Design of a score to identify hospitalized patients at risk of drug-related problems.

PURPOSE: The potential impact of drug-related problems (DRP) on morbidity and mortality is a serious concern in hospitalized patients. This study aimed to design a risk score to identify patients most at risk of a DRP. METHODS: Data from patients admitted to a tertiary university hospital between January and August 2009 were used to design the risk score (training set). DRP were detected through a pharmacy warning system integrated in the computerized medical history. The variables associated with developing a DRP were identified through a binary multivariate logistic regression analysis and were used to compute the DRP risk score, which was subsequently validated in patients admitted between September and December 2009 (validation set). RESULTS: Of the 8713 patients included in the training set, at least one DRP was detected in 2425 (27.8%). Prescription of a higher number of drugs, higher comorbidity, advanced age, certain groups of the Anatomical Therapeutic Chemical classification system, and some major diagnostic categories were associated with risk of DRP. These variables were used to compute the DRP risk score. The area under the receiver operator characteristic curve was 0.778 (95%CI [0.768, 0.789]). Of the 4058 admissions included in the validation set, at least one DRP was detected in 876 (21.6%). The area under the receiver operator characteristic curve was 0.776 (95%CI [0.759, 0.792]). CONCLUSIONS: Knowledge of the variables associated with DRP could aid their early detection in at-risk patients. The use of an application that can be continually updated in daily clinical practice helps to optimize resources.

Simplified therapy with zidovudine, lamivudine, and abacavir for very nonadherent, treatment-failing patients.

OBJECTIVE: To assess the effectiveness of a simplified therapy for very nonadherent patients who had previously failed with HAART. METHOD: We performed a prospective open-label study of antiretroviral-experienced patients. Dosing schedule comprised (co-formulated) zidovudine, lamivudine, and abacavir bid. Eligible patients had to have plasma HIV RNA >5000 copies/mL, previous therapy, and very poor adherence to the medication regimen. RESULTS: Eighty-five patients were included (mean viral load, 4.4 log/mL; mean CD4, 240 cells/mL; IDUs, 78%; methadone maintenance program, 42%; AIDS, 28%). Number of previous therapies: one, 53%; two, 28%; three or more, 19%. In the intent-to-treat analysis at 1 year, 38 patients (44.7%) achieved viral load below 500 copies/mL. Adherence greater than 90% of prescribed drugs was reported in 49% of patients, adverse events were reported in 17.6%, mortality in 6%, and lost to follow-up in 26%. The factors associated with virologic failure were nonadherence (odds ratio [OR], 4.4; 95% CI 1.5-12.3), baseline CD4 cell count <200 cells/mL (OR, 3.4; 95% CI 1.3-8.9; p =.01), and more than one previous treatment (OR, 2.7; 95% CI 1.1-6.9). CONCLUSION: Regarding previously very nonadherent patients, this simplified combination therapy containing three NRTIs obtained satisfactory results in ART-experienced patients. However, more aggressive interventions to enhance adherence are needed to improve results.

[Cardiovascular disease in HIV-infected patients on highly active antiretroviral therapy]. / Enfermedad cardiovascular sintomática en pacientes infectados por el virus de la inmunodeficiencia humana que reciben tratamiento antirretroviral de gran actividad.

BACKGROUND AND OBJECTIVE: Our goal was to assess the main characteristics of cardiovascular disease in HIV-infected patients on highly active antiretroviral therapy (HAART). PATIENTS AND METHOD: Retrospective analysis of the clinico-epidemiological characteristics of 16 HIV-infected patients treated with HAART who had suffered a cardiovascular event from a 1,459 patients' cohort. RESULTS: Clinical presentation of cardiovascular disease was an acute coronary syndrome in 12 cases, ischemic stroke in 2 and peripheral vascular disease in 2. Patients included in the study had a mean of 3.2 cardiovascular risk factors, smoking and low HDL levels being the more prevalent risk factors. Eight (50%, 95% CI, 25-75%) patients fulfilled the criteria of metabolic syndrome. The mean CD4 count was 548 x 10(6)/l. CONCLUSIONS: HIV-infected patients on HAART ha-ve a high cardiovascular risk. A strict management of modifiable risk factors must be warranted in these patients.

Enfermedad cardiovascular sintomática en pacientes infectados por el virus de la inmunodeficiencia humana que reciben tratamiento antirretroviral de gran actividad / Cardiovascular disease in HIV-infected patients on highly active antiretroviral therapy

FUNDAMENTO Y OBJETIVO: Conocer las características de la enfermedad cardiovascular (ECV) sintomática en pacientes con infección por el virus de la inmunodeficiencia humana (VIH) y tratamiento antirretroviral de gran actividad (TARGA). PACIENTES Y MÉTODO: Se analizaron retrospectivamente las características clínico-epidemiológicas de 16 pacientes con infección por el VIH que recibían TARGA con ECV de una cohorte de 1.459 pacientes. RESULTADOS: La forma de presentación clínica de la ECV fue un síndrome coronario agudo en 12 casos, un accidente cerebrovascular isquémico en dos y enfermedad arterial periférica en los dos restantes. Los pacientes incluidos presentaban una media de 3,2 factores de riesgo cardiovascular. El tabaquismo y el colesterol transportado por lipoproteínas de alta densidad bajo fueron los más prevalentes. El 50 por ciento (intervalo de confianza del 95 por ciento, 2575 por ciento) de los pacientes cumplían los criterios de síndrome metabólico. El recuento medio de linfocitos CD4 fue de 548 × 106/l. CONCLUSIONES: Los pacientes con infección por el VIH tratados con TARGA tienen un elevado riesgo cardiovascular. Ello implica el estricto control de los factores de riesgo modificables en estos pacientes (AU)

Impact of adherence and highly active antiretroviral therapy on survival in HIV-infected patients.

