Impact of proactive of infliximab monitoring using the Bayesian approach in the maintenance phase in patients with inflammatory bowel disease / Impacto de la monitorización proactiva de infliximab en fase de mantenimiento mediante estimación bayesiana en pacientes con enfermedad inflamatoria intestinal

Background and objectives: There is increasing evidence that proactive monitoring is useful in improving the control of inflammatory bowel disease, although it remains controversial. The aim of this study was to evaluate the efficacy of proactive TDM based on the Bayesian approach to optimise the IFX dose compared with the standard of care dosing in patients with IBD. Methods: Retrospective observational cohort of inflammatory bowel disease patients>18 years. Patients were classified into two groups according to the strategy used to optimise the dose of IFX: a standard therapy group (ST-group) with clinically based dose adjustment and therapeutic drug monitoring group (TDM-group), with estimation of pharmacokinetic parameters calculated by Bayesian prediction. Results: A total of 153 patients were included. Of these, 75 were in the TDM-group. Clinical response at week 52 was evaluated in 114 patients. The proportion of patients who achieved clinical remission was higher in the TDM than in the ST-group (80.7% vs 61.4%, respectively, p=0.023). A total of 28 patients (24.6%) met the parameters for the composite variable ‘poor clinical outcome’ at week 52. The proportion of patients who reached this outcome was lower in the TDM-group than in the ST-group (12.3% vs 36.8%, respectively, p=0.002). Conclusions: Proactive therapeutic drug monitoring using Bayesian approach is associated with higher secondary response and fewer long-term complications.(AU)

Antecedentes y objetivos: Cada vez hay más evidencia de que la monitorización proactiva es útil para mejorar el control de la enfermedad inflamatoria intestinal (EII), aunque sigue siendo controvertida. El objetivo de este estudio fue evaluar la eficacia de la monitorización de fármacos terapéuticos (TDM) proactiva basada en el enfoque bayesiano en comparación con el manejo estándar en pacientes con EII. Métodos: Cohorte observacional retrospectiva de pacientes con EEI > 18 años. Los pacientes se clasificaron en dos grupos de acuerdo con la estrategia utilizada para optimizar la dosis de infliximab (IFX): un grupo de terapia estándar (grupo-ST) con ajuste de dosis basado en la clínica y un grupo de monitorización terapéutica del fármaco (grupo-TDM), con estimación de parámetros farmacocinéticos calculados mediante estimación bayesiana. Resultados: Se incluyeron un total de 153 pacientes. De estos, 75 estaban en el grupo-TDM. La respuesta clínica en la semana 52 se evaluó en 114 pacientes. La proporción de pacientes que alcanzaron la remisión clínica fue mayor en el grupo-TDM que en el grupo-ST (80,7 vs. 61,4%, respectivamente, p = 0,023). Un total de 28 pacientes (24,6%) cumplieron los parámetros de la variable compuesta «resultado clínico deficiente» en la semana 52. La proporción de pacientes que alcanzaron este resultado fue menor en el grupo-TDM que en el grupo-ST (12,3 vs. 36,8%, respectivamente, p = 0,002). Conclusiones: La TDM proactiva mediante el enfoque bayesiano se asocia con una mayor respuesta secundaria y menos complicaciones a largo plazo.(AU)

Comparative effectiveness and drug survival of biosimilar infliximab CPT-13 vs. reference infliximab in inflammatory bowel disease: A retrospective cohort study.

BACKGROUND: Studies have investigated the efficacy and safety of switching to the biosimilar infliximab (CT-P13) in patients with inflammatory bowel disease (IBD). However, there is limited research directly comparing the effectiveness, drug survival, and pharmacokinetic profiles of the reference infliximab (IFX) and CT-P13 in real clinical settings. OBJECTIVE: To compare the effectiveness and drug survival of CPT-13 and reference IFX at weeks 26 and 52, and to determine the pharmacokinetic profiles and safety profile in real-world settings. METHODS: A retrospective observational cohort analysis was conducted at a single center. The study compared the proportion of patients achieving clinical remission and experiencing poor clinical outcomes at weeks 26 and 52. The drug survival rate of CT-P13 and reference infliximab was also assessed during the follow-up period. RESULTS: A total of 153 patients were included in the study, 39.2% receiving CPT-13 and 60.8% reference IFX. At week 26, clinical remission rates were 66.7% (CPT-13: 74.4% vs. reference IFX: 62.3%, p=0.178), and at week 52, they were 64% (CPT-13: 85.4% vs. reference IFX: 63.0%, p=0.012). Subgroup analysis with therapeutic drug monitoring (TDM) found no significant differences at week 26 (CPT-13: 74.4% vs. reference IFX: 58.8%, p=0.235) or at week 52 (CPT-13: 85.4% vs. reference IFX: 68.8%, p=0.153). CONCLUSION: Our study demonstrates comparable efficacy, drug survival, pharmacokinetic profiles, and incidence of immunogenicity between both drugs in a real clinical setting. Further studies with greater statistical power are needed to validate these findings.

Impact of proactive therapeutic drug monitoring of infliximab during the induction phase in IBD patients. A Bayesian approach.

