Adherencia al tratamiento en pacientes mayores de 65 años que sufren reingresos precoces / Treatment adherence in patients more than 65 years who experience early readmissions

Objetivo: Analizar la frecuencia del incumplimiento terapéutico en pacientes que sufren reingresos hospitalarios precoces e identificar los factores asociados al mismo. Método: Estudio observacional descriptivo de tres meses de duración (marzo-mayo de 2014). Se incluyeron todos los pacientes mayores de 65 años que reingresaron en los 3-30 días siguientes al alta hospitalaria. Fueron excluidos los reingresos programados y los reingresos en la Unidad de Cuidados Intensivos. Las variables recogidas fueron: edad, sexo, servicio médico, categoría diagnóstica mayor, polimedicación, número de días desde el alta, presencia de hipertensión y/o diabetes. Se evaluó el cumplimiento terapéutico y la dificultad en la administración de medicación mediante el test de Morisky-Green y el test de Haynes-Sackett, respectivamente. Se realizó un análisis descriptivo de las variables y se relacionaron estas con la adherencia terapéutica. Las variables con significación estadística se incluyeron en un modelo de regresión logística multivariante. Resultados: El 57% de los pacientes presentaron falta de adherencia al tratamiento farmacológico. El 23% presentaba dificultad en la administración de la medicación. Un 86% presentaba comorbilidades (hipertensión y/o diabetes) y el 79% tenía cuidador. El 86% de los pacientes estaban polimedicados (≥ 5 fármacos). Existe relación entre la falta de adherencia y la dificultad en la administración de los medicamentos (p = 0,021), la polimedicación (p = 0,002) y la presencia de diabetes mellitus (p=0,018). Conclusiones: La polimedicación, la presencia de diabetes mellitus y la existencia de dificultad en la administración de la medicación se evidencian como factores pronósticos de la falta de adherencia al tratamiento en pacientes mayores de 65 años

Objective: To analyse the rate of therapeutic nonadherence in patients who experience early readmissions, and identify the factors associated with nonadherence. Methods: An observational descriptive 3-month study (March-May 2014), which included all patients more than 65 years who were readmitted between 3 to 30 days following the last hospital discharge. Exclusion criteria: programmed re-admissions and readmissions to the Intensive Care Unit. Variables included in the study: age, sex, medical service, major diagnostic category, polypharmacy, number of days since the last hospital discharge, and hypertension and diabetes. Therapeutic adherence and difficulty in taking medication were assessed using the Morisky-Green test and the Haynes-Sackett test, respectively. A descriptive analysis of the variables was conducted, showing they were associated with therapeutic adherence. Statistically significant variables were included in a multivariate logistic regression model. Results: In total, 57% of the patients were nonadherent to pharmacological treatment; 23% had difficulty taking their medication; 86% had comorbidities (hypertension and diabetes); 79% had a caregiver; and 86% were polymedicated (≥ 5 medications). There was an association between lack of adherence and difficulty in taking medications (P = 0.021), polypharmacy (P = 0.002), and diabetes mellitus (P = 0.018). Conclusions: Polymedication, diabetes mellitus, and difficulty in taking medication were shown to be prognostic factors of lack of adherence to treatment in patients more than 65 years

Treatment adherence in patients older than 65 years who suffer early readmissions.

OBJECTIVE: Analyze the frequency of therapeutic noncompliance in patients who  suffer early readmissions, and identify the factors associated with it. METHOD: Observational, descriptive study of three months duration (March -  May 2014). All patients older than 65 years who readmitted in the 3-30 days  following the last hospital discharge were included. We excluded programmed  re-admissions and readmissions in the Intensive Care Unit. The variables  collected were: age, sex, medical service, major diagnostic category,  polypharmacy, number of days since the last hospital discharge, presence of  hypertension and/or diabetes. The therapeutic compliance and the difficulty in  the administration of medication were evaluated by means of the Morisky-Green  test and the Haynes-Sackett test respectively. A descriptive analysis of the  variables was carried out and they were related to the therapeutic adherence.  The variables with statistical significance were included in a multivariate logistic  regression model. RESULTS: Fifty seven percent of the patients presented lack of adherence to  pharmacological treatment. Twenty three percent had difficulty administering the medication. Eighty six percent had comorbidities  (hypertension and/or diabetes) and 79% had a caregiver. Eighty six percent of patients were polymedicated (≥ 5 drugs). There is a relationship between lack of adherence and difficulty in the administration of medications (p=0.021),  polypharmacy (p=0.002), and the presence of diabetes mellitus (p=0.018). CONCLUSIONS: Polymedication, the presence of diabetes mellitus and the existence of difficulty in the administration of medication are evidenced as prognostic factors of the lack of adherence to treatment in patients older than 65 years.

