2020. The survey comprised 147 items for evaluation grouped into 10 key elements. MAIN VARIABLES: Calculation was made of the mean scores and mean percentages based on the maximum possible values for the overall survey, for the key elements and for each individual item for evaluation. RESULTS: The mean score of the overall questionnaire among the participating ICUs was 436.8 (49.2% of the maximum possible score). No differences were found according to functional dependence, size of the hospital or type of ICU. The key elements referred to the incorporation of clinical pharmacists in these units, as well as the competence and training of the professionals in safety practices yielded the lowest values (31.2% and 33.2%, respectively). Three other key elements related to accessibility to information about patients and medicines; to the standardization, storage and distribution of medicines; and to the quality and risk management programs, yielded percentages below 50%. CONCLUSIONS: Numerous effective safety medication practices have been identified with a low level of implementation in ICUs. This situation must be addressed in order to reduce medication errors in critically ill patients.

Recommendations by the Spanish Society of Hospital Pharmacy, the Spanish Society of Oncology Nursing and the Spanish Society of Medical Oncology for the safe management of antineoplastic medication in cancer patients.

AIM: To define recommendations that permit safe management of antineoplastic medication, minimise medication errors and improve the safety of cancer patients undergoing treatment. METHODS: By reviewing the literature and consulting the websites of various health organisations and agencies, an expert committee from the Spanish Society of Hospital Pharmacy and the Spanish Society of Medical Oncology defined a set of safe practices covering all stages of providing cancer therapy to patients. The Spanish Society of Oncology Nursing revised and endorsed the final list. RESULTS: In total, 68 recommendations arranged in five sections were defined. They include issues concerning the training of health professionals, the technological resources needed, treatment planning, informing the patient and his/her family, the processes of prescribing, preparing, dispensing and administering cancer therapy (orally, parenterally or intrathecally), assessing patient adherence and treatment toxicity. CONCLUSIONS: It is essential for healthcare establishments to implement specific measures designed to prevent medication errors, in order to ensure the safety of cancer patients treated with antineoplastic medication.

Influx of recent thymic emigrants into autoimmune thyroid disease glands in humans.

Autoimmune thyroid diseases (AITD) are considered as prototypic organ-specific autoimmune diseases, yet their underlying aetiology remains poorly understood. Among the various pathophysiological mechanisms considered, a failure of central tolerance has received little attention. Here we present evidence in favour of dysregulated thymic function playing a role in AITD. Flow-cytometric analyses conducted in peripheral blood lymphocytes from 58 AITD patients and 48 age- and-sex-matched controls showed that AITD patients have significantly higher blood levels of CD4(+)CD45RA(+), CD4(+)CD31(+) and CD4/CD8 double-positive T lymphocytes, all markers of recent thymic emigrants (RTE). In addition, the alpha-signal joint T cell receptor excision circles (TRECs) content (a molecular marker of RTEs) was higher in the group of AITD patients older than 35 years than in age-matched controls. This was independent from peripheral T cell expansion as assessed by relative telomere length. Comparisons of TREC levels in peripheral blood lymphocytes and intrathyroidal lymphocytes in paired samples showed higher levels within the thyroid during the initial 30 months of the disease, indicating an influx of RTE into the thyroid during the initial stages of AITD. Additionally, a lack of correlation between TREC levels and forkhead box P3 expression suggests that the intrathyroidal RTE are not natural regulatory T cells. These results uncover a hitherto unknown correlation between altered thymic T cell export, the composition of intrathyroidal T cells and autoimmune pathology.

[A bibliometric analysis of the Farmacia Hospitalaria journal (2001-2006)]. / Análisis bibliométrico de la revista Farmacia Hospitalaria (2001-2006).