BACKGROUND AND OBJECTIVES: there is increasing evidence that proactive therapeutic drug monitoring in induction is useful to improve the control of inflammatory bowel disease (IBD), although it remains controversial. The primary objective of the study was to assess the short-term outcomes of proactive Bayesian therapeutic drug monitoring (TDM) during induction, to optimize infliximab (IFX) maintenance dose. METHODS: retrospective observational cohort of IBD patients > 18 years. They were divided into two cohorts, standard therapy group (ST-group), with clinically based dose adjustment, and monitoring group (iTDM-group), with pharmacokinetic parameters calculated by Bayesian prediction at week 6 and individualized dosage regimens thereafter. In patients with an infliximab trough level (ITL) at week 6 below the optimal therapeutic range, the dose adjustment was performed at the first maintenance dose. RESULTS: a total of 153 patients were included, 40 in the iTDM-group. Median ITL at week 6 during the induction period was 12.8 µg/ml (IRQ: 12.7) in this group. Only 16 patients (40.0 %) had ITL ≥ 15 µg/ml. Half of the patients (50.3 %) received intensified maintenance therapy during the study period (57.5 % iTDM vs 47.8 % ST, p = 0.291). The proportion of patients achieving primary response at week 14 was 51.8 %. When comparing the two groups, this proportion was higher in the iTDM group (74.3 % vs 44.2 %, p = 0.002). With regards to the variable "poor clinical outcomes" at week 26, this proportion was lower in the iTDM group (3.3 % iTDM vs 21.1 % ST, p = 0.024). CONCLUSIONS: proactive therapeutic drug monitoring using Bayesian approach is associated with higher primary response rates and fewer short-term complications.

Impact of proactive therapeutic drug monitoring of infliximab during the induction phase in IBD patients. A Bayesian approach

Background and objectives: there is increasing evidence that proactive therapeutic drug monitoring in induction is useful to improve the control of inflammatory bowel disease (IBD), although it remains controversial. The primary objective of the study was to assess the short-term outcomes of proactive Bayesian therapeutic drug monitoring (TDM) during induction, to optimize infliximab (IFX) maintenance dose. Methods: retrospective observational cohort of IBD patients > 18 years. They were divided into two cohorts, standard therapy group (ST-group), with clinically based dose adjustment, and monitoring group (iTDM-group), with pharmacokinetic parameters calculated by Bayesian prediction at week 6 and individualized dosage regimens thereafter. In patients with an infliximab trough level (ITL) at week 6 below the optimal therapeutic range, the dose adjustment was performed at the first maintenance dose. Results: a total of 153 patients were included, 40 in the iTDM-group. Median ITL at week 6 during the induction period was 12.8 µg/ml (IRQ: 12.7) in this group. Only 16 patients (40.0 %) had ITL ≥ 15 µg/ml. Half of the patients (50.3 %) received intensified maintenance therapy during the study period (57.5 % iTDM vs 47.8 % ST, p = 0.291). The proportion of patients achieving primary response at week 14 was 51.8 %. When comparing the two groups, this proportion was higher in the iTDM group (74.3 % vs 44.2 %, p = 0.002). With regards to the variable “poor clinical outcomes” at week 26, this proportion was lower in the iTDM group (3.3 % iTDM vs 21.1 % ST, p = 0.024). Conclusions: proactive therapeutic drug monitoring using Bayesian approach is associated with higher primary response rates and fewer short-term complications (AU)

Biosimilar infliximab CPT-13 for inflammatory bowel disease in a real clinical setting: pharmacokinetic outcomes, immunogenicity, and drug survival.

BACKGROUND: efficacy and safety were evaluated after switching to a biosimilar infliximab (CPT-13) in patients with inflammatory bowel disease (IBD). However, few cohort studies compare the pharmacokinetic profiles, immunogenicity, and safety of the reference infliximab (IFX) and CPT-13 in a real clinical setting. OBJECTIVE: to compare the pharmacokinetic profiles and drug survival on the long term of reference IFX and CPT-13 at weeks 54 and 104. A secondary objective was to determine the long-term immunogenicity and safety profile of CPT-13 in patients with IBD in a real clinical setting. METHODS: a retrospective, observational cohort analysis was performed in a single center, including patients with IBD under treatment with reference IFX or CPT-13. Serum drug concentrations were compared to determine if there were any significant differences in pharmacokinetic outcomes between reference IFX and CPT-13 at 26, 54, 78, and 104 weeks. The drug survival of reference IFX and CPT-13 was determined at weeks 54 and 104. RESULTS: one hundred and six patients were included during the study period. Forty-five (42.5 %) patients received CPT-13 and 61 (57.5 %) received reference IFX. A total of 347 serum samples were analyzed and no significant differences were observed between reference IFX and CPT-13. The percentage of patients who achieved serum concentrations within the target therapeutic range was similar in both groups (74.1 % for reference IFX and 72.5 % for CPT-13, p = 0.741). At week 54, withdrawal rates for reference IFX and CPT-13 were 11.5 % and 20.0 %, respectively (p = 0.226), whereas at week 104 they were 26.2 % and 28.9 %, respectively (p = 0.761). CONCLUSION: the pharmacokinetic characteristics and incidence of immunogenicity of CPT-13 in a real clinical setting are comparable to those of the infliximab originator. The two products also have similar long-term drug survival and the same safety profile.

Association between ustekinumab trough concentrations and biochemical outcomes in patients with Crohn's disease. A real life study.

