How Far Are We From Achieving Delabeling of False Penicillin/ß-Lactam Allergy Alerts? A Population Problem.

BACKGROUND: Interest in finding efficient ways to remove penicillin allergy alerts has grown as a result of awareness of the considerable excess of false-negative diagnoses in patients with penicillin allergy labels (90%-95%), the poorer course with non-ß-lactam antibiotics, the increase in bacterial resistance, and the fact that these problems can affect up to 20% of the population in some countries. The strategies proposed have generated many publications in countries where the number of allergists to conduct such studies is low. In many cases where delabeling is performed, the risk of ß-lactam allergy is low, and a single penicillin challenge is sufficient to delabel the alert. However, other less "ultrarapid" strategies can be used to administer a ß-lactam during an admission for infection and thus postpone delabeling until traditional drug allergy consultations. However, the definitive withdrawal of ß-lactam alerts is threatened by nonremoval of alerts in electronic health records and by the reactivation or nonsynchronization of alerts between electronic systems at different levels of care. Allergy departments need to reflect on how to implement practices that enable rapid and efficient delabeling of drug allergy alerts, especially in patients with major comorbidities.

Real-life analysis on safety and efficacy of asciminib for ponatinib pretreated patients with chronic myeloid leukemia.

Failure of second-generation tyrosine kinase inhibitors (2GTKI) is a challenging situation in patients with chronic myeloid leukemia (CML). Asciminib, recently approved by the US Federal Drug Administration, has demonstrated in clinical trials a good efficacy and safety profile after failure of 2GTKI. However, no study has specifically addressed response rates to asciminib in ponatinib pretreated patients (PPT). Here, we present data on responses to asciminib from 52 patients in clinical practice, 20 of them (38%) with prior ponatinib exposure. We analyzed retrospectively responses and toxicities under asciminib and compared results between PPT and non-PPT patients.After a median follow-up of 30 months, 34 patients (65%) switched to asciminib due to intolerance and 18 (35%) due to resistance to prior TKIs. Forty-six patients (88%) had received at least 3 prior TKIs. Regarding responses, complete cytogenetic response was achieved or maintained in 74% and 53% for non-PPT and PPT patients, respectively. Deeper responses such as major molecular response and molecular response 4.5 were achieved in 65% and 19% in non-PPT versus 32% and 11% in PPT, respectively. Two patients (4%) harbored the T315I mutation, both PPT.In terms of toxicities, non-PPT displayed 22% grade 3-4 TEAE versus 20% in PPT. Four patients (20% of PPT) suffered from cross-intolerance with asciminib as they did under ponatinib.Our data supports asciminib as a promising alternative in resistant and intolerant non-PPT patients, as well as in intolerant PPT patients; the resistant PPT subset remains as a challenging group in need of further therapeutic options.

Long-term outcome of older patients with newly diagnosed de novo acute promyelocytic leukemia treated with ATRA plus anthracycline-based therapy.

Treatment outcome in older patients with acute promyelocytic leukemia (APL) is lower compared with younger patients, mainly because of a higher induction death rate and postremission non-relapse mortality (NRM). This prompted us to design a risk- and age-adapted protocol (Programa Español de Tratamientos en Hematología (PETHEMA)/HOVON LPA2005), with dose reduction of consolidation chemotherapy. Patients aged ⩾60 years reported to the PETHEMA registry and were treated with all-trans retinoic acid (ATRA) plus anthracycline-based regimens according to three consecutive PETHEMA trials that were included. We compared the long-term outcomes of the LPA2005 trial with the preceding PETHEMA trials using non-age-adapted schedules (LPA96&LPA99). From 1996 to 2012, 389 older patients were registered, of whom 268 patients (69%) were eligible. Causes of ineligibility were secondary APL (19%), and unfit for chemotherapy (11%). Median age was 67 years, without relevant differences between LPA2005 and LPA96&LPA99 cohorts. Overall, 216 patients (81%) achieved complete remission with no differences between trials. The 5-year NRM, cumulative incidence of relapse, disease-free survival and overall survival in the LPA2005 vs the LPA96&99 were 5 vs 18% (P=0.15), 7 vs 12% (P=0.23), 87 vs 69% (P=0.04) and 74 vs 60% (P=0.06). A less intensive front-line regimen with ATRA and anthracycline monochemotherapy resulted in improved outcomes in older APL patients.

