IDENTIFICATION OF SAFETY ALERT BY MONITORING ANALYTICAL PARAMETERS AND HIGH-RISK DRUGS

Early detection of  adverse  drug  reactions  (ADR) increases patient  safety.  Our  objective  was  to  identify  ADR  by  monitoring laboratory  parameters  and  high-risk  drugs.  We  carried  out  a two-month  prospective  observational  study  in  a  Internal Medicine  Department,  with  daily  recording  of  drugs  prescribed and  the  following  parameters:  Na,  K,  Ca,  serum  creatinine, glomerular  filtration  rate  (GFR),  INR,  glucose,  haemoglobin, platelets,  ALT,  AST,  bilirubin,  GGT,  alkaline  phosphatase,  TSH, T4,  and  blood  digoxin.  High-risk  drugs  were  closely  monitored. 52  patients  included,  of  whom  46.2%  experienced  an  ADR.  We observed  an  association  with  drugs  in  25.5%,  as  follows: reduction  in  GFR,  26.9%  (associated  with  loop  diuretics [41.7%],  angiotensin-converting  enzyme  [ACE]  inhibitors [33.3%],  angiotensin  II  receptor  blockers  [ARB]  [16.6%],  andanti-diabetic  drugs  [8.3%]);  hypokalemia,  22.3%  (associated with  loop  diuretics  [50.0%],  potassium-free  fluid  [37.5%],  and salbutamol  [12.5%]);  hyperkalemia,  14.4%  (associated  with ACE  inhibitors  [60.0%]  and  ARB  [40.0%]);  INR  out  of  range, 10.8%  (associated  with  drug  interactions  [66.7%]); hyperglycemia,  8.1%  (associated  with  corticosteroids  [66.7%] and  anti-diabetic  drugs  [33.3%]);  and  other  conditions,  18.8%. We  conclued  that  patient  safety  could  be  improved  by implementing  warnings  in  electronic  prescriptions  in  cases  of  a decrease  in  GFR  or  modification  of  potassium  levels  in  patients who are prescribed loop diuretics, ACE inhibitors, or ARBs.Key words:   Adverse drug reaction,  clinical decision support,  high-risk drug, safety

Promoting clinical pharmacy services through advanced medication review in the emergency department

Objectives: To determine if an advanced medication review carried out in the emergency departmen t (ED) increases the number of pharmacotherapy recommendations (PR) and the severity of the detected prescribing errors.Methods: We designed an analytic observational prospective cohort study with preintervention assessment (PRE) and postintervention assessment (POST). In PRE, prescription review was done by pharmacists located in the pharmacy department; they took into account only the information provided by the computerised physician order entry system. In POST, pharmacists were physically present in the ED and performed an advanced medication review. The main variables were number of PR and the severity of detected prescribing errors according to the National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP) severity index. Clinical variables were number of calls to physicians on duty during the first 48 hours of admission, readmissions at 30 days, visits to the ED at 30 days, inhospital mortality and length of stay.Results: The study population comprised 102 patients (51 in PRE and 51 in POST). In PRE, the number of PR per patient was 1.1; in POST, this value increased by 53% (1.7 PR per patient; P=0.014), especially in the case of PR related to home medications. The severity of prescribing errors was higher in POST (P=0.004). There was a trend towards better results for all clinical outcomes in POST although statistical significance was not reached.Conclusions: An advanced medication review in the ED increases the number of PR and the severity of the detected prescribing errors

Influence on effectiveness of early treatment with anti-TNF therapy in rheumatoid arthritis

Purpose. To evaluate the association between starting early treatment with anti-TNF and effectiveness as well as the possibility of applying therapeutic spacing in daily practice in patients with rheumatoid arthritis (RA). Methods. Observational, retrospective study conducted in two universitary hospitals in Spain. RA patients who received the first anti-TNF (adalimumab: ADA, etanercept: ETN or infliximab: IFX) during the study period (October 2006-2010) were included. Demographic data, time since diagnosis, disease activity (DAS28-ESR) and anti-TNF dosage were analyzed. Therapeutic objective was defined as DAS28<2.6. Also the response related to criteria of the European League Against Rheumatism (EULAR) was evaluated. Therapeutic spacing was defined as the use of a lower dose or a higher interval according to label doses. The main endpoint was to assess the association between the effectiveness and the moment when the anti-TNF therapy begins. The secondary target was to evaluate the association between RA activity at the beginning of treatment with anti-TNF and dose used. Results. 82 patients were included. The prescription profile was: ADA (48.8%), ETN (31.7%) and IFX (19.5%). 71.4% of patients treated with anti-TNF during the first year since diagnosis, 57.1% of those who started after 1-5 years and 30.6% of patients who started after 5 years were in remission when the study ended. De-escalation strategy was performed in 25.6% of patients: ETN (38.5%), ADA (20.0%) and IFX (18.8%). The patients treated with a higher dose according to label doses were: IFX (81%), ADA, (12.5%) and ETN (7.7%). Conclusions. Results suggest that early treatment with anti-TNF can achieve a higher percentage of remissions. Therapeutic spacing is established as a strategy that improves the efficiency in those patients in remission, being the ETN the anti-TNF most susceptible for spacing, although a relation between the early beginning with anti-TNF and the used dose was not found.Instituto de Investigaciones Bioquímicas de La Plat