Objetivo: Analizar la frecuencia del incumplimiento terapéutico en pacientes que sufren reingresos hospitalarios precoces e identificar los factores asociados  al mismo.Método: Estudio observacional descriptivo de tres meses de duración (marzo­ mayo de 2014). Se incluyeron todos los pacientes mayores de 65 años que  reingresaron en los 3-30 días siguientes al alta hospitalaria. Fueron excluidos los reingresos programados y los reingresos en la Unidad de Cuidados Intensivos.  Las variables recogidas fueron: edad, sexo, servicio médico, categoría  diagnóstica mayor, polimedicación, número de días desde el alta, presencia de  hipertensión y/o diabetes. Se evaluó el cumplimiento terapéutico y la dificultad  en la administración de medicación mediante el test de Morisky-Green y el test  de Haynes-Sackett, respectivamente. Se realizó un análisis descriptivo de las  variables y se relacionaron estas con la adherencia terapéutica. Las variables  con significación estadística se incluyeron en un modelo de regresión logística multivariante.Resultados: El 57% de los pacientes presentaron falta de adherencia al tratamiento farmacológico. El 23% presentaba dificultad en la administración de la medicación. Un 86% presentaba comorbilidades  hipertensión y/o diabetes) y el 79% tenía cuidador. El 86% de los pacientes  estaban polimedicados (≥ 5 fármacos). Existe relación entre la falta de  adherencia y la dificultad en la administración de los medicamentos (p = 0,021), la polimedicación (p = 0,002) y la presencia de diabetes mellitus (p = 0,018).Conclusiones: La polimedicación, la presencia de diabetes mellitus y la  existencia de dificultad en la administración de la medicación se evidencian como factores pronósticos de la falta de adherencia al tratamiento en pacientes  mayores de 65 años.

Validation and clinical evaluation of a UHPLC method with fluorescence detector for plasma quantification of doxorubicin and doxorubicinol in haematological patients.

A rapid and simple UHPLC-fluorescence detection method for the quantification of doxorubicin and its main metabolite, doxorubicinol, in human plasma has been developed. The method was also validated for its application in therapeutic drug monitoring, a clinical approach used in the optimization of oncologic treatments. Following a single protein precipitation step, chromatographic separation was achieved using a C18 column (50mm×2.10mm, particle size 1.7µm) at 50°C with a mobile phase consisting of water (containing 0.4% triethylamine and 0.4% orthophosphoric acid)/acetonitrile (77:23, v/v). Flow rate was 0.50mL/min and fluorescence detection with an excitation wavelength of 470nm and an emission wavelength of 548nm was used. The method met the specifications of linearity, selectivity, sensitivity, accuracy, precision and stability of the FDA and EMA guidelines for the validation of bioanalytical methods. Linearity for the drug (8-3000ng/mL) and the metabolite (3-150ng/mL) was observed (R(2)>0.992) and the maximum intra-day and inter-day precision coefficients of variation were less than 14% for both. The lower limits of quantification were 8 and 3ng/mL for doxorubicin and doxorubicinol, respectively. The method was successfully applied to the quantify plasma concentrations of doxorubicin and doxorubicinol in 33 patients diagnosed with haematological malignancies in which broad ranges for drug (8.3-2766.0ng/mL) and metabolite (4.8-104.9ng/mL) levels were measured adequately.

Population pharmacokinetic/pharmacogenetic model of lopinavir/ritonavir in HIV-infected patients.

AIM: This study aims to develop a population pharmacokinetic/pharmacogenetic model for lopinavir/ritonavir (LPV/r) in European HIV-infected patients. MATERIALS & METHODS: A total of 693 LPV/r plasma concentrations were assessed and 15 single-nucleotide polymorphisms were genotyped. The population pharmacokinetic/pharmacogenetic model was created using a nonlinear mixed-effect approach (NONMEM® v.7.2.0., ICON Development Solutions, Dublin, Ireland). RESULTS: Covariates significantly related to LPV/r apparent clearance (CL/F) were ritonavir trough concentration (RTC), BMI, high-density lipoprotein cholesterol (HDL-C) and certain single-nucleotide polymorphisms in genes encoding for metabolizing enzymes, which are representable as follows: CL/F = (0.216BMI + 0.0125HDL-C) × 0.713RTC × 1.26rs28371764[C/T] × 0.528rs6945984[C/C] × 0.302 CYP3A4[1461insA/del] Conclusion: The LPV/r standard dose appears to be appropriate for the rs28371764[C/T] genotype. However, lower doses should be recommended for the rs6945984[C/C] and CYP3A4[1461insA/del] genotypes and even for those patients without any of these variants, as the standard dose seems to be higher than that which is required in order to achieve therapeutic levels.