Comparison of the traditional pharmaceutical validation method versus an assisted pharmaceutical validation in hospitalized patients.

OBJECTIVE: To analyze pharmaceutical interventions that have been carried out with the support of an automated system for validation of treatments vs. the traditional method without computer support. METHOD: The automated program, ALTOMEDICAMENTOS® version 0, has 925 052 data with information regarding approximately 20 000 medicines, analyzing doses, administration routes, number of days with such a treatment, dosing in renal and liver failure, interactions control, similar drugs, and enteral medicines. During eight days, in four different hospitals (high complexity with over 1 000 beds, 400-bed intermediate, geriatric and monographic), the same patients and treatments were analyzed using both systems. RESULTS: 3,490 patients were analyzed, with 42 155 different treatments. 238 interventions were performed using the traditional system (interventions 0.56% / possible interventions) vs. 580 (1.38%) with the automated one. Very significant pharmaceutical interventions were 0.14% vs. 0.46%; significant was 0.38% vs. 0.90%; non-significant was 0.05% vs. 0.01%, respectively. If both systems are simultaneously used, interventions are performed in 1.85% vs. 0.56% with just the traditional system. Using only the traditional model, 30.5% of the possible interventions are detected, whereas without manual review and only the automated one, 84% of the possible interventions are detected. CONCLUSIONS: The automated system increases pharmaceutical interventions between 2.43 to 3.64 times. According to the results of this study the traditional validation system needs to be revised relying on automated systems. The automated program works correctly in different hospitals.

Objetivo: Analizar las intervenciones farmacéuticas realizadas con el apoyo de un sistema automático de validación de tratamientos vs. el método tradicional sin apoyo informático. Metodos: El programa automatizado, ALTOMEDICAMENTOS ® version 0, cuenta con 925.052 celdas con información de aproximadamente 20.000 medicamentos, analizando dosis, vías de administración, días de tratamiento, dosificación en insuficiencia renal y hepática, control de interacciones, de medicamentos semejantes y de medicamentos por vía enteral. Durante ocho días distribuidos en cuatro hospitales diferentes (alta complejidad con más de 1.000 camas, intermedio de 400 camas, geriátrico y monográfico), los mismos pacientes y tratamientos se analizaron mediante los dos sistemas. Resultados: Se han analizado 3.490 pacientes diferentes con 42.155 tratamientos. Por el sistema tradicional se han realizado 238 intervenciones (0,56% intervenciones/posibles intervenciones) vs. 580 (1,38%) con el automatizado. Las intervenciones farmacéuticas muy significativas fueron 0,14 vs. 0,46%, las significativas 0,38 vs. 0,90%, las no significativas 0,05 vs. 0,01%. Las intervenciones fueron del 1,85% al utilizar los dos sistemas vs. 0.56% usando solo el sistema tradicional. El sistema tradicional detectó el 30,5% de las posibles intervenciones, sin embargo con el sistema automático se detectaron el 84% de dichas intervenciones. Conclusiones: La automatización multiplica entre 2,43 a 3,64 veces las intervenciones farmacéuticas. En base a los resultados de este estudio el sistema tradicional de validación debería ser modificado, apoyándose en sistemas automatizados. El programa automático funciona en diferentes hospitales.

Current opinion and consensus statement regarding the diagnosis, prognosis, and treatment of patients with essential thrombocythemia: a survey of the Spanish Group of Ph-negative Myeloproliferative Neoplasms (GEMFIN) using the Delphi method.

The current consensus on the diagnosis, prognosis, and treatment of essential thrombocythemia (ET) is based on experts' recommendations. However, several aspects of the diagnosis of, prognosis of, and therapy for ET are still controversial. The Delphi method was employed with an expert panel of members of the Spanish Group of Ph-negative Myeloproliferative Neoplasms in order to identify the degree of agreement on the diagnosis, prognosis, and treatment of ET. Nine leading experts selected a total of 41 clinical hematologists with well-known expertise in ET. An electronic questionnaire was used to collect the questions rated in a four-step scale. The questions were grouped into four blocks: diagnosis, risk stratification, goals of therapy, and treatment strategy. After the first round consisting of 80 questions, a second round including 14 additional questions focused on the recommendations advocated by experts of the European LeukemiaNet in 2011 was analyzed. The median and mean values for the first and second rounds were calculated. A summary of the conclusions considered as the most representative of each block of questions is presented. The Delphi method is a powerful instrument to address the current approaches and controversies surrounding ET.