INTRODUCTION: numerous studies have shown a positive correlation between serum biologic drug concentrations and favorable therapeutic outcomes during the induction and maintenance period in patients with Crohn's disease (CD). To our knowledge, only a few and contradictory studies have determined the association between ustekinumab (UST) trough concentrations and biological outcomes. This study aimed to investigate the relationship between ustekinumab trough concentrations and biological outcomes in a real-world setting. METHODS: a cross-sectional cohort study was performed. All adult patients with CD who received maintenance therapy (≥ 24 weeks) with ustekinumab were included in the study. Clinical response was determined using the Harvey-Bradshaw Index. Biochemical remission was defined as a fecal calprotectin level < 150 µg/g in feces and a biochemical response as > 50 % reduction of fecal calprotectin. RESULTS: a total of 58 CD patients were included in the study and the median UST trough concentration was 1.78 µg/ml (IQR: 2.56). Differences in ustekinumab trough concentrations were observed for clinical (2.25 µg/ml vs 0.65 µg/ml; p = 0.006) and biochemical remission (2.33 µg/ml vs 1.03 µg/ml; p = 0.047). According to ROC analysis, a cut-off of 1.4 µg/ml (AUC: 077) and 2.0 µg/ml (AUC: 0.65) were identified for predicting clinical and biochemical remission, respectively. Likewise, ustekinumab trough levels were also higher in "composite clinical/biochemical remission" (2.38 µg/ml vs 1.08 µg/ml; p = 0.042). The trough level that was best associated with composite clinical/biochemical remission was 2.2 µg/ml (AUC: 0.69). CONCLUSION: this real-life study shows the association between ustekinumab trough concentration and clinical and biochemical remission and we suggest an optimal cut-off point higher than 2.2 µg/ml. Further studies are needed to confirm the findings and to identify the optimal cut-off in different disease outcomes and disease phenotypes.

Usefulness of population pharmacokinetics to optimize the dosage regimen of infliximab in inflammatory bowel disease patients

INTRODUCTION: infliximab is used in inflammatory bowel disease, which has a great inter-individual pharmacokinetic variability. Thus, it is necessary to individualize the therapy in many cases. The main objective of our study was to compare two methods of a dose adjustment strategy using therapeutic drug monitoring: a) based on an algorithm and b) based on Bayesian prediction, to achieve an optimal infliximab trough level in patients with inflammatory bowel diseases. The secondary objective was to evaluate the predictive performance of a population pharmacokinetic model of infliximab in patients with inflammatory bowel diseases and therefore, its clinical utility. Furthermore, the factors associated with a suboptimal adjustment of the model were analyzed. METHODS: a retrospective observational cohort analysis was performed of patients with inflammatory bowel disease and available serum levels of infliximab. The relationship between trough concentration and dosing strategy was compared in both groups. The external validation of a previously published population pharmacokinetic model was performed using the NONMEM software. The mean prediction error and mean absolute prediction error were calculated to evaluate the predictive performance of the model. RESULTS: a total of 94 infliximab serum samples were obtained from 47 patients. After the adjustment, a total of 30 patients (63.8 %) achieved optimal infliximab trough levels. A dosing strategy based on Bayesian was associated with optimal infliximab trough levels that were higher than the strategy based on an algorithm (OR: 8.94 [95 % CI: 2.24 - 35.6], p = 0.001). For the individual predictions, the mean prediction error was 0.118 Mug/ml (95 % CI: -0.149-0.384) and the mean absolute prediction error was 0.935 Mug/ml (95 % CI: 0.569-1.075). CONCLUSIONS: the application of a population pharmacokinetic model based on Bayesian prediction is an important advance in the optimization of infliximab dosage in the treatment of inflammatory bowel disease

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Usefulness of population pharmacokinetics to optimize the dosage regimen of infliximab in inflammatory bowel disease patients.

INTRODUCTION: infliximab is used in inflammatory bowel disease, which has a great inter-individual pharmacokinetic variability. Thus, it is necessary to individualize the therapy in many cases. The main objective of our study was to compare two methods of a dose adjustment strategy using therapeutic drug monitoring: a) based on an algorithm and b) based on Bayesian prediction, to achieve an optimal infliximab trough level in patients with inflammatory bowel diseases. The secondary objective was to evaluate the predictive performance of a population pharmacokinetic model of infliximab in patients with inflammatory bowel diseases and therefore, its clinical utility. Furthermore, the factors associated with a suboptimal adjustment of the model were analyzed. METHODS: a retrospective observational cohort analysis was performed of patients with inflammatory bowel disease and available serum levels of infliximab. The relationship between trough concentration and dosing strategy was compared in both groups. The external validation of a previously published population pharmacokinetic model was performed using the NONMEM software. The mean prediction error and mean absolute prediction error were calculated to evaluate the predictive performance of the model. RESULTS: a total of 94 infliximab serum samples were obtained from 47 patients. After the adjustment, a total of 30 patients (63.8 %) achieved optimal infliximab trough levels. A dosing strategy based on Bayesian was associated with optimal infliximab trough levels that were higher than the strategy based on an algorithm (OR: 8.94 [95 % CI: 2.24 - 35.6], p = 0.001). For the individual predictions, the mean prediction error was 0.118 µg/ml (95 % CI: -0.149-0.384) and the mean absolute prediction error was 0.935 µg/ml (95 % CI: 0.569-1.075). CONCLUSIONS: the application of a population pharmacokinetic model based on Bayesian prediction is an important advance in the optimization of infliximab dosage in the treatment of inflammatory bowel disease.