Influencia de la atención avanzada en cuidados paliativos en la frecuentación de las urgencias hospitalarias / Influence of a special palliative care team on the frequency of emergency department visits

Objetivo: Describir el impacto de la atención a pacientes en situación terminal por parte de un equipo de soporte mixto de cuidados paliativos (hospitalario y domiciliario) en la frecuentación en un servicio de urgencias hospitalario. Método: Estudio descriptivo retrospectivo recogiendo los episodios de urgencias hospitalarias por todas las causas y por síntomas de la enfermedad avanzada, de todos los pacientes incluidos durante el año 2009 en el programa de cuidados paliativos (PCP), entre los 6 meses previos y los 6 meses posteriores a su inclusión (N=146). Los datos obtenidos son sometidos al análisis estadístico del programa R Project. Resultados: La edad media de los pacientes fue de 70,31 años (sd 12,46), siendo el 67,8%hombres y el 32,2% mujeres. Los 292 episodios de urgencias por todas las causas antes de la (..) (AU)

Aims: To describe the impact of care of the terminal patient by a mixed (hospital and home)palliative care support team on the frequency of visits to emergency department. Method: A retrospective descriptive study was performed on all patients with advanced disease included in the palliative care program (PCP) during the year 2009. Data on all hospital emergency department visits made in the 6 months before and the 6 months after their inclusion in the program (N=146) were collected and subjected to statistical analysis using the R Project program. Results: The mean age of the patients was 70.31 years (SD 12.46), of whom 67.8% were male and 32.2% female. A total of 292 hospital emergency episodes for all causes were incurred by (..) (AU)

Nuevas estrategias en la optimización posológica de lopinavir/ritonavir en pacientes infectados por el virus de la inmunodeficiencia humana / No disponible

El lopinavir/ritonavir (LPV/r) ha demostrado eflcacia virológica e inmunológica en el tratamiento antirretroviral (TAR) combinado, tanto en pacientes naïve como pretratados. Además presenta una alta barreragenética al desarrollo de resistencias y su perfll de tolerancia es aceptable, aunque son frecuentes alteraciones gastrointestinales y del perfll lipídico. Se revisan diferentes estrategias utilizadas en la optimización del TAR con este fármaco en la práctica clínica diaria, haciendo especial incidencia en la monitorización de concentraciones plasmáticas de LPV/r y la caracterización farmacogenética de las principales isoenzimas responsables de su metabolismoy transporte. En este sentido, la correlación del genotipo con el fenotipo establecida en la monitorización de niveles de LPV/r facilitaría la individualización posológica de los tratamientos con este fármaco. Así mismo, se revisa la estrategia de simpliflcación del tratamiento a monoterapia, lo que permitiría incrementar la seguridad y disminuir los costes (AU)

Lopinavir/ritonavir (LPV/r) has demonstrated virological and immunological efflcacy in the combined antiretroviral treatment (cART), in both naïve and experienced patients. Furthermore, LPV/r showed a high barrier to the development of resistance. Although generally well tolerated, adverse gastrointestinal side effects and metabolic disorders are frequent. The different tools used to optimise the cART with this drug combination in the daily clinical practice, emphasising the therapeutic drug monitoring (TDM) of LPV/r and the genetic analysis of the main enzymes responsible for the metabolism and transport, are reviewed. The relationship between phenotype and genotype, established through TDM, could be useful for the physician to improve the clinical management of the HIV infection, due to the possibility of individualising the dose with this drug. Monotherapyis also reviewed as a new strategy used in the simpliflcation of the treatment with this drug, which could increase safety and reduce costs (AU)

[New strategies in the optimisation of lopinavir/ritonavir doses in human immunodeficiency virus-infected patients]. / Nuevas estrategias en la optimización posológica de lopinavir/ritonavir en pacientes infectados por el virus de la inmunodeficiencia humana.