Influence on effectiveness of early treatment with anti-TNF therapy in rheumatoid arthritis

Purpose. To evaluate the association between starting early treatment with anti-TNF and effectiveness as well as the possibility of applying therapeutic spacing in daily practice in patients with rheumatoid arthritis (RA). Methods. Observational, retrospective study conducted in two universitary hospitals in Spain. RA patients who received the first anti-TNF (adalimumab: ADA, etanercept: ETN or infliximab: IFX) during the study period (October 2006-2010) were included. Demographic data, time since diagnosis, disease activity (DAS28-ESR) and anti-TNF dosage were analyzed. Therapeutic objective was defined as DAS28<2.6. Also the response related to criteria of the European League Against Rheumatism (EULAR) was evaluated. Therapeutic spacing was defined as the use of a lower dose or a higher interval according to label doses. The main endpoint was to assess the association between the effectiveness and the moment when the anti-TNF therapy begins. The secondary target was to evaluate the association between RA activity at the beginning of treatment with anti-TNF and dose used. Results. 82 patients were included. The prescription profile was: ADA (48.8%), ETN (31.7%) and IFX (19.5%). 71.4% of patients treated with anti-TNF during the first year since diagnosis, 57.1% of those who started after 1-5 years and 30.6% of patients who started after 5 years were in remission when the study ended. De-escalation strategy was performed in 25.6% of patients: ETN (38.5%), ADA (20.0%) and IFX (18.8%). The patients treated with a higher dose according to label doses were: IFX (81%), ADA, (12.5%) and ETN (7.7%). Conclusions. Results suggest that early treatment with anti-TNF can achieve a higher percentage of remissions. Therapeutic spacing is established as a strategy that improves the efficiency in those patients in remission, being the ETN the anti-TNF most susceptible for spacing, although a relation between the early beginning with anti-TNF and the used dose was not found.Instituto de Investigaciones Bioquímicas de La Plat

Evolution of adherence to antiretroviral treatment in a spanish hospital during 2001, 2005 and 2008

The aim of this study was to analyze the evolution of adherence to highly active antiretroviral therapy (HAART) in the Hospital General Universitario Gregorio Marañón (Madrid, Spain) over the last 8 years and determine the variables associated with the complexity of treatment and suboptimal adherence. An observational, retrospective method was used to measure adherence during the first 6 months of HAART in 3 cohorts: 2001 cohort (n = 90), 2005 cohort (n = 98), and 2008 cohort (n = 110). The adherence rate was determined using 2 methods: Pharmacy Department dispensation records and virologic response data. The evolution of the complexity of treatment and its influence on the adherence rate was analyzed by logistic regression. Adherence to HAART increased progressively from 45.6 % in 2001 to 56.1 % in 2005 and 77.3 % in 2008. Statistically significant differences were only observed between cohorts in 2005 and 2008. The average daily pill burden was 7, 4, and 4.5 tablets, respectively. The percentage of patients on twice-daily regimens decreased from 93.3 % in 2001 to 63.6 % in 2008, with a parallel increase in once-daily regimens. The proportion of patients with dietary restrictions decreased from 24.4 % to 3.6 %. A statistically significant association was found between the number of medication units per day and adherence and between frequency of administration and adherence. Adherence to HAART has improved significantly in the last 8 years. While the complexity of the treatment was significantly reduced in 2005, the largest increase in adherence occurred in the last cohort, which shows the influence of factors other than treatment simplification.Colegio de Farmacéuticos de la Provincia de Buenos Aire

