Miguel Ángel Calleja-Hernández

Impact of clinical pharmacist interventions in reducing paediatric prescribing errors

Objective To assess the impact of pharmacist intervention in reducing prescribing errors in paediatrics, and to analyse the clinical significance and reasons behind the errors detected. Methods Cross-sectional epidemiological study analysing the activities of the paediatric pharmacist in a maternity and childrens hospital with 180 paediatric beds, between January 2007 and December 2009. The following variables were analysed: impact of the pharmacists recommendation on patient care, reason for the intervention, clinical significance, type of negative outcome associated with the medication, acceptance rate, medication involved, intervention detection date and observations. Results A total of 1475 interventions in medical orders for 14 713 paediatric patients were recorded (40 (2.9%) extremely significant interventions and 155 (11.1%) very significant interventions). There were 1357 prescribing errors, 833 of which were dosing errors. 2.2% of the errors detected were potentially fatal (30 cases) and 14.3% (194 cases) were clinically serious. The main reason for interventions was detection of a dosage between 1.5 and 10 times higher than that recommended. The overall rate of acceptance of the pharmacists suggestions was 94.3%. The pharmacist carried out an average of 0.019 interventions per patient day throughout the study period. Conclusion Interventions by a clinical pharmacist had a major impact on reducing prescribing errors in the study period, thus improving the quality and safety of care provided.

PTEN and PI3K/AKT in non-small-cell lung cancer.

Non-small-cell lung cancer (NSCLC) is the leading cause of cancer deaths worldwide. In the last years, the identification of activating EGFR mutations, conferring increased sensitivity and disease response to tyrosine kinase inhibitors, has changed the prospect of NSCLC patients. The PTEN/PI3K/AKT pathway regulates multiple cellular functions, including cell growth, differentiation, proliferation, survival, motility, invasion and intracellular trafficking. Alterations in this pathway, mainly PTEN inactivation, have been associated with resistance to EGFR-tyrosine kinase inhibitor therapy and lower survival in NSCLC patients. In this review, we will briefly discuss the main PTEN/PI3K/AKT pathway alterations found in NSCLC, as well as the cell processes regulated by PTEN/PI3K/AKT leading to tumorigenesis.

Impact of implementing smart infusion pumps in a pediatric intensive care unit

PURPOSE The impact of smart infusion pumps on the interception of errors in the programming of i.v. drug administrations on a pediatric intensive care unit (PICU) is investigated. METHODS A prospective observational intervention study was conducted in the PICU of a hospital in Madrid, Spain, to estimate the patient safety benefits resulting from the implementation of smart pump technology (Alaris System, CareFusion, San Diego, CA). A systematic analysis of data stored by the devices during the designated study period (January 2010-June 2011) was conducted using the system software (Guardrails CQI Event Reporter, CareFusion). The severity of intercepted errors was independently classified by a group of four clinical pharmacists and a group of four intensive care pediatricians; analyses of intragroup and intergroup agreement in perceptions of severity were performed. RESULTS During the 17-month study period, the overall rate of user compliance with the safety software was 78%. The use of smart pump technology resulted in the interception of 92 programming errors, 84% of which involved analgesics, antiinfectives, inotropes, and sedatives. About 97% of the errors resulted from user programming of doses or infusion rates above the hard limits defined in the smart pump drug library. The potential consequences of the intercepted errors were considered to be of moderate, serious, or catastrophic severity in 49% of cases. CONCLUSION The use of smart pumps in a PICU improved patient safety by enabling the interception of infusion programming errors that posed the potential for severe injury to pediatric patients.

Implementing smart pump technology in a pediatric intensive care unit: A cost-effective approach

OBJECTIVE To analyze the cost effectiveness of implementing smart infusion pump technology in a pediatric intensive care unit (PICU). MATERIAL AND METHODS An observational, prospective, intervention study with analytical components was carried out. A drug library was developed and integrated into the Carefusion Alaris Guardrails® infusion systems. A systematic analysis of all the data stored on the devices during use was performed by the data processing program Guardrails® CQI v4.1 Event Reporter. Intercepted errors were classified in terms of their potential severity and probability of causing an adverse effect (PAE) had they reached the patient. Knowing the estimated cost of a preventable adverse effect (AE), we analyzed costs saved and the profit/cost ratio resulting from the implementation process. RESULTS Compliance with the drug library was 92% and during the study period 92 infusion-related programming errors were intercepted, leading to a saving of 172,279 euros by preventing AEs. This means that 2.15 euros would be obtained for each euro invested in hiring a pharmacist to implement this technology. DISCUSSION The high percentage of use of safety software in our study compared to others allowed for the interception of 92 errors. The estimation of the potential impact of these errors is based on clinical judgment. The cost saved might be underestimated because the cost of an AE is usually higher in pediatrics, indirect and intangible costs were not considered and pharmacists involved do not spend the whole day on this task. CONCLUSIONS Smart pumps have shown to be profitable in a PICU because they have the ability to intercept potentially serious medication errors and reduce costs associated with such errors.

Trends in survival of multiple myeloma: A thirty-year population-based study in a single institution

BACKGROUND Despite the progress made in recent years, multiple myeloma is still considered an incurable disease. Most survival data come from clinical trials. Little is known about the outcome in unselected real-life patients. METHODS Overall survival was analyzed in a cohort of newly diagnosed symptomatic multiple myeloma patients, over the last three decades, in a single institution population-based study. RESULTS 582 consecutive myeloma patients were included in the study. Survival increased over time in patients younger than 65 years but did not reach statistical significance in patients with 65 years or older. The prognostic factors associated with overall survival were the International Staging System, the serum lactate dehydrogenase level, the renal impairment, the realization of autologous stem cell transplantation, and the presence of concomitant amyloidosis. Overall survival shows a steady improvement over time. INTERPRETATION The survival of myeloma is improving progressively in real-life patients, particularly after the widespread use of the novel agents. A comprehensive assessment of comorbidity can help to explain the huge heterogeneity of myeloma outcome. The optimization of current therapeutic resources as well as the incorporation of new drugs will allow further improvement of survival in the coming years.