Lopinavir/ritonavir (LPV/r) has demonstrated virological and immunological efficacy in the combined antiretroviral treatment (cART), in both naïve and experienced patients. Furthermore, LPV/r showed a high barrier to the development of resistance. Although generally well tolerated, adverse gastrointestinal side effects and metabolic disorders are frequent. The different tools used to optimise the cART with this drug combination in the daily clinical practice, emphasising the therapeutic drug monitoring (TDM) of LPV/r and the genetic analysis of the main enzymes responsible for the metabolism and transport, are reviewed. The relationship between phenotype and genotype, established through TDM, could be useful for the physician to improve the clinical management of the HIV infection, due to the possibility of individualising the dose with this drug. Monotherapy is also reviewed as a new strategy used in the simplification of the treatment with this drug, which could increase safety and reduce costs.

Population pharmacokinetics of lopinavir/ritonavir (Kaletra) in HIV-infected patients.

BACKGROUND: A relationship between plasma concentrations and viral suppression in patients receiving lopinavir (LPV)/ritonavir (RTV) has been observed. Therefore, it is important to increase our knowledge about factors that determine interpatient variability in LPV pharmacokinetics (PK). METHODS: The study, designed to develop and validate population PK models for LPV and RTV, involved 263 ambulatory patients treated with 400/100 mg of LPV/RTV twice daily. A database of 1110 concentrations of LPV and RTV (647 from a single time-point and 463 from 73 full PK profiles) was available. Concentrations were determined at steady state using high-performance liquid chromatography with ultraviolet detection. PK analysis was performed with NONMEM software. Age, gender, height, total body weight, body mass index, RTV trough concentration (RTC), hepatitis C virus coinfection, total bilirubin, hospital of origin, formulation and concomitant administration of efavirenz (EFV), saquinavir (SQV), atazanavir (ATV), and tenofovir were analyzed as possible covariates influencing LPV/RTV kinetic behavior. RESULTS: Population models were developed with 954 drug plasma concentrations from 201 patients, and the validation was conducted in the remaining 62 patients (156 concentrations). A 1-compartment model with first-order absorption (including lag-time) and elimination best described the PK. Proportional error models for interindividual and residual variability were used. The final models for the drugs oral clearance (CL/F) were as follows: CL/F(LPV)(L/h)=0.216·BMI·0.81(RTC)·1.25(EFV)·0.84(ATV); CL/F(RTV)(L/h) = 8.00·1.34(SQV)·1.77(EFV)·1.35(ATV). The predictive performance of the final population PK models was tested using standardized mean prediction errors, showing values of 0.03 ± 0.74 and 0.05 ± 0.91 for LPV and RTV, and normalized prediction distribution error, confirming the suitability of both models. CONCLUSIONS: These validated models could be implemented in clinical PK software and applied to dose individualization using a Bayesian approach for both drugs.

The convergence of therapeutic drug monitoring and pharmacogenetic testing to optimize efavirenz therapy.

The aim of this study was to show the benefits of combining therapeutic drug monitoring (TDM) and pharmacogenetic analyses to optimize efavirenz (EFV) therapy. Patients were selected to minimize nongenetic differences between patients: 32 HIV adherent patients without drug interactions treated with an EFV nonindividualized dose over at least 1 year and included in a TDM program were genotyped according to minimum steady-state concentrations (C ss min). The EFV plasma concentrations (n = 158) were quantified by high-performance liquid chromatography-ultraviolet, and genetic polymorphisms were analyzed using the PHARMAchip. Central nervous system side effects were assessed systematically. Genetic polymorphisms were detected in 79.2% of patients with EFV Css min outside the therapeutic range (1-4 mg/L), showing the high diagnostic efficacy of combining TDM with pharmacogenetic testing. CYP2B6 (516 G>T) polymorphisms were associated with a significant decrease in EFV plasma clearance in 80% of the poor metabolizer patients (G/T, T/T). All homozygous patients had C ss min greater than 4 mg/L, 75% of them showing central nervous system side effects. For such patients, pharmacogenetic testing with TDM could be advantageous because the polymorphism is a determinant of these circumstances and TDM would allow reductions in dose to be specified without assuming an equal dose for any given genotype. In fact, poor metabolizer patients required less than a 600 mg standard starting dose, implying that if CYP2B6 screening were available, EFV therapy could be started at 400 mg and later TDM-individualized. The results of this study clarify the genotype versus phenotype debate for optimizing drug therapy. Pharmacogenetic testing together with TDM links genotype to phenotypic differences in drug concentrations and adverse events, providing additional support for dosage adjustment and a more efficient use of both approaches. As genotype screens become cheaper, and in combination with TDM, adjusting dosages in the light of genetic polymorphisms will become a reality.