A critical view on the current use of daptomycin in Spain: The daptomise study

Background: The Study on the Clinical Use of DAPTOMycin in Spain (DAPTOMISE Study) is a national surveillance program of daptomycin use. The objectives of this study are to evaluate the current variability in daptomycin consumption across the different hospitals and the adequacy of therapy, specially focused on underdosing. Methods: All adult and pediatric patients who received, at least, one dose of daptomycin in a single week in 98 institutions in Spain were included. The adequacy of daptomycin use was evaluated with respect to the indication, dosage, adjustments after microbiology results, switching to an oral agent and length of treatment. Results: A total of 615 patients received daptomycin during the study week. The prevalence use was 2.3 patients / 100,000 inhabitants per week, 12.4 patients / 1000 admissions and 9.2 Days of Therapy (DOT) / 1000 hospital stays. These rates varied between hospitals: from 0 to 13.9 patients / 100,000 inhabitants, from 0 to 76.1 patients / 1000 admissions and from 0 to 49.4 DOT / 1000 hospital stays. The most frequent infections were bacteremia (31.6 %) and skin and soft tissue infections (17.9 %). Microbiological results were available in only 65.4 % of infections. The most frequent microorganisms were Staphylococcus aureus (192 isolates, of which 87 were resistant to methicillin) and coagulase-negative staphylococci (124 isolates). A total of 136 prescriptions (22.1 %) were underdosed. Dosages < 8 mg/kg were used for 35.6 % of endovascular infections and for 26.2 % of osteoarticular infections. Overall, 57.2 % of prescriptions were not optimal in, at least, one item. Clinical cure rate was 76.1% and mortality attributable to the infection 8.1%. Conclusion: This is the first registry that identifies the prevalence of use of daptomycin in Spain and shows a high variability in the consumption between the different hospitals. Daptomycin underdosing was present in more than 20 % of cases. (c) 2023 Published by Elsevier Ltd on behalf of King Saud Bin Abdulaziz University for Health Sciences. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Gene signatures of early response to anti-TNF drugs in pediatric inflammatory bowel disease

T. Around a 20–30% of inflammatory bowel disease (IBD) patients are diagnosed before they are 18 years old. Anti-TNF drugs can induce and maintain remission in IBD, however, up to 30% of patients do not respond. The aim of the work was to identify markers that would predict an early response to anti-TNF drugs in pediatric patients with IBD. The study population included 43 patients aged &lt;18 years with IBD who started treatment with infliximab or adalimumab. Patients were classified into primary responders (n = 27) and non-responders to anti-TNF therapy (n = 6). Response to treatment could not be analyzed in 10 patients. Response was defined as a decrease in over 15 points in the disease activity indexes from week 0 to week 10 of infliximab treatment or from week 0 to week 26 of adalimumab treatment. The expression profiles of nine genes in total RNA isolated from the whole-blood of pediatric IBD patients taken before biologic administration and after 2 weeks were analyzed using qPCR and the 2−∆∆Ct method. Before initiation and after 2 weeks of treatment the expression of SMAD7 was decreased in patients who were considered as non-responders (p value &lt; 0.05). Changes in expression were also observed for TLR2 at T0 and T2, although that did not reach the level of statistical significance. In addition, the expression of DEFA5 decreased 1.75-fold during the first 2 weeks of anti-TNF treatment in responders, whereas no changes were observed in non-responders. Expression of the SMAD7 gene is a pharmacogenomic biomarker of early response to anti-TNF agents in pediatric IBD. TLR2 and DEFA5 need to be validated in larger studies.This work was funded by Instituto de Salud Carlos III (grants numbers PI16/00559 and PI19/00792), Consejería de Educación y Deporte de la Comunidad de Madrid (grant number PEJ16/MED/AI-1260), and by the Gregorio Marañón Health Research Institute (grant number PRE-2018-2), The study was cofunded by ERDF Funds (FEDER) from the European Commission, “A way of making Europe

DPYD Exome, mRNA Expression and Uracil Levels in Early Severe Toxicity to Fluoropyrimidines: An Extreme Phenotype Approach

Dihydropyrimidine dehydrogenase deficiency is a major cause of severe fluoropyrimidine-induced toxicity and could lead to interruption of chemotherapy or life-threatening adverse reactions. This study aimed to characterize the DPYD exon sequence, mRNA expression and in vivo DPD activity by plasma uracil concentration. It was carried out in two groups of patients with extreme phenotypes (toxicity versus control) newly treated with a fluoropyrimidine, during the first three cycles of treatment. A novel nonsense gene variant (c.2197insA) was most likely responsible for fluoropyrimidine-induced toxicity in one patient, while neither DPYD mRNA expression nor plasma uracil concentration was globally associated with early toxicity. Our present work may help improve pharmacogenetic testing to avoid severe and undesirable adverse reactions to fluoropyrimidine treatment and it also supports the idea of looking beyond DPYD