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.

Refeeding syndrome.

Refeeding syndrome is a complex syndrome that occurs as a result of reintroducing nutrition (oral, enteral or parenteral) to patients who are starved or malnourished. Patients can develop fluid-balance abnormalities, electrolyte disorders (hypophosphataemia, hypokalaemia and hypomagnesaemia), abnormal glucose metabolism and certain vitamin deficiencies. Refeeding syndrome encompasses abnormalities affecting multiple organ systems, including neurological, pulmonary, cardiac, neuromuscular and haematological functions. Pathogenic mechanisms involved in the refeeding syndrome and clinical manifestations have been reviewed. We provide suggestions for the prevention and treatment of refeeding syndrome. The most important steps are to identify patients at risk, reintroduce nutrition cautiously and correct electrolyte and vitamin deficiencies properly.

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.

[Adverse drug events in out-patients as the cause of an initial consultation to neurology]. / Acontecimientos adversos por medicamentos en pacientes ambulatorios como motivo de primera consulta a neurología.

INTRODUCTION: The aim of this study was to determine the incidence and type of neurological adverse drug events as the cause of an initial consultation to neurology, identify the medications involved and evaluate the possibilities of prevention. METHODS: Prospective observational study lasting 1 year (February 10, 2004 to February 9, 2005) that included all new adult outpatients at a neurology ward. Suspected adverse drug events were evaluated by two investigators in order to establish causality relationships, severity, preventability and types of medication errors associated with the preventable cases. RESULTS: In a total of 685 patients who attended the neurology consult, 60 neurological adverse drug events were detected (8.7%), of which 70% were moderate and 30% mild. The most frequent adverse events detected were medication overuse headache (51.6%), mainly due to acetaminophen and ergot derivatives, and drug-induced Parkinsonism (33.3%), especially related to trimetazidine or sulpiride. Fifty-five adverse events (91.6%) were considered potentially preventable. Medication errors associated were overuse and self-medication (33.7 %), failure to follow treatment adequately (25.6%), excessive duration of treatment (16.3%) and prescribing an unnecessary medication (14.0%) or an inappropriate one (10.5%). CONCLUSIONS: The incidence of adverse drug events motivating an initial visit to a neurologist is high and the majority of these cases are preventable. Greater knowledge on the part of physicians concerning medication overuse headache and drugs that induce Parkinsonism, as well as public health education on the risks involved with the use of analgesics, could contribute to prevention.

Cidofovir treatment of human polyomavirus-associated acute haemorrhagic cystitis.

We report the case of an 18-year-old patient who received an allogeneic bone marrow transplant from an HLA-identical unrelated donor for a Ph+ acute lymphoblastic leukemia, in his third complete remission. Cyclophosphamide and busulfan were used as conditioning treatment. Acute graft-versus-host disease developed on day +9, and the response to adequate treatment (steroids) was favourable. On day +45 the patient developed an acute severe haemorhragic cystitis, and BK polyomavirus was demonstrated in urine samples using electron microscopy and polymerase chain reaction. Urinary symptoms did not improve in spite of palliative treatment, but a response was evident after 2 weeks of cidofovir treatment.

Population estimation of valproic acid clearance in adult patients using routine clinical pharmacokinetic data.

The aim of the present study was to estimate valproic acid (VPA) clearance values for adult patients with epilepsy, using serum concentrations gathered during their routine clinical care. Retrospective steady state serum concentrations data (n=534) collected from 208 adult patients receiving VPA were studied. Data were analysed according to a one-compartment model using the NONMEM program. The influence of VPA daily dose (Dose), gender, age, total body weight (TBW), and comedication with carbamazepine (CBZ), phenytoin (PHT) and phenobarbital (PB) were investigated. The results of the population pharmacokinetics analysis were validated in a group of 30 epileptic patients. The final regression model for VPA clearance (Cl) was: $¿rm Cl¿left (¿rm L/h ¿right )=0¿rm. 004¿times TBW¿times Dose ¿0.304¿¿rm ¿times 1.363¿,¿rm CBZ¿times 1. 541¿,¿rm PHT¿times 1.397¿,¿rm PB.$ The inter-individual variability in VPA clearance, described by a proportional error model, had a variation coefficient (CV) of 23.4% and the residual variability, described using an additive model, was 11.4 mg/L. These results show that VPA clearance increased linearly with TBW, but increases nonlinearly with increasing VPA daily dose. Concomitant administration of CBZ, PHT and PB led to a significant increase in VPA clearance. The model predictions in the validation group were found to have satisfactory precision and bias. In conclusion, inter-individual variability in VPA clearance can be partly explained by TBW, daily dose and bitherapy with CBZ, DPH or PB. Inclusion of these factors allows this variability to be reduced by 37.23% which may be very useful for clinicians when establishing the initial VPA dosage regimen. However, the magnitude of inter-individual plus residual variabilities, remaining in the final model, render these dosage predictions imprecise and justify the need for VPA serum level monitoring in order to individualize dosage regimens more accurately.