OBJECTIVES: To assess the effect of antiretroviral therapy (ART) adherence on survival in HIV-infected patients. DESIGN: Cohort study at a single hospital in Barcelona, Spain. METHODS: Data on HIV-infected patients older than 18 years of age who began ART during the period 1990 to 1999 were analyzed. Patients were considered nonadherent if the total dose of antiretroviral drug was less than 90% of that prescribed. Adherence was assessed through self-report and hospital pharmacy appointments. Cox regression with time-dependent variables was used. RESULTS: A total of 1219 patients were included. The first ART was with monotherapy in 23.7% of cases, with two drugs in 30.5%, and with triple therapy in 45.8%. In multivariate analysis, the variables that presented significant differences with respect to mortality were clinical stage at the beginning of treatment (AIDS: relative hazard (RH) = 2.97; 95% confidence interval [CI]: 2.14-4.13), CD4 cell count (<200 cells/microL: RH = 5.89; CI: 3.44-10.10), type of treatment (monotherapy: RH = 9.76; CI: 4.56-20.90; bi-therapy: RH = 9.12; CI: 4.23-19.64), and adherence (nonadherence: RH = 3.87; CI: 1.77-8.46). CONCLUSIONS: The modifiable factors most strongly associated with survival were type of treatment and adherence. It would be desirable to accompany therapy with intervention strategies intended to improve adherence.

Validation of a simplified medication adherence questionnaire in a large cohort of HIV-infected patients: the GEEMA Study.

OBJECTIVE: To assess the effectiveness of the simplified medication adherence questionnaire (SMAQ) in identifying non-adherent patients. DESIGN: Prospective observational study of adherence. The six-item SMAQ was developed. The following aspects were evaluated: (i) criterion validity, comparison with electronic adherence monitoring; (ii) construct validity, association between adherence, as defined by the SMAQ, and virological outcomes; and (iii) reliability, internal consistency and reproducibility. PATIENTS: A group of 3004 unselected HIV patients who had initiated nelfinavir therapy combined with other antiretroviral drugs [21% naive, 15% protease inhibitor (PI)-naive, 64% PI-experienced] between January 1998 and December 1999 were enrolled in 69 hospitals in Spain. The SMAQ was administered at months 3, 6 and 12. RESULTS: The SMAQ showed 72% sensitivity, 91% specificity and a likelihood ratio of 7.94 to identified non-adherent patients, compared with the medication-event monitoring system (40 patients evaluated). At month 12, 1797 patients were evaluated, of whom 32.3% were defined as non-adherent; viral load < 500 copies/ml found in 68.3% of the adherent, and 46% of the non-adherent patients. A logistic regression analysis of PI-naive patients was performed, including age, sex, baseline viral load > 5 log10/ml, CD4 cell count < 200 x 10(6)/l, and non-adherence as independent variables. Non-adherence was the only significant risk factor in failing to achieve virological suppression. Cronbach's alpha internal consistency coefficient was 0.75, and overall inter-observer agreement was 88.2%. CONCLUSION: The SMAQ appears to be an adequate instrument with which to assess adherence in HIV-infected patients, and may be applied in most clinical settings.

Recomendaciones GESIDA/SEFH/PNS para mejorar la adherencia al tratamiento antirretroviral / The recommendations of GESIDA/SEFH/PNS for improving adherence to antiretroviral treatment

El objetivo del tratamiento antirretroviral es la supresión profunda y duradera de la replicación viral. Las especiales características virológicas del virus de la inmunodeficiencia humana (VIH) determinan que cuando existen concentraciones subterapéuticas de los fármacos el VIH puede multiplicarse y desarrollar resistencias. Esto puede justificar el fracaso terapéutico, la posible transmisión de cepas resistentes y la utilización inadecuada de los recursos económicos. Por tanto, uno de los factores más importantes para conseguir unos niveles terapéuticos adecuados es la correcta adherencia terapéutica. En esta revisión se analizan los factores que influyen en la adherencia, los métodos de evaluación y se recomiendan las posibles estrategias de intervención y de actuación de un equipo multidisciplinario que debe ser integrado por médicos, farmacéuticos, enfermeras, psicólogos y personal de soporte. El inicio del tratamiento antirretroviral no es habitualmente urgente. Dada la importancia que tiene realizar de manera correcta este primer tratamiento conviene, antes de iniciar la terapia, preparar al paciente, tratar de identificar las potenciales situaciones concomitantes que puedan dificultar una correcta adherencia y corregirlas. Si se decide que el paciente inicie el tratamiento es imprescindible que en el momento de la prescripción y la dispensación de los fármacos se ofrezcan una información detallada, soporte y accesibilidad en todos los aspectos relacionados con el tratamiento. Durante éste, la evaluación de la adherencia es imprescindible y deberá tenerse en cuenta en la toma de decisiones terapéuticas. Al no existir un único método fiable, recomendamos utilizar varias técnicas como la entrevista y el cuestionario estructurado, el recuento de la medicación sobrante y la asistencia a las citas de dispensación de fármacos junto con la evolución clínica y analítica del paciente. Para ello es indispensable que exista una buena coordinación entre todos los estamentos implicados. Si se detecta una falta de adherencia debe intervenirse de forma activa para corregirla, y en situaciones extremas puede valorarse la suspensión del tratamiento. Los beneficios que aporta un programa para mejorar la adherencia justifica disponer de suficientes recursos económicos, humanos y de infraestructura que faciliten el desarrollo de estas actividades. (AU)