[Pharmaceutical intervention on the therapeutic adherence in patients with chronic renal disease]. / Intervención farmacéutica en la adherencia al tratamiento de pacientes con enfermedad renal crónica.

OBJECTIVES: To assess the therapeutic adherence in patients with stage 3-5 chronic renal disease (CRD), and evaluate whether pharmaceutical intervention improves medication adherence. MATERIAL AND METHODS: A prospective uncontrolled before-after study (July 2008-March 2009) was carried out in the Pharmaceutical Care Unit of a tertiary hospital. Polymedicated patients >65 years with stage 3-5 CRD, and on treatment with erythropoietin. Infowin(®) program was used to provide written information during the interviews with patients, who signed the informed consent. The Haynes-Sackett and Morisky-Green questionnaires were used to assess the therapeutic adherence. RESULTS: Of a total of 103 candidates, we asked 94 patients to participate, of whom 53 agreed; women 60.4%, mean age: 76.8 ± 6.9 years. EXCLUSION CRITERIA: refusal to participate (19.5%), non-appearance of patient or usual caregiver (70.7%), and institutionalised patients (9.8%). Average number of drugs per patient: 10.8 ± 2.97. A total of 88.7% had no difficulty in taking medication (Haynes-Sackett) and 73.6% were considered compliant (Morisky-Green). Differences were observed when comparing both methods (P=.036). Patients with difficulty in taking medication were less compliant (45.6%). The Morisky-Green questionnaire was used for a second time on 78.6% of unreliable patients, and obtained a 45.5% increase in compliance, increasing the overall compliance to 87.8% (P=.00003). Fifty-two drug-related problems (DRP) were detected. CONCLUSIONS: The initial compliance of patients with stage 3-5 CRD was was noteworthy. However, after pharmaceutical intervention there was a statistically significant improvement in adherence to therapy.

[Updated classification for medication errors by the Ruiz-Jarabo 2000 Group]. / Actualización de la clasificación de errores de medicación del grupo Ruiz-Jarabo 2000.

OBJECTIVE: To update the classification system created by the Ruiz-Jarabo 2000 group to standardize detection, analysis, and recording of medication errors, with the aim of improving its capacity and functionality. METHOD: The classification update was carried out by the Ruiz-Jarabo 2000 working group considering: a) other classifications used by incident reporting systems initiated after the original version had been created; b) suggestions offered by healthcare professionals with respect to the original version; and c) the experiences of the working group itself based on analyses of medication errors gathered in hospitals, and on analyses of reports notified to the ISMP-Spain medication error reporting and learning program. RESULTS: This article presents the updated version of the medication error classification system and describes the main changes made on to the different sections and categories. CONCLUSIONS: The new version may prove to be a useful tool for analyzing and reporting errors with regard to those detected within the framework of activities for improving safety in hospitals and primary care, as well as for those detected as a direct result of patient safety research. Thus, this document is expected to improve medication safety information management in such a way as to allow data to be used ever more efficiently for making medication use systems safer for patients.

[Orbital lymphomas. Presentation of nine cases]. / Linfomas orbitarios. Presentación de nueve casos.

PURPOSE: To report nine cases of orbital lymphomas. METHODS: We reviewed the clinical records of nine patients diagnosed with orbital lymphoma and performed a literature search related to this condition. RESULTS: We present a series of five women and four males with orbital lymphoma involving the orbital region. In our cases, most patients presented concurrent extraorbital lymphoma when the orbital disease was first noticed (seven out of nine patients). We found three MALT lymphomas, two follicular lymphomas, two non-Hodgkin large B cell lymphomas, one low grade B cell lymphoma, and one mantle cell lymphoma. Eight patients were alive and one had died as a consequence of his lymphoma at the time this report was written. CONCLUSIONS: An increase in the incidence of non-Hodgkin orbital lymphomas has been observed over the last three decades. The most common type in the orbital region is the MALT lymphoma. The clinical features observed in our series are similar to those reported in the literature. Since lymphomas are the most frequent malignant tumours in the orbit, usually with extraorbital involvement, and can be successfully treated in many cases, it is important for the ophthalmologist to be aware of this condition.