Usefulness of therapeutic drug monitoring of infliximab during the induction period in patients with inflammatory bowel disease

INTRODUCTION: previous studies have shown that higher infliximab trough levels are associated with favorable shortterm and long-term therapeutic outcomes in inflammatory bowel disease. There is a need to determine which patients could benefit from proactive therapeutic drug monitoring in the induction phase. The aim of this study was to evaluate the pharmacokinetic variability of infliximab, determine the factors associated with achieving target infliximab trough levels in the induction phase and analyze the clinical and biochemical response at week 26 of treatment. PATIENTS AND METHODS: a retrospective observational study was performed of patients with inflammatory bowel disease and data available on serum levels of infliximab during the induction period. The percentage of patients that achieved target infliximab trough levels at week 6 was determined. Clinical remission and response and biochemical remission were evaluated at week 26. RESULTS: thirty patients were included and only 13 (43.3 %) had infliximab trough levels > 15 μg/mL at week 6. A clinical response was observed during the maintenance period in 71.4 % of patients, their infliximab levels were significantly higher than in non-responders (6.3 μg/mL [IQR: 6.7] vs 1.0 μg/mL [IQR: 5.0], respectively; p = 0.016). Likewise, 53.6 % of patients achieved biochemical remission (responders 6.2 μg/mL [IQR: 5.2] vs non-responders 3.2 μg/mL [IQR: 5.0]; p = 0.031). CONCLUSION: less than half of patients had target infliximab levels during the induction period. Therapeutic drug monitoring during this period is related to the achievement of therapeutic levels of infliximab and may lead to a better clinical response in these patients

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Usefulness of therapeutic drug monitoring of infliximab during the induction period in patients with inflammatory bowel disease.

INTRODUCTION: previous studies have shown that higher infliximab trough levels are associated with favorable short-term and long-term therapeutic outcomes in inflammatory bowel disease. There is a need to determine which patients could benefit from proactive therapeutic drug monitoring in the induction phase. The aim of this study was to evaluate the pharmacokinetic variability of infliximab, determine the factors associated with achieving target infliximab trough levels in the induction phase and analyze the clinical and biochemical response at week 26 of treatment. PATIENTS AND METHODS: a retrospective observational study was performed of patients with inflammatory bowel disease and data available on serum levels of infliximab during the induction period. The percentage of patients that achieved target infliximab trough levels at week 6 was determined. Clinical remission and response and biochemical remission were evaluated at week 26. RESULTS: thirty patients were included and only 13 (43.3 %) had infliximab trough levels > 15 µg/mL at week 6. A clinical response was observed during the maintenance period in 71.4 % of patients, their infliximab levels were significantly higher than in non-responders (6.3 µg/mL [IQR: 6.7] vs 1.0 µg/mL [IQR: 5.0], respectively; p = 0.016). Likewise, 53.6 % of patients achieved biochemical remission (responders 6.2 µg/mL [IQR: 5.2] vs non-responders 3.2 µg/mL [IQR: 5.0]; p = 0.031). CONCLUSION: less than half of patients had target infliximab levels during the induction period. Therapeutic drug monitoring during this period is related to the achievement of therapeutic levels of infliximab and may lead to a better clinical response in these patients.

Comparison of drug survival between infliximab and adalimumab in inflammatory bowel disease.

Background Conventional therapy of inflammatory bowel disease with traditional immunosuppressant medication is increasingly being replaced by biological agents. However, the response to these biological agents may be lost over time, with discontinuation being a marker of loss of effectiveness. There are few published reports on the treatment drug survival of infliximab and adalimumab in patients with inflammatory bowel disease. Objective This study compared the drug survival of infliximab versus adalimumab as first- and second-line treatments, identified factors associated with drug survival, and described reasons for treatment withdrawal. Setting A pharmacy department of a university hospital in Spain. Method A retrospective single-centre cohort study of all patients with inflammatory bowel disease treated with biological agents between 2008 and 2017 at a regional referral hospital. The primary outcome was drug survival and associated factors during a follow-up of 52 months. Main outcome measure Drug survival of infliximab versus adalimumab. Results One hundred thirty-four patients with inflammatory bowel disease (73.9% Crohn's disease and 26.1% ulcerative colitis) were treated with biological therapy. The overall mean drug survival of first-line treatment with an anti-tumour necrosis factor agent was 18.6 months (SD 14.9), with mean values of 20.2 months (SD 16.6) for adalimumab and 17.1 months (SD 13.1) for infliximab. As a second-line treatment, the drug survival of anti-tumour necrosis factor agents was 17.9 months (SD 15.6), with mean values of 22.9 months (SD 17.1) for adalimumab and 12.5 months (SD 11.7) for infliximab. The difference in time to discontinuation at 52 months of follow-up between the infliximab and adalimumab subgroups, as either first- or second-line treatment, was not statistically significant (p = 0.547 and p = 0.676, respectively). Therapeutic drug monitoring was the only factor associated with greater drug survival in first-line treatment (HR 0.27; 95% confidence interval, CI 0.15-0.50) and second-line treatment (HR 0.26; 95% CI 0.10-0.65). Secondary failure to treatment was the most frequent reason for withdrawal. Conclusion Infliximab and adalimumab showed similar drug survival as first- and second-line anti-tumour necrosis factor treatments. Therapeutic drug monitoring was associated with higher drug survival for both first- and second-line anti-tumour necrosis factor treatments.

Potential and clinical relevant drug-drug interactions among elderly from nursing homes: a multicentre study in Murcia, Spain.

This study purposes to determine the prevalence of potential and clinical relevant Drug-Drug-Interactions (pDDIs) in institutionalized older adults and to identify the pertinent factors associated. We conduct an observational, multicenter and cross-sectional study during the last quarter of 2010. We selected a sample of 275 subjects (aged ≥ 65 years) from 10 nursing homes of Murcia (Spain) by a two-stage complex sampling. pDDIs were identified using the College of Pharmacists Database. We only considered pDDIs of clinical relevance, and thereafter the relevant factors were identified through uni-level and multi-level regression analyses. A total of 210 pDDIs were identified, 120 of which were considered clinically relevant (57.1%), affecting a total of 70 elderly (25.8%). Eight pharmacological groups made up 70.2% of the clinically relevant pDDIs. More clinically relevant DDIs were found in people suffering several pathologies (OR = 2.3; 95%CI = 1.4-4.5), and also in people who take ten or more drugs daily (OR = 9.6; 95%CI = 4.8-19.1), and people who take anti-inflammatory drugs (OR = 3.9; 95%CI = 1.4-10.4). This study reveals that clinically relevant pDDIs are very common in institutionalized elderly people, and that caregivers should aim at improving their practice in order to reduce the prevalence of this phenomenon.