Valproate population pharmacokinetics in children.

OBJECTIVE: A population analysis of the kinetics of valproic acid (VPA) in children with epilepsy was performed in order to characterize the covariates which influence VPA clearance (CL). METHODS: A total of 770 steady-state serum concentration samples was analysed. These were collected during VPA therapy from 255 children, aged 0.1-14 years and weighting 4-74 kg. Age, total body weight (TBW), VPA daily dose, sex and comedication with carbamazepine (CBZ) were considered as covariates. Population analysis was made with NONMEM program, assuming a one-compartment model, fixing the VPA absorption rate, bioavailability and distribution volume at values found in the literature. The results of the population pharmacokinetics analysis were validated in a group of 45 epileptic patients. RESULTS: The final regression model for VPA clearance, that included TBW (kg), daily dose (mg/kg) and CBZ comedication as covariates with a significant influence on this parameter, was as follows: CL (L/h) = 0.012 TBW0.715 DOSE0.306(1.359 CBZ). The coefficient of variation for interpatient variability in CL was 21.4% and the residual variability estimated was 23.9% for a concentration of 65 mg/l. In order to estimate the predictive performance of the selected final model, predictions of the VPA serum concentrations were calculated and compared with VPA measured concentrations in the validation group. This assessment revealed an important improvement in the predictive performance of VPA concentrations in comparison with the basic model that did not include any covariates (root squared mean error: 19.50 vs. 39.73 mg/l). CONCLUSION: A population pharmacokinetic model is proposed to estimate the individual CL for paediatric patients receiving VPA in terms of patient's dose, weight and concomitant CBZ, in order to establish a priori dosage regimens.

Normal and clonal B lineage cells can be distinguished by their differential expression of B cell antigens and adhesion molecules in peripheral blood from multiple myeloma (MM) patients--diagnostic and clinical implications.

Human MM is a haematologic disorder characterized by the accumulation of malignant plasma cells (PC), primarily in the bone marrow (BM). Although these cells characteristically home to the BM, in recent years several groups have detected the presence of related malignant B cells in the peripheral blood (PB) which could be implicated in the progression and spread of the disease. However, the proportion and origin of these clonotypic circulating B cells is still controversial. In this study, using a triple-staining flow cytometric procedure and a whole blood lysis method, PB B lineage cells could be divided into two populations according to their distinct repertoires of cell adhesion molecules and B cell antigens in untreated MM patients. The results show that: (i) the percentage and the absolute number of PB CD19+ B cells were decreased in MM patients compared with controls; (ii) the quantity and percentage of B cell antigens (CD20, CD22, CD24, DR, CD138) and adhesion molecules (beta1- and beta2-integrins, CD44, CD54, CD56, CD61 and CD62L) expressed by these PB CD19+ cells of MM patients and healthy subjects were similar and all of them were virtually polyclonal cells; (iii) a very minor circulating CD19-CD38++CD45-/dim subset was also detected which expressed CD138 (B-B4) (high intensity), monoclonal cytoplasmic immunoglobulin (cIg), and was negative for pan-B antigens (CD19, CD20, CD24, DR), surface immunoglobulin (sIg) and several adhesion molecules such as CD62L, CD18 and CD11a; this CD19-CD38++CD45-/dim CD138++ subset was not found in normal blood and exhibited a phenotypic profile which was closely related to that of malignant BM plasma cells, with the exception of the CD56 antigen. Polymerase chain reaction (PCR) analysis of IgH clonotypic rearrangements confirmed these results. We postulate that, in MM patients, circulating B lineage cells may be divided into two different categories: polyclonal CD19+ B cells and a very minor proportion of clonal CD138++ PC that escape from the BM.