[Assessment of safety practices for medication-use systems in Spanish hospitals (2007)]. / Evaluación de las prácticas de seguridad de los sistemas de utilización de medicamentos en los hospitales españoles (2007).

BACKGROUND AND OBJECTIVE: To examine the current status of safety practices for medication-use systems in Spanish hospitals and to identify major areas of risk. MATERIAL AND METHOD: Those hospitals that completed the "Medication use-system safety self-assessment for hospitals" between June 1 and July 15, 2007, were included in the study. The survey contained 232 items for evaluation grouped into 20 core characteristics. RESULTS: A total of 105 hospitals from the 17 autonomous communities in Spain participated in the study. The average aggregate score for the survey of all the participating hospitals was 612.7 (39.7% of the maximum possible score) and there were no differences found with regard to number of beds, training activity or type of hospital. When core characteristics were analyzed, there were 3 criteria with the lowest values (< 25%), associated with professional training, skills, and the establishment of a system for reporting errors. Another 9 criteria, with percentages between 25% and 50%, reflected practices related to: access to information regarding patients and medications; communication of medication orders; prevention of errors due to naming, labeling, and packaging problems; standardization of medication delivery devices; restriction of medications in patient care units; and safety culture and double-checking procedures. CONCLUSIONS: Many opportunities for improvement have been identified, particularly in areas related to training, risk management, incorporating new technologies and patient participation. The information obtained may prove useful for prioritizing practices when establishing patient safety strategies, and as a baseline for successfully monitoring the effectiveness of the initiatives and programs consequently set into motion.

A randomized study of intermediate as compared with high doses of interferon-alpha for chronic myeloid leukemia: no differences in cytogenetic responses.

Interferon-alpha (IFN-alpha) is a therapy of unquestionable efficacy in chronic myeloid leukemia (CML) patients. The best dose of IFN-alpha in the treatment of CML still remains controversial. Our primary objective was to compare cytogenetic responses in patients treated with intermediate versus high doses of IFN-alpha. A multicenter randomized controlled trial was conducted involving 109 patients with untreated CML in chronic phase from 26 Spanish hospitals. Patients were assigned to receive either an intermediate (2.5 MU/m(2) per day) or high (5 MU/m(2) per day) target dose of IFN-alpha. Hydroxyurea was allowed in both groups. In total, 108 patients were analyzed, 53 in the intermediate- and 55 in the high-dose group. Median follow-up was 47.5 months. The dose of IFN-alpha actually given was lower in the intermediate-dose group (3.83 MU/day) than in the high-dose group (6.6 MU/day) ( p<0.001). The rate of complete cytogenetic response was 24.5% in the intermediate- and 12.7% in the high-dose group (NS). A partial cytogenetic response was obtained in 7.5% and 10.9%, respectively. Cox analysis did not reveal any influence of the randomization arm on cytogenetic response rate. Ten patients in each group discontinued IFN-alpha because of toxicity. Albeit not our primary objective, no differences were found in terms of survival or transformation rate between both groups. Median survival was 73 months; 64% of patients remained free of transformation at 5 years. In terms of cytogenetic response, intermediate doses of IFN-alpha are as effective as high doses in the treatment of CML.

[Medication errors: standarizing the terminology and taxomany. Ruiz Jarabo 2000 grand results]. / Errores de medicación: estandarización de la terminología y clasificación. Resultados de la beca Ruiz Jarabo 2000.

OBJECTIVE: To make available a consistent terminology and taxonomy that permits standardization in medication error detection, analysis, classification, and recording. METHODS: A working group consisting of healthcare professionals from four hospitals of varying characteristics was established to develop the terminology and the taxonomy, which was validated through a qualitative analysis of 423 medication errors registered in the participating hospitals. RESULTS: A document with a terminology and a taxonomy for classifying medication errors is presented. CONCLUSIONS: This document will facilitate analysis of the information collected on incidents caused by medication, and will allow comparisons to be made among data gathered in different kinds of settings. In addition, it will be a useful tool for medication safety committees in hospitals in their efforts to set up internal reporting programs designed to identify shortcomings in their medication use systems and to adopt effective measures to reduce the incidence of medication errors.

Stage, percentage of basophils at diagnosis, hematologic response within six months, cytogenetic response in the first year: the main prognostic variables affecting outcome in patients with chronic myeloid leukemia in chronic phase treated with interferon-alpha. Results of the CML89 trial of the Spanish Collaborative Group on interferon-alpha2a and CML.