Potential and clinical relevant drug-drug interactions among elderly from nursing homes: a multicentre study in Murcia, Spain / Interações medicamentosas potenciais e clinicamente relevantes em instituições de longa permanência para idosos: um estudo multicêntrico em Murcia, Espanha

Abstract This study purposes to determine the prevalence of potential and clinical relevant Drug-Drug-Interactions (pDDIs) in institutionalized older adults and to identify the pertinent factors associated. We conduct an observational, multicenter and cross-sectional study during the last quarter of 2010. We selected a sample of 275 subjects (aged ≥ 65 years) from 10 nursing homes of Murcia (Spain) by a two-stage complex sampling. pDDIs were identified using the College of Pharmacists Database. We only considered pDDIs of clinical relevance, and thereafter the relevant factors were identified through uni-level and multi-level regression analyses. A total of 210 pDDIs were identified, 120 of which were considered clinically relevant (57.1%), affecting a total of 70 elderly (25.8%). Eight pharmacological groups made up 70.2% of the clinically relevant pDDIs. More clinically relevant DDIs were found in people suffering several pathologies (OR = 2.3; 95%CI = 1.4-4.5), and also in people who take ten or more drugs daily (OR = 9.6; 95%CI = 4.8-19.1), and people who take anti-inflammatory drugs (OR = 3.9; 95%CI = 1.4-10.4). This study reveals that clinically relevant pDDIs are very common in institutionalized elderly people, and that caregivers should aim at improving their practice in order to reduce the prevalence of this phenomenon.

Resumo Este estudo pretende identificar a prevalência de interações medicamentosas potenciais (IMP) em idosos institucionalizados e seus fatores associados. Realizamos um estudo observacional, multicêntrico e transversal, durante o último trimestre de 2010. Selecionamos uma amostra de 275 sujeitos (≥ 65 anos) de 10 instituições para idosos de Murcia (Espanha) mediante amostragem aleatória complexa em duas etapas. As IMP foram identificadas usando a base de dados do College of Pharmacists. Estimamos a prevalência de IMP de relevância clínica e analisamos os fatores associados com análise de regressão uni e multinível. Identificamos 210 IMP, das quais 120 foram consideradas clinicamente relevantes (57,1%) e afetaram 70 idosos (25,8%). Oito grupos farmacológicos constituíram 70,2% das IMP clinicamente relevantes. A prevalência de IMP esteve associada à multimorbidade (OR = 2,3; IC 95% = 1,4-4,5) e tomar dez ou mais medicamentos diariamente (OR = 9,6; IC95% = 4,8-19,1) e uso de medicamentos anti-inflamatórios (OR = 3,9; IC 95% = 1,4-10,4). Este estudo revela que as IMP clinicamente relevantes são muito comuns em idosos institucionalizados e que os serviços devem melhorar seus processos para reduzir a prevalência deste fenômeno.

Incorporación de los anticoagulantes de acción directa al arsenal terapéutico disponible: ¿progresa adecuadamente? / Incorporation of direct-acting oral anticoagulants to available therapeutic arsenal: Progress adequately?

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Effect of drug interactions involving antiretroviral drugs on viral load in HIV population.

BACKGROUND: Most studies focus on potential drug interactions, without considering the effect of these on the response to antiretroviral (ARV) therapy. We assess the effect of potential drug-drug interactions (pDDIs) that could have lowered the ARV concentration (pDDI-lowerARV) on HIV viral load. METHODS: Retrospective observational cohort study was conducted on all HIV-infected outpatients attending the Pharmacy Service of a regional reference hospital in Murcia (south-eastern Spain). The complete treatment was subsequently screened for pDDIs using the database 'InteraccionesHIV.com'. The study focused on interactions involving at least one ARV drug and, especially, any pDDI-lowerARV. RESULTS: Two hundred and twenty-nine patients were included in the study. A total of 168 pDDIs were identified, of which 62 (36.9%) had the potential to lower ARV concentrations. In 77% of cases, the drug involved in the reduction of plasma concentrations was a protease inhibitor (PI), and in the rest of the drug interactions the ARV drug affected was a non-nucleoside reverse-transcriptase inhibitor. Baseline viral suppression was noted in 57.1% of patients with pDDI-lowerARV compared with 61.5% of patients without pDDI-lowerARV (p=0.605), and in 85.7% versus 79.7%, respectively, after a 24-week follow-up period (p=0.516). CONCLUSIONS: This study shows that prevalence of pDDI-lowerARV was high; however, no association was found between the presence of these interactions and virological failure. These results confirm the need for further studies to understand the consequences of interactions in real-life clinical practice, since most pharmacokinetic studies tend to evaluate the ability of interaction between two drugs under controlled conditions.

[MALNUTRITION IN THE ELDERLY PATIENT TO HOSPITAL ADMISSION, AN OLD PROBLEM UNSOLVED]. / DESNUTRICIÓN EN EL PACIENTE ANCIANO AL INGRESO HOSPITALARIO, UN VIEJO PROBLEMA SIN SOLUCIONAR.