OBJECTIVE: To carry out a bibliometric analysis of the Farmacia Hospitalaria journal from 2001 to 2006. METHOD: A retrospective analysis of all of the articles published in Farmacia Hospitalaria from 2001-2006 was performed and the main bibliometric indicators for production, circulation, distribution and sales were calculated. RESULTS: 416 articles by 1,515 authors were analysed. Original articles were the most predominant with a growth of 30%. There were 4.6 +/- 2.3 authors per article. The Community of Valencia, Catalonia, Madrid and Andalusia were the autonomous communities with the highest levels of production. Four authors had a productivity index of > 1, with one group of 15 authors having an index of > 0.75. Only 14% of articles were included in presentations to congresses and 17% had funding. The subject matters of drug treatment and safety had the highest production levels. The publication delay remained constant. There was a circulation index of 0.74 in Medline. CONCLUSIONS: Farmacia Hospitalaria maintained or improved their bibliometric indicators between 2001 and 2006. There has been an increase in the publication of original articles and letters to the editor over recent years and this increase was in line with the journal s strategies. There has also been a decrease in literature reviews. There were some generational changes among the authors although the main authors remained the same. The subject matters and geographical origin of the authors corresponded to areas with the largest development of the specialty in Spain.

Protein-primed replication of bacteriophage phi 29 DNA.

The replication of phi 29 DNA-protein p3 represents a simple model system to study the protein-priming mechanism of initiation of replication. The phi 29 DNA polymerase involved both in the initiation and elongation steps of phi 29 DNA-protein p3 replication, is a very processive enzyme and it is able to produce strand-displacement in the absence of other proteins. To correlate functional and structural domains in the phi 29 DNA polymerase point mutants in the most carboxyl region of amino-acid homology with other DNA polymerases have been constructed. Most of the mutations had a decreased initiation and elongation activity, but normal 3'----5' exonuclease activity, suggesting that this region contributes to the active domain for initiation and elongation. Point and deletion mutants in the terminal protein have allowed the mapping of one DNA-binding region and two DNA-polymerase-binding regions. The viral protein p6, which stimulates the initiation of replication, binds to a set of specific signals present at both phi 29 DNA ends. A good correlation of binding and stimulation of replication has been obtained by using fragments containing phi 29 DNA-terminal sequences and deletion mutants of protein p6. The viral protein p5 has been shown to bind to single-stranded DNA, to protect the latter against nuclease digetion, and to stimulate phi 29 DNA-protein p3 replication in vitro.

Modification of membrane permeability by animal viruses.

Animal viruses modify membrane permeability during lytic infection. There is a co-entry of macromolecules and virion particules during virus penetration and a drastic change in transport and membrane permeability at the late stages of the lytic cycle. Both events are of importance to understand different molecular aspects of viral infection, as virus entry into the cell and the interference of virus infection with cellular metabolism. Other methods of cell permeabilization of potential relevance to understand the mechanism of viral damage of the membrane are also discussed.

Deletions at the N terminus of bacteriophage phi 29 protein p6: DNA binding and activity in phi 29 DNA replication.

Deletions corresponding to the first 5 or 13 amino acids (aa), not counting the initial Met, have been introduced into the N terminus of the phage phi 29 protein p6. The activity of such proteins in the in vitro phi 29 DNA replication system, their capacity to interact with the phi 29 DNA ends, and their interference with the wild type (wt) protein p6 activity have been studied. The initiation activity of protein p6 decreased considerably when 5 as were deleted and was undetectable when 13 aa were removed. The mutant proteins were unable to specifically interact with the phi 29 DNA ends. These results indicate the need of an intact N terminus for the activity of protein p6. However, such N-truncated proteins inhibited both the specific binding of the wt protein p6 to the phi 29 DNA ends and its activity in phi 29 DNA replication.

Erythropoietin treatment in allogeneic BMT accelerates erythroid reconstitution: results of a prospective controlled randomized trial.

Twenty-eight allogeneic BMT patients (16 with acute leukemia, 12 with chronic myeloid leukemia) were included in a single center, prospective, randomized, controlled trial to assess the value of recombinant human erythropoietin (rh-Epo) in this setting. rh-Epo was administered through a central venous catheter as a single bolus injection (days 0-7: 100 U/kg/d; days 7-30: 150 U/kg/d). No secondary effects to rh-Epo treatment were detected. An earlier appearance of reticulocytes and a diminished need of red blood cells (RBCs) transfusions were observed in patients who were treated with rh-Epo (4 units vs 12 units; p < 0.05). The time to unsupported platelets above 25 x 10(9)/l was less in patients treated with rh-Epo than in control patients (19 days vs 31; p < 0.05), and they received significantly fewer platelet transfusions (36 units vs 138.5; p < 0.05). Our results show that rh-Epo treatment is capable of accelerating the erythroid reconstitution and decreasing the need for RBC transfusions. A beneficial effect on platelet reconstitution is also suggested, but further studies are necessary to confirm this point.