MET: a new promising biomarker in non-small-cell lung carcinoma.

Non-small-cell lung cancer (NSCLC) leads cancer-related deaths worldwide. Mutations in the kinase domain of the EGFR gene provide sensitivity to tyrosine kinase inhibitors (TKI) drugs. TKI show initial response rates over 75% in mutant EGFR-NSCLC patients, although most of these patients acquire resistance to EGFR inhibitors after therapy. EGFR-TKI resistance mechanisms include amplification in MET and its ligand, and also MET mutations. MET signaling dysregulation has been involved in tumor cell growth, survival, migration and invasion, angiogenesis and activation of several pathways, therefore representing an attractive target for anticancer drug development. In this review, we will discuss MET-related mechanisms of EGFR-TKI resistance in NSCLC, as well as the main drugs targeted to inhibit MET pathway.

Contribution of genetic factors to platinum-based chemotherapy sensitivity and prognosis of non-small cell lung cancer

Although platinum-based chemotherapy remains the standard treatment for advanced NSCLC patients, clinical outcomes are poor and most patients develop high-grade toxicities. Genetic factors, such as single nucleotide polymorphisms (SNPs) involved in platinum pharmacodynamics, metabolism and mechanism of action, may account for inter-individual differences shown in effectiveness and toxicity. Polymorphisms in genes involved in DNA repair and others such as PI3K/PTEN/AKT and TGF-β pathways have been demonstrated to be associated with response, survival and toxicity in advanced NSCLC patients treated with platinum-based chemotherapy. Other cellular processes, like DNA methylation and proliferation have been connected with clinical outcome for platinum-based chemotherapy regimens through folate metabolism and cytokine signaling. The influence of gene polymorphisms in the NER pathway on clinical outcome has been extensively investigated in advanced NSCLC patients treated with platinum-based chemotherapy but contradictory results have been reported. The most recent and thorough meta-analyses have failed to show an association between ERCC1 C118T/C8092A and ERCC5 rs1047768 polymorphisms and response to platinum based chemotherapy. However, other polymorphisms in ERCC2 (Lys751Gln and Asp312Asn) and ERCC5 (rs2094258 and rs2296147) and have been related with overall survival (OS) and progression-free survival (PFS), respectively. The Arg194Trp and Gln399Arg polymorphisms in XRCC1, have also been extensively investigated. Their effects seem to be dependent on ethnicity, and recent meta-analyses have confirmed an association with response in Asian but not in Caucasian patients. The influence on overall response rate (ORR) of the rs861539 polymorphism in XRCC3, part of (DSB) repair pathway, has also been confirmed in a meta-analysis. Finally, SNPs in genes coding proteins of the p53, PI3K, TGF-β, membrane transporters, gluthatione metabolism enzymes and cytokine pathways have been less extensively investigated. Some polymorphisms have been reported to be associated with toxicity or clinical outcome, but data generally come from a limited number of studies and need to be confirmed.

Gene polymorphisms as predictors of response to biological therapies in psoriasis patients.

Psoriasis is a chronic inflammatory autoimmune skin disease, characterized by the formation of erythematous scaly plaques on the skin and joints. The therapies for psoriasis are mainly symptomatic and sometimes with poor response. Response among patients is very variable, especially with biological drugs (adalimumab, etarnecept, infliximab and ustekimumab). This variability may be partly explained by the effect of different genetic backgrounds. This has prompted the investigation of many genes, such as FCGR3A, HLA, IL17F, IL23R, PDE3A-SLCO1C1, TNFα and other associated genes, as potential candidates to predict response to the different biological drugs used for the treatment of psoriasis. In this article, we will review the influence of gene polymorphisms investigated to date on response to biological drugs in psoriasis patients.

Prediction of stable acenocoumarol dose by a pharmacogenetic algorithm.

Aim To develop an acenocoumarol (ACN) dosing algorithm for patients with atrial fibrillation or venous thromboembolism, considering the influence on the stable ACN dose of clinical factors and gene polymorphisms, including CYP2C9*2/*3, VKORC1, CYP4F2*3, ABCB1, APOE, CYP2C19*2/*17, and GGCX. Methods and results A retrospective observational study was carried out to obtain clinical and pharmacogenetic dose algorithms by multiple linear regression of results in a cohort of 134 patients under treatment with a stable ACN dose for atrial fibrillation or venous thromboembolism and to test them in an independent validation cohort of 30 patients. The pharmacogenetic dosing algorithm included CYP2C9, VKORC1, and APOE, which explained 56.6% of the variability in the stable ACN dose. Lower deviation from the stable dose and increased accuracy were shown by the pharmacogenetic algorithm, which correctly classified 67% of patients with a deviation of up to 20%. Conclusion The variability in the stable ACN dose was better explained by a pharmacogenetic algorithm including clinical and genetic factors (CYP2C9, VKORC1, and APOE) than by a clinical algorithm, providing a more accurate dosage prediction.

Safe implementation of standard concentration infusions in paediatric intensive care.

To evaluate safety, following introduction of standard concentrations of morphine infusions in paediatric critical care.