OBJETIVE: to determine the prevalence of malnutrition in patients aged 65 years or more at admission and factors associated with its presence. Analyze excess hospital stay (EHS), economic impact and premature readmission rate associated with hospital malnutrition in elderly patient. MATERIAL AND METHOD: retrospective study conducted at the University Hospital Reina Sofía. All patients aged 65 years or older admitted to internal medicine in 2011. The sample size was calculated taking into account the income of the previous year, and considering a prevalence of malnutrition of 50% with a 95% and included error of 5%. To define the degree of malnutrition nutritional control tool (CONUT), which establishes a score based on albumin, total cholesterol and lymphocyte determination was used. To determine the factors associated with the presence of moderate to severe malnutrition analysis of multivariate logistic regression was performed. For each patient the EHS, premature readmissions and the associated cost to EHS was calculated. A threshold of statistical significance of 0.05 was used for all analyzes and were performed with SPSS v15.0. RESULTS: 310 patients, of whom 54.2% were women were included, the mean age was 80.1 years (SD: 6.8), ranging between 65 and 95 years. Regarding diagnosis at admission 27.4% were respiratory diseases, 22.6% of the circulatory and digestive 11.6%. The median Charlson index was 2.0, found that 36.8% of patients had high comorbidity. The most prevalent chronic diseases were diabetes mellitus (44.2%), chronic kidney disease (25.2%) and dementia (10.6). Regarding the CONUT, 75.8% of patients met the criteria of malnutrition: 42.6% mild, 28.7% moderate and severe 4.5%, of which only 46.6% had some nutritional support during admission. Factors associated with the presence of moderate to severe malnutrition were female gender (OR: 1.7; 95%: 1.1 - 2.8), age over 80 years (OR: 2.0, IC 95%: 1.2 - 3.5), and dementia (OR: 2.4; IC 95%:1.2 - 5.2). No association with comorbidity or with other chronic diseases was found. Regarding the EHS (days) differences between patients with moderate to severe malnutrition (4.7; IC 95%: 2.3 - 7.1) and normally nourished (-0.1; IC 95%: -1.4 - 1.2) (p = 0.001) were found, but were not for cases of mild malnutrition (1.6, 95%: 0.5-2.8) (p = 0.07).Regarding the rate of premature readmission in malnourished patients was 28/235 (11.9%). The cost associated with EHS / 100 patients was € 195 479.4 for moderate malnutrition, mild malnutrition € 73 484.8, and normally nourished patients represented a saving of € 12 353. CONCLUSIONS: hospital malnutrition in elderly patients remains an unsolved problem, given the high prevalence found, associated to an excess of hospital stay and increased hospital costs, especially in patients with moderate to severe malnutrition. The CONUT is a nutritional screening tool very useful for the speed and validity of their results, and allows detecting patients at risk or nutritional alert without lead to increased costs.

Objetivo: determinar la prevalencia de desnutrición en pacientes con edad igual o superior a 65 años al ingreso hospitalario y los factores asociados a su presencia. Analizar el exceso de estancia hospitalaria (EEH), el impacto económico y la tasa de reingresos prematuros asociados a la desnutrición hospitalaria en pacientes de edad avanzada. Material y métodos: estudio retrospectivo realizado en el Hospital Universitario Reina Sofía. Se incluyeron todos los pacientes con edad igual o mayor a 65 años que ingresaron en Medicina Interna durante 2011. Se calculó el tamaño muestral teniendo en cuenta los ingresos del año anterior, y considerando una prevalencia de desnutrición del 50% con un IC 95% y un error del 5%. Para definir el grado de desnutrición se empleó la herramienta Control Nutricional (CONUT), que establece una puntuación basada en la determinación de albúmina, colesterol total y linfocitos. Para determinar los factores asociados a la presencia de desnutrición moderada-grave se realizó un análisis de regresión logística multivariante. Para cada paciente se calculó el EEH, los reingresos prematuros y el coste asociado al EEH. Para todos los análisis se utilizó un dintel de significación estadística de 0,05 y se realizaron con el paquete estadístico SPSS v15.0. Resultados: se incluyeron 310 pacientes, de los cuales el 54,2% fueron mujeres, la edad media fue de 80,1 años (DE: 6,8), con un rango entre 65 y 95 años. En cuanto al diagnóstico al ingreso, el 27,4% correspondían a enfermedades del aparato respiratorio, 22,6% del circulatorio y 11,6% del digestivo. La mediana del Índice de Charlson fue de 2,0, encontrando que el 36,8% de los pacientes presentaban una comorbilidad alta. Las patologías crónicas más prevalentes fueron la diabetes mellitus (44,2%), la enfermedad renal crónica (25,2%) y la demencia (10,6). En relación con el CONUT, el 75,8% de los pacientes presentaban criterios de desnutrición: el 42,6% leve, el 28,7% moderada y el 4,5% grave, de estos, solo un 46,6% tuvo algún tipo de soporte nutricional durante el ingreso. Los factores asociados a la presencia de desnutrición moderada-grave fueron el sexo femenino (OR: 1,7; IC 95%: 1,1 ­ 2,8), edad mayor de 80 años (OR: 2,0, IC 95%: 1,2 ­ 3,5), y la demencia (OR: 2,4; IC 95%:1,2 ­ 5,2). No se encontró asociación con la comorbilidad ni con otras patologías crónicas. Respecto al EEH (días), se encontraron diferencias entre los pacientes con desnutrición moderada-grave (4,7; IC 95%: 2,3 ­ 7,1) y normonutridos (-0,1; IC 95%: -1,4 ­ 1,2) (p = 0,001), no siendo así para los casos de desnutrición leve (1,6; IC 95%: 0,5-2,8) (p = 0,07). En relación a la tasa de reingresos prematuros en pacientes desnutridos fue de 28/235 (11,9%). El coste asociado al EEH/100 pacientes fue de 195.479,4 € para la desnutrición grave-moderada, 73.484,8 € desnutrición leve, mientras que en los pacientes normonutridos supuso un ahorro de 12.353 €. Conclusiones: la desnutrición hospitalaria en el paciente anciano sigue siendo un problema sin resolver, dada la elevada prevalencia encontrada, asociándose a un exceso de estancia hospitalaria y a un aumento del gasto hospitalario, especialmente en pacientes con desnutrición moderada- severa. El CONUT es una herramienta de cribado nutricional de gran utilidad por la rapidez y validez de sus resultados, y permite detectar pacientes con riesgo o alerta nutricional, sin suponer un incremento de costes.