BACKGROUND AND OBJECTIVE: Interferon-a (IFN) is increasingly being used as the drug of choice in chronic myeloid leukemia patients. The main objectives of the study were to study the influence of the classic prognostic variables and response to IFN, and to assess the influence of this response on the course of the disease and survival. DESIGN AND METHODS: Single arm, prospective, multicenter study, without a control group. Only Ph1-positive CML patients were included. The treatment scheme was biphasic: the patients first received standard chemotherapy and thereafter IFN-a2a was used as monotherapy, with a target dose of 9 MU/d/s.c. RESULTS: Twenty-one centers in Spain enrolled 132 patients (72 men, 60 women). The median dose of IFN given was 5.8 MU/d, and the median treatment duration was 431 days (range: 18-2,597). Seventy-two percent of patients obtained a hematologic response in the first six months of IFN treatment. Genetic response was obtained in 47% of the patients, and the response was major or complete in 27% and 19%, respectively. The median time to obtain this response was 7, 9, and 18 months for minimal, partial and complete genetic response, respectively. Multivariant analysis showed that only a higher percentage of basophils at diagnosis was associated with a worse hematologic response at six months (p=0.001) (OR: 1.23) and with a worse cytogenetic response in the first year of IFN therapy (p=0.018) (OR: 1.4). Over an observation period of 8 years, 35.6% of the patients died, and 85 (64.4%) remained alive. With a median follow-up of 42 months (3.7-98), the 6-year projected probabilities of survival and transformation-free survival were 0.61+/-0.07 vs. 0.54+/-0.07, respectively. Patients with Kantarjian's stage 3 disease or in a high-risk Sokal group had lower probabilities of survival, but these systems did not adequately discriminate in our series. Obtaining a complete hematologic response in the first six months of IFN therapy was favorable in terms of overall survival (p=0.05; HR=0.33). Cox's analysis demonstrated that obtaining a cytogenetic response in the first year was independently associated with better overall survival (p=0.04; HR=0.19) and better transformation-free survival (p=0.0035; HR=0.11). INTERPRETATION AND CONCLUSIONS: Nearly half of the patients obtained some degree of Philadelphia suppression, which was major in 27%, and complete in 19%. A higher percentage of basophils at diagnosis was the only variable associated with a lower probability of cytogenetic response. Obtaining a cytogenetic response during the first year of IFN treatment was a favorable and independent variable in terms of survival and transformation-free survival. Obtaining a major cytogenetic response during this period decreased the risk of transformation twenty times. Our results suggest that the effect of IFN on survival is independent of the classic prognostic variables.

Correlation and prognostic value of serum soluble ICAM-1, beta-2 microglobulin, and IL-2alphaR levels in non-Hodgkin's lymphoma.

Serum levels of sICAM-1, sIL-2alphaR, and beta-2 microglobulin were measured in 63 patients with non-Hodgkin's lymphoma (NHL). The correlation between these serum markers as well as their relationship with NHL features and disease outcome were analyzed. Although in high-grade NHL sICAM-1 levels correlated with tumor mass, no correlation was found between sICAM-1 levels and tumor burden in low-grade NHL. When compared with sICAM-1 and beta-2 microglobulin, sIL-2alphaR showed the strongest correlation with the tumor burden. However, in multivariate analysis, including serum markers employed as continuous variables, the only parameteres which entered the regression model were beta-2 microglobulin (p=0.012) and sICAM-1 (p=0.019). In a dichotomized model, beta-2 microglobulin, aggressive histology, sICAM-1, age and number of nodal involved sites were found to be prognostically significant. Finally, by combining sICAM-1 and beta-2 microglobulin serum levels, a simple prognostic model useful for NHL was obtained.

Hydroxyurea-induced acute interstitial pneumonitis in a patient with essential thrombocythemia.

Hydroxyurea is a drug widely used to control myeloproliferative disorders, due in part to its relative lack of severe side effects. We present a case of acute interstitial pneumonitis in a patient who was treated with hydroxyurea for essential thrombocythemia. The clinical course suggests that the interstitial pneumonitis was induced by hydroxyurea. This is the first case of hydroxyurea-induced acute interstitial pneumonitis reported in the literature.