Clinical results in 50 multiply transfused patients with severe aplastic anemia treated with bone marrow transplantation or immunosuppressive therapy.

Fifty patients with aplastic anemia (AA) were treated with BMT or immunosuppressive therapy (IST). Twenty-one patients underwent BMT using cyclophosphamide (CY) and 7 Gy total lymphoid irradiation (TLI) and cyclosporin A (CsA) plus methotrexate (MTX). Actuarial survival is 71% at 5.3 years with an incidence of graft failure of 0% and of acute GVHD of 38.9%. Univariate analysis of variables influencing survival showed a trend for a poorer outcome in patients who received > 30 transfusions prior to BMT and in male recipients from female donors. Twenty-nine patients > 40 years of age or without matched siblings received antithymocyte/antilymphocyte globulin (ATG/ALG). Response rate to the first course of treatment was 46.4%. Subsequent courses of IST rescued 33% of patients who relapsed or had not responded. Actuarial survival is 62% at 8.6 years. In our experience both treatment strategies have given encouraging results although overall morbidity is higher in the IST group because 25% of patients are therapy or transfusion-dependent. The role of irradiation in the conditioning regimen of BMT patients, recently challenged, is discussed.

Hypoalgesic action of bestatin analogues that inhibit central aminopeptidases, but not neutral endopeptidase.

Two analogues of the aminopeptidase inhibitor bestatin, Z 4212 (N-[(2S, 3R)-3-Amino-2-hydroxy-4-(4-methylsulphonyl-phenyl)-1-oxobutyl]-1- aminocyclopentanecarboxylic) and Z 1796 ((2S)-N-[(2S,3R)-3-Amino-2-hydroxy-4-(4-methylsulphonyl-phenyl)-1- oxobutyl]-L-leucine) were found to behave as hypoalgesics when intracerebroventricularly (i.c.v.) administered to mice in the hot-plate test. At high doses, Z 4212 was also found to reduce the pain threshold after intraventricular (i.v.) administration. Hypoalgesia induced by bestatin analogues was prevented by prior treatment with the opiate receptor blocker naloxone. Thiorphan, a potent inhibitor of NEP, was found to enhance the hypoalgesic effect of low doses of either Z 4212 or Z 1796. These results indicate that both the major opioid-degrading peptidases, i.e. aminopeptidases and neutral endopeptidase (NEP), are individually implicated in the hypoalgesia induced by peptidase inhibitors. In vitro studies showed that these new bestatin analogues readily inhibit aminopeptidases in membranes from mouse c. striatum whereas more than 1000 times the concentration was required for NEP to be blocked. Ex vivo experiments showed that, at variance with bestatin, the hypoalgesic action of Z 4212 or Z 1796 appeared to implicate central aminopeptidases but not NEP, so partially sparing the metabolism of other NEP substrates that might produce additional alterations (substance P and ANP). On the basis of the antitumour and immunomodulatory actions of bestatin, these new analogues might be potentially useful as mixed antitumour and hypoalgesic agents in malignancy.

Disposition of cefoxitin in patients with pleural effusion.

The pharmacokinetics of cefoxitin were studied in nine patients with pleural effusion of varied etiologies. All patients received a single intravenous bolus of 30 mg/kg. Cefoxitin levels were determined simultaneously in plasma and pleural fluid by means of a microbiologic plate diffusion method. The antibiotic follows a two-compartment open kinetic model. In the pleural fluid, maximum concentrations of cefoxitin of 19.72 +/- 9.72 microgram/ml were reached two hours after administration. The fraction of the antibiotic that reaches the pleural fluid represents 0.22% to 4.03% of the dose administered. The disappearance constant of the antibiotic from the pleural fluid is significantly smaller (Kd = 0.15 +/- 0.03 hours-1) than the elimination constant determined from the plasma levels (K13 = 2.27 +/- 0.90 hours-1). Cefoxitin was always found in antibacterial concentration in the pleural fluid for a considerable period of time.