Desnutrición en el paciente anciano al ingreso hospitalario, un viejo problema sin solucionar / Malnutrition in the elderly patient to hospital admission, an old problem unsolved

Objetivo: determinar la prevalencia de desnutrición en pacientes con edad igual o superior a 65 años al ingreso hospitalario y los factores asociados a su presencia. Analizar el exceso de estancia hospitalaria (EEH), el impacto económico y la tasa de reingresos prematuros asociados a la desnutrición hospitalaria en pacientes de edad avanzada. Material y métodos: estudio retrospectivo realizado en el Hospital Universitario Reina Sofía. Se incluyeron todos los pacientes con edad igual o mayor a 65 años que ingresaron en Medicina Interna durante 2011. Se calculó el tamaño muestral teniendo en cuenta los ingresos del año anterior, y considerando una prevalencia de desnutrición del 50% con un IC 95% y un error del 5%. Para definir el grado de desnutrición se empleó la herramienta Control Nutricional (CONUT), que establece una puntuación basada en la determinación de albúmina, colesterol total y linfocitos. Para determinar los factores asociados a la presencia de desnutrición moderada-grave se realizó un análisis de regresión logística multivariante. Para cada paciente se calculó el EEH, los reingresos prematuros y el coste asociado al EEH. Para todos los análisis se utilizó un dintel de significación estadística de 0,05 y se realizaron con el paquete estadístico SPSS v15.0. Resultados: se incluyeron 310 pacientes, de los cuales el 54,2% fueron mujeres, la edad media fue de 80,1 años (DE: 6,8), con un rango entre 65 y 95 años. En cuanto al diagnóstico al ingreso, el 27,4% correspondían a enfermedades del aparato respiratorio, 22,6% del circulatorio y 11,6% del digestivo. La mediana del Índice de Charlson fue de 2,0, encontrando que el 36,8% de los pacientes presentaban una comorbilidad alta. Las patologías crónicas más prevalentes fueron la diabetes mellitus (44,2%), la enfermedad renal crónica (25,2%) y la demencia (10,6). En relación con el CONUT, el 75,8% de los pacientes presentaban criterios de desnutrición: el 42,6% leve, el 28,7% moderada y el 4,5% grave, de estos, solo un 46,6% tuvo algún tipo de soporte nutricional durante el ingreso. Los factores asociados a la presencia de desnutrición moderada-grave fueron el sexo femenino (OR: 1,7; IC 95%: 1,1 - 2,8), edad mayor de 80 años (OR: 2,0, IC 95%: 1,2 - 3,5), y la demencia (OR: 2,4; IC 95%:1,2 - 5,2). No se encontró asociación con la comorbilidad ni con otras patologías crónicas. Respecto al EEH (días), se encontraron diferencias entre los pacientes con desnutrición moderada-grave (4,7; IC 95%: 2,3 - 7,1) y normonutridos (-0,1; IC 95%: -1,4 - 1,2) (p = 0,001), no siendo así para los casos de desnutrición leve (1,6; IC 95%: 0,5-2,8) (p = 0,07). En relación a la tasa de reingresos prematuros en pacientes desnutridos fue de 28/235 (11,9%). El coste asociado al EEH/100 pacientes fue de 195.479,4 Euros para la desnutrición grave-moderada, 73.484,8 Euros desnutrición leve, mientras que en los pacientes normonutridos supuso un ahorro de 12.353 Euros. Conclusiones: la desnutrición hospitalaria en el paciente anciano sigue siendo un problema sin resolver, dada la elevada prevalencia encontrada, asociándose a un exceso de estancia hospitalaria y a un aumento del gasto hospitalario, especialmente en pacientes con desnutrición moderada-severa. El CONUT es una herramienta de cribado nutricional de gran utilidad por la rapidez y validez de sus resultados, y permite detectar pacientes con riesgo o alerta nutricional, sin suponer un incremento de costes (AU)

Objetive: to determine the prevalence of malnutrition in patients aged 65 years or more at admission and factors associated with its presence. Analyze excess hospital stay (EHS), economic impact and premature readmission rate associated with hospital malnutrition in elderly patient. Material and method: retrospective study conducted at the University Hospital Reina Sofía. All patients aged 65 years or older admitted to internal medicine in 2011. The sample size was calculated taking into account the income of the previous year, and considering a prevalence of malnutrition of 50% with a 95% and included error of 5%. To define the degree of malnutrition nutritional control tool (CONUT), which establishes a score based on albumin, total cholesterol and lymphocyte determination was used. To determine the factors associated with the presence of moderate to severe malnutrition analysis of multivariate logistic regression was performed. For each patient the EHS, premature readmissions and the associated cost to EHS was calculated. A threshold of statistical significance of 0.05 was used for all analyzes and were performed with SPSS v15.0. Results: 310 patients, of whom 54.2% were women were included, the mean age was 80.1 years (SD: 6.8), ranging between 65 and 95 years. Regarding diagnosis at admission 27.4% were respiratory diseases, 22.6% of the circulatory and digestive 11.6%. The median Charlson index was 2.0, found that 36.8% of patients had high comorbidity. The most prevalent chronic diseases were diabetes mellitus (44.2%), chronic kidney disease (25.2%) and dementia (10.6). Regarding the CONUT, 75.8% of patients met the criteria of malnutrition: 42.6% mild, 28.7% moderate and severe 4.5%, of which only 46.6% had some nutritional support during admission. Factors associated with the presence of moderate to severe malnutrition were female gender (OR: 1.7; 95%: 1.1 - 2.8), age over 80 years (OR: 2.0, IC 95%: 1.2 - 3.5), and dementia (OR: 2.4; IC 95%:1.2 - 5.2). No association with comorbidity or with other chronic diseases was found. Regarding the EHS (days) differences between patients with moderate to severe malnutrition (4.7; IC 95%: 2.3 - 7.1) and normally nourished (-0.1; IC 95%: -1.4 - 1.2) (p = 0.001) were found, but were not for cases of mild malnutrition (1.6, 95%: 0.5-2.8) (p = 0.07).Regarding the rate of premature readmission in malnourished patients was 28/235 (11.9%). The cost associated with EHS / 100 patients was Euros 195 479.4 for moderate malnutrition, mild malnutrition Euros 73 484.8, and normally nourished patients represented a saving of Euros 12 353. Conclusions: hospital malnutrition in elderly patients remains an unsolved problem, given the high prevalence found, associated to an excess of hospital stay and increased hospital costs, especially in patients with moderate to severe malnutrition. The CONUT is a nutritional screening tool very useful for the speed and validity of their results, and allows detecting patients at risk or nutritional alert without lead to increased costs (AU)

Effectiveness of pharmacist intervention in patients with chronic kidney disease.

BACKGROUND: Collaboration between pharmacists and physicians in the care of patients with chronic kidney disease (CKD) may improve the quality of drug dosage regimens that require adjustment according to the renal function. OBJECTIVE: To demonstrate that the intervention of a pharmacist in a monitoring program for patients with CKD improves the outcome of renal function in these patients. Setting A 330-bed regional referral hospital in the city of Murcia (Spain). METHOD: All patients with CKD and taking nephrotoxic medication admitted to the internal medicine service were included in the study. Depending on the department of the hospital to which the patients were admitted, they were assigned to an intervention or control group. In the control group, the renal function at the time of admission and discharge was measured. In the intervention group, in addition to measuring kidney function at the time of admission and at discharge, the patients were followed daily and recommendation for dose adjustment were made when nephrotoxic drugs were not properly dosed. MAIN OUTCOME MEASURE: Glomerular filtration rate on admission and at discharge. RESULTS: A total of 249 patients were included in the study, 124 in the control group and 125 in the intervention group. Significant differences were noted when comparing creatinine clearance (CrCl) between discharge and admission in both the control and intervention groups (5.1 ± 0.9 vs. 6.4 ± 1.0 p < 0.01). In a comparison of the observed improvement in the two groups, we found significant differences in adjusted relative CrCl according to sex, age and stage (19.9 [1.2-38.5] p < 0.05). When the disease was analyzed by stage, we observed significant differences that favored the intervention group in regards CrCl (3.1 ± 2.1 vs. 7.9 ± 3.8 p < 0.05) and relative CrCl (16.1 ± 10.3 vs. 36.6 ± 16.7) in stages 4-5. The rate of acceptance of the pharmacists' recommendations was 74 %. CONCLUSION: The implementation of a monitoring program for CKD patients was effective in the group in which monitoring was conducted, especially in patients with more advanced stage of CKD.

[Follow-up of analytical parameters in Internal Medicine patients to detect adverse events]. / Seguimiento de parámetros analíticos en pacientes de medicina.

OBJECTIVE: To analyze the prevalence of prescription drugs, previously selected, that should be monitored by their analytical test, and the rate of alteration in these tests, with the aim of establishing priorities to facilitate monitoring. METHOD: Prospective observational study in the Internal Medicine department of a referral hospital of 350 beds. In a first phase, we selected some drugs which analytical monitoring is recommended for the medical literature, and after that, we reviewed the pharmacological treatment of all patients admitted with any of these drugs. The study was conducted in the last two month of 2011. RESULTS: We included 271 patients, 128 (47%) were women. The mean age was 74.5 ± 14.4 years and the average stay of 7 ± 5.8 days. These patients accounted for 83% of all patients admitted to Internal Medicine during the study period. There were 828 drugs that must be monitored; each patient had an average of 3.1 ± 2.3. We reviewed 1837 analytical test, of which 401 (22%) were altered and 154 patients (57%) were affected for it. The pairs drug-analytical test altered most frequently found were creatinine increased and nephrotoxic drugs, hypokalemia in patients taking high efficiency diuretics and thrombocytopenia in patients treated with low molecular weight heparins. CONCLUSIONS: Our study highlights the importance of monitoring laboratory test associated with some drugs from the pharmacy department, as it demonstrates a high incidence of warning results. Our proposal for selection of drugs makes monitoring easier, and reaches large numbers of patients.